bluuebunny/crossref_metadata_2025 huggingface dataset:
The feasibility of mechanical thrombectomy versus medical management for acute stroke with a large ischemic territory
Authors: Aslan Assala , Abuzahra Saad , Adeeb Nimer , Musmar Basel , Salim Hamza A , Kandregula Sandeep , Dmytriw Adam A , Griessenauer Christoph J , De Alba Luis , Arevalo Octavio , Burkhardt Jan Karl , Pereira Vitor M , Jabbour Pascal , Guthikonda Bharat , Cuellar Hugo H
Published: March 2024

Background

Mechanical thrombectomy (MT) for acute ischemic stroke is generally avoided when the expected infarction is large (defined as an Alberta Stroke Program Early CT Score of <6).

Objective

To perform a meta-analysis of recent trials comparing MT with best medical management (BMM) for treatment of acute ischemic stroke with large infarction territory, and then to determine the cost-effectiveness associated with those treatments.

Methods

A meta-analysis of the RESCUE-Japan, SELECT2, and ANGEL-ASPECT trials was conducted using R Studio. Statistical analysis employed the weighted average normal method for calculating mean differences from medians in continuous variables and the risk ratio for categorical variables. TreeAge software was used to construct a cost-effectiveness analysis model comparing MT with BMM in the treatment of ischemic stroke with large infarction territory.

Results

The meta-analysis showed significantly better functional outcomes, with higher rates of patients achieving a modified Rankin Scale score of 0–3 at 90 days with MT as compared with BMM. In the base-case analysis using a lifetime horizon, MT led to a greater gain in quality-adjusted life-years (QALYs) of 3.46 at a lower cost of US$339 202 in comparison with BMM, which led to the gain of 2.41 QALYs at a cost of US$361 896. The incremental cost-effectiveness ratio was US$−21 660, indicating that MT was the dominant treatment at a willingness-to-pay of US$70 000.

Conclusions

This study shows that, besides having a better functional outcome at 90-days' follow-up, MT was more cost-effective than BMM, when accounting for healthcare cost associated with treatment outcome.
Prolonged venous transit on perfusion imaging is associated with higher odds of mortality in successfully reperfused patients with large vessel occlusion stroke
Authors: Yedavalli Vivek S , Koneru Manisha , Hoseinyazdi Meisam , Greene Cynthia , Lakhani Dhairya A , Xu Risheng , Luna Licia P , Caplan Justin M , Dmytriw Adam A , Guenego Adrien , Heit Jeremy J , Albers Gregory W , Wintermark Max , Gonzalez L Fernando , Urrutia Victor C , Huang Judy , Nael Kambiz , Leigh Richard , Marsh Elisabeth B , Hillis Argye E , Llinas Rafael H
Published: March 2024

Background

Poor venous outflow (VO) profiles are associated with unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO), despite achieving successful reperfusion. The objective of this study is to assess the association between mortality and prolonged venous transit (PVT), a novel visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps.

Methods

We performed a retrospective analysis of prospectively collected data from consecutive adult patients with AIS-LVO with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s timing on CTP Tmax maps in at least one of the following: superior sagittal sinus (proximal venous drainage) and/or torcula (deep venous drainage). PVT− was defined as lacking this in both regions. The primary outcome was mortality at 90 days. In a 1:1 propensity score-matched cohort, regressions were performed to determine the effect of PVT on 90-day mortality.

Results

In 127 patients of median (IQR) age 71 (64–81) years, mortality occurred in a significantly greater proportion of PVT+ patients than PVT− patients (32.5% vs 12.6%, P=0.01). This significant difference persisted after matching (P=0.03). PVT+ was associated with a significantly increased likelihood of 90-day mortality (OR 1.22 (95% CI 1.02 to 1.46), P=0.03) in the matched cohort.

Conclusions

PVT+ was significantly associated with 90-day mortality despite successful reperfusion therapy in patients with AIS-LVO. PVT is a simple VO profile marker with potential as an adjunctive metric during acute evaluation of AIS-LVO patients. Future studies will expand our understanding of using PVT in the evaluation of patients with AIS-LVO.
Health-related quality of life and frailty in liver cirrhosis
Authors: Hui Yangyang , Wang Han , Guo Gaoyue , Yang Wanting , Wang Xiaoyu , Cui Binxin , Fan Xiaofei , Sun Chao
Published: March 2024

Background and objectives

There is limited evidence concerning the predictive value of health-related quality of life (HRQoL) on the presence of frailty in the context of cirrhosis. We aimed to elucidate the relationship between HRQoL and multidimensional frailty and to determine which HRQoL dimension independently impacted frail phenotype in our established cohort.

Methods

This was a prospective observational study by consecutively enrolling 355 patients with cirrhotic with decompensated signs in China. The HRQoL and frail phenotype were evaluated by the EuroQol-5D (EQ-5D) Questionnaire and Frailty Index, respectively. The relationship between EQ-5D utility index, as well as respective EQ-5D dimension, and Frailty Index was analysed according to the multiple linear regression analyses.

Results

More than half of the patients (56.3%) reported problems in any dimension of the EQ-5D, suggestive of impaired HRQoL. Moreover, the proportion of patients experiencing some/extreme problems significantly increased across all five dimensions (all p<0.001) in correspondence to transition from the robust to frail phenotype. Multiple linear regression analyses demonstrated that age, ascites and hepatic encephalopathy were positively associated with Frailty Index, while EQ-5D utility index (standardised β coefficient= −0.442, p<0.001) negatively associated with Frailty Index. Notably, usual activities, self-care and mobility were the most influencing predictors associated with frailty.

Conclusions

Our results support a rapid HRQoL assessment via EQ-5D may assist in predicting multidimensional frailty, and usual activities, self-care and mobility tend to be remediable targets while taking their effect on frail phenotype into consideration among patients with cirrhosis.
The effect of feeding flaxseed as a source of omega-3 fatty acids to broiler and layer breeders during rearing and lay on body weight, reproductive performance, and hatchability performance indices
Authors: Whittle Rosemary H. , Kiarie Elijah G. , Widowski Tina M.
Published: March 2024

Omega-3 fatty acids (n-3 FA) are fed to chickens to enrich eggs for human consumption. Feeding n-3 FA to breeder flocks could benefit the breeders and improve their offspring’s health, welfare, and productivity. This study assessed the impacts of feeding flaxseed (n-3 FA source) on broiler breeders’ and layer breeders’ production performance. In experiment one, Ross 708 broiler breeders were fed a control or flaxseed (2.57% co-extruded flaxseed and pulses) diet during rearing and laying. In experiment two, Shaver White and ISA Brown layer breeders were fed a control or flaxseed diet. Diet tended to affect broiler breeder body weight (BW) ( P = 0.06) and significantly affected BW uniformity ( P = 0.045). There were no significant pairwise comparisons. Broiler breeders fed flaxseed produced more eggs than control breeders ( P < 0.001) and had better feed conversion per egg mass ( P < 0.001). Maternal diet tended to affect broiler offspring sex ( P = 0.08), but there were no significant pairwise comparisons. Flaxseed diet did not affect layer breeder weight ( P = 0.90) but decreased uniformity ( P = 0.07). Strain ( P = 0.04), but not diet ( P = 0.95), influenced the sex of layer offspring. More female chicks hatched from Shaver White than ISA Brown breeders. Feeding flaxseed did not negatively affect productivity. Feeding n-3 FA may benefit broiler breeder egg production.
Novel interaction solutions to the (3+1)-dimensional Hirota bilinear equation by bilinear neural network method
Authors: Ma Wenbo , Bilige Sudao
Published: March 2024

Solving differential equations is an ancient and very important research topic in theory and practice. The exact analytical solution to differential equations can describe various physical phenomena such as vibration and propagation wave. In this paper, the bilinear neural network method (BNNM), which uses neural network to unify all kinds of classical test function methods, is employed to obtain some new exact analytical solutions of the ([Formula: see text])-dimensional Hirota bilinear (HB) equation. Based on the Hirota form of the HB equation, we constructed four kinds of new solutions which contain the breather solution, rogue wave solution, breather lump-type soliton solution and the interaction solution between the periodic waves and two-kink wave by introducing a series of test functions in both single-layer and multi-layer neurons such as [4–2–2] and [4–2–3] neural network models. In addition, we compared them to those that had already been published. It is clear that our results are not consistent with those found in these publications. Their corresponding dynamic features are vividly demonstrated in some 3D, contour, x-curves and y-curves plots. The results obtained demonstrate the potential of the proposed methods to solve other nonlinear partial differential equations in fields.
Effect of non-metallic doping on the electronic structure and optical properties of ZrSe2
Authors: Sun Shihang , Yang Lu , Liu Huaidong , Zhao Yanshen , Wei Xingbin , Tang Xinying , Ni Junjie
Published: March 2024

The optoelectronic properties of non-metal (B, N, O, C, F) doped and biaxial tensile strain in the x–y direction of O-doped and N-doped ZrSe2, including energy band structure, density of states, dielectric function, and absorption coefficients, have been calculated by a first-principles approach based on density-functional theory. It is shown that the doped system has a low formation energy, indicating that the structure can exist stably. The B, C, and N atom-doped systems show impurity energy levels near the Fermi energy level, narrowing the bandgap, enhancing the electron transport ability, and increasing the electrical conductivity. Biaxial stretching was applied to the ZrSe2 structure before and after O and N doping, and it was found that the stability of the ZrSe2, Zr9Se[Formula: see text]O[Formula: see text] and Zr9Se[Formula: see text]N1 structures was found to decrease gradually with increasing strain. The energy bandwidth of the doped system in the Zr9Se[Formula: see text] O1system at a tensile strain of 4% is a maximum of 0.924[Formula: see text]eV; from the density of states, it is found that there is a very obvious orbital hybridization of Se-4p and Zr-d. The doped system has the largest effect on the dielectric function at 6% tensile strain and on the absorption coefficient at 8%. In the Zr9Se[Formula: see text]N1 system, stretching 8% energy bandwidth is a maximum of 0.788[Formula: see text]eV, the tensile strain of 8% has the greatest effect on the dielectric function, and a tensile strain of 6% has the most significant effect on the absorption coefficient.
Soluble zinc phthalocyanines as chemical probes for Δ-9-tetrahydrocannabinol in different solvents
Authors: Karlin Laura , Lamontagne Halynne R. , Chaurasia Sumit , Triglav Michael , Harris Cory S. , Shuhendler Adam J. , Brusso Jaclyn L. , Lessard Benoît H.
Published: March 2024

The detection of [Formula: see text]-9-tetrahydrocannabinol (THC) is important for several applications from agriculture and pharmaceuticals to law enforcement. Two novel soluble zinc phthalocyanines were synthesized and their interaction with THC was studied. We report the change in the electrochemical and spectroelectrochemical response of the two zinc derivatives in the presence of THC using different organic solvents (DCM, THF, and DMF). The greatest change in spectroelectrochemical response was found when DCM was employed, whereas when THF was used an increase in higher energy [Formula: see text]-[Formula: see text]* transitions within the Pc cores was observed. Using DMF on the other hand demonstrated little change in response. We also found that the functional group used to solubilize the ZnPc played a significant role in the observed spectrochemical response to THC. These results demonstrate the potential for ZnPc-based chemical probes for the use in detection of THC.
Mesozoic–Cenozoic tectonic–palaeogeographical evolution of Bayingobi Basin: response to subduction and collision of the Mongol–Okhotsk Ocean plate
Authors: Liu Bo , Hao Peng , Li Peng , Zhang Haiyun , Guo Xujie , Zhang Pengfei , Qin Yanwei
Published: March 2024

The structures, sedimentary fill and magmatic rocks of sedimentary basins are the products of regional tectonic evolution and are crucial to studying the basin's tectonic–palaeogeographical environment and regional tectonic evolution. The present study discusses the zircon U–Pb dating of volcanic rock samples,
in situ
Hf isotope and whole-rock geochemistry analysis, and the palaeogeographical, sedimentary filling and tectonic background of the Bayingobi basin through outcrop and core descriptions of Meso-Cenozoic strata, stratigraphic correlation and lithofacies analysis. The U–Pb age of the volcanic rocks is 132–102 Ma, and the
in situ
Hf isotopic values range from −20.99 to +29.48. The
87
Sr/
86
Sr and
143
Nd/
144
Nd isotopic ratios of the volcanic rocks are 0.707049–0.879761 and 0.511846–0.512540, respectively, and the Nd isotopic values range from −0.62 to −6.83. The volcanic rocks in the basin have the characteristics of continental margin island arc volcanic rocks (CAA) with loss of Nb and Ta and enrichment of Pb, originating mainly from dehydration melting of the subducting plate. The lower Cretaceous Bayingobi, Suhongtu and Yingen Formations developed specifically delta–lacustrine deposits. The lower and upper member of the Bayingobi Formation was deposited in the Berriasian to Valanginian and Valanginian to late Aptian, respectively. The Suhongtu Formation was deposited during the late Aptian to early Albian and was controlled by the strike of the Engeer Us fault. The Yingen Formation was deposited in the late faulted depression stage in the late Albian. Because of the subduction of the Mongol–Okhotsk Ocean plate in the Early Cretaceous, several depressions (sags) were formed in the Bayingobi basin, accompanied by the eruption of continental plate margin island arc magmas. With the closure of the Mongol–Okhotsk Ocean in the late Early Cretaceous, the basin was uplifted as a whole and the Upper Cretaceous Ulansuhai Formation was deposited.

Supplementary material
: Supplementary figures and tables are available at
https://doi.org/10.6084/m9.figshare.c.7105807
Multilingual Neural Machine Translation for Indic to Indic Languages
Authors: Bala Das Sudhansu , Panda Divyajyoti , Kumar Mishra Tapas , Kr. Patra Bidyut , Ekbal Asif
Published: March 2024

The method of translation from one language to another without human intervention is known as Machine Translation (MT). Multilingual neural machine translation (MNMT) is a technique for MT that builds a single model for multiple languages. It is preferred over other approaches, since it decreases training time and improves translation in low-resource contexts, i.e., for languages that have insufficient corpus. However, good-quality MT models are yet to be built for many scenarios such as for Indic-to-Indic Languages (IL-IL). Hence, this article is an attempt to address and develop the baseline models for low-resource languages i.e., IL-IL (for 11 Indic Languages (ILs)) in a multilingual environment. The models are built on the Samanantar corpus and analyzed on the Flores-200 corpus. All the models are evaluated using standard evaluation metrics i.e., Bilingual Evaluation Understudy (BLEU) score (with the range of 0 to 100). This article examines the effect of the grouping of related languages, namely, East Indo-Aryan (EI), Dravidian (DR), and West Indo-Aryan (WI) on the MNMT model. From the experiments, the results reveal that related language grouping is beneficial for the WI group only while it is detrimental for the EI group and it shows an inconclusive effect on the DR group. The role of pivot-based MNMT models in enhancing translation quality is also investigated in this article. Owing to the presence of large good-quality corpora from English (EN) to ILs, MNMT IL-IL models using EN as a pivot are built and examined. To achieve this, English-Indic Language (EN-IL) models are developed with and without the usage of related languages. Results show that the use of related language grouping is advantageous specifically for EN to ILs. Thus, related language groups are used for the development of pivot MNMT models. It is also observed that the usage of pivot models greatly improves MNMT baselines. Furthermore, the effect of transliteration on ILs is also analyzed in this article. To explore transliteration, the best MNMT models from the previous approaches (in most of cases pivot model using related groups) are determined and built on corpus transliterated from the corresponding scripts to a modified Indian language Transliteration script (ITRANS). The outcome of the experiments indicates that transliteration helps the models built for lexically rich languages, with the best increment of BLEU scores observed in Malayalam (ML) and Tamil (TA), i.e., 6.74 and 4.72, respectively. The BLEU score using transliteration models ranges from 7.03 to 24.29. The best model obtained is the Punjabi (PA)-Hindi (HI) language pair trained on PA-WI transliterated corpus.
Metabolic signatures of acute respiratory distress syndrome: COVID versus non-COVID
Authors: Ji Xiangming , Ji Hong-Long
Published: March 2024

Acute respiratory distress syndrome (ARDS) is a fatal pulmonary disorder characterized by severe hypoxia and inflammation. ARDS is commonly triggered by systemic and pulmonary infections, with bacteria and viruses. Notable pathogens include Pseudomonas aeruginosa, Streptococcus aureus, Enterobacter species, coronaviruses, influenza viruses, and herpesviruses. COVID-19 ARDS represents the latest etiological phenotype of the disease. The pathogenesis of ARDS caused by bacteria and viruses exhibits variations in host immune responses and lung mesenchymal injury. We postulate that the systemic and pulmonary metabolomics profiles of ARDS induced by COVID-19 pathogens may exhibit distinctions compared with those induced by other infectious agents. This review aims to compare metabolic signatures in blood and lung specimens specifically within the context of ARDS. Both prevalent and phenotype-specific metabolomic signatures, including but not limited to glycolysis, ketone body production, lipid oxidation, and dysregulation of the kynurenine pathways, were thoroughly examined in this review. The distinctions in metabolic signatures between COVID-19 and non-COVID ARDS have the potential to reveal new biomarkers, elucidate pathogenic mechanisms, identify druggable targets, and facilitate differential diagnosis in the future.
Endoplasmic reticulum stress enhances the expression of TLR3-induced TSLP by airway epithelium
Authors: Pathinayake Prabuddha S. , Hsu Alan C.-Y. , Nichol Kristy S. , Horvat Jay C. , Hansbro Philip M. , Wark Peter A. B.
Published: March 2024

TSLP is an epithelial-derived cytokine and a key regulator in the pathogenesis of severe uncontrolled asthma. We demonstrate a novel mechanism by which endoplasmic reticulum stress signaling upregulates airway epithelial TSLP mRNA expression via the PERK-CHOP signaling pathway and enhances TLR3-mediated TSLP protein secretion.
Functional roles of CD26/DPP4 in lipopolysaccharide-induced lung injury
Authors: Sato Shun , Kawasaki Takeshi , Hatano Ryo , Koyanagi Yu , Takahashi Yukiko , Ohnuma Kei , Morimoto Chikao , Dudek Steven M. , Tatsumi Koichiro , Suzuki Takuji
Published: March 2024

We aimed to clarify the functional roles of CD26/DPP4 in ARDS pathophysiology using Dpp4-deficient mice and siRNA reduction techniques in cultured lung cells. Our results suggest that CD26/DPP4 expression plays a proinflammatory role in alveolar macrophages while also playing a protective role in the endothelial barrier. Dpp4 genetic deficiency attenuates inflammatory responses but not permeability in LPS-induced lung injury in mice, potentially through differential roles of CD26/DPP4 expression in the resident cellular components of the lung.
Global Basic Reproduction Number of African Swine Fever in Wild Boar and a Mental Model to Explore the Disease Dynamics
Authors: Tiwari Shraddha , Dhakal Thakur , Kim Tae-Su , Kim Seong-Hyeon , Lee Sang-Joon , Yoo Dae-Sung , Cho Ho-Seong , Jang Gab-Sue , Oh Yeonsu
Published: March 2024

Basic reproduction number (R0) is a mathematical expression used in epidemiology to address expected number of secondary cases. R0 helps to predict outbreak diffusion and preventive measures. As African swine fever (ASF) is a viral infectious disease, there are significant studies related to R0 of the ASF outbreak, but most of them are investigated in a zonal and geospecific boundary. This study explores the general overview of African swine fever virus (ASFV) R0 based on existing literature and examines for the global scale using a doubling time approach using wild boar outbreaks. Further, a qualitative mental model is developed to explore the ASF disease dynamics. It was found that the average R0 was 3.56 from existing literature. Based on the global scenario, ASFV spread in wild boar was above the threshold line (R0 ≥ 1). The recent growth trend (R0 = 5.87) flagging the very high risk. ASFV is threatening the world. The qualitative mental model highlighted the veterinary services as awareness and R&D support are highlighted as the control measures. This study provides a reference to researchers and veterinarians in setting strategies of developing preventive measures and highlights the importance of awareness programs and R&D support for mitigating the ASFV spread.
Surgical Periodontal Management of Peripheral Ossifying Fibroma: A Series of Three Cases
Authors: Parsegian Karo , Arce Roger M. , Angelov Nikola
Published: March 2024

Peripheral ossifying fibroma (POF) is a benign swelling of the gingival connective tissue commonly associated with dental biofilm and biofilm‐retentive dental appliances. In the present case report, we described three cases of POF with different clinical presentations and treatment approaches. The treatment consisted of the removal of supra‐ and subgingival calculus, followed by a flap surgery with excision of the entire lesion ensuring the inclusion of the periosteal bed. The first patient developed POF during her pregnancy that remained clinically noticeable postpartum. The second case represented a rare case of POF appearing on the palatal aspect of the anterior maxilla of an African American male. The third case represented POF that developed on the mandible, and contrary to the first two cases, it was excised using a diode laser and not a scalpel blade. All patients showed uneventful healing during follow‐up appointments; however, poor patient compliance did not allow for evaluation of long‐term healing responses and possible recurrence of the lesion. Within the limitations of this clinical report, it is evident that the periodontal surgical approach was effective in managing POF with stable short‐term clinical outcomes.
Unsteady Mixed Convection Flows in a Rectangular Duct and Dynamical Behaviors of Flow Channel Insert
Authors: Liu Zhi-Hong , Wang Jie , Ni Ming-Jiu , Zhang Nian-Mei
Published: March 2024

Buoyancy‐assisted upward MHD flows and dynamical behaviors of flow channel insert (FCI) in the dual‐coolant lead‐lithium (DCLL) blanket are studied numerically. Based on our internally developed and validated solver, the dynamical behaviors of magneto‐thermo‐fluid‐structure coupled multiphysical field are investigated. A large amplitude, low frequency, and quasiperiodic unsteady reverse flow at high Re (31000), high Gr (3.5 × 1011), and moderate magnetic field (0.7~1.7T) is found in the DCLL blanket. This intricate phenomenon has been discovered for the first time, representing a combination of separate experimental results from Melnikov et al. (2016) and Khanal and Lei (2012). In our study of this large amplitude, low frequency, and quasiperiodic unsteady reverse flows, the importance of the cold helium gas to the instability of fluid flow in the bulk region and the thermal conductivity of the FCI to convection structure and instability are first found and recognized. Additionally, we take into account the effects of the temperature field and flow field on structural deformation and mechanical behavior of FCI, and we have discovered several intriguing phenomena, such as (1) the stability of fluid flow in the bulk region depends on the strength of the heat source, the magnitude of the magnetic field, and thermal conductivity of FCI; (2) the instability and periodicity of the fluid flow are primarily related to the unsteady reverse flow, which rises up and falls down periodically in the bulk region; (3) the physical mechanism of unsteady flow influenced by reverse flow, pressure drop, and Lorentz force has been concluded. It has been discovered that the breakdown of a reverse flow vortex causes a rapid reduction in pressure drop. (4) To avoid this phenomenon in engineering, a phase map of unsteady and steady flows in the DCLL blanket has been created. (5) The quasiperiodic characteristics of solid (flow channel insert) affected by flow are found and analyzed.
The Role of Pharmaceutical Innovation in Clinical Practice Guidelines for Chronic Diseases
Authors: Roach Meaghan , Land Natalie , Hernandez Jennifer , Rau Reina , Chou Jacquelyn W. , Hickson Stacey S. , Rollmann Danielle F. , Maclean J. Ross
Published: March 2024

Background. Over the last 25 years, clinical practice guidelines have emerged as a means to standardize and improve care. As pharmaceutical innovations develop, guidelines are updated to incorporate new interventions. However, the extent to which pharmacotherapies are represented as treatment options in guideline recommendations has not been well elucidated. This study aimed to quantify the role pharmacotherapy has played in clinical practice guidelines across a range of chronic diseases over the past 20 years. Methods. Clinical practice guidelines published from 2000 to 2021 were identified for five chronic diseases: ischemic heart disease (IHD), non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), Alzheimer’s disease (AD), and type 2 diabetes (T2D). Guidelines were reviewed and data on treatment recommendations were collected, including the type of intervention, line of therapy, and, for pharmacotherapies, year of regulatory approval and year of inclusion in guidelines. Results. In total, 92 clinical practice guidelines were reviewed. Among the 184 discrete recommended interventions across the five disease areas, 146 (79.3%) were pharmacotherapies, 21 (11.4%) were behavioral modifications, 6 (3.3%) were surgical interventions, and 11 (6%) were other interventions. Across guidelines, when a line of therapy was specified, behavioral modifications and pharmacotherapies were most frequently recommended as first-line interventions, whereas surgical interventions were more often recommended for subsequent lines of treatment. The time from regulatory approval of novel pharmacotherapies to inclusion in guideline recommendations varied considerably by disease area and geography. Conclusions. Across the reviewed disease areas, behavioral interventions and pharmacotherapies are shown to be critical components of clinical practice. Over the last 20 years, novel pharmaceutical innovations have been incorporated into clinical practice guideline recommendations; however, with varying speeds of adoption. Given the increasing pace of pharmacologic innovation, timely updates of clinical practice guidelines are critical to evolving the standard of care and practicing evidence-based medicine.
Exploring the Challenges in Covering Dental Services through Complementary Insurance in Iran: A Qualitative Study
Authors: Pouraskari Zahra , Yazdani Reza , Hessari Hossein
Published: March 2024

Background. Financial protection is crucial for attaining universal health coverage. The inclusion of costly dental services in insurance plans poses a significant challenge for all parties involved in the insurance sector. This study aimed to investigate the challenges of covering dental services by complementary insurance in Iran during 2020–2021. Materials and Methods. This qualitative research was conducted in Iran during 2020–2021. A triangulation of methods and data sources were employed to achieve a comprehensive perspective. In‐depth semistructured interviews were conducted on an individual basis, and all national documents, rules, regulations, and instructions pertaining to complementary dental insurance were thoroughly reviewed. Purposeful sampling was used to select participants from all stakeholder groups engaged in dental insurance coverage, including (1) health system policymakers, (2) insurers, (3) policyholders, (4) care providers (dentists), and (5) insured people. Six open‐ended questions were formulated to explore various facets of dental insurance, including (1) development, (2) management, (3) population coverage, (4) premium calculation, (5) services coverage, and (6) payment and reimbursement mechanisms. With the consent of the participants, all interviews were recorded and transcribed verbatim. The gathered data were evaluated using a framework analysis approach in the MAXQDA20 software. Finally, the primary themes, each encompassing multiple subthemes, were identified and presented. Results. A total of 26 interviews were conducted with five groups of interviewees, and nine national documents were evaluated. Six themes were extracted, which included 18 codes from the interviews and seven codes from the documents. The extracted themes were as follows: (1) Insurance commitments and service coverage, (2) reimbursement system, (3) information system, (4) economic issues, (5) population coverage, and (6) regulation and supervision. The high cost of dental services was the most frequent challenge, followed by the insurance commitments and service coverage. Conclusions. The delivery of dental services through complementary insurance in Iran primarily faces economic and service coverage challenges. The resolution hinges on the collaboration between basic and complementary insurance sectors, the development of a unified information system for insured individuals, and the implementation of a risk‐adjusted premium plan.
A Case of Hepatotoxicity Induced by Therapeutic Ketamine Use for Sedation
Authors: Yoo Noah , Thomas Sarun , Bender Michael , Cheng Xian Jie Cindy
Published: March 2024

Ketamine, initially developed as an anesthetic, has shown versatility in medical applications, including pain management, treatment‐resistant depression, and sedation in the intensive care unit (ICU). While generally well‐tolerated, long‐term use at high doses raises concerns about potential toxicities, particularly in the liver. We present a case of a 27‐year‐old female with a complex medical history who received ketamine infusion for ICU sedation and experienced a sudden rise in liver function tests (LFTs), indicating possible ketamine‐induced liver injury (KILI). The patient’s liver function normalized after ketamine discontinuation. KILI is infrequent with short‐term ketamine use, but emerging case reports suggest it may be associated with chronic or intermittent exposure. The underlying mechanisms for KILI are not fully understood but may involve the accumulation of ketamine metabolites, causing direct toxic effects on the liver. As ketamine’s use expands, especially in critical care settings, clinicians should be vigilant for the potential development of KILI. Further research is needed to better understand its risk factors and mechanisms, as early detection and management of KILI are crucial to ensuring patient safety and optimizing ketamine’s therapeutic benefits.
Evaluation of Monomer Releasing from Dentin Replacement Materials
Authors: Tuncer Nurgül Çetin , Batmaz Sevde Gül , Özdemir Sergen , Barutçugil Çağatay , Dündar Ayşe , Yıldırım Kardelen
Published: March 2024

The aim of this study is to determine and quantify the monomer elution from four different resin‐based composite dentin replacement materials for 3 months using HPLC. Four different composite dentin replacement materials were used in the present study: EverX (EVX), X‐tra base (XTB), SDR (SDR), and GrandioSO Heavy Flow (GHF). Fifteen samples from each material were prepared (5 × 5 × 4 mm). After preparation, each specimen was immersed in a 10 ml 75% ethanol/distilled water solution for three different periods: 1 h, 24 h, and 3 months (n = 5). After the immersion period, 0.5 ml of solutions were taken from each bottle and analyzed using HPLC. At the end of the 3‐month immersion period, the elution of monomers was determined mostly from SDR, GHF, EVX, and XTB, respectively. TEGDMA, the most released monomer of all groups, was released from all samples after 1 h, 24 h, and 3 months. The amount of monomer released in all composite groups at the end of the 3‐month immersion period was significantly higher than the monomer amounts released after the 1‐hour immersion period. The monomers were eluted from the composite dentin replacement materials during all immersion periods, and the amount of eluted monomers was increased with time.
Antihypertensive Property of Celery: A Narrative Review on Current Knowledge
Authors: Alobaidi Sondos , Saleh Eman
Published: March 2024

Background. The incidence of hypertension is increasing significantly on a global scale, and it is considered the leading cause of heart disease and death. Despite the availability of hypotensive drugs, they have many side effects that decrease adherence to treatments and lead to uncontrolled blood pressure. Studies have revealed that celery contains bioactive compounds that oppose hypotensive effect. Methods. A thorough literature review was conducted using Scopus, PubMed, and Google Scholar databases. To identify relevant studies on the topic, our search strategy employed keywords such as “celery,” “Apium gravenols L,” “hypertension,” “high blood pressure,” “apigenin,” “antihypertensive,” and “hypotensive.” The search was limited to articles published between January 2013 and December 2023. The inclusion criteria were original research articles that involved both animal and human subjects, published in English, and reported results applicable to the subject of this review. Review articles or articles in the form of theses or books were excluded. Results. The available evidence revealed that celery enhances blood pressure parameters. Clinical trials clarified that celery possesses its effect through many bioactive compounds, specifically 3-n-butylphthalide and apigenin. Based on animal and human studies, celery seems to elicit blood pressure regulation mainly by the vasodilatory, diuretic, and calcium channel-blocking properties. Furthermore, celery seed extract seems to exert a bradycardia effect. Conclusion. The current literature review showed a considerable number of studies on the hypertensive models, which confirmed that celery and its extracts are effective hypotensive agents. Some limitations in comparing published data should be considered, including differences in doses, extracts, species of celery, and administration form.
Comparative Effectiveness of Antidiabetic Drugs as an Additional Therapy to Metformin in Women with Polycystic Ovary Syndrome: A Systematic Review of Metabolic Approaches
Authors: Heidarpour Maryam , Mojarad Mehrzad , Mazaheri-Tehrani Sadegh , Kachuei Ali , Najimi Arash , Shafie Davood , Rezvanian Hassan
Published: March 2024

Background. Metformin is commonly prescribed to treat polycystic ovary syndrome (PCOS) patients, but in some cases, it may not be effective even at high doses or may cause intolerable side effects. Therefore, recent studies have examined the impact of combining metformin with other antidiabetic medications. Methods. A systematic search was performed in Scopus, PubMed, Web of Science, and Embase up to 30 June 2023. All interventional studies that assessed the efficacy of different antidiabetic agents were included. Results. Among the 3488 records found in the primary search, 16 papers were included. Our study showed that dipeptidyl peptidase-4 inhibitors (DPP4i) had the most significant impact on glycemic profile, while thiazolidinediones (TZDs) had the most influence on lipid levels. However, it was observed that patients taking only metformin experienced a greater increase in high-density lipoprotein cholesterol (HDL-C) levels. Glucagon-like peptide-1 receptor agonists (GLP1RAs) effectively modified various anthropometric measurements, such as weight, body mass index, waist circumference, and waist-to-hip ratio. The effects of different antidiabetic drugs on hormone levels were inconclusive, although testosterone levels were more affected by GLP1RA, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and TZDs. None of the combined therapies showed a significant change in blood pressure. Conclusion. Since PCOS is a metabolic disorder, choosing the best combination of antidiabetic drugs in the clinical course of PCOS patients will be very important. Today, it seems that we need a new metabolic approach for better treatment of the metabolic aspects of these patients.
Data from Combinatorial Chemoprevention Reveals a Novel Smoothened-Independent Role of GLI1 in Esophageal Carcinogenesis
Authors: Rizvi Sumera , DeMars Cathrine J. , Comba Andrea , Gainullin Vladimir G. , Rizvi Zaheer , Almada Luciana L. , Wang Kenneth , Lomberk Gwen , Fernández-Zapico Martin E. , Buttar Navtej S.
Published: March 2024

Abstract
Reflux-induced injury promotes esophageal adenocarcinoma, one of the most rapidly increasing, highly lethal cancers in Western countries. Here, we investigate the efficacy of a combinatorial chemoprevention strategy for esophageal adenocarcinoma and characterize the underlying molecular mechanisms. Specifically, our approach involves the use of ursodeoxycholic acid (Urso) due to its ability to decrease injury-inducing bile salts in combination with Aspirin to mitigate the consequences of injury. We find that Urso-Aspirin combination reduces the risk of adenocarcinoma in vivo in animals with reflux, decreases the proliferation of esophageal adenocarcinoma cells, and downregulates a key cell cycle regulator, CDK2. Mechanistically, using cell growth, luciferase reporter, expression, and chromatin immunoprecipitation assays, we identify GLI1, a Hedgehog-regulated transcription factor, as a novel target of Urso-Aspirin combination. We show that GLI1 is upregulated during esophageal carcinogenesis, and GLI1 can bind to the CDK2 promoter and activate its expression. Although the Urso-Aspirin combination downregulates GLI1, the GLI1 overexpression not only abrogates the effect of this combination on proliferation but it also restores CDK-2 expression. These findings support that the chemopreventive effect of the Urso-Aspirin combination occurs, at least in part, through a novel GLI1-CDK2–dependent mechanism. To further understand the regulation of CDK2 by GLI1, both pharmacologic and RNAi-mediated approaches show that GLI1 is a transcriptional activator of CDK2, and this regulation occurs independent of Smoothened, the central transducer of the Hedgehog canonical pathway. Collectively, these results identify a novel GLI1-to-CDK2 pathway in esophageal carcinogenesis, which is a bona fide target for effective combinatorial chemoprevention with Urso and Aspirin. Cancer Res; 70(17); 6787–96. ©2010 AACR.
Data from Single-Cell Transcriptomic Heterogeneity in Invasive Ductal and Lobular Breast Cancer Cells
Authors: Chen Fangyuan , Ding Kai , Priedigkeit Nolan , Elangovan Ashuvinee , Levine Kevin M. , Carleton Neil , Savariau Laura , Atkinson Jennifer M. , Oesterreich Steffi , Lee Adrian V.
Published: March 2024

Abstract
Invasive lobular breast carcinoma (ILC), one of the major breast cancer histologic subtypes, exhibits unique features compared with the well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations, but the contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single-cell RNA sequencing on a panel of IDC and ILC cell lines, and an IDC cell line (T47D) with CRISPR-Cas9–mediated E-cadherin knockout (KO). Inspection of intracell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a preadaptation signature to estrogen deprivation. Investigation of E-cadherin KO–induced alterations showed transcriptomic membranous systems remodeling, elevated resemblance to ILCs in regulon activation, and increased sensitivity to IFNγ-mediated growth inhibition via activation of IRF1. This study reveals single-cell transcriptional heterogeneity in breast cancer cell lines and provides a resource to identify drivers of cancer progression and drug resistance.
Significance:
This study represents a key step towards understanding heterogeneity in cancer cell lines and the role of E-cadherin depletion in contributing to the molecular features of invasive lobular breast carcinoma.
Data from LncRNA SAMMSON Mediates Adaptive Resistance to RAF Inhibition in BRAF-Mutant Melanoma Cells
Authors: Han Shujun , Yan Yuwei , Ren Yibo , Hu Yiming , Wang Yan , Chen Lei , Zhi Zhe , Zheng Yan , Shao Yongping , Liu Jiankang
Published: March 2024

Abstract
The long noncoding RNA (lncRNA) SAMMSON is required for human melanoma cell growth and survival. However, whether SAMMSON regulates the response of mutant BRAF melanoma cells to RAF inhibitors remains unknown. In this work, we showed that SAMMSON is rapidly induced upon inhibition of ERK signaling, and SAMMSON overexpression conferred resistance to vemurafenib-induced cytotoxicity in melanoma cells. SOX10 mediated transcriptional induction of SAMMSON by vemurafenib, and SOX10 sumoylation at K55 was essential for this function. In addition, depletion of SAMMSON activated p53 signaling, which is dependent on the SAMMSON-interacting protein CARF. Depletion of SAMMSON sensitized mutant BRAF melanoma cells to RAF inhibitors in vitro and in vivo, while CARF knockdown reversed the enhanced sensitivity. In summary, these findings suggest that SAMMSON may function as a new mediator of adaptive resistance to RAF inhibitors in melanoma by modulating CARF-p53 signaling.
Significance:
This study highlights the role of a SAMMSON/CARF/p53 signaling axis in modulating the adaptive resistance of mutant BRAF melanoma to RAF inhibitors.
Data from Extracellular Vesicle-Mediated Transfer of LncRNA IGFL2-AS1 Confers Sunitinib Resistance in Renal Cell Carcinoma
Authors: Pan Yihui , Lu Xuanxuan , Shu Guannan , Cen Junjie , Lu Jun , Zhou Mi , Huang Kangbo , Dong Jiaqi , Li Jiaying , Lin Haishan , Song Hongde , Xu Quanhui , Han Hui , Chen Zhenhua , Chen Wei , Luo Junhang , Wei Jinhuan , Zhang Jiaxing
Published: March 2024

Abstract
Sunitinib resistance remains a serious challenge to the treatment of advanced and metastatic renal cell carcinoma (RCC), yet the mechanisms underlying this resistance are not fully understood. Here, we report that the long noncoding RNA IGFL2-AS1 is a driver of therapy resistance in RCC. IGFL2-AS1 was highly upregulated in sunitinib-resistant RCC cells and was associated with poor prognosis in patients with clear cell RCC (ccRCC) who received sunitinib therapy. IGFL2-AS1 enhanced TP53INP2 expression by competitively binding to hnRNPC, a multifunctional RNA-binding protein that posttranscriptionally suppresses TP53INP2 expression through alternative splicing. Upregulated TP53INP2 enhanced autophagy and ultimately led to sunitinib resistance. Meanwhile, IGFL2-AS1 was packaged into extracellular vesicles through hnRNPC, thus transmitting sunitinib resistance to other cells. N6-methyladenosine modification of IGFL2-AS1 was critical for its interaction with hnRNPC. In a patient-derived xenograft model of sunitinib-resistant ccRCC, injection of chitosan-solid lipid nanoparticles containing antisense oligonucleotide-IGFL2-AS1 successfully reversed sunitinib resistance. These findings indicate a novel molecular mechanism of sunitinib resistance in RCC and suggest that IGFL2-AS1 may serve as a prognostic indicator and potential therapeutic target to overcome resistance.
Significance:
Extracellular vesicle-packaged IGFL2-AS1 promotes sunitinib resistance by regulating TP53INP2-triggered autophagy, implicating this lncRNA as a potential therapeutic target in renal cell carcinoma.
Data from Phage Display-Derived Peptide-Based Dual-Modality Imaging Probe for Bladder Cancer Diagnosis and Resection Postinstillation: A Preclinical Study
Authors: Peng Li , Shang Wenting , Guo Pengyu , He Kunshan , Wang Hongzhi , Han Ziyu , Jiang Hongmei , Tian Jie , Wang Kun , Xu Wanhai
Published: March 2024

Abstract
Bladder cancer is a common human malignancy. Conventional ultrasound and white-light cystoscopy are often used for bladder cancer diagnosis and resection, but insufficient specificity results in a high bladder cancer recurrence rate. New strategies for the diagnosis and resection of bladder cancer are needed. In this study, we developed a highly specific peptide-based probe for bladder cancer photoacoustic imaging (PAI) diagnosis and near-infrared (NIR)-imaging-guided resection after instillation. A bladder cancer–specific peptide (PLSWT7) was selected by in vivo phage-display technology and labeled with IRDye800CW to synthesize a bladder cancer–specific dual-modality imaging (DMI) probe (PLSWT7-DMI). The feasibility of PLSWT7-DMI–based dual-modality PAI-NIR imaging was assessed in vitro, in mouse models, and ex vivo human bladders. An air-pouch bladder cancer (APBC) model suitable for probe instillation was established to evaluate the probe-based bladder cancer PAI diagnosis and NIR-imaging–guided resection. Human bladders were used to assess whether the PLSWT7-DMI–based DMI strategy is a translatable approach for bladder cancer detection and resection. The probe exhibited excellent selectivity and specificity both in vitro and in vivo. Postinstillation of the probe, tumors <3 mm were detectable by PAI, and NIR-imaging–guided tumor resection decreased the bladder cancer recurrence rate by 90% and increased the survival in the mouse model. Additionally, ex vivo NIR imaging of human bladders indicated that PLSWT7-DMI–based imaging would potentially allow precise resection of bladder cancer in clinical settings. This PLSWT7-DMI–based DMI strategy was a translatable approach for bladder cancer diagnosis and resection and could potentially lower the bladder cancer recurrence rate. Mol Cancer Ther; 17(10); 2100–11. ©2018 AACR.