bluuebunny/crossref_metadata_2025 huggingface dataset:
Laryngeal mask airway versus endotracheal tube during percutaneous dilatational tracheostomy in critically ill adult patients
Authors: Elnafad Sobhy Ali , Fahmy Tamer Salah Eldin , Aqabawy Hazem Abdel Hamid El , Elansary Mohamed Gamal
Published: August 2024

Background

One of the most often used bedside surgical techniques in critical care units (ICUs) for critically ill individuals who need prolonged mechanical ventilation is percutaneous dilatational tracheostomy (PDT). Numerous difficulties may arise from puncturing the esophagus or making a false passage during surgery.

Objectives

To compare the use of laryngeal mask airway (LMA) and endotracheal tube (ETT) during PDT guided by ultrasonography (US) or bronchoscopy.

Methods

Our study was a prospective cohort of 120 patients admitted to the Critical Care Department at Kasr Alainy Hospital and Damanhur Medical National Institute between March 2020 and November 2021. Hemodynamics, arterial blood gasses, complications, and outcomes of the patients were recorded.

Results

The studied patients were divided into the ETT and LMA groups (60 patients in each group). Then, each group was subdivided into two subgroups (ETT-US, ETT-Bronch, LMA-US, and LMA-Bronch; 30 patients in each subgroup) according to the guiding procedure used for puncturing the trachea: US-guided or bronchoscopy-guided. Regarding HR, there was no statistically significant difference between the two groups or four subgroups before, during, and after the procedure. In addition, there was no statistically significant difference between the two studied groups regarding MAP before the procedure. However, during and after the procedure, MAP was significantly higher in the ETT group. There was no discernible change in oxygen saturation or PaO2 before, during, or after the procedure. However, there was no discernible difference in PaCO2 levels before and after the procedure; it was much greater in the ETT group and ETT-Bronch subgroup during the process. Furthermore, there was no statistically significant variation in the number of punctures between the two groups or the four subgroups. The length of the process varied significantly across the two major groups and the four evaluated subgroups. The LMA group had the shortest procedure duration (5.05 ± 1.28 min), the LMA-Bronch subgroup (4.79 ± 1.42 min), and the LMA-US subgroup (5.31 ± 1.10 min), while the ETT had the longest procedure duration group (5.86 ± 1.11 min), the ETT-Bronch subgroup (6.09 ± 1.23 min), and ETT-US (5.63 ± 0.94 min). Regarding complications, there was no considerable difference between the two groups or four subgroups except aerophagia. Aerophagia was considerably more common in the LMA group (7 candidates) and was not observed in the ETT group.

Conclusions

Our study concluded that the laryngeal mask airway improves ventilation during percutaneous dilatation tracheostomy, especially when used with ultrasound, and thus can be used for candidates with traumatic brain injury and brain edema.
What EU Conditionality Says about the Rule of Law
Authors: Fromont Louise
Published: August 2024

The Covid-19 crisis provided an opportunity for the European Union to offer an alternative regulatory response to the crisis of values by systemically linking European funding to respect for the rule of law. A rule of law conditionality mechanism for spending was introduced in the Recovery and Resilience Facility and in Regulation 2020/2092. It is both positive – in that it encourages Member States to implement reforms and investments aimed at improving the rule of law – and negative – in that it takes the form of financial sanctions. However, the development of the rule of law conditionality is leading to an economisation of the concept of the rule of law, insofar as it mainly concerns those dimensions of the rule of law that are conducive to growth – such as justice systems and the fight against corruption. As a result, it could paradoxically exacerbate the very crisis it is designed to resolve.
The Development Risks Defence in the Digital Age
Authors: Izquierdo Grau Guillem
Published: August 2024

One of the pillars on which product liability law is based is the defence for development risks. According to this defence, the producer is not liable for the damage caused to the injured party if, at the time the product was put into circulation, the state of scientific and technical knowledge did not allow the existence of the defect to be discovered. The Proposal for a Directive drafted by the European Commission and published on 28 September 2022 continues to provide, in Article 10.1.e), the defence for development risks. The Proposal for a Directive refers to this particular issue in Recital 39, which introduces some requirements for the assessment of such defence.

However, despite this recognition, does this defence fit into the digital paradigm, and how can it be applied to damage caused by defects in products with digital elements that incorporate artificial intelligence?
Exploring the electrophysiology of Parkinson’s disease with magnetoencephalography and deep brain recordings
Authors: Rassoulou Fayed , Steina Alexandra , Hartmann Christian J. , Vesper Jan , Butz Markus , Schnitzler Alfons , Hirschmann Jan
Published: August 2024

Aberrant information processing in the basal ganglia and connected cortical areas are key to many neurological movement disorders such as Parkinson’s disease. Investigating the electrophysiology of this system is difficult in humans because non-invasive methods, such as electroencephalography or magnetoencephalography, have limited sensitivity to deep brain areas. Recordings from electrodes implanted for therapeutic deep brain stimulation, in contrast, provide clear deep brain signals but are not suited for studying cortical activity. Therefore, we combine magnetoencephalography and local field potential recordings from deep brain stimulation electrodes in individuals with Parkinson’s disease. Here, we make these data available, inviting a broader scientific community to explore the dynamics of neural activity in the subthalamic nucleus and its functional connectivity to cortex. The dataset encompasses resting-state recordings, plus two motor tasks: static forearm extension and self-paced repetitive fist clenching. Most patients were recorded both in the medicated and the unmedicated state. Along with the raw data, we provide metadata on channels, events and scripts for pre-processing to help interested researchers get started.
Distance and similarity measures on belief and plausibility under q-rung orthopair fuzzy sets with applications
Authors: Hussain Rashid , Hussain Zahid , Sarhan Nadia M. , Juraev Nizomiddin , Ur Rahman Shams
Published: August 2024

Belief and plausibility functions based on evidence theory (ET) have been widely used in managing uncertainty. Various generalizations of ET to fuzzy sets (FSs) have been reported in the literature, but no generalization of ET to q-rung orthopair fuzzy sets (q-ROFSs) has been made yet. Therefore, this paper proposes a novel, simple, and intuitive approach to distance and similarity measures for q-ROFSs based on belief and plausibility functions within the framework of ET. This research addresses a significant research gap by introducing a comprehensive framework for handling uncertainty in q-ROFSs using ET. Furthermore, it acknowledges the limitations inherent in the current state of research, notably the absence of generalizations of ET to q-ROFSs and the challenges in extending belief and plausibility measures to certain aggregation operators and other generalizations including Hesitant fuzzy sets, Bipolar fuzzy sets, Fuzzy soft sets etc. Our contribution lies in the proposal of a novel approach to distance and similarity measures for q-ROFSs under ET, utilizing Orthopairian belief and plausibility intervals (OBPIs). We establish new similarity measures within the generalized ET framework and demonstrate the reasonability of our method through useful numerical examples. Additionally, we construct Orthopairian belief and plausibility GRA (OBP-GRA) for managing daily life complex issues, particularly in multicriteria decision-making scenarios. Numerical simulations and results confirm the usability and practical applicability of our proposed method in the framework of ET.
Sediment Evaluation of Manganese Concentrations in Limay Shoreline: A Monitoring Approach
Authors: Santos Nanette , Garcia Marck Aren , Villegas Keith Clieve
Published: August 2024

The current study on sediment quality at the shoreline of Limay is very limited. This study examined the levels of manganese (Mn) concentrations on the shoreline of Limay, Bataan, by analyzing of sediment samples. The concentration of the metals was determined by the use of a Flame Atomic Absorption Spectrometer, applying the Standard Addition Method. The tests were conducted at the First Analytical Service and Technical Cooperative Laboratories (F.A.S.T. Laboratories). The findings of the study conducted at two sampling locations indicated that the concentration of the heavy metal manganese was beyond the Maximum Allowable Limit for Sediment set by the Environmental Protection Agency (EPA); however, it did not exceed the World Health Organization (WHO). For barangay Bo. Luz has concentrations as high as 595 ppm, 602 ppm, and 534 ppm. In the case of Barangay Lamao, it is seen that it exhibits the highest concentration levels, detecting 948 ppm, 958 ppm, and 758 ppm. The development of intensive farming techniques that depend on inorganic fertilizers, the lack of household waste management practices, the use of feeds and pesticides in the fishery industry, the discharge of waste from industrial sources, including the production of steel and fabrication, textile production, and mining company waste that flows into the ocean are potential sources that can be attributed to the high concentration of manganese.
Optimization of heterogeneous photo-Fenton process parameters by RSM-BBD for decolorization of pulp and paper effluent using Fe2O3/TiO2 catalyst under UV-C irradiation
Authors: Quiton Khyle Glainmer , Santuyo Jodalyn Claire , Tendenilla Gian Marco
Published: August 2024

The pulp and paper (P&P) industry is considered one of the production and manufacturing industries that consume immense amounts of natural resources, such as wood, water, and energy. It is also a significant contributor of pollutants to the environment, where various organic and inorganic contaminants are immensely produced into the environment. In this study, the color removal efficiency from P&P wastewater using a 1.5-L three-phase fluidized-bed reactor in combination with heterogeneous photo-Fenton reaction process was investigated. The process used synthesized Fe2O3/TiO2 catalyst by ultrasonic-assisted impregnation technique and applied UV-C light irradiation for the decolorization treatment of the P&P wastewater. The RSM-BBD was also used to optimize the color reduction efficiency of the P&P wastewater between three independent variables: pH, photocatalyst dose, and H2O2 dose. Under the optimal conditions (initial effluent pH = 3, [Fe2O3/TiO2] = 1.25 g/L, [H2O2] = 50 mM) with an air flow rate of 2 L min-1 at a reaction time of 30 min, the color reduction efficiency was achieved as 73.5%. Additionally, pH was found to be the most significant parameter for the decolorization of the P&P wastewater.
Contribution of runoffs to declining water quality of urban lakes: Status and management approaches
Authors: Baluyot Charena , Calamiong Jefta Jade , Cruz Yunika Aloha , Pedimonte Erica , Sebastian John Luis , Santos Franz
Published: August 2024

The water quality of many lakes around the world have declined due to continuous urbanization with runoffs being one of the significant contributors. This narrative review focuses on the presentation of existing papers that dis-cussed runoff as a contributing factor to urban lakes’ declining water quality and the different management approaches that researchers might want to prioritize in future studies. The review paper also explores the different sources of runoffs and the significant contributors to the contamination of lakes in urban areas such as sewage discharges, industrial effluents, and runoff, and their resulting impacts on the quality of these water bodies. Different management practices adopted to enhance Urban Lake water quality such as watershed management, pollution management, stormwater management, and limiting nutrient loading in lakes are also explored in this review paper. The effectiveness of these practices is evaluated, and future research directions are suggested. The findings of this review indicate that runoffs play a significant role in the declining water quality of urban lakes, and effective management practices are necessary to protect these valuable water resources.
Rapid decomposition of leaf litter from fast-growing tropical wood jabon (Anthocephalus cadamba Miq.)
Authors: Atunnisa Rifa , Mansur Irdika , Rusdiana Omo
Published: August 2024

Nutrient releases are considered functional processes related to soil fertility. In fast-growing tree plantation, maintaining the nutrient supply in soil is crucial for sustaining productivity. Jabon (Anthocephalus cadamba Miq.) is one of Indonesia’s native species that belongs to fast-growing species. In fast-growing tree plantation, leaf litter decomposition is considered an essential process of soil fertility. This study was conducted to gain information on the decomposition rate of a 4-year-old jabon plantation. The rate decay constant (k) is 0.09 week-1, and the relative decomposition rate is 0.086 g g-1 week-1. The 50 % (half lifetime) mass loss projection ranged between 53 days. The results suggested that jabon has rapid decomposition rates, implying that jabon has the high prospect for revegetation, particularly in degraded areas.
Identification of the morphological features of indigenous microbial from bauxite residue disposal areas in Indonesia
Authors: Yulikasari Andriyan , Tangahu Bieby Voijant , Nurhayati Ervin , Arliyani Isni , Mashudi  , Titah Harmin Sulistiyaning , Lam Yeng Ming , Wang Yamin , In Hurun , Soesilo Mery Maryanawati
Published: August 2024

The increasing amount of annual red mud generation is becoming a global concern because of the environmental problems caused by its high metal content, alkalinity, and salinity. To manage red mud deposits, various green technologies have been implemented, such as phytoremediation and bioremediation. Accordingly, this study aimed to assess the morphological features of indigenous microbes in bauxite residue disposal areas (BRDA) in Indonesia. Using Gram staining method and microscopic analysis, indigenous microbial species were characterised based on morphological features such as colony profile, colour, size, margin, elevation and cell shape. As many as 10 isolates of indigenous microbes were successfully identified. All isolated were Gram positive and mostly white. The shape of colonies varied from irregular, circular, and filamentous with flat elevation, whereas the cell shape was identified as rod-shape and round-shape. Based on the similarity of the morphological characteristics of these microbes, there are five suspected genus, i.e., Micrococcus, Microbacterium, Bacillus, Cylindrogloea, Eubacterium, and Staphylococcus.
Soil carbon and land use dynamics in the greater part of Cerrado biome, Brazil
Authors: Nwaogu Chukwudi , Nwaiwu Enyinnaya R. , Diagi Bridget E. , Umar Nasir A. , Uche Cosmas C. , Ulor Chukwuemeka , Ajeyomi Samuel A. , Cherubin Mauricio R.
Published: August 2024

This study is aimed at assessing the dynamics of soil carbon (C) and land-use in the greater part of Cerrado biome between 2015 and 2020, and to predict the future scenario. Increasing anthropogenic activities, especially agriculture, has significantly impacted land-use, consequently the balance inflow and outflow of carbon under different land use. Data on soil C, land use-land cover (LULC), and other variables were collected from USGS EarthData, FAO, and Mapbiomas. By applying support vector machine and InVEST models, we identified the LULC and quantified the soil C stocks under each land use. Pastures (2,016,793 km2) and savanna (1,789,150 km2) covered more than 70% of entire biome. Significant landuse transitions occurred between 2015 and 2025 with croplands increasing by more than 10% in area. Integrated agricultural system (IAS) accounted for ~ 40% more SOC stock than business as usual (BAU). Unlike the BAU which involves the conventional farming systems, the IAS is a low-carbon agricultural practice which serves as a nature-based solution to enhance C sequestration. The findings from the study might contribute to closing the gap in knowledge about soil C stocks in the region, and in smart-climate agriculture agendas to improve carbon stocks, food security and other SDGs.
Towards Sustainable Development through Food Security Nexus
Authors: Supartoyo Yesi , Setiawan Sigit , Buhaerah Pihri , Hasanah Asia , Hatmanto Tria
Published: August 2024

Food security as an indicator of macroeconomic stability. Food security in a region is a fundamental foundation of the country’s economic security and one of the most important prerequisites for sustainable development. This study aimed to analyze the correlation in between food strategy nexus through food availability, food affordability, and food utilization to food security in Indonesia, particularly in East Kalimantan Province. Method of this research is correlation analysis. Highlight of the result analysis are all indicators of food security nexus have a correlation significantly.
ATAD5 functions as a regulatory platform for Ub–PCNA deubiquitination
Authors: Ryu Eunjin , Yoo Juyeong , Kang Mi-Sun , Ha Na Young , Jang Yewon , Kim Jinwoo , Kim Yeongjae , Kim Byung-Gyu , Kim Shinseog , Myung Kyungjae , Kang Sukhyun
Published: August 2024

Ubiquitination status of proliferating cell nuclear antigen (PCNA) is crucial for regulating DNA lesion bypass. After the resolution of fork stalling, PCNA is subsequently deubiquitinated, but the underlying mechanism remains undefined. We found that the N-terminal domain of ATAD5 (ATAD5-N), the largest subunit of the PCNA-unloading complex, functions as a scaffold for Ub–PCNA deubiquitination. ATAD5 recognizes DNA-loaded Ub–PCNA through distinct DNA-binding and PCNA-binding motifs. Furthermore, ATAD5 forms a heterotrimeric complex with UAF1–USP1 deubiquitinase, facilitating the deubiquitination of DNA-loaded Ub–PCNA. ATAD5 also enhances the Ub–PCNA deubiquitination by USP7 and USP11 through specific interactions. ATAD5 promotes the distinct deubiquitination process of UAF1–USP1, USP7, and USP11 for poly-Ub–PCNA. Additionally, ATAD5 mutants deficient in UAF1-binding had increased sensitivity to DNA-damaging agents. Our results ultimately reveal that ATAD5 and USPs cooperate to efficiently deubiquitinate Ub–PCNA prior to its release from the DNA in order to safely deactivate the DNA repair process.
Zika virus NS5 protein inhibits type I interferon signaling via CRL3 E3 ubiquitin ligase-mediated degradation of STAT2
Authors: Ren Wenlin , Fu Chonglei , Zhang Yu , Ju Xiaohui , Jiang Xi , Song Jingwei , Gong Mingli , Li Zhuoyang , Fan Wenchun , Yao Jun , Ding Qiang
Published: August 2024

The ZIKA virus (ZIKV) evades the host immune response by degrading STAT2 through its NS5 protein, thereby inhibiting type I interferon (IFN)-mediated antiviral immunity. However, the molecular mechanism underlying this process has remained elusive. In this study, we performed a genome-wide CRISPR/Cas9 screen, revealing that ZSWIM8 as the substrate receptor of Cullin3-RING E3 ligase is required for NS5-mediated STAT2 degradation. Genetic depletion of ZSWIM8 and CUL3 substantially impeded NS5-mediated STAT2 degradation. Biochemical analysis illuminated that NS5 enhances the interaction between STAT2 and the ZSWIM8–CUL3 E3 ligase complex, thereby facilitating STAT2 ubiquitination. Moreover, ZSWIM8 knockout endowed A549 and Huh7 cells with partial resistance to ZIKV infection and protected cells from the cytopathic effects induced by ZIKV, which was attributed to the restoration of STAT2 levels and the activation of IFN signaling. Subsequent studies in a physiologically relevant model, utilizing human neural progenitor cells, demonstrated that ZSWIM8 depletion reduced ZIKV infection, resulting from enhanced IFN signaling attributed to the sustained levels of STAT2. Our findings shed light on the role of ZIKV NS5, serving as the scaffold protein, reprograms the ZSWIM8–CUL3 E3 ligase complex to orchestrate STAT2 proteasome-dependent degradation, thereby facilitating evasion of IFN antiviral signaling. Our study provides unique insights into ZIKV–host interactions and holds promise for the development of antivirals and prophylactic vaccines.
Thirst-driven hygrosensory suppression promotes water seeking in
Drosophila
Authors: Chu Li-An , Tai Chu-Yi , Chiang Ann-Shyn
Published: August 2024

Survival in animals relies on navigating environments aligned with physiological needs. In
Drosophila melanogaster
, antennal ionotropic receptors (IRs) sensing humidity changes govern hygrotaxis behavior. This study sheds light on the crucial role of IR8a neurons in the transition from high humidity avoidance to water-seeking behavior when the flies become thirsty. These neurons demonstrate a heightened calcium response toward high humidity stimuli in satiated flies and a reduced response in thirsty flies, modulated by fluctuating levels of the neuropeptide leucokinin, which monitors the internal water balance. Optogenetic activation of IR8a neurons in thirsty flies triggers an avoidance response similar to the moisture aversion in adequately hydrated flies. Furthermore, our study identifies IR40a neurons as associated with dry avoidance, while IR68a neurons are linked to moist attraction. The dynamic interplay among these neurons, each with opposing valences, establishes a preference for approximately 30% relative humidity in well-hydrated flies and facilitates water-seeking behavior in thirsty individuals. This research unveils the intricate interplay between sensory perception, neuronal plasticity, and internal states, providing valuable insights into the adaptive mechanisms governing hygrotaxis in
Drosophila
.
Mechanism of gabapentinoid potentiation of opioid effects on cyclic AMP signaling in neuropathic pain
Authors: Garza-Carbajal Anibal , Bavencoffe Alexis , Herrera Juan J. , Johnson Kayla N. , Walters Edgar T. , Dessauer Carmen W.
Published: August 2024

Over half of spinal cord injury (SCI) patients develop opioid-resistant chronic neuropathic pain. Safer alternatives to opioids for treatment of neuropathic pain are gabapentinoids (e.g., pregabalin and gabapentin). Clinically, gabapentinoids appear to amplify opioid effects, increasing analgesia and overdose-related adverse outcomes, but in vitro proof of this amplification and its mechanism are lacking. We previously showed that after SCI, sensitivity to opioids is reduced by fourfold to sixfold in rat sensory neurons. Here, we demonstrate that after injury, gabapentinoids restore normal sensitivity of opioid inhibition of cyclic AMP (cAMP) generation, while reducing nociceptor hyperexcitability by inhibiting voltage-gated calcium channels (VGCCs). Increasing intracellular Ca
2+
or activation of L-type VGCCs (L-VGCCs) suffices to mimic SCI effects on opioid sensitivity, in a manner dependent on the activity of the Raf1 proto-oncogene, serine/threonine-protein kinase C-Raf, but independent of neuronal depolarization. Together, our results provide a mechanism for potentiation of opioid effects by gabapentinoids after injury, via reduction of calcium influx through L-VGCCs, and suggest that other inhibitors targeting these channels may similarly enhance opioid treatment of neuropathic pain.
Capturing RAS oligomerization on a membrane
Authors: Yun Sangho D. , Scott Elena , Chang Jing-Yuan , Bahramimoghaddam Hanieh , Lynn Michael , Lantz Carter , Russell David H. , Laganowsky Arthur
Published: August 2024

RAS GTPases associate with the biological membrane where they function as molecular switches to regulate cell growth. Recent studies indicate that RAS proteins oligomerize on membranes, and disrupting these assemblies represents an alternative therapeutic strategy. However, conflicting reports on RAS assemblies, ranging in size from dimers to nanoclusters, have brought to the fore key questions regarding the stoichiometry and parameters that influence oligomerization. Here, we probe three isoforms of RAS [Kirsten Rat Sarcoma viral oncogene (KRAS), Harvey Rat Sarcoma viral oncogene (HRAS), and Neuroblastoma oncogene (NRAS)] directly from membranes using mass spectrometry. We show that KRAS on membranes in the inactive state (GDP-bound) is monomeric but forms dimers in the active state (GTP-bound). We demonstrate that the small molecule BI2852 can induce dimerization of KRAS, whereas the binding of effector proteins disrupts dimerization. We also show that RAS dimerization is dependent on lipid composition and reveal that oligomerization of NRAS is regulated by palmitoylation. By monitoring the intrinsic GTPase activity of RAS, we capture the emergence of a dimer containing either mixed nucleotides or GDP on membranes. We find that the interaction of RAS with the catalytic domain of Son of Sevenless (SOS
cat
) is influenced by membrane composition. We also capture the activation and monomer to dimer conversion of KRAS by SOS
cat
. These results not only reveal the stoichiometry of RAS assemblies on membranes but also uncover the impact of critical factors on oligomerization, encompassing regulation by nucleotides, lipids, and palmitoylation.
Phosphorylation of Insig-2 mediates inhibition of fatty acid synthesis by polyunsaturated fatty acids
Authors: Tian Jing , Goldstein Joseph L. , Li Shili , Schumacher Marc M. , Brown Michael S.
Published: August 2024

Insig-1 and Insig-2 are endoplasmic reticulum (ER) proteins that inhibit lipid synthesis by blocking transport of sterol regulatory element-binding proteins (SREBP-1 and SREBP-2) from ER to Golgi. In the Golgi, SREBPs are processed proteolytically to release their transcription-activating domains, which enhance the synthesis of fatty acids, triglycerides, and cholesterol. Heretofore, the two Insigs have redundant functions, and there is no rationale for two isoforms. The current data identify a specific function for Insig-2. We show that eicosapentaenoic acid (EPA), a polyunsaturated fatty acid, inhibits fatty acid synthesis in human fibroblasts and rat hepatocytes by activating adenylate cyclase, which induces protein kinase A (PKA) to phosphorylate serine-106 in Insig-2. Phosphorylated Insig-2 inhibits the proteolytic processing of SREBP-1, thereby blocking fatty acid synthesis. Phosphorylated Insig-2 does not block the processing of SREBP-2, which activates cholesterol synthesis. Insig-1 lacks serine-106 and is not phosphorylated at this site. EPA inhibition of SREBP-1 processing was reduced by the replacement of serine-106 in Insig-2 with alanine or by treatment with KT5720, a PKA inhibitor. Inhibition did not occur in mutant human fibroblasts that possess Insig-1 but lack Insig-2. These data provide an Insig-2-specific mechanism for the long-known inhibition of fatty acid synthesis by polyunsaturated fatty acids.
Interstitial cells of the sip syncytium regulate basal membrane potential in murine gastric corpus
Authors: Hwang Sung Jin , Kim MinKyung , Jones Amanda , Basma Naseer , Baker Salah A. , Sanders Kenton M. , Ward Sean M.
Published: August 2024

Smooth muscle cells (SMCs), Interstitial cells of Cajal (ICC) and Platelet‐derived growth factor receptor α positive (PDGFRα+) cells form an integrated, electrical syncytium within the gastrointestinal (GI) muscular tissues known as the SIP syncytium. Immunohistochemical analysis of gastric corpus muscles showed that c‐KIT+/ANO1+ ICC‐IM and PDGFRα+ cells were closely apposed to one another in the same anatomical niches. We used intracellular microelectrode recording from corpus muscle bundles to characterize the roles of intramuscular ICC and PDGFRα+ cells in conditioning membrane potentials of gastric muscles. In muscle bundles, that have a relatively higher input impedance than larger muscle strips or sheets, we recorded an ongoing discharge of stochastic fluctuations in membrane potential, previously called unitary potentials or spontaneous transient depolarizations (STDs) and spontaneous transient hyperpolarizations (STHs). We reasoned that STDs should be blocked by antagonists of ANO1, the signature conductance of ICC. Activation of ANO1 has been shown to generate spontaneous transient inward currents (STICs), which are the basis for STDs. Ani9 reduced membrane noise and caused hyperpolarization, but this agent did not block the fluctuations in membrane potential quantitatively. Apamin, an antagonist of small conductance Ca2+‐activated K+ channels (SK3), the signature conductance in PDGFRα+ cells, further reduced membrane noise and caused depolarization. Reversing the order of channel antagonists reversed the sequence of depolarization and hyperpolarization. These experiments show that the ongoing discharge of STDs and STHs by ICC and PDGFRα+ cells, respectively, exerts conditioning effects on membrane potentials in the SIP syncytium that would effectively regulate the excitability of SMCs.
Toward Precision in Critical Care Research: Methods for Observational and Interventional Studies
Authors: Graham Linck Emma J. , Goligher Ewan C. , Semler Matthew W. , Churpek Matthew M.
Published: August 2024

Critical care trials evaluate the effect of interventions in patients with diverse personal histories and causes of illness, often under the umbrella of heterogeneous clinical syndromes, such as sepsis or acute respiratory distress syndrome. Given this variation, it is reasonable to expect that the effect of treatment on outcomes may differ for individuals with variable characteristics. However, in randomized controlled trials, efficacy is typically assessed by the average treatment effect (ATE), which quantifies the average effect of the intervention on the outcome in the study population. Importantly, the ATE may hide variations of the treatment’s effect on a clinical outcome across levels of patient characteristics, which may erroneously lead to the conclusion that an intervention does not work overall when it may in fact benefit certain patients. In this review, we describe methodological approaches for assessing heterogeneity of treatment effect (HTE), including expert-derived subgrouping, data-driven subgrouping, baseline risk modeling, treatment effect modeling, and individual treatment rule estimation. Next, we outline how insights from HTE analyses can be incorporated into the design of clinical trials. Finally, we propose a research agenda for advancing the field and bringing HTE approaches to the bedside.
Lymphovenous Bypass as an Alternative Strategy for Managing Phleboedema and Venous Leg Ulcers: Preliminary Results
Authors: Chao Sungchuan , Kuan Chenhisang , Lin Yingsheng , Tai Haochih , Cheng Naichen
Published: August 2024

Background:

Chronic venous leg ulcers (VLUs) are a common manifestation of chronic venous insufficiency, accounting for up to 70% of all chronic leg ulcers. Patients sustained refractory ulcers and persistent phleboedema even with a combination of different treatment methods. Lymphovenous bypass (LVB) has shown promising results in patients with lymphedema. We hypothesize that LVB could potentially alleviate VLUs and phleboedema, given their symptom similarities with lymphedema.

Methods:

From May 2021 to June 2023, we prospectively deployed LVB in patients with nonhealing stasis ulcers after 4-week traditional care, or in those with persistent phleboedema despite prior surgery for vein etiologies. Demographics, healing course and recurrence, lymphoscintigraphy, and VLU quality of life (QoL) questionnaires were collected.

Results:

Thirty-one patients were treated with LVB and additional skin grafting as necessary. Their mean age was 62.6 ± 14.7 years, with male predominance (20, 64.5%), and most patients sustained clinical, etiologic, anatomic, pathophysiologic classification C6 (25, 80.6%). Postoperatively, wound healing and phleboedema decongestion were observed mostly within 2 months. The VLU QoL questionnaire (39.3% response rate) showed improvement in QoL in activities, and psychological and symptom distress aspects.

Conclusions:

Using LVB for chronic venous insufficiency showed an increase in the success rate of ulcer healing and decompression of the swollen limbs with durable results. Patient-reported outcome measures disclosed the potential benefits of LVB. Large-scale randomized controlled trials and pathophysiological studies are warranted to elucidate its efficacy.
Social Environment and Neurobehavioral Outcomes 1 Year After Severe Pediatric TBI in the Intensive Care Unit
Authors: Miley Aimee E. , Patronick Jamie , Zhang Nanhua , Bode Rachel L. , Fabio Anthony , Treble-Barna Amery , Chima Ranjit S. , Adlam Anna-Lynne R. , Bell Michael J. , Wisniewski Stephen R. , Beers Sue R. , Wade Shari L. , Kurowski Brad G.
Published: August 2024

Objective:

To examine the association of home and neighborhood environment with neurobehavioral outcomes after severe pediatric traumatic brain injury (TBI).

Setting:

Domestic and international children’s medical centers.

Participants:

Participants enrolled in the study were 18 years or younger at the time of their severe TBI (Glasgow Coma Scale [GCS] ≤ 8), admitted to the intensive care unit, and underwent placement of an intracranial pressure (ICP) monitor. Exclusionary criteria included less severe injury (GCS > 8), pregnancy, and/or ICP monitor placement occurred at a non-participating hospital.

Design:

A multicenter, observational cohort study.

Main Measures:

Outcomes assessed at 12 months post-injury included measures of global functioning, intellectual ability, caregiver-report measures of family functioning, executive functioning behaviors, behavior problems, and health-related quality of life. We examined mortality risk (assessed acutely after injury), family functioning (assessed at 12 months post-injury) and parenting practices, social environment, and neighborhood stressors (all assessed > 12 months post-injury), as correlates and moderators of the 12-month post-injury outcomes.

Results:

Home and neighborhood factors were associated with neurobehavioral outcomes (ie, intellectual ability, executive functioning, behavioral adjustment, and health-related quality of life) but not with global functioning outcomes. A negative association between a more vulnerable home and neighborhood environment and neurobehavioral outcomes was more consistent in older children compared with younger children, based on age of injury. The influence of mortality risk on neurobehavioral outcomes was variable.

Conclusion:

Parenting practices and quality of social and neighborhood environment are associated with neurobehavioral outcomes 12 months after severe pediatric TBI. More research is needed to better understand the relationship between home/neighborhood stressors and TBI recovery to develop and implement strategies for patients and families to optimize outcomes. Future intervention development should focus on addressing parenting practices and social environment in a developmentally sensitive way for children who have sustained a severe TBI.
Evaluation of a Slim Modiolar Electrode Array: A Temporal Bone Study
Authors: Asfour Leena , Risi Frank , Treaba Claudiu , Kirk Jonathon , Roland Thomas J.
Published: August 2024

Hypothesis

Evaluation of the Slim Modiolar (SM) electrode in temporal bones (TB) will elucidate the electrode's insertion outcomes.

Background

The SM electrode was designed for atraumatic insertion into the scala tympani, for ideal perimodiolar positioning and with a smaller caliber to minimize interference with cochlear biological processes.

Methods

The SM electrode was inserted into TBs via a cochleostomy. First, the axial force of insertion was measured. Next, TBs were inserted under fluoroscopy to study insertion dynamics, followed by histologic evaluation of electrode placement and cochlear trauma. A subset of TBs were inserted with the Contour Advance (CA) electrode for comparison.

Results

Sixteen of 22 insertions performed to measure the axial force of insertion had flat or near zero insertion force profiles. Six insertions had increased insertion forces, which were attributed to improper sheath depth before electrode insertion. Under real-time fluoroscopy, 23 of 25 TBs had uneventful insertion and good perimodiolar placement. There was 1 scala vestibuli insertion due to suboptimal cochleostomy position and 1 tip roll over related to premature electrode deployment. When compared with the CA electrode, 14 of 15 insertions with the SM electrode resulted in a more perimodiolar electrode position. No evidence of trauma was found in histologic evaluation of the 24 TBs with scala tympani insertions.

Conclusion

TB evaluation revealed that the SM electrode exerts minimal insertion forces on cochlear structures, produces no histologic evidence of trauma, and reliably assumes the perimodiolar position. Nonstandard cochleostomy location, improper sheath insertion depth, or premature deployment of the electrode may lead to suboptimal outcomes.
Utility of MRI in the Outpatient Evaluation of Patients With Chronic Continuous or Recurrent Dizziness
Authors: Gupta Ankur , Thai Anthony , Steenerson Kristen K. , Alyono Jennifer
Published: August 2024

Objective

This study aimed to assess the utility of magnetic resonance imaging (MRI) in outpatient evaluation of patients with chronic continuous or recurrent dizziness (CCRD) and determine whether certain patient characteristics, symptoms, or examination findings are associated with diagnostic MRI findings.

Study Design

Retrospective cohort study.

Setting

Ambulatory center.

Patients

304 patients who received an MRI for CCRD.

Intervention

Diagnostic utility of MRI in patients with CCRD.

Main Outcome Measure

MRI diagnostic findings in patients with CCRD and associated patient characteristics, symptoms, or examination findings.

Materials and Methods

In this retrospective analysis, 304 patients who visited an outpatient clinic between 1998 and 2023 and underwent MRI for CCRD, without previously diagnosed neurological abnormalities, were examined. The study investigated the relationship between demographic characteristics, comorbidities, clinical symptoms, and examination findings with diagnostic MRI findings. Univariate analysis was used to identify factors predictive of diagnostic MRI findings.

Results

Out of 304 patients, 11 (3.6%; 95% confidence interval [CI], 1.5–5.72%) had diagnostic MRI findings. The most common diagnostic finding (36.4%) was brain metastasis, seen only in patients with previously diagnosed metastatic cancer. Univariate analysis revealed that hypertension (p = 0.004, likelihood ratio [LR] = 2.51), hyperlipidemia (p = 0.004, LR = 2.91), and cancer (p = 0.021, LR = 2.96) were significantly associated with diagnostic MRI findings. Incidental findings were observed in 73 patients (24%; 95% CI, 19.2–28.8%). Outside of cancer patients, six (2.3%; 95% CI, 1.1–5.0%) had diagnostic MRI findings.

Conclusion

In our study, MRI rarely displayed diagnostic findings in patients with CCRD and normal neurologic examination. However, individuals with hypertension, hyperlipidemia, or cancer were significantly more likely to display positive MRI findings. It is essential to carefully consider the need for MRI when assessing patients with CCRD.
Determining the Impact of Preoperative Psychiatric Comorbidities on Readmission After Resection of Vestibular Schwannoma
Authors: Patel Aneesh A. , Kennedy Dean , Dupuis Genevieve , Levi Jessica R. , Weber Peter C.
Published: August 2024

Objective

To determine the impact of comorbid depression on readmission after vestibular schwannoma resection.

Study design

Retrospective database analysis.

Setting

National database of readmitted patients.

Patients

The Nationwide Readmission Database (NRD) was retrospectively reviewed for patients with history of vestibular schwannoma, identified by International Classification of Disease, Ninth Revision (ICD-9) code 225.1 and ICD-10 code D33.3, who underwent surgical resection (ICD-9 04.01, ICD-10-PCS 00BN0ZZ) in 2020.

Interventions

Therapeutic.

Main outcome measures

Need for rehabilitation, need for procedures, length of stay, cost of readmission, and insurance status.

Results

A total of 1997 patients were readmitted after resection of vestibular schwannoma in 2020. Of these patients, 290 had history of a comorbid depressive disorder.

A significantly higher proportion of patients with history of comorbid depression were transferred to a rehabilitation facility after readmission (11.30% versus 4.30%, p < 0.001). Length of stay (p = 0.227) and total readmission cost (p = 0.723) did not differ significantly, but a significantly lower proportion had private insurance (55.40% versus 64.40%, p = 0.027).

Conclusion

Depression is associated with higher utilization of postoperative rehabilitation services and higher rates of medical comorbidities, and should be considered during preoperative evaluation.
Improving Linkages Between Sexual and Reproductive Health and Substance Use Providers: The Partnership to Advance Integrated Referrals
Authors: Dublin Sonya , Bermudez Dayana , Ortiz Christina , Tobier Natalie , Levy Joslyn , Hargarten Leah
Published: August 2024

Background and Objectives:

Women of reproductive age with substance use (SU) disorders have lower rates of contraceptive use and higher rates of unintended pregnancy than women without SU disorders and are less likely to access treatment than men. Integration of SU and sexual and reproductive health (SRH) services, using a model known as Screening, Brief Intervention, and Referral to Treatment (SBIRT), has been proven effective in reducing SU and improving health care equity. The SBIRT model includes screening, brief intervention (a short client-centered conversation providing an opportunity to identify/discuss concerns), and referral to treatment. The purpose of this study was to test whether an established quality improvement (QI) learning collaborative model could be used to support SU and SRH sites in implementing an SBIRT/SBIRT-like model to improve health outcomes for women. Five SRH sites and 4 SU sites across New York State participated in the Partnership to Advance Integrated Referrals (PAIR), an 18-month QI learning collaborative designed and implemented by Public Health Solutions.

Methods:

Six standardized mixed-methods data collection tools were used over 18 months to gather process and outcome data from over 130 QI team members and site staff and over 5000 clients.

Results:

By the end of PAIR, QI team members and site staff showed a reduction in bias, increased knowledge and comfort, increased rating of organizational practices related to client-centered care, and increased access to peer learning, information about best practices, and training and technical assistance. SU sites increased SRH screening from 47.9% in the first quarter of data collection to 67.4% in the final quarter and increased brief interventions from 92.5% in the first quarter to 100.0% in the final quarter. Similarly, SRH sites increased SU screening from 51.6% to 75.6% and increased brief interventions from 81.3% to 85.1%. The processes and outcomes were very different for the SU and SRH sites, and their varying successes and challenges are discussed. Making and verifying referrals remained challenging.

Conclusions:

The results of PAIR demonstrated the feasibility of SU and SRH sites implementing an SBIRT/SBIRT-like model when supported by a QI learning collaborative. Larger community and organizational challenges (COVID-19, staff turnover) still present barriers to improved reproductive health and SU outcomes for women.
The Human–Technology Continuum
Authors: Shen Gordon C. , Mullen Deborah M. , DePuccio Matthew J. , Kerrissey Michaela
Published: August 2024

Background and Objectives:

Managers in health care today face an array of digital technologies that assist or augment certain human tasks. But these technologies are often fraught and present challenges to managers, whose competencies must evolve to keep pace with technological advancements.

Methods:

Drawing on theory about technology, work, and organizations, we present a human-technology continuum to facilitate this discussion for managers. Furthermore, we illustrate how managerial competencies are linked to the entire human–technology continuum, rather than to specific technologies, using diabetes management examples.

Results:

The human–technology continuum indicates that augmentative technologies are layered onto assistive ones in health care settings. This suggests that technological advancements not only enhance but alter managerial competencies.

Conclusions:

Digital technology stretches the boundaries of managers’ day-to-day work in health care. Therefore, we make the following suggestions so the managers can be responsive to ongoing digital transformations: restructuring work, training the workforce, neutralizing threats, establishing ethical boundaries, and building partnerships.
The Role of CT-guided Core Needle Biopsy in Pancreatic Tumors: An Initial Evaluation in Modern Oncology
Authors: Eyheremendy Eduardo P. , Angeramo Cristian A. , Méndez Patricio
Published: August 2024

Purpose:

Neoadjuvant chemotherapy has recently become the standard of care for borderline resectable pancreatic ductal adenocarcinoma (PDAC), and there have even been numerous reports evaluating its potential benefits in resectable PDAC. However, neoadjuvant therapy first requires a histological or cytological diagnosis. This study aimed to analyze the safety and diagnostic yield of CT-guided core needle biopsy (CNB).

Material and Methods:

A retrospective analysis of patients with pancreatic tumor requiring a CNB during the period 2015 to 2023 were included. Biopsies were performed with an 18-20 G Tru-Core needle using a coaxial system and automatic biopsy gun. Demographics, procedural variables, postoperative outcomes, and histological results were analyzed.

Results:

A total of 43 pancreatic biopsies were performed in 42 patients. The mean age was 60 years (35 to 81 y), and 24 (56%) were males. Tumors were more frequently localized in the head (42%) and body (42%) of the pancreas. The mean size of the pancreatic lesions was 53.77 mm (17 to 181 mm) and the mean number of samples per biopsy was 4 (1 to 12). Most procedures were performed via direct access (81%). No major complications were observed. Histological diagnosis was obtained in 40 (93%) patients, with a sensitivity of 93%, specificity of 100% and an overall accuracy rate of 93%. The probability of performing a molecular diagnostic test increased with the year of biopsy (OR 3.34, 95% CI 1.33-8.40, P=0.01)

Conclusions:

CNB is an efficient and safe method for obtaining high-quality material. This approach could be essential as molecular profiling continues to improve the diagnosis, prognosis, and treatment of PDAC.