bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibroblast growth factor receptor type 4 as a potential therapeutic target in clear cell renal cell carcinoma
Authors: Narisawa Takafumi , Naito Sei , Ito Hiromi , Ichiyanagi Osamu , Sakurai Toshihiko , Kato Tomoyuki , Tsuchiya Norihiko
Published: February 2023

Background

Several clear cell renal cell carcinoma (ccRCC) cases harbour fibroblast growth factor receptor 4 (FGFR4) gene copy number (CN) gains. In this study, we investigated the functional contribution of FGFR4 CN amplification in ccRCC.

Methods

The correlation between FGFR4 CN determined via real-time PCR and protein expression evaluated using western blotting and immunohistochemistry was assessed in ccRCC cell lines (A498, A704, and 769-P), a papillary RCC cell line (ACHN), and clinical ccRCC specimens. The effect of FGFR4 inhibition on ccRCC cell proliferation and survival was assessed via either RNA interference or using the selective FGFR4 inhibitor BLU9931, followed by MTS assays, western blotting, and flow cytometry. To investigate whether FGFR4 is a potential therapeutic target, a xenograft mouse model was administered BLU9931.

Results

60% of ccRCC surgical specimens harboured an FGFR4 CN amplification. FGFR4 CN was positively correlated with its protein expression. All ccRCC cell lines harboured FGFR4 CN amplifications, whereas ACHN did not. FGFR4 silencing or inhibition attenuated intracellular signal transduction pathways, resulting in apoptosis and suppressed proliferation in ccRCC cell lines. BLU9931 suppressed tumours at a tolerable dose in the mouse model.

Conclusion

FGFR4 contributes to ccRCC cell proliferation and survival following FGFR4 amplification, making it a potential therapeutic target for ccRCC.
A clinical study of topical treatment for thyroid-associated ophthalmopathy with dry eye syndrome
Authors: Sun Rou , Yang Muyue , Lin Chenyi , Wu Yu , Sun Jing , Zhou Huifang
Published: February 2023

Introduction

Clinically, thyroid-associated ophthalmopathy (TAO) patients were suffered from dry eye syndrome. Only a few relevant studies were about this topic. Our study was determined to provide high-level evidence for the treatment of TAO with dry eye syndrome.

Purpose

To compare the clinical effects of vitamin A palmitate eye gel and sodium hyaluronate eye drop forTAO patients with dry eye syndrome.

Methods

The study was conducted in the Ophthalmology Department of the Ninth People’s Hospital Affiliated with the Medical College of Shanghai Jiao Tong University from May to October 2020. A total of 80 mild or moderate-to-severe TAO patients with dry eye syndrome were randomly divided into two groups. The disease stages of all subjects were inactive. Patients in group A were treated with vitamin A palmitate eye gel three times/day for one month and sodium hyaluronate eye drop in group B. The index including break-up time (BUT) and Schirmer I test (ST), corneal fluorescence staining (FL), ocular surface disease index (OSDI), and adverse reactions were recorded by the same clinician at baseline and 1 month after treatment. The data were analyzed by SPSS 24.0.

Results

Finally, 65 subjects completed the treatment. The average age of the patients in Group A was 38.1 ± 11.4 years, and that in Group B was 37.26 ± 10.67 years. 82% of the subjects in group A were female and 74% in group B. There was no significant difference between the two groups at baseline, including the value of ST, BUT, OSDI, and FL grade. After the treatment, the effective rate was 91.2% in group A, of which the value of BUT and FL grade was significantly improved (P < 0.001). The effective rate in group B was 67.7%, of which the value of OSDI score and FL grade was significantly improved (P = 0.002). In addition, the BUT value of group A was significantly longer than that of group B (P = 0.009).

Conclusion

InTAO patients with dry eye syndrome, vitamin A palmitate gel and sodium hyaluronate eye drop improved the dry eye and promoted corneal epithelial repair. Vitamin A palmitate gel improves the stability of tear film, while sodium hyaluronate eye drop improves patients’ subjective discomfort.
Diagnosis-specific sickness absence among injured working-aged pedestrians: a sequence analysis
Authors: Kjeldgård Linnea , Stigson Helena , Bergsten Eva L. , Farrants Kristin , Friberg Emilie
Published: February 2023

Background

The knowledge about the long-term consequences in terms of sickness absence (SA) among pedestrians injured in a traffic-related accident, including falls, is scarce. Therefore, the aim was to explore diagnosis-specific patterns of SA during a four-year period and their association with different sociodemographic and occupational factors among all individuals of working ages who were injured as a pedestrian.

Methods

A nationwide register-based study, including all individuals aged 20–59 and living in Sweden, who in 2014–2016 had in- or specialized outpatient healthcare after a new traffic-related accident as a pedestrian. Diagnosis-specific SA (> 14 days) was assessed weekly from one year before the accident up until three years after the accident. Sequence analysis was used to identify patterns (sequences) of SA, and cluster analysis to form clusters of individuals with similar sequences. Odds ratios (ORs) with 95% confidence intervals (CIs) for association of the different factors and cluster memberships were estimated by multinomial logistic regression.

Results

In total, 11,432 pedestrians received healthcare due to a traffic-related accident. Eight clusters of SA patterns were identified. The largest cluster was characterized by no SA, three clusters had different SA patterns due to injury diagnoses (immediate, episodic, and later). One cluster had SA both due to injury and other diagnoses. Two clusters had SA due to other diagnoses (short-term and long-term) and one cluster mainly consisted of individuals with disability pension (DP). Compared to the cluster “No SA”, all other clusters were associated with older age, no university education, having been hospitalized, and working in health and social care. The clusters “Immediate SA”, “Episodic SA” and “Both SA due to injury and other diagnoses” were also associated with higher odds of pedestrians who sustained a fracture.

Conclusions

This nationwide study of the working-aged pedestrians observed diverging patterns of SA after their accident. The largest cluster of pedestrians had no SA, and the other seven clusters had different patterns of SA in terms of diagnosis (injury and other diagnoses) and timing of SA. Differences were found between all clusters regarding sociodemographic and occupational factors. This information can contribute to the understanding of long-term consequences of road traffic accidents.
Telehealth utilization in U.S. Medicare beneficiaries aged 65 years and older during the COVID-19 pandemic
Authors: Lu Min , Liao Xinyi
Published: February 2023

Background

The COVID-19 pandemic has become a serious public health concern for older adults and amplified the value of deploying telehealth solutions. The purpose of this study was to investigate telehealth offered by providers among U.S. Medicare beneficiaries aged 65 years and older during the COVID-19 pandemic.

Methods

This cross-sectional study analyzed Medicare beneficiaries aged 65 years and older using data from the Medicare Current Beneficiary Survey, Winter 2021 COVID-19 Supplement ($$n=9,185$$

n
=
9
,
185

). We identified variables that were associated with telehealth offered by primary care physicians and beneficiaries’ access to the Internet through a multivariate classification analysis utilizing Random Forest machine learning techniques.

Findings

For study participants interviewed by telephone, 81.06% of primary care providers provided telehealth services, and 84.62% of the Medicare beneficiaries had access to the Internet. The survey response rates for each outcome were 74.86% and 99.55% respectively. The two outcomes were positively correlated ($$\chi ^2=268.58,\,p<.001$$

χ
2

=
268.58
,

p
<
.
001

). The Our machine learning model predicted the outcomes accurately utilizing 44 variables. Residing area and race/ethnicity were most informative for predicting telehealth coverage, and Medicare-Medicaid dual eligibility and income were most informative for predicting Internet access. Other strong correlates included age, ability to access basic needs and certain mental and physical health conditions. Interactions were found among statuses of residing area, age, Medicare Advantage and heart conditions that intensified the disparity of outcomes.

Conclusions

We found that telehealth offered by providers likely increased during the COVID-19 pandemic for older beneficiaries, providing important access to care for certain subgroups. Policymakers must continue to identify effective means of delivering telehealth services, modernize the framework of regulatory, accreditation and reimbursement, and address disparities in access to telehealth with a particular focus on underserved communities.
Dental caries experience among qat chewers in dental college clinics, Jazan, Saudi Arabia
Authors: Halboub Esam , Alamri Abdulwahab Ahmed , Kamili Ghazi , Alqahtani Ahmed Shaher
Published: February 2023

Aims

There is a considerable debate on the impact of qat chewing on dental and oral health. Thereby, this study aimed at assessing the dental caries among qat chewers (QC) and non-qat chewers (NQC) who attend outpatient dental clinics, College of Dentistry, Jazan, Saudi Arabia.

Materials and methods

A sample of 100 QC and 100 NQC were recruited amongst those attended dental clinics, college of dentistry, Jazan University during the 2018–2019 academic year. Their dental health was assessed by three pre-calibrated male interns using DMFT index. The Care Index, Restorative Index and Treatment Index were calculated. Comparisons between both subgroups were done using independent t test. Multiple linear regression analyses were further conducted to stand on the independent determinants of the oral health among this population.

Results

QC were unintentionally older (36.55 ± 8.74 years) than NQC (32.96 ± 8.49 years; P = 0.004). Fifty-six percent of QC reported brushing their teeth compared to only 35% (P = 0.001). NQC with university and postgraduate educational levels were more than QC. The mean Decayed [5.91 (5.16)] and DMFT [9.15 (5.87)] were higher among QC compared to NQC [3.73 (3.62) and 6.7 (4.58); P = 0.001 and 0.001, respectively]. The other indices were not different between both subgroups. The multiple linear regression revealed that qat chewing and age, individually or together, as independent determinants for the dental decay, missing, DMFT and TI.

Conclusion

Qat chewing habit has a detrimental impact on dental health. It is associated with higher dental caries and missing teeth, and a lower treatment index.
Perceived guideline clarity impacts guideline-concordant care for breast cancer screening in women age 40–49
Authors: Nadler Michelle B. , Corrado Ann Marie , Wilson Brooke E. , Desnoyers Alexandra , Amir Eitan , Ivers Noah , Desveaux Laura
Published: February 2023

Background

Canadian and US Task Forces recommend against routine mammography screening for women age 40–49 at average breast cancer risk as harms outweigh benefits. Both suggest individualized decisions based on the relative value women place on potential screening benefits and harms. Population-based data reveal variation in primary care professionals (PCPs) mammography rates in this age group after adjusting for sociodemographic factors, highlighting the need to explore PCP screening perspectives and how this informs clinical behaviours. Results from this study will inform interventions that can improve guideline concordant breast screening for this age group.

Methods

Qualitative semi-structured interviews were performed with PCPs in Ontario, Canada. Interviews were structured using the theoretical domains framework (TDF) to explore determinants of breast cancer screening best-practice behaviours: (1) risk assessment; (2) discussion regarding benefits and harms; and (3) referral for screening.

Analysis

Interviews were transcribed and analyzed iteratively until saturation. Transcripts were coded deductively by behaviour and TDF domain. Data that did not fit within a TDF code were coded inductively. The research team met repeatedly to identify potential themes that influenced or were important consequences of the screening behaviours. The themes were tested against further data, disconfirming cases, and different PCP demographics.

Results

Eighteen physicians were interviewed. The theme of perceived guideline clarity (a lack of clarity on guideline-concordant practices) influenced all behaviours and moderated the extent to which the risk assessment and discussion occurred. Many were unaware of how risk-assessment factored into the guidelines and/or did not perceive that a shared-care discussion was guideline-concordant. Deferral to patient preference (screening referral without a complete discussion of benefits and harms) occurred when the PCPs had low knowledge regarding harms and/or if they experienced regret (TDF domain: emotion) resulting from prior clinical experiences. Older providers described patient’s influence impacting their decisions and physicians trained outside Canada, practicing in higher-resourced areas, and female physicians described being influenced by beliefs about consequences of benefits of screening.

Conclusion

Perceived guideline clarity is an important driver of physician behaviour. Improving guideline concordant care should start by clarifying the guideline itself. Thereafter, targeted strategies include building skills in identifying and overcoming emotional factors and communication skills important for evidence-based screening discussions.
Gestational trophoblastic neoplasia with primary lung cancer and mesenchymal tumor of sigmoid colon: a case report and literature review
Authors: Li HongYe , Sun Meng , Jiang Jing , Shi Bin , Wang BaoHua , Wang Lei , Wu WenXin , Wang WenYan
Published: February 2023

Background

Gestational trophoblastic neoplasia (GTN) is rare, and it is even rarer for GTN to merge with primary malignant tumors in other organs. Herein is described a rare clinical case of GTN combined with primary lung cancer and mesenchymal tumor of the sigmoid colon, followed with literature review.

Case presentation

The patient was hospitalized due to diagnosis of GTN with primary lung cancer. Firstly, two cycles of chemotherapy including 5-fluorouracil (5-FU) and actinomycin-D(Act-D) was given. Laparoscopic total hysterectomy and right salpingo-oophorectomy was performed during the third chemotherapy. During the operation, a 3*2 cm nodule was removed which was protruded from the serous surface of the sigmoid colon, and the nodule was confirmed mesenchymal tumor pathologically, in accord with gastrointestinal stromal tumor. During the treatment of GTN, Icotinib tablets were taken orally to control the progression of lung cancer. After 2 cycles of consolidation chemotherapy of GTN, she received thoracoscopic lower lobe of right lung lobectomy and the mediastinum lymph nodes removal. She undertook gastroscopy and colonoscopy and the tubular adenoma of the descending colon was removed. At present, the regular follow-up is taken and she remains free of tumors.

Conclusions

GTN combined with primary malignant tumors in other organs are extremely rare in clinical practice. When imaging examination reveals a mass in other organs, clinicians should be aware of the possibility of a second primary tumor. It will increase the difficulty of GTN staging and treatment. We emphasis the importance of the collaboration of multidisciplinary teams. Clinicians should choose a reasonable treatment plan according to the priorities of different tumors.
Efficacy and safety of topical 0.1% cannabidiol for managing recurrent aphthous ulcers: a randomized controlled trial
Authors: Umpreecha Chalapinyo , Bhalang Kanokporn , Charnvanich Dusadee , Luckanagul Jittima
Published: February 2023

Background

Although topical steroids constitute the first-line therapy for recurrent aphthous ulcers (RAUs), their long-term use often leads to candidiasis. Although cannabidiol (CBD) can be an alternative for pharmacologically managing RAUs due to its analgesic and anti-inflammatory in vivo effects, there is a lack of clinical and safety trials concerning its use. The aim of this study was to evaluate the clinical safety and efficacy of topical 0.1% CBD for managing RAU.

Methods

A CBD patch test was performed on 100 healthy subjects. CBD was applied on the normal oral mucosa of 50 healthy subjects 3 times/day for 7 days. Oral examination, vital signs, and blood tests were performed pre- and post-CBD use. Another 69 RAU subjects randomly received one of three topical interventions: 0.1% CBD, 0.1% triamcinolone acetonide (TA), or placebo. These were applied on the ulcers 3 times/day for 7 days. The ulcer and erythematous size were measured on day 0, 2, 5, and 7. Pain ratings were recorded daily. The subjects rated their satisfaction with the intervention and completed a quality-of-life questionnaire (OHIP-14).

Results

None of the subjects exhibited allergic reactions or side effects. Their vital signs and blood parameters were stable before and after the 7-day CBD intervention. CBD and TA significantly reduced ulcer size more than placebo at all time points. The erythematous size reduction was higher in the CBD intervention than the placebo on day 2, while TA reduced the erythematous size at all time points. The pain score in the CBD group was lower compared with placebo on day 5, whereas TA reduced pain more than placebo on day 4, 5, and 7. The subjects receiving CBD reported higher satisfaction than placebo. However, the OHIP-14 scores were comparable among the interventions.

Conclusions

Topical 0.1% CBD reduced ulcer size and accelerated ulcer healing without side effects. CBD exerted anti-inflammatory effects in the early stage and an analgesic effect in the late RAU stage. Thus, topical 0.1% CBD might be more appropriate for RAU patients who decline to take topical steroids, except for cases where CBD is contraindicated.

Trial registration

Thai Clinical Trials Registry (TCTR) Number TCTR20220802004. Retrospectively registered on 02/08/2022.
Empathy levels among health professional students at a large midwestern public university - a cross-sectional study
Authors: Wenger Kelsey , Reist Lauren , Achenbach Andrea , Dukes Kimberly , Fravel Michelle , Knockel Laura , Kuehnle Francis , Reist Jeffrey , Suneja Manish , Pendleton Chandler , Xie Xian Jin , Marchini Leonardo
Published: February 2023

Background

Empathic care is considered extremely important by patients and providers alike but there is still an ample need for assessing empathy among healthcare students and professionals and identifying appropriate educational interventions to improve it. This study aims to assess empathy levels and associated factors among students at different healthcare colleges at the University of Iowa.

Methods

An online survey was delivered to healthcare students, including nursing, pharmacy, dental, and medical colleges (IRB ID #202,003,636). The cross-sectional survey included background questions, probing questions, college-specific questions, and the Jefferson Scale of Empathy-Health Professionals Student version (JSPE-HPS). To examine bivariate associations, Kruskal Wallis and Wilcoxon rank sum tests were used. A linear model with no transformation was used in the multivariable analysis.

Results

Three hundred students responded to the survey. Overall JSPE-HPS score was 116 (± 11.7), consistent with other healthcare professional samples. There was no significant difference in JSPE-HPS score among the different colleges (P = 0.532).

Conclusion

Controlling for other variables in the linear model, healthcare students’ view of their faculty’s empathy toward patients and students’ self-reported empathy levels were significantly associated with students’ JSPE-HPS scores.
Factors affecting the transition to adulthood of Korean young adults with spina bifida: a qualitative study
Authors: Choi Eun Kyoung , Park Jisu , Kim Kyua , Bae Eunjeong , Ji Yoonhye , Yang Seung Hyeon , Chinbayar Altantuya , Yun Hyeseon
Published: February 2023

Background

Transition to adulthood to live independently while self-managing health and daily life without parental help is crucial for young adults with chronic conditions. Despite its importance as a precursor to effectively managing lifelong conditions, little is known about the experiences of young adults with spina bifida (SB) in transition to adulthood in Asian countries. This study aimed to explore the experiences of Korean young adults with SB to identify the facilitators or barriers to the transition from adolescence to adulthood from their perspectives.

Methods

This study used a qualitative descriptive design. The data were collected in South Korea through three focus group interviews with 16 young adults with SB, aged 19–26, from August to November 2020. We conducted a qualitative content analysis using a conventional approach to identify the factors that facilitated and hindered the participants’ transition to adulthood.

Results

Two themes emerged as facilitators and barriers to the transition to adulthood. a) Facilitators: understanding and acceptance of SB, acquiring self-management skills, parenting styles encouraging autonomy, parents’ emotional support, school teachers’ thoughtful consideration, and participation in self-help groups. b) Barriers: overprotective parenting style, experience of being bullied by peers, damaged self-concept, concealing one’s chronic condition from others, and the lack of privacy in school restrooms.

Conclusions

Korean young adults with SB shared their experiences of struggling to properly manage their chronic conditions on their own, particularly concerning regular bladder emptying, during the transition from adolescence to adulthood. To facilitate the transition to adulthood, education on the SB and self-management for adolescents with SB and on parenting styles for their parents are important. To eliminate barriers to the transition to adulthood, improving negative perceptions of disability among students and teachers and making school restrooms CIC-friendly are needed.
Monocyte, neutrophil, and whole blood transcriptome dynamics following ischemic stroke
Authors: Carmona-Mora Paulina , Knepp Bodie , Jickling Glen C. , Zhan Xinhua , Hakoupian Marisa , Hull Heather , Alomar Noor , Amini Hajar , Sharp Frank R. , Stamova Boryana , Ander Bradley P.
Published: February 2023

Background

After ischemic stroke (IS), peripheral leukocytes infiltrate the damaged region and modulate the response to injury. Peripheral blood cells display distinctive gene expression signatures post-IS and these transcriptional programs reflect changes in immune responses to IS. Dissecting the temporal dynamics of gene expression after IS improves our understanding of immune and clotting responses at the molecular and cellular level that are involved in acute brain injury and may assist with time-targeted, cell-specific therapy.

Methods

The transcriptomic profiles from peripheral monocytes, neutrophils, and whole blood from 38 ischemic stroke patients and 18 controls were analyzed with RNA-seq as a function of time and etiology after stroke. Differential expression analyses were performed at 0–24 h, 24–48 h, and >48 h following stroke.

Results

Unique patterns of temporal gene expression and pathways were distinguished for monocytes, neutrophils, and whole blood with enrichment of interleukin signaling pathways for different time points and stroke etiologies. Compared to control subjects, gene expression was generally upregulated in neutrophils and generally downregulated in monocytes over all times for cardioembolic, large vessel, and small vessel strokes. Self-organizing maps identified gene clusters with similar trajectories of gene expression over time for different stroke causes and sample types. Weighted Gene Co-expression Network Analyses identified modules of co-expressed genes that significantly varied with time after stroke and included hub genes of immunoglobulin genes in whole blood.

Conclusions

Altogether, the identified genes and pathways are critical for understanding how the immune and clotting systems change over time after stroke. This study identifies potential time- and cell-specific biomarkers and treatment targets.
The hepato-ovarian axis: genetic evidence for a causal association between non-alcoholic fatty liver disease and polycystic ovary syndrome
Authors: Liu Dong , Gao Xue , Pan Xiong-Fei , Zhou Tao , Zhu Cairong , Li Fei , Fan Jian-Gao , Targher Giovanni , Zhao Jian
Published: February 2023

Background

Recent studies found associations between non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS), but the causal nature of this association is still uncertain.

Methods

We performed a bidirectional two-sample Mendelian randomization (MR) analysis to test for the causal association between NAFLD and PCOS using data from a large-scale biopsy-confirmed NAFLD genome-wide association study (GWAS) (1483 cases and 17,781 controls) and PCOS GWAS (10,074 cases and 103,164 controls) in European ancestries. Data from glycemic-related traits GWAS (in up to 200,622 individuals) and sex hormones GWAS (in 189,473 women) in the UK Biobank (UKB) were used in the MR mediation analysis to assess potential mediating roles of these molecules in the causal pathway between NAFLD and PCOS. Replication analysis was conducted using two independent datasets from NAFLD and PCOS GWASs in the UKB and a meta-analysis of data from FinnGen and the Estonian Biobank, respectively. A linkage disequilibrium score regression was conducted to assess genetic correlations between NAFLD, PCOS, glycemic-related traits, and sex hormones using full summary statistics.

Results

Individuals with higher genetic liability to NAFLD were more likely to develop PCOS (OR per one-unit log odds increase in NAFLD: 1.10, 95% CI: 1.02–1.18; P = 0.013). Indirect causal effects of NAFLD on PCOS via fasting insulin only (OR: 1.02, 95% CI: 1.01–1.03; P = 0.004) and further a suggestive indirect causal effect via fasting insulin in concert with androgen levels were revealed in MR mediation analyses. However, the conditional F statistics of NAFLD and fasting insulin were less than 10, suggesting likely weak instrument bias in the MVMR and MR mediation analyses.

Conclusions

Our study suggests that genetically predicted NAFLD was associated with a higher risk of developing PCOS but less evidence for vice versa. Fasting insulin and sex hormones might mediate the link between NAFLD and PCOS.
Association between low-density lipoprotein cholesterol and sudden cardiac arrest in people with diabetes mellitus
Authors: Kim Yun Gi , Jeong Joo Hee , Han Kyung-Do , Roh Seung-Young , Min Kyongjin , Lee Hyoung Seok , Choi Yun Young , Shim Jaemin , Choi Jong-Il , Kim Young-Hoon
Published: February 2023

Background

Dyslipidemia measured as low-density lipoprotein (LDL)-cholesterol is an established risk factor of cardiovascular disease, which is more pronounced in diabetes population. Less is known about the association of LDL-cholesterol level and sudden cardiac arrest (SCA) risk in diabetes mellitus patients. This study investigated the association of LDL-cholesterol level and SCA risk in diabetes population.

Methods

This study was based on Korean National Health Insurance Service database. Patients who received general examination from 2009 to 2012 and diagnosed as type 2 diabetes mellitus were analyzed. Primary outcome was defined as SCA event identified with International Classification of Disease code.

Results

A total of 2,602,577 patients were included, with total follow-up duration of 17,851,797 person * year. Mean follow-up duration was 6.86 years, and 26,341 SCA cases were identified. Overall incidence of SCA was highest in the lowest LDL-cholesterol group (< 70 mg/dL) and decreased in a linear manner as LDL-cholesterol rises, till 160 mg/dL. Adjustment of covariates resulted in U-shape association, with highest risk of SCA in the highest LDL-cholesterol group (≥ 160 mg/dL) followed by lowest LDL-cholesterol group (< 70 mg/dL). In subgroup analysis, U-shape association between SCA risk and LDL-cholesterol was more pronounced in male, non-obese people, and those who did not use statins.

Conclusions

In people with diabetes, the association between SCA and LDL-cholesterol level was U-shaped with highest and lowest LDL-cholesterol group having higher risk of SCA than others. Low LDL-cholesterol level can be a surrogate marker for increased risk of SCA in people with diabetes mellitus and this paradoxical association should be recognized and extended to clinical preventive measures.
The role of fatty acid desaturase 2 in multiple tumor types revealed by bulk and single-cell transcriptomes
Authors: Chen Enli , Wang Cong , Lv Hongwei , Yu Jing
Published: February 2023

Background

Previous studies have demonstrated the important role of fatty acid desaturase 2 (FADS2) in governing tumorigenesis and tumor metastasis. Although FADS2 is an essential regulator of fatty acid metabolism, its prognostic and immunotherapeutic value remains uncertain.

Methods

The role of FADS2 was investigated across different types of tumors. Besides, the relationship between FADS2 and survival prognosis, clinicopathologic features, tumor-infiltrating immune cells, immunoregulatory genes, chemokines, chemokines receptor, tumor mutational burden (TMB), and microsatellite instability (MSI) was also explored. FADS2-related genes enrichment analysis was performed to further explore the molecular function of FADS2. Finally, the relationship between FADS2 expression and altered functional states in single-cell levels across different tumor cells was explored.

Results

FADS2 was increased in most tumor tissues. Elevated FADS2 expression was associated with a poor overall survival (OS) and disease-free survival (DFS). FADS2 amplification was germane to worse progress-free survival (PFS). In addition, FADS2 correlated with the majority of tumor-infiltrating immune cells, immunoregulatory genes, and chemokines. Especially, FADS2 expression positively correlated with cancer-associated fibroblast (CAFs) infiltration. Gene Ontology and KEGG analysis demonstrated that FADS2 was involved in the fatty acid metabolic process, arachidonic acid metabolism, RAS, PPAR, and VEGF pathway. FADS2 had a positive relationship with tumor biological behaviors such as inflammation, cell cycle, proliferation, DNA damage, and DNA repair response in single-cell levels.

Conclusions

FADS2 can serve as a potential prognostic and immunotherapeutic biomarker for multiple tumors, revealing new insights and evidence for cancer treatment.
P2RX7 promotes osteosarcoma progression and glucose metabolism by enhancing c-Myc stabilization
Authors: Sheng Gaohong , Gao Yuan , Ding Qing , Zhang Ruizhuo , Wang Tianqi , Jing Shaoze , Zhao Hongqi , Ma Tian , Wu Hua , Yang Yong
Published: February 2023

Background

Osteosarcoma is the most common malignant tumor in bone and its prognosis has reached a plateau in the past few decades. Recently, metabolic reprogramming has attracted increasing attention in the field of cancer research. In our previous study, P2RX7 has been identified as an oncogene in osteosarcoma. However, whether and how P2RX7 promotes osteosarcoma growth and metastasis through metabolic reprogramming remains unexplored.

Methods

We used CRISPR/Cas9 genome editing technology to establish P2RX7 knockout cell lines. Transcriptomics and metabolomics were performed to explore metabolic reprogramming in osteosarcoma. RT-PCR, western blot and immunofluorescence analyses were used to determine gene expression related to glucose metabolism. Cell cycle and apoptosis were examined by flowcytometry. The capacity of glycolysis and oxidative phosphorylation were assessed by seahorse experiments. PET/CT was carried out to assess glucose uptake in vivo.

Results

We demonstrated that P2RX7 significantly promotes glucose metabolism in osteosarcoma via upregulating the expression of genes related to glucose metabolism. Inhibition of glucose metabolism largely abolishes the ability of P2RX7 to promote osteosarcoma progression. Mechanistically, P2RX7 enhances c-Myc stabilization by facilitating nuclear retention and reducing ubiquitination-dependent degradation. Furthermore, P2RX7 promotes osteosarcoma growth and metastasis through metabolic reprogramming in a predominantly c-Myc-dependent manner.

Conclusions

P2RX7 plays a key role in metabolic reprogramming and osteosarcoma progression via increasing c-Myc stability. These findings provide new evidence that P2RX7 might be a potential diagnostic and/or therapeutic target for osteosarcoma. Novel therapeutic strategies targeting metabolic reprogramming appear to hold promise for a breakthrough in the treatment of osteosarcoma.
Amyloid-β accumulation in human astrocytes induces mitochondrial disruption and changed energy metabolism
Authors: Zyśk Marlena , Beretta Chiara , Naia Luana , Dakhel Abdulkhalek , Påvénius Linnea , Brismar Hjalmar , Lindskog Maria , Ankarcrona Maria , Erlandsson Anna
Published: February 2023

Background

Astrocytes play a central role in maintaining brain energy metabolism, but are also tightly connected to the pathogenesis of Alzheimer’s disease (AD). Our previous studies demonstrate that inflammatory astrocytes accumulate large amounts of aggregated amyloid-beta (Aβ). However, in which way these Aβ deposits influence their energy production remain unclear.

Methods

The aim of the present study was to investigate how Aβ pathology in astrocytes affects their mitochondria functionality and overall energy metabolism. For this purpose, human induced pluripotent cell (hiPSC)-derived astrocytes were exposed to sonicated Aβ42 fibrils for 7 days and analyzed over time using different experimental approaches.

Results

Our results show that to maintain stable energy production, the astrocytes initially increased their mitochondrial fusion, but eventually the Aβ-mediated stress led to abnormal mitochondrial swelling and excessive fission. Moreover, we detected increased levels of phosphorylated DRP-1 in the Aβ-exposed astrocytes, which co-localized with lipid droplets. Analysis of ATP levels, when blocking certain stages of the energy pathways, indicated a metabolic shift to peroxisomal-based fatty acid β-oxidation and glycolysis.

Conclusions

Taken together, our data conclude that Aβ pathology profoundly affects human astrocytes and changes their entire energy metabolism, which could result in disturbed brain homeostasis and aggravated disease progression.
Clinicopathological study of pseudomyogenic hemangioendothelioma
Authors: Yang Ningning , Huang Yuchen , Yang Panpan , Yan Wentian , Zhang Shan , Li Nan , Feng Zhenzhong
Published: February 2023

Objectives

Pseudomyogenic hemangioendothelioma (PHE) is a rare intermediate hemangioendothelioma. This article aims to study the clinicopathological features of PHE.

Methods

We collected the clinicopathological features of 10 new PHE, and examined their molecular pathological features by fluorescence in situ hybridization. In addition, we summarized and analyzed the pathological data of 189 reported cases.

Results

The case group consisted of six men and four women aged 12–83 years (median: 41 years). Five instances occurred in the limbs, three in the head and neck, and two in the trunk. Tumor tissues were composed of spindle cells and round or polygonal epithelioid cells, which were either arranged in sheets or interwoven, along with areas of transitional morphology. Scattered or patchy stromal neutrophil infiltration was observed. Tumor cells had abundant cytoplasm, and some contained vacuoles. The nuclei had mild to moderate atypia, with visible nucleoli, and mitosis was rare. PHE tissues diffusely expressed CD31 and ERG, but not CD34, Desmin, SOX-10, HHV8 or S100, while some samples expressed CKpan, FLI-1 and EMA. INI-1 stain is retained. The proliferation index of Ki-67 is 10–35%. Seven samples were detected by fluorescence in situ hybridization, six of which had breakages in FosB proto-oncogene (AP-1 transcription factor subunit). Two patients experienced recurrence; however, no metastasis or death occurred.

Conclusions

PHE is a rare soft tissue vascular tumor, which has biologically borderline malignant potential, local recurrence, little metastasis, and good overall survival and prognosis. Immunomarkers and molecular detection are valuable for diagnosis.
Optimal surgical treatment for periprosthetic distal femoral fractures after total knee arthroplasty: a Bayesian-based network analysis
Authors: Fu Peng , Liang Wenwei , Gao Zhenzhen , Chen Gang , Fan Weimin
Published: February 2023

Background

The surgical methods for periprosthetic distal femoral fractures (PDFFs) after total knee arthroplasty included locking compression plate (LCP), retrograde intramedullary nailing (RIMN), and distal femoral replacement (DFR). However, the optimal treatment remains controversial. We performed a network meta-analysis (NMA) to provide the optimal surgical method for PDFFs.

Materials and methods

Electronic databases, including Embase, Web of Science, Cochrane Library, and PubMed, were searched for studies that compared LCP, RIMN, and DFR for PDFFs. The quality of the included studies was assessed according to the Newcastle–Ottawa scale. Pairwise meta-analysis was performed by Review Manager version 5.4. The NMA was conducted in Aggregate Data Drug Information System software version 1.16.5. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for postoperative complications and reoperations.

Results

A total of 19 studies and 1198 patients were included, of whom 733 for LCP, 282 for RIMN, and 183 for DFR. Pairwise meta-analysis comparing LCP to RIMN and LCP to DFR showed no significant difference in complications and reoperations except that RIMN had a higher risk of malunion comparing to LCP (OR 3.05; 95% CI 1.46–6.34;P = 0.003). No statistically significant effects were found in the NMA of overall complications, infection, and reoperation. However, results of rank probabilities showed that DFR ranked best in overall complications and reoperation, RIMN ranked best in infection but worst in reoperation, and LCP ranked worst in infection and middle in reoperation.

Discussion

We found similar complication rate and reoperation rate between LCP, RIMN, and DFR. The results of rank probabilities favored DFR, and further studies with high-level evidence are expected to verify the optimal surgical method for PDFFs.

Level of evidence

Level II; network meta-analysis.
Identification of subgroups of children in the Australian Autism Biobank using latent class analysis
Authors: Montgomery Alicia , Masi Anne , Whitehouse Andrew , Veenstra-VanderWeele Jeremy , Shuffrey Lauren , Shen Mark D. , Karlov Lisa , Uljarevic Mirko , Alvares Gail , Woolfenden Sue , Silove Natalie , Eapen Valsamma
Published: February 2023

Background

The identification of reproducible subtypes within autistic populations is a priority research area in the context of neurodevelopment, to pave the way for identification of biomarkers and targeted treatment recommendations. Few previous studies have considered medical comorbidity alongside behavioural, cognitive, and psychiatric data in subgrouping analyses. This study sought to determine whether differing behavioural, cognitive, medical, and psychiatric profiles could be used to distinguish subgroups of children on the autism spectrum in the Australian Autism Biobank (AAB).

Methods

Latent profile analysis was used to identify subgroups of children on the autism spectrum within the AAB (n = 1151), utilising data on social communication profiles and restricted, repetitive, and stereotyped behaviours (RRBs), in addition to their cognitive, medical, and psychiatric profiles.

Results

Our study identified four subgroups of children on the autism spectrum with differing profiles of autism traits and associated comorbidities. Two subgroups had more severe clinical and cognitive phenotype, suggesting higher support needs. For the ‘Higher Support Needs with Prominent Language and Cognitive Challenges’ subgroup, social communication, language and cognitive challenges were prominent, with prominent sensory seeking behaviours. The ‘Higher Support Needs with Prominent Medical and Psychiatric and Comorbidity’ subgroup had the highest mean scores of challenges relating to social communication and RRBs, with the highest probability of medical and psychiatric comorbidity, and cognitive scores similar to the overall group mean. Individuals within the ‘Moderate Support Needs with Emotional Challenges’ subgroup, had moderate mean scores of core traits of autism, and the highest probability of depression and/or suicidality. A fourth subgroup contained individuals with fewer challenges across domains (the ‘Fewer Support Needs Group’).

Limitations

Data utilised to identify subgroups within this study was cross-sectional as longitudinal data was not available.

Conclusions

Our findings support the holistic appraisal of support needs for children on the autism spectrum, with assessment of the impact of co-occurring medical and psychiatric conditions in addition to core autism traits, adaptive functioning, and cognitive functioning. Replication of our analysis in other cohorts of children on the autism spectrum is warranted, to assess whether the subgroup structure we identified is applicable in a broader context beyond our specific dataset.
Exploring associations of adverse childhood experiences with patterns of 11 health risk behaviors in Chinese adolescents: focus on gender differences
Authors: Xu Huiqiong , Zhang Xinyu , Wang Jiaojiao , Xie Yang , Zhang Yi , Xu Shaojun , Wan Yuhui , Tao Fangbiao
Published: February 2023

Purpose

Adolescents exposed to adverse childhood experiences (ACEs) are at increased risk for health-compromising behaviors. However, few studies have investigated how ACEs correlate with patterns of health risk behaviors (HRBs) during adolescence, a crucial developmental period. The aim was to extend the current knowledge about the relationship between ACEs and HRB patterns among adolescents, and to explore gender differences.

Methods

A multi-centered population-based survey was conducted in 24 middle schools in three provinces across China between 2020 and 2021. A total of 16,853 adolescents effectively completed anonymous questionnaires covering exposure to eight ACE categories and 11 HRBs. Clusters were identified using latent class analysis. Logistic regression models were utilized to test the association between them.

Results

There were four classes of HRB patterns: “Low all” (58.35%), “Unhealthy lifestyle” (18.23%), “Self-harm” (18.42%), and “High all” (5.0%). There were significant differences between HRB patterns in terms of the different numbers and types of ACEs in three logistic regression models. Specifically, compared to “Low all,” different types of ACEs were positively associated with the three other HRB patterns, and there were significant trends toward increase in the three latent classes of HRBs with higher ACEs. In general, females with ACEs had a higher risk of “High all” except sexual abuse than males.

Conclusion

Our study comprehensively considers the association between ACEs and aggregation categories of HRBs. The results support efforts to improve clinical healthcare, and future work may explore protective factors based on individual, family, and peer education to mitigate the negative trajectory of ACEs.
Accessible mental well-being intervention for adolescents in school settings: a single-group intervention study using a pretest–post-test design
Authors: Tornivuori Anna , Kronström Kim , Aromaa Minna , Salanterä Sanna , Karukivi Max
Published: February 2023

Background

A growing number of adolescents seek treatment for mental health problems, a circumstance that stresses the importance of implementing accessible treatment options. This study evaluates the impacts of brief, mental well-being intervention for adolescents in a school environment. As mental health interventions are often targeted at specific disorders, we sought a comprehensive approach to reach adolescents with a range of mental health symptoms.

Methods

Single-group intervention study with a pretest–posttest design was utilized and conducted in lower, upper secondary, and vocational schools on adolescents ages 12–18 who sought medical attention for mental health symptoms. The cut-off point for inclusion was ≥ 14, for the Young Persons Clinical Outcomes for routine Evaluation (YP-CORE) measurement. The intervention included six face-to-face visits implemented by psychiatric nurses who received a 3-day training course. The impacts were evaluated after 6 weeks (n = 87) and again at 6 months (n = 68) and assessed using the YP-CORE, Beck Depression Inventory (BDI-II) and Overall Anxiety Severity and Impairment Scale (OASIS).

Results

The participants reported significant levels of mental distress at baseline with a YP-CORE mean score = 21.48, a BDI-II mean score = 23.60, OASIS mean score = 10.98. Post-intervention results at 6 weeks for the primary outcome YP-CORE showed a significant (p < .001) mean score decrease of − 3.82, a medium effect sized = .627. For participants attending upper secondary and vocational schools the YP-CORE scores changed significantly from baseline to 6-weeks (p = .005) and from baseline to 6-months (p < .001). Long-term outcomes at 6-months showed a − 1.14 decrease (p = non-significant), effect sized = .175. After the 6-week intervention, 12% of the participants were assessed as not requiring additional visits.

Conclusions

This easily accessible intervention in a school setting indicated improvement for those participants with mild to moderate mental disorder symptoms and attending upper secondary and vocational schools. After the 6-week intervention, significant positive effects were observed. Participants reported substantial levels of mental distress at the baseline, which could contribute to the decline of symptoms and need for extended care during the 6 months follow-up.

Trial registrationRetrospectively registered with Clinicaltrials.gov identifier NCT05356949
Prevention of incisional surgical site infection by subfascial closed suction drainage after open laparotomy: a single surgeon experience in 250 consecutive patients
Authors: Isozaki Hiroshi
Published: February 2023

Background

Open laparotomy with gastroenterological surgery is a surgical procedure results in a relatively high rate (about 10% or more) of incisional surgical site infection (SSI). To reduce incisional SSI after open laparotomy, mechanical preventors, such as subcutaneous wound drainage or negative-pressure wound therapy (NPWT), have been tried; however, conclusive results have not been obtained. This study evaluated the prevention of incisional SSI by first subfascial closed suction drainage after open laparotomy.

Methods

A total of 453 consecutive patients who underwent open laparotomy with gastroenterological surgery by one surgeon in one hospital (between August 1, 2011, and August 31, 2022) was investigated. Same absorbable threads and ring drapes were used in this period. Subfascial drainage was used in consecutive 250 patients in the later period (between January 1, 2016, and August 31, 2022). The incidences of SSIs in the subfascial drainage group were compared to those of in the no subfascial drainage group.

Results

(a) No incisional SSI (superficial and deep) occurred in the subfascial drainage group (superficial = 0% [0/250] and deep = 0% [0/250]). As a result, incidences of incisional SSI of the subfascial drainage group were significantly lower than those of the no subfascial drainage group (superficial = 8.9% [18/203]; deep = 3.4% [7/203]) (p < 0.001 and p = 0.003, respectively). (b) Four out of seven deep incisional SSI patients in the no subfascial drainage group underwent debridement and re-suture under lumbar or general anesthesia. (c) There was no significant difference in the incidences of organ/space SSI of the two groups (3.4% [7/203] in the no subfascial drainage group and 5.2% [13/250] in the subfascial drainage group) (P = 0.491).

Conclusion

Subfascial drainage was associated with no incisional SSI after open laparotomy with gastroenterological surgery.