bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulated Fibrosis and Mechanosensing of Fibroblasts by SB525334 in Pediatric Subglottic Stenosis
Authors: Ali Akbari Ghavimi Soheila , Aronson Matthew R. , Ghaderi Daniel D. , Friedman Ryan M. , Patel Neil , Giordano Terri , Borek Ryan C. , Devine Conor M. , Han Lin , Jacobs Ian N. , Gottardi Riccardo
Published: July 2023

Objective

Subglottic stenosis (SGS) may result from prolonged intubation where fibrotic scar tissue narrows the airway. The scar forms by differentiated myofibroblasts secreting excessive extracellular matrix (ECM). TGF‐β1 is widely accepted as a regulator of fibrosis; however, it is unclear how biomechanical pathways co‐regulate fibrosis. Therefore, we phenotyped fibroblasts from pediatric patients with SGS to explore how key signaling pathways, TGF‐β and Hippo, impact scarring and assess the impact of inhibiting these pathways with potential therapeutic small molecules SB525334 and DRD1 agonist dihydrexidine hydrochloride (DHX).

Methods

Laryngeal fibroblasts isolated from subglottic as well as distal control biopsies of patients with evolving and maturing subglottic stenosis were assessed by α‐smooth muscle actin immunostaining and gene expression for α‐SMA, FN, HGF, and CTGF markers. TGF‐β and Hippo signaling pathways were modulated during TGF‐β1‐induced fibrosis using the inhibitor SB525334 or DHX and analyzed by RT‐qPCR for differential gene expression and atomic force microscopy for ECM stiffness.

Results

SGS fibroblasts exhibited higher α‐SMA staining and greater inflammatory cytokine and fibrotic marker expression upon TGF‐β1 stimulation (p < 0.05). SB525334 restored levels to baseline by reducing SMAD2/3 nuclear translocation (p < 0.0001) and pro‐fibrotic gene expression (p < 0.05). ECM stiffness of stenotic fibroblasts was greater than healthy fibroblasts and was restored to baseline by Hippo pathway modulation using SB525334 and DHX (p < 0.01).

Conclusion

We demonstrate that distinct fibroblast phenotypes from diseased and healthy regions of pediatric SGS patients respond differently to TGF‐β1 stimulation, and SB525334 has the superior potential for subglottic stenosis treatment by simultaneously modulating TGF‐β and Hippo signaling pathways.

Level of Evidence

NA Laryngoscope, 134:287–296, 2024
Voice Improvement After Essential Tremor Treatment via Focused Ultrasound and Deep Brain Stimulation
Authors: Larner Peter , Jonas Rachel , Gutierrez Claudia N. , McGarey Patrick , Lott Joanna , Moosa Shayan , Elias W. Jeffrey , Daniero James
Published: July 2023

Objectives

The primary objective of this study was to determine whether two neurosurgical procedures, deep brain stimulation (DBS) and focused ultrasound (FUS), to treat essential tremor (ET) of the upper limb also reduce vocal tremor (VT) in patients with comorbid dysphonia.

Methods

Twelve patients with ET and concomitant VT scheduled for neurosurgical intervention (FUS or DBS) or returning for follow‐up after DBS implantation were assessed. FUS patients were assessed pre‐ and post‐intervention and DBS patients were assessed with the electrodes turned on and off post‐implantation. Three voice recordings of a sustained /a/ were obtained for each participant condition. Percent fundamental frequency variability (FFV) was calculated for each recorded sustained vowel. Additionally, blinded expert perceptual VT rating (VTR) was performed to assess subjective changes in tremors.

Results

Of the 12 patients, seven underwent unilateral FUS, and five underwent bilateral DBS. Mean FFV without neurosurgical intervention was 18.3%, SD = 7.8 and with neurosurgical intervention was 6.3%, SD = 3.0 (t (70) =8.7, p < 0.001). Mean FFV decreased in the FUS cohort from 22.0%, SD = 7.1 pre‐ablation to 6.7%, SD = 2.4 post‐ablation (t (40) = 7.7, p < 0.001). Mean FFV also decreased in the DBS cohort from 15.7%, SD = 7.0 to 6.0%, SD = 3.3 when stimulation was turned on (t (28)=5.7 p < 0.001). In the FUS group, mean VTR decreased from 4.0 to 1.4 post‐ablation (Z = 7.8, p < 0.001). In the DBS group, mean VTR decreased from 3.3 to 2.1 with stimulation (Z = 4.1, p < 0.001).

Conclusion

Neurosurgical interventions for ET (bilateral DBS and unilateral FUS) demonstrate acoustic and perceptual benefits for VT.

Level of Evidence

4 Laryngoscope, 134:367–373, 2024
Contrasting trends in water quality between adjacent ocean‐ and river‐dominated estuaries: Evidence for marsh porewaters as a source of nutrient enrichment?
Authors: Dunn Robert P. , Krask Julie L. , Pinckney James L. , Smith Erik M.
Published: July 2023

Degradation of estuarine water quality during the Anthropocene has largely resulted from discharges of nutrients leading to eutrophication. Recently, upstream management practices have led to comparatively reduced nutrient input into estuaries. Concurrently, climate cycles and impacts associated with anthropogenic climate warming can affect the long‐term conditions observed within estuaries. Using long‐term monitoring data from adjacent southeastern U.S. estuaries, we show that decadal‐scale trends in nutrient concentrations and phytoplankton standing stock differ between the two connected systems. These contrasting trends appear to result from differences in oceanic influence, the extent of adjacent vegetated marsh, watershed size, and upstream degradation. In the minimally impacted, ocean‐dominated North Inlet estuary, we document increasing ammonium and chlorophyll a (Chl a), while in the adjacent, river‐dominated Winyah Bay, ammonium, and Chl a concentrations are more variable but do not appear to have increased over the same time period. Surprisingly, total nitrogen exhibits the opposite pattern: temporal stability in North Inlet but increasing in Winyah Bay. We hypothesize that sea level rise associated with climate change has driven a complex set of interactions between salt marsh porewaters and tidal pumping, leading to the spillover of nutrients from salt marshes into tidal creeks in North Inlet. In Winyah Bay, this mechanism is less evident as a driver of ammonium concentrations, likely due to the outsized effect of watershed nutrient input and the narrow fringing marsh platform. The degree to which this mechanism operates in other estuaries, which vary in tidal range, the extent of vegetated marsh, watershed size, and degree of anthropogenic degradation warrants further study.
Numerical solution of multidimensional time‐space fractional differential equations of distributed order with Riesz derivative
Authors: Mohammed Ghuraibawi Amer Abdulhussein , Marasi H. R. , Derakhshan M. H. , Kumar Pushpendra
Published: July 2023

In this article, we derive a computational scheme joining the finite difference and operational matrix methods to numerically simulate fractional differential equations of distributed order with Riesz derivatives subject to the initial and Dirichlet boundary conditions. The finite difference method is used to discretize Riesz‐space fractional derivatives, and the operational matrix method is based on fractional shifted Gegenbauer functions for the approximation of time derivatives. The derived method transforms the given equation into a system of linear algebraic equations. For the numerical solution, we derive the optimal error bound and prove the theoretical unconditional stability with respect to the
‐norm. Furthermore, we numerically verify the stability of the proposed method. We observe the accuracy of the second order of the given schemes. The accuracy and effectiveness of the method are checked to solve some problems of telegraph equations. The CPU running time for the method with a fractional shifted Gegenbauer basis is much less than for methods with other bases.
An improved analytical approach to establish the soliton solutions to the time‐fractional nonlinear evolution models
Authors: İlhan Onur Alp , Islam M. Nurul , Akbar M. Ali , Soybaş Danyal
Published: July 2023

The time‐fractional Schrödinger (higher dimensional) and the Zakharov–Kuznetsov (ZK) models are the noteworthy modeling equations to interpret the propagation of signal in nonlinear optical fibers, small‐amplitude gravity waves on the surface water, high frequency acoustic waves, the interactions of small amplitude waves, the ion acoustic waves, nonlinear optics, Bose‐Einstein condensates, dynamics of plasma particles, etc. In this article, in order to develop advanced and broad‐spectrum closed‐form soliton solutions of the previously described nonlinear models, the advanced auxiliary equation approach has been put in used with reference to the beta‐derivative concept. The established soliton solutions are further comprehensive and typical and found in the form fractional, exponential, hyperbolic, and trigonometric functions and their variation. We depict 3D shape of the obtained solitons and explain the physical significance of the solitons. The accomplished solutions affirm that the method is effective and powerful and yields compatible solutions to fractional nonlinear evolution equations.
Dosimetric characterization of a rotating anode x‐ray tube for FLASH radiotherapy research
Authors: Miles Devin , Sforza Daniel , Wong John , Rezaee Mohammad
Published: July 2023

Purpose

Most current research toward ultra‐high dose rate (FLASH) radiation is conducted with advanced proton and electron accelerators, which are of limited accessibility to basic laboratory research. An economical alternative to charged particle accelerators is to employ high‐capacity rotating anode x‐ray tubes to produce kilovoltage x‐rays at FLASH dose rates at short source‐to‐surface distances (SSD). This work describes a comprehensive dosimetric evaluation of a rotating anode x‐ray tube for potential application in laboratory FLASH study.

Methods and materials

A commercially available high‐capacity fluoroscopy x‐ray tube with 75 kW input power was implemented as a potential FLASH irradiator. Radiochromic EBT3 film and thermoluminescent dosimeters (TLDs) were used to investigate the effects of SSD and field size on dose rates and depth‐dose characteristics in kV‐compatible solid water phantoms. Custom 3D printed accessories were developed to enable reproducible phantom setup at very short SSD. Open and collimated radiation fields were assessed.

Results

Despite the lower x‐ray energy and short SSD used, FLASH dose rates above 40 Gy/s were achieved for targets up to 10‐mm depth in solid water. Maximum surface dose rates of 96 Gy/s were measured in the open field at 47 mm SSD. A non‐uniform high‐to‐low dose gradient was observed in the planar dose distribution, characteristic of anode heel effects. With added collimation, beams up to 10‐mm diameter with reasonable uniformity can be produced. Typical 80%–20% penumbra in the collimated x‐ray FLASH beams were less than 1 mm at 5‐mm depth in phantom. Ramp‐up times at the maximum input current were less than 1 ms.

Conclusion

Our dosimetric characterization demonstrates that rotating anode x‐ray tube technology is capable of producing radiation beams in support of preclinical FLASH radiobiology research.
Characterization of renal fibrosis in rats with chronic kidney disease by in vivo tomoelastography
Authors: Krehl Karolina , Hahndorf Julia , Stolzenburg Nicola , Taupitz Matthias , Braun Jürgen , Sack Ingolf , Schnorr Jörg , Guo Jing
Published: July 2023

Chronic kidney disease (CKD) is characterized by structural changes, such as tubular atrophy, renal fibrosis, and glomerulosclerosis, all of which affect the viscoelastic properties of biological tissues. However, detection of renal viscoelasticity changes because diagnostic markers by in vivo elastography lack histopathological validation through animal models.

Therefore, we investigated in vivo multiparametric magnetic resonance imaging (mp‐MRI), including multifrequency magnetic resonance elastography‐based tomoelastography, in the kidneys of 10 rats with adenine‐induced CKD and eight healthy controls. Kidney volume (in mm3), water diffusivity (apparent diffusion coefficient [ADC] in mm2/s), shear wave speed (SWS; in m/s; related to stiffness), and wave penetration rate (PR; in m/s; related to inverse viscosity) were quantified by mp‐MRI and correlated with histopathologically determined renal fibrosis (collagen area fraction [CAF]; in %). Kidney volume (40% ± 29%, p = 0.009), SWS (11% ± 12%, p = 0.016), and PR (20% ± 15%, p = 0.004) were significantly increased in CKD, which was accompanied by ADC (−24% ± 27%, p = 0.02). SWS, PR, and ADC were correlated with CAF with R = 0.63, 0.75, and −0.5 (all p < 0.05), respectively. In the CKD rats, histopathology showed tubule dilation due to adenine crystal deposition. Collectively, our results suggest that collagen accumulation during CKD progression transforms soft‐compliant renal tissue into a more rigid‐solid state with reduced water mobility. We hypothesized that tubule dilation—a specific feature of our model—might lead to higher intraluminal pressure, which could also contribute to elevated renal stiffness. Tomoelastography is a promising tool for noninvasively assessing disease progression, detecting biomechanical properties that are sensitive to different pathologic features of CKD.
Registered Nurses' and nursing students' perspectives on moral distress and its effects: A mixed‐methods systematic review and thematic synthesis
Authors: Watts Tessa , Sydor Anna , Whybrow Dean , Temeng Eunice , Hewitt Rachael , Pattinson Rachael , Bundy Christine , Kyle Richard G. , Jones Bethan
Published: July 2023

Aim

To examine Registered Nurses (RNs') and nursing students' perspectives on factors contributing to moral distress and the effects on their health, well‐being and professional and career intentions.

Design

Joanna Briggs Institute mixed‐methods systematic review and thematic synthesis. Registered in Prospero (Redacted).

Methods

Five databases were searched on 5 May 2021 for studies published in English since January 2010. Methodological quality assessment was conducted in parallel with data extraction.

Results

Searches yielded 2343 hits. Seventy‐seven articles were included. Most were correlational design and used convenience sampling. Studies were mainly from North America and Asia and situated in intensive and critical care settings. There were common, consistent sources of moral distress across continents, specialities and settings. Factors related to perceived inability or failure to enact moral agency and responsibility in moral events at individual, team and structural levels generated distress. Moral distress had a negative effect on RNs health and psychological well‐being.

Patient or Public Contribution

No patient or public contribution to this systematic review.
Physiological responses and behavioural organization of very low birth weight infants during swaddled versus traditional weighing
Authors: Vicente‐Perez Silvia , Robleda Gemma , Gich Ignasi , Nolla Tania , Ponce‐Taylor Jaume , Verd Sergio , Ginovart Gemma
Published: July 2023

Aim

Despite the consequences of neonatal distress and agitation, preterm infants undergo stress owing to weighing procedures. The objective of this study was to enable very low birth weight infants to maintain adequate self‐regulation during weighing.

Design

This prospective crossover study utilizes a within‐subjects design, where intervention days were compared to control days.

Method

Infants were exposed to both swaddled and unswaddled weighing in an intensive care nursery setting. Nineteen very low birth weight infants were weighed on two consecutive days. Variables of heart rate, respiratory rate and ALPS‐Neo score were recorded.

Results

Stress score decreased significantly from 1.65 (pre‐weight) to 0.23 (weight measurement) in swaddled‐intervention periods; conversely, it increased significantly from 1.26 (pre‐weight) to 4.97 (weight measurement) in control periods. During weight measurement, heart and respiratory rate were significantly lower for swaddled‐intervention days when compared to control days. Given the significant impact of swaddled weighing in reducing stress, this method can be used as an appropriate weighing procedure in intensive care. This research has no patient or public contribution.
Refining and psychometric evaluation of the falling risk assessment tool in ophthalmology inpatients
Authors: Li Muling , Li Chunmei , Huang Qinghui , Zhou Hongzhen , Xie Ling , Chen Fangni , Lin Shaoqin , Yang Juan
Published: July 2023

Aims

The aim of this study was to refine the Falling Risk Assessment Tool in Ophthalmology Inpatients (FRAT) and assess its psychometric properties.

Design

A cross‐sectional design was used.

Methods

A convenience sample of 730 patients in the ophthalmology department was recruited in a level A tertiary hospital in Guangdong Province from July 2021 to January 2022. Data were analysed using item analysis, interrater reliability, content validation, internal consistency reliability and exploratory factor analysis.

Results

Five factors were extracted, accounting for 63.039% of the variance. The interrater reliability of the tool was 0.97. Cronbach's α was 0.658. The I‐CVI was 0.75–1.00, the S‐CVI/UA was 0.95 and the adjusted mean values of Kappa for indicators ranged from 0.72 to 1.00, as evaluated by the expert group. The FRAT showed satisfactory reliability and validity, and can be used to measure the fall risk assessment in ophthalmology inpatients.

Patient or Public Contribution

After explaining the purpose, the patients received our fall risk assessment and answered the corresponding questionnaire questions.
Investigation on mechanical, gas barrier, and biodegradation properties of graphene oxide reinforced bovine trimmings derived collagen biocomposite
Authors: Paul Adhir Chandra , Uddin Md. Elias , Layek Rama Kanta , Saha Tomas
Published: July 2023

Now‐a‐days, let out a huge number of bovine trimmings based solid waste from tanneries has caused significant environmental concerns. To overcome this problem, this study emphasizes on bovine trimmings derived collagen based high‐performance composite with graphene oxide (Col‐GO) by using solvent evaporation method. The Col‐GO composite film formation was governed by plasticization with glycerol, crosslinking reaction of collagen chain; and H‐bonding interaction between GO and collagen functional groups. The Col‐GO composite films were characterized by Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and contact angle measurements. FTIR and TGA results indicate that interfacial H‐bonding interaction between GO with collagen, and thermal stability of Col‐GO composites film. Contact angle results indicate that hydrophobicity of Col‐GO films was significantly enhanced compared to pure collagen film. The SEM analysis results indicate the homogeneous integration of GO in the Col‐GO composite film. The composite film exhibits improvement in tensile strength and Young's modulus (YM) by 45% and 33% respectively. The water and gas barrier properties of the composite film improved by 47.4%, 66.57%, and 87.34%, respectively compared to pure collagen film. The Col‐GO composite film showed excellent biodegradation in the soil burial test, degrading 79.47% in 42 days. The potential of the biodegraded Col‐GO composite sample as a biofertilizer has been investigated by cultivating Spinacia oleracea seeds. The Col‐GO composite film might be a very promising bio‐compostable flexible and sustainable packaging film alternative to plastic packaging made from oil.
Preparation of poly(2‐hydroxyethyl methacrylate)‐grafted chitosan‐montmorillonite superabsorbent nanocomposite for adsorption of bovine serum albumin
Authors: Öztürk Simge , Demir Nalan
Published: July 2023

In this paper, we examined adsorption process of bovine serum albumin (BSA) on [p(HEMA)‐g‐CTS]/MMT ([poly(2‐hydroxyethyl methacrylate)‐graft‐chitosan]/montmorillonite) superabsorbent nanocomposite. [p(HEMA)‐g‐CTS]/MMT superabsorbent nanocomposite was synthesized via free radical polymerization. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and thermal gravimetric analysis (TGA) techniques, and also swelling test have been utilized for the structural characterization of the synthesized [p(HEMA)‐g‐CTS]/MMT superabsorbent nanocomposite. The influence of numerious adsorption parameters (initial BSA concentration, contact time, pH, sorbent amount, temperature, and ionic strength) on adsorption process were evaluated. Adsorption results showed that the superabsorbent nanocomposite had high affinity to BSA, and maximum adsorption capacity of [p(HEMA)‐g‐CTS]/MMT superabsorbent nanocomposite is 75.8 mg/g. The BSA adsorption results showed that the adsorption kinetics parameters was found to be suitable for the pseudo‐second‐order kinetic adsorption model and the equilibrium BSA adsorption data were explicated according to the Freundlich adsorption isotherm model.
Return visit rates after an emergency department discharge for children with sickle cell pain episodes
Authors: Coleman Keli D. , McKinley Kenneth , Ellison Angela M. , Alpern Elizabeth R. , Hariharan Selena , Topoz Irina , Wurtz Morgan , Nielsen Blake , Cook Lawrence J. , Morris Claudia R. , Brandow Amanda M. , Campbell Andrew D. , Liem Robert I. , Nuss Rachelle , Quinn Charles T. , Thompson Alexis A. , Villella Anthony , King Allison A. , Baumann Ana , Frankenberger Warren , Brousseau David C.
Published: July 2023

Background

High return visit rates after hospitalization for people with sickle cell disease (SCD) have been previously established. Due to a lack of multicenter emergency department (ED) return visit rate data, the return visit rate following ED discharge for pediatric SCD pain treatment is currently unknown.

Procedure

A seven‐site retrospective cohort study of discharged ED visits for pain by children with SCD was conducted using the Pediatric Emergency Care Applied Research Network Registry. Visits between January 2017 and November 2021 were identified using previously validated criteria. The primary outcome was the 14‐day return visit rate, with 3‐ and 7‐day rates also calculated. Modified Poisson regression was used to analyze associations for age, sex, initial hospitalization rate, and a visit during the COVID‐19 pandemic with return visit rates.

Results

Of 2548 eligible ED visits, approximately 52% were patients less than 12 years old, 50% were female, and over 95% were non‐Hispanic Black. The overall 14‐day return visit rate was 29.1% (95% confidence interval [CI]: 27.4%–30.9%; site range 22.7%–31.7%); the 7‐ and 3‐day return visit rates were 23.0% (95% CI: 21.3%–24.6%) and 16.7% (95% CI: 15.3%–18.2%), respectively. Younger children had slightly lower 14‐day return visit rates (27.3% vs. 31.1%); there were no associations for site hospitalization rate, sex, and a visit occurring during the pandemic with 14‐day returns.

Conclusion

Nearly 30% of ED discharged visits after SCD pain treatment had a return visit within 14 days. Increased efforts are needed to identify causes for high ED return visit rates and ensure optimal ED and post‐ED care.
The effect of matrix and interface properties modified by annealing on solid particle erosion behavior of carbon fiber reinforced polyetheretherketone
Authors: Çetin Beysim , Korkusuz Orkan Baran , Özzaim Pelin , Şahin Alp Eren , Fidan Sinan , Sınmazçelik Tamer
Published: July 2023

In this study, various heat treatments (annealings) were applied to carbon fiber reinforced polyetheretherketone (CF/PEEK) samples at four different temperatures (185, 225, 265, and 305°C) along two different holding times (30 and 270 min). The effects of changing matrix morphology, degree of crystallinity, and fiber‐matrix interface properties on thermo‐mechanical properties were investigated by differential scanning calorimetry (DSC) and dynamic mechanical analysis analyzes. Also, annealed CF/PEEK samples were tested to determine solid particle erosion characteristics. It was observed that the matrix crystallinity, fiber/matrix interface properties, and tribological properties of the CF/PEEK composites changed significantly with the thermal history. There was an increase in the degree of crystallinity with the increase in annealing temperature. It was observed that the degree of crystallinity increased up to about 27% and the damping factor decreased up to about 45%. As a result of the solid particle erosion tests performed under normal impact conditions, it was determined that the formation of the transcrystalline layer formed by heat treatment adversely affected the solid particle erosion resistance of the CF/PEEK. Erosion resistance of the heat‐treated samples (having higher fiber/matrix interface) was approximately 50% lower compared to the quenched sample. While the erosion rate for quenched samples is 14.5 × 10−5 g/g, this rate rises to 26.1 × 10−5 g/g for annealed samples. In addition, surface topography was examined by means of an optical profilometry, and surface morphology was examined by means of scanning electron microscopy. These examinations confirmed the experimental results.
Vancomycin dosing in high‐intensity continuous renal replacement therapy: A retrospective cohort study
Authors: Srour Nina , Lopez Chelsea , Succar Luma , Nguyen Peter
Published: July 2023

Introduction

An inverse relationship exists between vancomycin serum concentrations and the intensity of continuous renal replacement therapy (CRRT), reflected through the dialysate flow rate (DFR). There remains a lack of evidence to guide initial vancomycin dosing in the setting of high‐intensity CRRT (i.e., DFR >30 mL/kg/h). Additionally, recommendations for pharmacokinetic monitoring of vancomycin have transitioned from a trough‐based to area under the curve (AUC)‐based dosing strategy to optimize efficacy and safety. Therefore, an improved understanding of the impact of CRRT intensity on AUC/MIC (minimum inhibitory concentration) has the potential to enhance vancomycin dosing in this patient population.

Objectives

The goal of this study is to evaluate current vancomycin dosing strategies and achievement of pharmacokinetic targets in patients on high‐intensity CRRT.

Methods

This was a single‐center, retrospective cohort study of adult critically ill patients admitted to Houston Methodist Hospital between May 2019 and October 2021 and received vancomycin therapy while on high‐intensity CRRT. High‐intensity CRRT was defined by a DFR that was both ≥3 L/h and >30 mL/kg/h. Depending on the initial vancomycin dosing strategy, patients were stratified into either the traditional (15 mg/kg/day) or enhanced (≥15 mg/kg/day) dosing group. The primary outcome was the percent of patients who attained steady‐state AUC24/MIC ≥400 mg*h/L at the first obtained vancomycin level in the enhanced group compared with the traditional group.

Results

A total of 125 patients were included in the final analysis, 56 in the traditional and 69 in the enhanced dosing group. The primary end point occurred in 74% and 54% of patients in the enhanced and traditional dosing groups, respectively (p = 0.029). Therapeutic vancomycin trough levels (10–20 μg/mL) were more commonly achieved in the enhanced dosing group compared with the traditional dosing group (66.7% vs. 45%, p = 0.013). As DFR rose, increasingly higher doses of vancomycin, up to 27 mg/kg/day, were required to achieve the therapeutic targets.

Conclusion

This is the first study to evaluate the influence of variable CRRT intensities on vancomycin AUC/MIC. Our findings suggest that vancomycin doses of ≥15 mg/kg/day are needed to achieve early therapeutic targets in patients on high‐intensity CRRT.
Interconnection and lamination technologies towards ubiquitous integration of photovoltaics
Authors: Govaerts Jonathan , Borgers Tom , Luo Bin , Van Dyck Rik , van der Heide Arvid , Reekmans Bart , Vastmans Luc , Moors Reinoud , Doumen Geert , Tous Loic , Poortmans Jef
Published: July 2023

In this paper, we first give some historical background and trends in PV module technologies with a focus on the growing trend towards ‘PV everywhere’, mainly targeting improved aesthetics, dimensional freedom including curved surfaces, weight concerns and specific reliability testing. This section acts as an introductory review of the field.

Then, in the following sections, we elaborate on two technological developments in this field where we are active: (i) multi‐wire interconnection and (ii) advanced encapsulation.

In terms of multi‐wire interconnection, this technology offers improved aesthetics, a similar performance and dimensional freedom compared to the traditional tabbing‐stringing process, and the experiments show promising results on extended reliability testing, including thermal cycling, damp heat and humidity freeze, as well as high‐temperature storage.

In terms of advanced encapsulation, we introduce our approach for curved surfaces using a double‐membrane laminator and present results on fabricating curved modules, targeting as demonstration examples on the one hand, glass–glass sunroofs, and on the other hand, lighter‐weight bonnets for automotive applications.

We mix examples targeting building and automotive applications, to illustrate the variety of requirements (colours, curvature, weight, reliability, safety), although this variety within building and vehicle applications is probably as large as between them.
Factors associated with pain pressure threshold in both local and remote sites in knee osteoarthritis
Authors: Imamura Marta , Rebello‐Sanchez Ingrid , Parente Joao , Marduy Anna , Vasquez‐Avila Karen , Pacheco‐Barrios Kevin , Castelo‐Branco Luis , Simis Marcel , Battistella Linamara , Fregni Felipe
Published: July 2023

Background

Knee osteoarthritis (KOA) is a prevalent condition, and its most frequent symptom is pain that often leads to disability. Pain sensitization is a core feature of KOA, and it can be measured through quantitative sensory testing protocols such as pain pressure threshold (PPT). However, there is a lack of understanding about the factors that may influence changes in PPTs in the KOA population.

Objective

To explore the clinical and functional factors associated with PPTs in a sample of people with chronic KOA pain and to compare models of local (knees) and remote (thenar regions) sites.

Design

Cross‐sectional analysis of a prospective cohort.

Setting

Primary care in public institution.

Participants

113 adults with KOA.

Intervention

N/A.

Main Outcome Measures

Multivariable regression analyses evaluating demographic, clinical, and functional variables that could be associated with local and remote PPTs (main outcomes) were performed.

Results

Both thenar region (adjusted‐R2: 0.29) and knee (adjusted‐R2: 0.45) models had the same significant negative association with being a female, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain levels (thenar: β: −0.15, p = .002; knee: β: −0.2, p < .001), and the 10‐Meter Walking Test (thenar: β: −0.05, p = .038; knee: β: −0.08, p = .004). A small significant positive association with depressive symptoms was identified in both models, which acted as a confounder for WOMAC pain and was likely affected by unmeasured confounders.

Conclusions

PPTs in KOA pain are associated with functional outcomes such as the 10‐Meter Walking Test and activity‐related pain intensity; thus more disability is associated with smaller pain thresholds. Similarity between models may suggest central sensitization.
Immunohistochemical and histopathological validation of 18F‐PSMA‐1007 PET/CT for intraprostatic cancerous lesions
Authors: Heetman Joris G. , Hermsen Rick , Exterkate Leonie , Küsters‐Vandevelde Heidi V. N. , Brouwer Lenneke J. M. , Somford Diederik M. , van den Bergh Roderick C. N. , van Basten Jean‐Paul A.
Published: July 2023

Introduction

Prostate‐specific membrane antigen (PSMA) is overexpressed in prostate cancer (PCa). In this study, we aim to immunohistochemically and histopathological validate the fluorine‐18 (18F)‐PSMA‐1007 positron emission tomography/computed tomography (PET/CT) for intraprostatic PCa lesions.

Methods

Between February 2019 and October 2020, patients with biopsy‐proven, treatment‐naïve intermediate‐to‐high‐risk PCa undergoing an 18F‐PSMA‐1007 PET/CT before robot‐assisted radical prostatectomy (RARP) were prospectively enrolled. For all PCa lesions found on whole‐mount histopathology, location, size, International Society of Urological Pathology (ISUP) grade group (GG), and immune reactive score (IRS) were assessed after PSMA staining. ISUP GG ≥ 3 PCa was defined as clinically significant (cs) PCa. All lesions were matched on PSMA PET/CT and the maximum standardized uptake value (SUVmax) was measured.

Results

A total of 125 lesions were analyzed in the 80 RARP specimens, of which 49 (40%) were csPCa and 76 (60%) non‐csPCa. Linear multivariable regressions showed that an increase in SUVmax significantly correlated with a higher ISUP GG (p values between 0.021 and 0.001) and a higher IRS (p = 0.017). Logistic multivariable regression showed that csPCa significantly correlated with a higher SUVmax (odds ratio, OR: 1.17 [95% confidence interval, CI: 1.04–1.21, p = 0.005]), an increase in tumor length (OR: 1.05 [95% CI 1.01–1.10, p = 0.020]) and a higher IRS (OR; 1.24 [95% CI 1.07–1.47, p = 0.006]). A SUVmax threshold of 4 would have resulted in one (2%) missed lesion with csPCa.

Conclusion

This prospective study revealed that 18F‐PSMA‐1007 PET/CT SUVmax is correlated with the ISUP GG and IRS, and thereby could be a tool to characterize intraprostatic PCa lesions.
Structure of a transmission blocking antibody in complex with Outer surface protein A from the Lyme disease spirochete, Borreliella burgdorferi
Authors: Rudolph Michael J. , Davis Simon A. , Haque H. M. Emranul , Ejemel Monir , Cavacini Lisa A. , Vance David J. , Willsey Graham G. , Piazza Carol Lyn , Weis David D. , Wang Yang , Mantis Nicholas J.
Published: July 2023

319‐44 is a human monoclonal antibody capable of passively protecting mice against tick‐mediated infection with Borreliella burgdorferi, the bacterial genospecies responsible for Lyme disease in North America. In vitro, 319‐44 has complement‐dependent borreliacidal activity and spirochete agglutinating properties. Here, we report the 2.2 Å‐resolution crystal structure of 319‐44 Fab fragments in complex with Outer surface protein A (OspA), the ~30 kDa lipoprotein that was the basis of the first‐generation Lyme disease vaccine approved in the United States. The 319‐44 epitope is focused on OspA β‐strands 19, 20, and 21, and the loops between β‐strands 16‐17, 18‐19, and 20‐21. Contact with loop 20‐21 explains competition with LA‐2, the murine monoclonal antibody used to estimate serum borreliacidal activities in the first‐generation Lyme disease vaccine clinical trials. A high‐resolution B‐cell epitope map of OspA will accelerate structure‐based design of second generation OspA‐based vaccines.
Investigation of the GnRH antagonist degarelix isomerization in biological matrices
Authors: Ferrazzano Lucia , Tolomelli Alessandra , Guryanov Ivan , Macis Marco , Abel Ulrich , Ricci Antonio , Cabri Walter
Published: July 2023

One of the main objectives of peptide drug design is the improvement of peptide pharmacokinetics with maintaining biological activity, which can be achieved by the complex modifications of the primary structure of the peptides. However, these changes often lead to the formation of peculiar impurities in the peptide drugs and their metabolites, which require the development of advanced analytical methods to properly assess their content. Here, we investigated the degradation of the potent long‐acting GnRH antagonist degarelix in various biologic media by the tailor‐made HPLC method, which allows precise determination of 5‐Aph(Hyd)‐degarelix isomer, an impurity found in the degarelix active pharmaceutical ingredient (API) during its manufacturing. Unexpectedly, we discovered a rapid and irreversible conversion of degarelix API into the corresponding hydantoin isomer in serum, suggesting that this impurity can be also a potential drug metabolite in vivo. This finding underlines the importance of the development of more accurate and performing analytical techniques to correctly characterize the chemical composition of the manufactured drugs and their behavior under physiological conditions.
Why the term “operational discipline” is not helpful, and better options for instilling positive process safety culture
Authors: Olsen Jody E.
Published: July 2023

Language matters for effective leadership and culture. And the language embedded in the term “operational discipline” is not helpful. This term is inconsistent with decades of learning on cause analysis, systems thinking, and human performance. Humans typically do not fail because they are not disciplined enough. Failures occur for other reasons that stem from the systems within which the humans are working. For many people, the term “discipline” has a negative or punitive connotation. And the term “operational” focuses the spotlight on operations. The two terms taken together may imply to some people that willful operator deviations are the root cause of some incidents. Failures typically involve a range of management processes and functional groups. Thorough failure analysis can identify systemic causes, and follow‐up corrective actions may be targeted at the upstream sources. Healthy culture requires a positive, inclusive, and curious environment that seeks to continuously learn and improve without casting blame. Even if the term “operational discipline” is not intended to place blame, the choice of words defeats that aspiration. When seeking to improve process safety culture, choose language that supports a positive learning environment of ownership and empowerment by the workforce. And support those words through management actions.
Hazard evaluation and safety assessment for subsea HIPPS
Authors: Ganaadhiban Murugesan , Arunshankar Jayabalan , Venkataraman Ramamirtham , Srinivasan Krishnamoorthy
Published: July 2023

The safety practice of depressurization of pipelines by flare system in the hydrocarbon industry is not sufficient for pipelines in the subsea production process. There are many challenges in the subsea production process due to multiphase fluid flow. Failure of a process to arrive at its safe state could result in fatality, significant property damage, and can lead to a disastrous environment. The safe state of a process is identified through the consequence of hazard and risk assessments at critical modes of operations. A well‐designed safety instrumented function (SIF) can prevent escalation of minor malfunction into an accident. The prime objective of this work is to obtain the required safety integrity level (SIL) for subsea High Integrity Pressure Protection System (HIPPS). Based on hazard assessment (HAZOP) and risk assessment (LOPA), SIL for SIF is recommended, and finally through reliability calculations, the SIL for subsea HIPPS is determined.
Praeruptorin C alleviates cognitive impairment in type 2 diabetic mice through restoring PI3K/AKT/GSK3β pathway
Authors: Li Long‐Fei , Gao Ying , Xu Yuan , Su Dan‐Jie , Yang Qi , Liu An , Wang Sai‐Ying , Tang Xiu‐Ling , Zhao Jun , Luo Li , Yan Tao , Wu Yu‐Mei , Liu Shui‐Bing , Zhao Ming‐Gao , Yang Le
Published: July 2023

Diabetic encephalopathy is a common consequence of diabetes mellitus that causes cognitive dysfunction and neuropsychiatric disorders. Praeruptorin C (Pra‐C) from the traditional Chinese medicinal herb Peucedanum praeruptorum Dunn. is a potential antioxidant and neuroprotective agent. This study was conducted to investigate the molecular mechanisms underlying the effect of Pra‐C on diabetic cognitive impairment. A novel object recognition test and the Morris water maze test were performed to assess the behavioral performance of mice. Electrophysiological recordings were made to monitor synaptic plasticity in the hippocampus. A protein–protein interaction network of putative Pra‐C targets was constructed, and molecular docking simulations were performed to predict the potential mechanisms of the action of Pra‐C. Protein expression levels were detected by western blotting. Pra‐C administration significantly lowered body weight and fasting blood glucose levels and alleviated learning and memory deficits in type 2 diabetic mice. Network pharmacology and molecular docking results suggested that Pra‐C affects the PI3K/AKT/GSK3β signaling pathway. Western blot analysis confirmed significant increases in phosphorylated PI3K, AKT, and GSK3β levels in vivo and in vitro upon Pra‐C administration. Pra‐C alleviated cognitive impairment in type 2 diabetic mice by activating PI3K/AKT/GSK3β pathway.
Ising Hamiltonians for Constrained Combinatorial Optimization Problems and the Metropolis‐Hastings Warm‐Starting Algorithm
Authors: Li Hui‐Min , Liang Jin‐Min , Wang Zhi‐Xi , Fei Shao‐Ming
Published: July 2023

Quantum approximate optimization algorithm (QAOA) is a promising variational quantum algorithm for combinatorial optimization problems. However, the implementation of QAOA is limited due to the requirement that the problems be mapped to Ising Hamiltonians and the nonconvex optimization landscapes. Although the Ising Hamiltonians for many NP hard problems have been obtained, a general method to obtain the Ising Hamiltonians for constrained combinatorial optimization problems (CCOPs) has not yet been investigated. In this paper, a general method is introduced to obtain the Ising Hamiltonians for CCOPs and the Metropolis‐Hastings warm‐starting algorithm for QAOA is presented which can provably converge to the global optimal solutions. The effectiveness of this method is demonstrated by tackling the minimum weight vertex cover (MWVC) problem, the minimum vertex cover (MVC) problem, and the maximal independent set problem as examples. The Ising Hamiltonian for the MWVC problem is obtained first time by using this method. The advantages of the Metropolis‐Hastings warm‐starting algorithm presented here is numerically analyzed through solving 30 randomly generated MVC cases with 1‐depth QAOA.
Urban entrepreneurship, public management and sustainability nexus: Evidence from developing countries
Authors: Kpegba Silas Apealete , Oppong Clement , Atchulo Abukari Salifu
Published: July 2023

Purpose

This study examines the nexus of urban entrepreneurship, public management and sustainability within the context of developing countries.

Design/Methodology/Approach

The study adopted a quantitative and descriptive approach, using data from the World Development Indicators (WDI) and the World Bank Entrepreneurship database for 12 developing countries from 2013 to 2018. The analysis was carried out using a panel regression model with fixed effect.

Findings

The results show a significant relationship between urban entrepreneurship and economic sustainability; and also, a significant relationship between public management and economic sustainability among developing African countries.

Practical Implications

This implies that developing countries need to offer incentives to the private sector to encourage entrepreneurial activities which will subsequently improve economic sustainability.

Originality/Value

This study adds to literature by examining the nexus of urban entrepreneurship, public management and sustainability among developing countries in a single model using quantitative approach.
Significance tests for covariates in the diagnostic accuracy index of a biomarker against a continuous gold standard
Authors: Wu Mixia , Sun Xian , Liu Aiyi , Peng Chenchen , Li Zhaohai
Published: July 2023

Receiver operating characteristic (ROC) curve is a popular tool to describe and compare the diagnostic accuracy of biomarkers when a binary‐scale gold standard is available. However, there are many examples of diagnostic tests whose gold standards are continuous. Hence, Several extensions of receiver operating characteristic (ROC) curve are proposed to evaluate the diagnostic potential of biomarkers when the gold standard is continuous‐scale. Moreover, in evaluating these biomarkers, it is often necessary to consider the effects of covariates on the diagnostic accuracy of the biomarker of interest. Covariates may include subject characteristics, expertise of the test operator, test procedures or aspects of specimen handling. Applying the covariate adjustment to the case that the gold standard is continuous is challenging and has not been addressed in the literature. To fill the gap, we propose two general testing frameworks to account for the covariates effect on diagnostic accuracy. Simulation studies are conducted to compare the proposed tests. Data from a study that assessed three types of imaging modalities with the purpose of detecting neoplastic colon polyps and cancers are used to illustrate the proposed methods.
Chinese cross‐border mergers and acquisitions: How communication practices impact integration outcomes
Authors: Wang Jean , Schweizer Lars
Published: July 2023

This study provides an empirical investigation on how communication practices impact the post‐acquisition integration outcomes, in the context of Chinese cross‐border mergers and acquisitions (CBMAs). We tailored our assessment to reflect communication practices during Chinese CBMA integration. The integration outcomes are measured by organizational commitment and strategic performance improvement. Using a data collected via survey from global executives and middle managers, we find that communication accuracy, channel efficiency, and overseas business management department positively impact organizational commitment. Moreover, inter‐organizational trust mediates the effect of communication accuracy on organizational commitment, and communication officer on organizational commitment. In addition, we find that the language barrier of the Chairman negatively impacts strategic performance improvement. Moreover, acquisition experience, business relatedness, industrial investors, private‐owned investors, and management consultant all positively affect strategic performance improvement. However, middle managers negatively impact the integration outcomes.
Pneumocoelom and secondary lung collapse treatment in a stranded loggerhead sea turtle (Caretta caretta) in the eastern Mediterranean Sea, Israel
Authors: Morick Danny , Levy Yaniv , Davidovich Nadav , Wosnick Natascha , Zemah‐Shamir Ziv , Tchernov Dan , Aizenberg Itzhak
Published: July 2023

This study describes a case of lung collapse and its successful repair in a stranded loggerhead sea turtle, utilising coelomic gas aspiration via the prefemoral region. This animal presented unbuoyant swimming, was diagnosed via computed tomography scanning, treated successfully and returned to the sea following a 6‐week rehabilitation period.
Does switching brands matter? Complications associated with switching between phenobarbital brands in two dogs with idiopathic epilepsy
Authors: Abouzeid Jad , De Risio Luisa , Stabile Fabio
Published: July 2023

Switching between brands of the same antiseizure medication has been associated with a loss of epileptic seizure control in people. No such reports are available in the veterinary literature. Here, we describe two cases in which client‐owned dogs with idiopathic epilepsy experienced complications following phenobarbital brand switch, despite no change in the administered dosage. Both dogs had been on treatment with oral phenobarbital for at least 23 months without complications. Following brand switching, one dog became markedly sedated, ataxic and anorexic, and the other dog experienced severe cluster seizures. The measured serum phenobarbital concentrations were significantly altered from the previously measured pre‐brand switching concentrations. Echoing what has been described in human medicine, these cases suggest that therapeutic complications can occur when switching phenobarbital brand in chronically treated dogs with idiopathic epilepsy. Such complications should be considered when modulating antiseizure treatment in dogs. The exact cause for the resulting complications is unclear.