bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness, safety, and costs of thromboprophylaxis with enoxaparin or unfractionated heparin in inpatients with obesity
Authors: Amin Alpesh , Kartashov Alex , Ngai Wilson , Steele Kevin , Rosenthal Ning
Published: June 2023

Background

Obesity is a frequent and significant risk factor for venous thromboembolism (VTE) among hospitalized adults. Pharmacologic thromboprophylaxis can help prevent VTE, but real-world effectiveness, safety, and costs among inpatients with obesity are unknown.

Objective

This study aims to compare clinical and economic outcomes among adult medical inpatients with obesity who received thromboprophylaxis with enoxaparin or unfractionated heparin (UFH).

Methods

A retrospective cohort study was performed using the PINC AI™ Healthcare Database, which covers more than 850 hospitals in the United States. Patients included were ≥18 years old, had a primary or secondary discharge diagnosis of obesity [International Classification of Diseases (ICD)-9 diagnosis codes 278.01, 278.02, and 278.03; ICD-10 diagnosis codes E66.0x, E66.1, E66.2, E66.8, and E66.9], received ≥1 thromboprophylactic dose of enoxaparin (≤40 mg/day) or UFH (≤15,000 IU/day) during the index hospitalization, stayed ≥6 days in the hospital, and were discharged between 01 January 2010, and 30 September 2016. We excluded surgical patients, patients with pre-existing VTE, and those who received higher (treatment-level) doses or multiple types of anticoagulants. Multivariable regression models were constructed to compare enoxaparin with UFH based on the incidence of VTE, pulmonary embolism (PE)­­­­­­­­–related mortality, overall in-hospital mortality, major bleeding, treatment costs, and total hospitalization costs during the index hospitalization and the 90 days after index discharge (readmission period).

Results

Among 67,193 inpatients who met the selection criteria, 44,367 (66%) and 22,826 (34%) received enoxaparin and UFH, respectively, during their index hospitalization. Demographic, visit-related, clinical, and hospital characteristics differed significantly between groups. Enoxaparin during index hospitalization was associated with 29%, 73%, 30%, and 39% decreases in the adjusted odds of VTE, PE-related mortality, in-hospital mortality, and major bleeding, respectively, compared with UFH (all p < 0.002). Compared with UFH, enoxaparin was associated with significantly lower total hospitalization costs during the index hospitalization and readmission periods.

Conclusions

Among adult inpatients with obesity, primary thromboprophylaxis with enoxaparin compared with UFH was associated with significantly lower risks of in-hospital VTE, major bleeding, PE-related mortality, overall in-hospital mortality, and hospitalization costs.
Pedagogical change and innovation culture in secondary education: a Delphi study
Authors: Valverde-Berrocoso Jesús , Rivas-Flores José Ignacio , Anguita-Martínez Rocío , Montes-Rodríguez Ramón
Published: June 2023

Secondary education in Spain is being the most controversial educational stage in educational reform processes, in relation to youth cultures and ways of learning and knowing in the emerging digital society. We present the results of the application of a Delphi methodology, as the first phase of a broader research on disruptive practices in Secondary Education. Its aim was to gather the opinion of 20 experts on how educational innovation processes are perceived at this educational level, as well as the mediations on which they are based. The Delphi questionnaire was applied in 3 Spanish regions (Andalusia, Castile and Leon, Extremadura) and was carried out in two consecutive rounds. Subsequently, focus groups were held with these experts in each of the regions. The results are grouped around 4 axes: the school institution, learning in non-formal contexts, educational innovation and innovation culture, and technological mediation. The conclusions reveal the main limitations of Secondary Education in Spain: lack of curricular flexibility, leadership for change and openness to the community, technocentric vision of educational innovation and insufficient training in digital competence of teachers.
Iodine deficiency and real-life supplementation ineffectiveness in Polish pregnant women and its impact on thyroid metabolism
Authors: Filipowicz Dorota , Szczepanek-Parulska Ewelina , Mikulska-Sauermann Aniceta A. , Karaźniewicz-Łada Marta , Główka Franciszek K. , Szymanowski Krzysztof , Ołtarzewski Mariusz , Schomburg Lutz , Ruchała Marek
Published: June 2023

Introduction

Iodine is a pivotal component of thyroid hormones, and its deficiency leads to negative pregnancy outcomes. Therefore, during gestation, additional iodine supplementation is recommended.

Objectives

By evaluating a group of women from western Poland, the study updated on iodine status during pregnancy and the effectiveness of iodine supplementation in relation to the maternal and neonatal thyroid function.

Patients and methods

A total of 91 women were recruited before the delivery between 2019 and 2021. During the medical interview, the patients declared their dietary supplements intake. Thyroid parameters (TSH, ft3, ft4, a-TPO, a-Tg, and TRAb) were measured in the serum of mothers and in the cord blood of newborns after birth. Urinary iodine concentration (UIC) and urine/creatinine (UIC/crea) ratio were assessed in single urine samples using a validated high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Neonatal TSH screening from dried blood spot was analyzed.

Results

Pregnant women showed a median (interquartile range) UIC of 106 (69–156) µg/liter and UIC/crea ratio of 104 (62–221) µg/g, whereas approximately 20% had UIC/crea below 50 µg/g, indicating iodine deficiency. The iodine supplementation ratio was 68%. No significant differences in UIC, UIC/crea and thyroid parameters were found between iodine supplemented and non-supplemented groups; however, the highest ioduria was detected when iodine was supplemented in addition to levothyroxine in comparison with both substances administered separately. Patients with UIC/crea within 150–249 µg/g demonstrated the lowest TSH and a-TPO levels. Screening TSH was above 5 mIU/liter in 6% of children.

Conclusions

Despite the national salt iodization and the recommendation to supplement iodine during gestation, the status of the abovementioned microelement and real-life intake revealed the ineffectiveness of the current iodine-deficiency prophylaxis model in pregnancy.
Identification and analysis of cellular senescence-associated signatures in diabetic kidney disease by integrated bioinformatics analysis and machine learning
Authors: Luo Yuanyuan , Zhang Lingxiao , Zhao Tongfeng
Published: June 2023

Background

Diabetic kidney disease (DKD) is a common complication of diabetes that is clinically characterized by progressive albuminuria due to glomerular destruction. The etiology of DKD is multifactorial, and numerous studies have demonstrated that cellular senescence plays a significant role in its pathogenesis, but the specific mechanism requires further investigation.

Methods

This study utilized 5 datasets comprising 144 renal samples from the Gene Expression Omnibus (GEO) database. We obtained cellular senescence-related pathways from the Molecular Signatures Database and evaluated the activity of senescence pathways in DKD patients using the Gene Set Enrichment Analysis (GSEA) algorithm. Furthermore, we identified module genes related to cellular senescence pathways through Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm and used machine learning algorithms to screen for hub genes related to senescence. Subsequently, we constructed a cellular senescence-related signature (SRS) risk score based on hub genes using the Least Absolute Shrinkage and Selection Operator (LASSO), and verified mRNA levels of hub genes by RT-PCR in vivo. Finally, we validated the relationship between the SRS risk score and kidney function, as well as their association with mitochondrial function and immune infiltration.

Results

The activity of cellular senescence-related pathways was found to be elevated among DKD patients. Based on 5 hub genes (LIMA1, ZFP36, FOS, IGFBP6, CKB), a cellular senescence-related signature (SRS) was constructed and validated as a risk factor for renal function decline in DKD patients. Notably, patients with high SRS risk scores exhibited extensive inhibition of mitochondrial pathways and upregulation of immune cell infiltration.

Conclusion

Collectively, our findings demonstrated that cellular senescence is involved in the process of DKD, providing a novel strategy for treating DKD.
Integrative analysis of DNA methylomes reveals novel cell-free biomarkers in lung adenocarcinoma
Authors: Chen Yifan , Ma Shanwu , Lin Chutong , Zhu Zhipeng , Bai Jie , Yin Zhongnan , Sun Yan , Mao Fengbiao , Xue Lixiang , Ma Shaohua
Published: June 2023

Lung cancer is a leading cause of cancer-related deaths worldwide, with a low 5-year survival rate due in part to a lack of clinically useful biomarkers. Recent studies have identified DNA methylation changes as potential cancer biomarkers. The present study identified cancer-specific CpG methylation changes by comparing genome-wide methylation data of cfDNA from lung adenocarcinomas (LUAD) patients and healthy donors in the discovery cohort. A total of 725 cell-free CpGs associated with LUAD risk were identified. Then XGBoost algorithm was performed to identify seven CpGs associated with LUAD risk. In the training phase, the 7-CpGs methylation panel was established to classify two different prognostic subgroups and showed a significant association with overall survival (OS) in LUAD patients. We found that the methylation of cg02261780 was negatively correlated with the expression of its representing gene GNA11. The methylation and expression of GNA11 were significantly associated with LAUD prognosis. Based on bisulfite PCR, the methylation levels of five CpGs (cg02261780, cg09595050, cg20193802, cg15309457, and cg05726109) were further validated in tumor tissues and matched non-malignant tissues from 20 LUAD patients. Finally, validation of the seven CpGs with RRBS data of cfDNA methylation was conducted and further proved the reliability of the 7-CpGs methylation panel. In conclusion, our study identified seven novel methylation markers from cfDNA methylation data which may contribute to better prognosis for LUAD patients.
Exploiting genetic and genomic resources to enhance productivity and abiotic stress adaptation of underutilized pulses
Authors: Dwivedi Sangam L. , Chapman Mark A. , Abberton Michael T. , Akpojotor Ufuoma Lydia , Ortiz Rodomiro
Published: June 2023

Underutilized pulses and their wild relatives are typically stress tolerant and their seeds are packed with protein, fibers, minerals, vitamins, and phytochemicals. The consumption of such nutritionally dense legumes together with cereal-based food may promote global food and nutritional security. However, such species are deficient in a few or several desirable domestication traits thereby reducing their agronomic value, requiring further genetic enhancement for developing productive, nutritionally dense, and climate resilient cultivars. This review article considers 13 underutilized pulses and focuses on their germplasm holdings, diversity, crop-wild-crop gene flow, genome sequencing, syntenic relationships, the potential for breeding and transgenic manipulation, and the genetics of agronomic and stress tolerance traits. Recent progress has shown the potential for crop improvement and food security, for example, the genetic basis of stem determinacy and fragrance in moth bean and rice bean, multiple abiotic stress tolerant traits in horse gram and tepary bean, bruchid resistance in lima bean, low neurotoxin in grass pea, and photoperiod induced flowering and anthocyanin accumulation in adzuki bean have been investigated. Advances in introgression breeding to develop elite genetic stocks of grass pea with low β-ODAP (neurotoxin compound), resistance toMungbean yellow mosaic India virusin black gram using rice bean, and abiotic stress adaptation in common bean, using genes from tepary bean have been carried out. This highlights their potential in wider breeding programs to introduce such traits in locally adapted cultivars. The potential of de-domestication or feralization in the evolution of new variants in these crops are also highlighted.
A shared genetic contribution to osteoarthritis and COVID-19 outcomes: a large-scale genome-wide cross-trait analysis
Authors: Huang Yi-Xuan , Tian Tian , Huang Ji-Xiang , Wang Jing , Sui Cong , Ni Jing
Published: June 2023

Background

Patients with osteoarthritis (OA) are exposed to an increased risk of adverse outcomes of COVID-19, and they tend to experience disruption in access to healthcare services and exercise facilities. However, a deep understanding of this comorbidity phenomenon and the underlying genetic architecture of the two diseases is still unclear. In this study, we aimed to untangle the relationship between OA and COVID-19 outcomes by conducting a large-scale genome-wide cross-trait analysis.

Methods

Genetic correlation and causal relationships between OA and COVID-19 outcomes (critical COVID-19, COVID-19 hospitalization, and COVID-19 infection) were estimated by linkage disequilibrium score regression and Mendelian Randomization approaches. We further applied Multi-Trait Analysis of GWAS and colocalization analysis to identify putative functional genes associated with both OA and COVID-19 outcomes.

Results

Significant positive genetic correlations between OA susceptibility and both critical COVID-19 (rg=0.266, P=0.0097) and COVID-19 hospitalization (rg=0.361, P=0.0006) were detected. However, there was no evidence to support causal genetic relationships between OA and critical COVID-19 (OR=1.17[1.00-1.36], P=0.049) or OA and COVID-19 hospitalization OR=1.08[0.97-1.20], P=0.143). These results were robustly consistent after the removal of obesity-related single nucleotide polymorphisms (SNPs). Moreover, we identified a strong association signal located near the FYCO1 gene (lead SNPs: rs71325101 for critical COVID-19, Pmeta=1.02×10-34; rs13079478 for COVID-19 hospitalization, Pmeta=1.09×10-25).

Conclusion

Our findings further confirmed the comorbidity of OA and COVID-19 severity, but indicate a non-causal impact of OA on COVID-19 outcomes. The study offers an instructive perspective that OA patients did not generate negative COVID-19 outcomes during the pandemic in a causal way. Further clinical guidance can be formulated to enhance the quality of self-management in vulnerable OA patients.
Anti-complement 5 antibody ameliorates antibody-mediated rejection after liver transplantation in rats
Authors: Tajima Tetsuya , Hata Koichiro , Kusakabe Jiro , Miyauchi Hidetaka , Badshah Joshua Sam , Kageyama Shoichi , Zhao Xiangdong , Kim Sung-Kwon , Tsuruyama Tatsuaki , Kirchner Varvara A. , Watanabe Takeshi , Uemoto Shinji , Hatano Etsuro
Published: June 2023

Antibody-mediated rejection (AMR) remains a refractory rejection after donor-specific antibody (DSA)-positive or blood-type incompatible liver transplantation (LT), even in the era of pre-transplant rituximab desensitization. This is due to the lack of not only effective post-transplant treatments but also robust animal models to develop/validate new interventions. Orthotopic LT from male Dark Agouti (DA) to male Lewis (LEW) rats was used to develop a rat LT-AMR model. LEW were pre-sensitized by a preceding skin transplantation from DA 4–6 weeks before LT (Group-PS), while sham procedure was performed in non-sensitized controls (Group-NS). Tacrolimus was daily administered until post-transplant day (PTD)-7 or sacrifice to suppress cellular rejections. Using this model, we validated the efficacy of anti-C5 antibody (Anti-C5) for LT-AMR. Group-PS+Anti-C5 received Anti-C5 intravenously on PTD-0 and -3. Group-PS showed increased anti-donor (DA) antibody-titers (P <0.001) and more C4d deposition in transplanted livers than in Group-NS (P <0.001). Alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bile acid (TBA), and total bilirubin (T-Bil) were all significantly higher in Group-PS than in Group-NS (all P <0.01). Thrombocytopenia (P <0.01), coagulopathies (PT-INR, P =0.04), and histopathological deterioration (C4d+h-score, P <0.001) were also confirmed in Group-PS. Anti-C5 administration significantly lowered anti-DA IgG (P <0.05), resulting in decreased ALP, TBA, and T-Bil on PTD-7 than in Group-PS (all P <0.01). Histopathological improvement was also confirmed on PTD-1, -3, and -7 (all P <0.001). Of the 9,543 genes analyzed by RNA sequencing, 575 genes were upregulated in LT-AMR (Group-PS vs. Group-NS). Of these, 6 were directly associated with the complement cascades. In particular, Ptx3, Tfpi2, and C1qtnf6 were specific to the classical pathway. Volcano plot analysis identified 22 genes that were downregulated by Anti-C5 treatment (Group-PS+Anti-C5 vs. Group-PS). Of these, Anti-C5 significantly down-regulated Nfkb2, Ripk2, Birc3, and Map3k1, the key genes that were amplified in LT-AMR. Notably, just two doses of Anti-C5 only on PTD-0 and -3 significantly improved biliary injury and liver fibrosis up to PTD-100, leading to better long-term animal survival (P =0.02). We newly developed a rat model of LT-AMR that meets all the Banff diagnostic criteria and demonstrated the efficacy of Anti-C5 antibody for LT-AMR.
A likely association between low mannan-binding lectin level and brain fog onset in long COVID patients
Authors: Bulla Roberta , Rossi Lucrezia , Furlanis Giovanni , Agostinis Chiara , Toffoli Miriam , Balduit Andrea , Mangogna Alessandro , Liccari Marco , Morosini Giorgia , Kishore Uday , Manganotti Paolo
Published: June 2023

Brain fog can be described as a constellation of new-onset neuropsychiatric sequelae in the post-acute phase of COVID-19 (long COVID). The symptoms include inattention, short-term memory loss, and reduced mental acuity, which may undermine cognition, concentration, and sleep. This cognitive impairment, persisting for weeks or months after the acute phase of SARS-CoV-2 infection, can significantly impact on daily activities and the quality of life. An important role for the complement system (C) in the pathogenesis of COVID-19 has emerged since the beginning of pandemic outbreak. A number of pathophysiological characteristics including microangiopathy and myocarditis have been attributed to dysregulated C activation due to SARS-CoV-2 infection. Mannan-binding lectin (MBL), the first recognition subcomponent of the C lectin pathway, has been shown to bind to glycosylated SARS-CoV-2 spike protein, genetic variants of MBL2 are suggested to have an association with severe COVID-19 manifestations requiring hospitalization. In the present study, we evaluated MBL activity (lectin pathway activation) and levels in the sera of a cohort of COVID-19 patients, presenting brain fog or only hyposmia/hypogeusia as persistent symptoms, and compared them with healthy volunteers. We found significantly lower levels of MBL and lectin pathway activity in the sera of patients experiencing brain fog as compared to recovered COVID-19 patients without brain fog. Our data indicate that long COVID-associated brain fog can be listed among the variegate manifestations of increased susceptibility to infections and diseases contributed by MBL deficiency.
Microsatellite markers for Monitipora digitata designed using restriction-site associated DNA sequencing
Authors: Jia Shuwen , Li Yuanchao , Chen Shiquan , Cai Zefu , Shen Jie , Wang Yi , Wu Zhongjie , Wang Daoru
Published: June 2023

Montipora digitata is a species belonging to the Acroporidae. In the Indo-Pacific region, M. digitata is widely distributed and is the dominant species of scleractinian coral in the South China Sea, however, there are currently no molecular markers suitable for assessing the species genetic diversity. Here, restriction-site associated DNA sequencing (RAD-seq) was used to isolate and characterize polymorphic microsatellite loci. A total of 317,361 RAD-tags were obtained using RAD-seq, including 6,778 microsatellite loci. Primer pairs for 106 loci were ordered and twenty-one polymorphic loci, that amplified reliably were identified. The number of alleles per locus were 2-7, observed heterozygosity was 0.111-0.556 with an average value of 0.285, and expected heterozygosity was 0.105- 0.802, with an average value of 0.536. Before Bonferroni correction 13 loci deviated significantly from the expectations of Hardy-Weinberg equilibrium (P < 0.05), after correction, two microsatellite loci deviated significantly (P < 0.0002). The polymorphic information content (PIC) ranged from 0.100-0.778, with 12 loci highly polymorphic (PIC > 0.5), six moderately polymorphic (0.25 < PIC < 0.5), and three loci with low polymorphism (PIC < 0.25). The microsatellite loci developed here will be effective tools for conservation genetic research on M. digitata.
Seasonal variation and nutrient jointly drive the community structure of macrophytes in lakes with different trophic states
Authors: Tian Yuqing , Lv Chaochao , Huang Liangliang , Shan Hang , Wang Hao , Wen Zihao , Yin Chengjie , Chou Qingchuan , Zhang Xiaolin , Ni Leyi , Cao Te
Published: June 2023

Introduction

Macrophytes are essential for maintaining the health of shallow lake ecosystems, however, the driving and responsive relationship between ecological factors (such as seasonal changes and nutrition, etc.) and plant communities is not yet clear.

Methods

In this study, we conducted seasonal surveys of macrophyte community composition in lakes with different nutrient states, aiming to understand the incidence relation between macrophyte community diversity, seasonal changes and environmental factors.

Results

According to the classification criteria of comprehensive nutritional index, there were significant differences in the trophic status of the three lakes. Among them, the Xihu Lake has reached mild eutrophication with a TLI value of 56.33, both Cibi Lake and Haixihai Lake are mesotrophic with TLI value of 36.03 and 33.48, respectively. The results of diversity analysis showed a significant negative correlation between α-diversity (include Species richness, Shannon-Wiener index, Simpson index and Pielou index) and lake nutrient status. Among them, Xihu Lake showed the lowest α-diversity in all seasons, Haixihai Lake exhibited the middle α-diversity, Cibi Lake indicated the highest α-diversity. Non-metric multidimensional ordination showed that there were obvious spatial structures differences among the macrophyte communities in the three lakes. Macrophyte community composition in the three lakes was more similar in summer and autumn, but there was a wider gap in spring and winter. The redundancy analysis indicated distinct differences between diversity index and ecological factors, the eigenvalues of Axis 1 and Axis 2 being, respectively, 36.13% and 8.15%. Environmental factors could explain 44.8% of the total variation in macrophyte communities structure. Among these, nitrogen, phosphorus, water transparency and water temperature contributed 50.2%, 3.5%, 3.8% and 27.5%, respectively.

Conclusions

In summary, the community structure of macrophytes in plateau shallow lakes is co-regulated by seasons and nutrients.
Sedative-sparing effect of acupuncture in gastrointestinal endoscopy: systematic review and meta-analysis
Authors: Yang Yun , Ji Haiyang , Lu Yunqiong , Hong Jue , Yang Guang , Kong Xiehe , Liu Jie , Ma Xiaopeng
Published: June 2023

Objective

This study aimed to perform a systematic review and meta-analysis to identify the efficacy of acupuncture therapy (including manual acupuncture and electroacupuncture) performed before or during gastrointestinal endoscopy with propofol as the main sedative, compared with placebo, sham acupuncture, or no additional treatment other than the same sedation.

Methods

A systematic search was performed through PubMed, Embase, Web of Science, Cochrane Library, Chinese Biomedical Databases (CBM), Wanfang database, China National Knowledge Infrastructure (CNKI), SinoMed, and Chinese Scientific Journal Database (VIP) to collect randomized controlled trials published before 5 November 2022. Bias assessment of the included RCTs was performed according to Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). Stata16.0 software was used to perform statistical analysis, sensitivity analysis, and publication bias analysis. The primary outcome was sedative consumption, and the secondary outcomes included the incidence of adverse events and wake-up time.

Results

A total of 10 studies with 1331 participants were included. The results showed that sedative consumption [mean difference (MD) = −29.32, 95% CI (−36.13, −22.50), P < 0.001], wake-up time [MD = −3.87, 95% CI (−5.43, −2.31), P < 0.001] and the incidence of adverse events including hypotension, nausea and vomiting, and coughing (P < 0.05) were significantly lower in the intervention group than in the control group.

Conclusion

Acupuncture combined with sedation reduces sedative consumption and wake-up time compared with sedation alone in gastrointestinal endoscopy; this combined approach allows patients to regain consciousness more quickly after examination and lower the risk of adverse effects. However, with the limited quantity and quality of relevant clinical studies, caution must be applied until more high-quality clinical studies verify and refine the conclusions.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?, identifier: CRD42022370422.
Clinical application of transcranial magnetic stimulation for functional bowel disease
Authors: Li Guangyao , Jin Binghui , Fan Zhe
Published: June 2023

Functional bowel disorder (FBD) is a common gastrointestinal disease syndrome characterized by dysmotility and secretion without known organic lesions. The pathogenesis of FBD is still unclear. In recent years, with the rise of neurogastroenterology, it has initially revealed its close relationship with the “brain-gut axis.” Transcranial magnetic stimulation (TMS) is a technique for detecting and treating the nervous system, that is characterized by non-invasiveness and painlessness. TMS plays an important role in the diagnosis and treatment of diseases, and provides a new method for the treatment of FBD. In this paper, we summarized and analyzed the research progress of using TMS therapy applied to patients with irritable bowel syndrome and functional constipation by domestic and foreign scholars in recent years by means of literature search, and found that TMS therapy could improve the intestinal discomfort and accompanying mental symptoms in patients with FBD.
Bidirectional recurrent learning of inverse dynamic models for robots with elastic joints: a real-time real-world implementation
Authors: Valencia-Vidal Brayan , Ros Eduardo , Abadía Ignacio , Luque Niceto R.
Published: June 2023

Collaborative robots, or cobots, are designed to work alongside humans and to alleviate their physical burdens, such as lifting heavy objects or performing tedious tasks. Ensuring the safety of human–robot interaction (HRI) is paramount for effective collaboration. To achieve this, it is essential to have a reliable dynamic model of the cobot that enables the implementation of torque control strategies. These strategies aim to achieve accurate motion while minimizing the amount of torque exerted by the robot. However, modeling the complex non-linear dynamics of cobots with elastic actuators poses a challenge for traditional analytical modeling techniques. Instead, cobot dynamic modeling needs to be learned through data-driven approaches, rather than analytical equation-driven modeling. In this study, we propose and evaluate three machine learning (ML) approaches based on bidirectional recurrent neural networks (BRNNs) for learning the inverse dynamic model of a cobot equipped with elastic actuators. We also provide our ML approaches with a representative training dataset of the cobot's joint positions, velocities, and corresponding torque values. The first ML approach uses a non-parametric configuration, while the other two implement semi-parametric configurations. All three ML approaches outperform the rigid-bodied dynamic model provided by the cobot's manufacturer in terms of torque precision while maintaining their generalization capabilities and real-time operation due to the optimized sample dataset size and network dimensions. Despite the similarity in torque estimation of these three configurations, the non-parametric configuration was specifically designed for worst-case scenarios where the robot dynamics are completely unknown. Finally, we validate the applicability of our ML approaches by integrating the worst-case non-parametric configuration as a controller within a feedforward loop. We verify the accuracy of the learned inverse dynamic model by comparing it to the actual cobot performance. Our non-parametric architecture outperforms the robot's default factory position controller in terms of accuracy.
Dynamic regulation of the extracellular matrix in reward memory processes: a question of time
Authors: Valeri Jake , Gisabella Barbara , Pantazopoulos Harry
Published: June 2023

Substance use disorders are a global health problem with increasing prevalence resulting in significant socioeconomic burden and increased mortality. Converging lines of evidence point to a critical role of brain extracellular matrix (ECM) molecules in the pathophysiology of substance use disorders. An increasing number of preclinical studies highlight the ECM as a promising target for development of novel cessation pharmacotherapies. The brain ECM is dynamically regulated during learning and memory processes, thus the time course of ECM alterations in substance use disorders is a critical factor that may impact interpretation of the current studies and development of pharmacological therapies. This review highlights the evidence for the involvement of ECM molecules in reward learning, including drug reward and natural reward such as food, as well as evidence regarding the pathophysiological state of the brain’s ECM in substance use disorders and metabolic disorders. We focus on the information regarding time-course and substance specific changes in ECM molecules and how this information can be leveraged for the development of therapeutic strategies.
Comparative efficacy and safety of six non-ergot dopamine-receptor agonists in early Parkinson's disease: a systematic review and network meta-analysis
Authors: Chen Xiang-Ting , Zhang Qian , Chen Fei-Fei , Wen Si-Yuan , Zhou Chang-Qing
Published: June 2023

Background

Non-ergot dopamine agonists (NEDAs) have been used as monotherapy or as an adjunctive therapy to levodopa for many years. Novel long-acting formulations of NEDAs including pramipexole extended-release (ER), ropinirole prolonged-release (PR), and rotigotine transdermal patch have been developed. However, there is no strong evidence that a given NEDA is more potent than another. We performed a systematic review and network meta-analysis to evaluate the efficacy, tolerability and safety of six commonly used NEDAs in early Parkinson's disease (PD).

Methods

Six NEDAs including piribedil, rotigotine transdermal patch, pramipexole immediate-release (IR)/ER, and ropinirole IR/PR were investigated. The efficacy outcomes including Unified Parkinson's Disease Rating Scale activities in daily life (UPDRS-II), motor function (UPDRS-III), and their subtotal (UPDRS-II + III), tolerability and safety outcomes were analyzed.

Results

A total of 20 RCTs (5,355 patients) were included in the current study. The result indicated that compared with placebo, all six investigated drugs had statistically significant differences in the improvement of UPDRS-II, UPDRS-III, and UPDRS-II + III (except ropinirole PR in UPDRS-II). There were no statistically significant differences between six NEDAs for the UPDRS-II and UPDRS-III. For UPDRS-II + III, the improvement of ropinirole IR/PR and piribedil were higher than that of rotigotine transdermal patch, and piribedil was higher than that of pramipexole IR. The surface under the cumulative ranking curve (SUCRA) indicated that piribedil resulted in best improvement in UPDRS-II and UPDRS-III (0.717 and 0.861, respectively). For UPDRS-II + III, piribedil and ropinirole PR exhibited similar improvement and both had high rates (0.858 and 0.878, respectively). Furthermore, piribedil performed better as monotherapy, ranking first in the improvement of UPDRS-II, III, and II + III (0.922, 0.960, and 0.941, separately). With regard to tolerability, there was a significant increase in overall withdrawals with pramipexole ER (0.937). In addition, the incidence of adverse reaction of ropinirole IR was relatively high (nausea: 0.678; somnolence: 0.752; dizziness: 0.758; fatigue: 0.890).

Conclusions

In this systematic review and network meta-analysis of six NEDAs, piribedil exhibited better efficacy, especially as monotherapy, and ropinirole IR was associated with a higher incidence of adverse events in patients with early PD.
Systematic review and meta-analysis of the diagnostic accuracy of spontaneous nystagmus patterns in acute vestibular syndrome
Authors: Wüthrich Martina , Wang Zheyu , Martinez Carlos Mario , Carmona Sergio , Mantokoudis Georgios , Tarnutzer Alexander Andrea
Published: June 2023

Objectives

For the assessment of patients presenting with acute prolonged vertigo meeting diagnostic criteria for acute vestibular syndrome (AVS), bedside oculomotor examinations are essential to distinguish peripheral from central causes. Here we assessed patterns of spontaneous nystagmus (SN) observed in AVS and its diagnostic accuracy at the bedside.

Methods

MEDLINE and Embase were searched for studies (1980–2022) reporting on the bedside diagnostic accuracy of SN-patterns in AVS patients. Two independent reviewers determined inclusion. We identified 4,186 unique citations, examined 219 full manuscripts, and analyzed 39 studies. Studies were rated on risk of bias (QUADAS-2). Diagnostic data were extracted and SN beating-direction patterns were correlated with lesion locations and lateralization.

Results

Included studies reported on 1,599 patients, with ischemic strokes (n = 747) and acute unilateral vestibulopathy (n = 743) being most frequent. While a horizontal or horizontal-torsional SN was significantly more often found in peripheral AVS (pAVS) than in central AVS (cAVS) patients (672/709 [94.8%] vs. 294/677 [43.4%], p < 0.001), torsional and/or vertical SN-patterns were more prevalent in cAVS than in pAVS (15.1 vs. 2.6%, p < 0.001). For an (isolated) vertical/vertical-torsional SN or an isolated torsional SN specificity (97.7% [95% CI = 95.1–100.0%]) for a central origin etiology was high, whereas sensitivity (19.1% [10.5–27.7%]) was low. Absence of any horizontal SN was more frequently observed in cAVS than in pAVS (55.2 vs. 7.0%, p < 0.001). Ipsilesional and contralesional beating directions of horizontal SN in cAVS were found at similar frequency (28.0 vs. 21.7%, p = 0.052), whereas for pAVS a contralesional SN was significantly more frequent (95.2 vs. 2.5%, p < 0.001). For PICA strokes presenting with horizontal SN, beating direction was ipsilesional more often than contralesional (23.9 vs. 6.4%, p = 0.006), while the opposite was observed for AICA strokes (2.2 vs. 63.0%, p < 0.001).

Conclusions

(Isolated) vertical and/or torsional SN is found in a minority (15.1%) of cAVS patients only. When present, it is highly predictive for a central cause. A combined torsional-downbeating SN-pattern may be observed in pAVS also in cases with isolated lesions of the inferior branch of the vestibular nerve. Furthermore, in cAVS patients the SN beating direction itself does not allow a prediction on the lesion side.
Machine learning approach for early onset dementia neurobiomarker using EEG network topology features
Authors: Rutkowski Tomasz M. , Abe Masato S. , Komendzinski Tomasz , Sugimoto Hikaru , Narebski Stanislaw , Otake-Matsuura Mihoko
Published: June 2023

Introduction

Modern neurotechnology research employing state-of-the-art machine learning algorithms within the so-called “AI for social good” domain contributes to improving the well-being of individuals with a disability. Using digital health technologies, home-based self-diagnostics, or cognitive decline managing approaches with neuro-biomarker feedback may be helpful for older adults to remain independent and improve their wellbeing. We report research results on early-onset dementia neuro-biomarkers to scrutinize cognitive-behavioral intervention management and digital non-pharmacological therapies.

Methods

We present an empirical task in the EEG-based passive brain-computer interface application framework to assess working memory decline for forecasting a mild cognitive impairment. The EEG responses are analyzed in a framework of a network neuroscience technique applied to EEG time series for evaluation and to confirm the initial hypothesis of possible ML application modeling mild cognitive impairment prediction.

Results

We report findings from a pilot study group in Poland for a cognitive decline prediction. We utilize two emotional working memory tasks by analyzing EEG responses to facial emotions reproduced in short videos. A reminiscent interior image oddball task is also employed to validate the proposed methodology further.

Discussion

The proposed three experimental tasks in the current pilot study showcase the critical utilization of artificial intelligence for early-onset dementia prognosis in older adults.
Cannabidiol and cannabis-inspired terpene blends have acute prosocial effects in the BTBR mouse model of autism spectrum disorder
Authors: Staben Jenika , Koch Megan , Reid Keelee , Muckerheide Jessica , Gilman Lauren , McGuinness Finn , Kiesser Sarina , Oswald Iain W. H. , Koby Kevin A. , Martin Thomas J. , Kaplan Joshua S.
Published: June 2023

Introduction

Cannabidiol (CBD) is a non-intoxicating phytocannabinoid with increasing popularity due to its purported therapeutic efficacy for numerous off-label conditions including anxiety and autism spectrum disorder (ASD). Those with ASD are commonly deficient in endogenous cannabinoid signaling and GABAergic tone. CBD has a complex pharmacodynamic profile that includes enhancing GABA and endocannabinoid signaling. Thus, there is mechanistic justification for investigating CBD’s potential to improve social interaction and related symptoms in ASD. Recent clinical trials in children with ASD support CBD’s beneficial effects in numerous comorbid symptoms, but its impact on social behavior is understudied.

Methods

Here, we tested the prosocial and general anxiolytic efficacy of a commercially available CBD-rich broad spectrum hemp oil delivered by repeated puff vaporization and consumed via passive inhalation in the female cohort of the BTBR strain, a common inbred mouse line for preclinical assessment of ASD-like behaviors.

Results

We observed that CBD enhanced prosocial behaviors using the 3-Chamber Test with a different vapor dose-response relationship between prosocial behavior and anxiety-related behavior on the elevated plus maze. We also identified that inhalation of a vaporized terpene blend from the popular OG Kush cannabis strain increased prosocial behavior independently of CBD and acted together with CBD to promote a robust prosocial effect. We observed similar prosocial effects with two additional cannabis terpene blends from the Do-Si-Dos and Blue Dream strains, and further reveal that these prosocial benefits rely on the combination of multiple terpenes that comprise the blends.

Discussion

Our results illustrate the added benefit of cannabis terpene blends for CBD-based treatment of ASD.
A clinically managed weight loss program evaluation and the impact of COVID-19
Authors: Cachero Katrina , Mollard Rebecca , Myrie Semone , MacKay Dylan
Published: June 2023

Introduction

With the prevalence of obesity increasing, many weight-loss programs were created to aid in combating the trend. The Weight Loss Clinic (WLC) was created to provide personalized support for lifestyle changes using a multidisciplinary team with medical oversight. This study evaluated the clinically-managed weight loss program at the Wellness Institute.

Methods

This was a prospective evaluation of a newly established program between January 2019–August 2020. Participants who entered the weight loss program were approached to learn about the evaluation. A total of 41 participants were included. The primary outcomes included changes in body weight and achievement of more than 5% initial body weight loss. Outcome measures were collected pre-and post-program and the data was analyzed through paired t-tests on R studio.

Results

Greater body weight-loss was seen in completers pre-COVID-19 compared to those who completed during the pandemic (Mean, ±SD; 7.51 ± 6.24 kg n = 13 p < 0.001 vs. 1.75 ± 4.43 kg n = 9, p = 0.02). Completers pre-COVID-19 demonstrated improvements in waist circumference, Framingham risk score, blood pressure, hemoglobin A1C, and body fat percentage.

Conclusions and implications

Though the sample size was small to show definitve evidence, the results may suggest the program worked well prior to the pandemic but the pandemic created barriers to weight-loss for participants.
Clinical and endoscopic features of primary small bowel lymphoma: a single-center experience from mainland China
Authors: Tian Feng-Yu , Wang Jue-Xin , Huang Gang , An Wen , Ai Li-Si , Wang Sui , Wang Pei-Zhu , Yu Yan-Bo , Zuo Xiu-Li , Li Yan-Qing
Published: June 2023

Objective

The worldwide incidence of primary small intestinal lymphoma (PSIL) is increasing. However, little is known about the clinical and endoscopic characteristics of this disease. The aim of this study was to investigate the clinical and endoscopic data of patients with PSIL, with the goal of enhancing our understanding of the disease, improving diagnostic accuracy, and facilitating more accurate prognosis estimation.

Methods

Ninety-four patients diagnosed with PSIL were retrospectively studied at Qilu Hospital of Shandong University between 2012 and 2021. The clinical data, enteroscopy findings, treatment modalities, and survival times were collected and analyzed.

Results

Ninety-four patients (52 males) with PSIL were included in this study. The median age of onset was 58.5 years (range: 19-80 years). Diffuse large B-cell lymphoma (n=37) was the most common pathological type. Abdominal pain (n=59) was the most frequent clinical presentation. The ileocecal region (n=32) was the most commonly affected site, and 11.7% of patients had multiple lesions. At the time of diagnosis, the majority of patients (n=68) were in stages I-II. A new endoscopic classification of PSIL was developed, including hypertrophic type, exophytic type, follicular/polypoid type, ulcerative type, and diffusion type. Surgery did not show a significant increase in overall survival; chemotherapy was the most commonly administered treatment. T-cell lymphoma, stages III-IV, “B” symptoms, and ulcerative type were associated with poor prognosis.

Conclusion

This study provides a comprehensive analysis of the clinical and endoscopic features of PSIL in 94 patients. This highlights the importance of considering clinical and endoscopic characteristics for accurate diagnosis and prognosis estimation during small bowel enteroscopy. Early detection and treatment of PSIL is associated with a favorable prognosis. Our findings also suggest that certain risk factors, such as pathological type, “B” symptoms, and endoscopic type, may affect the survival of PSIL patients. These results underscore the need for careful consideration of these factors in the diagnosis and treatment of PSIL.
Deep learning classification of deep ultraviolet fluorescence images toward intra-operative margin assessment in breast cancer
Authors: To Tyrell , Lu Tongtong , Jorns Julie M. , Patton Mollie , Schmidt Taly Gilat , Yen Tina , Yu Bing , Ye Dong Hye
Published: June 2023

Background

Breast-conserving surgery is aimed at removing all cancerous cells while minimizing the loss of healthy tissue. To ensure a balance between complete resection of cancer and preservation of healthy tissue, it is necessary to assess themargins of the removed specimen during the operation. Deep ultraviolet (DUV) fluorescence scanning microscopy provides rapid whole-surface imaging (WSI) of resected tissues with significant contrast between malignant and normal/benign tissue. Intra-operative margin assessment with DUV images would benefit from an automated breast cancer classification method.

Methods

Deep learning has shown promising results in breast cancer classification, but the limited DUV image dataset presents the challenge of overfitting to train a robust network. To overcome this challenge, the DUV-WSI images are split into small patches, and features are extracted using a pre-trained convolutional neural network—afterward, a gradient-boosting tree trains on these features for patch-level classification. An ensemble learning approach merges patch-level classification results and regional importance to determine the margin status. An explainable artificial intelligence method calculates the regional importance values.

Results

The proposed method’s ability to determine the DUV WSI was high with 95% accuracy. The 100% sensitivity shows that the method can detect malignant cases efficiently. The method could also accurately localize areas that contain malignant or normal/benign tissue.

Conclusion

The proposed method outperforms the standard deep learning classification methods on the DUV breast surgical samples. The results suggest that it can be used to improve classification performance and identify cancerous regions more effectively.
Therapy of childhood acute lymphoblastic leukemia in resource-poor geospaces
Authors: Gallardo-Pérez Moisés M. , Gale Robert Peter , Reyes-Cisneros Oscar A. , Sánchez-Bonilla Daniela , Fernández-Gutiérrez José A. , Stock Wendy , Murrieta-Álvarez Iván , Olivares-Gazca Juan Carlos , Ruiz-Delgado Guillermo J. , Fonseca Rafael , Ruiz-Argüelles Guillermo J.
Published: June 2023

The therapy of children with acute lymphoblastic leukemia (ALL) in limited resource geospaces is challenging and must balance safety, efficacy, availability, and affordability. We modified the control arm of the St. Jude Total XI protocol for outpatient delivery including once-weekly daunorubicin and vincristine in initial therapy, postponing intrathecal chemotherapy until day 22, prophylactic oral antibiotics/antimycotics, use of generic drugs, and no central nervous system (CNS) radiation. Data were interrogated from 104 consecutive children ≤12 years (median, 6 years [interquartile range (IQR), 3, 9 years]. All therapies were given in an outpatient setting in 72 children. Median follow-up is 56 months (IQR 20, 126 months). A total of 88 children achieved a hematological complete remission. Median event-free survival (EFS) is 87 months [95% confidence interval (CI), 39, 60], 7.6 years in low-risk children (3.4, 8 years) whereas 2.5 years (1, 10 years) in high-risk children. The 5-year cumulative incidence of relapse (CIR) is 28% (18, 35%), 26% (14, 37%) in low-risk children and 35% (14, 52%) in high-risk children. Median survival for all subjects is not reached but must exceed 5 years. A total of 36 children relapsed at a median of 12 months (5, 23 months). Outcomes were comparable to those reported in the control arm of the Total Therapy XI study, but inferior to current treatment protocols in high-income countries. The average cost of the first 2 years of therapy was $28,500 USD compared with an average cost of approximately $150,000 USD in the US, an 80% saving. In conclusion, using an outpatient-based modification of the St. Jude Total XI protocol, we obtained good results with relatively few hospitalizations or adverse events and at a substantial saving. This model can be applied in other resource-poor geospaces.