bluuebunny/crossref_metadata_2025 huggingface dataset:
A digital version of the nine-hole peg test: Speed may be a more reliable measure of upper-limb disability than completion time in patients with multiple sclerosis
Authors: Jiang Xiaotong , McGinley Marisa , Johnston Joshua , Alberts Jay , Bermel Robert , Ontaneda Daniel , Naismith Robert T , Hyde Robert , Levitt Nick , van Beek Johan , Sun Zhaonan , Campbell Nolan , Barro Christian
Published: December 2024

Background:

A digital adaptation of the nine-hole peg test (9HPT) was developed with the potential to provide novel disability features for patients with multiple sclerosis (PwMS).

Objectives:

The objectives were to evaluate the 9HPT features based on reliability, prognosis, and discrimination between treatment groups.

Methods:

The MS partners Advancing Technology and Health Solutions (MS PATHS) cohort data were used to derive new features including completion time and speed. Association and reliability between features and clinical outcomes were tested by intraclass correlation coefficients (ICCs) with repeated measures. The added prognostic value of the features for a clinically meaningful decline was assessed by time-to-event analyses with likelihood ratio tests. The estimated effect size between treatment efficacy groups was acquired from linear mixed-effects models. Sample size was calculated for a hypothetical randomized clinical trial.

Results:

For the 10,843 PwMS, speed and completion time were associated with MS disability. Compared with time, speed showed higher reliability (ICC = 0.78 vs 0.74), added benefits in predicting disability worsening ( p < 0.001), better discrimination between high- and low-efficacy groups (effect size: 0.035 vs 0.015), and an 18% reduction in required sample size for a 1-year clinical trial.

Conclusion:

Integrating horizontal hand distances traveled over the 9HPT pegboard can be a more reliable measure of hand function.
Evaluating the Health Information system implementation and utilization in healthcare delivery
Authors: Addo Kennedy , Agyepong Pabbi Kwaku
Published: December 2024

Introduction: Information and Communication Technology (ICT) with emphasis on Electronic Health Records (EHR) is growing steadily in most developing countries including Ghana. This is considered the impetus for achieving quality service delivery. The study is intended to evaluate the implementation and utilization of health information systems in health care delivery. Methodology: A descriptive cross-sectional study was conducted to achieve the study objective. The target population included health professionals from diverse settings who interact with Electronic Health Records, the District Health Information and Management System (DHIMS-2). The data collection approach relied on close and open-ended questionnaires, observations, and focus group discussions. The proportionate stratified and simple random sampling techniques were used to obtain a representative group of healthcare professionals. Descriptive statistics was used to analyze user satisfaction, benefits, and challenges of EHR/DHIMS-2. Moreover, Pearson correlation and linear regression analysis were used to analyze the Technology Acceptance Model for the end users. Results: The study revealed that perceived ease of use and usefulness could be significantly predicted to influence end-users’ attitude towards technology adoption. The results show significant association between the combined effects of attitude and usefulness on acceptance. Conclusion: Implementing EHR and DHIMS-2 within the confines of developing nations is recommended.
Characteristics of gut microbiota of premature infants in the early postnatal period and their relationship with intraventricular hemorrhage
Authors: Zhao Yunlong , Li Shan , Zhang Rui , Zhang Xin , Shen Qiuyue , Zhang Xingyun , Tian Tian , Hou Xinlin
Published: December 2024

Background

Studies have shown correlations between gut microbiota and neurocognitive function, but little was known about the early postnatal gut microbiota and intraventricular hemorrhage (IVH). We aimed to explore the characteristics of gut microbiota in premature infants and their relationship with IVH, further exploring potential therapeutic targets.

Methods

Premature infants delivered at Peking University First Hospital from February 2023 to August 2023 were recruited as a cohort. Feces samples were collected on postnatal days 1, 3, and 5. Premature infants were divided into normal, mild IVH, and severe IVH groups based on cranial ultrasound. 16S rRNA amplicon sequencing technology was used to determine the fecal microbiota, and the results were analyzed.

Results

Thirty-eight premature infants were enrolled. There was a significant difference in alpha and beta diversity among the three groups. The relative abundance of E. coli and A. muciniphila was different among the three groups. Further random forest analysis indicated that S. lutetiensis, L. mirabilis, and N. macacae can effectively distinguish premature infants with IVH. Finally, the phylogenetic investigation of communities by reconstruction of unobserved states2 (PICRUSt2) functional gene analysis predicted significant differences in energy metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, and membrane transport between normal and severe IVH groups.

Conclusions

The gut microbiota in the early postnatal period of premature infants is closely associated with the IVH status. As age increases, the differences in gut microbiota of premature infants with different degrees of IVH continue to increase, and the trend of changes with severity of IVH becomes more and more obvious. E. coli, A. muciniphila, S. lutetiensis, L. mirabilis, N. macacae, G. haemolysans, and S. oralis can effectively distinguish between IVH infants and normal premature infants. The results indicate that gut microbiota is expected to provide effective therapeutic targets for the diagnosis and treatment of IVH.
The impact of the Dementia Care in Hospitals Program on hospital acquired complications – a non-randomised stepped wedge hybrid effectiveness-implementation study
Authors: Yates Mark W. , Bail Kasia , MacDermott Sean , Skvarc David , Theobald Meredith , Morvell Michelle , Jebramek Jessica C. , Tebbut Ian , Draper Brian , Brodaty Henry
Published: December 2024

Background

Hospitalized older patients with cognitive impairment (CI) experience poor outcomes and high rates of hospital acquired complications (HACs). This study investigated the effectiveness of a multimodal hospital CI identification and education program.

Method

A prospective stepped-wedge, cross-sectional, continuous-recruitment, hybrid effectiveness-Implementation study was conducted in acute hospitals in four Australian states/territories. The intervention, the Dementia Care in Hospitals Program (DHCP) provided: clinical/ non-clinical hospital staff CI awareness support and education; CI screening for older patients and a bedside alert—the Cognitive Impairment Identifier (CII). The primary outcome was change in the rate of the combined risk of four HACs (urinary tract infection, pneumonia, new onset delirium, pressure injury).

Results

Participants were patients aged 65 years and over admitted for 24 h or more over a 12-month period between 2015–2017 (n = 16,789). Of the 11,309 (67.4%) screened, 4,277 (37.8%) had CI. HACs occurred in 27.4% of all screened patients and were three times more likely in patients with CI after controlling for age and sex (RR = 3.03; 95%CI:2.74–3.27). There was no significant change in HAC rate for patients with CI (RR = 1.084; 95%CI: 0.93; 1.26). In the intervention period the raw HAC rate for all screened patients was 27.0%, which when adjusted for age and sex suggested a small reduction overall. However, when adjusted for hospital site, this reduction in HAC risk not statistically significant (RR = 0.968; 95%CI:0.865–1.083). There was considerable interhospital variation in intervention implementation and outcomes which explains the final non-significant effect.

Conclusion

For patient with CI the implementation of the DCHP did not result in a reduction in HAC rates. Education for hospital staff regarding cognitive impairment screening, care support, carer engagement and bedside alerts, using the DCHP, can be feasibly implemented in acute hospitals. Reducing high frequency HACs in older hospital patients with CI, warrants further research.

Trial Registration. The trial was registered retrospectively with the Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12615000905561 on 01/09/2015 with 92 patients (0.8% of total sample) recruited in the baseline and none in the intervention before registration submission.
Plasma ferritin, C-reactive protein, and adenosine deaminase levels in tuberculous lymphadenitis and pleuritis and their role in monitoring treatment response
Authors: Nisa Zaib un , Zeshan Basit , Ambreen Atiqa , Mustafa Tehmina
Published: December 2024

Background

We aimed to assess the plasma levels of ferritin, C-reactive protein (CRP), and adenosine deaminase (ADA) at baseline and their utility as biomarkers to monitor response to treatment in extrapulmonary tuberculosis (EPTB) patients.

Methods

Prospective measurements of ferritin, CRP, and ADA were done in unstimulated plasma samples of 92 EPTB (49 TB lymphadenitis and 43 TB pleuritis) patients registered for anti-TB treatment. Blood samples were taken at the start, 2, and 6 months of treatment, plasma levels of ferritin and CRP were measured by the enzyme-linked immunosorbent assay and ADA levels by kinetic chemistry method at each time point. Data was analyzed using SPSS version 22. Non-parametric tests were used for paired analysis and two groups’ comparison. Spearman’s rank test was used for correlation analysis. A Chi-square test was used for categorical variables. A p-value < 0.05 was considered statistically significant.

Results

Before the start of treatment, plasma levels of ferritin were raised in 13% and 45%, CRP in 21% and 64%, and ADA in 70% and 60% of TB lymphadenitis and pleuritis cases respectively. Levels of all three biomarkers with raised values at baseline decreased significantly with treatment at both 2 and 6 months in all patients. [Ferritin (2 months p = 0.001, 6 months p < 0.001), CRP (2 months p < 0.001, 6 months p < 0.001), ADA (2 months p = 0.039, 6 months p < 0.004)]. Plasma levels of ferritin (median 300 ng/ml range = 145–758 ng/ml) and CRP (median 11.73 mg/L, range = 10.45–17.84 mg/L) were significantly higher in TB pleuritis patients, while the levels of ADA were not significantly different among the two groups. Biosignatures generated by different combinations showed that a combination of all three biomarkers could predict treatment response in 83% and 100% of all patients at 2 and 6 months of treatment respectively.

Conclusion

A combination of serum ferritin, CRP, and ADA shows a promising role in monitoring response to treatment in TB lymphadenitis and TB pleuritis patients. Similar studies in larger cohorts are needed to establish a definite role of these biomarkers in EPTB patients.
Reduced oxycodone brain delivery in rats due to lipopolysaccharide-induced inflammation: microdialysis insights into brain disposition and sex-specific pharmacokinetics
Authors: Bällgren Frida , Hammarlund-Udenaes Margareta , Loryan Irena
Published: December 2024

Background

Oxycodone, a widely used opioid analgesic, has an unbound brain-to-plasma concentration ratio (Kp,uu) greater than unity, indicating active uptake across brain barriers associated with the putative proton-coupled organic cation (H+/OC) antiporter system. With this study, we aimed to elucidate oxycodone's CNS disposition during lipopolysaccharide (LPS)-induced systemic inflammation in Sprague–Dawley rats.

Methods

Using brain microdialysis, we dynamically and simultaneously monitored unbound oxycodone concentrations in blood, striatum, lateral ventricle, and cisterna magna following intravenous administration of oxycodone post-LPS challenge.

Results

Our results indicated a reduced, sex-independent brain net uptake of oxycodone across the blood–brain barrier (BBB) measured in the striatum. Notably, the LPS challenge has significantly altered the systemic pharmacokinetics (PK) of oxycodone, in a sex-specific manner, leading to lower clearance and higher blood concentrations in females compared to LPS-treated males and healthy rats of both sexes. Proteomic analysis using Olink Target 96 Mouse Exploratory assay confirmed the induction of systemic inflammation and neuroinflammation. The inflammation led to an increased paracellular transport, measured using 4 kDa dextran, while preserving net active uptake of oxycodone across both BBB and the blood-cerebrospinal fluid barrier (BCSFB), with Kp,uu values of 2.7 and 2.5, respectively. The extent of uptake was 1.6-fold lower (p < 0.0001) at the BBB and unchanged at the BCSFB after the LPS challenge compared to that in healthy rats. However, the mean exposure of unbound oxycodone in the brain following LPS was similar to that in healthy rats, primarily due to the LPS-induced changes in systemic exposure.

Conclusions

These findings highlight the dissimilar responses at blood–brain interfaces during LPS-induced inflammation. Advancing the knowledge of neuropharmacokinetic mechanisms, specifically those involving the H+/OC antiporter system, will enable the development of more effective therapeutic strategies during inflammation conditions.

Graphical Abstract
Sexual dimorphism in the effects of maternal adipose tissue growth hormone receptor deficiency on offspring metabolic health
Authors: Ran Liyuan , Wang Xiaoshuang , Ma Rui , Wang Haoan , Wu Yingjie , Yu Zichao
Published: December 2024

Background

The global incidence of obesity continues to rise, which increases the prevalence of metabolic diseases. We previously demonstrated the beneficial effect of adipose-specific growth hormone receptor (Ghr) knockout (KO) on metabolic parameters in male mice exposed to high fat diet. Although the effect of the growth hormone (GH) axis on lipid metabolism has been well studied, sexual dimorphism has not been considered. Furthermore, the effects of the GH axis on intergenerational adipose development are understudied. The present study aimed to evaluate whether adipose-specific Ghr knockout is associated with sex-specific differences in metabolic health of female offspring.

Methods

Ghrflox/flox (LL) mice were crossed with Adipoq-Cre mice to generate adipose-specific Ghr knockout (KO) mice. Physiological phenotype and fertility of female LL and KO mice were measured. Body weight, organ weight, glucose homeostasis, liver and adipose histology, hepatic triglycerides (TG) content, serum TG and low-density lipoprotein cholesterol (LDL-C) levels of female offspring were detected.

Results

We found an increase in adipocyte size in female KO mice, but no change in glucose tolerance or insulin sensitivity. Adipose-specific Ghr deficiency impairs fertility in female KO mice. Maternal adipose-specific Ghr deficiency had a considerable beneficial effect on glucose metabolism in female offspring. The female offspring of the KO mice were protected against diet-induced obesity and the degree of hepatic steatosis and hyperlipidemia was reduced. The adipocyte size of the KO offspring did not change significantly despite the decrease in fat weight. Furthermore, the phenotypes of the offspring of LL mice fostered by the KO mothers differed from those of offspring remaining in the maternal nest.

Conclusions

The findings of our study suggest that adipose GH axis plays a complex and important role in the intergenerational effects of metabolic health and adipocytes on offspring in a sex-specific manner. Future studies are needed to reveal the mechanisms of these sexually dimorphic phenotypes and the feasibility of providing new interventions for improving offspring metabolic health.
Natural assemblages of the earliest Triassic conodont Hindeodus parvus from the Shangsi section, Sichuan province, Southwest China
Authors: Huang Jinyuan , Hu Shixue , Li Jun , Zhou Changyong , Zhang Qiyue , Wen Wen , Min Xiao , Jiang Haishui , Martínez-Pérez Carlos , Zhang Kexin
Published: December 2024

The morphology and number of elements in the Early Triassic conodont apparatus of the genus Hindeodus, particularly Hindeodus parvus (Kozur and Pjatakova, 1976), still remain controversial. In order to shed light on the apparatus composition of this iconic genus, here we report two well-preserved conodont natural assemblages of Hindeodus from the base of Member I of the Feixianguan Formation (Induan, lower Griesbachian, in age) at Shangsi section, Sichuan Province, Southwest China. These two natural assemblages preserve direct evidence of the number, morphology, and arrangement of elements in the apparatus of Hindeodus, and in particular H. parvus. The apparatus of H. parvus consists of six morphotype elements with S, M, and P positions, showing the typical ozarkodinid 15-element arrangement. The S1-S4 array comprises a set of nine ramiform elements: a crown-shaped alate element without a ‘posterior’ process situated at the S0 position, two inner pairs of digyrate elements positioned at the S1–2 positions, and two outer pairs of bipennate elements located at the S3 and S4 locations. A pair of dolabrate elements occupy the M position outside the S array. The paired P1 and P2 positions are occupied by carminiscaphate and angulate elements, respectively. The 15-element apparatus architecture for the genus, resembles the well-known template of ozarkodinid model, further indicating the conservative architecture of the apparatus in Order Ozarkodinida spanning more than 250 million years.
Numerical evaluation of urban-warming mitigation strategies in an urban-porous media. An application of stabilized finite elements methods
Authors: García-Chan Néstor , Licea-Salazar Juan A. , Gutierrez-Ibarra Luis G.
Published: December 2024

In this paper, we explore the effectiveness of strategies for mitigating urban warming from a numerical simulation standpoint. To achieve this, a reinterpretation of porosity on an urban context allows us to identify the urban surface covered by streets, and the urban surface covered by buildings as the fluid and solid phases of an urban-porous media, respectively. Using a Gaussian distribution we define the urban porosity at all points within an urban zone. Once the urban porosity is defined, a Darcy-Brinkman-Forchheimer type model is coupled with a thermal exchange model to obtain the wind field, and the air temperature. The convective nature of the model, and the porosity gradients lead us to use stabilized finite element methods in order to avoid the appearance of spurious oscillations in numerical solutions: we use a pressure stabilizer for the Darcy-Brinkman-Forchheimer model and a least-squares stabilizer for the thermal exchange model. Numerical experiments were conducted on a domain modeled after the Metropolitan Zone of Guadalajara City, Mexico, to evaluate strategies such as white roofs, concrete-paved streets instead of asphalt, and large urban parks. The results reveal significant differences in urban temperatures, which in turn helps to alleviate thermal stress for city inhabitants.
PET imaging of GABAA receptors in pancreatic islets by [11C]flumazenil
Authors: Maloum-Rami Faïza , Cheung Pierre , Antoni Gunnar , Jin Zhe , Eriksson Olof , Espes Daniel
Published: December 2024

Background

Type 1 diabetes (T1D) is an autoimmune disease characterized by a progressive β-cell destruction. There are no clinically established methods for quantifying endocrine cells of the pancreas and current knowledge is almost exclusively based on autopsy material and functional measurements. Based on the expression of the γ-aminobutyric acid A receptors (GABAARs) in pancreatic islets and the fact that GABAAR agonists are being explored as treatment for T1D, we hypothesized that the positron emission tomography (PET) tracer [11C]flumazenil ([11C]FMZ) could serve as a marker of the endocrine mass of the pancreas. The in vivo uptake of [11C]FMZ in pig pancreas was evaluated by PET/CT, either tracer alone or after blockade of GABAAR by unlabeled flumazenil. The pancreatic binding of [11C]FMZ was investigated in vitro with frozen sections of pig pancreas as well as human organ donors, in addition to isolated mouse and human islets and exocrine preparations. The expression of GABAAR subunits in pig, human and mouse pancreas was explored by immunohistochemistry.

Results

Strong specific in vivo uptake of [11C]FMZ was observed in the pig brain as expected, but in the pancreas the signal was moderate and only partially reduced by blockade. In vitro experiments revealed a positive but weak and variable binding of [11C]FMZ in islets compared to exocrine tissue in the mouse, pig and human pancreas. In pig and mouse pancreatic islets we identified the GABAAR subunits β2 and γ2 but not α2. In the human pancreas from non-diabetic donors, we have identified the α2, β2 (although weak) and γ2 subunits, whereas from a T2D donor the α2 subunit was missing.

Conclusions

Our findings suggest that [11C]FMZ bind to GABAARs in the islets, but not with a sufficient contrast or magnitude to be implemented as an in vivo PET marker for the endocrine mass of the pancreas. However, GABAARs with different subunits are widely expressed in the endocrine cells within the pancreas in pig, human and mouse. Hence, the GABAAR could still be a potential imaging target for the endocrine cells of the pancreas but would require tracers with higher affinity and selectivity for individual GABAAR subunits.
The role of sense of ownership in rural community mini-grid management: qualitative case study from Tanzania
Authors: Ngoti Irene F.
Published: December 2024

Background

The majority of mini-grids in Tanzania are managed by private entities, faith-based institutions, and the government. In contrast, a limited number of mini-grids under community management strive to survive. Although the concept of “sense of ownership” is considered crucial for mini-grid sustainability in developing countries, there is limited theoretical exploration of the factors that drive this concept and its effects on community mini-grid management. This paper assesses the relationship between the sense of ownership among electricity users and the effective management of two solar community-based mini-grids with different sustainability experience.

Results

A sense of ownership plays a role in establishing the decision-making process of mini-grids among village energy committee members toward sustainable or unsustainable management. The mechanisms behind the sense of ownership among community members toward managing mini-grids are largely expedited by the strong leadership of village energy committee members, community participation in decision-making and resource mobilisation, especially in the preparation, design and implementation phases of mini-grids.

Conclusions

A sense of ownership is found to influence the effective management of community mini-grids in Tanzania. When designing mini-grid project policies and programs that target respective communities as prospective owners, energy practitioners and policy-makers should consider creating an environment that nurtures a sense of ownership.
Chlorogenic acid alleviates IPEC-J2 pyroptosis induced by deoxynivalenol by inhibiting activation of the NF-κB/NLRP3/caspase-1 pathway
Authors: Xue Yanmei , Li Fuchang , Li Rui , Zhang Xinru , Guo Huijun , Wang Chunyang
Published: December 2024

Background

Deoxynivalenol (DON) is a mycotoxin that severely pollutes feed ingredients, and methods for reducing DON toxicity have become a significant research direction. Chlorogenic acid (CGA) is an active polyphenol found in some plants, which has anti-inflammatory and antioxidant properties and a protective effect on animal intestinal health. The effects of CGA on DON-induced pyroptosis in the intestinal porcine epithelial cell line-J2 (IPEC-J2) and its potential mechanism were explored in this study.

Results

IPEC-J2 cells viability and membrane integrity were inversely correlated with DON concentration. Compared to those in the group treated with DON alone at 2,500 ng/mL, pretreatment with 80 μmol/L CGA for 4 h significantly improved cell viability (P < 0.01), and the alleviation of typical pyroptotic symptoms induced by DON were observed, including reduced cellular DNA fragmentation, decreased release of lactate dehydrogenase (LDH), normalized ROS levels, restoration of extracellular Ca2+ and K+ contents to normal levels (P < 0.01 ), as well as suppressed the enzyme activities of caspase-1 and caspase-4 (P < 0.01). Additionally, the mRNA expression levels of TNF, MDP, NOD2, TLR4, ASC and GSDMD were significantly improved (P < 0.01), while both mRNA and protein expression levels of NF-κB, NLRP3, caspase-1, IL-1β and IL-18 were significantly upregulated (P < 0.01) in the CGA + DON group, compare to those in the DON group.

Conclusion

Pretreatment with 80 μmol/L CGA for 4 h effectively alleviated pyroptosis in IPEC-J2 cells induced by 2,500 ng/mL of DON through inhibiting activation of the NF-κB/ NLRP3/capase-1 pathway.
Molecular basis of mucopolysaccharidosis type II (Hunter syndrome): first review and classification of published IDS gene variants
Authors: Zanetti Alessandra , D’Avanzo Francesca , Tomanin Rosella
Published: December 2024

Purpose

Mucopolysaccharidosis type II (MPS II) is a rare X-linked lysosomal storage disorder caused by genetic alterations in the iduronate 2-sulfatase (IDS) gene. A wide range of variants has been reported for different countries and ethnic groups. We collected, analyzed and uniformly summarized all published IDS gene variants reported in literature up to June 2023, here providing the first worldwide review and classification.

Methods

Data was obtained from a literature search, conducted in PubMed and Google. All data was analyzed to define the most common alleles, geographic distribution and genotype-phenotype correlation. Moreover, point variants were classified according to their pathogenicity, based on the ACMG guidelines.

Results

Several types of variants have been described in the IDS gene, including intrachromosomal homologous recombination occurring between the homologous regions of IDS gene and its pseudogene IDSP1. Overall, we collected 2852 individuals from 2798 families, including 24 female patients. Most families carried missense variants, followed by large deletions-insertions and complex rearrangements, small frameshift deletions/insertions and nonsense variants. Based on ACMG guidelines, 62.9% of the 779 point variants were classified as “pathogenic”, 35.4% as “likely pathogenic”, and the remaining 13 variants as having “uncertain significance”.

Conclusion

Data from this study confirmed that MPS II is a genetically very heterogeneous disorder, making genotype-phenotype correlation very challenging and in most cases merely unfeasible. Mutation updates are essential for the correct molecular diagnosis, genetic counseling, prenatal and preimplantation diagnosis, and disease management.
Clinical trials in neuromodulatory treatment of drug-resistant hypertension and the need for spinal cord stimulation trials: a PRISMA systematic review
Authors: Thrash Garrett W. , Wang Elijah , Sun Yifei , Walker Harrison C. , Shirvalkar Prasad , Becker Bryan K. , Holland Marshall T.
Published: December 2024

Background

Drug-resistant hypertension affects approximately 9–18% of the United States hypertensive population. Recognized as hypertension that is resistant to three or more medications, drug-resistant hypertension can lead to fatal sequelae, such as heart failure, aortic dissection, and other vast systemic disease. The disruption of the homeostatic mechanisms that stabilize blood pressure can be treated procedurally when medication fails. These procedures include carotid body stimulation, renal denervation, sympathectomies, dorsal root ganglia stimulation, and more recently spinal cord stimulation and have all been utilized in the treatment of drug-resistant hypertension.

Methods

To identify the clinical trials of neuromodulation in drug-resistant hypertension, a PubMed search was performed that included all original clinical trials of neuromodulation treating drug-resistant hypertension. The 838 articles found were sorted using Covidence to find 33 unique primary clinical trials. There were no methods used to assess risk of bias as a meta-analysis was not feasible due to heterogeneity.

Results

Renal denervation and carotid body stimulation have both shown promising results with multiple clinical trials, while sympathectomies have mostly been retired due to the irreversible adverse effects caused. Dorsal root ganglion stimulation showed varying success rates. Spinal cord stimulation is a novel treatment of drug-resistant hypertension that shows promising initial results but requires further investigation and prospective studies of the treatment to provide guidelines for future DRH treatment. The limitations of the review are reporting bias and absence of a meta-analysis that compares the treatment modality due to the heterogeneity of reported outcomes.

Conclusion

Innovation in neuromodulation is necessary to provide alternative avenues of treatment in the face of contraindications for standard treatment. Treatment of drug-resistant hypertension is essential to delay dangerous sequelae. This review’s objective is to summarize the clinical trials for treatment of drug-resistant hypertension following PRISMA guidelines and suggests future directions in the treatment of drug-resistant hypertension.
The implementation of speckle tracking echocardiography for cardiac resynchronization therapy optimisation. A rotational myocardial mechanics interpretation
Authors: Stefanidis Alexandros , Korlou Paraskevi , Margos Panagiotis , Ikonomidis Ignatios , Paraskevaidis Ioannis , Gatzoulis Konstantinos , Aivalioti Evmorfia , Kostopoulos Konstantinos
Published: December 2024

Background

Cardiac resynchronization therapy (CRT) has an additive therapeutic influence on left ventricular function in heart failure patients, but the underlying mechanisms through which it works are not completely explained. Our aim was to further elucidate the role of this intervention via rotational mechanics using 2D speckle tracking echocardiography (2D-STE).

Results

We investigated 46 patients (65 ± 9 years) who received CRT. All enrolled patients were assessed on admission by 2D-STE and 6 min walk test (6 min WT) and followed in the outpatient device clinic by 2D-STE (at 1 week and 6 months post-implantation) and 6 min WT (at 6 months post-implantation). On their first appointment all biventricular systems were optimised by atrioventricular delay optimisation and by changing the temporal activation of ventricular electrodes aiming to reach the highest left ventricular effective stroke volume across all activation options. A new 2D-STE based index (twist integral) targeting to assess the rotational mechanics of the whole cardiac cycle was also measured to further explain the CRT response. Twenty-two (48%) patients were responders at 6-month follow-up and most of them had dilated cardiomyopathy. The commonest selected mode that was related with the greatest left ventricular performance response was the simultaneous activation of the 2 ventricular leads (39%). The strongest predictor of CRT response was the improvement of effective stroke volume between admission and first appointment at clinic, followed by the improvement of twist integral, the absence of coronary artery disease, and the improvement of peak systolic twist.

Conclusions

Additional CRT optimisation via changing the temporal activation of ventricular electrodes is beneficial for left ventricular performance in heart failure patients. The success of biventricular pacing may also be explained by the improvement of left ventricular rotational mechanics.
Global Disparities in the Characteristics and Outcomes of Leukemia Clinical Trials: A Cross-Sectional Study of the ClinicalTrials.gov Database
Authors: Alhajahjeh Abdulrahman , Rotter Lara K. , Stempel Jessica M. , Grimshaw Alyssa A. , Bewersdorf Jan Philipp , Blaha Ondrej , Kewan Tariq , Podoltsev Nikolai A. , Shallis Rory M. , Mendez Lourdes , Stahl Maximilian , Zeidan Amer M.
Published: December 2024

PURPOSE

Most clinical trials are conducted exclusively in high-income countries (HICs), with only a small fraction involving centers from low-middle income countries (LMICs). However, studies evaluating the global distribution of clinical trials in leukemia are limited. Therefore, we sought to assess the present state of leukemia clinical trials that involve centers from LMICs and to compare those with trials conducted exclusively in HICs.

MATERIALS AND METHODS

We searched ClinicalTrials.gov to identify leukemia trials initiated between 2000 and 2020. In this cross-sectional study, the search strategy was developed by a medical librarian using controlled vocabulary and free-text terms. Data abstraction was independently executed by two reviewers. Trials were defined to be LMIC trials if they included centers from LMICs according to the World Bank Atlas country's income level classification for 2022-2023. Conversely, if a trial included centers from HICs only, the study was classified as a HIC trial.

RESULTS

Of 3,345 leukemia-related clinical trials identified, only 160 (4.8%) included centers from LMICs. Compared with HIC trials, LMIC trials had lower termination rates (12.5%
v
27.5%;
P
< .001) and were more likely randomized (52.5%
v
18.2%;
P
< .001), larger (sample sizes >50 patients: 69.0%
v
33.6%;
P
< .001), multicenter (81.9%
v
47.9%;
P
< .001), and later phase (phase III: 36.2%
v
8.98%;
P
< .001; phase IV: 6.25%
v
2.17%;
P
< .001). There was an increase in the proportion of randomized and diseased-focused clinical trials within the trials that involved LMIC centers between 2000-2005 and 2010-2015 (57.1%
v
47.1% and 85.7%
v
52.9%;
P
= .013 and 0.014, respectively).

CONCLUSION

We found a marked underrepresentation of LMICs in leukemia clinical trials reflecting limited access to novel leukemia therapies in LMICs.
Στρατηγική διαχείρισης κρίσεων από την Περιφέρεια Αττικής
Authors: Μανίκας Ανδρέας
Published: December 2024

Η διδακτορική διατριβή με τίτλο «Στρατηγική Διαχείρισης Κρίσεων από την Περιφέρεια Αττικής: Η Περίπτωση της Πανδημίας COVID-19» εξετάζει τις προκλήσεις, τις πρακτικές και τις στρατηγικές που υιοθετήθηκαν από την Περιφέρεια Αττικής κατά τη διάρκεια της πανδημίας COVID-19 για την αντιμετώπιση και διαχείριση της κρίσης που προέκυψε. Προκειμένου να επιτευχθεί ο σκοπός και οι επί μέρους στόχοι της διδακτορικής διατριβής, διενεργήθηκε εμπειρική έρευνα. Για την συλλογή των δεδομένων της έρευνας αναπτύχθηκε ένα κατάλληλα δομημένο ερωτηματολόγιο το οποίο απαντήθηκε από 423 μόνιμους κατοίκους της Περιφέρειας Αττικής, την περίοδο από την 1 Ιουνίου 2023 έως και την 31 Αυγούστου 2023, μετά δηλαδή το πέρας της πανδημίας. Τα δεδομένα που συλλέχθηκαν, αναλύθηκαν με την χρήση μεθόδων περιγραφικής και επαγωγικής στατιστικής, προκειμένου να επιτευχθεί ο σκοπός και οι στόχοι της έρευνας. Η έρευνα, αναλύει πώς η Περιφέρεια Αττικής ανταποκρίθηκε στην έκτακτη ανάγκη που προέκυψε από το ξέσπασμα της πανδημίας COVID-19, με έμφαση στην ταχεία προσαρμογή της σε ένα δυναμικά μεταβαλλόμενο περιβάλλον, εφαρμόζοντας στρατηγικές, οι οποίες μεταξύ άλλων, περιλαμβάνουν την εφαρμογή μέτρων δημόσιας υγείας, τη συνεργασία με την κεντρική κυβέρνηση και τη χρήση εφαρμογών τεχνολογίας και καινοτομίας για την υποστήριξη των πολιτών και την αντιμετώπιση της πανδημίας. Περεταίρω, η έρευνα αναφέρεται επίσης στη σημασία της επικοινωνίας και της διαφάνειας στη διαχείριση κρίσεων. Εξετάζει τις δράσεις που αναλήφθηκαν για την υποστήριξη των ευάλωτων ομάδων, την ενίσχυση του συστήματος υγείας, και την επανεκκίνηση της τοπικής οικονομίας. Με βάση τα αποτελέσματά της, η συνεισφορά της διατριβής είναι πολύπλευρη, καθώς αφενός μεν αποκαλύφθηκαν οι απόψεις των πολιτών για τα δυνατά και τα αδύναμα σημεία της διαχείρισης της κρίσης που προέκυψε από την πανδημία COVID-19 από την Περιφέρεια Αττικής, αφετέρου δε αναλύθηκαν οι στάσεις των πολιτών σε ό,τι αφορά την από πλευράς τους διαχείριση των κρίσεων. Κατά συνέπεια, με βάση τα αποτελέσματα της διατριβής, αποκαλύφθηκαν σημαντικές πληροφορίες για την αποτελεσματικότητα των πολιτικών που ακολουθήθηκαν, την ικανοποίηση του πληθυσμού από την ανταπόκριση της Περιφέρειας Αττικής, ενώ ταυτόχρονα, κατανοήθηκαν και οι στάσεις των πολιτών ως προς την διαχείριση των κρίσεων, γεγονός σημαντικό για την προετοιμασία τους για την διαχείριση μελλοντικών κρίσεων και καταστροφών. Η έρευνα ολοκληρώνεται με κριτική αξιολόγηση της στρατηγικής διαχείρισης κρίσεων που εφαρμόστηκε, προσφέροντας συστάσεις για τη κατάρτιση πολιτικών και στρατηγικών διαχείρισης μελλοντικών κρίσεων.
Building modern business models in industry
Authors: Tarabrin Filipp , Tumin Valeriy , Zenkina Elena , Iradionov Valeriy , Panova Elena , Vishlenkov Aleksandr , Artyuhov Georgiy , Pudov Aleksandr
Published: December 2024

The monograph is mainly aimed at senior management personnel of companies with systematic knowledge and practical experience in the field of business construction and development. The reader is given the opportunity to broaden his horizons in this area by familiarizing himself with a relatively new concept of business modeling, which is firmly rooted in the circle of foreign investment project management specialists.
In addition to the introductory function, the book also demonstrates the author's position on the issues of building and reforming business models of industrial enterprises, based on in-depth knowledge of the practices of domestic manufacturing companies.
The material, rich in practical examples, will also be useful for experienced entrepreneurs, specialists of consulting and research organizations, teachers, graduate students and university students studying in the fields of Economics, Management, State and Municipal Management, Housing and Communal Infrastructure, Quality Management, Trade, as well as in engineering and technological areas and specialties studying the disciplines of economic, organizational and managerial cycles.
Presuppositions and the Content Implication
Authors: Łukowski Piotr , Olszewski Adam , Rudnicki Konrad
Published: December 2024

In the 1950s Peter Strawson analyzed the works of Bertrand Russell regarding fundamental definitions of meaning, sentences and truth value. The debate between them uncovered many issues that Fregean, truth-functional logics have when defining concepts from natural language. To reconcile the Fregean paradigm with the reality of language use, Strawson proposed the concept of presuppositions  necessary preconditions for the truth of other sentences. We believe that his proposition stemmed primarily from the problem caused by the fact that Fregean, truth-functional logics are not sensitive to the contents of sentences and reduce them to their logical values. This is bound to produce a mismatch between the way logic models reasoning and the way language users reason since real-life reasoning is performed on the contents of sentences and not their logical values. Inspired by the ideas of Strawson and Roman Suszko, who initiated the paradigm of non-Fregean logics, we propose a new solution to the debate between Strawson and Russell. In our solution, the content implication connective is used to express content relations between sentences. We move away from truth and falsehood as the sole two semantic correlates of sentences and instead work in a system where the contents of sentences are their semantic correlates.
Profesor Ryszard Łużny (1927-1998) – Człowiek, Twórca, Mistrz
Authors: Duć-Fajfer Helena
Published: December 2024

The text attempts to evoke the figure of Professor Ryszard Luzhny, based mainly on the autobiographical sketch left for posterity by this outstanding scholar. The aspects of biography, which Professor Luzhny tried to emphasise in the sketch in particular, included the formation of the future researcher in an ethnically diverse environment, in direct contact with Russian-Ukrainian culture; the pedagogical heritage in the family of the Professor and his wife; the ethos-based, committed model of practising humanities, implemented by the scholar and introduced to his students. In the context of a very coherent
and consistently pursued own vision of research on Eastern Slavonic studies, the foundations of the Luzhny research school were outlined. The testimony to the values on which it was founded is the lasting memory of the Master, celebrated by his students and their successors as a cultural memory shaping the identity of contemporary Russian Studies in Poland.
Ryszard Łużny jako badacz folkloru rosyjskiego
Authors: Kowalska-Stus Hanna
Published: December 2024

Ryszard Luzhny’s interest in Russian oral tradition was reflected in scientifically mature and interesting works due to their methodological approach. Studies on the Russian folk tale allowed to formulate the thesis that the phenomenon of the Russian folk tale is a key to understanding the Russian national culture. It reflects deep layers of social and moral awareness of the people and refers to a system of values and customs. In another study, the researcher brilliantly showed and substantiated the cultural and historical determinants of the genre evolution of tales and legends in the 16th and 17th centuries. The insight of the research is worth emphasising, compelling the author to highlight the continuation of the legend genre in the newer Russian literature and the appreciation of its potential. The interpretation of spiritual poems presented by Professor Luzhny in the next study places them in the field of folklore works. Professor Luzhny’s research legacy is diverse, but towards the end of his life he returned to his initial scientific interests.
Symmetric Separable Convex Resource Allocation Problems with Structured Disjoint Interval Bound Constraints
Authors: Schoot Uiterkamp Martijn H. H.
Published: December 2024

Motivated by the problem of scheduling electric vehicle (EV) charging with a minimum charging threshold in smart distribution grids, we introduce the resource allocation problem (RAP) with a symmetric separable convex objective function and disjoint interval bound constraints. In this RAP, the aim is to allocate an amount of resource over a set of n activities, in which each individual allocation is restricted to a disjoint collection of m intervals. This is a generalization of classic RAPs studied in the literature in which, in contrast, each allocation is only restricted by simple lower and upper bounds, that is, m = 1. We propose an exact algorithm that, for four special cases of the problem, returns an optimal solution in [Formula: see text] time, where the term nF represents the number of flops required for one evaluation of the separable objective function. In particular, the algorithm runs in polynomial time when the number of intervals m is fixed. Moreover, we show how this algorithm can be adapted also to output an optimal solution to the problem with integer variables without increasing its time complexity. Computational experiments demonstrate the practical efficiency of the algorithm for small values of m and, in particular, for solving EV charging problems.

History: Accepted by Antonia Frangioni, Area Editor for Design & Analysis of Algorithms–Continuous.

Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2023.0263 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2023.0263 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .
A Machine Learning Method for Stackelberg Mean Field Games
Authors: Dayanıklı Gökçe , Laurière Mathieu
Published: December 2024

We propose a single-level numerical approach to solve Stackelberg mean field game (MFG) problems. In the Stackelberg MFG, an infinite population of agents plays a noncooperative game and chooses their controls to optimize their individual objectives while interacting with the principal and other agents through the population distribution. The principal can influence the mean field Nash equilibrium at the population level through policies, and she optimizes her own objective, which depends on the population distribution. This leads to a bilevel problem between the principal and mean field of agents that cannot be solved using traditional methods for MFGs. We propose a reformulation of this problem as a single-level mean field optimal control problem through a penalization approach. We prove convergence of the reformulated problem to the original problem. We propose a machine learning method based on (feed-forward and recurrent) neural networks and illustrate it on several examples from the literature. We also give a modified example to show the scalability of the proposed method and show its efficiency by comparing its performance with an alternative bilevel approach.
Recycling Standards, Green Inventions, and Spillover: Evidence from California’s Electronic Waste Recycling Act (EWRA)
Authors: Dhanorkar Suvrat , Muthulingam Suresh
Published: December 2024

Problem definition: The improper disposal of electronic and electrical goods at the end of their useful lives (i.e., e-waste) can have adverse effects on the environment and human health. The increased awareness of the negative consequences of e-waste has prompted many regulators to enact recycling standards that promote the proper disposal and recycling of e-waste. A large body of research has used analytical models to explore how recycling standards affect firms that make electronic and electrical goods. A key insight from this research is that e-waste recycling standards would induce firms to design products that have reduced environmental impact and are easier to recycle. In other words, e-waste recycling standards would enhance inventive activity at firms to better comply with regulatory requirements. But hardly any empirical work has validated the insights developed with analytical models. Methodology/results: We empirically examine whether California’s Electronic Waste Recycling Act (EWRA) affects the inventive output (i.e., measured as patents) of firms that manufacture electronic and electrical goods. We leverage a quasi-experimental setup that arises when California enacted the EWRA and use multiple identification strategies to isolate the law’s effect on the inventive output of firms. We disentangle two causal pathways, industry and headquarter location, by which EWRA affects manufacturers. We find that EWRA increased the environmentally focused inventive output (i.e., “green” patents) of affected firms in California by nearly 14% and by nearly 8% for firms in other states. Interestingly, we also observe spillover effects—EWRA increased other inventive output (i.e., patents other than green patents) of affected firms in California by nearly 41% and by nearly 24% for firms in other states. Managerial implications: Our study provides important insights for managers and policy makers by empirically quantifying the impact of recycling standards on environmentally focused inventions and by identifying spillover effects for other inventions.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.0444 .