Class B1 GPCRs: Insights into Multi-Receptor Pharmacology for the Treatment of Metabolic Disease.

The secretin-like, class B1 sub-family of seven transmembrane-spanning G protein coupled receptors (GPCRs) consists of 15 members that coordinate important physiological processes. These receptors bind peptide ligands and utilize a distinct mechanism of activation that is driven by evolutionarily conserved structural features. For the class B1 receptors, the C-terminus of the cognate ligand is initially recognized by the receptor via a large N-terminal extracellular domain that forms a hydrophobic ligand binding groove. This binding enables the N-terminus of the ligand to engage deep into a large volume, open transmembrane pocket of the receptor. Importantly, the phylogenetic basis of this ligand-receptor activation mechanism has provided opportunities to engineer analogues of several class B1 ligands for therapeutic use. Among the most successful of these are drugs targeting the glucagon-like peptide-1 (GLP-1) receptor for the treatment of type 2 diabetes and obesity. Recently, multi-functional agonists possessing activity at the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor, such as tirzepatide, and others that also contain glucagon receptor activity, have been developed. In this article, we review members of the class B1 GPCR family with focus on receptors for GLP-1, GIP, and glucagon, including their signal transduction and receptor trafficking characteristics. The metabolic importance of these receptors is also highlighted, along with the benefit of poly-pharmacologic ligands. Further, key structural features and comparative analyses of high-resolution cryogenic electron microscopy structures for these receptors in active-state complex with either native ligands or multi-functional agonists are provided, supporting the pharmacological basis of such therapeutic agents.

Cerebrospinal fluid immunoglobulins in primary progressive multiple sclerosis are pathogenic.

Multiple sclerosis is clinically characterized by relapses and remissions (relapsing-remitting multiple sclerosis) that over time may evolve to a progressive course (secondary progressive multiple sclerosis) or as having a progressive course from disease onset (primary progressive multiple sclerosis). At present, it is not definitively known whether these clinical entities constitute a single pathological disease or whether these manifestations represent two distinct disease entities sharing inflammatory demyelination as a pathological feature. Here we show using a novel mouse model that CSF of primary progressive multiple sclerosis patients is unique in its capacity to induce motor disability and spinal cord pathology including demyelination, impaired remyelination, reactive astrogliosis and axonal damage. Notably, removal of immunoglobulin G from primary progressive multiple sclerosis CSF via filtration or immunodepletion attenuates its pathogenic capacity. Furthermore, injection of recombinant antibodies derived from primary progressive multiple sclerosis CSF recapitulates the pathology. Our findings suggest that the clinical and pathological features of primary progressive multiple sclerosis are antibody-mediated and pathogenically distinct from relapsing-remitting and secondary progressive multiple sclerosis. Our study has potentially important implications for the development of specific therapies for patients with primary progressive multiple sclerosis.

Does Steal Phenomenon Exist in Multiple Neurotization?-An Experimental Rat Study.

BACKGROUND: Nerve transfers from one common donor nerve to recipient nerves with multiple target branches can yield slower and unpredictable recovery in the target nerves. Our hypothesis is that steal phenomenon exists when multiple nerve neurotization comes from one donor nerve. METHODS: In 30 Sprague-Dawley rats, the left ulnar nerve (UN) was selected as the donor nerve, and the musculocutaneous nerve (MCN) and median nerve (MN) as the recipient target nerves. The rats were separated into three groups (10 rats in each): group A, UN-to-MCN (one-target); group B, UN-to-MN (one-target); and group C, UN-to-MCN and MN (two-target). The right upper limbs were nonoperative as the control group. Outcome obtained at 20 weeks after surgery included grooming test, muscle weight, compound muscle action potential, tetanic muscle contraction force, axon counts, and retrograde labeling of the involved donor and target nerves. RESULTS: At 20 weeks after surgery, muscles innervated by neurotization resulted in significant worse outcomes than the control side. This was especially true in two-target neurotization in the parameter of muscle weight and forearm flexor muscle contraction force outcome when compared to one-target neurotization. Steal phenomenon does exist because flexor muscle contraction force was significantly worse during two-target neurotization. CONCLUSION: This study proves the existence of steal phenomenon in multiple target neurotization but does not significantly affect the functional results. Postoperative rehabilitative measures (including electrical stimulation, induction exercise) and patient compliance (ambition and persistence) are other crucial factors that hold equivalent importance to long-term successful recovery.

The efficacy of adjuvant chemotherapy for older adults with stage II/III gastric cancer: a retrospective cohort study.

BACKGROUND: Adjuvant chemotherapy is recommended as the standard treatment for patients with stage II/III resected gastric cancer. However, it is unclear whether older patients also benefit from an adjuvant chemotherapy strategy. This study aimed to investigate the clinical impact of adjuvant chemotherapy in older patients with stage II/III gastric cancer. METHODS: This retrospective, real-world study analyzed 404 patients with stage II/III gastric cancer visited at our institute between January 2009 and December 2019. The clinical characteristics and outcomes of patients aged 70 years or older who received adjuvant chemotherapy were compared with those who did not receive this type of treatment. Propensity score analysis was performed to mitigate selection bias. RESULTS: Of the 404 patients analyzed, 179 were aged 70 years or older. Fewer older patients received adjuvant chemotherapy than did younger patients (60.9% vs. 94.7%, respectively; P < 0.001). Among patients aged 70 years or older, those who received adjuvant chemotherapy had improved disease-free survival (DFS) (5-year DFS rate, 53.1% vs. 30.4%; P < 0.001) and overall survival (OS) (5-year OS rate, 68.7% vs. 52.1%; P = 0.002) compared to those who did not receive adjuvant chemotherapy. A similar survival benefit was observed in the propensity-matched cohort. Multivariate analysis showed that more advanced stage was associated with poorer OS. Receipt of adjuvant chemotherapy was independently associated with a decreased hazard of death (hazard ratio (HR), 0.37; 95% confidence intervals (CI), 0.20-0.68; P = 0.002). CONCLUSIONS: Adjuvant chemotherapy may benefit older stage II/III gastric cancer patients aged ≥ 70 years. Further prospective studies are needed to confirm these findings.

Chemoresistance in acute myeloid leukemia: An alternative single-cell RNA sequencing approach.

Our previous study demonstrated that myc, mitochondrial oxidative phosphorylation, mTOR, and stemness are independently responsible for chemoresistance in acute myeloid leukemia (AML) cells. This study aimed to identify potential mechanisms of chemoresistance of the "7 + 3" induction in AML by using a single-cell RNA sequencing (scRNA-seq) approach. In the present study, 13 untreated patients with de novo AML were enrolled and stratified into two groups: complete remission (CR; n = 8) and non-CR (n = 5). Single-cell RNA sequencing was used to analyze genetic profiles of 28,950 AML cells from these patients; results were validated using a previously published bulk RNA-seq dataset. Our study results showed chemoresistant AML cells had premature accumulation during early hematopoiesis. Hematopoietic stem cell-like cells from the non-CR group expressed more leukemic stem cell markers (CD9, CD82, IL3RA, and IL1RAP) than those from the CR group. Chemoresistant progenitor cells had impaired myeloid differentiation owing to early arrest of hematopoiesis. Notably, AML cells analyzed by scRNA-seq and bulk RNA-seq harbored a comparable myeloid lineage cell fraction, which internally validated our results. Using the TCGA database, our analysis demonstrated that patients with AML with higher expression of chemoresistant genetic markers (IL3RA and IL1RAP) had a worse overall survival (p < 0.01 for IL3RA; p < 0.05 for IL1RAP). In conclusion, AML cells responsive and resistant to the "7 + 3" induction were derived from a diverse cancerous hematopoietic stem cell population, as indicated by the specific genetic biomarkers obtained using scRNA-seq approach. Furthermore, arrest of hematopoiesis was shown to occur earlier in chemoresistant AML cells, furthering the current understanding of chemoresistance in AML.

Energy Aware Load Balancing Framework for Smart Grid Using Cloud and Fog Computing.

Data centers are producing a lot of data as cloud-based smart grids replace traditional grids. The number of automated systems has increased rapidly, which in turn necessitates the rise of cloud computing. Cloud computing helps enterprises offer services cheaply and efficiently. Despite the challenges of managing resources, longer response plus processing time, and higher energy consumption, more people are using cloud computing. Fog computing extends cloud computing. It adds cloud services that minimize traffic, increase security, and speed up processes. Cloud and fog computing help smart grids save energy by aggregating and distributing the submitted requests. The paper discusses a load-balancing approach in Smart Grid using Rock Hyrax Optimization (RHO) to optimize response time and energy consumption. The proposed algorithm assigns tasks to virtual machines for execution and shuts off unused virtual machines, reducing the energy consumed by virtual machines. The proposed model is implemented on the CloudAnalyst simulator, and the results demonstrate that the proposed method has a better and quicker response time with lower energy requirements as compared with both static and dynamic algorithms. The suggested algorithm reduces processing time by 26%, response time by 15%, energy consumption by 29%, cost by 6%, and delay by 14%.

The JMJD6/HURP axis promotes cell migration via NF-κB-dependent centrosome repositioning and Cdc42-mediated Golgi repositioning.

Golgi apparatus (GA) and centrosome reposition toward cell leading end during directional cell migration in a coupling way, thereby determining cell polarity by transporting essential factors to the proximal plasma membrane. The study provides mechanistic insights into how GA repositioning (GR) is regulated, and how GR and centrosome repositioning (CR) are coupled. Our previous published works reveals that PRMT5 methylates HURP at R122 and the HURP m122 inhibits GR and cell migration by stabilizing GA-associated acetyl-tubulin and then rigidifying GA. The current study further shows that the demethylase JMJD6-guided demethylation of HURP at R122 promotes GR and cell migration. The HURP methylation mimicking mutant 122 F blocks JMJD6-induced GR and cell migration, suggesting JMJD6 relays GR stimulating signal to HURP. Mechanistic studies reveal that the HURP methylation deficiency mutant 122 K promotes GR through NF-κB-induced CR and subsequently CR-dependent Cdc42 upregulation, where Cdc42 couples CR to GR. Taken together, HURP methylation statuses provide a unique opportunity to understand how GR is regulated, and the GA intrinsic mechanism controlling Golgi rigidity and the GA extrinsic mechanism involving NF-κB-CR-Cdc42 cascade collectively dictate GR.

Comparison of molecular responses and outcomes between BCR::ABL1 e14a2 and e13a2 transcripts in chronic myeloid leukemia.

Several studies have compared the molecular responses between e14a2 and e13a2 BCR::ABL1 transcripts in chronic myeloid leukemia (CML) patients treated with front-line imatinib, but there were very limited studies on nilotinib or dasatinib-treated patients. We retrospectively analyzed the molecular responses in 1124 CML patients with the e14a2 or e13a2 transcript receiving front-line imatinib, nilotinib or dasatinib treatment. Patients with the e14a2 transcript had higher optimal response rates than those with the e13a2 transcript at 12 months in the imatinib-treated group, and 6 and 12 months in the nilotinib-treated group. The optimal response rates were not significantly different between the two transcripts in the dasatinib-treated group at landmark molecular responses. With a median follow-up time of 48.4 months, higher cumulative incidences of BCR::ABL1 International Scale ≤1% and major molecular response were observed in patients with the e14a2 rather than the e13a2 transcript receiving front-line imatinib or nilotinib treatment, but not in dasatinib-treated patients. The progression-free survival and overall survival did not differ between the two transcripts in all three treatment groups. In view of the speed and depth of molecular responses, BCR::ABL1 transcript subtypes might provide helpful information in selecting a front-line tyrosine kinase inhibitor for individual young patients with future potential treatment-free remission.

Cytomegalovirus in the transplant setting: Where are we now and what happens next? A report from the International CMV Symposium 2021.

The CMV Symposium in September 2021 was an international conference dedicated to cytomegalovirus (CMV) infection after solid organ or hematopoietic stem cell transplantation. This review provides an overview of the presentations given by the expert faculty, supplemented with educational clinical cases. Topics discussed include CMV epidemiology and diagnosis, the burden of CMV infection and disease, CMV-specific immunity and management of CMV in transplant settings. Major advances in the prevention and treatment of CMV in the past decade and increased understanding of CMV immunity have led to improved patient outcomes. In the future, management algorithms may be individualized based on the transplant recipient's immune profile, which will mark the start of a new era for patients with CMV.

Investigating early progression of Hodgkin lymphoma in a two-center analysis.

BACKGROUND/PURPOSE: The early progression of disease (POD) of Hodgkin lymphoma (HL) leads to a poor prognosis. To identify risk factors for early POD, this retrospective two-center cohort analysis was conducted. METHODS: Medical records of HL patients between 1998 and 2020 from two referral centers were reviewed. RESULTS: Two-hundred and sixty-nine patients were analyzed. The distribution of early vs. advanced stages was 51.1 vs. 48.9%, respectively. The 5-year progression free survival (PFS) was 63%, and the overall survival (OS) was 87% with a median follow-up of 52.0 months. The complete remission (CR) rate was 85.7%. Disease progression or relapsed disease occurred in 33.9% (n = 85) of patients while 17.0% of this cohort had early POD within 12 months of induction therapy. Patients with early POD had a worse median OS than those without (p < 0.001). Failure to achieve post-induction CR and high international prognostic score (IPS, 3-7) were independent risk factors for early POD. Compared with chemotherapy alone, consolidative radiotherapy after induction chemotherapy was associated with a lower risk of early POD (21.3% vs. 6.2%, p = 0.006). CONCLUSION: High IPS was an independent risk factor for early POD, which was less observed in those with consolidative radiotherapy.

Reconfigurable Intelligent Surface-Aided Cooperative NOMA with p-CSI Fading Channel toward 6G-Based IoT System.

Addressing the challenges of internet-based 5G technology, namely increasing density through micro-cell systems, frequency spectrum, and reducing resource costs, is needed to meet the use of IoT-based 6G technology with the goal of high-speed, high-capacity, and low-latency communication. In this research, we considered the coverage performance and ergodic capacity of the Reconfigurable Intelligent Surface (RIS)-aided cooperative nonorthogonal multiple-access network (NOMA) of an IoT system. This enables the upgrading of 5G- toward 6G-technology-based IoT systems. We developed a closest-form formula of near and far user coverage probabilities as a function of perfect channel statistical information (p-CSI) using only a single-input single-output (SISO) system with a finite number of RIS elements under the Nakagami-m fading channel. We also define ergodic capacity as a simple upper limit by simplifying the use of symbolic functions and it could be used for a sustained period. The simulation findings suggest that RIS-assisted NOMA has a reduced risk of outage than standard NOMA. All of the derived closed-form formulas agree with Monte Carlo simulations, indicating that the distant user's coverage probability outperforms the nearby user. The bigger the number of RIS parts, however, the greater the chance of coverage. They also disclose the scaling law of the number of phase shifts at the RIS-aided NOMA based on the asymptotic analysis and the upper bound on channel capacity. In both arbitrary and optimum phase shifts, the distant user's ergodic capacity outperforms the near user.

Interaction of Secure Cloud Network and Crowd Computing for Smart City Data Obfuscation.

There can be many inherent issues in the process of managing cloud infrastructure and the platform of the cloud. The platform of the cloud manages cloud software and legality issues in making contracts. The platform also handles the process of managing cloud software services and legal contract-based segmentation. In this paper, we tackle these issues directly with some feasible solutions. For these constraints, the Averaged One-Dependence Estimators (AODE) classifier and the SELECT Applicable Only to Parallel Server (SELECT-APSL ASA) method are proposed to separate the data related to the place. ASA is made up of the AODE and SELECT Applicable Only to Parallel Server. The AODE classifier is used to separate the data from smart city data based on the hybrid data obfuscation technique. The data from the hybrid data obfuscation technique manages 50% of the raw data, and 50% of hospital data is masked using the proposed transmission. The analysis of energy consumption before the cryptosystem shows the total packet delivered by about 71.66% compared with existing algorithms. The analysis of energy consumption after cryptosystem assumption shows 47.34% consumption, compared to existing state-of-the-art algorithms. The average energy consumption before data obfuscation decreased by 2.47%, and the average energy consumption after data obfuscation was reduced by 9.90%. The analysis of the makespan time before data obfuscation decreased by 33.71%. Compared to existing state-of-the-art algorithms, the study of makespan time after data obfuscation decreased by 1.3%. These impressive results show the strength of our methodology.

Privacy Preserving Multi-Party Key Exchange Protocol for Wireless Mesh Networks.

Presently, lightweight devices such as mobile phones, notepads, and laptops are widely used to access the Internet throughout the world; however, a problem of privacy preservation and authentication delay occurs during handover operation when these devices change their position from a home mesh access point (HMAP) to a foreign mesh access point (FMAP). Authentication during handover is mostly performed through ticket-based techniques, which permit the user to authenticate itself to the foreign mesh access point; therefore, a secure communication method should be formed between the mesh entities to exchange the tickets. In two existing protocols, this ticket was not secured at all and exchanged in a plaintext format. We propose a protocol for handover authentication with privacy preservation of the transfer ticket via the Diffie-Hellman method. Through experimental results, our proposed protocol achieves privacy preservation with minimum authentication delay during handover operation.

Prevention of Cyber Security with the Internet of Things Using Particle Swarm Optimization.

High security for physical items such as intelligent machinery and residential appliances is provided via the Internet of Things (IoT). The physical objects are given a distinct online address known as the Internet Protocol to communicate with the network's external foreign entities through the Internet (IP). IoT devices are in danger of security issues due to the surge in hacker attacks during Internet data exchange. If such strong attacks are to create a reliable security system, attack detection is essential. Attacks and abnormalities such as user-to-root (U2R), denial-of-service, and data-type probing could have an impact on an IoT system. This article examines various performance-based AI models to predict attacks and problems with IoT devices with accuracy. Particle Swarm Optimization (PSO), genetic algorithms, and ant colony optimization were used to demonstrate the effectiveness of the suggested technique concerning four different parameters. The results of the proposed method employing PSO outperformed those of the existing systems by roughly 73 percent.

Applications of Wireless Sensor Networks and Internet of Things Frameworks in the Industry Revolution 4.0: A Systematic Literature Review.

The 21st century has seen rapid changes in technology, industry, and social patterns. Most industries have moved towards automation, and human intervention has decreased, which has led to a revolution in industries, named the fourth industrial revolution (Industry 4.0). Industry 4.0 or the fourth industrial revolution (IR 4.0) relies heavily on the Internet of Things (IoT) and wireless sensor networks (WSN). IoT and WSN are used in various control systems, including environmental monitoring, home automation, and chemical/biological attack detection. IoT devices and applications are used to process extracted data from WSN devices and transmit them to remote locations. This systematic literature review offers a wide range of information on Industry 4.0, finds research gaps, and recommends future directions. Seven research questions are addressed in this article: (i) What are the contributions of WSN in IR 4.0? (ii) What are the contributions of IoT in IR 4.0? (iii) What are the types of WSN coverage areas for IR 4.0? (iv) What are the major types of network intruders in WSN and IoT systems? (v) What are the prominent network security attacks in WSN and IoT? (vi) What are the significant issues in IoT and WSN frameworks? and (vii) What are the limitations and research gaps in the existing work? This study mainly focuses on research solutions and new techniques to automate Industry 4.0. In this research, we analyzed over 130 articles from 2014 until 2021. This paper covers several aspects of Industry 4.0, from the designing phase to security needs, from the deployment stage to the classification of the network, the difficulties, challenges, and future directions.

Dual-lumen power injectable peripherally inserted central catheters in allogeneic hematopoietic stem cell transplantation: A prospective observational study.

AIMS AND OBJECTIVES: To explore whether dual-lumen power injectable peripherally inserted central catheters (PICCs) could be effectively and safely applied in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and for serum cyclosporine level monitoring. BACKGROUND: Compared to conventional central venous access devices, PICC provides a feasible route not only for fluid infusion, but also for blood sample collection in patients undergoing oncological treatments. DESIGN: A prospective observational study was conducted according to the STROBE guidelines. METHODS: We prospectively evaluated the applications and complications of power injectable PICCs in 52 consecutive allo-HSCT recipients. We also compared the cyclosporine levels in 188 paired blood samples, simultaneously obtained via power injectable PICCs and percutaneous venous puncture, to investigate whether power injectable PICC is a feasible route for cyclosporine concentration monitoring in allo-HSCT. RESULTS: The median PICC placement duration was 29 days. The insertion-site blood oozing and central line-associated bloodstream infection rates were 36.5% (19/52) and 26.9% (14/52), respectively, indicating the feasibility of these PICCs for various applications in allo-HSCT. No power injectable PICC-related thrombotic adverse events were identified; 90.4% (47/52) of cases with power injectable PICC removal occurred because of lack of medical utility, suggesting that power injectable PICC-related complications were manageable. However, cyclosporine levels in samples obtained via these PICCs were significantly higher than those in samples obtained via percutaneous venous puncture (261.5 ± 139.2 vs. 232.4 ± 253.6 ng/ml; p = 0.019 [set 1]; 254.8 ± 89.3 vs. 225.1 ± 233.3 ng/ml; p<0.001 [set 2]; 283.6 ± 103.9 vs. 238.0 ± 254.7 ng/ml; p = 0.006 [set 3]; 291.0 ± 94.9 vs. 266.0 ± 274.7 ng/ml; p = 0.016 [set 4]). CONCLUSION: The power injectable PICC is a feasible venous access device for allo-HSCT. RELEVANCE TO CLINICAL PRACTICE: The dual-lumen power injectable PICCs provided a reliable access for blood sample collection, decreasing the number of blind percutaneous venous punctures in allo-HSCT. However, its application in cyclosporine level monitoring needs further investigation.

Preparation of Calcium Phosphate Compounds on Zirconia Surfaces for Dental Implant Applications.

Titanium is widely used in medical implants despite the release of heavy metal ions over long-term use. Zirconia is very close to the color of teeth; however, its biological inertness hinders bonding with bone tissue. Alkaline treatment and coatings of calcium phosphate can be used to enhance bone regeneration adjacent to dental implants. This study examined the effects of alkaline treatment, calcium phosphate coatings, and sintering, on the physical properties of implant material. Our analysis confirmed that the calcium phosphate species were octacalcium phosphate (OCP). The sintering of calcium phosphate was shown to create B-type HAP, which is highly conducive toward the differentiation of mesenchymal stem cells (MSCs) into osteoblasts for the facilitation of bone integration. Conclusions: This study demonstrated the room-temperature fabrication of dental implants with superhydrophilic surfaces to enhance biocompatibility.

Magnesium Modified ß-Tricalcium Phosphate Induces Cell Osteogenic Differentiation In Vitro and Bone Regeneration In Vivo.

In vitro, in vivo, and clinical studies have shown how the physicochemical and biological properties of ß-tricalcium phosphate (ß-TCP) work in bone regeneration. This study aimed to improve the properties of ß-TCP by achieving optimum surface and bulk ß-TCP chemical/physical properties through the hydrothermal addition of magnesium (Mg) and to later establish the biocompatibility of ß-TCP/Mg for bone grafting and tissue engineering treatments. Multiple in vitro and in vivo analyses were used to complete ß-TCP/Mg physicochemical and biological characterization. The addition of MgO brought about a modest rise in the number of ß-TCP surface particles, indicating improvements in alkaline phosphatase (ALP) activity on day 21 (p < 0.05) and in the WST-1assay on all days (p < 0.05), with a corresponding increase in the upregulation of ALP and bone sialoprotein. SEM analyses stated that the surfaces of the ß-TCP particles were not altered after the addition of Mg. Micro-CT and histomorphometric analysis from rabbit calvaria critical defects resulted in ß-TCP/Mg managing to reform more new bone than the control defects and ß-TCP control at 2, 6, and 8 weeks (* p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, and **** p ≤ 0.0001). The hydrothermal addition of MgO to the ß-TCP surfaces ameliorated its biocompatibility without altering its surface roughness resulting from the elemental composition while enhancing cell viability and proliferation, inducing more bone regeneration by osteoconduction in vivo and osteoblastic differentiation in vitro.

An edge-driven multi-agent optimization model for infectious disease detection.

This research work introduces a new intelligent framework for infectious disease detection by exploring various emerging and intelligent paradigms. We propose new deep learning architectures such as entity embedding networks, long-short term memory, and convolution neural networks, for accurately learning heterogeneous medical data in identifying disease infection. The multi-agent system is also consolidated for increasing the autonomy behaviours of the proposed framework, where each agent can easily share the derived learning outputs with the other agents in the system. Furthermore, evolutionary computation algorithms, such as memetic algorithms, and bee swarm optimization controlled the exploration of the hyper-optimization parameter space of the proposed framework. Intensive experimentation has been established on medical data. Strong results obtained confirm the superiority of our framework against the solutions that are state of the art, in both detection rate, and runtime performance, where the detection rate reaches 98% for handling real use cases.

Risk factors for nonresponsive hydration in patients with spinal cerebrospinal fluid leakage.

BACKGROUND: Spinal cerebrospinal fluid (CSF) leakage is frequently encountered clinically after lumbar puncture or spontaneous events. Although some patients recover without treatment or after intensive hydration, some require an epidural blood patch (EBP). The risks of nonresponsive hydration remain unknown. Therefore, we identified the risk factors for patients with spinal CSF leakage nonresponsive to hydration. METHODS: We retrospectively reviewed patients diagnosed with spinal CSF leakage between January 2010 and March 2021. Clinical data, including patient age, sex, etiology, and radiological indications in magnetic resonance imaging, were compared between patients who were responsive and non-responsive to hydration. RESULTS: Of the 74 patients with spinal CSF leakage, 25 were responsive to hydration and 49 required EBP. Patients who were nonresponsive to hydration were older (39.27 vs. 34.32 years, P = 0.01), had a higher percentage of spontaneous intracranial hypotension (93.88% vs. 68.00%, P = 0.005), had more spinal CSF leakage (12.04 vs. 8.04, P = 0.01), and had a higher percentage of dural sinus engorgement (81.63% vs. 60.00%, P = 0.044). Spontaneous intracranial hypotension (odds ratio [OR]: 4.63; 95% confidence interval [CI]: 1.00-21.38) and having ≥9 spinal CSF leakages (OR: 3.29; 95% CI: 1.08-10.01), as indicated by magnetic resonance myelography, are considered risk factors for noneffective hydration. CONCLUSIONS: Patients with spinal CSF leakage who have spontaneous intracranial hypotension and those with ≥9 spinal CSF leakages are considered at risk for noneffective hydration. EBP should be considered early in these patients.