bluuebunny/crossref_metadata_2025 huggingface dataset:
Bio-Electrocatalytic Reduction of Hydrogen Peroxide by Peroxidase from Guinea Grass (Panicum Maximum) Immobilized on Graphene and Graphene Oxide Screen-Printed Electrodes
Authors: Castillo John , Guarin-Guio Paula Andrea , Ortiz Ludy
Published: July 2022

Objective: In this article a comparison was made between graphene (SPGE) and graphene oxide screen-printed electrodes (SPGOE) to study the bio-electrocatalytic reduction of hydrogen peroxide (H2O2) by guinea grass peroxidase (GGP). Methods and materials: GGP was immobilized onto SPGE and SPGOE by a drop-casting procedure. Electrochemical techniques were carried out to monitor the electrochemical behavior of GGP and the efficiency of electrocatalytic reduction of H2O2. Results and discussion: GGP adsorbed on both electrodes exhibited a couple of well-defined redox peaks at 120 mV/10.5 mV and 184 mV/59 mV for anodic and cathodic peaks, respectively. Linearity between scan rates root and oxidation and reduction peak currents for both electrodes suggest a surface-controlled process. The GGP-modified electrodes exhibited a good electrocatalytic activity to H2O2 reduction at a redox potential of -0.6 V and -0.5 V for SPEG and SPEGO, respectively. Conclusions: SPGE and SPGOE electrodes modified with GGP showed excellent analytical performance towards different concentrations of hydrogen peroxide. This is a preliminary step to developing a bio-analytical portable system based on GGP for the detection of H2O2 in real environmental samples.
Simulation-Based Optimization Algorithm for the Vendor-Managed Inventory Problem for Blood Platelets
Authors: Carvajal-Hernandez Juan David , Osorio-Muriel Andres Felipe
Published: July 2022

Objective: Estimate an optimal policy for the blood platelets supply chain distribution problem using a vendor-managed inventory problems approach. Methods and materials: This paper uses an integrated simulation-based optimization model to develop a Vendor-Managed Inventory approach for blood platelets. Simulation is used to estimate the performance of a defined inventory policy. On the other hand, a genetic algorithm finds optimal or near-optimal inventory policies. This approach is evaluated using a case study inspired by a real blood center in Colombia. Results and discussion: Using the proposed approach, key indicators in the blood supply chain such as total cost and outdated units are significantly improved while maintaining the service level.  In terms of costs, the VMI model shows a 19.19% advantage over the non-VMI solution. Moreover, the proposed VMI solution can reduce by 42.25% the number of expired platelets. Conclusions: Using a VMI-based distribution system and a simulation-based optimization approach with genetic algorithms offers promising results in the proposed use case. This mixed methodology allows for flexible system configurations without the need for complex changes in the algorithm, and it does so without the need for excessive computational resources.
Medium and large-sized mammals in dry forests of the Colombian Caribbean
Authors: Pineda-Cendales Simón , Hernández-Rolong Elkin , Carvajal-Cogollo Juan E.
Published: July 2022

Mammalian populations are fundamental at functional and ecological levels within ecosystems and are inconstant threat of reduction world wide and in the Neotropic. We evaluated population variables, habitat use, and threats to medium and large mammals (weight > 1 kg) in the terrestrial part of the Tayrona National Natural Park (Santa Marta-Colombia). We carried out in direct annual observations with camera traps between 2012 and 2017, both in rainy and dry seasons. We estimated the richness, relative abundance (RAI), and functional diversity of the mammals present in the area. We recorded 15 species, distributed in seven orders (Carnivora, Rodentia, Pilosa, Cingulata, Lagomorpha, Didelphimorphia, and Cetartiodactyla), 11 families and 13 genera. The species with the highest capture frequency was Dasyprocta punctata (142, RAI = 0.85), followed by Cuniculus paca (56, RAI = 0.33), Odocoileus virginianus (51, RAI = 0.30), and Cerdocyon thous (41, RAI = 0.24). We observed a marked use and preference of habitat in the seasonal dry ever green forest. This finding coincides with the highest value of functional richness (S1= 293.88) for this ecosystem, probably due to its features, such as green vegetation and abundant water streams. Our results reveal stability of the species richness across the years studied, suggesting good health of the mammal populations in the studied area.
Seed bank responses after clearcutting Pinus patula plantations in Andean high montane areas
Authors: Basto Sofía , Roa-Fuentes Lilia , Moreno Ana Carolina , Barrera-Cataño José Ignacio
Published: July 2022

Clear cutting exotic plantations favours natural regeneration processes in which seed banks may play an important role. In Andean high montane areas, after Pinus patula clear cutting, changes in soil pH and litter lead to increased fauna and flora biodiversity. However, the impactof these changes on seed banks remains unknown. The aims of the present study were to understand how seed bank richness, abundance, and composition changes after p. patula clear cutting, and to identify the role of above ground cover, pH and litter cover on these seed bank variations. The study was conducted in three areas with different post-clear cutting ages (0,2.5,4.5 years), a p. patula plantation and in a high Andean forest patch. All these sites were located between 3033 and 3100 m.a.s.l. Seed bank abundance, richness and the number of seeds of the ten most abundant species increased in areas with 2.5 and 4.5 years after clear cutting. Moreover, seed bank composition was different among study areas. These changes were related to increasing above ground vegetation cover and soil pH, and to decreasing litter cover. Seed banks contributed almost exclusively to the recovery of some herbaceous species; were corded only one tree species recruit from the seed banks (Baccharislatifolia) in the forest soils; therefore, the natural regeneration processes may be constrained. Our results high light the need to implement active restoration to accelerate high montane forest recovery in areas previously covered with pine tree plantations.
Synthesis of zeolites P and evaluation of their activity as new and reusable heterogeneous catalysts in a three-component ABB’ Povarov model reaction
Authors: López Jefersson A. , Toro Robert A. , Romero-Bohórquez Arnold R. , Quintana Jose H. , Henao José A.
Published: July 2022

A Na-P zeolite was synthesized and subjected to ion exchange with Ca2+, Cu2+, Al3+, and In3+, and supported with H+/NH4Cl (NH4-P) by in situ reaction of EtOH and NH4Cl. All the exchanged zeolites showed catalytic activity in the ABB’ Povarov reaction. However, zeolite NH4-P promoted a better yield. In all reactions two products were obtained, 2,6-dimethyl-4-(2-oxopyrrolidin-1-yl)-1,2,3,4-tetrahydroquinoline and 1-(1-(4-methylphenylamino)ethyl)pyrrolidin 2-one. Synthesis using zeolite P as catalyst proves to be a simple method with high yields, short reaction times and easy preparation. The catalyst can be recovered by filtration and reused up to three times in good yields.
Diet of Dendropsophus molitor (Anura: Hylidae) in a High-Andean agricultural ecosystem, Colombia
Authors: Higuera -Rojas Diego F. , Carvajal-Cogollo Juan E.
Published: July 2022

Dendropsophus molitor is a generalist frog that makes optimal use of resources offered by highly transformed Andean ecosystems. Despite being one of the most researched amphibian species in Colombia, aspects of its diet as an indication of its trophic niche have not yet been evaluated. For this reason, we evaluated the diet of D. molitor, with interpretations of dietary composition to address this dimension of the niche. We chose an Andean agricultural system and in it we selected four jagüeyes (water-filled ditches) and carried out samplings between July and November 2017. We collected 32 individual frogs, extracted their stomach contents and analyzed the composition, diversity, relative importance of the prey and the amplitude of the trophic niche. Additionally, from a network analysis, we evaluated the interactions of the species with its prey. We obtained records of 69 prey, distributed in 29 categories; the prey with the highest frequency were Bibionidae1 with seven individuals, followed by Tipulidae1 and Tipulidae2 with six, which are equivalent to those of greater relative importance. The trophic niche was characterized as wide (Levins’ B = 0.7) and the interactions had a connectivity of 0.065, a link coefficient of 0.930 and a link density of 273.8, represented by a wide range of interactions with prey. The characterization of the diet and the trophic niche of D. molitor shows the broad use of resources consistent with its already documented generalist condition. The diversity of the diet together with the breadth could represent advantages for establishing large and healthy populations in transformed environments in the high mountains of the Andes.
A highly diverse phytobenthic community along a short coastal reef gradient in northeastern Brazil
Authors: César Ferreira Sol de Maria
Published: July 2022

This study aimed to inventory the species of marine macroalgae and analyze the distribution and biomass patterns of their communities along a short coastal reef gradient in northeastern Brazil. Samples were collected using the technique of random squares, distributed in the three habitats: reef front region (FR), tide pools (TP), and reef plateau (RP). These three make up the reef gradient from the sea to the beach. A total of 56 taxa were identified, with Ochrophyta and Rhodophyta standing out as the phyla with the greater taxonomic richness, and the largest biomass represented by the species Sargassum vulgare (30 % of total biomass) and     (16 %). The key emergening patterns along the reef gradient were the occurrence of groups of exclusive taxa in each habitat, and significant variation in biomass, greater in the TP (166.1 g m-2) and lower in the RP (70.5 g m-2). Despite being an environment under marked anthropogenic influence (i.e., tourism and development), we observed a high diversity of species, with a distribution pattern that reflects a high environmental heterogeneity and substantial ecological integrity.
Sensitivity of Internal Tibial Forces and Moments to Static Optimization Moment Constraints at the Subtalar and Ankle Joints
Authors: Baggaley Michael , Derrick Timothy R. , Brent Edwards W.
Published: July 2022

We examined the sensitivity of internal tibial forces and moments during running to different subtalar/ankle moment constraints in a static optimization routine. Seventeen participants ran at 2.20, 3.33, and 4.17 ms−1 while force and motion data were collected. Ankle joint contact force was estimated using inverse-dynamics-based static optimization. Three sets of joint moment constraints were tested. All sets included the flexion–extension and abduction–adduction moments at the hip and the flexion–extension moment at the knee but differed in the constraints used at the subtalar/ankle: (1) flexion–extension at the ankle (Sag), (2) flexion–extension and inversion–eversion at ankle (Sag + Front), and (3) flexion–extension at the ankle and supination–pronation at the subtalar (Sag + SubT). Internal tibial forces and moments were quantified at the distal one-third of the tibia, by ensuring static equilibrium with applied forces and moments. No interaction was observed between running speed and constraint for internal tibial forces or moments. Sag + SubT resulted in larger internal mediolateral force (+41%), frontal (+79%), and transverse (+29%) plane moments, compared to Sag and Sag + Front. Internal axial force was greatest in Sag + Front, compared to Sag and Sag + SubT (+37%). Faster running speeds resulted in greater internal tibial forces and moments in all directions (≥+6%). Internal tibial forces and moments at the distal one-third of the tibia were sensitive to the subtalar and ankle joint moment constraints used in the static optimization routine, independent of running speed.
Air Entrainment and Outlet Temperature Characteristics of a Modified Infrared Suppression Device With Inward and Outward Guides
Authors: Mishra Sachin K. , Barik Ashok K. , Swain Prafulla K.
Published: July 2022

A passive infrared suppression (IRS) device is an important and integral part of the modern naval/cargo ships, fighter jets, and helicopters to cool down the hot exhaust gas to suppress the infrared (IR) signatures. A modified IRS device has been proposed by putting inward/outward guides. The air entrainment and temperature ratios of the new type IRS device have been investigated by solving transport equations (continuity, momentum, energy, and turbulence) using the finite volume solver in ansys fluent. The Reynolds number (Ren), guide lengths (Lg/Dn), the inclination angle of guides (θg), overlap-height (Hov/Dn), and outlet temperature ratio (Tout/T∞) have been varied in the range of 1.5 × 10–1.5 × 106, 0–0.326, 0–75 deg, −0.326–0.018, and 1.243–2.576, respectively. It has been observed that the dimensional air entrainment increases with the Reynolds number and inlet temperature. The guide length alters the flow inside the IRS device and affects the entrainment ratio. We observed that, at the optimal value of guide length (Lg/Dn = 0.163) and inclination angle (θg = 15 deg), the IRS device entrains the maximum air, and attains a minimum temperature at the outlet. The mass suction and the outlet temperature of two different types of IRS devices have also been compared to choose the best one for the practical engineering application. An empirical correlation equation for air entrainment has been developed using nonlinear regression analysis.
Exergetic Performance Analysis of Energy Storage Unit Fitted With Wire Coil Inserts
Authors: Kumar Ravi , Kumar Manoj , Patil Anil Kumar
Published: July 2022

In a sensible storage system, energy is stored based on the distribution of energy and exergy at the specified conditions. It is believed that the least temperature gradient leads to a higher exergy availability and lower entropy generation in a storage system. An energy storage unit with multiple passages fitted with wire coil inserts is evaluated in the present work by assessing the exergy stored and the entropy generation number for heat transfer fluid (HTF) inlet temperature range of 45–75 °C and HTF flowrate of 0.022–0.029 kg/s. The wire coil inserts have a (p/d) ratio in the range of 0.25–0.75. The maximum exergy storage rate in the energy storage unit is found to be 55.43 W corresponding to an energy storage unit having wire coil insert (p/d = 0.25) at the HTF inlet temperature of 75 °C and HTF flowrate of 0.029 kg/s. Entropy generation number of the system with wire coil inserts (p/d = 0.5), compared to smooth HTF passage, is found to be 42.32% at HTF flowrate and inlet temperature of 0.026 kg/s and 45 °C, respectively.
Modal Analysis of Non-Conservative Combined Dynamic Systems
Authors: Bellos John , Inman Daniel J.
Published: July 2022

The emergence of the use of mechanical metamaterials for vibration suppression and the creation of frequency gaps in structures require an understanding of the fundament underlying dynamics partial differential equations coupled to ordinary differential equations. Essentially periodic structures consist of a distributed parameter structure connected (embedded) to a series of spring-mass-dampers. Such systems in the past have been studied as combined dynamical systems. This work deals with the modal analysis of non-conservative combined dynamic systems formed by assembling distributed parameter structures and linear, viscously damped, lumped parameter oscillators. The mathematical model of the forced response of such dynamic systems is presented via differential operators. The related non-linear eigenproblem is formulated next and a proper solution is provided. Furthermore, the orthogonality of the eigenfunctions is studied and the completeness of the generated solution space is verified. Coupled modal coordinate differential equations result through modal analysis, thus revealing the non-proportional damping configuration, while the proportional damping conditions are also derived and discussed. The theory is applied to non-conservative Euler–Bernoulli beams subject to different types of boundary conditions and coupled to linear, viscously damped oscillators. A numerical example yields interesting conclusions about the non-proportionality and the applicability of the associated methods to solving the coupled differential equations.
Lower-Extremity Neuromuscular Function Following Concussion: A Preliminary Examination
Authors: Lempke Landon B. , Call Jarrod A. , Hoch Matthew C. , Schmidt Julianne D. , Lynall Robert C.
Published: July 2022

Context: Neuromuscular function is altered acutely following concussion and theoretically linked to the subsequent postconcussion musculoskeletal injury risk. Existing research has only examined voluntary muscle activation, limiting mechanistic understanding. Therefore, our study aimed to examine voluntary and involuntary muscle activation between college-aged, concussed individuals when symptom-free and healthy matched controls. Design: Prospective, cross-sectional cohort laboratory study. Methods: Concussed and healthy participants (n = 24; 58% male, age: 19.3 [1.1] y, mass: 70.3 [16.4] kg, height: 177.3 [12.7] cm) completed the superimposed burst (SB) neuromuscular assessment on their dominant limb within 72 hours after self-reporting asymptomatic (22.4 [20.2] d postinjury). Unnormalized and bodyweight-normalized quadriceps maximal voluntary isometric contraction torque (in newton meters), unnormalized and bodyweight-normalized electrically stimulated SB torque, pain (numeric 1–10) during SB, and the central activation ratio (in percentage) were assessed via the SB. Parametric and nonparametric analyses, 95% confidence intervals (95% CIs), and Hedges g (parametric) and Spearman ρ (nonparametric) effect sizes were used to examine group differences (α = .05). Results: The maximal voluntary isometric contraction torque (concussed: 635.60 N·m [300.93] vs control: 556.27 N·m [182.46]; 95% CI, −131.36 to 290.02; P = .443; d = 0.33), SB torque (concussed: 203.22 N·m [97.17], control: 262.85 N·m [159.07]; 95% CI, −171.22 to 51.97; P = .280; d = −0.47), and central activation ratio (concussed: 72.16% [17.16], control: 70.09% [12.63]; 95% CI, −10.68 to 14.83; P = .740; d = 0.14) did not differ between the concussed and control groups regardless of bodyweight normalization (P ≥ .344). Pain during the SB was significantly higher with a medium effect for participants with a concussion versus healthy controls (concussed: median = 7, control: median = 5; P = .046; ρ = −0.42). Discussion: These findings suggest concussed participants do not have statistically altered voluntary or involuntary quadricep neuromuscular function once asymptomatic compared with controls. Therefore, the elevated postconcussion musculoskeletal injury risk may not be attributed to lower-extremity muscle activation. Concussed participants displayed greater pain perception during the SB, which suggests somatosensory or perception changes requiring further examination.
An implantable ultrasound-powered device for the treatment of brain cancer using electromagnetic fields
Authors: Yang Yilin , Hu Xiaoping , Liu Yuxin , Ouyang Bin , Zhang Jiaxi , Jin Huawei , Yu Zhenhua , Liu Ruiwei , Li Zhe , Jiang Lelun , Lin Xudong , Xu Bingzhe
Published: July 2022

Brain tumors have been proved challenging to treat. Here, we present a promising alternative by developing an implantable ultrasound-powered tumor treating device (UP-TTD) that electromagnetically disrupts the rapid division of cancer cells without any adverse effects on normal neurons, thereby safely inhibiting brain cancer recurrence. In vitro and in vivo experiments confirmed the significant therapeutic effect of the UP-TTD, with ~58% inhibition on growth rate of clinical tumor cells and ~78% reduction of cancer area in tumor-bearing rats. This UP-TTD is wireless ultrasound-powered, chip-sized, lightweight, and easy to operate on complex surfaces, with a largely boosting therapeutic efficiency and reducing energy consumption. Meanwhile, various treatment parameters could be tuned from the UP-TTD without increasing its size or adding circuits on the integrated chip. The tuning process was simulated and discussed, showing an excellent agreement with the experimental data. The encouraging results of the UP-TTD raise the possibility of a new modality for brain cancer treatment.
Momentum space imaging of σ orbitals for chemical analysis
Authors: Haags Anja , Yang Xiaosheng , Egger Larissa , Brandstetter Dominik , Kirschner Hans , Bocquet François C. , Koller Georg , Gottwald Alexander , Richter Mathias , Gottfried J. Michael , Ramsey Michael G. , Puschnig Peter , Soubatch Serguei , Tautz F. Stefan
Published: July 2022

Tracing the modifications of molecules in surface chemical reactions benefits from the possibility to image their orbitals. While delocalized frontier orbitals with π character are imaged routinely with photoemission orbital tomography, they are not always sensitive to local chemical modifications, particularly the making and breaking of bonds at the molecular periphery. For such bonds, σ orbitals would be far more revealing. Here, we show that these orbitals can indeed be imaged in a remarkably broad energy range and that the plane wave approximation, an important ingredient of photoemission orbital tomography, is also well fulfilled for these orbitals. This makes photoemission orbital tomography a unique tool for the detailed analysis of surface chemical reactions. We demonstrate this by identifying the reaction product of a dehalogenation and cyclodehydrogenation reaction.
Future seasonal changes in habitat for Arctic whales during predicted ocean warming
Authors: Chambault Philippine , Kovacs Kit M. , Lydersen Christian , Shpak Olga , Teilmann Jonas , Albertsen Christoffer M. , Heide-Jørgensen Mads Peter
Published: July 2022

Ocean warming is causing shifts in the distributions of marine species, but the location of suitable habitats in the future is unknown, especially in remote regions such as the Arctic. Using satellite tracking data from a 28-year-long period, covering all three endemic Arctic cetaceans (227 individuals) in the Atlantic sector of the Arctic, together with climate models under two emission scenarios, species distributions were projected to assess responses of these whales to climate change by the end of the century. While contrasting responses were observed across species and seasons, long-term predictions suggest northward shifts (243 km in summer versus 121 km in winter) in distribution to cope with climate change. Current summer habitats will decline (mean loss: −25%), while some expansion into new winter areas (mean gain: +3%) is likely. However, comparing gains versus losses raises serious concerns about the ability of these polar species to deal with the disappearance of traditional colder habitats.
14-3-3-zeta mediates GLP-1 receptor agonist action to alter α cell proglucagon processing
Authors: Holter Marlena M. , Phuong Daryl J. , Lee Isaac , Saikia Mridusmita , Weikert Lisa , Fountain Samantha , Anderson Elizabeth T. , Fu Qin , Zhang Sheng , Sloop Kyle W. , Cummings Bethany P.
Published: July 2022

Recent studies demonstrate that α cells contribute to glucose-stimulated insulin secretion (GSIS). Glucagon-like peptide-1 receptor (GLP-1R) agonists potently potentiate GSIS, making these drugs useful for diabetes treatment. However, the role of α and β cell paracrine interactions in the effects of GLP-1R agonists is undefined. We previously found that increased β cell GLP-1R signaling activates α cell GLP-1 expression. Here, we characterized the bidirectional paracrine cross-talk by which α and β cells communicate to mediate the effects of the GLP-1R agonist, liraglutide. We find that the effect of liraglutide to enhance GSIS is blunted by α cell ablation in male mice. Furthermore, the effect of β cell GLP-1R signaling to activate α cell GLP-1 is mediated by a secreted protein factor that is regulated by the signaling protein, 14-3-3-zeta, in mouse and human islets. These data refine our understanding of GLP-1 pharmacology and identify 14-3-3-zeta as a potential target to enhance α cell GLP-1 production.
An unusual ocular manifestation of multiple myeloma
Authors: McGrath Robert , Whitlow Shane , McCabe Grace Anne , McElnea Elizabeth Margaret
Published: July 2022

A man in his 70s with a history of multiple myeloma presented with a 4-day history of right ptosis and a rapidly enlarging upper eyelid mass. On examination, a large, firm, smooth, pink lesion was found to descend from the conjunctiva of the superior fornix. The patient underwent excision biopsy. Histopathological analysis demonstrated monoclonal plasma cells expressing light-chain kappa, consistent with extramedullary plasmacytoma. Clinical ophthalmic manifestations of multiple myeloma are rare but also diverse. Ocular surface manifestations of multiple myeloma are extremely uncommon. Variable examination findings mean those involving the conjunctiva and may be particularly challenging to diagnose. Secondary ocular extramedullary plasmacytoma, despite its rarity, should be considered in patients with multiple myeloma.
Esmolol for intractable ventricular arrhythmias in major amitriptyline toxicity
Authors: Garrett Peter , Klupfel Steven
Published: July 2022

A massive tricyclic overdose of 10 g of amitriptyline resulted in cardiovascular collapse with multiple episodes of ventricular tachycardia and ventricular fibrillation despite aggressive attention to current recommended therapy of sodium bicarbonate and hypertonic saline, and correction of electrolytes. Second-line antiarrhythmic therapies failed to reduce the recurrent deterioration to malignant ventricular rhythms. Progression to extracorporeal support was avoided by the use of a titrated esmolol infusion. We discuss the physiological rationale by which esmolol may prevent tachyarrhythmia and fibrillation in severe amitriptyline toxicity.
Intestinal perforation due to miliary tuberculosis in a patient with myasthenia gravis
Authors: Morgan Ahmed Ashraf , Mahmood Adil , Russell Georgina K , Kon Onn Min
Published: July 2022

A man in his early 70s presented to the emergency department with a fall, following a history of fatigue and malodorous urine. On presentation, he was feverish, tachycardic and confused and was treated for presumed urinary sepsis. A chest radiograph showed increased opacification in the left upper lobe with calcification. CT imaging and bronchoalveolar lavage demonstrated miliary tuberculosis infection. His background included myasthenia gravis, which led to challenges in selecting appropriate antituberculosis treatment. During his stay, he developed sudden-onset abdominal pain due to intestinal perforation. He subsequently deteriorated and underwent multiple interventions, including a Hartmann’s procedure and ileocaecal resection. Histological examination of his sigmoid colon revealed abundant acid-fast bacilli. Unfortunately, the patient died due to multiorgan failure in the context of several complications. This case highlights intestinal perforation as a rare complication of miliary tuberculosis and emphasises the importance of being vigilant for this potential complication.
PRIDE complex-like skin rash associated with bevacizumab
Authors: Singh Biplav , Rajput Akshay , Tripathi Manjul , Mahajan Rahul
Published: July 2022

Bevacizumab-induced rash is a rarely reported complication with very few insights into its epidemiology, pathophysiology, management and relationship with therapeutic efficacy. We report a case of ruptured occipital arteriovenous malformation treated with stereotactic radiosurgery. The patient developed steroid-resistant radiosurgery-induced brain oedema. Oedema partially responded to bevacizumab, and the patient tolerated the treatment well except for skin rash. He developed multiple discrete monomorphic papulopustular lesions with intervening hyperpigmented macules after bevacizumab intravenous infusion. The patient was further treated with benzoyl peroxide gel for local application and oral doxycycline. The rash reappeared whenever bevacizumab was reintroduced to the regimen beyond 7.5 mg/kg body weight at 3 weekly intervals. After dose modification to 5 mg/kg body weight, 6 cycles were administered with no further rash and resolution of oedema. There is no need to halt bevacizumab therapy, although it can be continued at a lesser dose as it may be a dose-dependent complication.
Utility of 5-ALA for resection of CNS tumours other than high-grade gliomas: a protocol for a systematic review
Authors: Solomou Georgios , Gharooni Aref-Ali , Patel Waqqas , Gillespie Conor S , Gough Melissa , Venkatesh Ashwin , Poon Michael T C , Wykes Victoria , Price Stephen John , Jenkinson Michael D , Watts Colin , Plaha Puneet
Published: July 2022

Introduction

5-aminolevulinic acid (5-ALA) is a proagent developed for fluorescent-guided surgery for high-grade glioma patients associated with a significant increase in resection conferring survival. 5-ALA was shown to penetrate the blood–brain barrier accumulating in malignant glioma cells with high selectivity, sensitivity and positive predictive value. However, those have yet to be explored aiding diagnosis for tumours of the central nervous system (CNS) other than high-grade gliomas (HGG). No up-to-date systematic review exists reporting the major surgical outcomes and diagnostic accuracy. We sought to conduct a systematic review of the literature summarising surgical outcomes, evaluate the quality of diagnostic accuracy reported in the literature and qualitatively assess the evidence to inform future studies.

Methods and analysis

We will search electronic databases (Medline, Embase) with subsequent interrogation of references lists of articles reporting the use of 5-ALA for brain tumours other than high-grade glioma adult patients, which also report the extent of resection and/or survival. Prospective and retrospective cohort and case–control studies with more than five patients will be included. Two independent reviewers will screen the abstracts and full articles, with a third reviewer resolving any conflicts. The data will be extracted in a standardised template and outcomes will be reported using descriptive statists. The quality of non-randomised studies will be appraised.

Ethics and dissemination

The study will summarise the available evidence on the effect of the clinical utility of 5-ALA in achieving resection and improving survival and its diagnostic accuracy for tumours of the CNS other than HGG. The data will be presented nationally and internationally and the manuscript will be published in a peer-reviewed journal. No ethical approvals were needed. The aim is to inform prospective studies minimising reporting bias allowing for more reliable, reproducible and generalisable results. The study has been registered in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

PROSPERO registration number

CRD42021260542.
Thresholds for clinical practice that directly link handgrip strength to remaining years of life: estimates based on longitudinal observational data
Authors: Scherbov Sergei , Spitzer Sonja , Steiber Nadia
Published: July 2022

Objective

Muscle strength is a powerful predictor of mortality that can quickly and inexpensively be assessed by measuring handgrip strength (HGS). What is missing for clinical practice, however, are empirically meaningful cut-off points that apply to the general population and that consider the correlation of HGS with gender and body height as well as the decline in HGS during processes of normal ageing. This study provides standardised thresholds that directly link HGS to remaining life expectancy (RLE), thus enabling practitioners to detect patients with an increased mortality risk early on.

Design

Relying on representative observational data from the Health and Retirement Study, the HGS of survey participants was z-standardised by gender, age and body height. We defined six HGS groups based on cut-off points in SD; we use these as predictors in survival analyses with a 9-year follow-up and provide RLE by gender based on a Gompertz model for each HGS group.

Participants

8156 US American women and men aged 50–80 years.

Main outcome measures

Z-standardised HGS and all-cause mortality.

Results

Even slight negative deviations in HGS from the reference group with [0.0 SD, 0.5 SD) have substantial effects on survival. RLE among individuals aged 60 years with standardised HGS of [−0.5 SD, 0.0 SD) is 3.0/1.4 years lower for men/women than for the reference group, increasing to a difference of 4.1/2.6 years in the group with HGS of [−1.0 SD, −0.5 SD). By contrast, we find no benefit of strong HGS related to survival.

Conclusions

HGS varies substantially with gender, age and body height. This confirms the importance of considering these heterogeneities when defining reference groups and risk thresholds. Moreover, survival appears to decrease at much higher levels of muscle strength than is assumed in previous literature, suggesting that medical practitioners should start to become concerned when HGS is slightly below that of the reference group.
Prospective cohort study of the evaluation of patient benefit from the redevelopment of a complete national forensic mental health service: the Dundrum Forensic Redevelopment Evaluation Study (D-FOREST) protocol
Authors: Davoren Mary , O’Reilly Ken , Mohan Damian , Kennedy Harry G
Published: July 2022

Introduction

Secure forensic mental health services are low volume, high cost services. They offer care and treatment to mentally disordered offenders who pose a high risk of serious violence to others. It is therefore incumbent on these services to systematically evaluate the outcomes of the care and treatment they deliver to ensure patient benefit in multiple domains. These should include physical and mental health outcomes, as well as offending related outcomes. The aim of Dundrum Forensic Redevelopment Evaluation Study (D-FOREST) is to complete a structured evaluation study of a complete national forensic mental health service, at the time of redevelopment of the National Forensic Mental Health Service for the Ireland.

Methods and analysis

D-FOREST is a multisite, prospective observational cohort study. The study uses a combination of baseline and repeated measures, to evaluate patient benefit from admissions to forensic settings. Patients will be rated for physical health, mental health, offending behaviours and other recovery measures relevant to the forensic hospital setting at admission to the hospital and 6 monthly thereafter.

Lagged causal model analysis will be used to assess the existence and significance of potential directed relationships between the baseline measures of symptomatology of schizophrenia and violence risk and final outcome namely length of stay. Time intervals including length of stay will be measured by median and 95% CI using Kaplan-Meier and Cox regression analyses and survival analyses. Patient related measures will be rated as changes from baseline using general estimating equations for repeated measures, analysis of variance, analysis of covariance or logistic regression.

Ethics and dissemination

The study has received approval from the Research Ethics and Effectiveness Committee of the National Forensic Mental Health Service, Ireland. Results will be made available to the funder and to forensic psychiatry researchers via international conferences and peer-reviewed publications.

Trial registration number

NCT05074732.
Prehospital care for ovarian cancer in Catalonia: could we do better in primary care? Retrospective cohort study
Authors: Vela-Vallespín Carmen , Manchon‐Walsh Paula , Aliste Luisa , Borras Josep M , Marzo-Castillejo Mercè
Published: July 2022

Objective

To assess the impact of prehospital factors (diagnostic pathways, first presentation to healthcare services, intervals, participation in primary care) on 1-year and 5-year survival in people with epithelial ovarian cancer (EOC).

Design

Retrospective quasi-population-based cohort study.

Setting

Catalan Integrated Public Healthcare System.

Participants

People with EOC who underwent surgery with a curative intent in public Catalan hospitals between 1 January 2013 and 31 December 2014.

Outcome measures

Data from primary and secondary care clinical histories and care processes in the 18 months leading up to confirmation (signs and symptoms at presentation, diagnosis pathways, referrals, diagnosis interval) of the EOC diagnosis (stage, histology type, treatment). Diagnostic process intervals were based on the Aarhus statement. 1-year and 5-year survival analysis was undertaken.

Results

Of the 513 patients included in the cohort, 67.2% initially consulted their family physician, while 36.4% were diagnosed through emergency services. In the Cox models, survival was influenced by advanced stage at 1 year (HR 3.84, 95% CI 1.23 to 12.02) and 5 years (HR 5.36, 95% CI 3.07 to 9.36), as was the type of treatment received, although this association was attenuated over follow-up. Age became significant at 5 years of follow-up. After adjusting for age, adjusted morbidity groups, stage at diagnosis and treatment, 5-year survival was better in patients presenting with gynaecological bleeding (HR 0.35, 95% CI 0.16 to 0.79). Survival was not associated with a starting point involving primary care (HR 1.39, 95% CI 0.93 to 2.09), diagnostic pathways involving referral to elective gynaecological care from non-general practitioners (HR 0.80, 95% CI 0.51 to 1.26), or self-presentation to emergency services (HR 0.82, 95% CI 0.52 to 1.31).

Conclusions

Survival in EOC is not associated with diagnostic pathways or prehospital healthcare, but it is influenced by stage at diagnosis, administration of primary cytoreduction plus chemotherapy and patient age.
Goal attainment scaling as an outcome measure for randomised controlled trials: a scoping review
Authors: Logan Benignus , Jegatheesan Dev , Viecelli Andrea , Pascoe Elaine , Hubbard Ruth
Published: July 2022

Objectives

(1) Identify the healthcare settings in which goal attainment scaling (GAS) has been used as an outcome measure in randomised controlled trials. (2) Describe how GAS has been implemented by researchers in those trials.

Design

Scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews approach.

Data sources

PubMed, CENTRAL, EMBASE and PsycINFO were searched through 28 February 2022.

Eligibility criteria

English-language publications reporting on research where adults in healthcare settings were recruited to a randomised controlled trial where GAS was an outcome measure.

Data extraction and synthesis

Two independent reviewers completed data extraction. Data collected underwent descriptive statistics.

Results

Of 1,838 articles screened, 38 studies were included. These studies were most frequently conducted in rehabilitation (58%) and geriatric medicine (24%) disciplines/populations. Sample sizes ranged from 8 to 468, with a median of 51 participants (IQR: 30–96). A number of studies did not report on implementation aspects such as the personnel involved (26%), the training provided (79%) and the calibration and review mechanisms (87%). Not all trials used the same scale, with 24% varying from the traditional five-point scale. Outcome attainment was scored in various manners (self-report: 21%; observed: 26%; both self-report and observed: 8%; and not reported: 45%), and the calculation of GAS scores differed between trials (raw score: 21%; T score: 47%; other: 21%; and not reported: 66%).

Conclusions

GAS has been used as an outcome measure across a wide range of disciplines and trial settings. However, there are inadequacies and inconsistencies in how it has been applied and implemented. Developing a cross-disciplinary practical guide to support a degree of standardisation in its implementation may be beneficial in increasing the reliability and comparability of trial results.

PROSPERO registration number

CRD42021237541.
Prevalence and risk factors for COPD in subjects with preserved ratio impaired spirometry
Authors: Kanetake Rina , Takamatsu Kazufumii , Park Kaechang , Yokoyama Akihito
Published: July 2022

Background

Chronic obstructive pulmonary disease (COPD) has been found to be caused by impairment of lung development. Preserved ratio impaired spirometry (PRISm) is thought to be a subtype of lung growth impairment and is associated with COPD. PRISm is heterogeneous and the prevalence and progression to COPD are not yet clear. To prove this, we examined the association by using the medical check-up data.

Methods

This retrospective study included medical check-up subjects who visited the Kochi Medical Check-up Clinic at least twice for both period 1 (P1) (2014–2016) for the first visit and period 2 (P2) (2017–2019) for the final visit. The mean duration between visits was 1042±323 days. COPD was defined as a forced expiratory volume in 1 s (FEV1):forced vital capacity (FVC) ratio LLN and per cent forced expiratory volume in 1 s (%FEV1) (FEV1/predicted FEV1) of <80% without bronchodilators in this study.

Results

Of 1672 subjects (mean age±SD 56.5±9.5), 976 (58.4%) were male. The prevalence of PRISm was 10.5% in P1 and 8.9% in P2. The percentage of subjects who progressed to COPD was higher in PRISm than in the normal lung function group (OR 2.62, p=0.014). In logistic regression analysis, PRISm was an independent risk factor for developing COPD (OR 3.75, p<0.001). The best cut-off value of %FEV1for prediction of progression to COPD was 86%. The proportion of the PRISm group increased (23.6%) in this cut-off.

Conclusion

The prevalence of PRISm was around 10% but increased up to 23.6% at the best cut-off for progression to COPD, and careful follow-up is necessary in these groups even if FEV1/FVC is normal.
Mutation burden-orthogonal tumor genomic subtypes delineate responses to immune checkpoint therapy
Authors: Takamatsu Shiro , Hamanishi Junzo , Brown J B , Yamaguchi Ken , Yamanoi Koji , Murakami Kosuke , Gotoh Osamu , Mori Seiichi , Mandai Masaki , Matsumura Noriomi
Published: July 2022

Background

In cancer therapy, higher-resolution tumor-agnostic biomarkers that predict response to immune checkpoint inhibitor (ICI) therapy are needed. Mutation signatures reflect underlying oncogenic processes that can affect tumor immunogenicity, and thus potentially delineate ICI treatment response among tumor types.

Methods

Based on mutational signature analysis, we developed a stratification for all solid tumors in The Cancer Genome Atlas (TCGA). Subsequently, we developed a new software (Genomic Subtyping and Predictive Response Analysis for Cancer Tumor ICi Efficacy, GS-PRACTICE) to classify new tumors submitted to whole-exome sequencing. Using existing data from 973 pan-cancer ICI-treated cases with outcomes, we evaluated the subtype-response predictive performance.

Results

Systematic analysis on TCGA samples identified eight tumor genomic subtypes, which were characterized by features represented by smoking exposure, ultraviolet light exposure, APOBEC enzyme activity,POLEmutation, mismatch repair deficiency, homologous recombination deficiency, genomic stability, and aging. The former five subtypes were presumed to form an immune-responsive group acting as candidates for ICI therapy because of their high expression of immune-related genes and enrichment in cancer types with FDA approval for ICI monotherapy. In the validation cohort, the samples assigned by GS-PRACTICE to the immune-reactive subtypes were significantly associated with ICI response independent of cancer type and TMB high or low status.

Conclusions

The new tumor subtyping method can serve as a tumor-agnostic biomarker for ICI response prediction and will improve decision making in cancer treatment.
Tumor cell SYK expression modulates the tumor immune microenvironment composition in human cancer via TNF-α dependent signaling
Authors: Aguirre-Ducler Adam , Gianino Nicole , Villarroel-Espindola Franz , Desai Shruti , Tang Daiwei , Zhao Hongyu , Syrigos Konstantinos , Trepicchio William L , Kannan Karuppiah , Gregory Richard C , Schalper Kurt A
Published: July 2022

Background

The expression of SYK in cancer cells has been associated with both tumor promoting and tumor suppressive effects. Despite being proposed as anticancer therapeutic target, the possible role of SYK in modulating local adaptive antitumor immune responses remains uncertain. Using detailed analysis of primary human tumors and in vitro models, we reveal the immunomodulatory effect of SYK protein in human solid cancer.

Methods

We spatially mapped SYK kinase in tumor cells, stromal cells and tumor-infiltrating leukocytes (TILs) in 808 primary non-small cell lung carcinomas (NSCLCs) from two cohorts and in 374 breast carcinomas (BCs) from two independent cohorts. We established the associations of localized SYK with clinicopathologic variables and outcomes. The immunomodulatory role of SYK on tumor cells was assessed using in vitro cytokine stimulation, transcriptomic analysis and selective SYK blockade using a small molecule inhibitor. Functional responses were assessed using cocultures of tumor cells with peripheral blood lymphocytes. T cell responses in baseline and post-treatment biopsies from patients with BC treated with a SYK inhibitor in a phase I clinical trial were also studied.

Results

Elevated tumor cell or leukocyte SYK expression was associated with high CD4+and CD8+TILs and better outcome in both NSCLC and BC. Tumor cell SYK was associated with oncogenic driver mutations in EGFR or KRAS in lung adenocarcinomas and with triple negative phenotype in BC. In cultured tumor cells, SYK was upregulated by TNFα and required for the TNFα-induced proinflammatory responses and T cell activation. SYK blockade after nivolumab in a phase I clinical trial including three patients with advanced triple negative BC reduced TILs and T cell proliferation. Our work establishes the proinflammatory function of tumor cell SYK in lung and breast cancer. SYK signaling in cultured tumor cells is required for T cell activation and SYK blockade limits adaptive antitumor immune responses and tumor rejection in patients with cancer.

Conclusions

Together, our results establish the immunomodulatory role of SYK expression in human solid tumors. This information could be used to develop novel biomarkers and/or therapeutic strategies.