bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adiponectin blood levels and autism spectrum disorders: a systematic review
Authors: Ali Mohsan , Kamran Maha , Talha Muhammad , Shad Mujeeb U. 
Published: January 2024

Abstract
Objective
To review the relationship between adiponectin levels and autism spectrum disorders (ASDs) in children.

Background
ASDs are associated with pervasive social interaction and communication abnormalities. Researchers have studied various pathophysiological mechanisms underlying ASDs to identify predictors for an early diagnosis to optimize treatment outcomes. Immune dysfunction, perhaps mediated by a decrease in anti-inflammatory adipokine, adiponectin, along with changes in other adipokines, may play a central role in increasing the risk for ASDs. However, other factors, such as low maternal vitamin D levels, atherosclerosis, diabetes, obesity, cardio-metabolic diseases, preterm delivery, and oxytocin gene polymorphism may also contribute to increased risk for ASDs.

Methods
Searches on the database; PubMed, Google Scholar, and Cochrane using keywords; adiponectin, adipokines, ASD, autism, autistic disorder, included English-language studies published till September 2022. Data were extracted on mean differences between adiponectin levels in children with and without ASDs.

Results
The search yielded six studies providing data on adiponectin levels in young patients with ASDs. As can be seen from Table 1, four of the six studies were positive for an inverse correlation between ASD and adiponectin levels. In addition, two of the four positive and one negative studies found low adiponectin levels associated with and the severity of autistic symptoms. However, results from one reviewed study were insignificant.

Conclusion
Most studies reviewed yielded lower adiponectin levels in children with ASDs as well as the severity of autistic symptoms.
Photobiomodulation therapy’s impact on angiogenesis and osteogenesis in orthodontic tooth movement: in vitro and in vivo study
Authors: Zhong Jietong , Zhang Xinyu , Ruan Yaru , Huang Yue 
Published: January 2024

Abstract
Background
This study explores the effectiveness of Photobiomodulation Therapy (PBMT) in enhancing orthodontic tooth movement (OTM), osteogenesis, and angiogenesis through a comprehensive series of in vitro and in vivo investigations. The in vitro experiments involved co-culturing MC3T3-E1 and HUVEC cells to assess PBMT’s impact on cell proliferation, osteogenesis, angiogenesis, and associated gene expression. Simultaneously, an in vivo experiment utilized an OTM rat model subjected to laser irradiation at specific energy densities.

Methods
In vitro experiments involved co-culturing MC3T3-E1 and HUVEC cells treated with PBMT, enabling a comprehensive assessment of cell proliferation, osteogenesis, angiogenesis, and gene expression. In vivo, an OTM rat model was subjected to laser irradiation at specified energy densities. Statistical analyses were performed to evaluate the significance of observed differences.

Results
The results revealed a significant increase in blood vessel formation and new bone generation within the PBMT-treated group compared to the control group. In vitro, PBMT demonstrated positive effects on cell proliferation, osteogenesis, angiogenesis, and gene expression in the co-culture model. In vivo, laser irradiation at specific energy densities significantly enhanced OTM, angiogenesis, and osteogenesis.

Conclusions
This study highlights the substantial potential of PBMT in improving post-orthodontic bone quality. The observed enhancements in angiogenesis and osteogenesis suggest a pivotal role for PBMT in optimizing treatment outcomes in orthodontic practices. The findings position PBMT as a promising therapeutic intervention that could be seamlessly integrated into orthodontic protocols, offering a novel dimension to enhance overall treatment efficacy. Beyond the laboratory, these results suggest practical significance for PBMT in clinical scenarios, emphasizing its potential to contribute to the advancement of orthodontic treatments. Further exploration of PBMT in orthodontic practices is warranted to unlock its full therapeutic potential.
Impact of grazing around industrial areas on milk heavy metals contamination and reproductive ovarian hormones of she-camel with assessment of some technological processes on reduction of toxic residue concentrations
Authors: Zakaria Asem Mohammed , Amin Yahia A. , Zakaria Haydi Mohamed , Farrag Foad , Fericean Liana , Banatean-Dunea Ioan , Abdo Mohamed , Hafez Ahmed , Mohamed Ragab Hassan 
Published: January 2024

AbstractHeavy metals are one of the most toxic chemical pollutants of the environment. Their hazards not restricted to human but extend to animal productivity and reproductively. The present study aimed to assess the impact of grazing around industrial areas on the levels of copper (Cu) and aluminum (Al) residues in milk samples collected from dromedary she-camels and studying their effects on some ovarian hormones. In addition, the study aimed to investigate methods of removal of the toxic concentrations of these heavy metals in milk by applying different technological processes. Blood and milk samples were collected from 30 dromedary she-camels, 15 grazing in non-industrial areas (group A) and 15 grazing in industrial areas (group B). Detection of the levels of these heavy metals in milk was done. Ovarian hormones investigation on the blood was performed. Different technological processes such as boiling, skimming and fermentation were applied to all contaminated samples to reduce the toxic concentrations of these heavy metals. Results revealed that all examined milk samples in both groups contained Cu, while 40% of group A and 100 % of group B contained Al residues with different concentrations. The levels of Cu and Al residues in samples of group A not exceeded the maximum residual limit (MRL) set by World Health Organization (WHO) while 60% and 100% of milk samples in group B contained Cu and Al residues exceeded MRL, respectively. Technological processes induce variant changes in the levels of these metals in milk. Heat treatment of milk in Al vats leads to leaching of Al from containers to the milk causing significant increase in Al load, while Cu level was not significantly affected. Boiling in stainless-steel containers decreased the levels of Al and Cu but in non-significant levels. Regarding skimming process, small amount of Cu and Al escaped into the skimmed milk while greater amount were recovered in the cream. Fermentation by probiotic bacteria showed that milk fermentation has non-significant effect on Cu and Al levels. Investigation of ovarian hormones (estrogen and progesterone) revealed presence of a signification reduction in the levels of these hormones in group B compared to group A. In addition, a negative correlation was found between these heavy metals and ovarian hormones concentrations in the blood. It is concluded that grazing of dromedary camels around industrial areas induce heavy metals toxicity represented by excretion of these metals in milk and significant reduction on ovarian function showed by reduction of estrogen and progesterone levels. Technological processes such as skimming decreased the levels of Al and Cu residues in milk.
PD-1 inhibitor plus oncolytic vaccinia virus is a safe and effective treatment option for metastatic renal cell carcinoma
Authors: Park Jee Soo , Lee Myung Eun , Kim Jongchan , Oh Keunhee , Lee Namhee , Jung Minsun , Jang Won Sik , Ham Won Sik 
Published: January 2024

Abstract
Background
Although a combination of immune checkpoint inhibitors (ICIs) is recommended as the first line treatment option for metastatic renal cell carcinoma (mRCC), several immune-related adverse events (irAEs) occur, especially hepatitis. We explored the therapeutic benefits and safety profile of combining oncolytic vaccinia virus, JX-594, with a programmed cell death protein-1 (PD-1) inhibitor.

Methods
We used early-stage and advanced-stage orthotopic murine mRCC models developed by our group. PD-1 inhibitor monotherapy or a PD-1 inhibitor combined with either JX-594 or a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor were systemically injected through the peritoneum. An immunofluorescence analysis was performed to analyze the tumor immune microenvironment (TIME). irAEs were assessed in terms of hepatitis.

Results
In the early-stage mRCC model mice, the combination of JX-594 and a PD-1 inhibitor significantly decreased the primary tumor size and number of lung nodules, compared with the ICI combination, but the JX-594 and PD-1 inhibitor combination and ICI combination did not differ significantly in the advanced-stage mRCC model mice. The JX-594 and PD-1 inhibitor combination induced tumor-suppressing TIME changes in both the early- and advanced-stage mRCC models. Furthermore, mice treated with the ICI combination had significantly greater hepatic injuries than those treated with the JX-594 and PD-1 inhibitor combination which was evaluated in early-stage mRCC model.

Conclusions
The JX-594 and PD-1 inhibitor combination effectively reduced primary tumors and the metastatic burden, similar to ICI combination therapy, through dynamic remodeling of the TIME. Furthermore, hepatitis was significantly decreased in the JX-594 and PD-1 inhibitor combination group, suggesting the potential benefit of that combination for reducing ICI-induced toxicity.
Robust machine−learning based prognostic index using cytotoxic T lymphocyte evasion genes highlights potential therapeutic targets in colorectal cancer
Authors: Wang Xu , Chan Shixin , Chen Jiajie , Xu Yuanmin , Dai Longfei , Han Qijun , Wang Zhenglin , Zuo Xiaomin , Yang Yang , Zhao Hu , Wang Ming , Wang Chen , Li Zichen , Zhang Huabing , Chen Wei 
Published: January 2024

Abstract
Background
A minute fraction of patients stands to derive substantial benefits from immunotherapy, primarily attributable to immune evasion. Our objective was to formulate a predictive signature rooted in genes associated with cytotoxic T lymphocyte evasion (CERGs), with the aim of predicting outcomes and discerning immunotherapeutic response in colorectal cancer (CRC).

Methods
101 machine learning algorithm combinations were applied to calculate the CERGs prognostic index (CERPI) under the cross−validation framework, and patients with CRC were separated into high− and low−CERPI groups. Relationship between immune cell infiltration levels, immune−related scores, malignant phenotypes and CERPI were further analyzed. Various machine learning methods were used to identify key genes related to both patient survival and immunotherapy benefits. Expression of HOXC6, G0S2, and MX2 was evaluated and the effects of HOXC6 and G0S2 on the viability and migration of a CRC cell line were in−vitro verified.

Results
The CERPI demonstrated robust prognostic efficacy in predicting the overall survival of CRC patients, establishing itself as an independent predictor of patient outcomes. The low−CERPI group exhibited elevated levels of immune cell infiltration and lower scores for tumor immune dysfunction and exclusion, indicative of a greater potential benefit from immunotherapy. Moreover, there was a positive correlation between CERPI levels and malignant tumor phenotypes, suggesting that heightened CERPI expression contributes to both the occurrence and progression of tumors. Thirteen key genes were identified, and their expression patterns were scrutinized through the analysis of single−cell datasets. Notably, HOXC6, G0S2, and MX2 exhibited upregulation in both CRC cell lines and tissues. Subsequent knockdown experiments targeting G0S2 and HOXC6 resulted in a significant suppression of CRC cell viability and migration.

Conclusion
We developed the CERPI for effectively predicting survival and response to immunotherapy in patients, and these results may provide guidance for CRC diagnosis and precise treatment.
Beyond timing and step counting in 360° turning-in-place assessment: a scoping review
Authors: Netukova Slavka , Horakova Lucie , Szabo Zoltan , Krupicka Radim 
Published: January 2024

Abstract
Background
Turning in place is a challenging motor task and is used as a brief assessment test of lower limb function and dynamic balance. This review aims to examine how research of instrumented analysis of turning in place is implemented. In addition to reporting the studied population, we covered acquisition systems, turn detection methods, quantitative parameters, and how these parameters are computed.

Methods
Following the development of a rigorous search strategy, the Web of Science and Scopus were systematically searched for studies involving the use of turning-in-place. From the selected articles, the study population, types of instruments used, turn detection method, and how the turning-in-place characteristics were calculated.

Results
Twenty-one papers met the inclusion criteria. The subject groups involved in the reviewed studies included young, middle-aged, and older adults, stroke, multiple sclerosis and Parkinson’s disease patients. Inertial measurement units (16 studies) and motion camera systems (5 studies) were employed for gathering measurement data, force platforms were rarely used (2 studies). Two studies used commercial software for turn detection, six studies referenced previously published algorithms, two studies developed a custom detector, and eight studies did not provide any details about the turn detection method. The most frequently used parameters were mean angular velocity (14 cases, 7 studies), turn duration (13 cases, 13 studies), peak angular velocity (8 cases, 8 studies), jerkiness (6 cases, 5 studies) and freezing-of-gait ratios (5 cases, 5 studies). Angular velocities were derived from sensors placed on the lower back (7 cases, 4 studies), trunk (4 cases, 2 studies), and shank (2 cases, 1 study). The rest (9 cases, 8 studies) did not report sensor placement. Calculation of the freezing-of-gait ratio was based on the acceleration of the lower limbs in all cases. Jerkiness computation employed acceleration in the medio-lateral (4 cases) and antero-posterior (1 case) direction. One study did not reported any details about jerkiness computation.

Conclusion
This review identified the capabilities of turning-in-place assessment in identifying movement differences between the various subject groups. The results, based on data acquired by inertial measurement units across studies, are comparable. A more in-depth analysis of tests developed for gait, which has been adopted in turning-in-place, is needed to examine their validity and accuracy.
Role of a novel circRNA-CGNL1 in regulating pancreatic cancer progression via NUDT4–HDAC4–RUNX2–GAMT-mediated apoptosis
Authors: Yuan Hao , Chen Chuang , Li Haonan , Qu Gexi , Chen Luyao , Liu Yaxing , Zhang Yufeng , Zhao Qiang , Lian Changhong , Ji Aifang , Hou Xuedong , Liu Xinjian , Jiang Kuirong , Zhu Yi , He Yuan 
Published: January 2024

Abstract
Background
Pancreatic cancer (PC) is an extremely malignant tumor with low survival rate. Effective biomarkers and therapeutic targets for PC are lacking. The roles of circular RNAs (circRNAs) in cancers have been explored in various studies, however more work is needed to understand the functional roles of specific circRNAs. In this study, we explore the specific role and mechanism of circ_0035435 (termed circCGNL1) in PC.

Methods
qRT-PCR analysis was performed to detect circCGNL1 expression, indicating circCGNL1 had low expression in PC cells and tissues. The function of circCGNL1 in PC progression was examined both in vitro and in vivo. circCGNL1-interacting proteins were identified by performing RNA pulldown, co-immunoprecipitation, GST-pulldown, and dual-luciferase reporter assays.

Results
Overexpressing circCGNL1 inhibited PC proliferation via promoting apoptosis. CircCGNL1 interacted with phosphatase nudix hydrolase 4 (NUDT4) to promote histone deacetylase 4 (HDAC4) dephosphorylation and subsequent HDAC4 nuclear translocation. Intranuclear HDAC4 mediated RUNX Family Transcription Factor 2 (RUNX2) deacetylation and thereby accelerating RUNX2 degradation. The transcription factor, RUNX2, inhibited guanidinoacetate N-methyltransferase (GAMT) expression. GAMT was further verified to induce PC cell apoptosis via AMPK–AKT–Bad signaling pathway.

Conclusions
We discovered that circCGNL1 can interact with NUDT4 to enhance NUDT4-dependent HDAC4 dephosphorylation, subsequently activating HDAC4–RUNX2–GAMT-mediated apoptosis to suppress PC cell growth. These findings suggest new therapeutic targets for PC.
Association of hysterectomy with nonalcoholic fatty liver disease among US women
Authors: Jin Shuanghong , Li Shaoxun , Fang Peipei , Pan Chenwei , Huang Shanshan 
Published: January 2024

Abstract
Background
A postmenopausal rise in the rates of nonalcoholic fatty liver disease (NAFLD) has been reported in women. This study thus sought to further probe the association of hysterectomy with NAFLD.

Methods
The data utilized in this investigation were attained from the 2017-March 2020 cycle of the National Health and Nutrition Examination Survey (NHANES), reflecting a strategic utilization of comprehensive health and nutrition information in the US population, to conduct a cross-sectional examination of the relationship between self-reported hysterectomy and NAFLD. Subjects included in this study were women aged 20 years or older. The multivariable logistic regression methodologies were utilized to determine the pertinent odds ratios (ORs) and their associated 95% confidence intervals (CIs).

Results
Of the 2,868 subjects enrolled in this study (mean age: 51.3 years, 95%CI: 50.0-52.6 years), 22.1% (95%CI: 19.7–24.7%) reported having undergone a hysterectomy, while 31.1% (95%CI: 28.1–34.1%) exhibited elastographic evidence of NAFLD, and 3.8% (95%CI: 2.6–5.6%) exhibited clinically significant fibrosis (CSF). Relative to women with no history of hysterectomy, those that had undergone hysterectomy exhibited a higher odd of NAFLD (OR:1.66, 95%CI: 1.24–2.21) in a multivariable model fully adjusted for age, ethnicity, body mass index, female hormone use, oophorectomy, diabetes, hyperlipidemia, and smoking status. Subgroup analyses revealed a stronger association among women who were not obese (OR:2.23, 95%CI:1.61–3.11), women who were not affected by diabetes (OR:1.76, 95%CI: 1.25–2.46), and without hyperlipidemia (OR: 1.87, 95%CI: 1.10–3.16). No significant association of hysterectomy with NAFLD encompassing CSF was identified.

Conclusions
The results of the present nationally representative analysis suggested an association between hysterectomy and increased NAFLD prevalence among US women. Knowledge of this relationship may better aid clinical efforts to screen for and manage NAFLD.
Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy
Authors: He Jiang , Zhou You , Sun Lunquan 
Published: January 2024

AbstractThe accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and activates the unfolded protein response (UPR). As an adaptive cellular response to hostile microenvironments, such as hypoxia, nutrient deprivation, oxidative stress, and chemotherapeutic drugs, the UPR is activated in diverse cancer types and functions as a dynamic tumour promoter in cancer development; this role of the UPR indicates that regulation of the UPR can be utilized as a target for tumour treatment. T-cell exhaustion mainly refers to effector T cells losing their effector functions and expressing inhibitory receptors, leading to tumour immune evasion and the loss of tumour control. Emerging evidence suggests that the UPR plays a crucial role in T-cell exhaustion, immune evasion, and resistance to immunotherapy. In this review, we summarize the molecular basis of UPR activation, the effect of the UPR on immune evasion, the emerging mechanisms of the UPR in chemotherapy and immunotherapy resistance, and agents that target the UPR for tumour therapeutics. An understanding of the role of the UPR in immune evasion and therapeutic resistance will be helpful to identify new therapeutic modalities for cancer treatment.
A novel online calculator based on clinical features and hematological parameters to predict total skin clearance in patients with moderate to severe psoriasis
Authors: Jiang Yuxiong , Huang Dawei , Chen Qianyu , Yu Yingyuan , Hu Yifan , Wang Yu , Chen Rongfen , Yao Lingling , Zhong Xiaoyuan , Kong Luyang , Yu Qian , Lu Jiajing , Li Ying , Shi Yuling 
Published: January 2024

Abstract
Background
Treatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience partial improvement.

Objective
This study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response.

Methods
A total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively.

Results
The following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670–0.773) and validation cohort (AUC, 0.715; 95% CI 0.665–0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications.

Conclusions
This study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility.
Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256.