bluuebunny/crossref_metadata_2025 huggingface dataset:
Theobromine versus casein phospho-peptides/Amorphous calcium phosphate with fluoride as remineralizing agents: effect on resin-dentine bond strength, microhardness, and morphology of dentine
Authors: Elmalawany Lamia M. , Sherief Dalia I. , Alian Ghada A.
Published: July 2023

Background

This study aimed to assess the impact of theobromine and casein phospho-peptides/amorphous calcium phosphate with fluoride (CPP-ACPF) on the resin-dentine bond strength, microhardness, and dentine morphology.

Methods

A total of 18 sound human molars for micro-tensile bond strength (µTBS), 20 sound human premolars for microhardness, and 30 premolars for Scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDX) were used. Based on the pre-treatment used, teeth were split into six groups; sound dentine, demineralized dentine, and demineralized dentine treated with theobromine (Sigma Aldrich) and MI paste plus (GC International, USA) for two-time intervals; 5 min and 1 month. The bonded teeth were sectioned to produce 1 mm2 resin-dentine sticks which were evaluated for µTBS using a universal testing device (Instron 3365, USA). The dentine microhardness was tested by using the Vickers microhardness tester (Nexus 4000 TM, Netherlands). The pre-treated dentine surface was examined using SEM/EDX (Neoscope JCM-6000 plus Joel benchtop SEM, Japan). µTBS results were analysed with two-way ANOVA. Microhardness and EDX results were analysed with two-way mixed model ANOVA. The significance level was set at (p ≤ 0.05).

Results

While both remineralizing materials at the two-time intervals demonstrated µTBS comparable to sound dentine (46.38 ± 12.18), the demineralized group demonstrated statistically the lowest µTBS (p < 0.001). Whether used for 5 min or 1 month, theobromine significantly increased the microhardness (50.18 ± 3.43) and (54.12 ± 2.66) respectively (p < 0.001), whereas MI paste only increased the hardness (51.12 ± 1.45) after 1 month (p < 0.001).

Conclusions

The pre-treatment of demineralized dentine with theobromine for 5 min or 1 month could enhance its bond strength and microhardness while for MI paste plus, only 1-month application was efficient to ensure remineralization.
Marginal gap and internal fit of 3D printed versus milled monolithic zirconia crowns
Authors: Refaie Ashraf , Fouda Ahmed , Bourauel Christoph , Singer Lamia
Published: July 2023

Background

This study aimed to evaluate and compare the marginal gap using two different methods and the internal fit of 3D printed and zirconia crowns.

Methods

3Y-TZP zirconia crowns (n = 20) were manufactured using subtractive milling (group M) and 3D printed (group P). The marginal gap was measured at 60 points using vertical marginal gap technique (VMGT). On the other hand, the silicone replica technique (SRT) was used to evaluate the internal fit and was divided into 4 groups: marginal gap, cervical gap, axial gap, and occlusal gap where the thickness of light impression was measured at 16 references. The numerical data was tested for normality using Shapiro–Wilk's test. They were found to be normally distributed and were analyzed using an independent t-test.

Results

Using VMGT, group P had significantly higher mean marginal gap values of 80 ± 30 µm compared to group M = 60 ± 20 µm (p < 0.001). Also, with the SRT, the marginal gap of group P (100 ± 10 µm) had significantly higher values compared to group M (60 ± 10 µm). The internal fit showed significant difference between the tested groups except for Axial Gap.

Conclusions

Although milled crowns showed better results. The 3D printed zirconia crowns offer clinically acceptable results in terms of marginal adaptation and internal fit. Both VMGT and SRT are reliable methods for the assessment of the marginal gap.
Rapid cycle training for non-critical care physicians to meet intensive care unit staff shortage at an academic training center in a developing country during the COVID-19 pandemic
Authors: Bakhsh Abdullah , Asiri Razan , Alotaibi Hadeel , Alsaeedi Rowida , Shahbar Raghad , Boker Abdulaziz
Published: July 2023

Background

The sudden unexpected increase in critically ill COVID-19 patients admitted to Intensive Care Units (ICUs), resulted in an urgent need for expanding the physician workforce. A COVID-19 critical care crash (5C) course was implemented to introduce physicians without formal critical care training to care for critically ill COVID-19 patients. Upon successful completion of the course, physicians were recruited to work in a COVID-19 ICU under the supervision of a board-certified critical care physician. The aim of this study is to describe the methods of a novel course designed specifically to teach the management critically ill COVID-19 patients, while assessing change in knowledge, skill competency, and self-reported confidence.

Methods

The blended focused 5C course is composed of both virtual and practical components. Candidates may register for the practical component only after successful completion of the virtual component. We assessed knowledge acquisition using a multiple-choice question test (pre- and post-test assessment), skill competency, and self-reported confidence levels during simulated patient settings. Paired T-test was used to compare before and after course results.

Results

Sixty-five physicians/trainees from different specialties were included in the analysis. Knowledge significantly increased from 14.92± 3.20 (out of 20 multiple-choice questions) to 18.81± 1.40 (p< 0.01), skill competence during practical stations had a mean minimum of 2 (out of 3), and self-reported confidence during a simulated patient setting increased significantly from 4.98± 1.15 (out of 10) to 8.76± 1.10 (out of 10) (p< 0.01).

Conclusion

We describe our initiative in increasing the ICU physician workforce in the midst of the COVID-19 pandemic. The blended 5C course is a valuable educational program designed by experts from different backgrounds. Future research should be directed at examining outcomes of patients associated with graduates of such program.
Explaining of existing challenges of community-based undergraduate nursing education in Iran: a qualitative study
Authors: Atashzadeh-Shoorideh Foroozan , Zeydani Arezoo , Hosseini Meimanat , Zohari-Anboohi Sima
Published: July 2023

Background

The education of nursing students should be such that the health needs of the community are met, but in Iran, due to some problems, students do not receive such education. Therefore, the present study was conducted to explain the existing challenges of community-based undergraduate nursing education in Iran.

Methods

Ten individual semi-structured interviews were conducted with the faculty members and nursing specialists in this qualitative study. Eight focus group interviews were conducted to the nurses and nursing students using a purpose-based sampling method in 2022. The interviews were recorded and transcribed and then content analysis was done by the Lundman and Granheim method.

Results

Five themes were obtained from the analysis of participants' responses, which include "weakness in community-based nursing education and curriculum", "treatment-oriented health system and education", "defect in the infrastructure and basic structures of community-based nursing education", "weakness in the implementation of community-based nursing education" and "weakness in the stakeholder engagement and cooperation of interested organizations".

Conclusion

Interviews with the participants provided a vision of the challenges of community-based nursing education so that the reviewers of the undergraduate nursing curriculum in the ministry and nursing schools, educators, policymakers and nursing managers can use the results of the present study to improve the quality of education and the effective use of nursing students in responding to the community’s needs and provide a proper context for improving students' learning.
The diversity of providers’ and consumers’ views of virtual versus inpatient care provision: a qualitative study
Authors: Clay-Williams Robyn , Hibbert Peter , Carrigan Ann , Roberts Natalie , Austin Elizabeth , Fajardo Pulido Diana , Meulenbroeks Isabelle , Nguyen Hoa Mi , Sarkies Mitchell , Hatem Sarah , Maka Katherine , Loy Graeme , Braithwaite Jeffrey
Published: July 2023

Background

A broad-based international shift to virtual care models over recent years has accelerated following COVID-19. Although there are increasing numbers of studies and reviews, less is known about clinicians’ and consumers’ perspectives concerning virtual modes in contrast to inpatient modes of delivery.

Methods

We conducted a mixed-methods study in late 2021 examining consumers’ and providers’ expectations of and perspectives on virtual care in the context of a new facility planned for the north-western suburbs of Sydney, Australia. Data were collected via a series of workshops, and a demographic survey. Recorded qualitative text data were analysed thematically, and surveys were analysed using SPSS v22.

Results

Across 12 workshops, 33 consumers and 49 providers from varied backgrounds, ethnicities, language groups, age ranges and professions participated. Four advantages, strengths or benefits of virtual care reported were: patient factors and wellbeing, accessibility, better care and health outcomes, and additional health system benefits, while four disadvantages, weaknesses or risks of virtual care were: patient factors and wellbeing, accessibility, resources and infrastructure, and quality and safety of care.

Conclusions

Virtual care was widely supported but the model is not suitable for all patients. Health and digital literacy and appropriate patient selection were key success criteria, as was patient choice. Key concerns included technology failures or limitations and that virtual models may be no more efficient than inpatient care models. Considering consumer and provider views and expectations prior to introducing virtual models of care may facilitate greater acceptance and uptake.
Using technology to reduce critical deterioration (the DETECT study): a cost analysis of care costs at a tertiary children's hospital in the United Kingdom
Authors: Costa Eduardo , Mateus Céu , Carter Bernie , Saron Holly , Eyton-Chong Chin-Kien , Mehta Fulya , Lane Steven , Siner Sarah , Dean Jason , Barnes Michael , McNally Chris , Lambert Caroline , Hollingsworth Bruce , Carrol Enitan D. , Sefton Gerri
Published: July 2023

Background

Electronic early warning systems have been used in adults for many years to prevent critical deterioration events (CDEs). However, implementation of similar technologies for monitoring children across the entire hospital poses additional challenges. While the concept of such technologies is promising, their cost-effectiveness is not established for use in children. In this study we investigate the potential for direct cost savings arising from the implementation of the DETECT surveillance system.

Methods

Data were collected at a tertiary children’s hospital in the United Kingdom. We rely on the comparison between patients in the baseline period (March 2018 to February 2019) and patients in the post-intervention period (March 2020 to July 2021). These provided a matched cohort of 19,562 hospital admissions for each group. From these admissions, 324 and 286 CDEs were observed in the baseline and post-intervention period, respectively. Hospital reported costs and Health Related Group (HRG) National Costs were used to estimate overall expenditure associated with CDEs for both groups of patients.

Results

Comparing post-intervention with baseline data we found a reduction in the total number of critical care days, driven by an overall reduction in the number of CDEs, however without statistical significance. Using hospital reported costs adjusted for the Covid-19 impact, we estimate a non-significant reduction of total expenditure from £16.0 million to £14.3 million (corresponding to £1.7 million of savings – 11%). Additionally, using HRG average costs, we estimated a non-significant reduction of total expenditure from £8.2 million to £ 7.2 million (corresponding to £1.1 million of savings – 13%).

Discussion and conclusion

Unplanned critical care admissions for children not only impose a substantial burden on patients and families but are also costly for hospitals. Interventions aimed at reducing emergency critical care admissions can be crucial to contribute to the reduction of these episodes’ costs. Even though cost reductions were identified in our sample, our results do not support the hypothesis that reducing CDEs using technology leads to a significant reduction on hospital costs.

Trial registration

Current Controlled Trials ISRCTN61279068, date of registration 07/06/2019, retrospectively registered.
Advances in PD-1 signaling inhibition-based nano-delivery systems for tumor therapy
Authors: Liu Songlin , Wang Haiyang , Shao Xinzhe , Chen Haonan , Chao Shushu , Zhang Yanyan , Gao Zhaoju , Yao Qingqiang , Zhang Pingping
Published: July 2023

In recent years, cancer immunotherapy has emerged as an exciting cancer treatment. Immune checkpoint blockade brings new opportunities for more researchers and clinicians. Programmed cell death receptor-1 (PD-1) is a widely studied immune checkpoint, and PD-1 blockade therapy has shown promising results in a variety of tumors, including melanoma, non-small cell lung cancer and renal cell carcinoma, which greatly improves patient overall survival and becomes a promising tool for the eradication of metastatic or inoperable tumors. However, low responsiveness and immune-related adverse effects currently limit its clinical application. Overcoming these difficulties is a major challenge to improve PD-1 blockade therapies. Nanomaterials have unique properties that enable targeted drug delivery, combination therapy through multidrug co-delivery strategies, and controlled drug release through sensitive bonds construction. In recent years, combining nanomaterials with PD-1 blockade therapy to construct novel single-drug-based or combination therapy-based nano-delivery systems has become an effective mean to address the limitations of PD-1 blockade therapy. In this study, the application of nanomaterial carriers in individual delivery of PD-1 inhibitors, combined delivery of PD-1 inhibitors and other immunomodulators, chemotherapeutic drugs, photothermal reagents were reviewed, which provides effective references for designing new PD-1 blockade therapeutic strategies.

Graphical Abstract
Myofiber directs macrophages IL-10-Vav1-Rac1 efferocytosis pathway in inflamed muscle following CTX myoinjury by activating the intrinsic TGF-β signaling
Authors: Liao Zhaohong , Lan Haiqiang , Jian Xiaoting , Huang Jingwen , Wang Han , Hu Jijie , Liao Hua
Published: July 2023

Background

To explore the role of skeletal muscle specific TGF-β signaling on macrophages efferocytosis in inflamed muscle caused by Cardiotoxin (CTX) injection.

Methods

CTX myoinjury was manipulated in TGF-βr2flox/flox (control) mice or transgenic mice with TGF-β receptor 2 (TGF-βr2) being specifically deleted in skeletal muscle (SM TGF-βr2−/−). Gene levels of TGF-β signal molecules, special inflammatory mediators in damaged muscle or in cultured and differentiated myogenic precursor cells (MPC-myotubes) were monitored by transcriptome microarray or qRT-PCR. TGF-β pathway molecules, myokines and embryonic myosin heavy chain in regenerating myofibers, the phenotype and efferocytosis of macrophages were evaluated by immunofluorescence, immunoblotting, Luminex, or FACS analysis. In vitro apoptotic cells were prepared by UV-irradiation.

Results

In control mice, TGF-β-Smad2/3 signaling were significantly up-regulated in regenerating centronuclear myofibers after CTX-myoinjury. More severe muscle inflammation was caused by the deficiency of muscle TGF-β signaling, with the increased number of M1, but the decreased number of M2 macrophages. Notably, the deficiency of TGF-β signaling in myofibers dramatically affected on the ability of macrophages to conduct efferocytosis, marked by the decreased number of Annexin-V−F4/80+Tunel+ macrophages in inflamed muscle, and the impaired uptake of macrophages to PKH67+ apoptotic cells transferred into damaged muscle. Further, our study suggested that, the intrinsic TGF-β signaling directed IL-10-Vav1-Rac1 efferocytosis signaling in muscle macrophages.

Conclusions

Our data demonstrate that muscle inflammation can be suppressed potentially by activating the intrinsic TGF-β signaling in myofibers to promote IL-10 dependent-macrophages efferocytosis.
Efficacy of low-dose risperidone in combination with sertraline in first-episode drug-naïve patients with schizophrenia: a randomized controlled open-label study
Authors: Lang Xiaoe , Xue Mei , Zang Xiaocui , Wu Fengchun , Xiu Meihong , Zhang Xiangyang
Published: July 2023

Objective

Despite advances in pharmacology, the treatment of schizophrenia (SZ) remains a challenge due to relapse after antipsychotic discontinuation and multiple adverse effects of antipsychotics. We hypothesized that a low dose of risperidone in combination with sertraline would reduce serious adverse effects without decreasing treatment response. This study aimed to examine the efficacy, safety, and tolerability of low-dose risperidone combined with sertraline to reduce risperidone dose and serious adverse effects in first-episode and medication-naive (FEMN) SZ patients.

Methods

A total of 230 patients with FEMN SZ were randomly assigned to receive low-dose risperidone in combination with sertraline (RS group) or regular-dose risperidone (control group). The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD), and Personal and Social Performance Scale (PSP) were assessed at baseline and the end of the first, second, third, and sixth months. In addition, serum prolactin levels and extrapyramidal symptoms were measured at baseline and follow-up.

Results

Repeated measures ANCOVA showed significant interaction effects of treatment by time on psychotic symptoms, as well as HAMD, PSP scores, prolactin levels, and extrapyramidal symptoms (all p < 0.05). Compared with the control group, the RS group had greater decreases in PANSS total score and its subscores and HAMD score (all p < 0.01) and a greater increase in PSP total score (p < 0.01). Notably, side effects were lower in the RS group relative to the control group. Improvements in HAMD and PANSS total scores, changes in prolactin levels and gender predicted improvements in PSP from baseline to month 6.

Conclusions

Our study suggests that low-dose risperidone in combination with sertraline was more effective for psychotic symptoms and psychosocial functioning, with significantly fewer adverse effects in patients with FEMN SZ.

Trial registration number: ClinicalTrials.gov, NCT04076371
Association of impaired sensitivity to thyroid hormones with hyperuricemia through obesity in the euthyroid population
Authors: Wu Zhiyuan , Jiang Yue , Li Pingan , Wang Yutao , Zhang Haiping , Li Zhiwei , Li Xia , Tao Lixin , Gao Bo , Guo Xiuhua
Published: July 2023

Background

Impaired sensitivity to thyroid hormones is a newly proposed clinical entity associated with hyperuricemia in the subclinical hypothyroid population. However, it is unknown whether the association exists in the euthyroid population. This study aimed to explore the association of impaired sensitivity to thyroid hormones (assessed by the thyroid feedback quantile-based index [TFQI], parametric thyroid feedback quantile-based index [PTFQI], thyrotrophic thyroxine resistance index [TT4RI] and thyroid-stimulating hormone index [TSHI]) with hyperuricemia and quantify the mediating effect of body mass index BMI in the euthyroid population.

Methods

This cross-sectional study enrolled Chinese adults aged ≥ 20 years who participated in the Beijing Health Management Cohort (2008–2019). Adjusted logistic regression models were used to explore the association between indices of sensitivity to thyroid hormones and hyperuricemia. Odds ratios [OR] and absolute risk differences [ARD] were calculated. Mediation analyses were performed to estimate direct and indirect effects through BMI.

Results

Of 30,857 participants, 19,031 (61.7%) were male; the mean (SD) age was 47.3 (13.3) years; and 6,515 (21.1%) had hyperuricemia. After adjusting for confounders, individuals in the highest group of thyroid hormone sensitivity indices were associated with an increased prevalence of hyperuricemia compared with the lowest group (TFQI: OR = 1.18, 95% CI 1.04–1.35; PTFQI: OR = 1.20, 95% CI 1.05–1.36; TT4RI: OR = 1.17, 95% CI 1.08–1.27; TSHI: OR = 1.12, 95% CI 1.04–1.21). BMI significantly mediated 32.35%, 32.29%, 39.63%, and 37.68% of the associations of TFQI, PTFQI, TT4RI and TSHI with hyperuricemia, respectively.

Conclusions

Our research revealed that BMI mediated the association between impaired sensitivity to thyroid hormones and hyperuricemia in the euthyroid population. These findings could provide useful evidence for understanding the interaction between impaired sensitivity to thyroid hormone and hyperuricemia in euthyroid individuals and suggest the clinical implications of weight control in terms of impaired thyroid hormones sensitivity.
The promoting effect and mechanism of Nrf2 on cell metastasis in cervical cancer
Authors: Zhang Mengwen , Hong Xiaoling , Ma Ning , Wei Zhentong , Ci Xinxin , Zhang Songling
Published: July 2023

Background

Cervical cancer (CC) has poor prognosis and high mortality rate for its metastasis during the disease progression. Epithelial-mesenchymal transition (EMT) and anoikis are initial and pivotal steps during the metastatic process. Although higher levels of Nrf2 are associated with aggressive tumor behaviors in cervical cancer, the detailed mechanism of Nrf2 in cervical cancer metastasis, especially EMT and anoikis, remains unclear.

Methods

Immunohistochemistry (IHC) was used to examine Nrf2 expression in CC. Wound healing assay and transwell analysis were used to evaluate the migration ability of CC cells. Western blot, qTR-PCR and immunofluorescent staining were used to verify the expression level of Nrf2, the EMT associated markers and anoikis associated proteins. Flow cytometry assays and cell counting were used to detect the apoptosis of cervical cancer cells. The lung and lymph node metastatic mouse model were established for studies in vivo. The interaction between Nrf2 and Snail1 was confirmed by rescue-of-function assay.

Results

When compared with cervical cancer patients without lymph node metastasis, Nrf2 was highly expressed in patients with lymph node metastasis. And Nrf2 was proved to enhance the migration ability of HeLa and SiHa cells. In addition, Nrf2 was positively correlated with EMT processes and negatively associated with anoikis in cervical cancer. In vivo, a xenograft assay also showed that Nrf2 facilitated both pulmonary and lymphatic distant metastasis of cervical cancer. Rescue-of-function assay further revealed the mechanism that Nrf2 impacted the metastasis of CC through Snail1.

Conclusion

Our fundings established Nrf2 plays a crucial role in the metastasis of cervical cancer by enhancing EMT and resistance to anoikis by promoting the expression of Snail1, with potential value as a therapeutic candidate.
Caudal DMN neurons innervate the spleen and release CART peptide to regulate neuroimmune function
Authors: Kobori Nobuhide , Moore Anthony N. , Redell John B. , Dash Pramod K.
Published: July 2023

Background

Inflammation is a fundamental biological response to injury and infection, which if unregulated can contribute to the pathophysiology of many diseases. The vagus nerve, which primarily originates from the dorsal motor nucleus (DMN), plays an important role in rapidly dampening inflammation by regulating splenic function. However, direct vagal innervation of the spleen, which houses the majority of immune and inflammatory cells, has not been established. As an alternative to direct innervation, an anti-inflammatory reflex pathway has been proposed which involves the vagus nerve, the sympathetic celiac ganglion, and the neurotransmitter norepinephrine. Although sympathetic regulation of inflammation has been shown, the interaction of the vagus nerve and the celiac ganglia requires a unique interaction of parasympathetic and sympathetic inputs, making this putative mechanism of brain–spleen interaction controversial.

Body

As neuropeptides can be expressed at relatively high levels in neurons, we reasoned that DMN neuropeptide immunoreactivity could be used to determine their target innervation. Employing immunohistochemistry, subdiaphragmatic vagotomy, viral tract tracing, CRISPR-mediated knock-down, and functional assays, we show that cocaine and amphetamine-regulated transcript (CART) peptide-expressing projection neurons in the caudal DMN directly innervate the spleen. In response to lipopolysaccharide (LPS) stimulation, CART acts to reduce inflammation, an effect that can be augmented by intrasplenic administration of a synthetic CART peptide. These in vivo effects could be recapitulated in cultured splenocytes, suggesting that these cells express the as yet unidentified CART receptor(s).

Conclusion

Our results provide evidence for direct connections between the caudal DMN and spleen. In addition to acetylcholine, these neurons express the neuropeptide CART that, once released, acts to suppress inflammation by acting directly upon splenocytes.
An unusual case of huge fibrotic sac of hematoma at saphenous vein harvest site for coronary artery bypass grafting: a case report
Authors: Lee June , Na Hye Rim , Hong Seok Beom , Kim Do Yeon , Kim Hwan Wook , Kim Yong Han
Published: July 2023

Great saphenous vein is a conduit commonly used for coronary artery bypass grafting. However, several complications could occur at leg wound site for vein harvesting. Here, we describe a huge sac of hematoma as an uncommon complication of saphenous vein harvest for coronary artery bypass grafting.

A 62-year-old gentleman was readmitted with swelling at left thigh 30 days after coronary artery bypass grafting. Lower extremity computed tomography was suggestive of an oval and thick sac implying a hematoma or seroma. After using ultrasound scanning for the mass, an incision through the previous surgical wound showed a huge mass. Inspection after incision the mass revealed an old hematoma within the sac.

Pathologic findings demonstrated chronic inflammation with the hematoma surrounded by a fibrotic sac. The patient’s postoperative course was uneventful without recurrence.

Our experience suggests the possibility of a huge hematoma within a thick fibrotic sac at the previous vein harvest site for coronary artery bypass grafting.
Optogenetic dissection of RET signaling reveals robust activation of ERK and enhanced filopodia-like protrusions of regenerating axons
Authors: Hyeon Bobae , Lee Heeyoung , Kim Nury , Heo Won Do
Published: July 2023

RET (REarranged during Transfection) is a receptor tyrosine kinase that transduces various external stimuli into biological functions, such as survival and differentiation, in neurons. In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET, combining the cytosolic region of human RET with a blue-light–inducible homo-oligomerizing protein. By varying the duration of photoactivation, we were able to dynamically modulate RET signaling. Activation of optoRET recruited Grb2 (growth factor receptor-bound protein 2) and stimulated AKT and ERK (extracellular signal-regulated kinase) in cultured neurons, evoking robust and efficient ERK activation. By locally activating the distal part of the neuron, we were able to retrogradely transduce the AKT and ERK signal to the soma and trigger formation of filopodia-like F-actin structures at stimulated regions through Cdc42 (cell division control 42) activation. Importantly, we successfully modulated RET signaling in dopaminergic neurons of the substantia nigra in the mouse brain. Collectively, optoRET has the potential to be developed as a future therapeutic intervention, modulating RET downstream signaling with light.
Role of protein tyrosine phosphatase receptor type M in epithelial ovarian cancer progression
Authors: Li Xiao , Ding Wei , Rao Yang , Qu Pengpeng
Published: July 2023

Background

Epithelial ovarian cancer (EOC) is often diagnosed at advanced stages with low survival rates. Protein tyrosine phosphatase receptor type M (PTPRM) is involved in cancer development and progression; however, its role in EOC remains unclear. In this study,we aimed to detect PTPRM expression in ovarian epithelial tumors, analyze its relationship with the clinicopathological features and survival prognosis of patients with EOC, and provide a theoretical basis for new targets for EOC treatment. Fifty-seven patients with EOC treated at our hospital between January 2012–January 2014 were included; along with 18 borderline and 30 benign epithelial ovarian tumors and 15 normal ovarian and uterine tube tissue samples from patients surgically treated at our hospital during the same period. PTPRM expression was immunohistochemically detected, and we analyzed its relationship with clinicopathological features and prognosis. Associations between PTPRM expression and survival prognosis of patients with EOC were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter databases.

Results

PTPRM had the highest expression rates in normal ovarian and uterine tube tissues, followed by benign and borderline epithelial ovarian tumors; the lowest positive expression rate was observed in EOC tumors. PTPRM expression differed significantly among groups (P < 0.05). The positive PTPRM expression rate significantly decreased with age, progressing clinical stage, and tumor recurrence, and the larger the mass diameter, the higher the positive PTPRM expression rate. PTPRM expression was significantly lower in ovarian cancer compared with that in normal tissues in the GEPIA database (P < 0.05). The overall survival (OS) and disease-free survival(DFS) rates were higher in the PTPRM high-expression group, with statistically significant (P < 0.05) and insignificant (P > 0.05) differences, respectively. The OS rate of the high-expression group compared with the low-expression group in the Kaplan–Meier Plotter database was higher, although without statistical significance (P > 0.05), and progression-free survival(PFS) was higher with statistical significance (P < 0.05).

Conclusion

PTPRM expression was low in patients with EOC, and the PTPRM positive-expression rate significantly decreased with progressing stages of EOC and tumor recurrence, suggesting that PTPRM acts as a tumor suppressor in EOC progression. Negative PTPRM expression may predict poor clinical outcomes in patients with EOC.
Characterization of large-scale genomic differences in the first complete human genome
Authors: Yang Xiangyu , Wang Xuankai , Zou Yawen , Zhang Shilong , Xia Manying , Fu Lianting , Vollger Mitchell R. , Chen Nae-Chyun , Taylor Dylan J. , Harvey William T. , Logsdon Glennis A. , Meng Dan , Shi Junfeng , McCoy Rajiv C. , Schatz Michael C. , Li Weidong , Eichler Evan E. , Lu Qing , Mao Yafei
Published: July 2023

Background

The first telomere-to-telomere (T2T) human genome assembly (T2T-CHM13) release is a milestone in human genomics. The T2T-CHM13 genome assembly extends our understanding of telomeres, centromeres, segmental duplication, and other complex regions. The current human genome reference (GRCh38) has been widely used in various human genomic studies. However, the large-scale genomic differences between these two important genome assemblies are not characterized in detail yet.

Results

Here, in addition to the previously reported “non-syntenic” regions, we find 67 additional large-scale discrepant regions and precisely categorize them into four structural types with a newly developed website tool called SynPlotter. The discrepant regions (~ 21.6 Mbp) excluding telomeric and centromeric regions are highly structurally polymorphic in humans, where the deletions or duplications are likely associated with various human diseases, such as immune and neurodevelopmental disorders. The analyses of a newly identified discrepant region—the KLRC gene cluster—show that the depletion of KLRC2 by a single-deletion event is associated with natural killer cell differentiation in ~ 20% of humans. Meanwhile, the rapid amino acid replacements observed within KLRC3 are probably a result of natural selection in primate evolution.

Conclusion

Our study provides a foundation for understanding the large-scale structural genomic differences between the two crucial human reference genomes, and is thereby important for future human genomics studies.
Agreement between questions about physical activity and sitting time, and device-based measures, used in Swedish targeted health dialogues in the context of primary health care
Authors: Johansson Lisbeth M. , Lingfors Hans , Golsäter Marie , Rolander Bo , Fransson Eleonor I.
Published: July 2023

Background

It is important that easy-to-use measures like subjective questions about physical activity (PA) and sedentary behaviour are valid and reliable providing accurate measures, when they are used in health promotion work aiming to support people to improve their lifestyle habits such as PA. The aim of this study was to evaluate the concurrent validity of a structured interview form estimating self-reported PA and a question about sitting time used in Swedish targeted health dialogues in the context of primary health care.

Method

The study was conducted in the southern part of Sweden. To evaluate concurrent validity of the interview form, time spent in moderate-to-vigorous physical activities (MVPA) and energy expenditure related to MVPA estimated by an interview form was compared with the same measures assessed by an ActiGraph GT3X-BT accelerometer. To evaluate a question about sitting time, the Swedish School of Sport and Health Sciences’ single-item question about sitting time (SED-GIH) was compared with measures from an activPAL inclinometer. Statistical analyses included deriving Bland‒Altman plots and calculating Spearman’s rank correlation coefficients.

Result

Bland‒Altman plots indicated lower absolute variation in the difference between self-reported and device-based PA measures for lower PA levels, both for energy expenditure and time spent in MVPA. No systematic over- or underestimation was observed. The Spearman’s correlation coefficient between self-reported and device-based PA measures was 0.27 (p = 0.014) for time spent in MVPA and 0.26 (p = 0.022) for energy expenditure. The correlation coefficient between the single item question and device-based sitting time measures was 0.31 (p = 0.002). Sitting time was underestimated by 74% of the participants.

Conclusion

The PA interview form and the SED-GIH question on sitting time may be of value in targeted health dialogues in primary health care with the intention to support sedentary and insufficiently physically active persons in increasing their physical activity and limiting their sitting time. The questionnaires are easy to use and are more cost effective than device-based measures, especially regarding population-based interventions conducted in primary health care for thousands of participants such as targeted health dialogues.

Clinical trial registration

Not applicable.
Evaluation of the performance of the IFN-γ release assay in bovine tuberculosis free herds from five European countries
Authors: Gomez-Buendia Alberto , Romero Beatriz , Bezos Javier , Saez José Luis , Archetti Ivonne , Pacciarini Maria Lodovica , Boschiroli Maria Laura , Girard Sébastien , Gutu Emanuela , Barbuceanu Florica , Karaoulani Ourania , Stournara Athanasia , de Juan Lucia , Alvarez Julio
Published: July 2023

The diagnostic methods for granting and maintenance of the official tuberculosis-free (OTF) status and for intra-Community movement of cattle are the tuberculin skin tests (single or comparative) and the interferon-γ (IFN-γ) release assay (IGRA). However, until now, IGRAs have been primarily applied in infected farms in parallel to the skin test to maximize the number of infected animals detected. Therefore, an evaluation of the performance of IGRAs in OTF herds to assess whether if their specificity is equal to or higher than that of the skin tests is needed. For this, a panel of 4365 plasma samples coming from 84 OTF herds in six European regions (five countries) was assembled and analysed using two IGRA kits, the ID Screen® Ruminant IFN-g (IDvet) and the Bovigam™ TB Kit (Bovigam). Results were evaluated using different cut-offs, and the impact of herd and animal-level factors on the probability of positivity was assessed using hierarchical Bayesian multivariable logistic regression models. The percentage of reactors ranged from 1.7 to 21.0% (IDvet: S/P ≥ 35%), and 2.1–26.3% (Bovigam: ODbovis–ODPBS ≥ 0.1 and ODbovis–ODavium ≥ 0.1) depending on the region, with Bovigam disclosing more reactors in all regions. The results suggest that specificity of IGRAs can be influenced by the production type, age and region of origin of the animals. Changes in the cut-offs could lead to specificity values above 98–99% in certain OTF populations, but no single cut-off yielding a sufficiently high specificity (equal or higher than that of skin tests) in all populations was identified. Therefore, an exploratory analysis of the baseline IFN-γ reactivity in OTF populations could help to assess the usefulness of this technique when applied for the purpose of maintaining OTF status.
Tolerance of clinical vancomycin-resistant Enterococcus faecium isolates against UV-C light from a mobile source
Authors: Knobling B. , Franke G. , Belmar Campos C. , Büttner H. , Christner M. , Klupp E. M. , Maurer P. M. , Knobloch J. K.
Published: July 2023

Background

Admission to a room previously occupied by patients carrying environmentally robust pathogens implies an increased risk of acquiring those pathogens. Therefore, ‘No-touch’ automated room disinfection systems, including devices based on UV-C irradiation, are discussed to improve terminal cleaning. It is still unclear if clinical isolates of relevant pathogens behave differently under UV-C irradiation compared to laboratory strains used in the approval process of disinfection procedures. In this study we analysed the susceptibility of well characterized clonally divergent vancomycin-resistant enterococci (VRE) strains, including a linezolid-resistant isolate, against UV-C radiation.

Methods

Susceptibility against UV-C of ten clonally divergent clinical isolates of VRE was determined in comparison to the commonly used test organism Enterococcus hirae ATCC 10541. Ceramic tiles contaminated with 105 to 106 colony forming units/25 cm² of the different enterococci were positioned at a distance of 1.0 and 1.5 m and irradiated for 20 s, resulting in a UV-C dose of 50 and 22 mJ/cm², respectively. Reduction factors were calculated after quantitative culture of the bacteria recovered from treated and untreated surfaces.

Results

Susceptibility to UV-C varied considerably among the strains studied, with the mean value of the most robust strain being up to a power of ten lower compared to the most sensitive strain at both UV-C doses. The two most tolerant strains belonged to MLST sequence types ST80 and ST1283. The susceptibility of the laboratory strain E. hirae ATCC 10541 ranged between the most sensitive and most tolerant isolates for both irradiation doses. However, for UV-C dose of 22 mJ/cm², the reduction of the most tolerant isolate of ST1283 was statistically significantly lower compared to E. hirae ATCC 10541. The most susceptible strains belonged to the MLST sequence types ST117 and ST203.

Conclusions

These results indicate that UV-C doses reported in the literature are sufficient for the reduction of commonly used reference strains of enterococci but could be insufficient for the reduction of tolerant patient VRE-isolates in a hospital setting. Therefore, for future studies, the most tolerant clinical isolates should be used to validate automated UV-C devices or longer exposure times should be expected to ensure efficacy in the real world.
Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas
Authors: Chang Ya-Sian , Tu Siang-Jyun , Chen Hong-Da , Chung Chin-Chun , Hsu Ming-Hon , Chou Yu-Pao , Lee Ya-Ting , Yen Ju-Chen , Jeng Long-Bin , Chang Jan-Gowth
Published: July 2023

Background

Comprehensive and integrative analysis of hepatocellular carcinoma (HCC) is important. In this study, we explored Taiwanese HCCs using multi-omics analyses.

Methods

We analyzed 254 HCCs by whole genome sequencing and total RNA sequencing, and then used bioinformatic tools to analyze genomic and transcriptomic alterations in coding and non-coding sequences to explore the clinical importance of each sequence.

Results

The frequencies of the five most commonly mutated cancer-related genes were TERT, TP53, CTNNB1, RB1, and ARID1A. Genetic alteration frequencies influenced the etiology of HCC; some alterations were also correlated with clinicopathological conditions. Many cancer-related genes had copy number alterations (CNAs) and structure variants (SVs) that changed according to etiology and exhibited potential associations with survival. We also identified several alterations in histone-related genes, HCC-related long non-coding RNAs, and non-coding driver genes that may contribute to the onset and progression of HCC. Transcriptomic analysis revealed that 229 differentially expressed and 148 novel alternative splicing (AS) genes, as well as the presence of fusion genes, were associated with patient survival. Moreover, somatic mutations, CNAs, and SVs were associated with immune checkpoint gene expression and tumor microenvironment. Finally, we identified relationships among AS, immune checkpoint gene expression and tumor microenvironment.

Conclusions

This study shows that genomic alterations are associated with survival, including DNA-based and RNA-based data. Moreover, genomic alterations and their associations with immune checkpoint genes and the tumor microenvironment may provide novel insights for the diagnosis and treatment of HCC.
Peer counselling as an approach to improve complementary feeding practices: a narrative review
Authors: Haque Nabila Binte , Mihrshahi Seema , Haider Rukhsana
Published: July 2023

Background

Appropriate complementary feeding can help reduce the risk of malnutrition and is especially important in Asian and African countries. Peer counselling has been used as an approach to improve complementary feeding practices and is often combined with other interventions, like food fortification or supplements, or as a part of broader nutrition education program. The aim of this narrative review is to assess the effectiveness of peer counselling on improving complementary feeding practices in Asian and African countries.

Methods

We searched through seven electronic databases: CINAHL, MEDLINE (OVID), PubMed, Embase, Web of Science, the Cochrane Library and WHO Global Health library from 2000 to April 2021, and had the following inclusion criteria. Studies were included if they were community- or hospital-based, had infants aged 5–24 months old, had individual or group peer counselling, and the effects of peer counselling on complementary feeding practices were measured. Methodological quality was assessed using the Joanna Briggs Institute’s critical appraisal checklist for evidence studies.

Results

Out of 6 studies that met the above criteria, 3 studies were randomised controlled trials and 3 were quasi-experimental studies. In Bangladesh, India, Nepal and Somalia, peer counselling was found to be effective in improving timely initiation of complementary feeding, minimum meal frequency and minimum dietary diversity in all of our selected studies. In addition, improvement in breastfeeding practices, complementary foods preparation, hygiene, psychological stimulation for cognitive development of children and mothers’ understanding of hunger cues were observed in some of our selected studies.

Conclusions

This review evaluates the effectiveness of peer counselling to improve complementary feeding practices in Asian and African countries. Peer counselling improves timely complementary feeding and ensures the correct proportions and consistency of foods including adequate amounts of food is given. Other important complementary feeding indicators like minimum dietary diversity, minimum meal frequency and minimum acceptable diet can also be increased through peer-counselling interventions. Peer counselling is well known to enhance the rate of breastfeeding practices, but this review suggests it is also effective for complementary feeding and may inform future nutrition programs to extend the length of peer counselling for mothers.
A comparison between incremental lines of cementum and aspartic acid racemization in age estimation: histological and biochemical study
Authors: Moawed Dena Mohamed Naguib Abdel , Ibrahim Nadia Mohsen Ali , Eid Ibrahim Mohamed , Soliman Amir , Mostafa Heba El-Sayed
Published: July 2023

Background

Age estimation is a vital aspect of the identification of an individual in forensic science. Teeth are one of the toughest structures in the human body and generally survive postmortem destruction. So, they can therefore be used more reliably than any other morphological or histological trait of the adult skeleton for estimating age.

Aim of the study

The present work aimed to compare cementum incremental lines and aspartic acid racemization in age estimation among Egyptian subjects.

Methods

Sixty-four subjects were assigned to two groups: males and females (each with 32 cases) to determine the effect of sex as a possible factor that might affect age estimation. For each group, in all subjects, age was estimated using histologic examination of ground, unstained section teeth by light and polarized microscopes, in addition to estimating the rate of aspartic acid racemization in the collagen of dentin by using the HPLC method.

Results

There was a statistically significant correlation between each method of age estimation and chronological age. However, the strongest degree of correlation was observed for the racemization method, with a correlation coefficient of r = 0.99 (95% CI 0.98 to 0.99), followed by the light method, r = 0.94 (95% CI 0.90 to 0.96), and the polarized method, r = 0.93 (95% CI 0.88 to 0.95).

Conclusions

Both methods, cementum incremental lines and aspartic acid racemization, could help in age estimation, but aspartic acid racemization is more reliable and accurate.