bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphometric studies on the appendicular bony skeleton of the ostriches (Struthio Camelus)
Authors: Kassem Menna Allah M. , Tahon Reem R. , Khalil Karim M. , El-Ayat Medhat A.
Published: August 2023

Background

Morphometric study of the bony elements of the appendicular skeleton in the ostrich was fully described and identified. The appendicular skeleton included the bones of the pectoral girdle, the wing, the pelvic girdle and the pelvic limb.

Results

The shoulder girdle of the ostrich included the scapula and coracoid bones. The scapula appeared as a flattened spoon-like structure. The coracoid bone appeared quadrilateral in outline. The mean length of the scapula and coracoid (sternal wing) were 15.00 ± 0.23 and 10.00 ± 0.17 cm, respectively. The wing included the humerus, ulna, radius, radial carpal bone, ulnar carpal bone, carpometacarpus and phalanges of three digits. The mean length of the humerus, radius, and ulna were 33.00 ± 0.46, 10.50 ± 0.40 and 11.50 ± 0.29 cm respectively. The carpometacarpus was formed by the fusion of the distal row of carpal bones and three metacarpal bones. Digits of the wing were three in number; the alular, major and minor digits. Os coxae comprised the ilium, ischium and pubis. Their mean lengths were 36.00 ± 0.82 cm, 32.00 ± 0.20 and 55.00 ± 0.2.9 cm, respectively. The femur was a stout short bone, that appeared shorter than the tibiotarsus. The mean length of the femur, tibiotarsus, and tarsometatarsus were 30.00 ± 0.23, 52.00 ± 0.50 and 46.00 ± 0.28 cm. Tibiotarsus was the longest bone in the pelvic limb. The fibula was a long bone (44.00 ± 0.41 cm) lying along the lateral surface of the tibiotarsus. The tarsometatarsus was a strong long bone formed by the fusion of the metatarsal (II, III, IV) and the distal row of tarsal bones. It was worth mentioning that metatarsal II was externally absent in adults.

Conclusions

In the appendicular skeleton of ostrich, there were special characteristic features that were detected in our study; the clavicle was absent, the coracoid bone was composed of a sternal wing and scapular wing, the ulna was slightly longer in length than the radius. The coupled patellae i.e., the proximal and distal patella were observed; and the ostrich pedal digits were only two; viz., the third (III) and fourth (IV) digits.
Prognostic importance of glycemic variability on left ventricular reverse remodeling after the first episode of ST-segment elevation myocardial infarction
Authors: Hanajima Yohei , Iwahashi Noriaki , Kirigaya Jin , Horii Mutsuo , Minamimoto Yugo , Gohbara Masaomi , Abe Takeru , Okada Kozo , Matsuzawa Yasushi , Kosuge Masami , Ebina Toshiaki , Hibi Kiyoshi
Published: August 2023

Background

This study aimed to investigate the effect of glycemic variability (GV), determined using a continuous glucose monitoring system (CGMS), on left ventricular reverse remodeling (LVRR) after ST-segment elevation myocardial infarction (STEMI).

Methods

A total of 201 consecutive patients with STEMI who underwent reperfusion therapy within 12 h of onset were enrolled. GV was measured using a CGMS and determined as the mean amplitude of glycemic excursion (MAGE). Left ventricular volumetric parameters were measured using cardiac magnetic resonance imaging (CMRI). LVRR was defined as an absolute decrease in the LV end-systolic volume index of > 10% from 1 week to 7 months after admission. Associations were also examined between GV and LVRR and between LVRR and the incidence of major adverse cardiovascular events (MACE; cardiovascular death, acute coronary syndrome recurrence, non-fatal stroke, and heart failure hospitalization).

Results

The prevalence of LVRR was 28% (n = 57). The MAGE was independent predictor of LVRR (odds ratio [OR] 0.98, p = 0.002). Twenty patients experienced MACE during the follow-up period (median, 65 months). The incidence of MACE was lower in patients with LVRR than in those without (2% vs. 13%, p = 0.016).

Conclusion

Low GV, determined using a CGMS, was significantly associated with LVRR, which might lead to a good prognosis. Further studies are needed to validate the importance of GV in LVRR in patients with STEMI.
An innovative model for predicting coronary heart disease using triglyceride-glucose index: a machine learning-based cohort study
Authors: Mirjalili Seyed Reza , Soltani Sepideh , Heidari Meybodi Zahra , Marques-Vidal Pedro , Kraemer Alexander , Sarebanhassanabadi Mohammadtaghi
Published: August 2023

Background

Various predictive models have been developed for predicting the incidence of coronary heart disease (CHD), but none of them has had optimal predictive value. Although these models consider diabetes as an important CHD risk factor, they do not consider insulin resistance or triglyceride (TG). The unsatisfactory performance of these prediction models may be attributed to the ignoring of these factors despite their proven effects on CHD. We decided to modify standard CHD predictive models through machine learning to determine whether the triglyceride-glucose index (TyG-index, a logarithmized combination of fasting blood sugar (FBS) and TG that demonstrates insulin resistance) functions better than diabetes as a CHD predictor.

Methods

Two-thousand participants of a community-based Iranian population, aged 20–74 years, were investigated with a mean follow-up of 9.9 years (range: 7.6–12.2). The association between the TyG-index and CHD was investigated using multivariate Cox proportional hazard models. By selecting common components of previously validated CHD risk scores, we developed machine learning models for predicting CHD. The TyG-index was substituted for diabetes in CHD prediction models. All components of machine learning models were explained in terms of how they affect CHD prediction. CHD-predicting TyG-index cut-off points were calculated.

Results

The incidence of CHD was 14.5%. Compared to the lowest quartile of the TyG-index, the fourth quartile had a fully adjusted hazard ratio of 2.32 (confidence interval [CI] 1.16–4.68, p-trend 0.04). A TyG-index > 8.42 had the highest negative predictive value for CHD. The TyG-index-based support vector machine (SVM) performed significantly better than diabetes-based SVM for predicting CHD. The TyG-index was not only more important than diabetes in predicting CHD; it was the most important factor after age in machine learning models.

Conclusion

We recommend using the TyG-index in clinical practice and predictive models to identify individuals at risk of developing CHD and to aid in its prevention.
LINC02159 promotes non-small cell lung cancer progression via ALYREF/YAP1 signaling
Authors: Yang Qiurong , Wang Maoye , Xu Jing , Yu Dan , Li Yixin , Chen Yanke , Zhang Xiaoxin , Zhang Jiahui , Gu Jianmei , Zhang Xu
Published: August 2023

Lung cancer is the leading cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have emerged as key regulators of cancer development and progression, and as promising biomarkers for the diagnosis and prognosis of cancer. In this study, we identified a new lncRNA (LINC02159) that was upregulated in the tumor tissues and serum of non-small cell lung cancer (NSCLC) patients. We demonstrated that knockdown of LINC02159 inhibited NSCLC cell proliferation, migration, and invasion, but induced cell apoptosis and cell cycle arrest in vitro and retarded tumor growth in vivo, while overexpression of LINC02159 led to the opposite effect. We discovered that LINC02159 was highly correlated with cancer growth and metastasis-related pathways by using transcriptomic analysis and that YAP1 was a potential target gene of LINC02159. Mechanistically, LINC02159 bound to the Aly/REF export factor (ALYREF) to enhance the stability of YAP1 messenger RNA (mRNA) via m5C modification, which led to the overexpression of YAP1 and the activation of the Hippo and β-catenin signaling pathways in NSCLC cells. Rescue experiments showed that LINC01259 promoted NSCLC progression in a YAP1- and ALYREF-dependent manner. In conclusion, LINC02159 plays an oncogenic role in NSCLC progression by regulating ALYREF/YAP1 signaling, and it has the potential to be utilized as a diagnostic marker and therapeutic target for NSCLC.
Metallic nanoplatforms for COVID-19 diagnostics: versatile applications in the pandemic and post-pandemic era
Authors: Li Yuqing , Chen Jingqi , Wei Jinchao , Liu Xueliang , Yu Lu , Yu Linqi , Ding Ding , Yang Yu
Published: August 2023

The COVID-19 pandemic, which originated in Hubei, China, in December 2019, has had a profound impact on global public health. With the elucidation of the SARS-CoV-2 virus structure, genome type, and routes of infection, a variety of diagnostic methods have been developed for COVID-19 detection and surveillance. Although the pandemic has been declared over, we are still significantly affected by it in our daily lives in the post-pandemic era. Among the various diagnostic methods, nanomaterials, especially metallic nanomaterials, have shown great potential in the field of bioanalysis due to their unique physical and chemical properties. This review highlights the important role of metallic nanosensors in achieving accurate and efficient detection of COVID-19 during the pandemic outbreak and spread. The sensing mechanisms of each diagnostic device capable of analyzing a range of targets, including viral nucleic acids and various proteins, are described. Since SARS-CoV-2 is constantly mutating, strategies for dealing with new variants are also suggested. In addition, we discuss the analytical tools needed to detect SARS-CoV-2 variants in the current post-pandemic era, with a focus on achieving rapid and accurate detection. Finally, we address the challenges and future directions of metallic nanomaterial-based COVID-19 detection, which may inspire researchers to develop advanced biosensors for COVID-19 monitoring and rapid response to other virus-induced pandemics based on our current achievements.
Anti-glioma effect of ginseng-derived exosomes-like nanoparticles by active blood–brain-barrier penetration and tumor microenvironment modulation
Authors: Kim Jisu , Zhu Ying , Chen Sunhui , Wang Dongdong , Zhang Shuya , Xia Jiaxuan , Li Shiyi , QIU Qiujun , Lee Hyukjin , Wang Jianxin
Published: August 2023

Inhibition of tumor growth and normalization of immune responses in the tumor microenvironment (TME) are critical issues for improving cancer therapy. However, in the treatment of glioma, effective nanomedicine has limited access to the brain because of the blood–brain barrier (BBB). Previously, we demonstrated nano-sized ginseng-derived exosome-like nanoparticles (GENs) consisting of phospholipids including various bioactive components, and evaluated anti-tumor immune responses in T cells and Tregs to inhibit tumor progression. It was found that the enhanced targeting ability of GENs to the BBB and glioma induced a significant therapeutic effect and exhibited strong efficacy in recruiting M1 macrophage expression in the TME. GENs were demonstrated to be successful candidates in glioma therapeutics both in vitro and in vivo, suggesting excellent potential for inhibiting glioma progression and regulating tumor-associated macrophages (TAMs).
Effects of probiotic administration on overweight or obese children: a meta-analysis and systematic review
Authors: Li Ya , Liu Tonghua , Qin Lingling , Wu Lili
Published: August 2023

Background

This paper aimed to examine the effects of probiotics on eight factors in overweight or obese children by meta-analysis, namely, body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), adiponectin, leptin and tumor necrosis factor-α (TNF-α) and summarize the mechanisms of action of probiotics based on the existing researches.

Methods

Six databases (PubMed, Web of Science, Embase, Cochrane Library, SinoMed and CNKI) were searched until March 2023. Review Manager 5.4 was used for meta-analysis. The data were analysed using weighted mean differences (WMDs) or standardized mean differences (SMDs) under a fixed effect model or random effect model to observe the effects of probiotic administration on the included indicators.

Results

Four publications with a total of 206 overweight or obesity children were included. According to the meta-analysis, probiotics were able to significantly decrease the levels of HDL-C (MD, 0.06; 95% CI 0.03, 0.09; P = 0.0001), LDL-C (MD, − 0.06; 95% CI − 0.12, − 0.00; P = 0.04), adiponectin (MD, 1.39; 95% CI 1.19, 1.59; P < 0.00001), leptin (MD, − 2.72; 95% CI − 2.9, − 2.54; P < 0.00001) and TNF-α (MD, − 4.91; 95% CI − 7.15, − 2.67; P < 0.0001) compared to those in the placebo group. Still, for BMI, the palcebo group seemed to be better than the probiotic group (MD, 0.85; 95% CI 0.04, 1.66; P = 0.04). TC (MD, − 0.05; 95% CI − 0.12, 0.02; P = 0.14) and TG (MD, − 0.16; 95% CI − 0.36, 0.05; P = 0.14) were not different between two groups.

Conclusions

This review drew that probiotics might act as a role in regulating HDL-C, LDL-C, adiponectin, leptin and TNF-α in overweight or obesity children. Additionally, our systematic review yielded that probiotics might regulate lipid metabolism and improve obese associated symptoms by some paths. This meta-analysis has been registered at PROSPERO with ID: CRD42023408359.
Utilization of overground exoskeleton gait training during inpatient rehabilitation: a descriptive analysis
Authors: Gillespie Jaime , Arnold Dannae , Trammell Molly , Bennett Monica , Ochoa Christa , Driver Simon , Callender Librada , Sikka Seema , Dubiel Rosemary , Swank Chad
Published: August 2023

Background

Overground exoskeleton gait training (OEGT) after neurological injury is safe, feasible, and may yield positive outcomes. However, no recommendations exist for initiation, progression, or termination of OEGT. This retrospective study highlights the clinical use and decision-making of OEGT within the physical therapy plan of care for patients after neurological injury during inpatient rehabilitation.

Methods

The records of patients admitted to inpatient rehabilitation after stroke, spinal cord injury, or traumatic brain injury who participated in at least one OEGT session were retrospectively reviewed. Session details were analyzed to illustrate progress and included: “up” time, “walk” time, step count, device assistance required for limb swing, and therapist-determined settings. Surveys were completed by therapists responsible for OEGT sessions to illuminate clinical decision-making.

Results

On average, patients demonstrated progressive tolerance for OEGT over successive sessions as shown by increasing time upright and walking, step count, and decreased assistance required by the exoskeleton. Therapists place preference on using OEGT with patients with more functional dependency and assess feedback from the patient and device to determine when to change settings. OEGT is terminated when other gait methods yield higher step repetitions or intensities, or to prepare for discharge.

Conclusion

Our descriptive retrospective data suggests that patients after neurological injury may benefit from OEGT during inpatient rehabilitation. As no guidelines exist, therapists’ clinical decisions are currently based on a combination of knowledge of motor recovery and experience. Future efforts should aim to develop evidence-based recommendations to facilitate functional recovery after neurological injury by leveraging OEGT.
Comparison of antibacterial activity and biocompatibility of non-leaching nitrofuran bone cement loaded with vancomycin, gentamicin, and tigecycline
Authors: Gao Zhe , Xu Yang , Kan Yuchen , Li Hailong , Guo Rui , Han Luyang , Bu Wenhan , Chu Jianjun
Published: August 2023

Background

Non-leaching antibacterial bone cement can generate long-term antibacterial activity, it cannot treat serious infections that have occurred like antibiotic-loaded bone cement. Currently, the antibacterial activity and biocompatibility of non-leaching cement when loaded with antibiotics have yet to be determined.

Methods

Non-leaching antibacterial nitrofuran bone cement (NFBC) specimens were prepared with low-dose and high-dose antibiotics. The antibacterial activity and biocompatibility of NFBC loaded with vancomycin, gentamicin, and tigecycline were compared. The agar diffusion method was employed to observe the inhibition zone of the samples against two bacterial strains from day one to day seven. The CCK-8 assay and acute liver and kidney toxicity test were conducted to assess the effects of the samples on mouse embryo osteoblast precursor cells and C57 mice, respectively.

Results

Gentamicin-loaded cement exhibited the most potent antibacterial activity, effectively inhibiting both bacterial strains at a low dose. Tigecycline-loaded cement demonstrated superior biocompatibility, showing no acute liver and kidney toxicity in mice and minimal cytotoxicity to osteoblasts.

Conclusions

NFBC loaded with gentamicin, vancomycin, and tigecycline not only maintains sustained antibacterial activity but also exhibits excellent biocompatibility.
Complications and hospitalization costs in patients with hypothyroidism following total hip arthroplasty
Authors: Huang Yuanyuan , Huang Yuzhi , Chen Yuhang , Yang Qinfeng , Yin Binyan
Published: August 2023

Background

Hypothyroidism is a common disease in the US population. The impact of hypothyroidism on perioperative complications of total hip arthroplasty is poorly understood. To examine risk factors and hospitalization costs in patients with hypothyroidism after total hip arthroplasty (THA) using a large-scale sample national database.

Methods

A case–control study was performed based on the national inpatient sample database from 2005 to 2014. With the use of propensity scores, patients with hypothyroidism were matched in a 1:1 ratio to those without hypothyroidism by age, gender, race, Elixhauser Comorbidity Index (ECI), and insurance type. Patient demographics, postoperative complications, length of stay (LOS), and hospital costs were compared between matched cohorts. Short-term complication rates after THA were compared using multivariate logistic analysis.

Results

The proportion of patients with hypothyroidism receiving THA was 12.97%. Linear regression analysis yielded that patients with hypothyroidism receiving THA were more likely to have postoperative acute anemia (odds ratio = 1.15; 95% confidence interval = 1.12–1.18) and higher mean hospital costs compared to the non-hypothyroid cohort.

Conclusions

This present study demonstrates that hypothyroid patients undergoing THA have a higher risk of short-term complications. Furthermore, it significantly increased the total cost of hospitalization, which deserves more attention from orthopedic surgeons.
Effects of different pelvic osteotomy surgeries on acetabular center and pelvic morphology
Authors: Liu Can , Wang Kongjian , Tang Zhongwen , Wen Jie , Xiao Sheng
Published: August 2023

Objective

To compare the effects of Salter pelvic osteotomy, Pemberton pelvic osteotomy, and triple pelvic osteotomy on the center of acetabulum and pelvic morphology in children with hip joint disease.

Methods

The data of children treated with Salter pelvic osteotomy (2 males and 14 females with an average age of 2.49 years), Pemberton pelvic osteotomy (4 males and 11 females with an average age of 6.11 years), and triple pelvic osteotomy(4 males and 8 females with an average age of 9.59 years) between January 2011 and December 2020 were collected. After discharge, the outpatient review was followed up for at least 1 year. All patients underwent anterior–posterior pelvic X-ray scanning before surgery, three months after surgery in the first year and every six months after the first year. The following X-ray features were analyzed: bilateral pelvic height (PH), iliac crest inclination (ICI), a horizontal distance of the acetabulum center (HD), and vertical distance of the acetabulum center (VD).

Results

The mean follow-up time was 16.9 ± 4.9 months in the Salter group, 20.7 ± 5.1 months in the Pemberton group, and 18.0 ± 5.4 months in the triple group (all P > 0.05). No significant differences between PH, HD, and VD of both sides on the preoperative AP pelvic x-ray were found. However, at the last follow-up, PH, HD,VD, and ICI increased in the Salter group (all P < 0.05), PH and VD increased in the Pemberton group (all P < 0.05), and VD decreased in the Triple group (P < 0.05).

Conclusion

Salter pelvic osteotomy may cause pelvic height to increase and the center of acetabulum to move outward and downward. In contrast, Pemberton pelvic osteotomy may cause pelvic height to increase and the center of acetabulum to move downward. Triple pelvic osteotomy only causes the center of acetabulum to move downward.
Genotype, phenotype and treatment outcomes of 17 Malaysian patients with infantile-onset Pompe disease and the identification of 3 novel GAA variants
Authors: Chan Mei-Yan , Jalil Julaina Abdul , Yakob Yusnita , Wahab Siti Aishah Abdul , Ali Ernie Zuraida , Khalid Mohd Khairul Nizam Mohd , Leong Huey-Yin , Chew Hui-Bein , Sivabalakrishnan Jeya Bawani , Ngu Lock-Hock
Published: August 2023

Background

Pompe disease is a rare glycogen storage disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to glycogen deposition in multiple tissues. Infantile-onset Pompe disease (IOPD) patients present within the first year of life with profound hypotonia and hypertrophic cardiomyopathy. Treatment with enzyme replacement therapy (ERT) has significantly improved survival for this otherwise lethal disorder. This study aims to describe the clinical and molecular spectrum of Malaysian IOPD patients, and to analyze their long term treatment outcomes.

Methods

Seventeen patients diagnosed with IOPD between 2000 and 2020 were included in this retrospective cohort study. Clinical and biochemical data were collated and analyzed using descriptive statistics. GAA enzyme levels were performed on dried blood spots. Molecular analysis of the GAA gene was performed by polymerase chain reaction and Sanger sequencing. Structural modelling was used to predict the effect of the novel mutations on enzyme structure.

Results

Our cohort had a median age of presentation of 3 months and median age of diagnosis of 6 months. Presenting features were hypertrophic cardiomyopathy (100%), respiratory insufficiency (94%), hypotonia (88%), failure to thrive (82%), feeding difficulties (76%), and hepatomegaly (76%). Fourteen different mutations in the GAA gene were identified, with three novel mutations, c.1552-14_1552-1del, exons 2–3 deletion and exons 6–10 deletion. The most common mutation identified was c.1935C > A p.(D645E), with an allele frequency of 33%. Sixteen patients received ERT at the median age of 7 months. Overall survival was 29%. Mean age of death was 17.5 months. Our longest surviving patient has atypical IOPD and is currently 20 years old.

Conclusions

This is the first study to analyze the genotype and phenotype of Malaysian IOPD patients, and has identified the c.1935C > A p.(D645E) as the most common mutation. The three novel mutations reported in this study expands the mutation spectrum for IOPD. Our low survival rate underscores the importance of early diagnosis and treatment in achieving better treatment outcomes.
Network approach in liquidomics landscape
Authors: Santini Daniele , Botticelli Andrea , Galvano Antonio , Iuliani Michele , Incorvaia Lorena , Gristina Valerio , Taffon Chiara , Foderaro Simone , Paccagnella Elisa , Simonetti Sonia , Fazio Federico , Scagnoli Simone , Pomati Giulia , Pantano Francesco , Perrone Giuseppe , De Falco Elena , Russo Antonio , Spinelli Gian Paolo
Published: August 2023

Tissue-based biopsy is the present main tool to explore the molecular landscape of cancer, but it also has many limits to be frequently executed, being too invasive with the risk of side effects. These limits and the ability of cancer to constantly evolve its genomic profile, have recently led to the need of a less invasive and more accurate alternative, such as liquid biopsy. By searching Circulating Tumor Cells and residues of their nucleic acids or other tumor products in body fluids, especially in blood, but also in urine, stools and saliva, liquid biopsy is becoming the future of clinical oncology. Despite the current lack of a standardization for its workflows, that makes it hard to be reproduced, liquid biopsy has already obtained promising results for cancer screening, diagnosis, prognosis, and risk of recurrence.

Through a more accessible molecular profiling of tumors, it could become easier to identify biomarkers predictive of response to treatment, such as EGFR mutations in non-small cell lung cancer and KRAS mutations in colorectal cancer, or Microsatellite Instability and Mismatch Repair as predictive markers of pembrolizumab response.

By monitoring circulating tumor DNA in longitudinal repeated sampling of blood we could also predict Minimal Residual Disease and the risk of recurrence in already radically resected patients.

In this review we will discuss about the current knowledge of limitations and strengths of the different forms of liquid biopsies for its inclusion in normal cancer management, with a brief nod to their newest biomarkers and its future implications.
Lysosome blockade induces divergent metabolic programs in macrophages and tumours for cancer immunotherapy
Authors: Ma Jing , Ma Ruijuan , Zeng Xueke , Zhang Liming , Liu Jianing , Zhang Wei , Li Tao , Niu Hanjing , Bao Guochen , Wang Chaojie , Wang Peng George , Wang Jiajia , Li Xia , Zou Taotao , Xie Songqiang
Published: August 2023

Background

Platinum-drugs based chemotherapy in clinic increases the potency of tumor cells to produce M2 macrophages, thus leading to poor anti-metastatic activity and immunosuppression. Lysosome metabolism is critical for cancer cell migration and invasion, but how it promotes antitumor immunity in tumours and macrophages is poorly understood and the underlying mechanisms are elusive. The present study aimed to explore a synergistic strategy to dismantle the immunosuppressive microenvironment of tumours and metallodrugs discovery by using the herent metabolic plasticity.

Methods

Naphplatin was prepared by coordinating an active alkaline moiety to cisplatin, which can regulate the lysosomal functions. Colorectal carcinoma cells were selected to perform the in vivo biological assays. Blood, tumour and spleen tissues were collected and analyzed by flow cytometry to further explore the relationship between anti-tumour activity and immune cells. Transformations of bone marrow derived macrophage (BMDM) and M2-BMDM to the M1 phenotype was confirmed after treatment with naphplatin. The key mechanisms of lysosome-mediated mucolipin-1(Mcoln1) and mitogen-activated protein kinase (MAPK) activation in M2 macrophage polarization have been unveiled. RNA sequencing (RNA-seq) was used to further explore the key mechanism underlying high-mobility group box 1(HMGB1)-mediated Cathepsin L(CTSL)-lysosome function blockade.

Results

We demonstrated that naphplatin induces divergent lysosomal metabolic programs and reprograms macrophages in tumor cells to terminate the vicious tumour-associated macrophages (TAMs)-MDSCs-Treg triangle. Mechanistically, macrophages treated with naphplatin cause lysosome metabolic activation by triggering Ca2+ release via Mcoln1, which induces the activation of p38 and nuclear factor-κB (NF-κB) and finally results in polarizing M2 macrophages. In contrast, HMGB1-mediated lysosome metabolic blockade in cancer cells is strongly linked to antitumor effects by promoting cytoplasmic translocation of HMGB1.

Conclusions

This study reveals the crucial strategies of macrophage-based metallodrugs discovery that are able to treat both immunologically “hot” and “cold” cancers. Different from traditional platinum-based antitumour drugs by inhibition of DNAs, we also deliver a strong antitumour strategy by targeting lysosome to induce divergent metabolic programs in macrophages and tumours for cancer immunotherapy.
The importance of clinical importance when determining the target difference in sample size calculations
Authors: Parker Richard A. , Cook Jonathan A.
Published: August 2023

Recently, it was argued that clinically important differences should play no role in sample size calculations. Instead, it was proposed that sample size calculations should focus on setting realistic estimates of treatment benefit. We disagree, and argue in this article that considering the importance of a target difference is necessary in the context of randomised controlled trials of effectiveness, particularly definitive phase III trials. Ignoring clinical importance could have serious ethical and practical consequences.
Odour-mediated oviposition site selection in Aedes aegypti depends on aquatic stage and density
Authors: Khan Zaid , Bohman Björn , Ignell Rickard , Hill Sharon Rose
Published: August 2023

Background

Olfaction plays an important role in the selection and assessment of oviposition sites by mosquitoes. Volatile organic compounds (VOCs) associated with potential breeding sites affect the behaviour of gravid mosquitoes, with VOCs from aquatic stages of conspecific mosquitoes influencing and regulating oviposition. The purpose of this study was to conduct a systematic analysis of the behavioural response of gravid Aedes aegypti to conspecific aquatic stage-conditioned water, to identify the associated bioactive VOCs and to determine how blends of these VOCs regulate oviposition site selection and stimulate egg-laying.

Methods

Using a multi-choice olfactory oviposition assay, controlling for other sensory modalities, the responses of individual females to water conditioned with different densities of conspecific aquatic stages were assessed. The conditioned water samples from the most preferred density of each aquatic stage were subsequently compared to each other using the same oviposition assay and analysed using an analysis of variance (ANOVA) followed by a Tukey post-hoc test. Using combined gas chromatography and electroantennographic detection or mass spectrometry, bioactive VOCs from the preferred density of each aquatic stage were identified. Synthetic blends were prepared based on the identified ratios of bioactive VOCs in the aquatic stages, and then tested to determine the oviposition choice of Ae. aegypti in a dose-dependent manner, against a solvent control, using a dual-choice assay. This dataset was analysed using nominal logistic regression followed by an odds ratio comparison.

Results

Gravid Ae. aegypti responded stage- and density-dependently to water conditioned with eggs, second- and fourth-instar larvae, and pupal exuviae, but not to water conditioned with pupae alone. Multi-choice assays demonstrated that gravid mosquitoes preferred to oviposit in water conditioned with fourth-instar larvae, over the other aquatic stage-conditioned water. Gravid Ae. aegypti were attracted, and generally stimulated, to oviposit in a dose-dependent manner to the individual identified synthetic odour blends for the different aquatic stages.

Conclusions

Intraspecific VOCs regulate oviposition site selection in Ae. aegypti in a stage- and density-dependent manner. We discuss the need for further studies to evaluate the identified synthetic blends to modulate the odour-mediated oviposition of Ae. aegypti under field conditions.

Graphical Abstract
Biomarkers of obesity-mediated insulin resistance: focus on microRNAs
Authors: Cai Yichen , Liu Pan , Xu Yumei , Xia Yuguo , Peng Xiaowan , Zhao Haiyan , Chen Qiu
Published: August 2023

Obesity and metabolic syndromes are becoming increasingly prevalent worldwide. Insulin resistance (IR) is a common complication of obesity. However, IR occurrence varies across individuals with obesity and may involve epigenetic factors. To rationalize the allocation of healthcare resources, biomarkers for the early risk stratification of individuals with obesity should be identified. MicroRNAs (miRNAs) are closely associated with metabolic diseases and involved in epigenetic regulation. In this review, we have summarized the changes in miRNA expression in the peripheral circulation and tissues of patients and animals with obesity-associated IR over the last 5 years and identified several candidate biomarkers that predict obesity-related IR. There are areas for improvement in existing studies. First, more than the predictive validity of a single biomarker is required, and a biomarker panel needs to be formed. Second, miRNAs are often studied in isolation and do not form a network of signaling pathways. We believe that early biomarkers can help clinicians accurately predict individuals prone to obesity-related IR at an early stage. Epigenetic regulation may be one of the underlying causes of different clinical outcomes in individuals with obesity. Future studies should focus on objectively reflecting the differences in miRNA profile expression in individuals with obesity-related IR, which may help identify more reliable biomarkers. Understanding the metabolic pathways of these miRNAs can help design new metabolic risk prevention and management strategies, and support the development of drugs to treat obesity and metabolic disorders.
Spontaneous remission of angioimmunoblastic T-cell lymphoma in a child with ataxia–telangiectasia: a case report
Authors: Abla Dima , Al-Battashi Abeer , Albiroty Khalil , Abu Qasida Khuloud , Al-Rahbi Nasser , Al-Awaidy Salah
Published: August 2023

Background

Angioimmunoblastic T-cell lymphoma is an uncommon subtype of peripheral T-cell lymphoma in children with fewer than 20 cases reported in literature.

Case presentation

A 3-year-old Omani boy was diagnosed with ataxia–talengectasia presenting with fever and generalized lymphadenopathy. His biopsy revealed atypical lymphocytic infiltrate consistent with the diagnosis of angioimmunoblastic T-cell lymphoma. Within 3 weeks from the initial presentation and without any neoadjuvant therapy, he showed complete recovery of symptoms with absence of fever and regression of all previously affected lymph nodes. He has remained in remission ever since.

Conclusion

This is the first report of spontaneous improvement of angioimmunoblastic T-cell lymphoma in a patient with ataxia–telangiectasia who was 3 years old at presentation. Owing to the paucity of similar cases, this report adds valuable diagnostic, therapeutic, and monitoring data.
The interwoven fibril-like structure of amyloid-beta plaques in mouse brain tissue visualized using super-resolution STED microscopy
Authors: Johansson Björn , Oasa Sho , Muntsant Soria Aida , Tiiman Ann , Söderberg Linda , Amandius Ebba , Möller Christer , Lannfelt Lars , Terenius Lars , Giménez-Llort Lydia , Vukojević Vladana
Published: August 2023

Background

Standard neuropathologic analysis of Alzheimer’s brain relies on traditional fluorescence microscopy, which suffers from limited spatial resolution due to light diffraction. As a result, it fails to reveal intricate details of amyloid plaques. While electron microscopy (EM) offers higher resolution, its extensive sample preparation, involving fixation, dehydration, embedding, and sectioning, can introduce artifacts and distortions in the complex brain tissue. Moreover, EM lacks molecular specificity and has limited field of view and imaging depth.

Results

In our study, we employed super-resolution Stimulated Emission Depletion (STED) microscopy in conjunction with the anti-human APP recombinant antibody 1C3 fluorescently labelled with DyLightTM633 (1C3-DyLight633). This combination allowed us to visualize amyloidogenic aggregates in vitro and in brain sections from a 17-month-old 3×Tg-AD mouse with sub-diffraction limited spatial resolution. Remarkably, we achieved a spatial resolution of 29 nm in vitro and 62 nm in brain tissue sections, surpassing the capabilities of conventional confocal microscopy by 5–10 times. Consequently, we could discern individual fibrils within plaques, an achievement previously only possible with EM.

Conclusions

The utilization of STED microscopy represents a groundbreaking advancement in the field, enabling researchers to delve into the characterization of local mechanisms that underlie Amyloid (Aβ) deposition into plaques and their subsequent clearance. This unprecedented level of detail is especially crucial for comprehending the etiology of Alzheimer’s disease and developing the next generation of anti-amyloid treatments. By facilitating the evaluation of drug candidates and non-pharmacological interventions aiming to reduce amyloid burden, STED microscopy emerges as an indispensable tool for driving scientific progress in Alzheimer’s research.
Effect of pyrolysis conditions on chemical properties of carbonized rice husks for efficient NH4+ adsorption
Authors: Kang Yun-Gu , Lee Jae-Han , Lee Jun-Yeong , Kim Jun-Ho , Oh Taek-Keun , Sung Jwa-Kyung
Published: August 2023

Ammonium ions (NH4+) are commonly found in contaminated water and are a contributing factor to water eutrophication. Carbonized rice husk, derived from various biomass sources, possesses a porous structure, and its characteristics are influenced by the feedstock and pyrolysis conditions. Hence, this study aimed to investigate the applicability of carbonized rice husk as an absorbent for NH4+ removal. The adsorption kinetics were analyzed using the Pseudo-first-order and Pseudo-second-order models, while the adsorption characteristics were assessed using the Langmuir and Freundlich isotherms. The adsorption rate of NH4+ by carbonized rice husk increased until 240 min and then gradually approached equilibrium state. Notably, the highest NH4+ adsorption rate was observed in pH 7.1 carbonized rice husk 36.045 mg/g∙min. Moreover, the NH4+ adsorption capacity exhibited an increase with increasing concentration and quantity of the solution. The pH of the carbonized rice husk was found to influence the NH4+ adsorption process, with higher pH values corresponding to increased NH4+ adsorption rates. The NH4+ sorption rate carbonized rice husk was higher in pH 11.0 at 31.440 mg/g compared to pH 6.1 (7.642 mg/g) and pH 7.1 (10.761 mg/g). These findings highlight the impact of pyrolysis conditions on the adsorption characteristics of carbonized rice husk.
Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre-malignant lesions and cancer
Authors: Khan Mohammed Muzamil , Frustino Jennifer , Villa Alessandro , Nguyen Bach-Cuc , Woo Sook-Bin , Johnson William Evan , Varelas Xaralabos , Kukuruzinska Maria , Monti Stefano
Published: August 2023

Head and neck cancers are a complex malignancy comprising multiple anatomical sites, with cancer of the oral cavity ranking among the deadliest and the most disfiguring cancers globally. Oral cancer (OC) constitutes a subset of head and neck cancer cases, presenting primarily as tobacco- and alcohol-associated oral squamous cell carcinoma (OSCC), with a 5-year survival rate of ~ 65%, partly due to the lack of early detection and effective treatments. OSCC arises from premalignant lesions (PMLs) in the oral cavity through a multi-step series of clinical and histopathological stages, including varying degrees of epithelial dysplasia. To gain insights into the molecular mechanisms associated with the progression of PMLs to OSCC, we profiled the whole transcriptome of 66 human PMLs comprising leukoplakia with dysplasia and hyperkeratosis non-reactive (HkNR) pathologies, alongside healthy controls and OSCC. Our data revealed that PMLs were enriched in gene signatures associated with cellular plasticity, such as partial EMT (p-EMT) phenotypes, and with immune response. Integrated analyses of the host transcriptome and microbiome further highlighted a significant association between differential microbial abundance and PML pathway activity, suggesting a contribution of the oral microbiome toward PML evolution to OSCC. Collectively, this study reveals molecular processes associated with PML progression that may help early diagnosis and disease interception at an early stage.

Graphical abstract
Mediating effects of motivation and socioeconomic status on reading achievement: a secondary analysis of PISA 2018
Authors: Michael Demos , Kyriakides Leonidas
Published: August 2023

Background

Research has shown that students from socially disadvantaged backgrounds are more likely to have lower academic performance compared to children from better-off families. However, the way that socioeconomic status (SES) influences student learning outcomes has not yet been fully examined. Thus, this study explores the indirect effects of students’ SES on reading achievement through academic motivation. Specifically, the mediating role of the following three motivation elements is investigated:mastery-approach orientation of achievement goals,enjoyment of reading, andexpected occupational status.

Methods

Structural Equation Modelling (SEM) was used to test the hypothesized mediation model in each European country (n = 38) that took part in the PISA 2018 cycle. Specifically, data was obtained from 237,366 15-year-old students. Common measures for SES, academic motivation, and reading achievement were employed to examine whether the selected academic motivation elements have similar effects in each country. Confirmatory Factor Analysis (CFA) was used to validate the factorial structure of mediators and test their measurement invariance across the samples.

Results

Within-country SEM analysis revealed thatexpected occupational statuspartially mediates the relationship between SES and reading achievement in all countries.Enjoyment of readingfitted well as a mediator in almost all countries (n = 37), whereasmastery-approach orientation of achievement goalsonly appeared as a mediator in 11 countries. The direct effect of SES on academic achievement was significantly reduced in all models.

Conclusions

This study provides evidence thatenjoyment of readingandexpected occupational statuscan be treated as mediators in the relationship between SES and reading achievement in European countries. Implications for research and theory for promoting equity in education are drawn. It is argued that schools and teachers should encourage students to participate in activities that foster their intrinsic motivation towards reading and raise their educational and occupational expectations, especially for those coming from socially disadvantaged backgrounds.
Evaluation of the seasonal to decadal variability in dynamic sea level simulations from CMIP5 to CMIP6
Authors: Jin Chenyang , Liu Hailong , Lin Pengfei
Published: August 2023

Previous studies have revealed little progress in the ensemble mean of Coupled Model Intercomparison Project Phase 6 (CMIP6) models compared to Phase 5 (CMIP5) models in simulating global dynamic sea level (DSL). This study investigates the performance of the CMIP5 and CMIP6 ensembles in simulating the spatial pattern and magnitude of DSL climatology, seasonal variability, interannual variability, and decadal variability by using the pattern correlation coefficient (PCC) and root-mean-square error (RMSE) as metrics. We show that the top models of the CMIP6 ensemble perform better than those of the CMIP5 ensemble in the simulation of DSL climatology and seasonal and interannual variability, but not DSL decadal variability. An intermodel linear relationship between the RMSE and PCC is found for both the CMIP5 and CMIP6 ensembles; however, this intermodel relationship is more linearly correlated in the CMIP6 ensemble and not significant for DSL decadal variability. The results show that the finer-horizontal resolution models tend to yield a smaller RMSE and a larger PCC in the DSL climatology, seasonal variability, interannual variability but not decadal variability simulations, and the relationship is more evident for the CMIP6 ensemble than for the CMIP5 ensemble.
What makes an orthopaedic paper highly citable? A bibliometric analysis of top orthopeadic journals with 10‐year follow up
Authors: Lutter Mirjam , Rudolf Henrik , Lenz Robert , Hotfiel Thilo , Tischer Thomas
Published: August 2023

Purpose

To examine a series of papers from top ranked orthopaedic journals with respect to the number of citations over a 10‐year observation period to identify factors that lead to high citation rates.

Methods

The Web of Science database was consulted to identify all published papers from the first‐year term of 2010 (January‐May) from four top orthopaedic journals: AJSM, Arthroscopy, JBJS Am and KSSTA. The database was used to analyze and compare the papers with respect to their characteristics and citations up to 2019. Basic information for each paper was collected including the author, country, study type and average citations per year (ACY). The most (Top20%) and least (Bottom20%) frequently cited papers were identified and differences were extracted.

Results

Five hundred sixteen papers were included with a total of 19,261 citations. Most of the published papers were from the United States (n = 245). On average, a paper received 37.3 citations over the 10‐year observation period. The most cited paper was cited 322 times. The most cited study type was randomized controlled trial (RCT) (Ø80.8). The Top20% papers were cited 37 times more often than the Bottom20%. Among the Top20%, the largest group was cohort study (n = 20) followed by case series (n = 19). Among others, the number of authors, the number of keywords and the number of references significantly correlated with the number of citations (p < 0.001).

Conclusions

Factors influencing citation frequency were identified.
Basidiomycete non-reducing polyketide synthases function independently of SAT domains
Authors: Löhr Nikolai A. , Rakhmanov Malik , Wurlitzer Jacob M. , Lackner Gerald , Gressler Markus , Hoffmeister Dirk
Published: August 2023

Background

Non-reducing polyketide synthases (NR-PKSs) account for a major share of natural product diversity produced by both Asco- and Basidiomycota. The present evolutionary diversification into eleven clades further underscores the relevance of these multi-domain enzymes. Following current knowledge, NR-PKSs initiate polyketide assembly by an N-terminal starter unit:acyl transferase (SAT) domain that catalyzes the transfer of an acetyl starter from the acetyl-CoA thioester onto the acyl carrier protein (ACP).

Results

A comprehensive phylogenetic analysis of NR-PKSs established a twelfth clade from which three representatives, enzymes CrPKS1-3 of the webcap mushroom Cortinarius rufoolivaceus, were biochemically characterized. These basidiomycete synthases lack a SAT domain yet are fully functional hepta- and octaketide synthases in vivo. Three members of the other clade of basidiomycete NR-PKSs (clade VIII) were produced as SAT-domainless versions and analyzed in vivo and in vitro. They retained full activity, thus corroborating the notion that the SAT domain is dispensable for many basidiomycete NR-PKSs. For comparison, the ascomycete octaketide synthase atrochrysone carboxylic acid synthase (ACAS) was produced as a SAT-domainless enzyme as well, but turned out completely inactive. However, a literature survey revealed that some NR-PKSs of ascomycetes carry mutations within the catalytic motif of the SAT domain. In these cases, the role of the domain and the origin of the formal acetate unit remains open.

Conclusions

The role of SAT domains differs between asco- and basidiomycete NR-PKSs. For the latter, it is not part of the minimal set of NR-PKS domains and not required for function. This knowledge may help engineer compact NR-PKSs for more resource-efficient routes. From the genomic standpoint, seemingly incomplete or corrupted genes encoding SAT-domainless NR-PKSs should not automatically be dismissed as non-functional pseudogenes, but considered during genome analysis to decipher the potential arsenal of natural products of a given fungus.