bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant splicing of CaV1.2 calcium channel induced by decreased Rbfox1 enhances arterial constriction during diabetic hyperglycemia
Authors: Hou Wei , Yin Shumin , Li Pengpeng , Zhang Ludan , Chen Tiange , Qin Dongxia , Mustafa Atta Ul , Liu Caijie , Song Miaomiao , Qiu Cheng , Xiong Xiaoqing , Wang Juejin 
Published: April 2024

AbstractDiabetic hyperglycemia induces dysfunctions of arterial smooth muscle, leading to diabetic vascular complications. The CaV1.2 calcium channel is one primary pathway for Ca2+ influx, which initiates vasoconstriction. However, the long-term regulation mechanism(s) for vascular CaV1.2 functions under hyperglycemic condition remains unknown. Here, Sprague–Dawley rats fed with high-fat diet in combination with low dose streptozotocin and Goto-Kakizaki (GK) rats were used as diabetic models. Isolated mesenteric arteries (MAs) and vascular smooth muscle cells (VSMCs) from rat models were used to assess K+-induced arterial constriction and CaV1.2 channel functions using vascular myograph and whole-cell patch clamp, respectively. K+-induced vasoconstriction is persistently enhanced in the MAs from diabetic rats, and CaV1.2 alternative spliced exon 9* is increased, while exon 33 is decreased in rat diabetic arteries. Furthermore, CaV1.2 channels exhibit hyperpolarized current–voltage and activation curve in VSMCs from diabetic rats, which facilitates the channel function. Unexpectedly, the application of glycated serum (GS), mimicking advanced glycation end-products (AGEs), but not glucose, downregulates the expression of the splicing factor Rbfox1 in VSMCs. Moreover, GS application or Rbfox1 knockdown dynamically regulates alternative exons 9* and 33, leading to facilitated functions of CaV1.2 channels in VSMCs and MAs. Notably, GS increases K+-induced intracellular calcium concentration of VSMCs and the vasoconstriction of MAs. These results reveal that AGEs, not glucose, long-termly regulates CaV1.2 alternative splicing events by decreasing Rbfox1 expression, thereby enhancing channel functions and increasing vasoconstriction under diabetic hyperglycemia. This study identifies the specific molecular mechanism for enhanced vasoconstriction under hyperglycemia, providing a potential target for managing diabetic vascular complications.
Immersive virtual reality in orthopedic surgery as elective subject for medical students
Authors: Schöbel Tobias , Schuschke Leonard , Youssef Yasmin , Rotzoll Daisy , Theopold Jan , Osterhoff Georg 
Published: April 2024

Abstract
Background
Virtual reality (VR) simulators have been introduced for skills training in various medical disciplines to create an approximately realistic environment without the risk of patient harm and have improved to more immersive VR (iVR) simulators at affordable costs. There is evidence that training on VR simulators improves technical skills but its use in orthopedic training programs and especially in curricular teaching sessions for medical students are currently not well established. The aim of this study was to describe the implementation of a VR operating theater as an elective course for undergraduate medical students and to evaluate its effect on student learning.

Methods
An elective course for 12 students was implemented during the summer semester of 2023. Using Oculus Quest 2 headsets (Reality Labs, Meta Platforms, USA) and controllers and the PrecisionOS platform, they were able to train five different surgical procedures. The courses were accompanied by weekly topic discussions and instructional videos. Students were assigned to two groups: group VR vs. group non-VR. The groups were switched after 5 weeks. User feedback and performance development (theoretical and procedural surgical knowledge) after VR training were assessed using three questionnaires.

Results
The students highly appreciated the implementation of VR training into their curriculum and 91% stated that they would opt for further VR training. All students stated that VR training improved their understanding of surgical procedures and that it should be obligatory in surgical training for undergraduate medical students. After 5 weeks of training, students in the VR group achieved significantly better results (100 out of maximum 180 points) than the non-VR group (70 points, p = 0.0495) in procedural surgical knowledge. After completion of the VR training the VR group achieved 106 points and the non-VR group 104 points (p = 0.8564). The procedural knowledge for non-VR group after 5 weeks significantly improved after VR training from 70 to 106 points (p = 0.0087).

Conclusion
The iVR can be easily integrated into the curriculum of medical students and is highly appreciated by the participants. The iVR statistically improves the procedural knowledge of surgical steps compared to conventional teaching methods. Further implementation of iVR training in curricular teaching of medical students should be considered.

Graphic abstract
Herbrandized modified realizability
Authors: Ferreira Gilda , Firmino Paulo 
Published: April 2024

AbstractRealizability notions in mathematical logic have a long history, which can be traced back to the work of Stephen Kleene in the 1940s, aimed at exploring the foundations of intuitionistic logic. Kleene’s initial realizability laid the ground for more sophisticated notions such as Kreisel’s modified realizability and various modern approaches. In this context, our work aligns with the lineage of realizability strategies that emphasize the accumulation, rather than the propagation of precise witnesses. In this paper, we introduce a new notion of realizability, namely herbrandized modified realizability. This novel form of (cumulative) realizability, presented within the framework of semi-intuitionistic logic is based on a recently developed star combinatory calculus, which enables the gathering of witnesses into nonempty finite sets. We also show that the previous analysis can be extended from logic to (Heyting) arithmetic.
Beyond surgery: bladder preservation and the role of systemic treatment in localised muscle-invasive bladder cancer
Authors: Swinton Martin , Devi Aarani , Song Yee Pei , Hoskin Peter , Choudhury Ananya 
Published: April 2024

AbstractOver the last two to three decades the non-surgical curative management of bladder cancer has significantly progressed. Increasing evidence supports the use of bladder preservation as an alternative to radical cystectomy (RC) for localised muscle-invasive bladder cancer (MIBC). Radiosensitisation with chemotherapy or hypoxia modification improves the efficacy of radiotherapy. Systemic treatments play an important role in the management of localised MIBC with the benefit of neoadjuvant chemotherapy prior to radical treatment well established. The use of immune checkpoint inhibitors (ICIs) in the radical treatment of bladder cancer, their safe combination with radical radiotherapy regimens and whether the addition of ICIs improve rates of cure are outstanding questions beginning to be answered by ongoing clinical trials. In this narrative review, we discuss the current evidence for bladder preservation and the role of systemic treatments for localised MIBC.
Auditory performance and language skills in children with auditory brainstem implants and cochlear implants
Authors: Yıldırım Gökay Nuriye , Demirtaş Beyza , Özbal Batuk Merve , Yücel Esra , Sennaroğlu Gonca 
Published: April 2024

Abstract
Purpose
This study aims to evaluate school-age language skills and auditory performance in different listening situations in children with cochlear implants and auditory brainstem implants.

Method
The study included 60 children between the ages of 5 and 9 years with cochlear implants (CI) and auditory brainstem implants (ABI). The volunteer children were divided into two groups: bimodal CI-ABI and bilateral CI users. Test of Language Development: Primary (TOLD-P:4), which assesses components of language such as phonology, morphology, syntax and semantics, was used to evaluate school-age language skills. Children’s Auditory Performance Scale (CHAPS) was used to measure their listening performance in quiet, noisy, multi-stimulus environments and their auditory attention and memory skills in daily life. The correlations between language and auditory performance were analyzed and compared between the two groups.

Results
Children with ABI showed poorer performance in school-age language skills and auditory performance in different listening environments (p < 0.05). Significant correlations were between school-age language skills and auditory performance (p < 0.05).

Conclusion
Improved auditory performance is crucial for the development of school-age language skills. To improve auditory performance in children with ABI in different listening environments, assistive listening devices, acoustic environmental arrangements, informative activities, etc., should be used.
Anxiety characteristics in benign paroxysmal positional vertigo: first vs. recurrent episodes
Authors: Mann Ben Yehuda Lotem , Rachima David , Katz-Leurer Michal 
Published: April 2024

Abstract
Purpose
To assess the difference in state and trait anxiety levels in patients with Benign Paroxysmal Positional Vertigo (BPPV) at the first episode (FE) versus recurrent episodes (RE), before and after vestibular physiotherapy. A secondary objective was to assess the difference in the prevalence of underlying health conditions between FE and RE BPPV patients.

Methods
Fifty-five patients with BPPV, aged 40–70, were recruited. The diagnosis of BPPV was confirmed based on subjective complaints of vertigo and positive results from the Dix–Hallpike and Supine Roll tests. Twenty-four patients were in their FE, and 31 had RE. All patients completed the State–Trait Anxiety Inventory (STAI) questionnaire three times; before, immediately after, and a week after vestibular physiotherapy treatment.

Results
The RE group demonstrated higher trait anxiety than the FE group in all testing points: before treatment (median value of 38 versus 29, p-value = 0.02), immediately after treatment (median value of 36 versus 28, p-value < 0.01) and a week later (median value of 38 versus 28, p-value < 0.01). State anxiety decreased immediately after treatment in both groups, but at the second session, it was significantly higher in the RE than in the FE group (median value of 38 versus 28.5, p-value = 0.03). Hypothyroidism was significantly more frequent in the RE group (RE 16%, FE 0%, p-value = 0.04).

Conclusions
Based on the current study’s findings, we recommend assessing anxiety levels in patients with recurrent BPPV and consider referring them for appropriate treatment when necessary.
Prevalence and epidemiology of stroke in patients with multiple sclerosis: a systematic review and meta-analysis
Authors: Stefanou Maria-Ioanna , Giannopapas Vasileios , Kitsos Dimitrios K. , Chondrogianni Maria , Theodorou Aikaterini , Kosmidou Maria , Vlotinou Pinelopi , Bakirtzis Christos , Andreadou Elizabeth , Tzartos John S. , Giannopoulos Sotirios , Tsivgoulis Georgios 
Published: April 2024

Abstract
Background
Epidemiological data are sparse regarding the risk of stroke in patients with multiple sclerosis (MS).

Objective
To estimate the following: (1) the pooled prevalence of all-cause stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) in MS patients; (2) the relative risk for all-cause stroke, AIS and ICH in MS patients compared to the general population; (3) associations between patient characteristics and the risk for AIS and ICH in MS patients.

Methods
Systematic review and meta-analysis of registry-based and cohort studies.

Results
Thirteen observational studies comprising 146,381 MS patients were included. The pooled prevalence of all-cause stroke was 2.7% (95% confidence interval [CI] 1.3–4.6%), with the relative risk of all-cause stroke being higher in MS patients compared to the general population (RR: 2.55; 95% CI 1.97–3.29). Subgroup analyses per stroke subtype revealed a pooled AIS prevalence of 2.1% (95% CI 0.8–4.1%) and a pooled ICH prevalence of 0.6% (95% CI 0.2–1.2%). Compared to the general population, patients with MS were found to harbour an increased risk for AIS (RR: 2.79; 95% CI 2.27–3.41) and ICH (RR: 2.31; 95% CI 1.04–5.11), respectively. The pooled prevalence of cardiovascular risk factors in MS patients was 11.5% (95% CI 2.9–24.7%) for dyslipidaemia, 18.2% (95% CI 5.9–35.3%) for hypertension and 5.4% (95% CI 2.1–10.2%) for diabetes. In meta-regression, age was negatively associated with AIS risk (β =  – .03, p = 0.04), with a 1-year increase in age resulting in a significant 3% (95%CI 0–5) attenuation of the risk of AIS.

Conclusion
The findings of the present meta-analysis indicate that MS is associated with an increased risk for ischaemic and haemorrhagic stroke. Future well-designed epidemiological studies are warranted to corroborate the robustness of the present findings in the MS population.
Isoperimetric Inequalities and Supercritical Percolation on High-Dimensional Graphs
Authors: Diskin Sahar , Erde Joshua , Kang Mihyun , Krivelevich Michael 
Published: April 2024

AbstractIt is known that many different types of finite random subgraph models undergo quantitatively similar phase transitions around their percolation thresholds, and the proofs of these results rely on isoperimetric properties of the underlying host graph. Recently, the authors showed that such a phase transition occurs in a large class of regular high-dimensional product graphs, generalising a classic result for the hypercube. In this paper we give new isoperimetric inequalities for such regular high-dimensional product graphs, which generalise the well-known isoperimetric inequality of Harper for the hypercube, and are asymptotically sharp for a wide range of set sizes. We then use these isoperimetric properties to investigate the structure of the giant component $$L_1$$

L
1

in supercritical percolation on these product graphs, that is, when $$p=\frac{1+\epsilon }{d}$$

p
=

1
+
ϵ

d

, where d is the degree of the product graph and $$\epsilon >0$$

ϵ
>
0

is a small enough constant. We show that typically $$L_1$$

L
1

has edge-expansion $$\Omega \left( \frac{1}{d\ln d}\right) $$

Ω

1

d
ln
d

. Furthermore, we show that $$L_1$$

L
1

likely contains a linear-sized subgraph with vertex-expansion $$\Omega \left( \frac{1}{d\ln d}\right) $$

Ω

1

d
ln
d

. These results are best possible up to the logarithmic factor in d. Using these likely expansion properties, we determine, up to small polylogarithmic factors in d, the likely diameter of $$L_1$$

L
1

as well as the typical mixing time of a lazy random walk on $$L_1$$

L
1

. Furthermore, we show the likely existence of a cycle of length $$\Omega \left( \frac{n}{d\ln d}\right) $$

Ω

n

d
ln
d

. These results not only generalise, but also improve substantially upon the known bounds in the case of the hypercube, where in particular the likely diameter and typical mixing time of $$L_1$$

L
1

were previously only known to be polynomial in d.
SERS biosensor with plastic antibodies for detection of a cancer biomarker protein
Authors: Oliveira Daniela , Carneiro Mariana C. C. G. , Moreira Felismina T. C. 
Published: April 2024

AbstractSurface-enhanced Raman scattering (SERS) is a powerful method for detecting breast cancer-specific biomarkers due to its extraordinary enhancement effects obtained by localized surface plasmon resonance (LSPR) in metallic nanostructures at hotspots. In this research, gold nanostars (AuNSs) were used as SERS probes to detect a cancer biomarker at very low concentrations. To this end, we combined molecularly imprinted polymers (MIPs) as a detection layer with SERS for the detection of the biomarker CA 15–3 in point-of-care (PoC) analysis. This required two main steps: (i) the deposition of MIPs on a gold electrode, followed by a second step (ii) antibody binding with AuNSs containing a suitable Raman reporter to enhance Raman signaling (SERS). The MPan sensor was prepared by electropolymerization of the monomer aniline in the presence of CA 15–3. The template molecule was then extracted from the polymer using sodium dodecyl sulfate (SDS). In parallel, a control material was prepared in the absence of the protein (NPan). Surface modification for the control was performed using electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The performance of the sensor was evaluated using the SERS technique, in which the MPan sensor is first incubated with the protein and then exposed to the SERS probe. Under optimized conditions, the device showed a linear response to CA 15–3 concentrations from 0.016 to 248.51 U mL−1 in a PBS buffer at pH 7.4 in 1000-fold diluted serum. Overall, this approach demonstrates the potential of SERS as an optical reader and opens a new avenue for biosensing applications.
Graphical Abstract
Computational studies on Mg ion conductivity in Mg2xHf1-x Nb(PO4)3 using neural network potential
Authors: Makino Keisuke , Tanibata Naoto , Takeda Hayami , Nakayama Masanobu 
Published: April 2024

AbstractLow Mg diffusivity in solid-state oxides is an obstacle for the development of materials for Mg ion batteries, which are expected to have high capacity. In this study, we focused on NASICON-type and β-iron sulfate-type Mg2xHf1-xNb(PO4)3 that exhibit relatively high Mg ionic conductivity and investigated the Hf/Nb configuration and composition dependence of phase stability and ion conductivity by atomistic simulation using neural network potentials. The calculations show that the NASICON-type structure is slightly more stable and has higher Mg ionic conductivity than that of the β-iron sulfate-type. The effect of the Hf/Nb configuration was investigated and showed that the ordered stable structure had much lower ionic conductivity than the disordered structure. Furthermore, as the Mg ion concentration increased, the ionic conductivity increased monotonically at low concentrations but tended to converge to a constant value above a certain concentration. The saturation of the ionic conductivity despite increasing the Mg concentration may be due to the trapping effect of the Mg ions caused by the Hf vacancies as well as the Hf/Nb arrangement.
Graphical Abstract
Perceptions and dilemmas around cyber-security in a Spanish research center after a cyber-attack
Authors: Navajas-Adán Joaquín , Badia-Gelabert Eulàlia , Jiménez-Saurina Laura , Marijuán-Martín Mª Jesús , Mayo-García Rafael 
Published: April 2024

AbstractInformation and Communication Technologies and Internet networks are present in all aspects of social reality and are essential elements in research, development and innovation centers (R&D&I). Cyber-security is crucial for the progress of the research activities developed in these centers, especially given the exponential growth of cyber-attacks and incidents. The present study aims to assess from a socio-technical approach, how a serious cyber-attack on a Spanish research center has affected staff’s perceptions of information and communication systems (ICT) security. This study employed a mixed-methods research strategy, combining quantitative and qualitative methods to provide a comprehensive and nuanced understanding of ICT security perceptions among employees. First a quantitative scale was administered to 1,321 employees 3 years before the cyber-attack and 4 months afterward, to measure ICT security perceptions. Then, qualitative techniques (semi-structured interviews, focus groups, and micro-ethnography) were applied to gain a deeper understanding of the arguments underpinning cyber-security at the center after the attack. The results show that the event had an impact on employees’ perceptions, increasing the perceived importance of ICT security, with positive behavioral changes noted, but with doubts about their sustainability over time. Also, the need for cyber-security governance was critically contrasted with organizational reality. Finally, the compatibility of science and cyber-security was a central dilemma, which seems to confront antagonistic poles (research and security ICT) and justify the non-compliance with security protocols by part of the staff.
Reverse engineering the last-minute on-line pricing practices: an application to hotels
Authors: Guizzardi Andrea , Ballestra Luca Vincenzo , D’Innocenzo Enzo 
Published: April 2024

AbstractWe suggest a nonlinear time series methodology to model the (last-minute) price adjustments that hotels active in the online market make to adapt their early-booking rates in response to unpredictable fluctuations in demand. We use this approach to reverse-engineer the pricing strategies of six hotels in Milan, Italy, each with different features and services. The results reveal that the hotels’ ability to align last-minute adjustments with early-booking decisions and account for stochastic demand seasonality varies depending on factors such as size, star rating, and brand affiliation. As a primary empirical finding, we show that the autocorrelations of the first four moments of the last-minute price adjustment can be used to gain crucial insights into the hoteliers’ pricing strategies. Scaling up this approach has the potential to equip policymakers in smart destinations with a reliable and transparent tool for the real-time monitoring of demand dynamics.
Evaluating 900 Potentially Harming Fires in Germany: Is the Prescriptive Building Code Effective? German Fire Departments Assessed Fire Safety Measures in Buildings Through On-Site Inspections
Authors: Maiworm Björn , Göldner Moritz , Mannl Kilian , Hammann Claudius 
Published: April 2024

AbstractFire statistics mirror the outcome of fire prevention. Most fire statistics in Germany deal with the loss of life, value, and fire department actions (number of interventions, nozzles used, or alarm category like a false alarm). However, these results also represent the safety level the legislator has set through the prescriptive building regulations. The current statistics cannot evaluate the level of fire safety and the fulfillment or necessity of fire safety precautions. Today, expert judgment from firefighters is necessary to fill this gap. Here, we show the first evaluation of fire prevention and hazard protection measures by evaluating 900 potentially harming fires throughout Germany. In contrast to minor fires, these fires have advanced to the extent that they could potentially violate the protection objectives outlined in building regulations. The fire department association developed a questionnaire to evaluate the fire safety level and possibly reduce unnecessary fire safety regulations. One hundred twenty-three fire departments carried out the questionnaire, which are responsible for 25% of the German population. Fire prevention officers of the fire departments went to the scene after the fire was extinguished, and the fire safety concept of the building could be evaluated. We found a high rate of injuries, smoke spread, need for rescue by firefighters, and higher than expected firefighter response times after arrival at the scene. Surprisingly, smoke spread rates correlated with building height and not with building age. It was even possible to assess the risk of multiple casualties. Overall, the questionnaire results give insight into the current level of fire safety in existing buildings. Ways and rates for smoke and fire spread prove the importance of second escape routes and the influence of human misconduct. According to these results, current building code regulations are sufficient to prevent fire spread. On the other hand, smoke spreading is a severe threat to people’s safety. For example, the data shown can be applied in Bayes nets or other risk calculations to optimize individual building designs or even governmental building codes concerning fire safety engineering. Based on our observations, science, and building codes, authorities could in the future establish a performance-based building code instead of the current prescriptive code. This paper presents the first approach in Germany to quantify the expert judgment of fire departments and use it as a source of knowledge for fire prevention.