bluuebunny/crossref_metadata_2025_split huggingface dataset:
Observational pilot study on the influence of an app-based self-management program on the quality of life of women with endometriosis
Authors: Rohloff Nadine , Rothenhöfer Markus , Götz Teresa , Schäfer Sebastian Daniel 
Published: June 2024

Abstract
Purpose
Endometriosis can significantly impair the quality of life of those affected. Multimodal self-help measures are recommended but often difficult to access. Smartphone apps have been shown to improve the quality of life for other conditions with chronic pain. The aim of this study was to examine whether there is evidence of beneficial effects of the smartphone app “Endo-App®” and whether a multicenter randomized controlled trial should be planned to substantiate these effects.

Methods
In a sample of N = 106 women affected by endometriosis the present study determined the influence of the use of Endo-App® on their quality of life. Among others, the validated questionnaire Endometriosis Health Profile from Oxford University was used for this purpose.

Results
The use of Endo-App® lead to a highly significant improvement in quality of life already after 2 weeks. A statistically significant change was found for nine out of ten measured variables of quality of life. A series of further analyses validated that the measured positive effects were not due to other confounding factors.

Conclusion
In summary, the results indicate that the quality of life of women with endometriosis improved by the digital self-management tool Endo-App®. More studies are needed to further explore the influence of the app on quality of life and as confirmatory evidence of beneficial effects. For this purpose, a randomized controlled trial should be conducted over a longer period of time.

Trial registration
This trial is registered at clinicaltrials.gov under the registration number NCT05528601 on August 18, 2022. It was retrospectively registered.
New valproate regulations, informed choice and seizure risk
Authors: Angus-Leppan Heather , Arkell Rachel , Watkins Lance , Heaney Dominic , Cooper Paul , Shankar Rohit 
Published: June 2024

AbstractValproate is the most effective medication for generalised epilepsies, and several specific epilepsy syndromes. For some people, it will be the only medication to establish seizure remission, and withdrawing it carries risks of seizure recurrence and Sudden Unexpected Death in Epilepsy (SUDEP). It is also of proven efficacy for bipolar disorder and migraine prevention. Guidelines based on observational and epidemiological studies stress that maternal valproate related teratogenicity and neurodevelopmental effects are significantly higher than for other antiseizure medications (ASMs). It should, therefore, only be used if other medications are ineffective and after balancing the teratogenicity risk. Regulatory restrictions have changed prescribing practices and reduced valproate use. The number of other medications that must be trialled in the different conditions for which valproate has effectiveness and the consequences of the lack of efficacy of those drugs leading to significant harm including death remains unexplored. Risk minimisation measures (RMMs) for valproate, chiefly Pregnancy Prevention practices (PPP), consider foetal risk and not risk to people living with epilepsy. In the United Kingdom (UK), limitations relating to valproate use in all people < 55 years commenced in January 2024. While the evidence in child-bearing women is not disputed, the data in males are based on animal models, case reports, and one commissioned, unpublished, non-peer reviewed report unavailable to the UK public, stakeholder charities or professionals. Evidence suggests that 30–40% of people switching from valproate have breakthrough seizures. Thus, an estimated 21,000–28000 people in the UK will imminently be exposed to the potential hazards of breakthrough seizures, including death. There is little government investment in monitoring the effects of these changes to valproate prescribing on patient health and quality of life. This review summarises the history of valproate regulation, evidence underpinning it and argues how the latest regulations in the UK do not align with the country’s medical regulatory bodies ethical principles nor with the Montgomery principles of informed patient choice and autonomy. It dissects how such regulations infringe Common Law principles, nor give due regard for patient outcomes beyond reproduction. The paper looks to provide recommendations to redress these concerns while appreciating the core need for such governance to emerge in the first place.
Changes in forced vital capacity over ≤ 13 years among patients with late-onset Pompe disease treated with alglucosidase alfa: new modeling of real-world data from the Pompe Registry
Authors: Berger Kenneth I. , Chien Yin-Hsiu , Dubrovsky Alberto , Kishnani Priya S. , Llerena Juan C. , Neilan Edward , Roberts Mark , Sheng Bun , Batista Julie L. , Periquet Magali , Wilson Kathryn M. , van der Ploeg Ans T. 
Published: June 2024

Abstract
Background
Chronic respiratory insufficiency from progressive muscle weakness causes morbidity and mortality in late-onset Pompe disease (LOPD). Previous Pompe Registry (NCT00231400) analyses for ≤ 5 years’ alglucosidase alfa treatment showed a single linear time trend of stable forced vital capacity (FVC) % predicted.

Methods
To assess longer term Pompe Registry data, piecewise linear mixed model regression analyses estimated FVC% predicted trajectories in invasive-ventilator-free patients with LOPD aged ≥ 5 years. We estimated annual FVC change 0–6 months, > 6 months–5 years, and > 5–13 years from treatment initiation, adjusting for baseline age, sex, and non-invasive ventilation.

Findings
Among 485 patients (4612 FVC measurements; 8.3 years median follow-up), median ages at symptom onset, diagnosis, and alglucosidase alfa initiation were 34.3, 41.1, and 44.9 years, respectively. FVC% increased during the first 6 months’ treatment (slope 1.83%/year; 95% confidence interval: 0.66, 3.01; P = 0.0023), then modestly declined −0.54%/year (−0.79, −0.30; P < 0.0001) during > 6 months–5 years, and −1.00%/year (−1.36, −0.63; P < 0.0001) during > 5–13 years. The latter two periods’ slopes were not significantly different from each other (Pdifference = 0.0654) and were less steep than published natural history slopes (−1% to −4.6%/year). Estimated individual slopes were ≥ 0%/year in 96.1%, 30.3%, and 13.2% of patients during the 0–6 month, > 6 month–5 year, and > 5–13 year periods, respectively.

Conclusion
These real-world data indicate an alglucosidase alfa benefit on FVC trajectory that persists at least 13 years compared with published natural history data. Nevertheless, unmet need remains since most individuals demonstrate lung function decline 5 years after initiating treatment. Whether altered FVC trajectory impacts respiratory failure incidence remains undetermined.

Trial registration
This study was registered (NCT00231400) on ClinicalTrials.gov on September 30, 2005, retrospectively registered.
Greater cortical thinning and microstructural integrity loss in myotonic dystrophy type 1 compared to myotonic dystrophy type 2
Authors: Krieger Britta , Schneider-Gold Christiane , Genç Erhan , Güntürkün Onur , Prehn Christian , Bellenberg Barbara , Lukas Carsten 
Published: June 2024

Abstract
Background
Myotonic dystrophy is a multisystem disorder characterized by widespread organic involvement including central nervous system symptoms. Although myotonic dystrophy disease types 1 (DM1) and 2 (DM2) cover a similar spectrum of symptoms, more pronounced clinical and brain alterations have been described in DM1. Here, we investigated brain volumetric and white matter alterations in both disease types and compared to healthy controls (HC).

Methods
MRI scans were obtained from 29 DM1, 27 DM2, and 56 HC. We assessed macro- and microstructural brain changes by surface-based analysis of cortical thickness of anatomical images and tract-based spatial statistics of fractional anisotropy (FA) obtained by diffusion-weighted imaging, respectively. Global MRI measures were related to clinical and neuropsychological scores to evaluate their clinical relevance.

Results
Cortical thickness was reduced in both patient groups compared to HC, showing similar patterns of regional distribution in DM1 and DM2 (occipital, temporal, frontal) but more pronounced cortical thinning for DM1. Similarly, FA values showed a widespread decrease in DM1 and DM2 compared to HC. Interestingly, FA was significantly lower in DM1 compared to DM2 within most parts of the brain.

Conclusion
Comparisons between DM1 and DM2 indicate a more pronounced cortical thinning of grey matter and a widespread reduction in microstructural integrity of white matter in DM1. Future studies are required to unravel the underlying and separating mechanisms for the disease courses of the two types and their neuropsychological symptoms.
Absence of orthopaedia homeobox protein (OTP) expression is associated with disease spread and adverse outcome in pulmonary carcinoid tumour patients
Authors: Niinimäki Jenni , Mononen Sanna , Kaprio Tuomas , Arola Johanna , Vesterinen Tiina 
Published: June 2024

AbstractPulmonary carcinoid (PC) tumours typically have a good prognosis, although metastases occur, and the disease may progress after a long period of time. Expression of orthopaedia homeobox protein (OTP) has been recognized as a possible independent prognostic marker in PCs. Immunohistochemical (IHC) OTP expression has been associated with better prognosis, but the staining has yet to be implemented in routine clinical diagnostics. In response to this, two new monoclonal OTP antibodies were recently developed.This retrospective study included 164 PC patients operated on at Helsinki University Hospital between 1990 and 2020. Tissue microarray slides, prepared from formalin-fixed and paraffin-embedded primary tumour samples, were stained with OTP IHC using one polyclonal and two novel monoclonal antibodies.Absence of OTP expression was associated with a shorter disease-specific survival (DSS) and disease progression (p < 0.001). Patients without OTP expression had a 5-year DSS of 73–79%, whereas 5-year DSS was 91–94% with OTP expression, depending on the primary antibody. In a univariable Cox regression model, absence of OTP expression was associated with adverse outcome along with atypical histological subtype, metastatic disease, Ki-67 proliferation index > 1%, and larger tumour size. In a multivariable Cox regression model, only absence of OTP expression and lymph node involvement at the time of diagnosis were associated with risk of worse prognosis. All three antibodies showed good concordance with each other.Our findings support the role of OTP as an independent prognostic marker in PCs and applicability of IHC staining in routine clinical use with novel monoclonal antibodies.
Parameterized Complexity of Streaming Diameter and Connectivity Problems
Authors: Oostveen Jelle J. , van Leeuwen Erik Jan 
Published: June 2024

AbstractWe initiate the investigation of the parameterized complexity of Diameter and Connectivity in the streaming paradigm. On the positive end, we show that knowing a vertex cover of size k allows for algorithms in the Adjacency List (AL) streaming model whose number of passes is constant and memory is $$\mathcal {O}(\log n)$$

O
(
log
n
)

for any fixed k. Underlying these algorithms is a method to execute a breadth-first search in $$\mathcal {O}(k)$$

O
(
k
)

passes and $$\mathcal {O}(k \log n)$$

O
(
k
log
n
)

bits of memory. On the negative end, we show that many other parameters lead to lower bounds in the AL model, where $$\Omega (n/p)$$

Ω
(
n
/
p
)

bits of memory is needed for any p-pass algorithm even for constant parameter values. In particular, this holds for graphs with a known modulator (deletion set) of constant size to a graph that has no induced subgraph isomorphic to a fixed graph H, for most H. For some cases, we can also show one-pass, $$\Omega (n \log n)$$

Ω
(
n
log
n
)

bits of memory lower bounds. We also prove a much stronger $$\Omega (n^2/p)$$

Ω
(

n
2

/
p
)

lower bound for Diameter on bipartite graphs. Finally, using the insights we developed into streaming parameterized graph exploration algorithms, we show a new streaming kernelization algorithm for computing a vertex cover of size k. This yields a kernel of 2k vertices (with $$\mathcal {O}(k^2)$$

O
(

k
2

)

edges) produced as a stream in $$\text {poly}(k)$$

poly
(
k
)

passes and only $$\mathcal {O}(k \log n)$$

O
(
k
log
n
)

bits of memory.
Association between triglyceride-glucose index and the risk of heart failure hospitalization in older diabetic patients received right ventricular pacing: a retrospective cohort study
Authors: Fu Bingqi , Yu Yu , Cheng Sijing , Huang Hao , Long Tianxin , Yang Juweig , Gu Min , Cai Chi , Chen Xuhua , Niu Hongxia , Hua Wei 
Published: June 2024

Abstract
Background
The prognostic value of triglyceride-glucose (TyG) index is not yet known for older diabetic patients received right ventricular pacing (RVP). We aimed to investigate the association between TyG index and the risk of heart failure hospitalization (HFH) in older diabetic patients received RVP.

Methods
This study was conducted between January 2017 and January 2018 at Fuwai Hospital, Beijing, China, and included older (age ≥ 65 years) diabetic patients that received RVP for the first time. TyG index were obtained before implantation. The primary endpoint was HFH.

Results
A total of 231 patients were divided into three groups according to the tertiles of TyG index: < 8.5 (T1, N = 77), 8.5–9.1 (T2, N = 77), and > 9.1 (T3, N = 77). T3 group had higher rate of HFH (Log-rank = 11.7, P = 0.003). Multivariate analyses showed that, TyG index served as an independent predictor for HFH, both as numerical variable (HR = 1.94, 95% CI 1.21–3.11, P = 0.006), and as categorical variable (HR = 2.31, 95% CI 1.09–4.89, P = 0.03). RCS demonstrated that the risk of HFH was relatively low until TyG index exceeded 8.8, beyond which the risk began to increase rapidly (P-non-linear = 0.006).

Conclusion
Preimplantation TyG index emerges as a robust, independent predictor for HFH in older diabetic patients received RVP, and TyG index > 8.8 might be the optimal cut-off value.
Constant-Head Step-Injection Tests Using a Conventional Straddle-Sliding-Packer System for Investigating the Shear Capabilities of Minor Faults
Authors: Ishii Eiichi 
Published: June 2024

AbstractLow-permeability rock is suitable as the host rock of an underground repository for radioactive waste disposal; however, minor faults might develop there. Investigating the shear capability (= shear compliance) of those faults is crucial because they could be elastically sheared by the thermal effect of the waste to damage the waste’s engineered barriers. This study performed constant-head step-injection tests along with a recently developed packer-pressure-based extensometer method for assessing the applicability of this method to investigate the shear capability of minor faults. Herein, two neighboring minor faults (A and B) in siliceous mudstone were evaluated. The results showed that fault A, with centimeter-thick fault breccia, exhibited high shear capability, whereas fault B, with millimeters or less-thick fault breccia, displayed low shear capability despite containing an incohesive fault rock. An elastic shear displacement occurred for fault A during injection and reached 15–66 mm when the test-section pressure increased from 4.1 to 4.3 MPa. Here, the shear capability was 101 mm/MPa or more. Conversely, fault B had cohesion, and no shear displacement was detected even when the test-section pressure increased from 4.0 to 6.0 MPa. In this case, the shear capability was 10−1 mm/MPa or less. The estimated shear capabilities were consistent with the results from previous shear experiments, and therefore, the applied method helps investigate the shear capabilities of minor faults.
Proving the automatic benchtop electrochemical station for the development of dopamine and paracetamol sensors
Authors: Haššo Marek , Kudr Jiří , Zítka Jan , Šílený Jan , Švec Pavel , Švorc Ľubomír , Zítka Ondřej 
Published: June 2024

AbstractThe introduced work represents an implementation of the automatic benchtop electrochemical station (BES) as an effective tool for the possibilities of high-throughput preparation of modified sensor/biosensors, speeding up the development of the analytical method, and automation of the analytical procedure for the determination of paracetamol (PAR) and dopamine (DOP) as target analytes. Within the preparation of gold nanoparticles modified screen-printed carbon electrode (AuNPs-SPCE) by electrodeposition, the deposition potential EDEP, the deposition time tDEP, and the concentration of HAuCl4 were optimized and their influence was monitored on 1 mM [Ru(NH3)6]3+/2+ redox probe and 50 μM DOP. The morphology of the AuNPs-SPCE prepared at various modification conditions was observed by SEM. The analytical performance of the AuNPs-SPCE prepared at different modification conditions was evaluated by a construction of the calibration curves of DOP and PAR. SPCE and AuNPs-SPCE at modification condition providing the best sensitivity to PAR and DOP, were successfully used to determine PAR and DOP in tap water by “spike-recovery” approach. The BES yields better reproducibility of the preparation of AuNPs-SPCE (RSD = 3.0%) in comparison with the case when AuNPs-SPCE was prepared manually by highly skilled laboratory operator (RSD = 7.0%).
Graphical abstract
Clinical utility of the at-risk for psychosis state beyond transition: A multidimensional network analysis
Authors: Boldrini Tommaso , Lo Buglio Gabriele , Cerasti Erika , Pontillo Maria , Muzi Laura , Salcuni Silvia , Polari Andrea , Vicari Stefano , Lingiardi Vittorio , Solmi Marco 
Published: June 2024

Abstract
To be relevant to healthcare systems, the clinical high risk for psychosis (CHR-P) concept should denote a specific (i.e., unique) clinical population and provide useful information to guide the choice of intervention. The current study applied network analyses to examine the clinical specificities of CHR-P youths compared to general help-seekers and non–CHR-P youth. 146 CHR-P (mean age = 14.32 years) and 103 non–CHR-P (mean age = 12.58 years) help-seeking youth were recruited from a neuropsychiatric unit and assessed using the Structured Interview for Psychosis-Risk Syndromes, Children’s Depression Inventory, Multidimensional Anxiety Scale for Children, Global Functioning: Social, Global Functioning: Role, and Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale. The first network structure comprised the entire help-seeking sample (i.e., help-seekers network), the second only CHR-P patients (i.e., CHR-P network), and the third only non–CHR-P patients (i.e., non–CHR-P network). In the help-seekers network, each variable presented at least one edge. In the CHR-P network, two isolated “archipelagos of symptoms” were identified: (a) a subgraph including functioning, anxiety, depressive, negative, disorganization, and general symptoms; and (b) a subgraph including positive symptoms and the intelligence quotient. In the non–CHR-P network, positive symptoms were negatively connected to functioning, disorganization, and negative symptoms. Positive symptoms were less connected in the CHR-P network, indicating a need for specific interventions alongside those treating comorbid disorders. The findings suggest specific clinical characteristics of CHR-P youth to guide the development of tailored interventions, thereby supporting the clinical utility of the CHR-P concept.
Diffusion of curcumin in PLGA-based carriers for drug delivery: a molecular dynamics study
Authors: De Giorgi Alessandro , Bellussi Francesco Maria , Parlani Stefano , Lucisano Andrea , Silvestri Emanuele , Aryal Susmita , Park Sanghyo , Key Jaehong , Fasano Matteo 
Published: June 2024

Abstract

Context:

The rapid growth and diversification of drug delivery systems have been significantly supported by advancements in micro- and nano-technologies, alongside the adoption of biodegradable polymeric materials like poly(lactic-co-glycolic acid) (PLGA) as microcarriers. These developments aim to reduce toxicity and enhance target specificity in drug delivery. The use of in silico methods, particularly molecular dynamics (MD) simulations, has emerged as a pivotal tool for predicting the dynamics of species within these systems. This approach aids in investigating drug delivery mechanisms, thereby reducing the costs associated with design and prototyping. In this study, we focus on elucidating the diffusion mechanisms in curcumin-loaded PLGA particles, which are critical for optimizing drug release and efficacy in therapeutic applications.

Methods:

We utilized MD to explore the diffusion behavior of curcumin in PLGA drug delivery systems. The simulations, executed with GROMACS, modeled curcumin molecules in a representative volume element of PLGA chains and water, referencing molecular structures from the Protein Data Bank and employing the CHARMM force field. We generated PLGA chains of varying lengths using the Polymer Modeler tool and arranged them in a bulk-like environment with Packmol. The simulation protocol included steps for energy minimization, T and p equilibration, and calculation of the isotropic diffusion coefficient from the mean square displacement. The Taguchi method was applied to assess the effects of hydration level, PLGA chain length, and density on diffusion.

Results:

Our results provide insight into the influence of PLGA chain length, hydration level, and polymer density on the diffusion coefficient of curcumin, offering a mechanistic understanding for the design of efficient drug delivery systems. The sensitivity analysis obtained through the Taguchi method identified hydration level and PLGA density as the most significant input parameters affecting curcumin diffusion, while the effect of PLGA chain length was negligible within the simulated range. We provided a regression equation capable to accurately fit MD results. The regression equation suggests that increases in hydration level and PLGA density result in a decrease in the diffusion coefficient.
In situ synthesis of cross-linking gel polymer electrolyte for lithium metal batteries
Authors: Chen Jiaxin , Wang Longxuan , Huang Zhipeng , Liang Yuxuan , Qu Juntian , Wang Ziqiang 
Published: June 2024

AbstractThe room temperature ionic conductivity of polyethylene oxide (PEO)-based polymer electrolytes is low, the electrochemical window is narrow, and the mechanical strength is relatively poor. In this work, a cross-linking gel-based solid composite polymer electrolyte (CG-SCPE) was synthesized by introducing electrochemically stable carbonate-based functional groups. The synthesized CG-SCPE presents excellent tensile strength (26 MPa) and a wide electrochemical stability window (> 4.5 V vs. Li/Li+). Meanwhile, the in situ polymerization method induced by thermal heating resulted in good compatibility between electrodes/electrolytes. In addition, the assembled LiNi0.5Co0.2Mn0.3O2/CG-SCPE/Li battery exhibited satisfactory electrochemical performance. Therefore, the gel polymer electrolyte CG-SCPE with cross-linking network provides the possibility for future application of safe and high-performance solid-state lithium metal batteries. The results indicate that the introduction of cross-linking framework can simultaneously improve the mechanical strength, thermal stability, and electrochemical performance of solid polymer electrolyte.