bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stiripentol for the treatment of refractory status epilepticus
Authors: Möller Leona , Simon Ole J. , Jünemann Clara , Austermann-Menche Meike , Bergmann Marc-Philipp , Habermehl Lena , Menzler Katja , Timmermann Lars , Strzelczyk Adam , Knake Susanne 
Published: October 2024

Abstract
Background
Status epilepticus (SE) is one of the most common neurological emergencies and an acutely life-threatening condition characterized by high mortality and morbidity. Despite the well-established staged therapy of status epilepticus, especially stages 1 and 2, more than one third of patients develop (super-) refractory SE. Despite a large variety of potential treatment options for super-refractory SE, there is an unmet clinical need of potential new treatment ideas in this often desperate clinical situation.
A number of studies have demonstrated the safety and efficacy of stiripentol (STP) in patients with Dravet syndrome (DS) and in children with focal epilepsy and generalized epilepsies. Some smaller series and case reports have documented the use of STP in the treatment of status epilepticus in adult patients.

Methods
We retrospectively analyzed all patients who were admitted to the Department of Neurology at Marburg University Hospital between 2013 and 2023 with a diagnosis of (super)-refractory status epilepticus and who received additional treatment of SE with STP. All patients who received STP during the SE were included, regardless of previous medication.

Results
SE ceased in 64% of 25 patients (13 female and 12 male). The mean age was 58.6 ± 21.9 years (mean ± SD). 72% had a structural epilepsy. In 20% of patients, SE was terminated by the administration of STP alone in 32% of cases, while in a further 32% of patients, the simultaneous administration of multiple anti-seizure medications (ASMs) including STP was potentially responsible for the cessation of the SE, with valproic acid (VPA), benzodiazepines and STP, being the most frequently implicated ASMs. In 12% of patients, there was at least a temporary improvement in the electroencephalogram (EEG). Stiripentol had to be discontinued in three cases due to a reduction in vigilance or hypercalcemia.

Conclusions
Stiripentol may represent a promising additional treatment option for refractory and super-refractory status epilepticus. The tolerability of this treatment has already been demonstrated in previous studies, and was also reflected in these data. Further prospective investigation in larger patient populations are necessary to ascertain the efficacy of stiripentol in SE.

Trial registration
NCT06540378, retrospectively registered.
Association of IL-6 G-174C (rs1800795) variant with the susceptibility to hepatocellular carcinoma in patients with chronic hepatitis
Authors: Abuelnadar Eman H. , Ramadan Lamiaa M. , Shahin Hanaa Elsayed , Alakilli Saleha Y. M. , Wahsh Eman , El-Beltagy Nanis S. , Salem Eman T. , Hatata Abdelrahman S. , El-Said Afaf M. , Alhelf Maha 
Published: October 2024

Abstract
Aim
An ineffective immune response resulting from dysregulation of cytokine production might encourage viral persistence and cause chronic viral hepatitis to worsen. This study examined the relationship between alterations in interleukin-6 (IL-6) levels and the IL-6 − 174 G > C (rs1800795) polymorphism, as well as how this polymorphism affects the development and progression of chronic hepatitis brought on by hepatitis B (HBV) and hepatitis C (HCV) into hepatocellular carcinoma (HCC).

Patients and methods
Whole blood samples from 126 Egyptian patients with HCC (111 with HCV and 15 with HBV), as well as 126 age- and sex-matched healthy individuals, were used to extract DNA. Using PCR-based allele-specific amplification (ASA), the existence of the IL-6 G-174C polymorphism was investigated. Additionally, each participant's serum IL-6 levels were determined using an enzyme-linked immunosorbent assay (ELISA).

Results
The primary observations revealed that HCC patients had greater serum levels of IL-6 compared to the control groups (p < 0.001). Patients with the variant (CG and GG) genotype in the HCC group were found to have more disease severity indicated by higher levels of alpha-fetoprotein (AFP) and a higher ascites grade, as well as increased inflammatory activity as defined by higher levels of IL-6 and C-reactive protein (CRP) (p < 0.001 for both) in comparison to patients with the wild-type (CC) genotype (p < 0.001 and p = 0.002, respectively).

Conclusion
The rs1800795 SNP in the IL-6 gene was associated with increased inflammatory activity and high levels of IL-6, indicating that this SNP may play a role in the development of HCC in Egyptian patients with chronic viral hepatitis.
Drug-induced liver injury during the era of COVID-19 polypharmacy: a statement of account, lessons learned, and a proposed approach
Authors: Badary Hedy A. , Hashem Mohamed B. , El-Kassas Mohamed 
Published: October 2024

AbstractThe coronavirus disease 2019 (COVID-19) causes a systemic illness that can result in various manifestations. In addition to severe acute respiratory syndrome, patients often exhibit complications unrelated to the respiratory system. Potential liver damage can occur in 14.8 to 53.0% of the affected patients. Liver impairment in COVID-19 can also occur because of the use of polypharmacy during disease management. It is essential to be aware of drug-induced liver injury (DILI) in patients diagnosed with COVID-19, especially when considering the off-label usage of medications in both preventative and therapeutic regimens used on a wide scale. This review aims to give pertinent information regarding drugs utilized thus far in COVID-19 patients and their potential toxicity to the liver. We also present a suggested management approach to DILI in COVID-19 patients and lessons learned from the pharmacological management of this pandemic.
Formulation and characterization of 5-fluorouracil and metformin biodegradable nanospheres for treating colon cancer
Authors: Bharathi Priya K. , Kulathuran Pillai K. , Nalini C. N. , Udhumansha Ubaidulla 
Published: October 2024

Abstract
Background
Cancer and diabetes mellitus are quite common diseases found together worldwide. A considerable amount of evidence is available for the rapid development and presentation of various types of cancer in the type 2 diabetes mellitus (DM2) population as compared with the population without diabetes. The objective of the study is to formulate and evaluate 5-fluorouracil (5-FU) and metformin (MET) nanoparticles (NPs) and to establish the characteristic features of the biodegradable NPs. 5-FU and MET NPs with chitosan as a biodegradable polymer were formulated by the ionotropic cross-linking method. 0.25 gm of MET and 0.25 gm of 5-FU were dissolved in 100 ml of distilled water, and stock solution was prepared. 5 ml of stock solution was slowly mixed into the chitosan solution to obtain the mixture of drugs and chitosan. The tripolyphosphate reserve liquid was dripped slowly into the chitosan solution with constant stirring until the opaline appearance was noticed in the mixture, then filtered, and dried. The NPs were evaluated for their physical properties and drug release kinetics. Cell proliferation assay was done using human colorectal carcinoma cell line (HCT 116).

Results
The formulation composed of 1.5 w/v of chitosan, 0.25 w/v of MET, and 5-FU had an average particle diameter of 198.7 nm. The polydispersity index was 0.757. Thermal and infrared spectroscopy results indicated the drugs and polymers selected for the formulation were unique without any identifiable interaction. The NPs were spherical in appearance, with numerous pours on the surface, which was evident when microscopically examined. Uniformity in drug release was observed, and the formulation demonstrated excellent release kinetics. HTC 116 cell line confirmed that the maximum percentage of cell death and minimum viability of cells were observed while using the combination of MET and 5-FU-NPs as compared to the pure MET or 5-FU alone.

Conclusion
MET and 5-FU-loaded chitosan NPs were found to have excellent physiochemical properties, particle size, and drug release from the polymer in a controlled manner. Half-maximal inhibitory concentration value (IC50) of MET and 5-FU-NPs was found to be significantly less as compared to MET and 5-FU alone or the combination.
Artificial Intelligence Hybrid Survival Assessment System for Robot-Assisted Proctectomy: A Retrospective Cohort Study
Authors: Zhang Shiqian , Zhang Ge , Wang Ming , Guo Song-Bin , Wang Fuqi , Li Yun , Kadier Kaisaierjiang , Zhou Zhaokai , Zhang Pengpeng , Chi Hao , Zhang Chuchu , Zhou Quanbo , Lyu Pin , Zhao Shuaiya , Yang Shuaixi , Yuan Weitang 
Published: October 2024

PURPOSE
Robotic-assisted proctectomy (RAP) has emerged as the predominant surgical approach for patients with rectal cancer in recent years; although good postoperative patient recovery with accurate prediction is a guarantee of adaptive surveillance management, there is still a lack of easy-to-use prognostic tools and risk scores designed specifically for those patients undergoing RAP.

METHODS
This study used the electronic health records of 506 RAP participants, including a National Specialist Center for da Vinci Robotic Colorectal Surgery (NSCVRCS) meta cohort, and an independent external validation Sun Yat-sen Memorial Hospital cohort. In the NSCVRCS meta cohort, patients were divided into a discovery cohort (70%, n = 268), where the best-fit model was applied to model our prediction system, RAP-AIscore. Subsequently, an internal validation process for RAP-AIscore was conducted using a replication cohort (30%, n = 116). The study designed and implemented a large-scale artificial intelligence (AI) hybrid framework to identify the best strategy for building a survival assessment system, the RAP-AIscore, from 132 potential modeling scenarios through a combination of iterative cross-validation, Monte Carlo cross-validation, and bootstrap resampling. The 10 variables most relevant to clinical interpretability were identified on the basis of the AI hybrid optimal model values, which helps provide reliable prognostic survival guidance for new patients.

RESULTS
The consistent evaluation of discrimination, calibration, generalization, and prognostic value across cohorts reaffirmed the accuracy and robust extrapolation capability of this system. The 10 feature variables most associated with clinical interpretability on the basis of Shapley values were identified, facilitating reliable prognostic survival guidance for new patients.

CONCLUSION
This study introduces a promising and informative tool, the RAP-AIscore, which can be explained through nomograms for interpreting clinical outcomes. It facilitates postoperative risk stratification management and enhances clinical management of prognosis for RAP patients.
Stomatal development in the changing climate
Authors: Chua Li Cong , Lau On Sun 
Published: October 2024

ABSTRACT
Stomata, microscopic pores flanked by symmetrical guard cells, are vital regulators of gas exchange that link plant processes with environmental dynamics. The formation of stomata involves the multi-step progression of a specialized cell lineage. Remarkably, this process is heavily influenced by environmental factors, allowing plants to adjust stomatal production to local conditions. With global warming set to alter our climate at an unprecedented pace, understanding how environmental factors impact stomatal development and plant fitness is becoming increasingly important. In this Review, we focus on the effects of carbon dioxide, high temperature and drought – three environmental factors tightly linked to global warming – on stomatal development. We summarize the stomatal response of a variety of plant species and highlight the existence of species-specific adaptations. Using the model plant Arabidopsis, we also provide an update on the molecular mechanisms involved in mediating the plasticity of stomatal development. Finally, we explore how knowledge on stomatal development is being applied to generate crop varieties with optimized stomatal traits that enhance their resilience against climate change and maintain agricultural productivity.
Viscous shear is a key force in Drosophila ventral furrow morphogenesis
Authors: Goldner Amanda Nicole , Cheikh Mohamad Ibrahim , Osterfield Miriam , Doubrovinski Konstantin 
Published: October 2024

ABSTRACT
Ventral furrow (VF) formation in Drosophila melanogaster is an important model of epithelial folding. Previous models of VF formation require cell volume conservation to convert apically localized constriction forces into lateral cell elongation and tissue folding. Here, we have investigated embryonic morphogenesis in anillin knockdown (scra RNAi) embryos, where basal cell membranes fail to form and therefore cells can lose cytoplasmic volume through their basal side. Surprisingly, the mesoderm elongation and subsequent folding that comprise VF formation occurred essentially normally. We hypothesized that the effects of viscous shear may be sufficient to drive membrane elongation, providing effective volume conservation, and thus driving tissue folding. Since this hypothesis may not be possible to test experimentally, we turned to a computational approach. To test whether viscous shear is a dominant force for morphogenesis in vivo, we developed a 3D computational model incorporating both accurate cell and tissue geometry, and experimentally measured material parameters. Results from this model demonstrate that viscous shear generates sufficient force to drive cell elongation and tissue folding in vivo.
Interplay Between Servicizing and Remanufacturing: Economic and Environmental Implications
Authors: Sun Xichen , Rajapakshe Tharanga , Oliva Rogelio 
Published: October 2024

Problem definition: To investigate the interplay between servicizing and remanufacturing, two widely used strategies in the circular economy, and its impact on firms’ economic and environmental performance, we consider a profit-maximizing manufacturer who explores the possibility of jointly adopting the two strategies. Methodology and results: We develop optimization models that capture the main attributes for servicizing (pay-per-use, demand pooling) and remanufacturing (lower production costs, higher operating costs). We show that the presence of remanufacturing always makes servicizing less attractive to adopt, and having servicizing may discourage the adoption of remanufacturing if the remanufacturing cost reduction effect is not sufficiently large. The joint adoption of servicizing and remanufacturing is preferred when the remanufacturing cost is neither too high nor too low and the range of the remanufacturing cost that favors the joint adoption is further moderated by the firm’s pooling level and the operating cost of remanufactured products. Lastly, we find that when the firm adopts servicizing in the presence of remanufacturing with relatively high remanufacturing costs, it can reduce the number of remanufactured products with low environmental impact in the market and, thus, harm the environment, resulting in a misalignment between economic and environmental goals. Managerial implications: Our findings suggest that managers considering jointly adopting servicizing and remanufacturing must balance their competition on the low-usage end of the market with the potential complementarity due to remanufacturing cost reduction. Further, by showing the win-win conditions under which the joint adoption of servicizing and remanufacturing improves firms’ economic and environmental performance, we demonstrate that there are no one-size-fits-all circular economy strategies and call for caution when promoting these strategies across industries. Supplemental Material: The electronic companion is available at https://doi.org/10.1287/msom.2022.0379 .
CPD: Bcla Clear 10
Authors: Nagra Manbir , Retallic Neil 
Published: October 2024

The 10th in a series of articles summarising the key findings of the BCLA CLEAR publication, a major review of the published evidence relating to all aspects of contact lens practice, Dr Manbir Nagra and Neil Retallic offer an overview of the contact lens fitting aspects from the BCLA CLEAR section relating to evidence based contact lens practice (C106621 suitable for one distance learning CPD point for optometrists, contact lens opticians and dispensing opticians). Upon successful completion of this CPD, you will be able to identify evidence-based elements of the contact lens fitting process and how these should be integrated with patient values and clinical judgement (s5) Upon successful completion of this CPD, you will be able to interpret preliminary clinical measurements and use history taking to manage the fitting of patients with contact lenses (s7)
Geographical indication of São Matheus as a boost to gastronomic tourism
Authors: Covalchuck Gabriela Cristina , De Lima Medeiros Mirna 
Published: October 2024

Yerba-mate has undeniable historical-cultural and economic value, especially in Southern Brazil. The consumption of yerba-mate as chimarrão or tea is usual, and the product can also be creatively used as an ingredient in other food preparations. In Paraná, the state flag has a branch of this plant on it, representing the importance of this production in its colonization, emancipation, and consolidation as a state. Aiming to protect and promote products in connection to their origin, appears the sign of geographical indications (GIs). Regarding this product, the first GI, namely, the GI São Matheus, was granted in 2017 and its territory comprises 06 municipalities located in the South of the state of Paraná. Taking that into consideration, this article sought to analyze how the implementation of a geographical indication might boost gastronomic tourism in a given region. To carry out the investigation, the potentiality of the territory of São Matheus, located in Southern Paraná – Brazil was observed. The data was organized and treated by developing an interpretive case study. The participants were 28 actors (producers, support organizations, and other relevant individuals, employing a process called “snowball”), document analysis and direct observation were also used. The data analysis employed content analysis aided by the software IRaMuTeQ for key questions. After crossing evidence, we verified the existence of actors promoting local gastronomy and tourism. However, strengthening the GI management is still needed along with the aggregation of other territorial assets to promote the rediscovery of its potentialities.
Low noise InGaAs/InP single-photon detector with DC to 1  GHz tunable gate frequency
Authors: Chen Jia-Lin , He De-Yong , Wang Shuang , Shi Ying-Liang , Geng Jia-Qi , Yin Zhen-Qiang , Chen Wei , Fan-Yuan Guan-Jie , Guo Guang-Can , Han Zheng-Fu 
Published: October 2024

An InGaAs/InP single-photon detector (SPD) typically operates in gated mode, but the capacitive response of a single-photon avalanche diode introduces spike noise, obscuring the avalanche signal. Most avalanche signal discrimination schemes cannot completely eliminate spike noise, resulting in residual noise. Limited by residual noise, these schemes have large noise and a limited frequency tuning range. However, for applications like quantum key distribution and laser ranging, a low noise, frequency-tunable InGaAs/InP SPD is crucial for enhancing system performance. Here, we propose a (residual noise assisted) discrimination method that aligns the maximum amplitude of the avalanche signal with the peak of the residual noise. This method turns the residual noise from adversity into an advantage for signal discrimination. With this method, we achieve tunable gating frequency from DC to 1 GHz. Additionally, this method enables the discrimination of weak avalanche signals, allowing effective single-photon detection at low avalanche gain. Across the entire tuning range, at a 20% detection efficiency, the dark count rate is approximately 5.0×10−7 per gate, and the afterpulse probability is less than 1.0%, significantly lower than in previous experiments. The proposed SPD exhibits low noise and a wide tunable gating frequency range, providing a reliable foundation for various applications.
Highly sensitive plasmonic nanoridge hyperbolic metamaterial for biosensing
Authors: Yue Xinzhao , Wang Tao , Cai Yaohua , Yan Ruoqin , Wang Lu , Wang Huimin , Lv Enze , Yuan Xuyang , Zeng Jinwei , Shu Xuewen , Wang Jian 
Published: October 2024

Artificially designed hyperbolic metamaterials (HMMs) with extraordinary optical anisotropy can support highly sensitive plasmonic sensing detections, showcasing significant potential for advancements in medical research and clinical diagnostics. In this study, we develop a gold nanoridge HMM and disclose the plasmonic sensing physical mechanism based on this type of HMM through theoretical and experimental studies. We determine that the high modal group velocity of plasmonic guided modes stemming from a large transverse permittivity of HMMs directly results in high sensitivity. By combining electron-beam lithography, oxygen plasma etching, and electroplating, the fabricated gold nanoridge array possesses an extremely high structural filling ratio that is difficult to obtain through conventional processes. This leads to a large transverse permittivity and enables highly confined and ultra-sensitive bulk plasmon–polariton (BPP) guided modes. By exciting these modes in the visible to near-infrared region, we achieve a record sensitivity of 53,300 nm/RIU and a figure of merit of 533. Furthermore, the developed plasmonic nanoridge HMM sensor exhibits an enhanced sensitivity of two orders of magnitude compared to that of the same type of HMM sensor in label-free biomolecule detection. Our study not only offers a promising avenue for label-free biosensing but also holds great potential to enhance early disease detection and monitoring.