bluuebunny/crossref_metadata_2025 huggingface dataset:
An epithelial gene signature of trans-IL-6 signaling defines a subgroup of type 2-low asthma
Authors: El-Husseini Zaid W. , Khalenkow Dmitry , Lan Andy , van der Molen Thys , Brightling Chris , Papi Alberto , Rabe Klaus F. , Siddiqui Salman , Singh Dave , Kraft Monica , Beghe Bianca , van den Berge Maarten , van Gosliga Djoke , Nawijn Martijn C. , Rose-John Stefan , Koppelman Gerard H. , Gosens Reinoud
Published: December 2023

Background

Asthma is stratified into type 2-high and type 2-low inflammatory phenotypes. Limited success has been achieved in developing drugs that target type 2-low inflammation. Previous studies have linked IL-6 signaling to severe asthma. IL-6 cooperates with soluble-IL-6Rα to activate cell signaling in airway epithelium.

Objective

We sought to study the role of sIL-6Rα amplified IL-6 signaling in airway epithelium and to develop an IL-6+ sIL-6Rα gene signature that may be used to select asthma patients who potentially respond to anti-IL-6 therapy.

Methods

Human airway epithelial cells were stimulated with combinations of IL-6, sIL-6Rα, and inhibitors, sgp130 (Olamkicept), and anti-IL-6R (Tocilizumab), to assess effects on pathway activation, epithelial barrier integrity, and gene expression. A gene signature was generated to identify IL-6 high patients using bronchial biopsies and nasal brushes.

Results

Soluble-IL-6Rα amplified the activation of the IL-6 pathway, shown by the increase of STAT3 phosphorylation and stronger gene induction in airway epithelial cells compared to IL-6 alone. Olamkicept and Tocilizumab inhibited the effect of IL-6 + sIL-6Rα on gene expression. We developed an IL-6 + sIL-6Rα gene signature and observed enrichment of this signature in bronchial biopsies but not nasal brushes from asthma patients compared to healthy controls. An IL-6 + sIL-6Rα gene signature score was associated with lower levels of sputum eosinophils in asthma.

Conclusion

sIL-6Rα amplifies IL-6 signaling in bronchial epithelial cells. Higher local airway IL-6 + sIL-6Rα signaling is observed in asthma patients with low sputum eosinophils.
A liquid biopsy signature of circulating extracellular vesicles-derived RNAs predicts response to first line chemotherapy in patients with metastatic colorectal cancer
Authors: Yang Ya’nan , Zhang Jieyun , Zhang Wen , Wang Yixuan , Zhai Yujia , Li Yan , Li Wenhua , Chang Jinjia , Zhao Xiaoying , Huang Mingzhu , Geng Qirong , Yang Yue , Gong Zhe , Yu Nuoya , Shen Wei , Li Qian , Huang Shenglin , Guo Weijian
Published: December 2023

Background

Colorectal cancer (CRC) is one of the most threatening tumors in the world, and chemotherapy remains dominant in the treatment of metastatic CRC (mCRC) patients. The purpose of this study was to develop a biomarker panel to predict the response of the first line chemotherapy in mCRC patients.

Methods

Totally 190 mCRC patients treated with FOLFOX or XEOLX chemotherapy in 3 different institutions were included. We extracted the plasma extracellular vesicle (EV) RNA, performed RNA sequencing, constructed a model and generated a signature through shrinking the number of variables by the random forest algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm in the training cohort (n = 80). We validated it in an internal validation cohort (n = 62) and a prospective external validation cohort (n = 48).

Results

We established a signature consisted of 22 EV RNAs which could identify responders, and the area under the receiver operating characteristic curve (AUC) values was 0.986, 0.821, and 0.816 in the training, internal validation, and external validation cohort respectively. The signature could also identify the progression-free survival (PFS) and overall survival (OS). Besides, we constructed a 7-gene signature which could predict tumor response to first-line oxaliplatin-containing chemotherapy and simultaneously resistance to second-line irinotecan-containing chemotherapy.

Conclusions

The study was first to develop a signature of EV-derived RNAs to predict the response of the first line chemotherapy in mCRC with high accuracy using a non-invasive approach, indicating that the signature could help to select the optimal regimen for mCRC patients.
Multifunctional gold nanoparticles for osteoporosis: synthesis, mechanism and therapeutic applications
Authors: Gao Weihang , Liang Chen , Zhao Ke , Hou Mingming , Wen Yinxian
Published: December 2023

Osteoporosis is currently the most prevalent bone disorder worldwide and is characterized by low bone mineral density and an overall increased risk of fractures. To treat osteoporosis, a range of drugs targeting bone homeostasis have emerged in clinical practice, including anti-osteoclast agents such as bisphosphonates and denosumab, bone formation stimulating agents such as teriparatide, and selective oestrogen receptor modulators. However, traditional clinical medicine still faces challenges related to side effects and high costs of these types of treatments. Nanomaterials (particularly gold nanoparticles [AuNPs]), which have unique optical properties and excellent biocompatibility, have gained attention in the field of osteoporosis research. AuNPs have been found to promote osteoblast differentiation, inhibit osteoclast formation, and block the differentiation of adipose-derived stem cells, which thus is believed to be a novel and promising candidate for osteoporosis treatment. This review summarizes the advances and drawbacks of AuNPs in their synthesis and the mechanisms in bone formation and resorption in vitro and in vivo, with a focus on their size, shape, and chemical composition as relevant parameters for the treatment of osteoporosis. Additionally, several important and promising directions for future studies are also discussed, which is of great significance for prevention and treatment of osteoporosis.
Multiplex immunohistochemistry defines two cholesterol metabolism patterns predicting immunotherapeutic outcomes in gastric cancer
Authors: Tang Wei , Li Guanghua , Lin Qi , Zhu Zhenzhen , Wang Zhao , Wang Zhixiong
Published: December 2023

Background

The role of cholesterol metabolism in gastric cancer (GC) and its implications for tumor characteristics and immunotherapy response remain poorly understood. In this study, our aim was to investigate this role, identify associated metabolic subtypes, and assess their clinical implications in GC.

Methods

We conducted a comprehensive analysis of cholesterol metabolism genes (CMGs) using transcriptomic data from TCGA and GEO. Based on 23 representative CMGs, we classified GC into metabolic subtypes. We evaluated clinical features and immune cell infiltration between these subtypes. Additionally, we identified a CMG signature and assessed its clinical relevance in GC. We retrospectively enrolled thirty-five GC patients receiving chemotherapy plus a PD-1 inhibitor to assess the CMG signature using multiplex immunohistochemistry.

Results

Our analysis revealed two cholesterol metabolism subtypes in GC: Cholesterol Metabolism Type 1 (CMT1) and Cholesterol Metabolism Type 2 (CMT2). These subtypes exhibited distinct patterns: CMT1 indicated heightened cholesterol biosynthesis, while CMT2 showed abnormal cholesterol transport. CMT2 was associated with unfavorable clinical features, enriched malignant pathways, and a pro-tumor immune microenvironment. Furthermore, we developed a five-CMG prognostic signature (ABCA1, NR1H3, TSPO, NCEH1, and HMGCR) that effectively predicted the prognosis of patients with GC and their response to chemotherapy plus a PD-1 inhibitor. This signature was validated in a clinical cohort using multiplex immunohistochemistry.

Conclusion

Our results highlight the effectiveness of cholesterol metabolism patterns as biomarkers for predicting the prognosis and immunotherapy response in GC. The expression of cholesterol metabolism genes and the assessment of cholesterol metabolism patterns have the potential to predict the outcome of immunotherapy and guide treatment strategies.
The hypothalamic steroidogenic pathway mediates susceptibility to inflammation-evoked depression in female mice
Authors: Xu Fu-Rong , Wei Zhen-Hong , Xu Xiao-Xia , Zhang Xiao-Gang , Wei Chao-Jun , Qi Xiao-Ming , Li Yong-Hong , Gao Xiao-Ling , Wu Yu
Published: December 2023

Background

Depression is two-to-three times more frequent among women. The hypothalamus, a sexually dimorphic area, has been implicated in the pathophysiology of depression. Neuroinflammation-induced hypothalamic dysfunction underlies behaviors associated with depression. The lipopolysaccharide (LPS)-induced mouse model of depression has been well-validated in numerous laboratories, including our own, and is widely used to investigate the relationship between neuroinflammation and depression. However, the sex-specific differences in metabolic alterations underlying depression-associated hypothalamic neuroinflammation remain unknown.

Methods

Here, we employed the LPS-induced mouse model of depression to investigate hypothalamic metabolic changes in both male and female mice using a metabolomics approach. Through bioinformatics analysis, we confirmed the molecular pathways and biological processes associated with the identified metabolites. Furthermore, we employed quantitative real-time PCR, enzyme-linked immunosorbent assay, western blotting, and pharmacological interventions to further elucidate the underlying mechanisms.

Results

A total of 124 and 61 differential metabolites (DMs) were detected in male and female mice with depressive-like behavior, respectively, compared to their respective sex-matched control groups. Moreover, a comparison between female and male model mice identified 37 DMs. We capitalized on biochemical clustering and functional enrichment analyses to define the major metabolic changes in these DMs. More than 55% of the DMs clustered into lipids and lipid-like molecules, and an imbalance in lipids metabolism was presented in the hypothalamus. Furthermore, steroidogenic pathway was confirmed as a potential sex-specific pathway in the hypothalamus of female mice with depression. Pregnenolone, an upstream component of the steroid hormone biosynthesis pathway, was downregulated in female mice with depressive-like phenotypes but not in males and had considerable relevance to depressive-like behaviors in females. Moreover, exogenous pregnenolone infusion reversed depressive-like behaviors in female mice with depression. The 5α-reductase type I (SRD5A1), a steroidogenic hub enzyme involved in pregnenolone metabolism, was increased in the hypothalamus of female mice with depression. Its inhibition increased hypothalamic pregnenolone levels and ameliorated depressive-like behaviors in female mice with depression.

Conclusions

Our study findings demonstrate a marked sexual dimorphism at the metabolic level in depression, particularly in hypothalamic steroidogenic metabolism, identifying a potential sex-specific pathway in female mice with depressive-like behaviors.
Effectiveness of a breastfeeding promotion intervention model based on Society ecosystems Theory for maternal women: a study protocol of randomized controlled trial
Authors: Ouyang Yan-Qiong , Zhou Jie , Guo Jin-Yi , Wang Shi-Yun , Wang Xin , Zhou-Chen Yi-Bei , Redding Sharon R. , Chen Hui-Jun
Published: December 2023

Background

Breastfeeding is recognized internationally as the most scientific and effective way to feed infants and young children. According to the World Health Organization in 2022, the exclusive breastfeeding rate within 6 months is 34.1% in China, which is still far from the goal of “more than 60% exclusive breastfeeding rate of infants within 6 months” by 2030 required by China’s State Council. It is necessary to promote breastfeeding and provide maternal breastfeeding guidance to increase exclusive breastfeeding. Factors influencing breastfeeding can be explained by the society ecosystems theory, distributed in macro, mezzo and micro systems. The interventions focused on breastfeeding promotion are mainly carried out in the health systems and services, home and family environment, community environment, work environment, policy environment or a combination of these facilities. But there is sparse research on integrating resources in the macro, mezzo and micro systems of maternal breastfeeding processes to promote breastfeeding behavior. A randomized controlled trial will test the effect of a breastfeeding promotion intervention model based on the society ecosystems theory versus usual prenatal and postnatal care on maternal and infant health and the exclusive breastfeeding rate at 6 months.

Methods/design

The study is a single-blind, parallel design, randomized controlled trial with an intervention group (n = 109) and a control group (n = 109) that compares the effect of a breastfeeding promotion intervention model based on the society ecosystems theory with usual prenatal and postnatal care. The intervention covers macro- (policy, culture), mezzo- (family-hospital-community) and micro- (biological, psychological and social) systems of the maternal breastfeeding process. Infant feeding patterns, neonatal morbidity and physical and mental health of antenatal and postpartum women will be collected at baseline (28 to 35 weeks of gestation), 1-, 4-, and 6-month postpartum.

Discussion

This is a multifaceted, multifactorial, and multi-environmental breastfeeding promotion strategy to help mothers and their families learn breastfeeding knowledge and skills. The study provides a new modality for adding breastfeeding interventions to prenatal and postnatal care for healthcare providers in the hospital and the community.

Trial registration: Chinese Clinical Trial Registry at www.chictr.org.cn, ChiCTR2300075795.
Using fuzzy logic to compare species distribution models developed on the basis of expert knowledge and sampling records
Authors: Romero David , Maneyro Raúl , Guerrero José Carlos , Real Raimundo
Published: December 2023

Background

Experts use knowledge to infer the distribution of species based on fuzzy logical assumptions about the relationship between species and the environment. Thus, expert knowledge is amenable to fuzzy logic modelling, which give to propositions a continuous truth value between 0 and 1. In species distribution modelling, fuzzy logic may also be used to model, from a number of records, the degree to which conditions are favourable to the occurrence of a species. Therefore, fuzzy logic operations can be used to compare and combine models based on expert knowledge and species records. Here, we applied fuzzy logic modelling to the distribution of amphibians in Uruguay as inferred from expert knowledge and from observed records to infer favourable locations, with favourability being the commensurable unit for both kinds of data sources. We compared the results for threatened species, species considered by experts to be ubiquitous, and non-threatened, non-ubiquitous species. We calculated the fuzzy intersection of models based on both knowledge sources to obtain a unified prediction of favourable locations.

Results

Models based on expert knowledge involved a larger number of variables and were less affected by sampling bias. Models based on experts had the same overprediction rate for the three types of species, whereas models based on species records had a lower prediction rate for ubiquitous species. Models based on expert knowledge performed equally as well or better than corresponding models based on species records for threatened species, even when they had to discriminate and classify the same set of records used to build the models based on species records. For threatened species, expert models predicted more restrictive favourable territories than those predicted based on records. Observed records generated the best-fitted models for non-threatened non-ubiquitous species, and ubiquitous species.

Conclusions

Fuzzy modelling permitted the objective comparison of the potential of expert knowledge and incomplete distribution records to infer the territories favourable for different species. Distribution of threatened species was able to be better explained by subjective expert knowledge, while for generalist species models based on observed data were more accurate. These results have implications for the correct use of expert knowledge in conservation planning.
Pre-trained protein language model sheds new light on the prediction of Arabidopsis protein–protein interactions
Authors: Zhou Kewei , Lei Chenping , Zheng Jingyan , Huang Yan , Zhang Ziding
Published: December 2023

Background

Protein–protein interactions (PPIs) are heavily involved in many biological processes. Consequently, the identification of PPIs in the model plant Arabidopsis is of great significance to deeply understand plant growth and development, and then to promote the basic research of crop improvement. Although many experimental Arabidopsis PPIs have been determined currently, the known interactomic data of Arabidopsis is far from complete. In this context, developing effective machine learning models from existing PPI data to predict unknown Arabidopsis PPIs conveniently and rapidly is still urgently needed.

Results

We used a large-scale pre-trained protein language model (pLM) called ESM-1b to convert protein sequences into high-dimensional vectors and then used them as the input of multilayer perceptron (MLP). To avoid the performance overestimation frequently occurring in PPI prediction, we employed stringent datasets to train and evaluate the predictive model. The results showed that the combination of ESM-1b and MLP (i.e., ESMAraPPI) achieved more accurate performance than the predictive models inferred from other pLMs or baseline sequence encoding schemes. In particular, the proposed ESMAraPPI yielded an AUPR value of 0.810 when tested on an independent test set where both proteins in each protein pair are unseen in the training dataset, suggesting its strong generalization and extrapolating ability. Moreover, the proposed ESMAraPPI model performed better than several state-of-the-art generic or plant-specific PPI predictors.

Conclusion

Protein sequence embeddings from the pre-trained model ESM-1b contain rich protein semantic information. By combining with the MLP algorithm, ESM-1b revealed excellent performance in predicting Arabidopsis PPIs. We anticipate that the proposed predictive model (ESMAraPPI) can serve as a very competitive tool to accelerate the identification of Arabidopsis interactome.
Exosomes from bone marrow mesenchymal stem cells ameliorate glucocorticoid-induced osteonecrosis of femoral head by transferring microRNA-210 into bone microvascular endothelial cells
Authors: Zheng Che , Wu Yuangang , Xu Jiawen , Liu Yuan , Ma Jun
Published: December 2023

Objectives

Bone microvascular endothelial cells (BMECs) played an important role in the pathogenesis of glucocorticoid-induced osteonecrosis of femoral head (GCS-ONFH), and exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may provide an effective treatment. This study aimed to evaluate the effects of BMSC-Exos and internal microRNA-210-3p (miRNA-210) on GCS-ONFH in an in vitro hydrocortisone-induced BMECs injury model and an in vivo rat GCS-ONFH model.

Methods

BMECs, BMSCs and BMSC-Exos were isolated and validated. BMECs after the treatment of hydrocortisone were cocultured with different concentrations of BMSC-Exos, then proliferation, migration, apoptosis and angiogenesis of BMECs were evaluated by CCK-8, Annexin V-FITC/PI, cell scratch and tube formation assays. BMSCs were transfected with miRNA-210 mimics and miRNA-210 inhibitors, then BMSC-ExosmiRNA−210 mimicand BMSC-ExosmiRNA−210 inhibitorsecreted from such cells were collected. The differences between BMSC-Exos, BMSC-ExosmiRNA−210 mimicand BMSC-ExosmiRNA−210 inhibitorin protecting BMECs against GCS treatment were analyzed by methods mentioned above. Intramuscular injections of methylprednisolone were performed on Sprague–Dawley rats to establish an animal model of GCS-ONFH, then tail intravenous injections of BMSC-Exos, BMSC-ExosmiRNA−210 mimicor BMSC-ExosmiRNA−210 inhibitorwere conducted after methylprednisolone injection. Histological and immunofluorescence staining and micro-CT were performed to evaluate the effects of BMSC-Exos and internal miRNA-210 on the in vivo GCS-ONFH model.

Results

Different concentrations of BMSC-Exos, especially high concentration of BMSC-Exos, could enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs treated with GCS. Compared with BMSC-Exos, BMSC-ExosmiRNA−210 mimiccould further enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs, while BMECs in the GCS + BMSC-ExosmiRNA−210 inhibitorgroup showed reduced proliferation, migration and angiogenesis ability and higher apoptosis rates. In the rat GCS-ONFH model, BMSC-Exos, especially BMSC-ExosmiRNA−210 mimic, could increase microvascular density and enhance bone remodeling of femoral heads.

Conclusions

BMSC-Exos containing miRNA-210 could serve as potential therapeutics for protecting BMECs and ameliorating the progression of GCS-ONFH.
Polygenic risk scores for cervical HPV infection, neoplasia and cancer show potential for personalised screening: comparison of two methods
Authors: Tisler Anna , Uusküla Anneli , Ojavee Sven Erik , Läll Kristi ,   Estonian Biobank research team, Metspalu Andres , Milani Lili , Esko Tõnu , Mägi Reedik , Nelis Mari , Hudjashov Georgi , Laisk Triin
Published: December 2023

The era of precision medicine requires the achievement of accurate risk assessment. Polygenic risk scores (PRSs) have strong potential for increasing the benefits of nationwide cancer screening programs. The current pool of evidence on the role of a PRS as a risk stratification model in actual practice and implementation is limited. To better understand the impact of possible method-induced variance, we constructed and validated two PRSs for cervical cancer (CC) using the Estonian Biobank female population (691 CC cases and 13,820 controls) and evaluated their utility in predicting incident cervical neoplasia (CIN), cancer, and human papillomavirus (HPV) infection using two methods (LDPred and BayesRR-RC). This study demonstrated that two genetic risk scores were significantly associated with CIN, CC, and HPV infection incidence. Independent of the method, we demonstrated that women with elevated PRS values reached the observed cumulative risk levels of CIN or CC much earlier. Our results indicated that the PRS-based discrimination rules could differ substantially when the PRSs contain similar predictive information. In summary, our analysis indicated that PRSs represent a personalized genetic component that could be an additional tool for cervical cancer risk stratification, and earlier detection of abnormalities provides invaluable information for those at high risk.
Patterns of surgical complications after delayed fixation of peripartum pubic symphysis rupture: a report of 5 cases
Authors: Doroszewski Grzegorz , Wasielewski Jan , Bartosz Paweł , Caban Adam , Scholz Anna , Białecki Jerzy
Published: December 2023

Background

The disruption of the pubic symphysis during the peripartum period is a rare injury to the pelvic ring. In most cases, conservative treatment is successful. Nonetheless, there are cases where surgical intervention is necessary. We analyzed five surgical cases treated in our department and performed a literature review.

Case presentations

Five women, ranging in age from 25 to 38, who experienced peripartum symphysis rupture were primarily treated with a conservative approach. Patients who did not show improvement and met certain criteria, such as experiencing pain starting from childbirth, having a separation in the pubic bone of more than 10 mm, and/or having a vertical instability greater than 5 mm, were recommended to undergo surgery. The average length of time between childbirth and surgery was 5.6 months, ranging from 1 to 14 months. One patient was treated with an external fixator, another patient received a combination of an external fixator and an anterior plate, and three patients were treated with anterior plates. In four cases, we observed a failure in fixation and a partial or complete loss of reduction. The plate and screws were removed in one case, and in three cases, revision surgery was performed. One case involved using a larger plate, while the other used 90-90 plating, known as “box plate fixation.” The mean follow-up was 7.4 years. Two cases had good results, and two had excellent results on the Lindahl scale.

Conclusion

For patients with peripartum pubic symphyseal dislocation, our case series and literature review demonstrated that early reduction and fixation correlate with improved clinical outcomes and lower implant failure. For patients with subacute/chronic injuries, there was a higher incidence of implant failure. Orthogonal plate fixation and/or pubic symphysiodesis was associated with improved clinical outcomes.
Pathological progress and remission strategies of osteoarthritic lesions caused by long-term joint immobilization
Authors: Gan Donghao , Jin Xiaowan , Wang Xiangpeng , Tao Chu , Yan Qinnan , Jia Qingyun , Huo Shaochuan , Chen Di , Yao Qing , Xiao Guozhi
Published: December 2023

Objective

While joint immobilization is a useful repair method for intra-articular ligament injury and periarticular fracture, prolonged joint immobilization can cause multiple complications. A better understanding how joint immobilization and remobilization impact joint function and homeostasis will help clinicians develop novel strategies to reduce complications.

Design

We first determined the effects of long-term immobilization on joint pain and osteophyte formation in patients after an extraarticular fracture or ligament injury. We then developed a mouse model of joint immobilization and harvested the knee joint samples at 2, 4, and 8 weeks. We further determined the effects of remobilization on recovery of the osteoarthritis (OA) lesions induced by immobilization in mice.

Results

We found that the long-term (6 weeks) joint immobilization caused significant joint pain and osteophytes in patients. In mice, 2-week immobilization already induced moderate sensory innervation and increased pain sensitivity and infiltration in synovium without inducing marked osteophyte formation and cartilage loss. Long-term immobilization (4 and 8 weeks) induced more severe sensory innervation and inflammatory infiltration in synovium, massive osteophyte formation on both sides of the femoral condyle, and the edge of the tibial plateau and significant loss of the articular cartilage in mice. Remobilization, which ameliorates normal joint load and activity, restored to certain extent some of the OA lesions and joint function in mice.

Conclusions

Joint immobilization caused multiple OA-like lesions in both mice and humans. Joint immobilization induced progressive sensory innervation, synovitis, osteophyte formation, and cartilage loss in mice, which can be partially ameliorated by remobilization.
The sensitivity of mTORC1 signaling activation renders tissue regenerative capacity
Authors: Dou Hanyu , Li Jianzhou , Huang Taomin , Ding Xiaolei
Published: December 2023

A better understanding of how and why the regenerative capacity differs among species will not only provide insights into the regeneration process but also hold value for the development of regenerative medicine and the improvement of healing procedures. In a recent Nature article, Zhulyn et al. identify a critical role played by the activation of mechanistic target of rapamycin complex 1 (mTORC1) signaling in enhancing tissue regenerative capacity in animals.
Inter-rater reliability of risk of bias tools for non-randomized studies
Authors: Kalaycioglu Isabel , Rioux Bastien , Briard Joel Neves , Nehme Ahmad , Touma Lahoud , Dansereau Bénédicte , Veilleux-Carpentier Ariane , Keezer Mark R.
Published: December 2023

Purpose

There is limited knowledge on the reliability of risk of bias (ROB) tools for assessing internal validity in systematic reviews of exposure and frequency studies. We aimed to identify and then compare the inter-rater reliability (IRR) of six commonly used tools for frequency (Loney scale, Gyorkos checklist, American Academy of Neurology [AAN] tool) and exposure (Newcastle–Ottawa scale, SIGN50 checklist, AAN tool) studies.

Methods

Six raters independently assessed the ROB of 30 frequency and 30 exposure studies using the three respective ROB tools. Articles were rated as low, intermediate, or high ROB. We calculated an intraclass correlation coefficient (ICC) for each tool and category of ROB tool. We compared the IRR between ROB tools and tool type by inspection of overlapping ICC 95% CIs and by comparing their coefficients after transformation to Fisher’s Z values. We assessed the criterion validity of the AAN ROB tools by calculating an ICC for each rater in comparison with the original ratings from the AAN.

Results

All individual ROB tools had an IRR in the substantial range or higher (ICC point estimates between 0.61 and 0.80). The IRR was almost perfect (ICC point estimate > 0.80) for the AAN frequency tool and the SIGN50 checklist. All tools were comparable in IRR, except for the AAN frequency tool which had a significantly higher ICC than the Gyorkos checklist (p = 0.021) and trended towards a higher ICC when compared to the Loney scale (p = 0.085). When examined by category of ROB tool, scales, and checklists had a substantial IRR, whereas the AAN tools had an almost perfect IRR. For the criterion validity of the AAN ROB tools, the average agreement between our raters and the original AAN ratings was moderate.

Conclusion

All tools had substantial IRRs except for the AAN frequency tool and the SIGN50 checklist, which both had an almost perfect IRR. The AAN ROB tools were the only category of ROB tools to demonstrate an almost perfect IRR. This category of ROB tools had fewer and simpler criteria. Overall, parsimonious tools with clear instructions, such as those from the AAN, may provide more reliable ROB assessments.
PDLB: Path Diversity-aware Load Balancing with adaptive granularity in data center networks
Authors: Gao Weimin , Huang Jiawei , Li Zhaoyi , Zou Shaojun , Wang Jianxin
Published: December 2023

Modern data center topologies often take the form of a multi-rooted tree with rich parallel paths to provide high bandwidth. However, various path diversities caused by traffic dynamics, link failures and heterogeneous switching equipment widely exist in the production datacenter network. Therefore, the multi-path load balancer in data center should be robust to these diversities. Although prior fine-grained schemes such as RPS and Presto make the best use of available paths, However, they are prone to experiencing packet reordering problem under the asymmetric topology. The coarse-grained solutions such as ECMP and LetFlow effectively avoid packet reordering, but easily lead to under-utilization of multiple paths. To cope with these inefficiencies, we propose a load balancing mechanism called PDLB, which adaptively adjusts flowcell granularity according to path diversity. PDLB increases flowcell granularity to alleviate packet reordering under large degrees of topology asymmetry, while reducing flowcell granularity to obtain high link utilization under small degrees of topology asymmetry. PDLB is only deployed on the sender without any modification on switch. We evaluate PDLB through large-scale NS2 simulations. The experimental results show that PDLB reduces the average flow completion time by up to $$\sim$$
∼
8-53% over the state-of-the-art load balancing schemes.
Reinforcement learning based task scheduling for environmentally sustainable federated cloud computing
Authors: Wang Zhibao , Chen Shuaijun , Bai Lu , Gao Juntao , Tao Jinhua , Bond Raymond R. , Mulvenna Maurice D.
Published: December 2023

The significant energy consumption within data centers is an essential contributor to global energy consumption and carbon emissions. Therefore, reducing energy consumption and carbon emissions in data centers plays a crucial role in sustainable development. Traditional cloud computing has reached a bottleneck, primarily due to high energy consumption. The emerging federated cloud approach can reduce the energy consumption and carbon emissions of cloud data centers by leveraging the geographical differences of multiple cloud data centers in a federated cloud. In this paper, we propose Eco-friendly Reinforcement Learning in Federated Cloud (ERLFC), a framework that uses reinforcement learning for task scheduling in a federated cloud environment. ERLFC aims to intelligently consider the state of each data center and effectively harness the variations in energy and carbon emission ratios across geographically distributed cloud data centers in the federated cloud. We build ERLFC using Actor-Critic algorithm, which select the appropriate data center to assign a task based on various factors such as energy consumption, cooling method, waiting time of the task, energy type, emission ratio, and total energy consumption of the current cloud data center and the details of the next task. To demonstrate the effectiveness of ERLFC, we conducted simulations based on real-world task execution data, and the results show that ERLFC can effectively reduce energy consumption and emissions during task execution. In comparison to Round Robin, Random, SO, and GJO algorithms, ERLFC achieves respective reductions of 1.09, 1.08, 1.21, and 1.26 times in terms of energy saving and emission reduction.
Epidemiology of multidrug-resistant Klebsiella pneumoniae infection in clinical setting in South-Eastern Asia: a systematic review and meta-analysis
Authors: Salawudeen Adamu , Raji Yakubu Egigogo , Jibo Garba Gidandawa , Desa Mohd Nasir Mohd , Neoh Hui-min , Masri Siti Norbaya , Di Gregorio Sabrina , Jamaluddin Tengku Zetty Maztura Tengku
Published: December 2023

The rising prevalence of multidrug-resistant (MDR) and extended-spectrum beta lactamase-resistant (ESBL) Klebsiella pneumoniae (K. pneumoniae) is an important global public health challenge. This threat is even more pertinent in clinical settings. Morbidity and mortality associated with this condition are alarming particularly in the developing regions of the world. A comprehensive evaluation of the epidemiology of this phenomenon will assist towards the global effort of reducing its burden. So, this systematic review and meta-analysis was conducted to evaluate the epidemiology of MDR K. pneumoniae in South-Eastern Asia (SEA). The study was done under the PRISMA guidelines and was preceded by the development of a priori protocol. The protocol was then registered in PROSPERO—the public registry for systematic reviews. Seven important outcomes which include the assessment of the overall MDR K. pneumoniae prevalence were designed to be evaluated. A literature search was carried out in five selected electronic databases and 4389 were screened. Of these articles, 21 studies that met the eligibility criteria were included in the review. Relevant data were extracted from the included studies. By conducting a quality effect meta-analysis, the pooled prevalence for MDR and ESBL K. pneumoniae in SEA was estimated at 55% (CI 9–96) and 27% (CI 32–100) respectively. The review also identified ESBL genes types of allodemic situations occurring mostly in respiratory tract infections. The high prevalence of MDR and ESBL K. pneumoniae in this subregion is highly significant and of both public health and clinical relevance. Overall, the findings of this review will assist in the effective prevention and control of this threat in SEA.
The coexistence of psychological drivers and deterrents of consumers’ willingness to try cultured meat hamburger patties: evidence from South Africa
Authors: Tsvakirai C. Z. , Nalley L. L.
Published: December 2023

The widespread consumption of alternative meat products, such as plant-based alternatives in the hamburger patty market, has provided insights into the potential of commercially produced cultured meat. Evidence from previous alternative meat studies shows mixed results on whether experience with commercially available alternative protein will help to overcome or compound consumers’ concerns about cultured meat. This study investigates the effect that South African consumers’ implicit perceptions developed by experience with and from attitudes about novel products and perceptions about the product could influence their acceptance of cultured meat. South African consumers’ perceptions were estimated using opinion statements, and the level of agreement was ranked on a Likert scale. Composite indices were extracted from these data, which were regressed against consumers’ willingness to try cultured meat burger patties. Results suggest that the implicit perceptions (worldviews) promoted both neophobic and neophilic attitudes, while explicit (product-specific) perceptions indicated that concerns of anticipated social, cultural and economic disruptions may drive non-adoption. The study’s results suggest targeted marketing approaches that can utilise implicit perceptions to promote consumer adoption. Other results indicated the areas of concern that should be addressed to facilitate acceptance and the population groups that could be targeted as early adopters. These results contribute to a better understanding of the potential market for cultured meat in the world's eighth-largest per capita beef consumer and provide insights into drivers and deterrents of cultured meat in an environment that struggles with food security.
AI and machine learning for soil analysis: an assessment of sustainable agricultural practices
Authors: Awais Muhammad , Naqvi Syed Muhammad Zaigham Abbas , Zhang Hao , Li Linze , Zhang Wei , Awwad Fuad A. , Ismail Emad A. A. , Khan M. Ijaz , Raghavan Vijaya , Hu Jiandong
Published: December 2023

Sustainable agricultural practices help to manage and use natural resources efficiently. Due to global climate and geospatial land design, soil texture, soil–water content (SWC), and other parameters vary greatly; thus, real time, robust, and accurate soil analytical measurements are difficult to be developed. Conventional statistical analysis tools take longer to analyze and interpret data, which may have delayed a crucial decision. Therefore, this review paper is presented to develop the researcher’s insight toward robust, accurate, and quick soil analysis using artificial intelligence (AI), deep learning (DL), and machine learning (ML) platforms to attain robustness in SWC and soil texture analysis. Machine learning algorithms, such as random forests, support vector machines, and neural networks, can be employed to develop predictive models based on available soil data and auxiliary environmental variables. Geostatistical techniques, including kriging and co-kriging, help interpolate and extrapolate soil property values to unsampled locations, improving the spatial representation of the data set. The false positivity in SWC results and bugs in advanced detection techniques are also evaluated, which may lead to wrong agricultural practices. Moreover, the advantages of AI data processing over general statistical analysis for robust and noise-free results have also been discussed in light of smart irrigation technologies. Conclusively, the conventional statistical tools for SWCs and soil texture analysis are not enough to practice and manage ergonomic land management. The broader geospatial non-numeric data are more suitable for AI processing that may soon help soil scientists develop a global SWC database.

Graphical Abstract
Adherence of denosumab treatment for low bone mineral density in Japanese people living with HIV: a retrospective observational study
Authors: Kunimoto Yusuke , Matamura Ryosuke , Ikeda Hiroshi , Horiguchi Hiroto , Fujii Satoshi , Kobune Masayoshi , Fukudo Masahide , Toda Takaki
Published: December 2023

Background

Long-term care issues, specifically metabolic bone disorders, are a concern for people living with human immunodeficiency virus (PLWH) who undergo life-long antiretroviral therapy (ART). Previous clinical trials with denosumab, an anti-RANKL antibody inhibitor, have revealed its effectiveness in increasing bone mineral density (BMD) in patients with osteoporosis. However, there are limited data on adherence and effectiveness of denosumab treatment for osteoporosis in PLWH. Hence, this study aimed to investigate the adherence and effectiveness of denosumab treatment for osteoporosis in Japanese PLWH.

Methods

This study is a retrospective exploratory analysis of 29 Japanese PLWH who initiated denosumab treatment for osteoporosis, between 2013 and 2021. The study included patients who received at least one dose of denosumab every 6 months. Adherence and persistence were defined as receiving two consecutive injections of denosumab 6 months ± 4 weeks apart and 6 months + 8 weeks apart, respectively. The primary outcome measure of the study was the adherence of denosumab treatment for 24 months. The secondary outcome measures included treatment persistence and BMD. The period after January 2020 was defined as the coronavirus disease 2019 (COVID-19) pandemic period, and its impact on adherence was investigated.

Results

The treatment adherence rates at 12 and 24 months were 89.7% and 60.7%, respectively. By contrast, the treatment persistence at 12 and 24 months was 100% and 85.7%, respectively. More patients in the group who initiated denosumab treatment after the COVID-19 pandemic reached non-adherence than in the group who initiated denosumab treatment before the pandemic. BMD at the lumbar spine and femoral neck significantly increased compared to that at baseline, with median percentage changes of 8.7% (p < 0.001) and 3.5% (p = 0.001), respectively.

Conclusions

The results showed that patients in the study had a high rate of non-adherence but a lower rate of non-persistence. Additionally, PLWH on ongoing ART experienced increased BMD with denosumab treatment. This study provides an opportunity to improve future strategies for denosumab treatment in the Japanese PLWH.
Effect of 1,25-dihydroxyvitamin D3-glycosides on postpartum health, uterine involution and litter performance of sows in a free farrowing system
Authors: Jahn Laura , Grahofer Alexander
Published: December 2023

Background

Vitamin D is essential for the reproductive efficiency in animals. There are indications that 1,25-vitD influenced the farrowing process and thus can decrease postpartum health problems. Therefore, the aim of this study was to investigate the effect of 1,25-vitD on postpartum health of the sow and uterine involution as well as the litter performance.

Results

The rectal body temperature in the 1,25-vitD group was significantly (p < 0.05) lower during the first five days after farrowing compared to the negative control group (D1: 38.6 vs. 38.9 °C; D2: 38.5 vs. 38.7 °C; D3: 38.4 vs. 38.7 °C; D4: 38.4 vs. 38.6 °C; D5: 38.5 vs. 38.9 °C). Although there was no difference between the live born piglets after farrowing, a significant higher number of piglets at day 7 and at weaning (Dw) was detected in the 1,25-vitD group compared to the control group (D7: 14.1 ± 0.9 vs. 13.4 ± 1.0, p = 0.002; Dw: 14.0 ± 0.9 vs. 13.4 ± 1.0, p = 0.02). Furthermore, the litter weight gain was significantly higher in the 1,25-vitD group when compared to the control group (94.3 vs. 86.4 kg; p = 0.045), and the weight loss of the sows was significantly lower (52 vs. 59 kg; p = 0.03). No differences in other parameter were detected.

Conclusion

This study showed a positive effect of 1,25-vitD on the body temperature, the litter performance and the body condition of the sows during lactation in comparison with the negative control group. However, more studies are needed to describe the mechanism of 1,25-vitD in detail.
Protocol for a randomised controlled feasibility trial of parent-delivered early language intervention for children with Down syndrome (PACT-DS)
Authors: Burgoyne Kelly , Pagnamenta Emma , Hartwell Kirstie , Stojanovik Vesna
Published: December 2023

Background

Down syndrome is the most common genetic cause of intellectual disability, affecting 700–800 babies annually in the UK (Wu J, Morris J, Eur J Hum Genet 21:1016–9, 2013). Children with Down syndrome have difficulties developing language skills. These difficulties can have long-term negative consequences for all aspects of their lives including social development, education and employment opportunities, and emotional wellbeing and mental health (Irwin LG et. al 2007). These aspects all have the potential to be improved through targeted early language intervention. Parents and Children Together (PACT) is a parent-delivered early language teaching programme for typically developing pre-school children at risk of language delays. A previous project (Burgoyne K, J Child Psychol Psychiatry 59(5):545–55, 2018) showed that PACT leads to improvements in children’s language and early literacy skills. Our team has worked closely with six families to adapt PACT for children with Down syndrome. The aim of the current study is to conduct a feasibility randomised controlled trial (RCT) to evaluate the feasibility of a definitive RCT and explore initial evidence of the adapted programme’s potential to support children’s language and literacy development.

Method

This is a two-arm feasibility randomised controlled trial in which children will be randomly allocated to either a PACT-DS group or to a waiting control group (who will receive intervention at the end of the project). We aim to recruit 28–30 children with Down syndrome (aged 3–6 years) and their parents/caregivers to take part. The PACT-DS group will be trained to deliver PACT-DS every day (20 min a day; 5 days a week) to their child over 30 weeks. We will collect data using assessments of child language and early literacy, measures of parent wellbeing, qualitative surveys and interviews, and monitoring data to explore trial feasibility (including recruitment and retention of families and adherence and acceptability of intervention) and cost and benefits. Data will be collected before intervention, immediately after the 30-week intervention programme, and 6 months after intervention ends. Clear progression criteria will be used to assess suitability for a definitive trial.

Discussion

This study represents initial steps in developing a definitive trial of the PACT-DS programme and will add to the limited evidence base on early language intervention for children with Down syndrome. This programme of research has the potential to make significant advancements in early language intervention research and practice for this group.

Trial registration

The trial is registered with the ISRCTN registry: study ID ISRCTN63251282. Registered on 14 July 2023.