bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance intravenous fluid therapy in infants with sepsis and hyponatremia: a clinical trial
Authors: Milani Hani , Tajalli Saleheh , Behrouzi Kamran , Homan Nakisa , Zamaniashtiani Fateme , Vafaee Ali , Vahedi Zahra , Khalesi Nasrin 
Published: August 2024

Abstract
Background
This study aimed to compare the effect of two methods of maintenance intravenous fluid therapy on hyponatremia in hospitalized infants with sepsis.

Methods
In a double-blinded randomized clinical trial, 60 term infants with sepsis were enrolled. Blood samples were taken to determine sodium, potassium, Creatinine, and BUN levels before the initiation of treatment. Urine samples were taken to assess specific gravity and urinary output. Infants in the intervention group received half saline in 10% dextrose and infants in the control group were assigned to receive the conventional solution as maintenance. The above indicators were re-evaluated 24 and 48 h after the initiation of treatment. Two groups were compared concerning the incidence of hyponatremia, and other criteria such as urinary output and urinary specific gravity, blood urea nitrogen (BUN), and creatinine levels.

Results
Hyponatremia was more common in the control group. Sodium levels were significantly higher in half saline recipients 24 h (137.83 ± 2.86 vs. 134.37 ± 1.91 mmol/L), and 48 h (138.10 ± 2.41 vs. 133.66 ± 1.98 mmol/L) after treatment (P < 0.001). Although BUN in the intervention group was significantly higher in comparison to the control group, the difference in urinary output, urine specific gravity, potassium, and Creatinine levels were not significant in the two groups.

Conclusions
The use of a half-saline solution as maintenance fluid reduces the risk of hyponatremia after 48 h when compared to 0.18%NaCl.

Trial registration
This has been registered at Iranian Registry of Clinical Trials (Retrospectively registered, Registration date: 2017-10-12, identifier: IRCT2017053034223N1, https://irct.behdasht.gov.ir/trial/26204).
Evaluation of probiotics’ efficiency on cariogenic bacteria: randomized controlled clinical study
Authors: Sakaryalı Uyar Didem , Üsküdar Güçlü Aylin , Çelik Ekin , Memiş Özgül Betül , Altay Koçak Aylin , Başustaoğlu Ahmet Celal 
Published: August 2024

Abstract
Background
Probiotics are live beneficial bacteria to human health and their efficiency on oral health is still being investigated. The purpose of this study was to evaluate the level of Streptococcus mutans and Lactobacillus species with and without the use of probiotics for six-months after the treatment of all dental caries under general anesthesia.

Methods
Fifty-eight pediatric patients without any systemic diseases, whose dental treatments were completed under general anesthesia (GA), were included in the study. The patients were recruited in two-groups; Group A: Patients started using probiotics after GA and Group B: Patients did not use probiotics after GA. Saliva samples were taken from all patients on the day before GA (T0), at one-month (T1), three-month (T2) and six-month (T3) follow-up after GA. The counts of cariogenic bacteria were determined by the analysis of saliva samples using real-time polymerase chain reaction. Statistical significance level was accepted as p < 0.05.

Results
There was statistically significant difference between Group A and B for T0, T1, T2 and T3 regarding S. mutans (p = 0.001, p = 0.04, p = 0.04, p = 0.03; p < 0.05). However, there was no statistically significant difference between groups regarding Lactobacillus species (p ≥ 0.05).

Conclusions
Probiotic use and treatment of all caries significantly reduced the level of S. mutans but not Lactobacillus species. Furthermore, S. mutans decreased after cessation of probiotics, but it was not statistically significant.

Trial registration
Study was registered as “Effects of Probiotics on Streptococcus mutans and Lactobacillus species” with the registration number of NCT05859646 (16/05/2023) at https://www.clinicaltrials.gov Protocol Registration and Results System.
The CAREPAL-8: a short screening tool for multidimensional family caregiver burden in palliative care
Authors: Ullrich Anneke , Bergelt Corinna , Marx Gabriella , Daubmann Anne , Benze Gesine , Heine Julia , Dickel Lisa-Marie , Wowretzko Feline , Zhang Youyou , Bokemeyer Carsten , Nauck Friedemann , Oechsle Karin 
Published: August 2024

Abstract
Background
Family caregivers of terminally ill and dying people do not only experience varying levels but also different dimensions of caregiver-related strain and burden. The aim of the study was to develop a short multidimensional screening tool for the detection of burden in family caregivers in palliative care.

Methods
Family caregivers of cancer patients newly admitted to specialist inpatient palliative care (N = 232) completed questionnaires on psychological burden, quality of life, social support and need fulfillment. A latent class mixture model was used to identify discrete classes of family caregivers related to their multidimensional caregiver burden. Multinomial logistic regression analyses were performed to identify the most predictive items from a set of established questionnaires.

Results
Four latent classes of family caregivers were identified: Currently stable caregivers (37%), Caregivers with unmet needs (20%), Psychologically burdened caregivers (30%), and High-risk caregivers (13%). Each of these classes describes a different risk profile of multidimensional family caregiver burden, although family caregivers exhibit high levels of distress across all classes. From a set of 48 items, we identified eight items that predicted the class membership best. These items represent the items of the novel multidimensional screening tool: The 8-item Screening Tool for Family Caregiver Burden in Palliative Care (CAREPAL-8). Except for social support, the items maintained fidelity to the conceptualization of multidimensional caregiver burden used in this study. A preliminary classification system was developed, which has yet to be validated.

Conclusions
This study represents the first step in the establishment of a practical, self-administered screening tool that might help healthcare providers to tailor caregiver care according to their burden in daily practice. Brevity of the 8-item tool might facilitate its use in routine clinical care.
A randomized controlled trial of acupuncture and receptive music therapy for sleep disorders in the elderly—ELAMUS: study protocol
Authors: Klocke C. , Rhein K. , Cramer H. , Kröger B. , Wetzel A-J. , Vagedes J. , Mauch H. , Beißner F. , Joos S. , Valentini J. 
Published: August 2024

Abstract
Background
Globally, the demographic shift towards an aging population leads to significant challenges in healthcare systems, specifically due to an increasing incidence of multimorbidity resulting in polypharmacy among the elderly. Simultaneously, sleep disorders are a common complaint for elderly people. A treatment with pharmacological therapies often leads to side effects causing a high potential for dependency. Within this context, there is a high need to explore non-pharmacological therapeutic approaches. The purpose of this study is to evaluate the effectiveness of acupuncture and music therapy, both individually and combined as a multimodal therapy, in the treatment of sleep disorders in individuals aged 70 years and older.

Methods
We conduct a confirmatory randomized controlled trial using a two-factorial study design. A total of n = 100 elderly people receive evidence-based standard care information for age-related sleep disorders. Beyond that, patients are randomly assigned into four groups of n = 25 each to receive acupuncture, receptive music therapy with a monochord, multimodal therapy with both acupuncture and music therapy, or no further therapy. The study’s primary outcome measurement is the improvement in sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) (global score), at the end of intervention. Additionally, depression scores (Geriatric Depression Scale), health-related quality of life (Short-Form-Health Survey-12), neurovegetative activity measured via heart rate variability, and safety data are collected as secondary outcomes. Using a mixed-methods approach, a qualitative process evaluation will be conducted to complement the quantitative data.

Discussion
The study is ongoing and the last patient in is expected to be enrolled in April 2024. The results can provide valuable insights into the effectiveness of non-pharmacological interventions for sleep disorders among the elderly, contributing to a more personalized and holistic approach in geriatric healthcare.

Trial registration
German Clinical Trials Register (DRKS00031886).
IGF-I and GH Genes polymorphism and their association with milk yields, composition and reproductive performance in Holstein–Friesian dairy cattle
Authors: Saleh Ahmed A. , Hassan Tarek G. M. , EL-Hedainy Dalia K. A. , El-Barbary Adel S. A. , Sharaby Mahmoud A. , Hafez Elsayed E. , Rashad Amr M. A. 
Published: August 2024

Abstract
Background
The insulin-like growth factor (IGF-I) and growth hormone (GH) genes have been identified as major regulators of milk yield and composition, and reproductive performance in cattle. Genetic variations/polymorphism in these genes have been found to influence milk production, yield and quality. This investigation aimed to explore the association between IGF-I and GH polymorphisms and milk yield and composition, and reproductive performance in a herd consisting of 1000 Holstein–Friesian (HF) dairy cattle from El-Alamia farm. The experimental animals were 76 ± 7.25 months in age, with an average live weight of 750 ± 50.49 kg, and raised under the same conditions of feeding and weather. The studied animals were divided into three categories; high producers (n = 280), medium producers (n = 318) and low producers (n = 402).

Results
The digestion of 249 bp for IGF-I-SnaBI using the Restriction-fragment-length-polymorphism (RFLP) technique yielded two alleles; T (0.59) and C (0.41) and three genotypes; TT (0.52), TC (0.39) and CC (0.09) and this agrees with the results of DNA/gene sequencing technique. The sequencing analysis of the IGF-I gene revealed polymorphism in position 472 (C > T). Nucleotide sequencing of the amplified fragment of the IGF-I gene of different genotypes was done and submitted to the NCBI GenBank with Accession no. MH156812.1 and MH156811.1. While the digestion of 432 bp for GH-AluI using the RFLP technique yielded two alleles; A (0.81) and G (0.19) and two genotypes; AA (0.77) and AG (0.23) and this agrees with the results of DNA/gene sequencing technique. The sequencing analysis of the GH gene revealed polymorphism in the position 1758 C > G and in turn led to changes in amino acid sequence as Alanine for (A) compared to Glycine for (G). Nucleotide sequencing of the amplified fragment of the GH gene was done and submitted to the NCBI GenBank with Accession no. MH156810.1. The results of this study demonstrate the effects of variants of the GH-IGF-I somatotrophic axis on milk production and composition traits in commercial HF cattle. The greatest values of milk yield and reproductive performance were observed on IGF-I-SnaBI-TC and GH-AluI-AG genotypes. While the greatest % fat and % protein values were observed on IGF-I-SnaBI-CC and GH-AluI-AA genotyped individuals.

Conclusion
The genetic variation of the studied genes can be utilized in selecting animals with superior milk yield, composition and reproductive performance in Holstein–Friesian Dairy Cattle under subtropical conditions.
Single-cell tumor heterogeneity landscape of hepatocellular carcinoma: unraveling the pro-metastatic subtype and its interaction loop with fibroblasts
Authors: Guo De-Zhen , Zhang Xin , Zhang Sen-Quan , Zhang Shi-Yu , Zhang Xiang-Yu , Yan Jia-Yan , Dong San-Yuan , Zhu Kai , Yang Xin-Rong , Fan Jia , Zhou Jian , Huang Ao 
Published: August 2024

Abstract
Background
Tumor heterogeneity presents a formidable challenge in understanding the mechanisms driving tumor progression and metastasis. The heterogeneity of hepatocellular carcinoma (HCC) in cellular level is not clear.

Methods
Integration analysis of single-cell RNA sequencing data and spatial transcriptomics data was performed. Multiple methods were applied to investigate the subtype of HCC tumor cells. The functional characteristics, translation factors, clinical implications and microenvironment associations of different subtypes of tumor cells were analyzed. The interaction of subtype and fibroblasts were analyzed.

Results
We established a heterogeneity landscape of HCC malignant cells by integrated 52 single-cell RNA sequencing data and 5 spatial transcriptomics data. We identified three subtypes in tumor cells, including ARG1+ metabolism subtype (Metab-subtype), TOP2A+ proliferation phenotype (Prol-phenotype), and S100A6+ pro-metastatic subtype (EMT-subtype). Enrichment analysis found that the three subtypes harbored different features, that is metabolism, proliferating, and epithelial-mesenchymal transition. Trajectory analysis revealed that both Metab-subtype and EMT-subtype originated from the Prol-phenotype. Translation factor analysis found that EMT-subtype showed exclusive activation of SMAD3 and TGF-β signaling pathway. HCC dominated by EMT-subtype cells harbored an unfavorable prognosis and a deserted microenvironment. We uncovered a positive loop between tumor cells and fibroblasts mediated by SPP1-CD44 and CCN2/TGF-β-TGFBR1 interaction pairs. Inhibiting CCN2 disrupted the loop, mitigated the transformation to EMT-subtype, and suppressed metastasis.

Conclusion
By establishing a heterogeneity landscape of malignant cells, we identified a three-subtype classification in HCC. Among them, S100A6+ tumor cells play a crucial role in metastasis. Targeting the feedback loop between tumor cells and fibroblasts is a promising anti-metastatic strategy.
Manipulating host secreted protein gene expression: an indirect approach by HPV11/16 E6/E7 to suppress PBMC cytokine secretion
Authors: Zhong Mei-zhen , Xu Mei-nian , Zheng Si-qi , Cheng Shu-qiong , Zeng Kang , Huang Xiao-wen 
Published: August 2024

AbstractHuman papillomavirus (HPV) 11/16 E6/E7 proteins have been recognized to be pivotal in viral pathogenesis. This study sought to uncover the potential mechanisms of how HPV11/16 E6/E7-transfected keratinocytes inhibit cytokine secretion in peripheral blood mononuclear cells (PBMC). Upon co-culturing HPV11/16 E6/E7-transfected keratinocytes with PBMC in a non-contact manner, we observed a marked decrease in various cytokines secreted by PBMC. To determine if this suppression was mediated by specific common secreted factors, we conducted transcriptomic sequencing on these transfected cells. This analysis identified 53 common differentially secreted genes in all four HPV-transfected cells. Bioinformatics analysis demonstrated these genes were predominantly involved in immune regulation. Results from quantitative PCR (qPCR) and an extensive literature review suggested the downregulation of 12 genes (ACE2, BMP3, BPIFB1, CLU, CST6, CTF1, HMGB2, MMP12, PDGFA, RNASE7, SULF2, TGM2), and upregulation of 7 genes (CCL17, CCL22, FBLN1, PLAU, S100A7, S100A8, S100A9), may be crucial in modulating tumor immunity and combating pathogenic infections, with genes S100A8 and S100A9, and IL-17 signaling pathway being particularly noteworthy. Thus, HPV11/16 E6/E7 proteins may inhibit cytokine secretion of immune cells by altering the expression of host-secreted genes. Further exploration of these genes may yield new insights into the complex dynamics of HPV infection.
Demographic characteristics, diagnostic challenges, treatment patterns, and caregiver burden of mitochondrial diseases: a retrospective cross-sectional study
Authors: Zhao Xutong , Yu Meng , Zhang Wei , Hou Yue , Yuan Yun , Wang Zhaoxia 
Published: August 2024

Abstract
Background
This study aimed to explore the demographic characteristics, diagnostic challenges, treatment patterns, and caregiver burden of mitochondrial diseases.

Methods
This retrospective cross-sectional study enrolled patients diagnosed with mitochondrial diseases from the Department of Neurology at Peking University First Hospital between January 2010 and December 2021. A questionnaire covering demographic characteristics, diagnostic dilemma, treatment, economic aspects, and caregiver stress was administered, and disability was assessed using the modified Rankin Scale (mRS).

Results
A total of 183 patients (mean age: 16 (IQR: 12–25), 49.72% males) were enrolled, including 124 pediatric patients and 59 adult patients. MELAS (106. 57.92%) and Leigh syndrome (37, 20.22%) were predominant among the mitochondrial disease subtypes. Among them, 132 (72.13%) patients were initially misdiagnosed with other diseases, 58 (31.69%) patients visited 2 hospitals before confirmed as mitochondrial disease, and 39 (21.31%) patients visited 3 hospitals before confirmed as mitochondrial disease. Metabolic modifiers were the most common type of drugs used, including several dietary supplements such as L-carnitine (117, 63.93%), Coenzyme Q10 (102, 55.74%), idebenone (82, 44.81%), and vitamins (99, 54.10%) for proper mitochondrial function. Mothers are the primary caregivers for both children (36.29%) and adults (38.98%). The mRS score ranged from 0 to 5, 92.35% of the patients had different degrees of disability due to mitochondrial disease. The average monthly treatment cost was 3000 RMB for children and 3100 RMB for adults.

Conclusions
This study provided valuable insights into the characteristics and challenges of mitochondrial diseases, which underscores the need for improved awareness, diagnostic efficiency, and comprehensive support for patients and caregivers.
Intraplantar aminoglutethimide, a P450scc inhibitor, reduced the induction of mechanical allodynia in a rat model of thrombus-induced ischemic pain
Authors: Kwon Soon-Gu , Choi Hoon-Seong , Yoon Seo-Yeon , Roh Dae-Hyun , Lee Jang-Hern 
Published: August 2024

AbstractNeuroactive steroids (NASs) directly affect neuronal excitability. Despite their role in the nervous system is intimately linked to pain control, knowledge is currently limited. This study investigates the peripheral involvement of NASs in chronic ischemic pain by targeting the cytochrome P450 side-chain cleavage enzyme (P450scc). Using a rat model of hind limb thrombus-induced ischemic pain (TIIP), we observed an increase in P450scc expression in the ischemic hind paw skin. Inhibiting P450scc with intraplantar aminoglutethimide (AMG) administration from post-operative day 0 to 3 significantly reduced the development of mechanical allodynia. However, AMG administration from post-operative day 3 to 6 did not affect established mechanical allodynia. In addition, we explored the role of the peripheral sigma-1 receptor (Sig-1R) by co-administering PRE-084 (PRE), a Sig-1R agonist, with AMG. PRE reversed the analgesic effects of AMG during the induction phase. These findings indicate that inhibiting steroidogenesis with AMG alleviates peripheral ischemic pain during the induction phase via Sig-1Rs.
Efficacy of tranexamic acid versus placebo in reducing blood loss during burn excisional surgery: a multi-center, double-blind, parallel, randomized placebo-controlled clinical trial (TRANEX)
Authors: Gigengack R. K. , Slob J. , Vries A. Meij-de , Bosma E. , Loer S. A. , Koopman J. S. H. A. , van der Vlies C. H. 
Published: August 2024

Abstract
Background
Despite an increase in knowledge, blood loss during burn excisional surgery remains a major challenge and is an independent predictor of mortality. During burn surgery, limited measures are available to control the bleeding. Increased fibrinolysis could be one of the contributing factors of blood loss during burn excisional surgery. Tranexamic acid inhibits the fibrinolytic response, and a small body of evidence shows positive effects of tranexamic acid on the volume of blood loss.

Methods
The main objectives of this study are twofold, (1) to investigate whether tranexamic acid reduces blood loss and (2) to investigate the changes in coagulation after burn trauma and during burn excisional surgery. This study is a multicenter double-blind randomized clinical trial in patients scheduled for burn excisional surgery within the Dutch burn centers. All adult patients scheduled for burn surgery with an expected blood loss of ≥ 250 are eligible for inclusion in this study. The study is powered on a blood loss reduction of 25% in the intervention group. In total, 95 subjects will be included. The intervention group will receive 1500 mg tranexamic acid versus placebo in the other group. Primary endpoint is reduction of blood loss. Secondary endpoints include occurrence of fibrinolysis during surgery, graft take of the split skin graft, and differences in coagulation and blood clot formation.

Discussion
This protocol of a randomized controlled trial aims to investigate the efficacy of tranexamic acid in reducing blood loss during burn excisional surgery. Furthermore, this study aims to clarify the coagulation status after burn trauma and during the surgical process.

Trial registration
EudraCT: 2020-005405-10; ClinicalTrial.gov: NCT05507983 (retrospectively registered in August 2022, inclusion started in December 2021).
Anticoccidial activity of a botanical natural product based on eucalyptus, apigenin and eugenol against Eimeria tenella in broiler chickens
Authors: Geng Tiantian , Ruan Xiaodie , Xie Ying , Shen Bang , Fang Rui , Zhao Junlong , Zhou Yanqin 
Published: August 2024

Abstract
Background
Chicken coccidiosis is an intracellular parasitic disease that presents major challenges to the development of the commercial poultry industry. Perennial drug selective pressure has led to the multi-drug resistance of chicken coccidia, which makes the prevention and control of chicken coccidiosis extremely difficult. In recent years, natural plant products have attracted the attention of researchers due to their inherent advantages, such as the absence of veterinary drug residues. The development of these natural products provides a new direction for the prevention and treatment of chicken coccidiosis.

Methods
The anticoccidial effect of a natural plant product combination formulation (eucalyptus oil + apigenin + eugenol essential oil) was tested against Eimeria tenella in broilers. To search for the optimal concentration of the combination formulation, we screened 120 broilers in a chicken cage trial in which 100 broilers were infected with 5 × 104 sporulated Eimeria tenella oocysts; broilers receiving a decoquinate solution was set up as a chemical control. The optimal anticoccidial concentration was determined by calculating the anticoccidial index (ACI), and the suitable concentration was used as the recommended dose for a series of safety dose assessment tests, such as feed conversion ratio (FCR), hematological indices and serum biochemical indices, as well as liver and kidney sections, at onefold (low dose), threefold (medium dose) and sixfold (high dose) the recommended dose (RD).

Results
The results showed that this combination formulation of three plant natural products had a better anticoccidial effect than formulations containing two plant natural products or a single one, with an ACI of 169.3. The dose gradient anticoccidial test revealed that the high-dose formulation group had a better anticoccidial effect (ACI = 169.2) than the medium- and low-dose groups. The safety evaluation test showed that concentrations of the formulation at one-, three- and sixfold the RD were non-toxic to Arbor Acres broilers, indicating the high safety of the combination formulation.

Conclusions
The combination formulation showed not only a moderate anticoccidial effect but also had a high safety profile for broilers. The results of this study indicate a new alternative for the prevention and control of coccidiosis in broilers.

Graphical Abstract