bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated metabolome and transcriptome analysis unveils novel pathway involved in the fruit coloration of Nitraria tangutorum Bobr.
Authors: Zhang Huilong , Hu Aishuang , Wu Haiwen , Zhu Jianfeng , Zhang Jingbo , Cheng Tielong , Shabala Sergey , Zhang Huaxin , Yang Xiuyan
Published: February 2023

Background

The desert shrub Nitraria tangutorum Bobr. is important for its resistance to salt and alkali in Northwest China. It is an ecologically important species in this region and provides edible and medicinal berries. This study showed a mutant of N. tangutorum (named Jincan, JC) that has a strong yellow pericarp vs red in a wild type (represented by NT).

Results

In this study, the secondary metabolic and molecular mechanisms responsible for Nitraria fruit coloration were investigated using LC–MS-based widely targeted metabolomics and transcriptomics data. As a result of our study, 122 and 104 flavonoid metabolites were differentially expressed throughout the mature and transition stages between JC and NT, respectively. Furthermore, two cyanidin derivatives (cyanidin 3-O-glucoside and cyanidin-3-O-(2''-O-glucosyl) glucoside) and one pelargonidin derivative (pelargonidin-3-O-glucoside) were identified only in the NT phenotype. The functional genes F3H (flavanone 3-hydroxylase), F3'H (flavonoid 3′-hydroxylase) and UFGT (flavonoid 3-O-glucosyltransferase) and the transcription factors MYB, bHLH, NAC and bZIP were significantly downregulated in JC. Meanwhile, the activity of UFGT was extremely low in both periods of JC, with a five-fold higher enzymatic activity of UFGT in RT than in YT. In summary, due to the lack of catalysis of UGFT, yellow fruit of JC could not accumulate sufficient cyanidin and pelargonidin derivatives during fruit ripening.

Conclusion

Taken together, our data provide insights into the mechanism for the regulation of anthocyanin synthesis and N. tangutorum fruit coloration and provide a theoretical basis to develop new strategies for developing bioactive compounds from N. tangutorum fruits.
Prevalence and factors associated with post-traumatic stress disorder among internally displaced people in camps at Debre Berhan, Amhara Region, Ethiopia: a cross-sectional study
Authors: Makango Belay , Alemu Zewdie Aderaw , Solomon Tesfaye , Lemma Nigussie , Girma Tewodros , Mohammednur Tijani , Alayu Mikias , Fufa Yaregal
Published: January 2023

Background

Post-traumatic stress disorder (PTSD) is a common mental disorder after traumatic exposure that can have long-lasting physical and mental health consequences. In 2021, Ethiopia saw the highest number of internally displaced people (IDP) due to conflict and war with the scope of the internal displacement being very high in the study area and less attention has been given to mental health.

Objective

To determine the prevalence and associated factors of PTSD among internally displaced people in camps at Debre Berhan, Ethiopia.

Methods

A cross-sectional study was conducted from December 1–30, 2021 among 406 IDPs, who were selected by random systematic sampling from the registration and proportionally allocated to three IDP camps in Debre Berhan. Post-traumatic stress disorder was measured by the PTSD checklist (DSM-5). Data were collected through an interviewer-administered pre-tested questionnaire, entered into EpiData version 3.1, and analyzed by Statistical Package for Social Sciences version 25. Bivariate binary logistic regression was used to select candidate variables with p < 0.25. Multicollinearity was checked by using the variance inflation factor and it was less than 10. Model adequacy was checked by Hosmer & Lemeshow goodness of test (p > 0.05). In the multivariable binary logistic regression, the association between outcome and independent variables was declared at p < 0.05 with its adjusted odds ratio (AOR) at a 95% confidence level.

Results

The prevalence of PTSD among the respondents was 67.5% (95% CI: 63–72). Being a merchant (AOR = 0.41 [95% CI: 0.02–0.85]), witnessing the destruction of property (AOR = 1.67 [95% CI: 1.01–2.74]), facing trauma during displacement (AOR = 6.00 [95% CI: 2.75–13.10]), frequency of displacement (AOR = 0.31 [95% CI: 0.11–0.85]), being distressed (AOR = 5.42 [95% CI: 3.25–9.05]), and unemployment (AOR = 2.09 [95% CI: 1.24–3.54]) were factors significantly associated with PTSD.

Conclusion

This study provides evidence of the high prevalence of PTSD among internally displaced people. Therefore, mental health and psychosocial support are urgently required to address the identified factors and help the displaced people against long-term avoidable suffering.
What roles does physical activity play following the death of a parent as a young person? A qualitative investigation
Authors: Williams Jane , Howlett Neil , Shorter Gillian W. , Zakrzewski-Fruer Julia K. , Chater Angel Marie
Published: January 2023

Background

Physical activity benefits physical and mental health. However, limited research investigates if physical activity can improve outcomes from the grieving process following the death of a parent.

Methods

Semi-structured interviews were conducted with 14 individuals (n = 8 female; age M = 31.2 years), who had experienced the death of a parent when they were aged between 10 and 24 years old, using retrospective recall. Data were analysed inductively using thematic analysis.

Results

Six themes were identified. Physical activity was seen as; 1) ‘Therapeutic’; providing an 2) ‘Emotional Outlet’ and created a strong sense of 3) ‘Social Support’. Alongside it 4) ‘Builds Confidence’, and led to 5) ‘Finding Yourself’ and 6) ‘Improved Health and wellbeing’ (physical and psychological).

Conclusion

Physical activity has the potential to provide positive experiences following a parental bereavement. It can provide a sense of freedom and was seen to alleviate grief outcomes, build resilience, enable social support and create a stronger sense of self. Bereavement support services for young people who have experienced death of a parent should consider physical activity as a viable intervention to support the grieving process.
Perceptions of the health impacts of climate change among Canadians
Authors: Casson Nora , Cameron Laura , Mauro Ian , Friesen-Hughes Karl , Rocque Rhéa
Published: January 2023

Background

Understanding public perceptions of the health risks of climate change is critical to inform risk communication and support the adoption of adaptive behaviours. In Canada, very few studies have explored public understandings and perceptions of climate impacts on health. The objective of this study was to address this gap by exploring perceptions of the link between climate change and health.

Methods

We conducted a survey of Canadians (n = 3,014) to address this objective. The 116-question survey measured prior consideration of the link between climate change and health, affective assessment of climate health impacts, unprompted knowledge of climate health impacts, and concern about a range of impacts. ANOVA tests were used to assess differences among sociodemographic groups.

Results

Overall, Canadian’s have a similar level of concern about health impacts of climate change compared with concern about other impacts (e.g. biophysical, economic, and national security). Among health-related impacts, respondents were more concerned about impacts on water, food and air quality, compared with impacts on mental health, infectious diseases and heat-related illnesses. There were differences among sociodemographic groups; women were significantly more concerned than men about all of the health-related impacts; respondents with a high school level of education were significantly less concerned about all health-related impacts compared with respondents with more education; and respondents on the political left were more concerned with those in the political centre, who were more concerned than those on the political right.

Conclusion

There is emerging literature suggesting that framing communication around climate change in terms of the health risks it poses may increase perceptions of the proximity of the risks. These results suggest that it is important to be specific in the types of health risks that are communicated, and to consider the concerns of the target sociodemographic groups. The differential knowledge, awareness, and concern of climate health impacts across segments of the Canadian population can inform targeted communication and engagement to build broader support for adaptation and mitigation measures.
Sex-specific effects of calving season on joint health and biomarkers in Montana ranchers
Authors: Thompson Matthew A. , Martin Stephen A. , Hislop Brady D. , Younkin Roubie , Andrews Tara M. , Miller Kaleena , June Ronald K. , Adams Erik S.
Published: January 2023

Background

Agricultural workers have a higher incidence of osteoarthritis (OA), but the etiology behind this phenomenon is unclear. Calving season, which occurs in mid- to late-winter for ranchers, includes physical conditions that may elevate OA risk. Our primary aim was to determine whether OA biomarkers are elevated at the peak of calving season compared to pre-season, and to compare these data with joint health survey information from the subjects. Our secondary aim was to detect biomarker differences between male and female ranchers.

Methods

During collection periods before and during calving season, male (n = 28) and female (n = 10) ranchers completed joint health surveys and provided samples of blood, urine, and saliva for biomarker analysis. Statistical analyses examined associations between mean biomarker levels and survey predictors. Ensemble cluster analysis identified groups having unique biomarker profiles.

Results

The number of calvings performed by each rancher positively correlated with plasma IL-6, serum hyaluronic acid (HA) and urinary CTX-I. Thiobarbituric acid reactive substances (TBARS), a marker of oxidative stress, was significantly higher during calving season than pre-season and was also correlated with ranchers having more months per year of joint pain. We found evidence of sexual dimorphism in the biomarkers among the ranchers, with leptin being elevated and matrix metalloproteinase-3 diminished in female ranchers. The opposite was detected in males. WOMAC score was positively associated with multiple biomarkers: IL-6, IL-2, HA, leptin, C2C, asymmetric dimethylarginine, and CTX-I. These biomarkers represent enzymatic degradation, inflammation, products of joint destruction, and OA severity.

Conclusions

The positive association between number of calvings performed by each rancher (workload) and both inflammatory and joint tissue catabolism biomarkers establishes that calving season is a risk factor for OA in Montana ranchers. Consistent with the literature, we found important sex differences in OA biomarkers, with female ranchers showing elevated leptin, whereas males showed elevated MMP-3.
Menopausal hormone therapy, oral contraceptives and risk of chronic low back pain: the HUNT Study
Authors: Heuch Ingrid , Heuch Ivar , Hagen Knut , Storheim Kjersti , Zwart John-Anker
Published: January 2023

Background

There are indications that use of menopausal hormone therapy (MHT) and oral contraceptives (OC) increases the risk of low back pain (LBP), with higher oestrogen levels involved in the underlying mechanisms. The purpose of the present study was to investigate associations between use of systemic MHT or OC and risk of chronic LBP in a large population-based data set.

Methods

Data were obtained from two surveys in the Trøndelag Health Study in Norway, HUNT2 (1995–1997) and HUNT3 (2006–2008). A cross-sectional study of association between use of systemic MHT and prevalence of chronic LBP comprised 12,974 women aged 40–69 years in HUNT2, with 4007 women reporting chronic LBP. A cohort study involving MHT comprised 6007 women without chronic LBP at baseline in HUNT2, and after 11 years 1245 women reported chronic LBP at follow-up in HUNT3. The cross-sectional study of association with use of OC included 23,593 women aged 20–69 years in HUNT2, with 6085 women reporting chronic LBP. The corresponding cohort study included 10,586 women without chronic LBP at baseline in HUNT2, of whom 2084 women reported chronic LBP in HUNT3. Risk of chronic LBP was examined in both study designs in generalised linear models with adjustment for potential confounders.

Results

In the cohort study, current users of systemic MHT at baseline showed a greater risk of chronic LBP (relative risk (RR) 1.30; 95% CI: 1.14–1.49; compared with never users). The risk increased according to duration of MHT use (P for linear trend = 0.003). Known users of systemic MHT based exclusively on oestrogen experienced the highest risk (RR 1.49; 95% CI: 1.16–1.91), but an increased risk was also seen among known users of oestrogen-progestin combination MHT (RR 1.35; 95% CI: 1.16–1.57). A slight increase in risk of chronic LBP was found in the cohort study among former users of OC (RR 1.17; 95% CI: 1.06–1.30; compared with never users).

Conclusions

Long-lasting use of systemic MHT, in particular therapy based on oestrogen only, is associated with greater risk of chronic LBP. Having been a user of OC most likely entails a minor increase in risk.
Treatment and outcomes of chronic locked posterior shoulder dislocations: a retrospective case series
Authors: Haritinian Emil George , Stoica Ioan Cristian , Popescu Roman , Gheorghievici Gavril Lucian , Nové-Josserand Laurent
Published: January 2023

Background

Posterior shoulder dislocations are rare injuries that are often missed on initial presentation. Cases left untreated for more than three weeks are considered chronic, cannot be reduced closely (they become locked) and are usually associated with a significant reverse Hill-Sachs defect. The aim of this study was to evaluate the outcomes of chronic locked posterior shoulder dislocations treated with the McLaughlin procedure (classic or modified).

Methods

This retrospective study included 12 patients with chronic locked posterior shoulder dislocation operated on between 2000 and 2021 by two surgeons in two institutions. Patients received a thorough clinical examination and radiological assessment before and after surgery. Shoulders were repaired with the McLaughlin or modified McLaughlin procedure. Outcomes were assessed by comparing pre- and postoperative values of clinical variables.

Results

Most of the dislocations were of traumatic origin. The average delay between dislocation and surgical reduction was 13.5 ± 9.7 weeks. Postoperative clinical outcomes were favourable, with an average subjective shoulder value of 86.4 ± 11.1 and a normalized Constant –Murley score of 90 ± 8.3. None of the patients had a recurrence of shoulder dislocation, but one patient developed avascular necrosis of the humeral head and two patients developed glenohumeral osteoarthritis.

Conclusions

In this group of patients with chronic locked posterior shoulder dislocation, the clinical outcomes of McLaughlin and modified McLaughlin procedures were satisfactory, even when surgery was significantly delayed.
A nomogram model for determining optimal patients for local therapy in metastatic prostate cancer: a SEER database-based study
Authors: Yang Lin , Li Sheng , Liu Xiaoqiang , Liu Jiahao , Zheng Fuchun , Deng Wen , Liu Weipeng , Fu Bin , Xiong Jing
Published: January 2023

Background

Numerous studies have shown that local therapy can improve long-term survival in patients with metastatic prostate cancer. However, it is unclear which patients are the potential beneficiaries.

Methods

We obtained information on prostate cancer patients from the Surveillance, Epidemiology, and End Results database and divided eligible patients into the local treatment group and non-local treatment group. Propensity score matching (PSM) was used to reduce the influence of confounding factors. In the matched local treatment (LT) group, if the median overall survival time (OS) was longer than the Nonlocal treatment (NLT) group, it was defined as a benefit group, otherwise, it was a non-benefit group. Then, univariate and multivariate logistic regression were used to screen out predictors associated with benefits, and a nomogram model was constructed based on these factors. The accuracy and clinical value of the models were assessed through calibration plots and decision curve analysis.

Results

The study enrolled 7255 eligible patients, and after PSM, each component included 1923 patients. After matching, the median OS was still higher in the LT group than in the NLT group [42 (95% confidence interval: 39–45) months vs 40 (95% confidence interval: 38–42) months, p = 0.03]. The independent predictors associated with benefit were age, PSA, Gleason score, T stage, N stage, and M stage. The nomogram model has high accuracy and clinical application value in both the training set (C-index = 0.725) and the validation set (C-index = 0.664).

Conclusions

The nomogram model we constructed can help clinicians identify patients with potential benefits from LT and formulate a reasonable treatment plan.
Exploring new therapeutic potentials of curcumin against post-surgical adhesion bands
Authors: Askarnia-Faal Mohammad-Mostafa , Sayyed-Hosseinian Sayyed-Hadi , Nazari Seyedeh Elnaz , Asgharzadeh Fereshteh , Vahedi Ehsan , Eskandari Moein , Ghasemi Haniyeh , Avan Amir , Alaei Maryam , Naimi Hamideh , Daghiani Maryam , Soleimani Atena , Alalikhan Abbas , Mohammadzadeh Reza , Ferns Gordon , Ryzhikov Mikhail , Khazaei Majid , Hassanian Seyed Mahdi
Published: January 2023

Background

Adhesion band formation is a common cause of morbidity for patients undergoing surgeries. Anti-inflammatory and anti-fibrotic properties of curcumin, a pharmacologically active component of Curcuma longa, have been investigated in several studies. The aim of this study is to explore the therapeutic potential of curcumin in attenuating post-operative adhesion band (PSAB) formation in both peritoneal and peritendinous surgeries in animal models.

Methods

Bio-mechanical, histological and quantitative evaluation of inflammation, and total fibrosis scores were graded and measured in the presence and absence of phytosomal curcumin.

Results

Results showed that phytosomal curcumin significantly decreased severity, length, density and tolerance of mobility of peritendinous adhesions as well as incidence and severity of abdominal fibrotic bands post-surgery. Curcumin may decrease inflammation by attenuating recruitment of inflammatory cells and regulating oxidant/anti-oxidant balance in post-operative tissue samples. Moreover, markedly lower fibrosis scores were obtained in the adhesive tissues of phytosomal curcumin-treated groups which correlated with a significant decrease in quantity, quality and grading of fibers, and collagen deposition in animal models.

Conclusion

These results suggest that protective effects of phytosomal curcumin against PSAB formation is partially mediated by decreasing inflammation and fibrosis at site of surgery. Further studies are needed to investigate the therapeutic potential of this molecule in preventing PSAB.
Analysis of the potential biological mechanisms of Danyu Gukang Pill against osteonecrosis of the femoral head based on network pharmacology
Authors: Guo Yongchang , Li Wenxi , Cao Yuju , Feng Xiaoyan , Shen Caihong , Gong Shunguo , Hou Fengzhi , Yang Zhimin , Chen Xifeng , Song Jingbo
Published: January 2023

Background

Osteonecrosis of the femoral head (ONFH) is still a challenge for orthopedists worldwide and can lead to disability if patients are not treated effectively. Danyu Gukang Pill (DGP), a traditional Chinese medicine (TCM) formulation, is recognized to be effective against ONFH. Nevertheless, its molecular mechanisms remain to be clarified.

Methods

The active ingredients of DGP were collected from the online databases according to oral bioavailability (OB) and drug-likeness (DL). The potential targets of DGP were retrieved from the TCMSP database, while the potential targets of ONFH were obtained from the GeneCards and NCBI databases. The functions and signaling pathways of the common targets of DGP and ONFH were enriched by GO and KEGG analyses. Subsequently, molecular docking and in vitro cell experiments were performed to further validate our findings.

Results

In total, 244 active ingredients of DGP and their corresponding 317 targets were obtained, and 40 ONFH-related targets were predicted. Afterwards, 19 common targets of DGP and ONFH were obtained and used as potential targets for the treatment of ONFH. Finally, combined with network pharmacology analysis, molecular docking and in vitro cell experiments, our study first demonstrated that the treatment effect of DGP on ONFH might be closely related to the two targets, HIF1A (HIF-1α) and VEGFA, and the HIF-1 signaling pathway.

Conclusions

This study is the first to investigate the molecular mechanisms of DGP in the treatment of ONFH based on network pharmacology. The results showed that DGP might up-regulate the expression of HIF-1α and VEGFA by participating in the HIF-1 signaling pathway, thus playing an anti-ONFH role.
Effect of a computerized decision support system on the treatment approach of stage III or IV pressure injury in patients with spinal cord injury: a feasibility study
Authors: Scheel-Sailer Anke , Koligi Kamran , Lampart Patricia , Fähndrich Carina , Gmünder Hans Peter , Metzger Stefan , Schaefer Dirk , Schmitt Klaus , Stalder Stefan , Wettstein Reto , Gemperli Armin
Published: January 2023

Background

Stage III and IV pressure injuries (PIs) in patients with spinal cord injury (SCI) require complex interdisciplinary and interprofessional treatment approaches that are difficult to implement. Practical aspects, such as information exchange and coordination, remain challenging. We investigated whether a computerized decision support system (CDSS) could increase treatment adherence and improve clinical outcomes and interprofessional collaboration.

Method

In this feasibility study, a core team developed the initial treatment process and adapted it based on several discussions with clinical experts and information technologists. The CDSS followed the Basel Decubitus Approach and was used in a clinic specializing in SCI. Thirty patients with SCI admitted for stage III/IV PI between July 2016 and May 2017 were randomly allocated to standard or CDSS-supported care. Between-group differences in treatment adherence, complication rates, length of stay, and costs were analyzed using descriptive statistics. The use of the CDSS and potential barriers and facilitators were evaluated through interprofessional focus groups, transcribed verbatim, and thematically analyzed (30 participants).

Results

No differences in SCI characteristics, comorbidities, or PI characteristics (localization: ischium [number (n) = 19 PI, 63%], sacrum [n = 10 PI, 33%], recurrent PI [n = 21, 70%]) were found between the two groups. Furthermore, no statistically significant differences were observed in treatment adherence, frequency of major (20% vs. 13% between CDSS and control group) and minor (33% vs 27%) complications, and length of stay (98 [±28] vs 81 [±23] days). Healthcare professionals found the CDSS to be helpful for visualizing the treatment process. However, the high workload and difficulties in the information technology processes, such as missing reminders, slow computer performance and data processing, and poor accessibility, hindered the effective implementation of the CDSS.

Conclusion

The implementation of the CDSS to support the treatment of stage III/IV PI in patients with SCI was feasible and included definitions of milestones, interventions, and outcomes. However, to assess the impact of the CDSS, a longer observation period is required. Further, the technical difficulties must be addressed, and solid integration of the CDSS into the clinical information system is necessary.

Trial Registration

This quality improvement project received a declaration of no objection from the Ethics Committee of Northwest and Central Switzerland (EKNZ UBE-16/003), and ethical approval was received for the focus groups (EKNZ Req-2017-00860).
Allele-specific quantitation of ATXN3 and HTT transcripts in polyQ disease models
Authors: Joachimiak Paweł , Ciesiołka Adam , Kozłowska Emilia , Świtoński Paweł M. , Figura Grzegorz , Ciołak Agata , Adamek Grażyna , Surdyka Magdalena , Kalinowska-Pośka Żaneta , Figiel Maciej , Caron Nicholas S. , Hayden Michael R. , Fiszer Agnieszka
Published: February 2023

Background

The majority of genes in the human genome is present in two copies but the expression levels of both alleles is not equal. Allelic imbalance is an aspect of gene expression relevant not only in the context of genetic variation, but also to understand the pathophysiology of genes implicated in genetic disorders, in particular, dominant genetic diseases where patients possess one normal and one mutant allele. Polyglutamine (polyQ) diseases are caused by the expansion of CAG trinucleotide tracts within specific genes. Spinocerebellar ataxia type 3 (SCA3) and Huntington’s disease (HD) patients harbor one normal and one mutant allele that differ in the length of CAG tracts. However, assessing the expression level of individual alleles is challenging due to the presence of abundant CAG repeats in the human transcriptome, which make difficult the design of allele-specific methods, as well as of therapeutic strategies to selectively engage CAG sequences in mutant transcripts.

Results

To precisely quantify expression in an allele-specific manner, we used SNP variants that are linked to either normal or CAG expanded alleles of the ataxin-3 (ATXN3) and huntingtin (HTT) genes in selected patient-derived cell lines. We applied a SNP-based quantitative droplet digital PCR (ddPCR) protocol for precise determination of the levels of transcripts in cellular and mouse models. For HD, we showed that the process of cell differentiation can affect the ratio between endogenous alleles of HTT mRNA. Additionally, we reported changes in the absolute number of the ATXN3 and HTT transcripts per cell during neuronal differentiation. We also implemented our assay to reliably monitor, in an allele-specific manner, the silencing efficiency of mRNA-targeting therapeutic approaches for HD. Finally, using the humanized Hu128/21 HD mouse model, we showed that the ratio of normal and mutant HTT transgene expression in brain slightly changes with the age of mice.

Conclusions

Using allele-specific ddPCR assays, we observed differences in allele expression levels in the context of SCA3 and HD. Our allele-selective approach is a reliable and quantitative method to analyze low abundant transcripts and is performed with high accuracy and reproducibility. Therefore, the use of this approach can significantly improve understanding of allele-related mechanisms, e.g., related with mRNA processing that may be affected in polyQ diseases.
Characterization and expression of domains of Alphaherpesvirus bovine 1/5 envelope glycoproteins B in Komagataella phaffi
Authors: Quintero Barbosa Juan Sebastián , Rojas Heidy Yohana Triana , Gonzalez Janneth , Espejo-Mojica Angela Johana , Díaz Carlos Javier Alméciga , Gutierrez María Fernanda
Published: January 2023

Background

Bovine herpes virus (BoHV 1 and BoHV-5) are the causative agents of infectious bovine rhinotracheitis (IBR). IBR is responsible for important economic losses in the cattle industry. The envelope glycoprotein B (gB) is essential for BoHV infection of cattle's upper respiratory and genital tract. gB is one of the main candidate antigens for a potential recombinant vaccine since it induces a strong and persistent immune response.

Results

In this study, gB of BoHV-1 and BoHV-5 was characterized in terms of function, structure, and antigenicity through bioinformatics tools. gB showed conserved sequence and structure, so, both domains named PH Like 1 and 2 domains of each virus were selected for the design of a bivalent vaccine candidate. The immunoinformatic study showed that these two domains have epitopes recognizable by B and T lymphocytes, followed by this, the cDNA domains from BoHV-1/5 gB (Domains-gB) were transformed into the yeast Komagataella phaffii GS115 (previously known as Pichia pastoris). A recombinant protein with molecular weight of about 110 kDa was obtained from the culture media. The vaccine candidate protein (Domains-gB) was recognized by a monoclonal antibody from a commercial ELISA kit used for IBR diagnostic, which may suggest that the epitopes are conserved of the entire infectious virus.

Conclusion

Overall, it was shown that the recombinant domains of BoHV-1/5 gB have antigenic and immunogenic properties similar to the native gB. This vaccine candidate is promising to be used in future studies to assess its immunogenicity in an animal model.
Protection of the marginal mandibular branches of the facial nerves by different surgical procedures in comprehensive cervical lymphadenectomy for locally advanced oral and oropharyngeal cancer: a multicenter experience
Authors: Zhao Jiuzhou , Zeng Wen , Qiu Chengyu , Liu Jiafeng , Li Ke , Huang Jing , Tong Michael C. F. , Zhang Xiangmin
Published: January 2023

Objective

According to the different characteristics of patients and cervical lymph node metastasis of oral and oropharyngeal cancer, the marginal mandibular branches of facial nerves were treated by different surgical procedures, and the safety and protective effects of different surgical procedures were investigated.

Methods

One hundred ninety-seven patients with oral and oropharyngeal cancer satisfying the inclusion criteria were selected. According to the different characteristics of patients and cervical metastatic lymph nodes, three different surgical procedures were used to treat the marginal mandibular branches of the facial nerve: finding and exposing the marginal mandibular branches of the facial nerves at the mandibular angles of the platysma flaps, finding and exposing the marginal mandibular branches of facial nerves at the intersections of the distal ends of facial arteries and veins with the mandible, and not exposing the marginal mandibular branches of the facial nerves. The anatomical position, injury, and complications of the marginal mandibular branches of the facial nerves were observed.

Results

The marginal mandibular branches of the facial nerves were found and exposed at the mandibular angles of the platysma flaps in 102 patients; the marginal mandibular branches of facial nerves were found and exposed at the intersections of the distal ends of the facial arteries and veins with the mandibles in 64 patients; the marginal mandibular branches of facial nerves were not exposed in 31 patients; among them, four patients had permanent injury of the marginal mandibular branches of the facial nerves, and temporary injury occurred in seven patients. There were statistically significant differences in the protection of the mandibular marginal branch of the facial nerve among the three different surgical methods (P = 0.0184). The best protective effect was to find and expose the mandibular marginal branch of the facial nerve at the mandibular angle of the platysma muscle flap, and the injury rate was only 2.94%.

Conclusion

The three different surgical procedures were all safe and effective in treating the marginal mandibular branches of the facial nerves, the best protective effect was to find and expose the mandibular marginal branch of the facial nerve at the mandibular angle of the platysma muscle flap.
An optimized pipeline for live imaging whole Arabidopsis leaves at cellular resolution
Authors: Harline Kate , Roeder Adrienne H. K.
Published: February 2023

Background

Live imaging is the gold standard for determining how cells give rise to organs. However, tracking many cells across whole organs over large developmental time windows is extremely challenging. In this work, we provide a comparably simple method for confocal live imaging entire Arabidopsis thaliana first leaves across early development. Our imaging method works for both wild-type leaves and the complex curved leaves of the jaw-1D mutant.

Results

We find that dissecting the cotyledons, affixing a coverslip above the samples and mounting samples with perfluorodecalin yields optimal imaging series for robust cellular and organ level analysis. We provide details of our complementary image processing steps in MorphoGraphX software for segmenting, tracking lineages, and measuring a suite of cellular properties. We also provide MorphoGraphX image processing scripts we developed to automate analysis of segmented images and data presentation.

Conclusions

Our imaging techniques and processing steps combine into a robust imaging pipeline. With this pipeline we are able to examine important nuances in the cellular growth and differentiation of jaw-D versus WT leaves that have not been demonstrated before. Our pipeline is approachable and easy to use for leaf development live imaging.
Letter to the editor regarding “efficacy and safety of platelet-rich plasma combined with hyaluronic acid versus platelet-rich plasma alone for knee osteoarthritis: a systematic review and meta-analysis”
Authors: Wu Ruibang , Li Qiujiang , Feng Ganjun , Liu Limin
Published: February 2023

In this letter to the editor, we discuss the article by Zhang et al., published recently in the Journal of Orthopaedic Surgery and Research. The authors reviewed the efficacy and safety of platelet-rich plasma combined with hyaluronic acid versus platelet-rich plasma alone for knee osteoarthritis. Whether the authors' purpose in grouping was to investigate the role of hyaluronic acid in the treatment of knee osteoarthritis is a question we would like to raise. In terms of the methodology of the study, combining randomized controlled trials with cohort studies in this meta-analysis is a methodological error. Secondly, the study methodology of the four included randomized controlled trial studies lacked a clear method of randomization. In addition to this, the completeness of the search needs to be taken into consideration. Some of the results of this study were highly heterogeneous, and no sensitivity analysis or meta-regression was performed to further analyse the sources of heterogeneity. The above issues will affect the conclusions of the article, and we believe this needs further improvement and discussion.
Mid-term outcomes of an alternative remodelling technique for aortic root replacement without coronary ostial mobilisation or reimplantation
Authors: Hadjinikolaou Leonidas , Acharya Metesh , Dominici Carmelo , Biancari Fausto , Raheel Furqan , Ahmed Aamer , Mariscalco Giovanni
Published: February 2023

Background

We compare the early and late outcomes of a modified aortic root remodelling (ARR) technique for aortic root replacement without mobilisation or reimplantation of the coronary ostia, with those of the modified Bentall-de Bono procedure.

Methods

A retrospective observational study was performed comprising 181 consecutive patients who underwent aortic root replacement with a modified Bentall-de Bono procedure (104 patients) or ARR (77 patients) between January 2013 and December 2019. Primary endpoints included hospital mortality and late survival. Secondary endpoints included incidence of post-operative complications and freedom from late re-operation.

Results

ARR procedures were performed with shorter cross-clamp times and comparable cardiopulmonary bypass times to modified Bentall-de Bono procedures. The incidence of early post-complications was comparable between groups. 30-day mortality was numerically lower with ARR than the modified Bentall-de Bono procedure. Over 7-year follow-up, 4 patients (3.8%) required repeat aortic surgery after a modified Bentall-de Bono procedure, and none after ARR. Long-term mortality after ARR and after modified Bentall-de Bono procedures was 17.1% and 22.7%, respectively. The cumulative incidence of reintervention on the aortic root/valve was 3.2% after a modified Bentall-de Bono procedure and 0% after ARR. When adjusted for other independent risk factors, late mortality was not influenced by the procedure performed, although competing risk adjusted for age showed that the modified Bentall-de Bono procedure was associated with an increased risk of aortic root/aortic valve re-operation.

Conclusions

The modified ARR technique is associated with reduced myocardial ischaemia time, lower post-operative mortality and aortic re-intervention rates compared to a modified Bentall-de Bono procedure. It may be considered a safe and feasible procedure for aortic root/ascending aortic replacement offering good long-term outcomes.
C1-inhibitor/C1-inhibitor antibody complexes in acquired angioedema due to C1-inhibitor deficiency
Authors: Polai Zsofia , Kajdacsi Erika , Cervenak Laszlo , Balla Zsuzsanna , Benedek Szabolcs , Varga Lilian , Farkas Henriette
Published: February 2023

Background

Autoantibodies against C1-inhibitor (C1-INH-Ab) have a diagnostic value in acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE), even though antibodies can circulate in complexes, which can be undetectable by proven methods. Our aim was to measure C1-INH/C1-INH-Ab complexes (CAC) and investigate their connection to C1-INH-Ab and the changes in their titer over time.

Results

19 patients were diagnosed with C1-INH-AAE in the Hungarian Angioedema Center of Reference and Excellence; 79% of them had an underlying disease. Samples were examined with a newly developed in-house complex ELISA method. Patients with high C1-INH-Ab titer had a CAC titer which did not exceed the normal level and the ones with high CAC titer had a C1-INH-Ab titer which did not exceed the normal level. In case of those patients who had C1-INH-Ab and CAC of the same type of immunoglobulin, the increasing titer of C1-INH-Ab went together with the decreasing level of CAC and vice versa. CAC titer was already increased before the diagnosis of the underlying disease.

Conclusions

Free circulating and complex antibodies are in a dynamically changing equilibrium. CAC measurements can help to predict the development of an underlying disease. The efficiency of the treatment for underlying disease can be monitored by the decreasing CAC titers.

Our results show that the CAC can be of important additional information besides the complement panel examination in case of C1-INH-AAE. Measurement of CAC is recommended to be done parallelly with C1-INH-Ab, so as to detect both free and bound antibodies.
Using ecological niche modeling to predict the potential distribution of scrub typhus in Fujian Province, China
Authors: Li Xuan , Wei Xianyu , Yin Wenwu , Soares Magalhaes Ricardo J. , Xu Yuanyong , Wen Liang , Peng Hong , Qian Quan , Sun Hailong , Zhang Wenyi
Published: January 2023

Background

Despite the increasing number of cases of scrub typhus and its expanding geographical distribution in China, its potential distribution in Fujian Province, which is endemic for the disease, has yet to be investigated.

Methods

A negative binomial regression model for panel data mainly comprising meteorological, socioeconomic and land cover variables was used to determine the risk factors for the occurrence of scrub typhus. Maximum entropy modeling was used to identify the key predictive variables of scrub typhus and their ranges, map the suitability of different environments for the disease, and estimate the proportion of the population at different levels of infection risk.

Results

The final multivariate negative binomial regression model for panel data showed that the annual mean normalized difference vegetation index had the strongest correlation with the number of scrub typhus cases. With each 0.1% rise in shrubland and 1% rise in barren land there was a 75.0% and 37.0% increase in monthly scrub typhus cases, respectively. In contrast, each unit rise in mean wind speed in the previous 2 months and each 1% increase in water bodies corresponded to a decrease of 40.0% and 4.0% in monthly scrub typhus cases, respectively. The predictions of the maximum entropy model were robust, and the average area under the curve value was as high as 0.864. The best predictive variables for scrub typhus occurrence were population density, annual mean normalized difference vegetation index, and land cover types. The projected potentially most suitable areas for scrub typhus were widely distributed across the eastern coastal area of Fujian Province, with highly suitable and moderately suitable areas accounting for 16.14% and 9.42%, respectively. Of the total human population of the province, 81.63% reside in highly suitable areas for scrub typhus.

Conclusions

These findings could help deepen our understanding of the risk factors of scrub typhus, and provide information for public health authorities in Fujian Province to develop more effective surveillance and control strategies in identified high risk areas in Fujian Province.
Genome-wide allele and haplotype-sharing patterns suggested one unique Hmong–Mein-related lineage and biological adaptation history in Southwest China
Authors: He Guanglin , Wang Jiawen , Yang Lin , Duan Shuhan , Sun Qiuxia , Li Youjing , Wu Jun , Wu Wenxin , Wang Zheng , Liu Yan , Tang Renkuan , Yang Junbao , Liu Chao , Yuan Buhong , Wang Daoyong , Xu Jianwei , Wang Mengge
Published: January 2023

Background

Fine-scale genetic structure of ethnolinguistically diverse Chinese populations can fill the gap in the missing diversity and evolutionary landscape of East Asians, particularly for anthropologically informed Chinese minorities. Hmong–Mien (HM) people were one of the most significant indigenous populations in South China and Southeast Asia, which were suggested to be the descendants of the ancient Yangtze rice farmers based on linguistic and archeological evidence. However, their deep population history and biological adaptative features remained to be fully characterized.

Objectives

To explore the evolutionary and adaptive characteristics of the Miao people, we genotyped genome-wide SNP data in Guizhou HM-speaking populations and merged it with modern and ancient reference populations via a comprehensive population genetic analysis and evolutionary admixture modeling.

Results

The overall genetic admixture landscape of Guizhou Miao showed genetic differentiation between them and other linguistically diverse Guizhou populations. Admixture models further confirmed that Miao people derived their primary ancestry from geographically close Guangxi Gaohuahua people. The estimated identity by descent and effective population size confirmed a plausible population bottleneck, contributing to their unique genetic diversity and population structure patterns. We finally identified several natural selection candidate genes associated with several biological pathways.

Conclusions

Guizhou Miao possessed a specific genetic structure and harbored a close genetic relationship with geographically close southern Chinese indigenous populations and Guangxi historical people. Miao people derived their major ancestry from geographically close Guangxi Gaohuahua people and experienced a plausible population bottleneck which contributed to the unique pattern of their genetic diversity and structure. Future ancient DNA from Shijiahe and Qujialing will provide new insights into the origin of the Miao people.
Targeting EphA2 and DDR signaling can overcome the BRAF and MEK inhibitors acquired resistance in melanoma cell lines
Authors: Belli Valentina , Napolitano Stefania , De Falco Vincenzo , Suarato Gabriella , Perrone Alessandra , Guerrera Luigi Pio , Martini Giulia , Della Corte Carminia Maria , Martinelli Erika , Morgillo Floriana , Turano Mimmo , Furia Maria , Argenziano Giuseppe , Ciardiello Davide , Ciardiello Fortunato , Troiani Teresa
Published: February 2023

The BRAF and MEK inhibitors combined strategies have dramatically changed the outcome of BRAF-mutated metastatic melanoma patients. However, despite the initial promising results, the onset of primary or acquired resistance occurs in nearly half of the patients at about one year from the diagnosis. Understanding the mechanisms of resistance to these inhibitors is therefore critical for planning more effective therapeutic strategies able to improve patient outcomes. To this aim we generated BRAF and MEK inhibitors resistant melanoma cells starting from the SAN and A375 lines, both harboring the most common BRAF-V600 mutation and sensitive to these drugs. The obtained double-resistant cell lines were characterized by MTT cell proliferation, migration, invasion assays, phosphoarray and western blot analysis. Here we report that the overexpression of several Tyrosine Kinase Receptors (TKRs), such as EphA2 and DDRs, drives the resistance to these drugs and that this resistance can be overcome by treatment with ALW‑II‑41‑27 multikinase inhibitor. ALW‑II‑41‑27 blocks not only TKRs expression, but also the related downstream AKT and MAPK signaling pathways and its efficacy is documented by decreased cell viability and reduced cell invasion/migration of the resistant cells. Our results can delineate a novel promising therapeutic approach to overcoming the drug resistance occurring in BRAF-mutated metastatic melanoma.
Qualitative interviews to evaluate content validity of the ACTIV-2 COVID-19 Symptom Diary (ACSD)
Authors: Matza Louis S. , Stewart Katie D. , Naegeli April N. , Mills Kayla M. , Coyne Karin S. , Chew Kara W. , Hughes Michael D. , Smith Davey M.
Published: January 2023

Background

Patient-reported outcome measures are needed to assess the impact of treatments for COVID-19 on symptoms. The ACTIV-2 COVID-19 Symptom Diary (ACSD) is being used in the ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines-2 (ACTIV-2) platform clinical trial. The purpose of the current study was to conduct qualitative interviews to assess content validity of the ACSD.

Methods

Interviews were conducted with adults who had tested positive for SARS-CoV-2. The ACSD begins with global items, followed by a symptom checklist. Each interview began with concept elicitation focusing on participant experiences with COVID-19. Then, participants completed the ACSD, and cognitive interviews were conducted to evaluate the questionnaire. Interviews were recorded, transcribed, and coded following a qualitative content analysis. For the qualitative analysis, a coding dictionary was developed with a list of all potential codes and instructions for how the codes should be applied and combined.

Results

Interviews were conducted with 30 participants (mean age = 39 years; 57% female; 17% Latinx; 17% Black/African American; 40% meeting at least one criterion for classification as high risk of progression to severe COVID-19). Commonly reported symptoms included fatigue (reported by 100% of the sample), body pain/muscle pain/aches (87%), headaches (87%), cough (83%), loss of smell (73%), shortness of breath/difficulty breathing (70%), and chills (70%). The 13 symptoms most commonly reported in this study are included in the ACSD. After completing the ACSD, participants consistently reported that it was clear and easy to complete, and all items were generally interpreted as intended. Based on participants’ input, the ACSD was edited slightly after the first 13 interviews, and the revised version was used for the final 17 interviews. Two additional items assessing “brain fog” and dizziness were recommended for addition to the ACSD in future research.

Conclusions

This qualitative study supports the content validity of the ACSD for assessment of COVID-19 symptoms. Quantitative research with larger samples will be needed to examine the questionnaire’s measurement properties.