bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundPTENhamartoma 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 presentationA 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 reviewA 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.ConclusionWhen 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

Abstract
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

Abstract
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.