bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenomedullin has a pivotal role in trophoblast differentiation: A promising nanotechnology-based therapeutic target for early-onset preeclampsia
Authors: Zhang Qingqing , Lee Cheuk-Lun , Yang Tingyu , Li Jianlin , Zeng Qunxiong , Liu Xiaofeng , Liu Zhongzhen , Ruan Degong , Li Zhuoxuan , Kan Anita S. Y. , Cheung Ka-Wang , Mak Annisa S. L. , Ng Vivian W. Y. , Zhao Huashan , Fan Xiujun , Duan Yong-Gang , Zhong Liuying , Chen Min , Du Meirong , Li Raymond H. W. , Liu Pengtao , Ng Ernest H. Y. , Yeung William S. B. , Gao Ya , Yao Yuanqing , Chiu Philip C. N.
Published: November 2023

Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation of its phenotypes is in late pregnancy. There is no reliable method for early prediction and treatment of EOPE. Adrenomedullin (ADM) is an abundant placental peptide in early pregnancy. Integrated single-cell sequencing and spatial transcriptomics confirm a high ADM expression in the human villous cytotrophoblast and syncytiotrophoblast. The levels of ADM in chorionic villi and serum were lower in first-trimester pregnant women who later developed EOPE than those with normotensive pregnancy. ADM stimulates differentiation of trophoblast stem cells and trophoblast organoids in vitro. In pregnant mice, placenta-specific ADM suppression led to EOPE-like phenotypes. The EOPE-like phenotypes in a mouse PE model were reduced by a placenta-specific nanoparticle-based forced expression of ADM. Our study reveals the roles of trophoblastic ADM in placental development, EOPE pathogenesis, and its potential clinical uses.
Acceleration and deceleration of chirality inversion speeds in a dynamic helical metallocryptand by alkali metal ion binding
Authors: Ikbal Sk Asif , Zhao Pei , Ehara Masahiro , Akine Shigehisa
Published: November 2023

We report that the chirality inversion kinetics of a trinickel(II) cryptand can be controlled by guest recognition in the cryptand cavity. When the guest was absent, the nickel(II) cryptand underwent a dynamic interconversion between the
P
and
M
forms in solution, preferring the
M
form, with a half-life of
t
1/2
= 4.99 min. The
P
/
M
equilibrium is reversed to
P
-favored by binding with an alkali metal ion in the cryptand cavity. The timescale of this
M→P
inversion kinetics was both notably accelerated and decelerated by the guest binding (
t
1/2
= 0.182 min for K
+
complex; 186 min for Cs
+
complex); thus, the equilibration rate constants differed by up to 1000-fold depending on the guest metal ions. This acceleration/deceleration can be explained in terms of the virtual binding constants at the transition state of the
P
/
M
chirality inversion; K
+
binding more stabilizes the transition state rather than the
P
and
M
forms to result in the acceleration.
Trends in the susceptibility of U.S.
Acinetobacter baumannii-calcoaceticus
species complex and
Stenotrophomonas maltophilia
isolates to minocycline, 2014–2021
Authors: Pfaller Michael A. , Shortridge Dee , Carvalhaes Cecilia G. , Castanheira Mariana
Published: November 2023

Acinetobacter baumannii
-
calcoaceticus
species complex (ACB) and
Stenotrophomonas maltophilia
(SM) are opportunistic, non-fermentative organisms that can cause serious hospital-acquired infections in immunocompromised patients. These pathogens are inherently resistant to several common drug classes and often acquire other resistance mechanisms, making them difficult to treat. In this study, we analyzed the susceptibility of 1,029 contemporary ACB and 1,522 SM isolates to minocycline (MIN) and levofloxacin (LEV) as well as meropenem (MER) for ACB and trimethoprim-sulfamethoxazole (TMP/SMX) for SM using the CLSI broth microdilution method. Isolates were collected as a part of the SENTRY Antimicrobial Surveillance Program from 2014 to 2021. Pneumonia in hospitalized patients was the most common infection from which ACB (57.0%) and SM (73.9%) were isolated. MIN had the highest
in vitro
activity for ACB (86.2%) and SM (99.5%). The activity of ACB and SM to all three agents varied over the period studied. MIN activity to ACB decreased in 2020 (80.6%) but rebounded in 2021 (86.2%). LEV and MER showed an overall trend of increasing susceptibility for ACB, with slightly lower activity in 2020–2021. MIN and TMP/SMX (>98.3% and >93.7%, respectively) activities were stable against SM isolates. LEV activity decreased from 84.3% (2015) to 69.2% (2018). The activity of MIN remained stable and higher than other agents tested for both ACB and SM, pathogens that have limited therapeutic alternatives. These
in vitro
data suggest that MIN is a useful treatment option for infections caused by ACB or SM.

IMPORTANCE

Acinetobacter baumannii-calcoaceticus
species complex and
Stenotrophomonas maltophilia
are opportunistic, non-fermentative Gram-negative organisms that can cause serious hospital-acquired infections in immunocompromised patients. These pathogens are inherently resistant to several common drug classes and often acquire other resistance mechanisms, making them difficult to treat. In this study, we analyzed the trends of susceptibility of over 2,500 U.S. bacterial isolates collected from hospitalized patients over an 8-year period to minocycline, which is used to treat infections caused by these pathogens. These
in vitro
data suggest that minocycline is a useful treatment option for infections caused by
Acinetobacter baumannii-calcoaceticus
species complex or
Stenotrophomonas maltophilia
.
Rare case of duplicated middle cerebral artery and acute ischaemic stroke managed successfully with mechanical thrombectomy
Authors: Phuyal Subash , Thapa Lekhjung , Mishra Biswa Mohan , Nayak Manoj Kumar
Published: November 2023

A man in his early 80s presented with acute onset aphasia and right-sided weakness with an NIH Stroke Scale (NIHSS) of 17. He was last seen normal 9 hours before the presentation. MRI of the brain showed acute infarcts in the left caudate, lentiform nucleus and corona radiata. MRI angiogram (MRA) revealed an occluded left main middle cerebral artery (MCA) and an associated ipsilateral patent duplicated middle cerebral artery (DMCA). Mechanical thrombectomy (MT) was performed, and he was discharged with an NIHSS of 8. In this report, we review and discuss the challenges during the intervention of MCA occlusion in the presence of duplicated MCA, a rare anomaly.
Sciatic nerve palsy after direct anterior approach for total hip replacement
Authors: Prakash Saket , Rai Alok , Manhas Vikrant , Malhotra Rajesh
Published: November 2023

Sciatic nerve injury after total hip replacement is rare with a reported incidence of about 0.09%–3.7%. The most commonly reported causes include traction on the nerve during reduction, compression of the nerve from subfascial haematoma, significant leg lengthening, improper retractor placement, thermal burns from cautery and extraneous cement. We present a case of complete sciatic nerve palsy in a patient operated on using direct anterior approach (DAA). To date, there are no reports describing sciatic nerve palsy secondary to haematoma immediately after primary arthroplasty through the DAA. We performed an MRI of lumbosacral spine with both hips, which revealed a haematoma. Consequently, we promptly took the patient to the operation theatre for re-exploration. Using the same approach, we dislocated the hip and removed the clots. By the end of 2 weeks, the patient was able to dorsiflex the ankle and had fully recovered from sciatic nerve palsy.
Spontaneous muscle haematoma in a patient with cirrhosis
Authors: Suja Lakshmanan , Logithasan Nanthakumar , Senthil Narayanasamy , Anil Archa Anna
Published: November 2023

Decompensated liver disease is associated with alterated haemostasis that can either lead to spontaneous bleeding or development of thrombosis. Alcohol consumption coupled with advanced liver disease favours spontaneous bleeding. There have been only few documented cases of spontaneous muscle haematoma (SMH) in patients with cirrhosis. The pathogenesis of SMH is hypothesised to be multifactorial and it has been seen in patients on anticoagulation or with haemostatic disorders. We report a case of alcohol-related cirrhosis presenting with an expanding, voluminous haematoma in the intermuscular plane between the trapezius and the teres major muscles. This patient also had a retroperitoneal haemorrhage, clinically evidenced by the Grey Turner’s and Cullen’s signs. Haemorrhage was confirmed radiologically by CT. The patient was managed in an intensive care facility and treated with multiple blood products, including packed red blood cells, fresh frozen plasma and cryoprecipitates. However, as his clinical condition deteriorated, he required surgical intervention by incision and drainage, followed by evacuation. Early identification of coagulopathy and aggressive treatment are essential in these cases of cirrhosis to avoid unfavourable outcomes.
Severe lactic acidosis during tenofovir disoproxil fumarate and cobicistat combination for HIV patient
Authors: Isoda Atsushi , Mihara Masahiro , Matsumoto Morio , Sawamura Morio
Published: November 2023

Lactic acidosis is a rare but serious side effect in individuals receiving nucleoside reverse transcriptase inhibitors. An underweight woman with HIV was admitted to our hospital because of nausea and diffuse myalgia. Her antiretroviral regimen had been changed to tenofovir disoproxil fumarate (TDF)/emtricitabine and darunavir/cobicistat 3 months prior, after which her renal function had gradually declined. After admission, she was diagnosed with lactic acidosis, and a liver biopsy suggested mitochondrial damage. Her plasma tenofovir levels were elevated at the onset of lactic acidosis. We hypothesise that the patient’s low body weight, combined with the addition of cobicistat, induced renal dysfunction and led to elevated plasma tenofovir concentrations, resulting in mitochondrial damage and lactic acidosis. Careful monitoring of renal function and lactic acidosis is required during use of TDF-containing regimens for underweight HIV patients, particularly when combined with cobicistat.
Pathogenic variant inSERPING1gene causing autosomal dominant hereditary angioedema in early childhood
Authors: Kron Kevin , Joshi Shyam
Published: November 2023

A female in early childhood presented with 6 months of transient swelling of multiple areas of her body, often, but not always, associated with minor trauma. Labs drawn were significant for low C4, low CH50, low C1 esterase inhibitor (C1-INH) antigen and low C1-INH function, which is concerning for hereditary angioedema (HAE) with abnormal C1-INH. Genetic testing through the Invitae Hereditary Angioedema Panel revealed a variant in theSERPING1gene, c.686-7C>G (Intronic), which was classified as a variant of unknown significance, but is likely pathogenic given patient’s clinical presentation and recent functional proof of pathogenicity. HAE should be recognised in paediatric patients even without family history. Recognising the symptoms of HAE and confirming diagnosis in early childhood has become more important recently as the first prophylactic therapy, lanadelumab, was approved in February 2023 for long-term prophylaxis in early childhood, which can significantly improve morbidity and quality of life.
Half-wormholes and ensemble averages
Authors: Peng Cheng , Tian Jia , Yang Yingyu
Published: November 2023

Recently, the concept of half-wormholes is introduced to give a resolution to the factorization puzzle in holography and help understand better the relation between ensemble average theories and gravity in the bulk. Half-wormholes are proposed to be the contributions to the gravitational path integral that correspond to fluctuations of each individual theory around the average of the whole ensemble of theories. In this paper, we further explore the extent to which the half-wormhole interpretation is applicable. In particular, to further demonstrate that the half-wormhole interpretation is not merely a feature of a specific theory but is a general feature of ensemble average theories, we examine various models, including different enriched 0-dimensional SYK-like models, the 1-dimensional Brownian SYK model and its generalization. To further demonstrate that the half-wormhole interpretation applies to more general probability distributions apart from the zero-mean Gaussian distribution, we consider random couplings with other non-trivial moments. Specifically, introducing a non-trivial mean value to the random coupling renders the spectral correlators to exhibit both disconnected saddles and connected saddles. The inclusion of higher-order moments leads to new “multi-linked half-wormhole” saddles. We also clarify the distinctions between the unlinked half-wormhole and the linked half-wormhole in our modified Brownian SYK model.
An anisotropic area-preserving flow and its geometric application
Authors: Yang Yunlong , Liu Lina
Published: November 2023

This paper centers its attention on an anisotropic area-preserving flow with the goal of establishing the existence of smooth solutions to the even, planar logarithmic Minkowski problem by the asymptotic behavior of this flow.
DIGITAL ECONOMY DEVELOPMENT AND URBAN ECONOMIC RESILIENCE: EVIDENCE AT CHINA’S CITY LEVEL
Authors: ZHONG MIN , XU SHULIN , ZENG XIHAO
Published: November 2023

In the face of uncertainty in the global economy’s development, this paper investigates the relationships between the growth of digital economy and economic resilience using Chinese cities data spanning 2011 to 2019. Results indicate that the growth of the digital economy is positively related to economic resilience, which still holds after robustness tests. The effect is heterogeneous by city type, city location and stage of growth for the digital economy. The impact mechanism of the two is explored from a supply and demand standpoint such as industrial upgrading, innovation, green development, population agglomeration, income gap and market integration.
Design and construction of tunable solid-state dye laser pumped by flashlamp
Authors: Al-Shamiri Hamdan A. S.
Published: November 2023

Over the past six decades, dye laser technology has improved substantially. The usage of solid matrices containing laser dyes is becoming more and more popular as a viable substitute for the traditional liquid dye solutions. In this research, we designed and built a tunable solid dye laser device which consists of three main parts. (i) The active material producing the laser beam, which is a polymer rod [glycidyl methacrylate (GMA) polymer] doped with the laser dyes pyrromethene 597 (PM-597) or Nile blue (Nb-690). (ii) The pumping source is xenon linear flashlamp driven by a homemade power supply. (iii) Two broadband mirrors providing the optical feedback stable optical resonator. The properties of the gain medium and hence the laser emission characteristics were determined, and the results showed the efficiency of the homemade tunable solid dye laser device, that is suitable for a variety of applications.
Minimal generating sets of moves for surfaces immersed in the four-space
Authors: Jabłonowski Michał
Published: November 2023

For immersed surfaces in the four-space, we have a generating set of the Swenton–Hughes–Kim–Miller spatial moves that relate singular banded diagrams of ambient isotopic immersions of those surfaces. We also have Yoshikawa–Kamada–Kawauchi–Kim–Lee planar moves that relate marked graph diagrams of ambient isotopic immersions of those surfaces. One can ask if the former moves form a minimal set and if the latter moves form a generating set. In this paper, we derive a minimal generating set of spatial moves for diagrams of surfaces immersed in the four-space, which translates into a generating set of planar moves. We also show that the complements of two equivalent immersed surfaces can be transformed one another by a Kirby calculus not requiring the 1-1-handle or 2-1-handle slides. We also discuss the fundamental group of the immersed surface-link complement in the four-space and a quandle coloring invariant of an oriented immersed surface-link.
EXPERIMENTAL ANALYSIS OF WIRE-EDM ON SUB-COOLED LOW-CARBON TOOL STEEL USING HYBRID MARCOS METHOD AND HONEY BADGER ALGORITHM
Authors: PRIYADARSHINI MANISHA , PRADHAN SWASTIK , BARUA ABHISHEK , BEHERA AJIT , KANCHAN SUMIT
Published: November 2023

AISI P20 tool steel is commonly used for engineering of die holders, rails, plastic molds, wear strips, bolsters, shafts, and backers. When normally heated and sub-cooled, it experiences metallurgical modifications. Because the essential aspect of the “wire-electro discharge machine (WEDM)” is product finishing, this research examines the parametric responses when machining parent metal and sub-cooled metal (AISI P20). Thus, it is always necessary to choose a proper parametric arrangement for reaching maximum material removal rate (MRR), cutting speed with minimum surface roughness (SR), and kerf width. The effects of pulse on time, wire speed, discharge current, wire tension, and flushing pressure on individual machining reactions are also discussed in this study. An orthogonal array was created using Taguchi’s mixed experimental approach. The measurement alternatives and ranking according to compromise solution (MARCOS) method, the Honey Badger Algorithm, and the Taguchi-MARCOS method are engaged to obtain the important machining constraints and the optimal parametric settings for each response. When compared to the parent material, sub-cooled material has a greater cutting speed, SR, kerf breadth, and MRR. Here, cutting speed, MRR, and fitness were maximized along with minimization of SR and kerf width using the Honey Badger Algorithm as compared to both the MARCOS and Taguchi-MARCOS methods. According to ANOVA, for both parent and sub-cooled material, discharge current was the most significant and influential factor. The sub-cooled material’s machined surface contains smaller deposits and more spherical globules than the parent material, which has bigger melted deposits.
Cohomology of partially ordered sets and ext’s
Authors: Sancho de Salas Fernando
Published: November 2023

We give an elementary proof and broadly generalize a formula of Brun et al. on the local cohomology of section rings.
Factorization in group algebras
Authors: Benelmekki M. , El Baghdadi S. , Najib S.
Published: November 2023

Let [Formula: see text] be a field, and let [Formula: see text] be a torsion-free abelian group. In this paper, we study some factorization properties in the group algebra of [Formula: see text] over [Formula: see text], [Formula: see text]. Among other results, we obtain necessary and sufficient conditions in order that [Formula: see text] should be an idf-domain. As an application, we get various results concerning factorization in [Formula: see text].
A Perspective on Cognitive Robot Research and Development
Authors: Kawamura Kazuhiko
Published: November 2023

The purpose of this paper is to present my personal journey in the last 30-plus years of research and development efforts on a cognitive robotic system called Intelligent Soft Arm Control (ISAC). In doing so, I will highlight how our team approached solving certain robot intelligence, communication, and control problems.
A New Approximation Method for Multi-Pantograph Type Delay Differential Equations Using Boubaker Polynomials
Authors: Yüzbaşı Şuayip , Çetin Beyza
Published: November 2023

In this paper, a new approaching technique is offered to unravel multi-pantograph-type delay differential equations. The suggested new method is a collocation method based on integration and Boubaker polynomials. As the main idea of the method, the process starts by approaching the first derivative function in the equation in the form of truncated Boubaker series. Then this approximating form is composed in the matrix form. The unknown function is then obtained by integrating the approximate derivative function and expressing it as a matrix. Using the approximation, the matrix forms for the proportionally delayed terms in the equation are derived. In addition, operational matrix forms are constructed for convenience in the method. By using these matrix forms and matrix operations, the problem is reduced to a system of algebraic linear equations. The method is illustrated through numerical implementations and compared with existing techniques in the literature. The results demonstrate the effectiveness and reliability of the proposed approach, highlighting its superiority over other methods.
Redefining the Innovation Capacity of Design Thinking Approach Through In-Depth Understanding of Designerly Capabilities
Authors: Faridizad Amir Masoud , Naghizadeh Mohammad , Ghazinoori Soroush , Mirvahedi Saeed
Published: November 2023

In recent years, there has been growing interest in studying design thinking from a capability perspective, given the need for deep implementation at the organizational mindset level. However, the impact of the cognitivist paradigm on design thinking has led to a narrow conceptualization of it as a problem-solving process, which overlooks some of its essential capacities. As a result, the ability of design thinking to extract the real capabilities of designers has been weakened. To address this shortcoming, this study focused on extracting designerly capabilities from the original resource by engaging with designers themselves. In-depth interviews were conducted, and the results were thematically analyzed. The findings reveal that designerly capabilities are significantly different in depth and scope from those derived from the conventional academic view of design thinking. The study identifies some key features of design thinking as practiced by real designers, as follows: Engaging with multiple layers of a problem, Skipping and releasing ideas, Adjusting iteratively, Recognizing patterns, Translating concepts, Incorporating and extending existing solutions, and Balancing ambiguity and clarity, as well as Envisioning and imagining possibilities, Expanding the scope of inquiry and Facilitating confrontation and feedback. These features can be grouped into four dimensions: (1) reflection, (2) generation, (3) inspiration and (4) engagement, which show the dynamic capability of design thinking. This complements previous research and suggests ways to improve the innovation potential of design thinking in organizations.
Research on the Absorption Performance of Silicon-Based Pyramidal Microstructure with Ultra-Low Reflectivity
Authors: Fang Zhiwei , Wang Kai , Gao Kai , Ge Daohan , Zhang Liqiang
Published: November 2023

Anti-reflective structure can effectively suppress the light reflection on the surface of the object, thereby increasing the absorption of light, it has a wide range of applications in photovoltaics, such as optical sensors and photodetectors. Due to the limitation of low refractive index materials, it is difficult for existing anti-reflective coatings to achieve the expected low reflectance effect. Based on Maxwell’s electromagnetic wave theory, this paper uses Finite-Difference Time-Domain (FDTD)-solutions software to research the reflection spectrum of silicon-based pyramidal microstructure in the wavelength range of 200–1400nm, explores the influence of the height (H) and bottom side length (L) of the pyramidal on its reflection spectrum, and studies the changes of its electromagnetic field. On this basis, the absorption performance of the silicon-based pyramidal microstructure is further studied, and it is found that the absorption efficiency of silicon-based pyramidal microstructure for ultraviolet light reaches almost 100%, which provides important significance for its application in optical sensors and photodetectors.
Ride comfort of patient transport robot chassis
Authors: Chen Ya , Cui Zhiguo , wang Dianjun , Zhu Yadong , wang Peng
Published: November 2023

The ride comfort is a significant property of patient transport robots, which is directly related to the performance of rescue instruments and the cause of secondary damage. Previous studies overlook the design optimization of patient transport robots to improve ride comfort in hospital environments. This study designs a mobility system with an improved chassis that enables a more comfortable ride for patients. The system incorporates a longitudinal arm-independent suspension, which has a regulating device that changes the shock absorber angle and longitudinal arm length. A four-wheel vibration coupling response model of the robot vehicle is established. An optimization model with variable stiffness and damping coefficients is built and analyzed. The effective and maximum values of the body’s vertical, pitch angular, and roll angular accelerations are used as evaluation criteria of the robot’s ride comfort, which is analyzed on random roads and roadblocks, comparing its performance before and after the optimization. The results show that the weighted acceleration of the optimized body reduces by 61.9%, and the optimized suspension system improves the overall robot’s ride comfort. The evaluation indices of the optimized robot are measured through experiments. The weighted acceleration in the three directions of the optimized body is 0.18[Formula: see text]m/s2, which is less than 0.315[Formula: see text]m/s2 as required by ISO 2631-1, indicating that the patient does not feel uncomfortable, rendering an excellent evaluation, and verifying the rationality of the suspension system modeling analysis. The establishment of the multi-objective optimization model provides a theoretical basis for improving the ride comfort of mobile robots.
DAG-Order: An Order-Based Dynamic DAG Scheduling for Real-Time Networks-on-Chip
Authors: Chen Peng , Chen Hui , Liu Weichen , Long Linbo , Chang Wanli , Guan Nan
Published: November 2023

With the high-performance requirement of safety-critical real-time tasks, the platforms of many-core processors with high parallelism are widely utilized, where network-on-chip (NoC) is generally employed for inter-core communication due to its scalability and high efficiency. Unfortunately, large uncertainties are suffered on NoCs from both the overly parallel architecture and the distributed scheduling strategy (e.g., wormhole flow control), which complicates the response time upper bounds estimation (i.e., either unsafe or pessimistic). For DAG-based real-time parallel tasks, to solve this problem, we propose DAG-Order, an order-based dynamic DAG scheduling approach, which strictly guarantees NoC real-time services. First, rather than build the new analysis to fit the widely used best-effort wormhole NoC, DAG-Order is built upon a kind of advanced low-latency NoC with SLT (
S
ingle-cycle
L
ong-range
T
raversal) to avoid the unpredictable parallel transmission on the shared source-destination link of wormhole NoCs. Second, DAG-Order is a non-preemptive dynamic scheduling strategy, which jointly considers communication as well as computation workloads, and fits SLT NoC. With such an order-based dynamic scheduling strategy, the provably bound
safety
is ensured by enforcing certain order constraints among DAG edges/vertices that eliminate the execution-timing anomaly at runtime. Third, the order constraints are further relaxed for higher average-case runtime performance without compromising bound safety. Finally, an effective heuristic algorithm seeking a proper schedule order is developed to
tighten
the bounds. Experiments on synthetic and realistic benchmarks demonstrate that DAG-Order performs better than the state-of-the-art related scheduling methods.
Finite Element Analysis of the Shear Capacity of Recycled Aggregate Concrete Beams with Corroded Stirrups
Authors: Zou Zhenghao , Zhao Lin , Wu Jin , Chen Fang , Yang Guojiao , You Qing , Chen Zhiyou , Zhang Chenglin , Rao Li , Liu Xianger
Published: November 2023

In this paper, a model to predict the residual shear capacity of RAC beams with corroded stirrups was established, and the simulation analysis was conducted on recycled concrete beams with different corrosion level using ANSYS. The reliability of the finite element analysis model was verified by comparing the finite element results with experimental results.
Deep Learning‐Based Ensembling Technique to Classify Alzheimer’s Disease Stages Using Functional MRI
Authors: Tajammal Taliah , Khurshid Syed Khaldoon , Jaleel Abdul , Qayyum Wahla Samyan , Ziar Riaz Ahmad
Published: November 2023

The major issue faced by elderly people in society is the loss of memory, difficulty learning new things, and poor judgment. This is due to damage to brain tissues, which may lead to cognitive impairment and eventually Alzheimer’s. Therefore, the detection of such mild cognitive impairment (MCI) becomes important. Usually, this is detected when it is converted into Alzheimer’s disease (AD). AD is irreversible and cannot be cured whereas mild cognitive impairment (MCI) can be cured. The goal of this research is to diagnose Alzheimer’s patients for timely treatment. For this purpose, functional MRI images from the publicly available dataset are used. Various deep‐learning models have been used by the scientific community for the automatic detection of Alzheimer’s subjects. These include the binary classification of scans of patients into MCI and AD stages, and limited work is carried out for multiclass classification of Alzheimer’s disease up to six different stages. This study is divided into two steps. In the first step, a binary classification of the subject’s scan is performed using Custom CNN. The second step involves the use of different deep learning models along with Custom CNN for multiclass classification of a subject’s scan into one of the six stages of Alzheimer’s disease. The models are evaluated based on different evaluation metrics, and the overall result of the models is improved using the max‐voting ensembling technique. The experimental results show that an overall average accuracy of 98.8% is achieved for Alzheimer’s stages classification.
Study of the Roof Deformation Characteristics of Roadway Excavation Face and Unsupported Roof Distance
Authors: Zhang Jie , Gao Shoushi , He Yifeng , Yang Tao , Wang Bing , Wang Li , Pang Haibo , Peng Bing
Published: November 2023

In order to address the issue of slow excavation speed caused by various factors affecting the stability of the roof in the excavation face and the unreasonable distance of the unsupported roof, a mechanical model of the roof in the excavation face area is established. This model is based on the superposition method in the material mechanics. The immediate roof deflection curve equation and the maximum unsupported roof distance discriminant formula of the heading head are derived. The allowable deflection is used as the discriminant method of the maximum unsupported roof distance. The calculation method of the key parameters in the formula is obtained and compared with the existing maximum unsupported roof distance calculation formula. Using the single-variable sensitivity analysis method and the bivariate interaction analysis method, we determine the key factors affecting the deformation of the roof in the excavation face and their interaction relationships. The results indicate that among the 10 factors affecting the deformation of the roof in the temporary support area of the excavation face, there are 3 key factors. Under unchanged geological and mechanical conditions, the deformation of the roof primarily depends on the length of the temporary support area and the temporary support load. To provide a practical example, we calculate the maximum unsupported roof distance of 30304 tailgate in the Yanghuopan Coal Mine to be 3.4 m. Numerical simulation and field monitoring results confirm that the deformation of the roof in the excavation face is minimal, and the stability of the rock is good.
Mathematical Modeling Identifies Optimum Palbociclib-fulvestrant Dose Administration Schedules for the Treatment of Patients with Estrogen Receptor–positive Breast Cancer
Authors: Cheng Yu-Chen , Stein Shayna , Nardone Agostina , Liu Weihan , Ma Wen , Cohen Gabriella , Guarducci Cristina , McDonald Thomas O. , Jeselsohn Rinath , Michor Franziska
Published: November 2023

Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors such as palbociclib are approved for the treatment of metastatic estrogen receptor–positive (ER+) breast cancer in combination with endocrine therapies and significantly improve outcomes in patients with this disease. However, given the large number of possible pairwise drug combinations and administration schedules, it remains unclear which clinical strategy would lead to best survival. Here, we developed a computational, cell cycle–explicit model to characterize the pharmacodynamic response to palbociclib-fulvestrant combination therapy. This pharmacodynamic model was parameterized, in a Bayesian statistical inference approach, using in vitro data from cells with wild-type estrogen receptor (WT-ER) and cells expressing the activating missense ER mutation, Y537S, which confers resistance to fulvestrant. We then incorporated pharmacokinetic models derived from clinical data into our computational modeling platform. To systematically compare dose administration schedules, we performed in silico clinical trials based on integrating our pharmacodynamic and pharmacokinetic models as well as considering clinical toxicity constraints. We found that continuous dosing of palbociclib is more effective for lowering overall tumor burden than the standard, pulsed-dose palbociclib treatment. Importantly, our mathematical modeling and statistical analysis platform provides a rational method for comparing treatment strategies in search of optimal combination dosing strategies of other cell-cycle inhibitors in ER+ breast cancer.

Significance:

We created a computational modeling platform to predict the effects of fulvestrant/palbocilib treatment on WT-ER and Y537S-mutant breast cancer cells, and found that continuous treatment schedules are more effective than the standard, pulsed-dose palbociclib treatment schedule.
Efficacy of a Non-Pharmacological Intervention in Seasonal Allergic Rhinitis Symptoms
Authors: Caimmi Davide , Clark Evangéline , Fogel Paul , Heddebaut Nicolas , Aubier Michel , Demoly Pascal
Published: November 2023

Background: Patients suffering from allergic rhinitis seek for several therapeutic symptomatic options, including nonconventional treatments, to control their symptoms. Objectives: Through the present proof-of-concept study, we prospectively investigated the potential role of Puressentiel® nasal protection spray (SNPA) in patients suffering from cypress pollen allergic rhinitis. Methods: In 15 adults, we performed two nasal provocation tests, with a cypress pollen extract, with a 15-day interval, with and without previous randomized administration of SNPA, and evaluated a nasal symptom score, the nasal inspiratory peak flow, and the concentration of inflammatory cytokines in the nasal lavage after the procedures. Results: Comparing results in patients challenged with and without the SNPA spray before the nasal challenge, we found a 57% mean decrease in symptoms, and a 62% average difference in inspiratory peak flow, after the use of the spray. Conclusions: Puressentiel® SNPA is effective in reducing nasal symptoms, as assessed by nasal symptoms score and nasal inspiratory peak flow, and could be a valid natural non-pharmacological option in patients suffering from allergic rhinitis.
The Clearance of Midazolam and Metabolites during Continuous Renal Replacement Therapy in Critically Ill Patients with COVID-19
Authors: Smeets Tim J.L. , de Geus Hilde R.H. , Valkenburg Abraham J. , Baidjoe Lauren , Gommers Diederik A.M.P.J. , Koch Birgit C.P. , Hunfeld Nicole G.M. , Endeman Henrik
Published: November 2023

Introduction: Midazolam-based continuous intravenous sedation in patients admitted to the intensive care unit (ICU) was a necessity during the COVID-19 pandemic. However, benzodiazepine-based sedation is associated with a high incidence of benzodiazepine-related delirium and additional days on mechanical ventilation. Due to the requirement of high midazolam doses in combination with the impaired renal clearance (CL) of the pharmacological active metabolite 1-OH-midazolam-glucuronide (10% compared to midazolam), ICU patients with COVID-19 and continuous renal replacement therapy (CRRT) were at risk of unintended prolonged sedation. Several CRRT-related factors may have influenced the delivered CL of midazolam and its metabolites. Therefore, the aim of the study was to identify and describe these CRRT-related factors. Methods: Pre-filter blood samples and ultrafiltrate samples were collected simultaneously. Midazolam, 1-OH-midazolam, and 1-OH-midazolam-glucuronide plasma samples were analyzed using an UPLC-MS/MS method. The prescribed CRRT dose was corrected for downtime and filter integrity using the urea ratio (urea concentration in effluent/urea concentration plasma). CL of midazolam and its metabolites were calculated with the delivered CRRT dose (corrected for downtime and saturation coefficient [SD]). Results: Three patients on continuous venovenous hemodialysis (CVVHD) and 2 patients on continuous venovenous hemodiafiltration (CVVHDF) were included. Midazolam, 1-OH-midazolam, and 1-OH-midazolam-glucuronide concentrations were 2,849 (0–6,700) μg/L, 153 (0–295) μg/L, and 27,297 (1,727–39,000) μg/L, respectively. The SD was 0.03 (0.02–0.03) for midazolam, 0.05 (0.05–0.06) for 1-OH-midazolam, and 0.33 (0.23–0.43) for 1-OH-midazolam-glucuronide. The delivered CRRT CL was 1.4 (0–1.7) mL/min for midazolam, 2.7 (0–3.5) mL/min for 1-OH-midazolam, and 15.7 (4.0–27.7) mL/min for 1-OH-midazolam-glucuronide. Conclusions: Midazolam and 1-OH-midazolam were not removed during CVVHD and CVVHDF. However, 1-OH-midazolam-glucuronide was removed reasonably, approximately up to 43%. CRRT modality, filter integrity, and downtime affect this removal. These data imply a personalized titration of midazolam in critically ill patients with renal failure and awareness for the additional sedative effects of its active metabolites.
Exploring the Expression of Adenosine Pathway-Related Markers CD73 and CD39 in Colorectal and Pancreatic Carcinomas Characterized by Multiplex Immunofluorescence: A Pilot Study
Authors: Lima Cibelle Freitas , Tamegnon Auriole , Rodriguez Saxon , Maru Dipen , Martin Philip L. , Cooper Zachary A. , Rodriguez-Canales Jaime , Parra Edwin Roger
Published: November 2023

Introduction: Generating high levels of immunosuppressive adenosine (ADO) in the tumor microenvironment contributes to cancer immune evasion. CD39 and CD73 hydrolyze adenosine triphosphate into ADO; thus, efforts have been made to target this pathway for cancer immunotherapy. Our objective was optimizing a multiplex immunofluorescence (mIF) panel to explore the role of CD39 and CD73 within the tumor microenvironment. Materials and Methods: In three-time points, a small cohort (n = 8) of colorectal and pancreatic adenocarcinomas were automated staining using an mIF panel against CK, CD3, CD8, CD20, CD39, CD73, and CD68 to compare them with individual markers immunohistochemistry (IHC) for internal panel validation. Densities of immune cells and distances from different tumor-associated immune cells to tumor cells were exploratory assessment and compared with clinicopathologic variables and outcomes. Results: Comparing the three-time points and individual IHC staining results, we demonstrated high reproducibility of the mIF panel. CD39 and CD73 expression was low in malignant cells; the exploratory analysis showed higher densities of CD39 expression by various cells, predominantly stromal cells, followed by T cells, macrophages, and B cells. No expression of CD73 by B cells or macrophages was detected. Distance analysis revealed proximity of cytotoxic T cells, macrophages, and T cells expressing CD39 to malignant cells, suggesting a close regulatory signal driven by this ADO marker. Conclusions: We optimized an mIF panel for detection of markers in the ADO pathway, an emerging clinically relevant pathway. The densities and spatial distribution demonstrated that this pathway may modulate aspects of the tumor immune microenvironment.
Efficacy and Safety of Secukinumab for the Treatment of Psoriasis: A Meta-Analysis of Pivotal Phase III Trials
Authors: Zhou Yu , Zhang Kaihui , Ma Xueting , Xie Zhiyin
Published: November 2023

Background: Secukinumab, a fully humanized monoclonal antibody against IL-17A, was approved for the treatment of moderate-to-severe plaque psoriasis in the USA and European Union in 2015. Objectives: Secukinumab, a fully humanized monoclonal antibody against IL-17A, was approved for the treatment of moderate-to-severe plaque psoriasis in the USA and European Union in 2015. The aim of this study was to systematically evaluate the efficacy and safety of secukinumab for the treatment of moderate and severe plaque psoriasis and provide an evidence-based reference for clinical practice. Methods: PubMed, Google Scholar, Cochrane Library, and Clinical Trials databases were searched. Pivotal phase III clinical trials were analysed. RevMan was used for the statistical analysis of the data. Results: Seven pivotal phase III clinical trials were analysed. All trials evaluated secukinumab in moderate-to-severe plaque psoriasis and had two common primary end points: the proportion of respondents to the Psoriasis Area and Severity Index (PASI) and the proportion of respondents to the Investigator’s Global Assessment (IGA). The total response ratios of PASI and IGA respondents in the secukinumab group were 82.8 and 71.3%, respectively, compared to placebo. Secukinumab was superior to etanercept, with risk ratios of 1.7 and 2.1, respectively. Secukinumab was generally well tolerated during the 1-year trial period. However, adverse events also occurred. Conclusion: Secukinumab was found to be more effective than etanercept and had an acceptable safety profile. Since psoriasis is an autoimmune disease that requires lifelong treatment, attention should be paid to its adverse effects.
Inhibition of Galectin-3 in a Rat Model of Epilepsy and Kainate-Activated BV2 Cells Limits Microglial Activation Through the NLRP3/Pyroptosis Pathway
Authors: Sun Weiwei , Hao Ying , Li Chunxiang , Zhao Yuanyuan , Yu Haishao , Wang Lin
Published: November 2023

Introduction: This study aimed to investigate the possible role of galectin-3 in epilepsy and further explore its underlying mechanisms. Methods: Sprague-Dawley rats were intraperitoneally injected with 30 mg/kg pilocarpine to induce an animal model of epilepsy. To inhibit galectin-3, the epilepsy model of rats was intraperitoneally injected with TD139. The severity of the seizure was graded according to the Racine score. The pathological changes in hippocampal CA1 regions were observed by hematoxylin and eosin and Nissl staining. Enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and Western blot were used to detect the levels of cytokines and pyroptosis-related factors. The in vitro effects of galectin-3 were confirmed on BV2 cells and rat primary microglia by transfection with lentivirus vectors carrying Lgals3 shRNA or by treatment with TD139. Results: A higher expression of galectin-3 was observed in the hippocampal CA1 regions of epilepsy rats than in sham rats. Inhibition of galectin-3 by administration of TD139 improved the severity of the seizure, hippocampal damage, and neuron loss. TD139 administration suppressed the expression of NLRP3, ASC, c-caspase-1, and GSDMD-N, and reduced the levels of cytokines. In kainic acid-treated microglia, Lgals3 shRNA or TD139 significantly inhibited Iba1 expression and limited NLRP3/pyroptosis-triggered inflammation. Conclusion: Galectin-3 activates the NLRP3/pyroptosis signaling pathway to promote microglial activation and neuroinflammation during epilepsy disease progression.
Review of Intraoral Vasculature and Implications on Incision Designs of Periodontal and Implant Surgeries
Authors: Rodriguez Amanda , Velasquez Diego , Chan Hsun-Liang
Published: November 2023

Currently, the incision design for periodontal and implant surgeries is mainly based on the surgeon’s personal preference. The primary aim of this study is to review the intricate periodontal microvascular system and to illustrate the potential impact of commonly applied flap designs on the integrity of this system. A complete literature electronic search resulted in 37 relevant articles. The maxillary, facial, and lingual arteries supply the microvasculature system, including the supraperiosteal, intraligamental, and intraosseous arterioles. These arterioles have their own territories yet are extensively interconnected. The impact of common papilla management techniques are discussed, including tunneling; papilla base, incision, and preservation; and flap-releasing incisions. Flap design can impact reperfusion and blood inflow in the early healing phase, which eventually influences wound closure probability, healing speed, surgical predictability, tissue volume change, and postoperative morbidity. Future studies on the three-dimensional distribution of microvasculature and clinical impact of various flap designs on tissue reperfusion can lead to evidence-based incision selection and improved wound-healing outcomes.
Aristotle‐Only Direct Aspiration First‐Pass Technique (AO‐ADAPT) for Endovascular Mechanical Thrombectomy: A Technical Series of a Novel Technique Demonstrating Safety and Efficacy
Authors: Ares William J. , Chowdhry Shakeel , Tonetti Daniel A. , Salah Walid K. , Jankowitz Brian T. , Grandhi Ramesh
Published: November 2023

Background

The introduction of soft, large‐profile microwires has improved aspiration catheter delivery for intracranial large‐vessel occlusions. The Aristotle‐only direct aspiration first‐pass technique (AO‐ADAPT) uses the Aristotle 24 microwire to deliver a large‐bore aspiration catheter to the target occlusion without a microcatheter. We characterized rates of technical success achieved using this technique for mechanical aspiration thrombectomy.

Methods

A retrospective review of prospectively collected thrombectomy databases at 4 academic institutions identified patients undergoing procedures in which AO‐ADAPT was used. Patient demographics, clinical considerations, technical details, and radiographic outcomes were collected. Rates of successful aspiration catheter delivery without adjunctive devices and of successful reperfusion (Thrombolysis in Cerebral Infarction≥2B) were collected.

Results

Forty‐five patients met inclusion criteria (mean age 72.2±13.2 years, 62.2% female; 71.1% M1 occlusions). With a first‐line AO‐ADAPT approach, 42/45 (93.3%) patients achieved Thrombolysis in Cerebral Infarction≥2B reperfusion, with first‐pass recanalization in 26/45 (57.8%). We delivered the aspiration catheter to the target occlusion without adjunctive device in 35/45 (77.8%) patients. Of these, 29 (82.9%) underwent successful contact aspiration. This entire cohort (64.4% of the population) achieved Thrombolysis in Cerebral Infarction≥2B, with a mean time to reperfusion of 16 minutes and a first‐pass recanalization rate of 66%. Of the 16 patients who did not achieve successful AO‐ADAPT reperfusion, 6 needed a microcatheter for aspiration catheter delivery but underwent successful contact aspiration, 6 achieved microcatheter‐free delivery but needed a stentriever for final recanalization, and 4 required both microcatheter for delivery and stentriever for final recanalization. No intracranial vascular complications occurred during the procedures; 1 patient (2.2%) experienced symptomatic intracranial hemorrhage secondary to reperfusion injury.

Conclusion

The AO‐ADAPT approach to mechanical thrombectomy safely and effectively achieved reperfusion for patients with large‐vessel occlusions, with first‐pass success and successful recanalization rates comparable with other techniques. For most cases in this series, this technique obviated the need for a microcatheter and/or stentriever.