bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body measurement changes in adults with pectus excavatum after the Nuss procedure: a study of 272 patients
Authors: Htut Nay , Tzeng I-Shiang , Fan Yu-Jiun , Cheng Yeung-Leung 
Published: February 2024

Abstract
Background
Pectus excavatum (PE) is the most common congenital abnormality of the chest wall. Most patients with PE have slim bodies. Some studies have been conducted on the physical growth of children and adolescents who underwent the Nuss procedure. This study aimed to evaluate body measurement changes in adult patients with PE after the Nuss procedure.

Methods
A total of 272 adult PE patients, who underwent the Nuss procedure and pectus bars removal from August 2014 to December 2020, were evaluated retrospectively. Body measurement [body height (BH), body weight (BW), and body mass index (BMI)] of the patients were collected before Nuss repair and after bar removal. We used the interquartile range (IQR) to identify and exclude outliers. Associations between changes in body measurement and clinical and radiological features were evaluated.

Results
The BH, BW and BMI showed significantly increased after pectus bar removal, compared to pre-Nuss procedure parameters (BH 173.8 ± 5.9 cm vs. 173.9 ± 5.9 cm, P < 0.001; BW 60.3 ± 8.1 kg vs. 61.1 ± 8.8 kg, P = 0.005; BMI 19.9 ± 2.2 kg/m2 vs. 20.1 ± 2.4 kg/m2, P = 0.02). The same result were observed in the male subgroup, the HI ≥ 4 group and the male subgroup within the HI ≥ 4 group.

Conclusions
The BH, BW and BMI were significantly increased after completing surgical correction of PE using the Nuss procedure, particularly in young males and patients with more pronounced deformities.
Comparative transcriptome analysis and identification of candidate R2R3-MYB genes involved in anthraquinone biosynthesis in Rheum palmatum L.
Authors: Zhao Xia , Yan Feng , Li Yi-min , Tang Jing , Hu Xiao-chen , Feng Zhao , Gao Jing , Peng Liang , Zhang Gang 
Published: February 2024

Abstract
Background
Rheum palmatum L. has important medicinal value because it contains biologically active anthraquinones. However, the key genes and TFs involved in anthraquinone biosynthesis and regulation in R. palmatum remain unclear.

Methods
Based on full length transcriptome data, in this study, we screened the differentially expressed genes in the anthraquinone biosynthesis pathway. The R2R3-MYB family genes of R. palmatum were systematically identified based on full-length transcriptome sequencing followed by bioinformatics analyses. The correlation analysis was carried out by using co-expression analysis, protein interaction analysis, and real-time fluorescence quantitative analysis after MeJA treatment. The RpMYB81 and RpMYB98 genes were amplified by RT-PCR, and their subcellular localization and self-activation characteristics were analyzed.

Results
Comparative transcriptome analysis results revealed a total of 3525 upregulated and 6043 downregulated DEGs in the CK versus MeJA group; 28 DEGs were involved in the anthraquinone pathway. Eleven CHS genes that belonged to the PKS family were differentially expressed and involved in anthraquinone biosynthesis. Twelve differentially expressed MYBs genes were found to be co-expressed and interact with CHS genes. Furthermore, 52 MYB genes were identified as positive regulators of anthraquinone biosynthesis and were further characterized. Three MYB genes including RpMYB81, RpMYB98, and RpMYB100 responded to MeJA treatment in R. palmatum, and the levels of these genes were verified by qRT-PCR. RpMYB81 was related to anthraquinone biosynthesis. RpMYB98 had an interaction with genes in the anthraquinone biosynthesis pathway. RpMYB81 and RpMYB98 were mainly localized in the nucleus. RpMYB81 had self-activation activity, while RpMYB98 had no self-activation activity.

Conclusion
RpMYB81, RpMYB98, and RpMYB100 were significantly induced by MeJA treatment. RpMYB81 and RpMYB98 are located in the nucleus, and RpMYB81 has transcriptional activity, suggesting that it might be involved in the transcriptional regulation of anthraquinone biosynthesis in R. palmatum.
Implementation of thyroid eye disease registry in Iran: rationale and research protocol
Authors: Akbarian Shadi , Sheikhtaheri Abbas , Khorrami Farid , Ghahvechian Hossein , Karimi Nasser , Kashkouli Mohsen Bahmani 
Published: February 2024

Abstract
Background
To describe the implementation of a registry system for patients with thyroid eye disease (TED) in Iran to obtain more information about its nature, prevalence, and annual incidence, as well as extend insight into the etiology, pathogenesis, and eventually make an accurate prognosis of different medical or surgical treatment methods.

Methods
After receiving approval from the Disease Registry Committee of Iran University of Medical Sciences (IUMS) in 2019 and the Ministry of Health and Medical Education (MOHME) in 2020, the protocol was introduced in three consecutive phases at regional, provincial and national levels. The establishment of a registry committee in Rassoul Akram Hospital, one of the medical centers affiliated to IUMS, was the first step to organizing the registry project's main core. The steering committee included six subgroups of required subject fields. The members are experts in developing a guideline, providing a new dataset, drawing an outline for the next steps, and structuring user-friendly software through several panel discussion meetings. The data is collected from clinical and para-clinical/imaging findings, laboratory evaluations, and their selected treatment strategy, retrospectively and prospectively.

Results
The purpose is to broaden our knowledge about the profile of TED; accordingly, data related to patients’ demographics, thyroid gland disease (status, duration, treatments, and function tests), general medical and ocular history, along with visual/ocular exams resulting TED status are collected and recorded in a 2- language software. The web-based software system is accessible at https://orc.iums.ac.ir. To maintain data security, prioritized user access was defined for different members. Furthermore, diverse methods, such as employing trained staff and utilizing software validation rules, were implemented to control data quality in every step of data collection, entry, and registration. Medical records of retrospective subjects were also evaluated and entered after accuracy verification.

Conclusion
Iran's TED registry provides practitioners with comprehensive data on natural history and phenotype variations in clinical features and outcomes. It facilitates patient recruitment and, consequently, earlier diagnosis on a large scale which helps improve treatment and quality of life for patients.
Low 25-hydroxyvitamin D concentrations in wild rabbits (Oryctolagus cuniculus) in southern Finland
Authors: Mäkitaipale Johanna , Hietanen Pinja , Grönthal Thomas 
Published: February 2024

Abstract
Background
Diet and endogenous vitamin D synthesis are possible sources of vitamin D in wild rabbits. Higher 25-hydroxyvitamin D (25(OH)D) concentrations have been reported in rabbits after artificial UVB light exposure than in rabbits without this exposure, suggesting that endogenous vitamin D synthesis occurs in the former group. In Finnish pet rabbits, diet was reported as main source of vitamin D, while outdoor access was not. Finland’s northern location only enables endogenous synthesis from mid-March to mid-October in people with light skin type. Living conditions during winter are challenging for Finnish wild rabbits. This study aimed to measure serum 25(OH)D concentrations and possible natural seasonal variation of vitamin D concentrations in Finnish wild rabbits.

Results
Post-mortem blood samples (n = 78) were collected between 2013 and 2021 from wild rabbits hunted for reduction of the wild rabbit population. Separated sera were stored at − 80 °C until 25(OH)D concentrations were measured by enzyme immunoassay. Data regarding sex were available from 50 rabbits, 29 (58%) of which were females. Mean 25(OH)D concentration was 3.3 (range 0.3–7.1) ng/ml. 25(OH)D concentration was statistically similar between season (autumn, winter, summer), month or year of sample collection, and sex.

Conclusions
Wild rabbits living in Finland have very low serum 25(OH)D concentrations. This is far below the previously suggested threshold of vitamin D deficiency in rabbits (17 ng/mL) or the mean 25(OH)D concentration reported in Finnish pet rabbits (26.0 ng/mL). Seasonal variation was not observed in 25(OH)D concentrations between winter and summer months. Even though rabbits are crepuscular animals and may spend the mid-day in underground burrows, the very low observed 25(OH)D concentrations raise doubt about whether vitamin D synthesis occurs efficiently in the skin of rabbits and whether the diet of wild rabbits provides adequate amounts of vitamin D. Cutaneous vitamin D synthesis, possible long-term consequences of low 25(OH)D concentrations, and the association of low vitamin D status with other health disorders warrant further investigations in rabbits.
PARD3 drives tumorigenesis through activating Sonic Hedgehog signalling in tumour-initiating cells in liver cancer
Authors: Wu Junyu , Tan Hor-Yue , Chan Yau-Tuen , Lu Yuanjun , Feng Zixin , Yuan Hongchao , Zhang Cheng , Feng Yibin , Wang Ning 
Published: February 2024

Abstract
Background
Par-3 Family Cell Polarity Regulator (PARD3) is a cellular protein essential for asymmetric cell division and polarized growth. This study aimed to study the role of PARD3 in hepatic tumorigenesis.

Methods
The essential role of PARD3 in mediating hepatic tumorigenesis was assessed in diet-induced spontaneous liver tumour and syngeneic tumour models. The mechanism of PARD3 was delineated by bulk and single-cell RNA sequencing. The clinical significance of PARD3 was identified by tissue array analysis.

Results
PARD3 was overexpressed in tumour tissues and PARD3 overexpression was positively correlated with high tumour stage as well as the poor prognosis in patients. In models of spontaneous liver cancer induced by choline-deficient, amino acid-defined (CDAA) and methionine-choline-deficient (MCD) diets, upregulation of PARD3 was induced specifically at the tumorigenesis stage rather than other early stages of liver disease progression. Site-directed knockout of PARD3 using an adeno-associated virus 8 (AAV8)-delivered CRISPR/Cas9 single-guide RNA (sgRNA) plasmid blocked hepatic tumorigenesis, while PARD3 overexpression accelerated liver tumour progression. In particular, single-cell sequencing analysis suggested that PARD3 was enriched in primitive tumour cells and its overexpression enhanced tumour-initiating cell (TICs). Overexpression of PARD3 maintained the self-renewal ability of the CD133+ TIC population within hepatocellular carcinoma (HCC) cells and promoted the in vitro and in vivo tumorigenicity of CD133+ TICs. Transcriptome analysis revealed that Sonic Hedgehog (SHH) signalling was activated in PARD3-overexpressing CD133+ TICs. Mechanistically, PARD3 interacted with aPKC to further activate SHH signalling and downstream stemness-related genes. Suppression of SHH signalling and aPKC expression attenuated the in vitro and in vivo tumorigenicity of PARD3-overexpressing CD133+ TICs. Tissue array analysis revealed that PARD3 expression was positively associated with the phosphorylation of aPKC, SOX2 and Gli1 and that the combination of these markers could be used to stratify HCC patients into two clusters with different clinicopathological characteristics and overall survival prognoses. The natural compound berberine was selected as a potent suppressor of PARD3 expression and could be used as a preventive agent for liver cancer that completely blocks diet-induced hepatic tumorigenesis in a PARD3-dependent manner.

Conclusion
This study revealed PARD3 as a potential preventive target of liver tumorigenesis via TIC regulation.
Thiamine administration in septic shock: a post hoc analysis of two randomized trials
Authors: Vine Jacob , Lee John H. , Kravitz Max S. , Grossestreuer Anne V. , Balaji Lakshman , Leland Shannon B. , Berlin Noa , Moskowitz Ari , Donnino Michael W. 
Published: February 2024

Abstract
Background
This is a post hoc analysis of combined cohorts from two previous Phase II clinical trials to assess the effect of thiamine administration on kidney protection and mortality in patients with septic shock.

Methods
Patient-level data from the Thiamine in Septic Shock Trial (NCT01070810) and the Thiamine for Renal Protection in Septic Shock Trial (NCT03550794) were combined in this analysis. The primary outcome for the current study was survival without the receipt of renal replacement therapy (RRT). Analyses were performed on the overall cohort and the thiamine-deficient cohort (thiamine < 8 nmol/L).

Results
Totally, 158 patients were included. Overall, thiamine administration was associated with higher odds of being alive and RRT-free (adjusted odds ratio [aOR]: 2.05 [95% confidence interval (CI) 1.08–3.90]) and not needing RRT (aOR: 2.59 [95% CI 1.01–6.62]). In the thiamine-deficient group, thiamine administration was associated with higher odds of being alive and RRT-free (aOR: 8.17 [95% CI 1.79–37.22]) and surviving to hospital discharge (aOR: 6.84 [95% CI 1.54–30.36]). There was a significant effect modification by baseline thiamine deficiency for alive and RRT-free (interaction, p = 0.016) and surviving to hospital discharge (p = 0.019).

Conclusion
In the combined analysis of two previous randomized trials, thiamine administration was associated with higher odds of being alive and RRT-free at hospital discharge in patients with septic shock. This signal was stronger in patients with thiamine deficiency.
qSOFA combined with suPAR for early risk detection and guidance of antibiotic treatment in the emergency department: a randomized controlled trial
Authors: Adami Maria Evangelia , Kotsaki Antigone , Antonakos Nikolaos , Giannitsioti Efthymia , Chalvatzis Stamatios , Saridaki Maria , Avgoustou Christina , Akinosoglou Karolina , Dakou Konstantina , Damoraki Georgia , Katrini Konstantina , Koufargyris Panagiotis , Lekakis Vasileios , Panagaki Antonia , Safarika Asimina , Eugen-Olsen Jesper , Giamarellos-Bourboulis Evangelos J. 
Published: February 2024

Abstract
Background
Sepsis guidelines suggest immediate start of resuscitation for patients with quick Sequential Organ Failure Assessment (qSOFA) 2 or 3. However, the interpretation of qSOFA 1 remains controversial. We investigated whether measurements of soluble urokinase plasminogen activator receptor (suPAR) may improve risk detection when qSOFA is 1.

Methods
The study had two parts. At the first part, the combination of suPAR with qSOFA was analyzed in a prospective cohort for early risk detection. At the second part, the double-blind, randomized controlled trial (RCT) SUPERIOR evaluated the efficacy of the suPAR-guided medical intervention. SUPERIOR took place between November 2018 and December 2020. Multivariate stepwise Cox regression was used for the prospective cohort, while univariate and multivariate logistic regression was used for the RCT. Consecutive admissions at the emergency department (ED) with suspected infection, qSOFA 1 and suPAR ≥ 12 ng/mL were allocated to single infusion of placebo or meropenem. The primary endpoint was early deterioration, defined as at least one-point increase of admission Sequential Organ Failure Assessment (SOFA) score the first 24 h.

Results
Most of the mortality risk was for patients with qSOFA 2 and 3. Taking the hazard ratio (HR) for death of patients with qSOFA = 1 and suPAR < 12 ng/mL as reference, the HR of qSOFA = 1 and suPAR ≥ 12 ng/mL for 28-day mortality was 2.98 (95% CI 2.11–3.96). The prospective RCT was prematurely ended due to pandemia-related ED re-allocations, with 91 patients enrolled: 47 in the placebo and 44 in the meropenem arm. The primary endpoint was met in 40.4% (n = 19) and 15.9% (n = 7), respectively (difference 24.5% [5.9–40.8]; odds ratio 0.14 [0.04–0.50]). One post hoc analysis showed significant median changes of SOFA score after 72 and 96 h equal to 0 and − 1, respectively.

Conclusions
Combining qSOFA 1 with the biomarker suPAR improves its prognostic performance for unfavorable outcome and can help decision for earlier treatment.
Trial registration EU Clinical Trials Register (EudraCT, 2018-001008-13) and Clinical-Trials.gov (NCT03717350). Registered 24 October 2018.
Molecular monitoring of insecticide resistance in major disease vectors in Armenia
Authors: Paronyan Lusine , Babayan Lilit , Vardanyan Haykuhi , Manucharyan Arsen , Papapostolou Kyriaki Maria , Balaska Sofia , Vontas John , Mavridis Konstantinos 
Published: February 2024

Abstract
Background
Armenia is considered particularly vulnerable to life-threatening vector-borne diseases (VBDs) including malaria, West Nile virus disease and leishmaniasis. However, information relevant for the control of the vectors of these diseases, such as their insecticide resistance profile, is scarce. The present study was conducted to provide the first evidence on insecticide resistance mechanisms circulating in major mosquito and sand fly populations in Armenia.

Methods
Sampling sites were targeted based mainly on previous historical records of VBD occurrences in humans and vertebrate hosts. Initially, molecular species identification on the collected vector samples was performed. Subsequently, molecular diagnostic assays [polymerase chain reaction (PCR), Sanger sequencing, PCR-restriction fragment length polymorphism (RFLP), quantitative PCR (qPCR)] were performed to profile for major insecticide resistance mechanisms, i.e. target site insensitivity in voltage-gated sodium channel (vgsc) associated with pyrethroid resistance, acetylcholinesterase (ace-1) target site mutations linked to organophosphate (OP) and carbamate (CRB) resistance, chitin synthase (chs-1) target site mutations associated with diflubenzuron (DFB) resistance and gene amplification of carboxylesterases (CCEs) associated with resistance to the OP temephos.

Results
Anopheles mosquitoes were principally represented by Anopheles sacharovi, a well-known malaria vector in Armenia, which showed no signs of resistance mechanisms. Contrarily, the knockdown resistance (kdr) mutations V1016G and L1014F/C in the vgsc gene were detected in the arboviral mosquito vectors Aedes albopictus and Culex pipiens, respectively. The kdr mutation L1014S was also detected in the sand fly, vectors of leishmaniasis, Phlebotomus papatasi and P. tobbi, whereas no mutations were found in the remaining collected sand fly species, P. sergenti, P. perfiliewi and P. caucasicus.

Conclusions
This is the first study to report on molecular mechanisms of insecticide resistance circulating in major mosquito and sand fly disease vectors in Armenia and highlights the need for the establishment of systematic resistance monitoring practices for the implementation of evidence-based control applications.

Graphical Abstract
Associations between cardiometabolic multimorbidity and cerebrospinal fluid biomarkers of Alzheimer’s disease pathology in cognitively intact adults: the CABLE study
Authors: Li Qiong-Yao , Hu He-Ying , Zhang Gao-Wen , Hu Hao , Ou Ya-Nan , Huang Liang-Yu , Wang An-Yi , Gao Pei-Yang , Ma Li-Yun , Tan Lan , Yu Jin-Tai 
Published: February 2024

Abstract
Background
Cardiometabolic multimorbidity is associated with an increased risk of dementia, but the pathogenic mechanisms linking them remain largely undefined. We aimed to assess the associations of cardiometabolic multimorbidity with cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology to enhance our understanding of the underlying mechanisms linking cardiometabolic multimorbidity and AD.

Methods
This study included 1464 cognitively intact participants from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Cardiometabolic diseases (CMD) are a group of interrelated disorders such as hypertension, diabetes, heart diseases (HD), and stroke. Based on the CMD status, participants were categorized as CMD-free, single CMD, or CMD multimorbidity. CMD multimorbidity is defined as the coexistence of two or more CMDs. The associations of cardiometabolic multimorbidity and CSF biomarkers were examined using multivariable linear regression models with demographic characteristics, the APOE ε4 allele, and lifestyle factors as covariates. Subgroup analyses stratified by age, sex, and APOE ε4 status were also performed.

Results
A total of 1464 individuals (mean age, 61.80 years; age range, 40–89 years) were included. The markers of phosphorylated tau-related processes (CSF P-tau181: β = 0.165, P = 0.037) and neuronal injury (CSF T-tau: β = 0.065, P = 0.033) were significantly increased in subjects with CMD multimorbidity (versus CMD-free), but not in those with single CMD. The association between CMD multimorbidity with CSF T-tau levels remained significant after controlling for Aβ42 levels. Additionally, significantly elevated tau-related biomarkers were observed in patients with specific CMD combinations (i.e., hypertension and diabetes, hypertension and HD), especially in long disease courses.

Conclusions
The presence of cardiometabolic multimorbidity was associated with tau phosphorylation and neuronal injury in cognitively normal populations. CMD multimorbidity might be a potential independent target to alleviate tau-related pathologies that can cause cognitive impairment.
A patient with multiple primary malignant neoplasms with high variant allele frequencies of RB1, TP53, and TERT
Authors: Ma Mingyang , Shang Kun , Wang Jiewei , Teng Xiaojing , Li Peng , Wang Jing 
Published: February 2024

AbstractMultiple primary malignant neoplasms are a rare disease with tumors of different histology or morphology arising in various sites. Next-generation sequencing is essential in the etiology, diagnosis, treatment, and surveillance of this disease. No eight primary malignant neoplasm cases with high variant allele frequencies of RB1, TP53, and TERT have been reported. Herein, we report a 65-year-old male who exhibited eight primary malignancies of the vocal cord, pharynx, kidney, mouth floor, esophagus, and urinary bladder with different pathological types. The first seven tumors were early-stage tumors; the last tumor, small cell carcinoma of urinary bladder, showed liver metastasis at diagnosis. Next-generation sequencing results revealed extremely high somatic variant allele frequencies of RB1 c.1472 T > C, TP53 c.576A > G, and TERT c.-58-u66C > T (95.5%, 95.1%, and 51.0%, respectively). No germline mutations were detected. These findings denoted a heavy tumor burden and poor prognosis. This is the first report of eight primary malignant neoplasm cases with high variant allele frequencies of RB1, TP53, and TERT.
Reflective mode conversions between extensional and flexural waves by ultrathin oblique anisotropic tri-component resonators
Authors: Chen Fengyi , Du Qiujiao , Liu Fengming , Peng Pai 
Published: February 2024

Abstract
In this letter, we report a theoretical study for the conversions between extensional and flexural modes for Lamb waves. The incident extensional waves can be completely converted into reflected flexural waves, or vice versa. The used structure is oblique anisotropic tri-component resonators with locally dipolar resonators. Without special optimization designs, the thickness of conversion device is much smaller than the working wavelengths (1/150 and 1/15 for the extensional and flexural waves, respectively). Our proposed design is more feasible for low-frequency application scenarios.