bluuebunny/crossref_metadata_2025 huggingface dataset:
Advocating for an Advanced Cardiac POCUS Curriculum Among Internal Medicine Residents
Authors: Eromosele Oseiwe B. , Pipilas Alexandra , Sherer Jason A. , Schwartz Michael C.
Published: December 2024

Advocating for integrating a cardiac point-of-care ultrasound (POCUS) curriculum into Internal Medicine residency, this letter emphasizes the unique advantages of cardiac POCUS, particularly its rapid utility and safety, while highlighting existing knowledge gaps among trainees. This perspective research letter underscores the need for a structured advanced cardiac POCUS elective to address the knowledge and skill gaps among internal medicine trainees who have taken the introductory POCUS elective, providing a career preparatory course for internal medicine residents interested in cardiology, critical care, hospital medicine, primary care, and rural medicine. The perspective research paper also underscores the feasibility and benefits of such training, ultimately supporting the implementation of an advanced cardiac POCUS elective in the United States Internal Medicine residency programs.
Anti-inflammatory effects of cyclodextrin nanoparticles enable macrophage repolarization and reduce inflammation
Authors: Brettner Felix E. B. , Gier Stefanie , Haessler Annika , Schreiner Jonas , Vogel-Kindgen Sarah , Windbergs Maike
Published: December 2024

Inflammation plays a critical role in the pathophysiology of many diseases, and dysregulation of the involved signaling cascades often culminates in uncontrollable disease progression and, ultimately, chronic manifestation. Addressing these disorders requires balancing inflammation control while preserving essential immune functions. Cyclodextrins (CDs), particularly β-CD, have gained attention as biocompatible biomaterials with intrinsic anti-inflammatory properties, and chemical modification of their backbone offers a promising strategy to enhance their physicochemical properties, adaptability, and therapeutic potential. This study evaluated and characterized the immunomodulatory effects of amphiphilic CD derivatives, which self-assemble into nanoparticles, compared to soluble parent β-CD. In a human macrophage model, CD nanoparticles demonstrated superior anti-inflammatory activity, with derivative-specific effects tied to their physicochemical properties, surpassing the soluble β-CD control. Alongside the downregulation of key pro-inflammatory markers, significant reductions in inflammasome activation and changes in lipid profiles were observed. The findings of this study underscore the potential of cyclodextrin-based nanoparticles as versatile biomaterials for treating the complex pathophysiology of various acute and chronic inflammation-associated disorders.
Built-in selection or confounder bias? Dynamic Landmarking in matched propensity score analyses
Authors: Strobel Alexandra , Wienke Andreas , Gummert Jan , Bleiziffer Sabine , Kuss Oliver
Published: December 2024

Background

Propensity score matching has become a popular method for estimating causal treatment effects in non-randomized studies. However, for time-to-event outcomes, the estimation of hazard ratios based on propensity scores can be challenging if omitted or unobserved covariates are present. Not accounting for such covariates could lead to treatment estimates, differing from the estimate of interest. However, researchers often do not know whether (and, if so, which) covariates will cause this divergence.

Methods

To address this issue, we extended a previously described method, Dynamic Landmarking, which was originally developed for randomized trials. The method is based on successively deletion of sorted observations and gradually fitting univariable Cox models. In addition, the balance of observed, but omitted covariates can be measured by the sum of squared z-differences.

Results

By simulation we show, that Dynamic Landmarking provides a good visual tool for detecting and distinguishing treatment effect estimates underlying built-in selection or confounding bias. We illustrate the approach with a data set from cardiac surgery and provide some recommendations on how to use and interpret Dynamic Landmarking in propensity score matched studies.

Conclusion

Dynamic Landmarking is a useful post-hoc diagnosis tool for visualizing whether an estimated hazard ratio could be distorted by confounding or built-in selection bias.
The analysis and reporting of multiple outcomes in mental health trials: a methodological systematic review
Authors: Stringer Dominic , Payne Mollie , Carter Ben , Emsley Richard
Published: December 2024

Background

The choice of a single primary outcome in randomised trials can be difficult, especially in mental health where interventions may be complex and target several outcomes simultaneously. We carried out a systematic review to assess the quality of the analysis and reporting of multiple outcomes in mental health RCTs, comparing approaches with current CONSORT and other regulatory guidance.

Methods

The review included all late-stage mental health trials published between 1st January 2019 to 31st December 2020 in 9 leading medical and mental health journals. Pilot and feasibility trials, non-randomised trials, and early phase trials were excluded. The total number of primary, secondary and other outcomes was recorded, as was any strategy used to incorporate multiple primary outcomes in the primary analysis.

Results

There were 147 included mental health trials. Most trials (101/147) followed CONSORT guidance by specifying a single primary outcome with other outcomes defined as secondary and analysed in separate statistical analyses, although a minority (10/147) did not specify any outcomes as primary. Where multiple primary outcomes were specified (33/147), most (26/33) did not correct for multiplicity, contradicting regulatory guidance. The median number of clinical outcomes reported across studies was 8 (IQR 5–11 ).

Conclusions

Most trials are correctly following CONSORT guidance. However, there was little consideration given to multiplicity or correlation between outcomes even where multiple primary outcomes were stated. Trials should correct for multiplicity when multiple primary outcomes are specified or describe some other strategy to address the multiplicity. Overall, very few mental health trials are taking advantage of multiple outcome strategies in the primary analysis, especially more complex strategies such as multivariate modelling. More work is required to show these exist, aid interpretation, increase efficiency and are easily implemented.

Registration

Our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 11th January 2023 (CRD42023382274).
Influence of an enhanced recovery programme on clinical outcomes and health-related quality of life after pancreaticoduodenectomy ad modum Whipple – an explorative and comparative single-centre study
Authors: Andersson Thomas , Engström My , Wennerblom Johanna , Gyllensten Hanna , Bjerså Kristofer
Published: December 2024

Background

The introduction of enhanced recovery programmes (ERP) in pancreatic surgery has significantly improved clinical outcomes by decreasing the length of hospital stay, cost and complications without increasing readmissions and reoperations. To complement evidence on these outcomes, there is a need to explore patients’ perspectives of a structured ERP. Therefore, this study aimed to explore the health-related quality of life (HRQoL) of patients before and after implementing ERP in pancreaticoduodenectomy ad modum Whipple (PD) at a regional surgical centre.

Method

This was an explorative and comparative single-centre study in Sweden. A prospective cohort receiving ERP was included between October 2019 and December 2022 (n = 73) and was compared with a retrospective pre-ERP cohort between October 2011 and December 2013 (n = 65). EQ-5D, the European Organization for Research and Treatment of Cancer (EORCT) Quality of Life Questionnaire Cancer 30 items (QOL-C30), and EORCT Quality of Life Questionnaire pancreatic cancer module (QOL-PAN26) were collected preoperatively and at three and six months postoperatively. Demographic and clinical variables were collected from patient charts. Complications were expressed using the Clavien-Dindo Classification and the Comprehensive Complications Index (CCI).

Results

There were no significant differences in general health, cancer- or disease-specific HRQoL between the pre-ERP and ERP cohorts. Length of stay was significantly shorter in the ERP cohort (16 vs. 11 days; p < 0.001). There was no significant difference in CCI.

Conclusion

No significant differences were found in the HRQoL of patients who participated in an ERP compared to those who did not. However, a significant decrease in LoS was found when ERP was applied.

Trial registration

Not applicable.
Prognostic factors in patients with gastrointestinal perforation under the acute care surgery model : a retrospective cohort study
Authors: Sung Kiyoung , Hwang Sanguk , Lee Jaeheon , Cho Jinbeom
Published: December 2024

Background

Gastrointestinal perforation (GIP) is a life-threatening condition that necessitates immediate surgical intervention. This study aims to identify prognostic factors in patients with GIP treated within a standardized acute care surgery (ACS) framework.

Materials and methods

This single center retrospective cohort study analyzed patients diagnosed with GIP who underwent emergent surgery and were admitted to the intensive care unit between January 2013 and March 2023.

Results

Among 354 patients, the mortality was 11%, and 38% of survivors experienced significant complications (Clavien-Dindo class III or higher). Independent prognostic factors for mortality included initial sequential organ failure assessment (SOFA) scores (at the time of admission or ACS activation), postoperative SOFA (p-SOFA) scores, and postoperative body temperatures. For morbidity, independent predictors were the extent of peritonitis, the open surgery, postoperative albumin levels, and p-SOFA scores. These factors showed significant predictive accuracy for patient outcomes, as evidenced by the area under the receiver operating characteristic curve. The Random Forest model identified p-SOFA scores and postoperative albumin levels as the most significant predictors for both survival and complications, with feature importances of 40.46% and 36.61% for survival, and 39.97% and 37.28% for complications, respectively. Postoperative body temperature also played a moderately important role, contributing 14.63% to mortality and 15.9% to morbidity predictions. Patients with a p-SOFA score ≥ 7, postoperative albumin ≤ 2, and body temperature ≤ 36 °C, as well as those with a p-SOFA score ≥ 10, albumin ≤ 2.9, and body temperature ≤ 36 °C, had a 100% mortality rate. These factors are critical indicators for predicting patient outcomes.

Conclusion

It is crucial to establish a system that ensures rapid preoperative work-up, accurate surgical intervention, and evidence-based postoperative critical care. Implementing such a system and assessing patient outcomes after surgery using the identified factors could provide a more detailed evaluation.
Laparoscopic-assisted versus ultrasound-guided transversus abdominis plane block for laparoscopic cholecystectomy: a systematic review and meta-analysis
Authors: Ghani Sundus Abdul , Hussain Hassan Ul , Wahid Maryam Abdul , Majeed Neha , Burney Sheeba , Tanveer Areesha , Asghar Muhammad Sohaib
Published: December 2024

Background

Laparoscopic-assisted (LTAP) and ultrasound-guided (UTAP) transversus abdominis plane (TAP) blocks are widely used for postoperative analgesia in laparoscopic cholecystectomy (LC), yet their comparative effectiveness remains unclear. The aim of this meta-analysis was to systematically evaluate and compare postoperative outcomes of LTAP and UTAP in LC.

Materials and methodology

A comprehensive literature search of five electronic databases was conducted from the inception of the paper till 2 June 2024 following PRISMA guidelines. Eligibility criteria included: (a) randomized controlled trials (RCTs); (b) adult patients (≥ 18 years) undergoing elective LC; (c) intervention group undergoing LTAP; (d) control group receiving UTAP; (e) outcomes: postoperative pain intensity using VAS score; time to first analgesic need; postoperative morphine consumption; postoperative nausea vomiting (PONV); time to first bowel evacuation; time to first flatus. Mendeley Desktop 1.19.8 was used for article retrieval and for the removal of duplicates. Risk of bias was assessed using the Cochrane Risk of Bias Tool, and statistical analysis was performed using Review Manager, applying a random-effects model. Forest plots represented combined effects of Risk Ratios (RRs) for dichotomous outcomes and weighted mean differences (WMDs) for continuous outcomes with a 95% confidence interval (CI). P-value ≤ 0.05 was considered statistically significant and Higgin’s I² test was employed to assess heterogeneity.

Results

Seven RCTs in total involving 603 patients were included in the analysis, with 236 patients in the LTAP group and 232 in the UTAP group. No statistically significant differences observed between LTAP and UTAP in postoperative pain intensity at 6, 12, and 24 h, time to first analgesic need, postoperative morphine consumption, PONV, time to first stools, and time to first flatus, initially. Sensitivity analysis revealed a significant reduction in 6-hour postoperative pain in the LTAP group (WMD = 0.39; 95% CI = 0.10,0.67; P = 0.008; I² = 0%), but no significant differences were found in later time points (12 h: WMD = 0.12; 95% CI = -0.17,0.40; P = 0.42; I² = 0%; 24 h: WMD = -0.04; 95% CI = -0.26, 0.18; P = 0.73; I² = 5%) or in other outcomes. Moderate levels of heterogeneity and an overall low risk of bias in quality assessment were observed among the studies.

Conclusion

Our meta-analysis indicated no clear advantage of LTAP over UTAP in managing postoperative pain and related outcomes in LC. Although LTAP may offer logistical benefits by reducing the need for equipment and personnel, further large-scale RCTs focusing on procedure-specific outcomes are needed to establish definitive conclusions.
The potential of AB-free kava in enabling tobacco cessation via management of abstinence-related stress and insomnia: study protocol for a randomized clinical trial
Authors: Xing Chengguo , Malaty John , Malham Melissa Bou , Orlando Frank A. , Lynch Allison , Huo Zhiguang , François Magda , Firpi-Morell Roberto , Fisher Carla L. , Christou Demetra D. , Salloum Ramzi G.
Published: December 2024

Background

As the primary cause of various preventable illnesses, smoking results in approximately five million premature deaths each year in the US and a multitude of adults living with serious illness. The majority of smokers know the health risks associated with smoking and intend to quit. However, quitting is very difficult partly because of insomnia and stress associated with it. Current tobacco cessation medications are not designed to address these problems, which may have contributed to their limited success in enabling cessation. Novel interventions are thus urgently needed to enhance success rates in tobacco cessation. Based on its historical usage and our preliminary data, kava is such a candidate. Kava, customarily enjoyed by South Pacific Islanders, is known for its relaxing effects, stress-relieving properties, and ability to enhance sleep. In the US, it is marketed and distributed as a dietary supplement due to its recognized calming properties. A pilot trial was performed among active smokers with a one-week ingestion of a kava supplement. The results for the first-time revealed kava’s potential in enabling tobacco cessation with effects on a panel of biological signatures. The primary goal of this trial is to replicate kava’s effects on the biological signatures of tobacco use, stress, and sleep in addition to its compliance and safety among those who smoke.

Methods

A double-blind randomized placebo controlled two-arm trial will enroll 76 smokers with intention to quit, who will consume AB-free kava at a dietary supplement dose or placebo, 3 times per day for 4 weeks with two follow-ups.

Discussion

The study will (1) monitor the adherence to and safety of AB-free kava consumption among smokers and evaluate changes in smoking habits, and (2) quantify a panel of non-invasive translatable biomarkers to objectively evaluate AB-free kava’s holistic effects on biological signatures associated with tobacco use, stress, and sleep. We hypothesize that AB-free kava is a novel and promising intervention to facilitate tobacco cessation via its holistic effects associated with managing stress and insomnia during abstinence. If the results from this study support our hypothesis, kava could emerge as an affordable and accessible dietary supplement candidate for tobacco cessation.

Trial Registration

registered on 04/14/2023 in ClinicalTrials.gov with the identifier NCT05814055.
The conflict between oral health and patient autonomy in dentistry: a scoping review
Authors: Kovács Szilárd Dávid , Irawan Anggi Septia , Zörgő Szilvia , Kovács József
Published: December 2024

Background

Respect for patient autonomy, the principle that patients are capable to make informed decisions about medical interventions, is fundamental in present-day medicine. However, if a patient’s request is medically not indicated, the practitioner faces an ethical dilemma represented by the conflict of the principles of patient autonomy, beneficence, and maleficence. Adjacent to topics such as medical assistance in dying and healthy limb amputation, this ethical dilemma also manifests in the care of the maxillofacial region (the oral cavity and its surroundings), an area crucial to esthetic appearance, but also to everyday functions including mastication, speech, and facial expression, all of which are related to well-being. Our aim was to explore the manifestations and resolutions of the conflict between oral health and patient autonomy in relevant literature in order to contribute to the discourse of ethical challenges concerning patient autonomy, beneficence, and nonmaleficence.

Methods

We screened all journal articles discussing the researched ethical dilemma obtained from three databases. Two researchers developed a hierarchical coding scheme, where the parent and grandparent codes were designated deductively as: Case (situations involving the researched ethical dilemma), Judgement (decisions made in the ethical dilemma), and Principle (ideas, rules, propositions explaining the judgements); child codes were developed inductively. After coding the sources, we utilized thematic analysis to construct code constellations.

Results

Most themes identified in our sources advocated for the practitioner to choose the alternative that benefits the patient from a medical perspective, although no theme excluded the consideration of patient autonomy. Instances where respect for patient autonomy was encouraged concerned oral preventive care or when the requested intervention was expected to have an insignificant impact on oral health.

Conclusions

Ethical conflicts concerning patient autonomy, beneficence, and nonmaleficence have a marked presence in oral care. These conflicts arise through the issue of body modification, evident in cosmetic dentistry and requests for tooth extraction. Our sources generally support the argumentation for beneficence, despite the rise of cosmetic procedures in dentistry.
Assessing the comparative effects of interventions in COPD: a tutorial on network meta-analysis for clinicians
Authors: Haeussler Katrin , Ismaila Afisi S. , Malmenäs Mia , Noorduyn Stephen G. , Green Nathan , Compton Chris , Thabane Lehana , Vogelmeier Claus F. , Halpin David M. G.
Published: December 2024

To optimize patient outcomes, healthcare decisions should be based on the most up-to-date high-quality evidence. Randomized controlled trials (RCTs) are vital for demonstrating the efficacy of interventions; however, information on how an intervention compares to already available treatments and/or fits into treatment algorithms is sometimes limited. Although different therapeutic classes are available for the treatment of chronic obstructive pulmonary disease (COPD), assessing the relative efficacy of these treatments is challenging. Synthesizing evidence from multiple RCTs via meta-analysis can help provide a comprehensive assessment of all available evidence and a “global summary” of findings. Pairwise meta-analysis is a well-established method that can be used if two treatments have previously been examined in head-to-head clinical trials. However, for some comparisons, no head-to-head studies are available, for example the efficacy of single-inhaler triple therapies for the treatment of COPD. In such cases, network meta-analysis (NMA) can be used, to indirectly compare treatments by assessing their effects relative to a common comparator using data from multiple studies. However, incorrect choice or application of methods can hinder interpretation of findings or lead to invalid summary estimates. As such, the use of the GRADE reporting framework is an essential step to assess the certainty of the evidence. With an increasing reliance on NMAs to inform clinical decisions, it is now particularly important that healthcare professionals understand the appropriate usage of different methods of NMA and critically appraise published evidence when informing their clinical decisions. This review provides an overview of NMA as a method for evidence synthesis within the field of COPD pharmacotherapy. We discuss key considerations when conducting an NMA and interpreting NMA outputs, and provide guidance on the most appropriate methodology for the data available and potential implications of the incorrect application of methods. We conclude with a simple illustrative example of NMA methodologies using simulated data, demonstrating that when applied correctly, the outcome of the analysis should be similar regardless of the methodology chosen.
Environmental constraints for improving motor flexibility during obstacle crossing in older adults
Authors: Suda Yuki , Higuchi Takahiro
Published: December 2024

Background

An age-related decline in motor flexibility, which is the ability to synergistically control the degrees of freedom of the body to ensure stable performance of a task, is a factor that contributes to falls. We investigated whether providing environmental constraints to increase the movement repertoire (i.e., the motor solution that works to achieve one’s goal), in combination with aiming at precise control of the performance, would be effective for improving motor flexibility, and whether the effect on the leading limb would extend to the trailing limb.

Methods

Fifteen older adults (75.1 ± 6.2 years and 14 younger adults (34.6 ± 5.0 years) performed under three walking conditions: walking normally and crossing the obstacle (normal), walking and crossing the obstacle with constraints of foot placement after stepping over it (constrained), and walking and crossing the obstacle with constraints as in the constrained condition, in addition to aiming for maintaining a constant clearance height at the moment of obstacle crossing (precision). An uncontrolled manifold analysis was used to quantify motor flexibility as the synergy index. The foot height at the moment of obstacle crossing was used as the performance variable and seven segmental angles were used as the elemental variables. A higher synergy index indicates greater motor flexibility.

Results

For the leading limb, the synergy index was significantly higher under the precision condition than those under the other conditions. This suggests that not only providing environmental constraints but also keeping constant the performance variable is critical to improving motor flexibility. Moreover, the effects of an increase in the synergy index in the leading limb extended to the trailing limb.

Conclusions

Providing environmental constraints to increase the movement repertoire while also aiming for precision in the performance variable was an effective method of improving motor flexibility during obstacle crossing for older adults.
Targeting SARS-CoV-2 main protease: a comprehensive approach using advanced virtual screening, molecular dynamics, and in vitro validation
Authors: Gevorgyan Smbat , Khachatryan Hamlet , Shavina Anastasiya , Gharaghani Sajjad , Zakaryan Hovakim
Published: December 2024

The COVID-19 pandemic, driven by the SARS-CoV-2 virus, necessitates the development of effective therapeutics. The main protease of the virus, Mpro, is a key target due to its crucial role in viral replication. Our study presents a novel approach combining ligand-based pharmacophore modeling with structure-based advanced virtual screening to identify potential inhibitors of Mpro. We screened around 200 million compounds using this integrated methodology, resulting in a shortlist of promising compounds. These were further scrutinized through molecular dynamics simulations, revealing their interaction dynamics with Mpro. Subsequent in vitro assays using the Mpro enzyme identified two compounds exhibiting significant micromolar inhibitory activity. These findings provide valuable scaffolds for the development of advanced therapeutics targeting Mpro. The comprehensive nature of our approach, spanning computational predictions to experimental validations, offers a robust pathway for rapid and efficient identification of potential drug candidates against COVID-19.
Minimal encephalopathy in hereditary hemorrhagic telangiectasia patients with portosystemic vascular malformations
Authors: Villanueva B. , Cañabate A. , Torres-Iglesias R. , Cerdà P. , Gamundí E. , Ordi Q. , Alba E. , Sanz-Astier L. A. , Iriarte A. , Ribas J. , Castellote J. , Pintó X. , Riera-Mestre A.
Published: December 2024

Background

Hereditary hemorrhagic telangiectasia (HHT) is characterized by telangiectasia and larger vascular malformations. Liver malformations are the most frequent visceral involvement including the presence of portosystemic malformations (PSM) that can cause hepatic encephalopathy. Minimal hepatic encephalopathy (mHE) is characterized by alterations of brain function in neuropsychological or neurophysiological tests and decreases quality of life. The evidence of mHE in HHT patients is scarce. The aim of this study is to assess the prevalence and health impact of mHE in patients with and without PSM.

Methods

We performed a cross-sectional observational study in a cohort of patients from an HHT referral unit. Adult patients with definite HHT and PSM and age and sex matched HHT controls without PSM (1:1) were included. Baseline clinical, imaging and laboratory tests and different neuropsychological tests for the screening of mHE were compared between both groups.

Results

Eighteen patients with PSM and 18 controls out of 430 HHT patients were included. Patients with PSM showed higher prevalence of attention disturbances (50% vs. 11.1%, p = 0.027), falls during last 12 months (22.2% vs. 5.6%, p = 0.338), sleep disorders (50% vs. 16.7%, p = 0.075) and a worst performance in s-ANT1 test (14 vs. 19.5 points score, p = 0.739) than HHT controls.

Conclusions

HHT patients with PSM showed higher attention difficulties than HHT controls, though both PSM and HHT controls showed findings of mHE. Specific neuropsychological tests for early detection of mHE should be considered in HHT patients.
Clinical efficacy of efgartigimod combined with intravenous methylprednisolone in the acute phase of neuromyelitis optica spectrum disorders
Authors: Yang Wenjing , Chen Pei , Guo Jiaxuan , Feng Huiyu , Huang Xin
Published: December 2024

Background

Neuromyelitis Optica Spectrum Disorders (NMOSD) comprise a group of autoimmune-mediated, inflammatory, demyelinating central nervous system diseases caused by aquaporin-4 (AQP4) IgG autoantibodies. Efgartigimod is a human IgG Fc fragment that reduces antibody titers by targeting the neonatal Fc receptor (FcRn). This study documents the efficacy of efgartigimod combined with intravenous methylprednisolone (IVMP) in the acute phase of NMOSD.

Methods

In this retrospective study, the medical records of NMOSD patients with acute attack who received efgartigimod plus IVMP or IVMP were reviewed. Treatment efficacy was assessed by the Expanded Disability Scale Score (EDSS) before and one month after treatment. Any side effects that occurred during the treatment period were recorded.

Results

This study was performed on 11 patients (efgartigimod plus IVMP group [n = 4] and IVMP group [n = 7]). Efgartigimod plus IVMP was effective and had a satisfactory safety profile. EDSS was reduced by 0.5 ± 0.32 compared with the IVMP group (0.27 ± 0.02). Immunoglobulin was decreased in three patients, and the immunoglobulin G (IgG) levels gradually increased approximately 8 weeks after the last administration. Hyperlipidemia and elevated white blood cell count were common side effects. No infections or deaths occurred.

Conclusions

Efgartigimod plus IVMP treatment is safe and well-tolerated in patients with acute-phase NMOSD.
International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA
Authors: Downs Jenny , Pichard Dominique C. , Kaufmann Walter E. , Horrigan Joseph P. , Raspa Melissa , Townend Gillian , Marsh Eric D. , Leonard Helen , Motil Kathleen , Dietz Andrew C. , Garg Nupur , Ananth Amitha , Byiers Breanne , Peters Sarika , Beatty Christopher , Symons Frank , Jacobs Aleksandra , Youakim James , Suter Bernhard , Santosh Paramola , Neul Jeffrey L. , Benke Tim A.
Published: December 2024

Introduction

The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods

Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted. The clinical outcome assessments measured clinical severity, functional abilities, comorbidities and quality of life, and electrophysiological biomarkers. An international and multidisciplinary panel of 29 experts with clinical, research, psychometric, biostatistical, industry and lived experience was identified through International Rett Syndrome Foundation networks, to discuss validation of the clinical outcome assessments, gaps and next steps, during a workshop and in a follow-up questionnaire. The identified gaps and limitations were coded using inductive content analysis.

Results

Variable validation profiles across 26 clinical outcome assessments of clinical severity, functional abilities, and comorbidities were discussed. Reliability, validity, and responsiveness profiles were mostly incomplete; there were limited content validation data, particularly parent-informed relevance, comprehensiveness and comprehensibility of items; and no data on meaningful change or cross-cultural validity. The panel identified needs for standardised administration protocols and systematic validation programmes.

Conclusion

A pipeline of collaborative clinical outcome assessment development and validation research in Rett syndrome can now be designed, aiming to have fit-for-purpose measures that can evaluate meaningful change, to serve future clinical trials and clinical practice.
SIRT6 deficiency impairs the deacetylation and ubiquitination of UHRF1 to strengthen glycolysis and lactate secretion in bladder cancer
Authors: Wang Xiaojing , Zhang Peipei , Yan Jiaqi , Huang Jingyi , Shen Yan , He Hongchao , Dou Hongjing
Published: December 2024

Background

Aberrant interplay between epigenetic reprogramming and metabolic rewiring events contributes to bladder cancer progression and metastasis. How the deacetylase Sirtuin-6 (SIRT6) regulates glycolysis and lactate secretion in bladder cancer remains poorly defined. We thus aimed to study the biological functions of SIRT6 in bladder cancer.

Methods

Bioinformatic analysis was used to study the prognostic significance of SIRT6/UHRF1 in BLCA. Both in vitro and in vivo assays were used to determine the roles of SIRT6/UHRF1 in BLCA. Deacetylation and ubiquitin assays were performed to uncover the regulations of SIRT6-UHRF1. Measurement of extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) was used to assess glycolytic abilities.

Results

Here, we show that protein deacetylase SIRT6 was down-regulated in BLCA, and predicts poor overall survival. SIRT6 deficiency notably enhances BLCA cell proliferation, self-renewal, and migration capacities in vitro and in vivo. Mechanistically, SIRT6 interacts with, deacetylates, and promotes UHRF1 degradation mediated by β-TrCP1. Thus, SIRT6 deficiency leads to stabilized UHRF1 and depends on UHRF1 to accelerate BLCA malignant progression. Furthermore, UHRF1 significantly increased aerobic glycolysis via activating MCT4/HK2 expressions. Down-regulated SIRT6 thus depended on UHRF1 to promote glycolysis and lactate secretion in BLCA. Targeting UHRF1 or MCT4 notably impaired the extracellular lactate accumulations in BLCA. Significantly, a specific small-molecule inhibitor (NSC232003) targeting UHRF1 substantially inhibited SIRT6-deficient BLCA progression.

Conclusion

Together, our study uncovered an epigenetic mechanism of the SIRT6/UHRF1 axis in driving BLCA glycolysis and lactate secretion, creating a novel vulnerability for BLCA treatment.
Business models and strategies for the internalization of externalities in agri-food value chains
Authors: Mehrabi Sepide , Giagnocavo Cynthia
Published: December 2024

Current food systems have significant negative environmental, social, and economic impacts. Externalized costs and benefits create false market incentives favoring less healthy and unsustainable options. Transitioning to sustainable agri-food systems requires that businesses internalize these externalities. Internalization of externalities (IOE) is often addressed through policy measures and regulatory initiatives. However, IOE can also be carried out through business models (BMs) and strategies which involve creating positive externalities, mitigating/preventing negative ones, as well as ensuring fair distribution of risks, costs, and benefits. Accordingly, sustainable and innovative BMs and strategies offer pathways to achieving IOE. This paper identifies existing sustainable and innovative BMs and strategies and explains how they can achieve IOE. Using an integrative literature review methodology, we reconcile both economics and business literature approaches. We subsequently carry out two levels of analysis including abductive coding and interrelationship evaluation. The paper explores the characteristics of BMs and strategies that address IOE, using the well-known concept of value and introduces a conceptual framework for categorizing business models and strategies for the internalization of externalities (BM4IOE). The article initiates a discourse on the role of BMs in the IOE within agri-food value chains and provides insights into how businesses can develop and implement models that effectively internalize externalities, thereby enhancing sustainability and driving innovation in the transition of agri-food systems.
Towards a real-time simulation of elastoplastic deformation using multi-task neural networks
Authors: Schmeitz R. , Remmers J. J. C. , Mula O. , van der Sluis O.
Published: December 2024

This study introduces a surrogate modeling framework merging proper orthogonal decomposition, long short-term memory networks, and multi-task learning, to accurately predict elastoplastic deformations in real-time. Superior to single-task neural networks, this approach achieves a mean absolute error below 0.40% across various state variables, with the multi-task model showing enhanced generalization by mitigating overfitting through shared layers. Moreover, in our use cases, a pre-trained multi-task model can effectively train additional variables with as few as 20 samples, demonstrating its deep understanding of complex scenarios. This is notably efficient compared to single-task models, which typically require around 100 samples. Significantly faster than traditional finite element analysis, our model accelerates computations by approximately a million times, making it a substantial advancement for real-time predictive modeling in engineering applications. While it necessitates further testing on more intricate models, this framework shows substantial promise in elevating both efficiency and accuracy in engineering applications, particularly for real-time scenarios.
Preliminary design and evaluation of a ducted-fan type pipeline robot
Authors: Miyake Shota , Yoshida Kento , Sugano Shigeki , Kamezaki Mitsuhiro
Published: December 2024

Pipelines are crucial infrastructure supporting human life, yet their maintenance costs are substantial, necessitating the development of time-efficient robotic systems. Therefore, this study proposes an in-pipe mobile robot powered by wind generated using a ducted fan rotor, enabling faster movement within pipelines than conventional methods, e.g., inchworm. Deriving the propulsion force from wind requires analyzing airflow within the pipeline, which is challenging due to the confined space and complexity, especially when considering the presence of robots. Hence, we developed a prototype of a ducted-fan type pipeline robot (DPR) and experimentally investigated duct shapes that enhance the propulsion of the DPR within pipelines. As a result, we identified duct shapes that amplify the propulsion force generated by the ducted fan within pipelines. Additionally, we also experimentally elucidated the relationship between the distance from the pipe’s end and the propulsion force of the robot. Furthermore, we demonstrated the capabilities of the DPR by traversing a pipeline with a diameter of 110 mm, achieving speeds of 1500 mm/s in horizontal pipes and 700 mm/s while ascending vertical pipes. The results show that DRP has the potential for in-pipe inspection.
InSAR-based investigation of ground subsidence due to excavation: a case study of Incheon City, South Korea
Authors: Park Kyungwon , Kim Yong Je , Chen Jiannan , Nam Boo Hyun
Published: December 2024

Ground subsidence is one of geohazards, particularly in urban environment due to its negative impact to nearby buildings and civil infrastructures. This study investigates the amount and spatial distribution of ground subsidence in Incheon City, South Korea, where ground excavation was made. Interferometric Synthetic Aperture Radar (InSAR) was used to monitor surface deformation around the excavation site. The study analyzed subsidence during an excavation project using Sentinel-1b satellite data, and the InSAR results were compared with traditional leveling methods and field measurements. Notable subsidence during the early construction phase was identified, which demonstrates the effectiveness of InSAR in urban environment. The research contributes to understanding of the excavation-inducing ground subsidence due to the reclamation layer.
Impact of integrating type-1 distributed generation on distribution network using modified genetic algorithm and voltage stability index: a technical and cost–benefit analysis approach
Authors: Olabode Olakunle Elijah , Akinyele Daniel Oluwaseun , Ajewole Titus Oluwasuji , Omogoye Samuel Okeolu , Raji Akeem Abimbola
Published: December 2024

The position of the distribution network and its peculiar topology calls for viable means of addressing the issue of severe power loss and voltage instability confronting its ability to truly wheel out the received energy from the transmission arm of the network to the end users. Based on this premise, the current work employed a Lévy flight genetic algorithm (LF-GA) for the placement of type-1 photovoltaic-based distributed generation (PV-DG) into a radial network. The IEEE 33 and Government Residential Area (GRA) 11 kV and 34-bus feeder in Nigeria were used to investigate the effectiveness of the proposed approach. The backward-forward sweep formed the backbone of the load flow, while the voltage stability index was used to select the suitable buses where type-1 DG was integrated for optimal performance. The criteria considered for performance evaluation were the cost of energy loss, payback time, active power loss, and network voltage profile improvement without violating the essential network constraints. The paper proposed a relevant policy framework on DG integration, which filled knowledge gap in the previous studies. A multi-objective factor-based LF-GA subjected to appropriate constraints was used to optimize both the sizing and the locations of type-1 DG with the arrangements implemented in a MATLAB environment. The results obtained when compared with the existing contributions in the literature showed a credible improvement in line-loss reduction, voltage profile, and the system voltage stability index, including reduced cost of energy loss with minimal payback time on the investment of compensating devices.
Diachronic derivation: Mari etymologies
Authors: Metsäranta Niklas
Published: December 2024

This article discusses the etymology of four Mari words: Proto-Mari *čükte- ‘light, set fire to’, *poδəla- ‘spoon, slurp’, *pükte- ‘brood (eggs)’, and *püəž- ‘sweat’. After examining the words structurally, an argument is put forth that the words represent historical derivatives. This analysis is the key to unlocking their phonological development, which then allows us to find suitable cognates elsewhere in Uralic. It is concluded that Proto-Mari *čükte- ‘light, set fire to’ has a cognate in Saami, e.g. SaaN cahkat ‘smolder’, while *poδəla- ‘spoon, slurp’ belongs to the well-established cognate set Proto-Uralic *pala- ‘eat up’. Proto-Mari *pükte- ‘brood (eggs)’ is proposed as a cognate of Saami *pive̮ - ‘stay warm, withstand cold’. It is tentatively suggested in the article that *püəž- ‘sweat’ belongs etymologically together with Proto-Mari *pükte- ‘brood’ and Proto-Saami *pive̮ - ‘stay warm, withstand cold’. Whether these represent a separate Proto-Uralic etymon *pejwə- ‘stay warm’ or whether they belong together with PU *päjwä ‘sun, heat, warm(th)’ is also explored. These findings, despite some of the uncertainties involved in their specific interpretation, highlight the importance of taking historical derivation into account in etymology.

Kokkuvõte. Niklas Metsäranta: Ajalooline sõnatuletus: mari etümoloogiaid. Artiklis käsitletakse nelja mari sõna etümoloogiat: algmari *čükte- ‘süütama’, *poδəla- ‘lusikaga sööma, lürpima’, *pükte- ‘hauduma (mune)’ ja *püəž- ‘higi’. Nende sõnade struktuuri uurimus näitab, et nad esindavad ajaloolisi tuletisi. Struktuuriline analüüs on võti ka nende fonoloogilise arengu seletamiseks, mis seejärel võimaldab leida sobivaid vasteid mujalt uurali keeltest. Leitakse, et algmari sõnal *čükte- ‘süütama’ on vaste saami keeltes, näiteks põhjasaami cahkat ‘küdema’, ja sõna *poδəla- ‘lusikaga sööma, lürpima’ kuulub kokku sugulaskeelte sõnadega, mis peegeldavad uurali algkeele *pala- ‘sööma, ahmima’. Algmari *pükte- ‘hauduma (mune)’ vasteks pakutakse artiklis saami sõna *pive̮ - ‘soojust hoidma, külma taluma’. Artiklis tehakse esialgne ettepanek, et mari *püəž- ‘higi’ on etümoloogiliselt seotud algmari sõnadega *pükte- ‘hauduma (mune)’ ja algsaami *pive̮ - ‘soojust hoidma, külma taluma’. Samuti kaalutakse, kas need sõnad esindavad eraldiolevat uraali algkeele sõna *pejwə- ‘soojust hoidma’ või kas kõik kolm kuuluvad kokku uraali algkeele *päjwä ‘päike, kuumus, soe, soojus’ sõnaga. Artikli tulemused, vaatamata mõningale ebakindlusele nende täpse tõlgenduse osas, rõhutavad sõnatuletuse ajalooga arvestamise tähtsust etümoloogias.
Genetic map of the Wielka Żuława soil cover: blanks to be filled using existing cartographic materials and remote-sensing data
Authors: Świtoniak Marcin , Sykuła Marcin , Markiewicz Maciej , Dziczek Julia , Radomski Paweł
Published: December 2024

Poland is considered to have a very well mapped soil cover and detailed soil cartographic materials. Despite this, some areas have “blank spots” on soil-agricultural or soil-habitat maps. These include the Wielka Żuława island on Jeziorak Lake (on the Iława Plain). This island is almost deserted and inaccessible, making detailed field research there very difficult. The aim of the work was to check the possibility of using existing cartographic materials and remote-sensing data to develop a genetic map of the soils of this area. In order to interpret the existing materials, preliminary field works were carried out: six soil pits and 22 manual drillings to an average depth of 2 m. These studies showed significant diversity of soil cover. The largest share within the central, upland part of the island have autogenous rusty soils (Brunic Arenosols according to the World Reference Base [WRB]) and clay-illuvial soils (Luvisols – WRB). The lower locations (mainly along the coast of the island) were dominated by organic soils (Histosols – WRB). The digital elevation model (DEM) enables precise determination of the boundary between THE mentioned autogenous and hydrogenic soils. In the group of organic pedons, a large area was degraded, which was expressed by the occurrence of murshic soils (Murshic Histosols – WRB). The DEM obtained from LiDAR data shows networks of (almost invisible in aerial photos) drainage ditches and channels, which turned out to be very useful in determining the extent of the mentioned degradation. The greatest difficulties concerned the extent of soil developed as a result of human influence – colluvial (Solimovic Arenosols) and anthropogenic soils. In the first case, a relief model combined with archival orthophotomosaics allowed for an approximate estimation of the places where these soils occur. Both elements (DEM and archival aerial photos) were also used to estimate the extent of occurrence of technogenic soils (Technosols – WRB).
Application of a statistical model to identify villages at risk of depopulation in Poland
Authors: Wesołowska Monika , Matuła Przemysław
Published: December 2024

Rural settlements are dynamic structures, and each historical period is characterised by certain directions of changes in the countryside, visible mainly in demographic processes. Based on an analysis of statistical data for the years 1950–2021, the authors determine those directions of future demographic changes in Polish villages that are causing changes in the rural settlement structure. The authors, using a statistical model, indicate the regions of the country that are at risk of village desertification and identify villages facing permanent population regression. This article presents the changes that took place in the rural settlement structure of Polish villages between 1950 and 2021 and forecasts future changes. The research aims to create a probabilistic projection of the population in Polish villages. Factors influencing the rural population are also discussed. The research is addressed to state and local administrations with the message that they should implement timely and responsible measures to revitalise the countryside and stop the demographic shrinkage leading to the emptying of villages in some regions of Poland.