bluuebunny/crossref_metadata_2025 huggingface dataset:
Progressive osseous heteroplasia in a 5-year-old boy with a novel mutation in exon 2 of GNAS: a case presentation and literature review
Authors: Ma Jing , Mo Wenxiu , Sun Jiapeng , Li Yan , Han Tongxin , Mao Huawei
Published: April 2023

Background

Progressive osseous heteroplasia (POH) is a rare genetic condition that causes progressive ossification. This usually results from an inactivating mutation of the paternal GNAS gene. Herein, we report a case of POH caused by a novel mutation in exon 2 of the GNAS gene.

Case presentation

A 5-year-old Chinese boy was referred to our hospital for a growing mass in his right foot. Although laboratory findings were normal, radiographic imaging revealed severe ossification in his right foot and smaller areas of intramuscular ossification in his arms and legs. A de novo mutation (c.175C > T, p.Q59X) in exon 2 of the GNAS gene was identified, prompting a diagnosis of POH. We conducted a systematic literature review to better understand this rare disease.

Conclusion

We have discovered that a de novo nonsense mutation in exon 2 of GNAS can lead to POH. Our literature review revealed that ankylosis of the extremities is the primary clinical outcome in patients with POH. Unlike other conditions such as fibrodysplasia ossificans progressiva (FOP), patients with POH do not experience respiratory failure. However, much remains to be learned about the relationship between the type of GNAS gene mutation and the resulting POH symptoms. Further research is needed to understand this complex and rare disease. This case adds to our current understanding of POH and will contribute to future studies and treatments.
Association between obesity and cervical intraepithelial neoplasia: results from a case control study in south western Uganda
Authors: Ssedyabane Frank , Ngonzi Joseph , Kajabwangu Rogers , Najjuma Josephine Nambi , Tusubira Deusdedit , Randall Thomas C
Published: April 2023

Background

Though obesity has been said to be associated with a number of malignancies including cervical cancer, its association with cervical intraepithelial neoplasia (CIN) is still a contentious issue. This study was designed to determining the prevalence and association between obesity and CIN.

Methods

This was an unmatched case control study, involving women with cervical intraepithelial neoplasia (cases) and those negative for intraepithelial lesions or malignancy (controls) at the cervical cancer clinic of Mbarara Regional Referral Hospital, in south-western Uganda, between April and November 2022. Cases and controls provided written informed consent and were recruited in a ratio of 1:1. Cases were identified by visual inspection with acetic acid (VIA) and subsequent confirmation with cytology and/or histology. Demographic information was collected using an enrolment form and height, weight and waist circumference were recorded. We calculated body mass index (BMI) and identified obese women as those with body mass index of ≥ 30 kg/m2 from both case and control groups. Central obesity was defined as waist: height ration of ≥ 0.5. Data was analysed using STATA version 17. Categorical variables were analysed using proportions, chi-square and logistic regression analysis to determine association between obesity and CIN. Our level of statistical significance was set at ≤ 0.05.

Results

The prevalence of general and central obesity among cases was 25.5% (24/94) and 0% (0/94) respectively while the prevalence of general and central obesity among controls was 33.3% (37/111) and 0% (0/111) respectively. There was an increased prevalence of general obesity among women with low grade squamous intraepithelial lesions (LSIL). However, there was no statistically significant association between general obesity and CIN. Factors associated with general obesity included residing in Mbarara city (AOR 2.156, 95%CI 1.085–4.282, P-value 0.028), age group of 31–45 years (AOR 2.421, 95%CI 1.577–9.705, P-value 0.003) and ≥ 46 years (AOR 1.971, 95%CI 1.022–11.157, P-value 0.046).

Conclusion

We observed an increased prevalence of general obesity among women with LSIL. However, there was no association between obesity and CIN. Factors associated with general obesity included residing in Mbarara city, and being in the age groups of 31–40 and ≥ 46 years. This highlights the need to rethink management of CIN to control other non-communicable diseases that could arise due to general obesity.
Are students performing the same in E-learning and In-person education? An introspective look at learning environments from an Iranian medical school standpoint
Authors: Mastour Haniye , Emadzadeh Ali , Hamidi Haji Abadi Omid , Niroumand Shabnam
Published: April 2023

Introduction

This study investigated medical students’ intended learning outcomes based on e-learning and in-person education.

Methods

In this cross-sectional comparative analytical study, a group of 126 undergraduate medical students’ intended learning outcomes under two different teaching methods, including e-learning and in-person, were repeatedly measured based on the census sampling method. Participants were in the preclinical curriculum phase (physiopathology) at Mashhad University of Medical Sciences (MUMS), Iran. Due to expert panel opinion, the same medical teachers and similar difficulty of lessons were considered in two investigated academic semesters. In addition, difficulty and discrimination indexes of formative and summative assessments were controlled for two study groups. The students’ learning outcome index was the knowledge test scores participants received in the relevant lessons of the General Medicine (GM) curriculum preclinical courses.

Results

The findings indicated that students learning outcomes were significantly higher during e-learning than in in-person education for all examined variables (P < 0.05). Moreover, the difference between students’ Grade Point Average (GPA) categories among the two groups was significant (P = 0.022). Students with a GPA of less than 14 experienced higher increments in their average scores after the e-learning compared to in-person education. Compared to face-to-face courses, improvements in pharmacology, theoretical semiology, and pathology scores after e-learning courses were statistically significant (P < 0.001). The differences in mean scores related to practical pathology and semiology in the two approaches were not statistically significant, P = 0.624 and P = 0.149, respectively. Furthermore, the overall students’ average scores increased significantly during e-learning versus in-person education (P < 0.001).

Conclusion

We concluded that e-learning could be appreciated as a successful method of medical education and can be used as an alternative educational method. However, considering the importance of practical or clinical courses in medical education, further research about the efficacy of the e-learning approach is highly recommended.
Measurement of person-centred consultation skills among healthcare practitioners: a systematic review of reviews of validation studies
Authors: van Dongen Anne , Stewart Duncan , Garry Jack , McCambridge Jim
Published: April 2023

Background

Person-centred care is integral to high-quality health service provision, though concepts vary and the literature is complex. Validated instruments that measure person-centred practitioner skills, and behaviours within consultations, are needed for many reasons, including in training programmes. We aimed to provide a high-level synthesis of what was expected to be a large and diverse literature through a systematic review of existing reviews of validation studies a of instruments that measure person-centred practitioner skills and behaviours in consultations. The objectives were to undertake a critical appraisal of these reviews, and to summarise the available validated instruments and the evidence underpinning them.

Methods

A systematic search of Medline, EMBASE, PsycINFO and CINAHL was conducted in September 2020. Systematic reviews of validation studies of instruments measuring individual practitioner person-centred consultation skills or behaviours which report measurement properties were included. Review quality was assessed with the Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. Details of the reviews, the included validation studies, and the instruments themselves are tabulated, including psychometric data, and a narrative overview of the reviews is provided.

Results

Four reviews were eligible for inclusion. These used different conceptualisations of person-centredness and targeted distinct, sometimes mutually exclusive, practitioners and settings. The four reviews included 68 unique validation studies examining 42 instruments, but with very few overlaps. The critical appraisal shows there is a need for improvements in the design of reviews in this area. The instruments included within these reviews have not been subject to extensive validation study.

Discussion

There are many instruments available which measure person-centred skills in healthcare practitioners and this study offers a guide to what is available to researchers and research users. The most relevant and promising instruments that have already been developed, or items within them, should be further studied rigorously. Validation study of existing material is needed, not the development of new measures.
How to choose a preceptor: aspects to consider based on a grounded theory study
Authors: Amaral Guida , Figueiredo Amélia Simões
Published: April 2023

Background

Nurses in clinical practice settings share responsibility with academy teachers in the education of nursing students in clinical teaching. This dynamic is essential for the students’ learning and their skill development. During preceptorship, the nurse has to mobilize the available resources to act competently and effectively. The purpose of this article is to identify the aspects that should be considered when selecting a nurse preceptor.

Methods

A qualitative study was carried out based on Grounded Theory using Strauss and Corbin’s version. The study took place in a medicine ward and a surgery ward of a hospital in the Lisbon metropolitan area. The authors conducted fourteen semi-structured interviews with nurses who were at different stages of Benner’s Professional Development Model and with different outlooks on nursing preceptorship. The initial script was reorganized after the pilot test. It was also adjusted after the first exploratory interviews and after the in-depth interviews in order to reflect the interviewees’ work experience and outlooks on preceptorship. The interviews had an average duration of 45 min and were audio recorded. Theoretical sampling was conducted considering the needs identified in data coding until we reached theoretical saturation. Data analysis began after the first interview, first by open coding, followed by axial and selective coding, always in a logic of constant comparison with theory. Ethical principles, scientific integrity and methodological rigour were ensured throughout the study.

Results

Two categories emerged that were supported by all nurses: skills and individual characteristics. The former includes communication skills, relational skills, reflective skills, technical-scientific skills, and emotional skills, while the latter includes perceptiveness, responsibility, motivation, and professional initiative.

Conclusion

Nurses value both the individual characteristics they possess and the skills they have developed throughout their career. The recognition of the aspects found in this study for the selection of nurse preceptors allows for an informed and reasoned decision making, with a view to the success of the preceptorship and to the improvement of the quality of nursing education.
Association of pain management and positive expectations with psychological distress and spiritual well‑being among terminally ill cancer patients admitted to a palliative care unit
Authors: Yang Yilong , Cui Meng , Zhao Xinxin , Wang Simeng , Wang Yumei , Wang Xiaohe
Published: April 2023

Background

Although palliation of psycho-spiritual distress is of great importance in terminally ill cancer patients, there is a little information about screening patients who benefit from palliative care and identifying the cancer care targets. This study explored the relationship of pain management and positive expectations with depression, anxiety and spiritual well-being (SWB) in terminal cancer patients admitted to a palliative care unit.

Methods

Eighty-four terminal cancer inpatients were recruited from the Hospice Ward, Shengjing Hospital of China Medical University. Optimism and general self-efficacy (GSE) were evaluated at admission. Patients completed self-report questionnaires on SWB, depression, anxiety and pain both on admission and one week later. The repeated designed analysis of variance was used to explore the correlates of depression, anxiety and SWB (meaning, peace, faith).

Results

In our sample, only cancer pain diminished significantly one week later. For depression (p = 0.041) and faith (p = 0.013), there was a significant pain group (relieved vs. not relieved) × time interaction effect, such that those with satisfied pain control experienced the improved psycho-spiritual outcomes at 1 week. The relationship between positive expectations, peace and faith was also statistically significant, indicating that the improvement of peace or faith was significant in the low group of optimism and GSE.

Conclusions

Our findings indicated that pain management lied at the center of depression and SWB, meaning that effective pain management may reduce depression, and improve SWB among terminal cancer patients. Moreover, positive expectations, especially for optimism, may be the new target for SWB-related intervention research. Palliative care nurse should require the identification of terminal cancer patients who may more benefit from short-term palliative care, and target them with effective cancer care.
Overcoming the struggle of living with type 2 diabetes – diabetes specialist nurses’ and patients’ perspectives on digital interventions
Authors: Jarl Frida , Davelid Anna , Hedin Katarina , Stomby Andreas , Petersson Christina
Published: April 2023

Background

Diabetes self-management education and support (DSMES) is a cornerstone in the treatment of type 2 diabetes mellitus (T2DM). It is unclear whether delivering DSMES as a digital health intervention (DHI) might meet the needs experienced by patients with T2DM and diabetes specialist nurses (DSN) of the primary health care system in Sweden.

Methods

Fourteen patients with T2DM and four DSN participated in three separate focus groups: two groups comprised patients and one group comprised DSN. The patients discussed the questions: “What needs did you experience after your T2DM diagnosis?” and “How might these needs be met with a DHI?” The DSN discussed the questions: “What needs do you experience when treating a patient with newly diagnosed T2DM?” and “How might these needs be met with a DHI?”. Furthermore, data were collected in the form of field notes from group discussions at a meeting including 18 DSNs working with T2DM in PHCCs. The discussions from focus groups were transcribed verbatim and analyzed together with the field notes from the meeting using inductive content analysis.

Results

The analysis yielded the overall theme: “Overcoming the struggle of living with T2DM”, which was summarized in two categories: “learning and being prepared” and “giving and receiving support”. Important findings were that, for success, a DHI for DSMES must be integrated into routine care, provide structured, high-quality information, suggest tasks to stimulate behavioral changes, and provide feedback from the DSN to the patient.

Conclusion

This study highlighted several important aspects, from the perspectives of both the patient with T2DM and the DSN, which should be taken into consideration for the successful development and use of a DHI for DSMES.
The willingness and attitudes of speech-language pathologists towards the use of mobile health technology: a survey study
Authors: Saeedi Soheila , Ghazisaeedi Marjan , Ebrahimi Maryam , Seifpanahi Mohammad-Sadegh , Bouraghi Hamid
Published: April 2023

Background

Mobile health (mHealth) technology could be used in different ways to treat various speech and language disorders. The attitude of speech-language pathologists (SLPs) towards this technology and their willingness to use it can play a significant role in the success of the therapies they provide. This study was conducted to investigate the willingness and attitude of SLPs towards the use of mHealth technology.

Methods

This cross-sectional study was conducted from September 2021 to April 2022 in Iran. A researcher-made questionnaire consisting of three parts (information related to demographic variables, attitude and willingness) was designed based on the past studies, and then given to all SLPs throughout Iran. Data were analyzed by SPSS software, using descriptive and inferential statistics (frequency, mean, Fisher’s exact test, and analysis of variance). Also, the SLPs’ willingness to use the desired technology was interpreted as a percentage as follows: 0–20% = not at all willing, 21–40% = slightly willing, 41–60% = moderately willing, 61–80% = highly willing, and above 80% = extremely willing.

Results

One hundred sixty speech-language pathologists from all over Iran participated in this study. The results showed that the willingness of 65.25% of SLPs to use the mentioned technology was at a good level, and according to the mentioned category, they had a high willingness to use this technology. In regard to the attitude of SLPs, the findings showed that SLPs believed that patients receive a higher quality of care during in-person visits than through mHealth technology. Also, this survey showed that SLPs were more inclined to use this technology to answer patients’ questions. Non-payment of services provided through mHealth technology and privacy concerns were the reasons for the lack of use of this technology by SLPs.

Conclusions

SLPs are willing to use mHealth technology after solving the related challenges, including payment of costs and privacy concerns. However, SLPs believed that this technology will not be a suitable alternative to face-to-face sessions.
Cost of childhood RSV management and cost-effectiveness of RSV interventions: a systematic review from a low- and middle-income country perspective
Authors: Wittenauer Rachel , Pecenka Clint , Baral Ranju
Published: April 2023

Background

Approximately 97% of global deaths due to RSV occur in low- and middle-income countries (LMICs). Until recently, the only licensed preventive intervention has been a shortacting monoclonal antibody (mAb), palivizumab (PVZ) that is expensive and intensive to administer, making it poorly suited for low-resource settings. Currently, new longer acting RSV mAbs and maternal vaccines are emerging from late-stage clinical development with promising clinical effectiveness. However, evidence of economic value and affordability must also be considered if these interventions are to be globally accessible. This systematic review’s objective was to summarise existing evidence on the cost-of-illness (COI) and cost-effectiveness of RSV prevention interventions in LMICs.

Methods

We conducted a systematic literature review using the Embase, MEDLINE, and Global Index Medicus databases for publications between Jan 2000 and Jan 2022. Two categories of studies in LMICs were targeted: cost-of-illness (COI) of RSV episodes and cost-effectiveness analyses (CEA) of RSV preventive interventions including maternal vaccines and long-acting mAbs. Of the 491 articles reviewed, 19 met the inclusion criteria.

Results

COI estimates varied widely: for severe RSV, the cost per episode ranged from $92 to $4114. CEA results also varied—e.g. evaluations of long-acting mAbs found ICERs from $462/DALY averted to $2971/DALY averted. Study assumptions of input parameters varied substantially and their results often had wide confidence intervals.

Conclusions

RSV represents a substantial disease burden; however, evidence of economic burden is limited. Knowledge gaps remain regarding the economic value of new technologies specifically in LMICs. Further research is needed to understand the economic burden of childhood RSV in LMICs and reduce uncertainty about the relative value of anticipated RSV prevention interventions. Most CEA studies evaluated palivizumab with fewer analyses of interventions in development that may be more accessible for LMICs.
Genetic contribution of caspase-8 variants and haplotypes to breast cancer risk and prognosis: a case-control study in Iran
Authors: Afzaljavan Fahimeh , Vahednia Elham , Barati Bagherabad Matineh , Vakili Fatemeh , Moezzi Atefeh , Hosseini Azar , Homaei Shandiz Fatemeh , Kooshyar Mohammad Mahdi , Nassiri Mohammadreza , Pasdar Alireza
Published: April 2023

Purpose

Multiple genome-wide and candidate-gene association studies have been conducted to search for common risk variants of breast cancer. Recent large meta-analyses and consolidating evidence have highlighted the role of the caspase-8 gene in breast cancer pathogenesis. Therefore, this study aimed to identify common variations and haplotypes associated with risk and overall survival of breast cancer with respect to underlying susceptibility variants in the CASP8 gene region in a group of the Iranian population.

Methods

In a case-control study with a total of 1008 samples (455 cases and 553 controls), genotyping of 12 candidate polymorphisms, consisting of rs3834129, rs2037815, rs7608692, rs12990906, rs3769821, rs6435074, rs3754934, rs3817578, rs10931936, rs1045485, rs1045487, and rs13113, were performed using PCR-based methods, including ARMS-PCR, AS-PCR, RFLP-PCR, HRM-PCR, and TaqMan-PCR.

Results

rs3834129, rs3754934, rs12990906, and rs10931936 were associated with the risk and overall survival of breast cancer. Several haplotypes were also identified an associated with a higher risk of breast cancer, including a three-SNP haplotype rs3817578-rs10931936-rs1045485 [p < 0.001, OR = 1.78(1.32–2.41)]. rs3754934-C allele showed an association with a lower risk of death in all patients [p = 0.022; HR = 0.46(0.23–0.89)] and in the hormone-receptor-positive group [p = 0.038; HR = 0.37(0.14–0.95)], as well as CC genotype in the hormone-receptor-positive group [p = 0.002; HR = 0.09(0.02–0.43)].

Conclusion

The present study suggests a diagnostic and prognostic role of CASP8 gene variations in breast cancer. The risky haplotypes are likely to have one or more underlying breast cancer susceptibility alleles. Understanding the mode of action of these alleles will aid individual-level risk prediction. It also may help identify at-risk patients to provide them with better surveillance.
Highly efficient bioconversion of icariin to icaritin by whole-cell catalysis
Authors: Lin Yu , Chen Wen-wen , Ding Bo , Guo Man , Liang Meng , Pang Hao , Wei Yu-tuo , Huang Ri-bo , Du Li-qin
Published: April 2023

Background

Icaritin is an aglycone of flavonoid glycosides from Herba Epimedii. It has good performance in the treatment of hepatocellular carcinoma in clinical trials. However, the natural icaritin content of Herba Epimedii is very low. At present, the icaritin is mainly prepared from flavonoid glycosides by α-L-rhamnosidases and β-glucosidases in two-step catalysis process. However, one-pot icaritin production required reported enzymes to be immobilized or bifunctional enzymes to hydrolyze substrate with long reaction time, which caused complicated operations and high costs. To improve the production efficiency and reduce costs, we explored α-L-rhamnosidase SPRHA2 and β-glucosidase PBGL to directly hydrolyze icariin to icaritin in one-pot, and developed the whole-cell catalytic method for efficient icaritin production.

Results

The SPRHA2 and PBGL were expressed in Escherichia coli, respectively. One-pot production of icaritin was achieved by co-catalysis of SPRHA2 and PBGL. Moreover, whole-cell catalysis was developed for icariin hydrolysis. The mixture of SPRHA2 cells and PBGL cells transformed 200 g/L icariin into 103.69 g/L icaritin (yield 95.23%) in 4 h in whole-cell catalysis under the optimized reaction conditions. In order to further increase the production efficiency and simplify operations, we also constructed recombinant E. coli strains that co-expressed SPRHA2 and PBGL. Crude icariin extracts were also efficiently hydrolyzed by the whole-cell catalytic system.

Conclusions

Compared to previous reports on icaritin production, in this study, whole-cell catalysis showed higher production efficiency of icaritin. This study provides promising approach for industrial production of icaritin in the future.
A novel NHEJ gene signature based model for risk stratification and prognosis prediction in hepatocellular carcinoma
Authors: Lin Zhu , Huang Zhenkun , Shi Yunxing , Yuan Yichuan , Niu Yi , Li Binkui , Yuan Yunfei , Qiu Jiliang
Published: April 2023

Background

Non-homologous DNA end joining (NHEJ) is the predominant DNA double-strand break (DSB) repair pathway in human. However, the relationship between NHEJ pathway and hepatocellular carcinoma (HCC) is unclear. We aimed to explore the potential prognostic role of NHEJ genes and to develop an NHEJ-based prognosis signature for HCC.

Methods

Two cohorts from public database were incorporated into this study. The Kaplan–Meier curve, the Least absolute shrinkage and selection operator (LASSO) regression analysis, and Cox analyses were implemented to determine the prognostic genes. A NHEJ-related risk model was created and verified by independent cohorts. We derived enriched pathways between the high- and low-risk groups using Gene Set Enrichment Analysis (GSEA). CIBERSORT and microenvironment cell populations-counter algorithm were used to perform immune infiltration analysis. XRCC6 is a core NHEJ gene and immunohistochemistry (IHC) was further performed to elucidate the prognostic impact. In vitro proliferation assays were conducted to investigate the specific effect of XRCC6.

Results

A novel NHEJ-related risk model was developed based on 6 NHEJ genes and patients were divided into distinct risk groups according to the risk score. The high-risk group had a poorer survival than those in the low-risk group (P < 0.001). Meanwhile, an obvious discrepancy in the landscape of the immune microenvironment also indicated that distinct immune status might be a potential determinant affecting prognosis as well as immunotherapy reactiveness. High XRCC6 expression level associates with poor outcome in HCC. Moreover, XRCC6 could promote HCC cell proliferation in vitro.

Conclusions

In brief, this work reveals a novel NHEJ-related risk signature for prognostic evaluation of HCC patients, which may be a potential biomarker of HCC immunotherapy.
Parental feeding practices as a response to child appetitive traits in toddlerhood and early childhood: a discordant twin analysis of the Gemini cohort
Authors: Kininmonth Alice R. , Herle Moritz , Tommerup Kristiane , Haycraft Emma , Farrow Claire , Croker Helen , Pickard Abigail , Edwards Katie , Blissett Jacqueline , Llewellyn Clare
Published: April 2023

Background

Parental feeding practices (PFPs) have been implicated in the development of children’s eating behaviours. However, evidence suggests that feeding practices may also develop in response to their child’s weight or emerging appetitive traits. We used the twin design to test the hypothesis that parents develop their feeding practices partly in response to their child’s appetite.

Methods

Data were from Gemini, a population-based cohort of 2402 British families with twins born in 2007. Psychometric measures of PFPs and appetite were completed by parents when their twins were 16-months and 5-years. Within-family analyses including all twins with available data in the sample (n = 1010–1858 pairs), examined if within-pair differences in PFPs were associated with differences in appetitive traits, controlling for differences in birth weight-SDS, early feeding method and child sex. In a subsample of twin pairs who were considerably discordant for appetitive traits by ≥ 1SD (n = 122–544 pairs), the direction and magnitude of within-pair differences in feeding practices was explored.

Results

Within-family variation in parental feeding practices in toddlerhood and early childhood was low (discordance ranged from 0.1 to 6% of the sample), except for pressure to eat (toddlerhood: 19%; early childhood: 32%). Within-pair differences in all appetitive traits were associated with differential use of ‘pressure to eat’ at both 16-months and 5-years. In the subsample of twins most discordant for appetitive traits, parents used more pressure with the twin expressing lower food responsiveness, lower emotional overeating, lower food enjoyment, higher satiety responsiveness, slower speed of eating, higher emotional undereating and greater fussiness in toddlerhood and early childhood (p-values < 0.001). Effect sizes were small to large at 16-months (η2=0.02–0.09) and 5-years (η2=0.05–0.21).

Conclusion

Parents rarely varied their feeding practices between twins in toddlerhood and early childhood, except for pressure. Parents exerted greater pressure on their twin who expressed a poorer appetite compared to their co-twin, suggesting that parents develop a pressuring feeding style when their child expresses a poorer appetite or lower interest in, and enthusiasm for, eating. These findings could be used to guide interventions seeking to support parents in feeding their children in a way that nurtures the development of healthy eating behaviours.
Microfat exerts an anti-fibrotic effect on human hypertrophic scar via fetuin-A/ETV4 axis
Authors: Yu Qian , Dai Qiang , Huang Zonglin , Li Chen , Yan Li , Fu Xin , Wang Qian , Zhang Yi , Cai Lei , Yang Zhigang , Xiao Ran
Published: April 2023

Background

Hypertrophic scar is a fibrotic disease following wound healing and is characterized by excessive extracellular matrix deposition. Autologous microfat grafting proves an effective strategy for the treatment thereof as it could improve the texture of scars and relieve relevant symptoms. This study aims to explore the potential mechanisms underlying the anti-fibrotic effect of microfat on hypertrophic scars.

Methods

In this study, we injected microfat into transplanted hypertrophic scars in mouse models and investigated the subsequent histological changes and differential expression of mRNAs therein. As for in vitro studies, we co-cultured microfat and hypertrophic scar fibroblasts (HSFs) and analyzed molecular profile changes in HSFs co-cultured with microfat by RNA sequencing. Moreover, to identify the key transcription factors (TFs) which might be responsible for the anti-fibrotic function of microfat, we screened the differentially expressed TFs and transfected HSFs with lentivirus to overexpress or knockdown certain differentially expressed TFs. Furthermore, comparative secretome analyses were conducted to investigate the proteins secreted by co-cultured microfat; changes in gene expression of HSFs were examined after the administration of the potential anti-fibrotic protein. Finally, the relationship between the key TF in HSFs and the microfat-secreted anti-fibrotic adipokine was analyzed.

Results

The anti-fibrotic effect of microfat was confirmed by in vivo transplanted hypertrophic scar models, as the number of α-SMA-positive myofibroblasts was decreased and the expression of fibrosis-related genes downregulated. Co-cultured microfat suppressed the extracellular matrix production of HSFs in in vitro experiment, and the transcription factor ETV4 was primarily differentially expressed in HSFs when compared with normal skin fibroblasts. Overexpression of ETV4 significantly decreased the expression of fibrosis-related genes in HSFs at both mRNA and protein levels. Fetuin-A secreted by microfat could also downregulate the expression of fibrosis-related genes in HSFs, partially through upregulating ETV4 expression.

Conclusions

Our results demonstrated that transcription factor ETV4 is essential for the anti-fibrotic effect of microfat on hypertrophic scars, and that fetuin-A secreted by microfat could suppress the fibrotic characteristic of HSFs through upregulating ETV4 expression. Microfat wields an alleviative influence over hypertrophic scars via fetuin-A/ETV4 axis.
Comparisons of 25 cerebrospinal fluid cytokines in a case–control study of 106 patients with recent-onset depression and 106 individually matched healthy subjects
Authors: Sørensen Nina Vindegaard , Borbye-Lorenzen Nis , Christensen Rune Haubo Bojesen , Orlovska-Waast Sonja , Jeppesen Rose , Skogstrand Kristin , Benros Michael Eriksen
Published: April 2023

Background

Neuroinflammation has been suggested as a contributor to the pathophysiology of depression; however, large case–control studies investigating cytokine levels in the cerebrospinal fluid (CSF) from patients with recent-onset depression by multiplex analyses are missing.

Methods

An individually matched (sex and age) prospective case–control study comparing patients with recent-onset depression to healthy controls. CSF was analyzed with the Mesoscale V-PLEX Neuroinflammation Panel 1. Outcomes: comparisons of analyte levels in the CSF between groups with interleukin (IL)-6 and IL-8 as primary outcomes and 23 other cytokines as secondary outcomes.

Results

We included 106 patients (84.0% outpatients) with recent-onset depression and 106 healthy controls. There were no significant differences in the primary outcomes IL-6 (relative mean difference (MD): 1.10; 95% confidence interval (CI) 0.93–1.30; p = 0.276) or IL-8 levels (MD: 1.05; 95% CI 0.96–1.16; p = 0.249) relative to healthy controls. IL-4 was 40% higher (MD: 1.40; 95% CI 1.14–1.72; p = 0.001), monocyte chemoattractant protein (MCP)-1 was 25% higher (MD: 1.25; 95% CI 1.06–1.47; p = 0.009) and macrophage inflammatory protein (MIP)-1β was 16% higher (MD: 1.16; 95% CI 1.02–1.33; p = 0.025) in patients with depression relative to healthy controls. However, only IL-4 was significantly elevated after correction for multiple testing of secondary outcomes (p = 0.025).

Conclusion

We found no significant differences in CSF levels of the co-primary outcomes IL-6 and IL-8, however, the higher CSF levels of IL-4, MCP-1 and MIP-1β among patients with recent-onset depression compared to healthy controls indicate a potential role of these cytokines in the neuroinflammatory response to depression.
PTEN hamartoma tumour syndrome: case report based on data from the Iranian hereditary colorectal cancer registry and literature review
Authors: Rahmatinejad Zahra , Goshayeshi Ladan , Bergquist Robert , Goshayeshi Lena , Golabpour Amin , Hoseini Benyamin
Published: April 2023

Background

PTENhamartoma tumour syndrome (PHTS) is a rare hereditary disorder caused by germline pathogenic mutations in thePTENgene. This study presents a case of PHTS referred for genetic evaluation due to multiple polyps in the rectosigmoid area, and provides a literature review of PHTS case reports published between March 2010 and March 2022.

Case presentation

A 39-year-old Iranian female with a family history of gastric cancer in a first-degree relative presented with minimal bright red blood per rectum and resistant dyspepsia. Colonoscopy revealed the presence of over 20 polyps in the rectosigmoid area, while the rest of the colon appeared normal. Further upper endoscopy showed multiple small polyps in the stomach and duodenum, leading to a referral for genetic evaluation of hereditary colorectal polyposis. Whole-exome sequencing led to a PHTS diagnosis, even though the patient displayed no clinical or skin symptoms of the condition. Further screenings identified early-stage breast cancer and benign thyroid nodules through mammography and thyroid ultrasound.

Method and results of literature review

A search of PubMed using the search terms “Hamartoma syndrome, Multiple” [Mesh] AND “case report” OR “case series” yielded 43 case reports, predominantly in women with a median age of 39 years. The literature suggests that patients with PHTS often have a family history of breast, thyroid and endometrial neoplasms along with pathogenic variants in thePTEN/MMAC1gene. Gastrointestinal polyps are one of the most common signs reported in the literature, and the presence of acral keratosis, trichilemmomas and mucocutaneous papillomas are pathognomonic characteristics of PHTS.

Conclusion

When a patient presents with more than 20 rectosigmoid polyps, PHTS should be considered. In such cases, it is recommended to conduct further investigations to identify other potential manifestations and the phenotype of PHTS. Women with PHTS should undergo annual mammography and magnetic resonance testing for breast cancer screening from the age of 30, in addition to annual transvaginal ultrasounds and blind suction endometrial biopsies.
Total knee arthroplasty in the outpatient vs inpatient settings: impact of site of care on early postoperative economic and clinical outcomes
Authors: Mantel Jack , Ruppenkamp Jill W. , Cantu Maricruz , Holy Chantal E.
Published: April 2023

Background

The incidence of total knee arthroplasty (TKA) surgery performed in the outpatient setting has increased as a result of improved perioperative recovery protocols, bundled payments, and challenges brought by the coronavirus disease of 2019 (COVID-19) pandemic on health systems. This study evaluates early postoperative clinical and economic outcomes of patients treated in the inpatient vs outpatient setting using the Attune Knee System (AKS).

Methods

Patients with an elective, primary TKA implanted with the AKS, from Q4 2015 to Q1 2021, were identified within the Premier Healthcare Database. The index was defined as the admission date for inpatient cases and the service day for outpatient procedures. Inpatient and outpatient cases were matched on patient characteristics. Outcomes included 90-day all-cause readmissions, 90-day knee reoperations, and index- and 90-day costs of care. Generalized linear models were used to evaluate outcomes (Reoperation: binomial distribution; costs: Gamma distribution with log link).

Results

Before matching, 39,337 inpatient and 9,365 outpatient cases were identified, with greater comorbidities in the inpatient cohort. The outpatient cohort had a lower average Elixhauser Index (EI) compared to the inpatient cohort (1.94 (standard deviation (SD): 1.46) vs 2.17 (SD: 1.53), p < 0.001), and the rates for each individual comorbidities were also slightly lower in the outpatient compared to the inpatient cohorts. Post-match, 9,060 patients were retained in each cohort [mean age: ~ 67, EI = 1.9 (SD: 1.5), 40% male]. Post-match comorbidity rates were similar between inpatient and outpatient cohorts (outpatient EI: 1.94 (SD: 1.44)–inpatient EI: 1.96 (SD: 1.45), p = 0.3516): in both, 54.1% of patients had an EI between 1 and 2, and 5.1% had an EI ≥ 5. No differences were observed in 3-month reoperation rates (0.6% in outpatient, 0.7% in inpatient cohort). Index and post-index 90-day costs were lower in the outpatient vs inpatient cases [(savings for index-only costs: $2,295 (95% CI: $1,977–$2,614); 90 days post-index knee-related care only: $2,540 (95% CI: $2,205–$2,876); 90 days post-index all-cause care: $2,679 (95% CI: $2,322–$3,036)].

Conclusions

Compared to matched inpatient cases, outpatient TKA cases treated with AKS showed similar 90-day outcomes, at lower cost.
Minimally invasive excision and reconstruction of Achilles tendon xanthoma using free autologous semitendinosus tendon transfer: a surgical technique
Authors: Oliva Francesco , Marsilio Emanuela , Mastrodonato Federica , Migliorini Filippo , Maffulli Nicola
Published: April 2023

Background

Tendon xanthomatosis is often associated with familial hypercholesterolemia, but it can also occur in other medical conditions. The Achilles tendon is the most common site of tendon xanthomas. Reconstruction of large defects after the xanthoma excision, can be challenging.

Methods

We propose a novel technique for Achilles tendon reconstruction with the use of an ipsilateral autologous semitendinosus tendon graft. The technique consists of six steps.

Results

This procedure has a low rate of complications and provides results that are at least comparable with those reported with other surgical approaches.
Aqueous extract of Platycodon grandiflorus attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling
Authors: Zhou Yang , Jin Tianzi , Gao Mingtong , Luo Zichen , Mutahir Sadaf , Shi Chen , Xie Tong , Lin Lili , Xu Jianya , Liao Yingzhao , Chen Ming , Deng Haishan , Zheng Min , Shan Jinjun
Published: April 2023

Background

Acute lung injury (ALI), an acute inflammatory lung disease, can cause a rapid inflammatory response in clinic, which endangers the patient's life. The components of platycodon grandiflorum, such as platycodins have a wide range of pharmacological activities such as expectorant, anti-apoptotic, anti-inflammatory, anti-tumor and anti-oxidant properties, and can be used for improving human immunity. Previous studies have shown that aqueous extract of platycodon grandiflorum (PAE) has a certain protective effect on ALI, but the main pharmacodynamic components and the mechanism of action are not clear.

Methods

The anti-inflammatory properties of PAE were studied using the lipopolysaccharide (LPS)-induced ALI animal model. Hematoxylin and eosin stains were used to assess the degree of acute lung damage. Changes in RNA levels of pro-inflammatory cytokines in the lungs were measured using quantitative RT-qPCR. The potential molecular mechanism of PAE preventing ALI was predicted by lipidomics and network pharmacology. To examine the anti-apoptotic effects of PAE, TdT-mediated dUTP nick-end labelling (TUNEL) was employed to determine apoptosis-related variables. The amounts of critical pathway proteins and apoptosis-related proteins were measured using Western blotting.

Results

Twenty-six chemical components from the PAE were identified, and their related pathways were obtained by the network pharmacology. Combined with the analysis of network pharmacology and literature, it was found that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is related to ALI. The results of lipidomics show that PAE alleviates ALI via regulating lung lipids especially phosphatidylinositol (PI). Finally, the methods of molecular biology were used to verify the mechanism of PAE. It can be found that PAE attenuates the inflammatory response to ALI by inhibiting apoptosis through PI3K/Akt signaling pathway.

Conclusion

The study revealed that the PAE attenuates lipopolysaccharide-induced apoptosis and inflammatory cell infiltration in mouse lungs by inhibiting PI3K/Akt signaling. Furthermore, our findings provide a novel strategy for the application of PAE as a potential agent for preventing patients with ALI.
Asymmetric gene expression and cell-type-specific regulatory networks in the root of bread wheat revealed by single-cell multiomics analysis
Authors: Zhang Lihua , He Chao , Lai Yuting , Wang Yating , Kang Lu , Liu Ankui , Lan Caixia , Su Handong , Gao Yuwen , Li Zeqing , Yang Fang , Li Qiang , Mao Hailiang , Chen Dijun , Chen Wei , Kaufmann Kerstin , Yan Wenhao
Published: April 2023

Background

Homoeologs are defined as homologous genes resulting from allopolyploidy. Bread wheat, Triticum aestivum, is an allohexaploid species with many homoeologs. Homoeolog expression bias, referring to the relative contribution of homoeologs to the transcriptome, is critical for determining the traits that influence wheat growth and development. Asymmetric transcription of homoeologs has been so far investigated in a tissue or organ-specific manner, which could be misleading due to a mixture of cell types.

Results

Here, we perform single nuclei RNA sequencing and ATAC sequencing of wheat root to study the asymmetric gene transcription, reconstruct cell differentiation trajectories and cell-type-specific gene regulatory networks. We identify 22 cell types. We then reconstruct cell differentiation trajectories that suggest different origins between epidermis/cortex and endodermis, distinguishing bread wheat from Arabidopsis. We show that the ratio of asymmetrically transcribed triads varies greatly when analyzing at the single-cell level. Hub transcription factors determining cell type identity are also identified. In particular, we demonstrate that TaSPL14 participates in vasculature development by regulating the expression of BAM1. Combining single-cell transcription and chromatin accessibility data, we construct the pseudo-time regulatory network driving root hair differentiation. We find MYB3R4, REF6, HDG1, and GATAs as key regulators in this process.

Conclusions

Our findings reveal the transcriptional landscape of root organization and asymmetric gene transcription at single-cell resolution in polyploid wheat.
The importance of NOT being Other: Time to address the invisibility of nuanced gender and sexuality in clinical trials
Authors: Williams Adam D. N. , Hood Kerenza , Bracken Karen , Shorter Gillian W.
Published: April 2023

Background

Representation of all members of society within research, especially those typically underserved, is needed to ensure that trial evidence applies to the relevant population, and that effective interventions are available to all. The lack of appropriate and representative options in demographic questions around sex, gender and sexuality may result in the exclusion of LGBTQIA + people from health research.

Main body

Sex and gender are not the same, yet this is rarely recognised in trial data collection, with the terms sex and gender often being used interchangeably. Sex or gender is often used as a stratification factor at randomisation and/or to define sub-groups at the time of data analysis, so correct data collection is essential for producing high-quality science. Sexuality also suffers from ‘othering’ with identities not being acknowledged but simply provided as an alternative to the perceived main identities. When collecting sexuality information, it is important to consider the purposes of collecting this data.

Conclusion

We call on those involved in trials to consider how sex, gender and sexuality data are collected, with an active consideration of inclusivity. Through the description of all non-straight, non-cisgender people as ‘other’ you may be ignoring the needs of these populations and doing science, yourself, and them a disservice. Inclusivity may require small but important changes to ensure your research findings are inclusive and develop the evidence base for often overlooked populations.