bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing screen layout in multimedia applications through integer programming and metaheuristic
Authors: González Pedro Henrique , Amorim Glauco , Souza Ueverton S. , Morais Igor , dos Santos Joel , Guimarães Vanessa de A. , Ribeiro Glaydston M.
Published: October 2021

Binding audiovisual content into multimedia applications requires the specification of each media item, including its size and position, to define a screen layout. The multimedia application author must plan the application’s screen layout (ASL), considering a variety of screen sizes where the application shall be executed. An ASL that maximizes the area occupied by media items on the screen is essential, given that screen space is a valuable asset for media broadcasters. In this paper, we introduce the Application Screen Layout Optimization Problem, and present its 𝒩P-hardness. Besides, two integer programming formulations and an Iterated Local Search (ILS) metaheuristic are proposed to solve it. The efficiency of the proposed methods is evaluated, showing that the metaheuristic achieves better results and is at least 12 times faster, on average, than the mathematical formulations. Also, the proposed approaches were compared to a layout design algorithm, showing their effectiveness.
Physische Belastungsreaktionen bei fahrradergometrischen Untersuchungen in sitzender- und halbliegender Position
Authors: Richter Lutz
Published: October 2021

Fahrradergometrische Untersuchungen werden zur Therapiesteuerung und zur Feststellung der körperlichen Leistungsfähigkeit und Belastbarkeit bei sportmedizinischen Untersuchungen eingesetzt. Dabei haben sich die sitzende und halbliegende Fahrradergometrie etabliert. Zur Übertragbarkeit der durch die unterschiedlichen Belastungssituationen ermittelten Ergebnisse gibt es nur wenige Veröffentlichungen, die zudem ohne eindeutige Aussagen sind. Ziel der Studie ist es, durch eine Einzelfalluntersuchung exemplarisch die Vergleichbarkeit der beiden Belastungssituationen anhand von spirometrischen und kardiozirkulatorischen Parametern zu ermitteln. Die vorliegenden Ergebnisse legen die Vermutung nahe, dass eine Limitierung der Übertragbarkeit von spiroergometrisch gewonnenen Belastbarkeitswerten auf die jeweils adäquate Sitz- bzw. Halbliegeposition im Ergometertraining nicht angebracht scheint.
Rehabilitation von Patienten mit Interstitieller Cystitis/Bladder Pain Syndrom (IC/BPS)
Authors: Vahlensieck Winfried , El Idrissi Raschid , Gerhard-Franke Ursula , Huber Maren , Jenner Jennifer , Zermann Dirk-Henrik
Published: October 2021

Nach nicht erfolgreicher ambulanter konservativer oder auch stationär invasiver Therapie und nach Zystektomie bei interstitieller Cystitis/Bladder Pain Syndrom (IC/BPS) soll laut deutscher IC-Leitlinie eine fachspezifische stationäre urologische Rehabilitation (Reha) beantragt werden. Während dieser wird die Diagnostik bei Bedarf vervollständigt. Die multimodale Therapie umfasst insbesondere die Optimierung des eigenen Lebensstils und der Medikation. Eine intensive psychologische Betreuung kann oft die Krankheitsverarbeitung verbessern. Verschiedene Formen der Bewegungstherapie und die physikalische Therapie mit Wasseranwendungen, Wärmeanwendungen, diversen Formen der Massage und Elektro- bzw. Magnettherapie sowie eine Ernährungsberatung führen häufig zur Linderung der Beschwerden. Die Behandlungsmaßnahmen werden bei Bedarf im Verlauf der Reha angepasst. In der Reha erfolgt auch eine sozialmedizinische Beurteilung und Beratung der Patienten, u.a. zum zu erwartenden Grad der Behinderung und zur Arbeitsfähigkeit. Zwei Drittel der Patienten weisen zum Ende der Reha eine wesentliche Besserung auf, die bei ca. 50% der Patienten auch über einen längeren Zeitraum anhält.
Pleurabrade: A Spiral Brush for Mechanical Pleurodesis and a Review of the Literature
Authors: Young John S. , Steimer Desiree A. , Polhemus Emily , Bueno Raphael
Published: October 2021

Background While the optimal treatment for primary spontaneous pneumothorax remains unclear, mechanical pleurodesis is a well-established treatment. The Pleurabrade is a spiral brush designed for mechanical pleurodesis during thoracoscopy. We present two patients who underwent mechanical pleurodesis with the Pleurabrade.

Case Description Two patients with spontaneous pneumothorax underwent operative intervention including mechanical pleurodesis with the Pleurabrade. Chest tubes were removed within 48 hours postoperatively and they were discharged home. Both patients remain recurrence free at 11 and 22 months, respectively.

Conclusion While further testing is needed, these case reports and operative video highlight the Pleurabrade as an efficient device for thoracoscopic mechanical pleurodesis.
Titanium doped nanoporous hematite photoanode modified with NiFeCoAlOOH nanoparticles for efficient photoelectrochemical water splitting
Authors: Minja Antony Charles , Wang Taotao , Cao Hongyun , Du Pingwu
Published: October 2021

Herein, we present the decoration of NiFeCoAlOOH nanoparticles onto titanium doped nanoporous hematite (Ti-PH) utilizing a simple electroless ligand-controlled oxidation method for photoelectrochemical water splitting. Owing to the improved oxygen evolution reaction kinetics and reduced charge transfer resistance, the resulting Ti-PH/NiFeCoAlOOH photoanode presents an excellent photocurrent density of 2.46 mA/cm2 at 1.23 V vs. RHE and good stability compared to Ti-PH or bare hematite. Furthermore, the onset potential of the photocurrent density is shifted cathodically by ∼60 mV with reference to the titanium doped nanoporous hematite. This work offers a promising method for designing high-performance, stable, and inexpensive catalysts for photoelectrochemical applications.
A pair of dopamine neurons mediate chronic stress signals to induce learning deficit in
Drosophila melanogaster
Authors: Jia Jia , He Lei , Yang Junfei , Shuai Yichun , Yang Jingjing , Wu Yalan , Liu Xin , Chen Tianli , Wang Guaxiu , Wang Xingyu , Song Xiaoxu , Ding Zhaowen , Zhu Yan , Zhang Li , Chen Peng , Qin Hongtao
Published: October 2021

Significance

Chronic stressful life events could induce learning and memory impairments and increase the risk of developing psychiatric disorders such as depression. Understanding the underlying mechanism is critical for developing effective drugs and treatments. Here, we show that chronic stress induces learning and memory deficits in
Drosophila melanogaster
. Furthermore, the dopaminergic system is important for regulating susceptibility to chronic stress– induced learning deficit (CSLD). Significantly, a single pair of dopamine neurons, PPL1-γ1pedc neurons, are indispensable for CSLD. We show that PPL1-γ1pedc mediates chronic stress signals to induce abnormal neural activities in mushroom bodies that lead to a learning deficit. Together, these suggest that
Drosophila
melanogaster
can be a powerful model organism for studying the etiology of chronic stress–induced memory impairments.
A cell–ECM mechanism for connecting the ipsilateral eye to the brain
Authors: Su Jianmin , Sabbagh Ubadah , Liang Yanping , Olejníková Lucie , Dixon Karen G. , Russell Ashley L. , Chen Jiang , Pan Yuchin Albert , Triplett Jason W. , Fox Michael A.
Published: October 2021

Significance

Distinct features of the visual world are transmitted from the retina to the brain through anatomically segregated circuits. Despite this being an organizing principle of visual pathways in mammals, we lack an understanding of the signaling mechanisms guiding axons of different types of retinal neurons into segregated layers of brain regions. We explore this question by identifying how axons from the ipsilateral retina innervate a specific lamina of the superior colliculus. Our studies reveal a unique cell–extracellular matrix recognition mechanism that specifies precise targeting of these axons to the superior colliculus. Loss of this mechanism not only resulted in the absence of this eye-specific visual circuit, but it led to an impairment of innate predatory visual behavior as well.
Curvature thylakoid 1 proteins modulate prolamellar body morphology and promote organized thylakoid biogenesis inArabidopsis thaliana
Authors: Sandoval-Ibáñez Omar , Sharma Anurag , Bykowski Michał , Borràs-Gas Guillem , Behrendorff James B. Y. H. , Mellor Silas , Qvortrup Klaus , Verdonk Julian C. , Bock Ralph , Kowalewska Łucja , Pribil Mathias
Published: October 2021

Significance

Chloroplast biogenesis is a fundamental process occurring during seedling ontogenesis and leading to plant autotrophy. Which membrane components sterically organize the light-triggered transition of etioplast prolamellar bodies (PLBs) into chloroplast thylakoids, and thus mediate cubic–lamellar transformation, is poorly understood. Here, we used combined two- and three-dimensional electron microscopy, spectroscopy, and biochemical methods to determine the role of CURT1 proteins in the formation of etioplast cubic membranes and their transformation to photosynthetically active chloroplast thylakoids. CURT1 proteins were previously recognized as significant contributors to thylakoid membrane folding. We found that CURT1 proteins are integral proteins of etioplast membranes and act as factors modulating PLBs and prothylakoid nanomorphology. They are also required for concerted thylakoid maturation under de-etiolation.
Cavin4 interacts with Bin1 to promote T-tubule formation and stability in developing skeletal muscle
Authors: Lo Harriet P. , Lim Ye-Wheen , Xiong Zherui , Martel Nick , Ferguson Charles , Ariotti Nicholas , Giacomotto Jean , Rae James , Floetenmeyer Matthias , Moradi Shayli Varasteh , Gao Ya , Tillu Vikas A. , Xia Di , Wang Huang , Rahnama Samira , Nixon Susan J. , Bastiani Michele , Day Ryan D. , Smith Kelly A. , Palpant Nathan J. , Johnston Wayne A. , Alexandrov Kirill , Collins Brett M. , Hall Thomas E. , Parton Robert G.
Published: October 2021

The cavin proteins are essential for caveola biogenesis and function. Here, we identify a role for the muscle-specific component, Cavin4, in skeletal muscle T-tubule development by analyzing two vertebrate systems, mouse and zebrafish. In both models, Cavin4 localized to T-tubules, and loss of Cavin4 resulted in aberrant T-tubule maturation. In zebrafish, which possess duplicated cavin4 paralogs, Cavin4b was shown to directly interact with the T-tubule–associated BAR domain protein Bin1. Loss of both Cavin4a and Cavin4b caused aberrant accumulation of interconnected caveolae within the T-tubules, a fragmented T-tubule network enriched in Caveolin-3, and an impaired Ca2+ response upon mechanical stimulation. We propose a role for Cavin4 in remodeling the T-tubule membrane early in development by recycling caveolar components from the T-tubule to the sarcolemma. This generates a stable T-tubule domain lacking caveolae that is essential for T-tubule function.
A review of the effects of wildfire smoke on the health and behavior of wildlife
Authors: Sanderfoot O V , Bassing S B , Brusa J L , Emmet R L , Gillman S J , Swift K , Gardner B
Published: October 2021

Climate change is intensifying global wildfire activity, and people and wildlife are increasingly exposed to hazardous air pollution during large-scale smoke events. Although wildfire smoke is considered a growing risk to public health, few studies have investigated the impacts of wildfire smoke on wildlife, particularly among species that are vulnerable to smoke inhalation. In this review, we synthesized research to date on how wildfire smoke affects the health and behavior of wildlife. After executing a systematic search using Web of Science, we found only 41 relevant studies. We synthesized findings from this literature and incorporated knowledge gained from fields outside wildlife science, specifically veterinary medicine and air pollution toxicology. Although studies that directly investigated effects of smoke on wildlife were few in number, they show that wildfire smoke contributes to adverse acute and chronic health outcomes in wildlife and influences animal behavior. Our review demonstrates that smoke inhalation can lead to carbon monoxide poisoning, respiratory distress, neurological impairment, respiratory and cardiovascular disease, oxidative stress, and immunosuppression in wildlife, including terrestrial and aquatic species, and these health effects can contribute to changes in movement and vocalization. Some species also use smoke as a cue to engage in fire-avoidance behaviors or to conserve energy. However, our review also highlights significant gaps in our understanding of the impacts of wildfire smoke on wildlife. Most notably, the lack of robust air pollution measurements in existing studies limits meta-analyses and hinders construction of dose-response relationships, thereby precluding predictions of health outcomes and behaviors under different air quality conditions, especially during extreme smoke events. We recommend that future studies leverage existing data sets, infrastructure, and tools to rapidly advance research on this important conservation topic and highlight the potential value of interdisciplinary collaborations between ecologists and atmospheric chemists.
Effect of nitrogen deposition on centennial forest water-use efficiency
Authors: Gharun Mana , Klesse Stefan , Tomlinson Gregory , Waldner Peter , Stocker Benjamin , Rihm Beat , Siegwolf Rolf , Buchmann Nina
Published: October 2021

The uptake of carbon dioxide (CO2) from the atmosphere through photosynthesis is accompanied by an inevitable loss of water vapor through the stomata of leaves. The rate of leaf-level CO2 assimilation per unit stomatal conductance, i.e. intrinsic water-use efficiency (WUEi), is thus a key characteristic of terrestrial ecosystem functioning that is central to the global hydroclimate system. Empirical evidence and theory suggest a positive response of forest WUE to increased CO2 levels globally. Although evidence exists for a positive effect of ecosystem nitrogen (N) inputs on WUEi, it is not clear how trends in atmospheric N deposition have affected WUEi in the past. Here we combine twentieth-century climate and nitrogen deposition with stable isotope signature in tree rings and document a WUEi trend reversal at two sites in Switzerland, that matches the timing of a trend reversal in atmospheric N deposition. Using generalized additive models (GAMs), we fitted observed WUEi time series to multiple environmental covariates. This suggested N deposition to have a significant effect on long-term WUEi at the site that was exposed to higher N deposition levels. The ratio of the increase in WUEi in response to increase in CO2 (dWUEi/dCO2) declined by 96% after 1980 (from 0.53 to 0.02) in the beech forest and declined by 72% in the spruce forest (from 0.46 to 0.13) concurrent with a sharp decline in N deposition. Using the GAM model for two scenarios, we show that had N deposition levels not declined after 1980s, WUEi would have increased more strongly in response to increasing CO2. Although the increase in N deposition was limited to the 1950–1980 decades and the signals have declined with improvements in air quality across Europe, the role of atmospheric pollution must be reconsidered in interpretation of tree ring studies and for building environmental proxies that are pivotal to understanding future sink capacity of terrestrial ecosystems in response to climate change.
Surging dynamics of South Rimo Glacier, Eastern Karakoram
Authors: Jiang Zongli , Wu Kunpeng , Liu Shiyin , Wang Xin , Zhang Yong , Tahir Adnan Ahmad , Long Sichun
Published: October 2021

Describing the dynamic characteristics of glacier surge events is a precursor to being able to understand their driving mechanisms. Here, a comprehensive suite of surface velocities and surface elevation changes for the surging South Rimo Glacier (SRG), situated in the East Karakoram region, are obtained by offset-tracking from Sentinal-1A and geodetic method from TerraSAR-X/TanDEM-X and Ice, Cloud, and land Elevation Satellite-2 Advanced Topographic Laser Altimeter System. The surge of SRG initiated in the summer of 2018, and the rapid and dramatic increase in surface velocities reached a peak (∼12 m d−1) in August 2019. By the summer of 2020, the surface velocity of SRG had returned to its pre-surge level. We interpret that the evolution of the latest SRG surge was probably triggered by changes in subglacial thermal conditions, and was ultimately accelerated by hydrological processes. Based on historical analysis, a surge return period of ∼25–30 years prevails at SRG. Spatiotemporal analyses of surface velocities and elevation changes such as these can provide useful information about surge mechanisms and their controls.
On free semigroups of affine maps on the real line
Authors: Kolpakov Alexander , Talambutsa Alexey
Published: October 2021

In this note we generalise some of the work of Klarner on free semigroups of affine maps acting on the real line by using a classical approach from geometric group theory (the Ping-Pong lemma). We also investigate the boundaries up to which the Klarner’s necessary condition for a semigroup to be related is applicable.
Allo-preening is linked to vocal signature development in a wild parrot
Authors: Arellano Caleb M M , Canelón Nurialby Viloria , Delgado Soraya , Berg Karl S
Published: October 2021

Allo-grooming networks in primate social groups are thought to have favored the evolution of vocal recognition systems, including vocal imitation in humans, as a more effective means of maintaining social bonds in large groups. Select avian taxa converged on vocal learning, but it is not clear what role analogues of allo-grooming might have played. Unlike allo-grooming in most primates, allo-preening in birds is usually limited to pair-bonds. One exception to this is during nestling development when siblings preen each other, but it is unknown how allo-preening influences vocal learning. We addressed this question in wild Green-rumped Parrotlets (Forpus passerinus) in Venezuela. Nestlings learn signature contact calls from adult templates. Large broods, age hierarchies and protracted development in this species create the potential for complex allo-preening networks and a unique opportunity to test how early sociality makes the development of vocal learning labile. From audio-video recordings inside nest cavities and a balanced design of different brood sizes, we quantified allo-preening interactions between marked nestlings, to compare to signature contact calls. Controlling for brood size and age hierarchy, the propensity to preen a larger number of individuals (i.e., out-strength) correlated positively with the age at first contact call. Allo-preening and acoustic similarity matrices did not reveal clear correlations within broods, instead larger broods produced greater contact call diversity. Results indicate that allo-preening elongates the period during which contact calls develop, which might allow individuals time to form a unique signature under the computationally challenging social conditions inherent to large groups.
Condition- and context-dependent alternative reproductive tactic in Drosophila prolongata
Authors: Perdigón Ferreira Jhoniel , Lüpold Stefan
Published: October 2021

Species with intense male–male competition for access to females often show alternative reproductive tactics (ARTs) where males of lower competitive ability adopt a sneaky behavior to gain access to mates. These ARTs are usually associated with intrasexual dimorphisms, in that males with distinct morphologies show different tactics. In some cases, however, males adopt different tactics without being dimorphic. Male Drosophila prolongata exhibit continuous variation in body size and shape, with enlarged forelegs that they use in male-male contests and in courtship, including stimulation of the female’s abdomen. During this “leg vibration,” however, nearby males can intercept the courted female and mate without their own courtship. Here, we studied the causes and consequences of these different mating tactics in competitive mating trials between males varying in their size and shape. We found that male mating tactics were condition-dependent. Whereas large, high-condition males were more likely to show leg vibration in their courtship, smaller, lower-condition males were more likely to intercept. However, the number of offspring produced was independent of male condition and reproductive tactic. We discuss possible scenarios for the evolution and maintenance of the ARTs and some future directions for the study of ARTs in this species and in general.
AncestralClust: clustering of divergent nucleotide sequences by ancestral sequence reconstruction using phylogenetic trees
Authors: Pipes Lenore , Nielsen Rasmus
Published: October 2021

Motivation

Clustering is a fundamental task in the analysis of nucleotide sequences. Despite the exponential increase in the size of sequence databases of homologous genes, few methods exist to cluster divergent sequences. Traditional clustering methods have mostly focused on optimizing high speed clustering of highly similar sequences. We develop a phylogenetic clustering method which infers ancestral sequences for a set of initial clusters and then uses a greedy algorithm to cluster sequences.

Results

We describe a clustering program AncestralClust, which is developed for clustering divergent sequences. We compare this method with other state-of-the-art clustering methods using datasets of homologous sequences from different species. We show that, in divergent datasets, AncestralClust has higher accuracy and more even cluster sizes than current popular methods.

Availability and implementation

AncestralClust is an Open Source program available at https://github.com/lpipes/ancestralclust.

Supplementary information

Supplementary data are available at Bioinformatics online.
Current and future potential global distribution of the invading species Drosophila nasuta (Diptera: Drosophilidae)
Authors: Lauer Garcia Ana Cristina , Pessoa Da Silva Felipe , Campos Bezerra Neves Carlos Henrique , Montes Martín Alejandro
Published: October 2021

Species distribution modelling has been widely employed to indicate probable areas of invasion and to guide management strategies. Drosophila nasuta is native to Asia and has invaded Africa, islands of the Indian and Pacific Oceans and, more recently, the Americas. This species has been dispersing rapidly in the past decade, dominating the assemblage of drosophilids in numerous invaded territories, especially in protected areas. Here, we model the potential geographic distribution of D. nasuta for the present and two future scenarios. We also determine the environmental variables that most influence its distribution and investigate the risk of invasion in protected areas. Drosophila nasuta has the potential to expand its occurrence, especially on continents that have already been invaded. Variables related to greater rainfall were those that most influenced its distribution. The projections for the two future scenarios revealed a small increase in the distribution of the species compared to the projection for the present. The largest overlaps between the projected areas to be invaded by D. nasuta and territories in protected areas were found for Central and South America. The predictive maps delineated here can assist in the establishment of management plans directed at the conservation of biodiversity.
1396 Improving Documentation During A General Surgical Ward Round
Authors: Gidwani R , Kilkenny J , Lawther R
Published: October 2021

Introduction

Clear documentation at ward rounds is essential to patient safety. The purpose of this audit was to identify areas that could be improved in the documentation at surgical ward round.

Method

A retrospective audit of the most recent ward round entry, in two surgical wards, was carried out against the Royal College of Physicians ‘Generic Medical Record Keeping Standards’. Patient name, Health & Care number (HCN), date, time(24hr), senior doctor present, signature, printed name, GMC/contact details of the scribe were analysed. After data collection, the standards were circulated to all doctors during departmental teaching and displayed on note trollies. A re-audit was then undertaken. Chi-square test was used to compare the two audit cycles and p value of < 0.05 was considered significant.

Results

21 patient notes were analysed in the initial audit. Patient name and HCN was noted in 86%(18/21) and 67%(14/21) respectively. 100% of notes included date and senior doctor. Time of entry, signature and printed name/Bleep/GMC number were noted in 81%(17/21), 90.5%(19/21) and 57%(12/21) respectively. 24 patients were included in the re-audit. Results revealed improvement in all parameters as follows: patient name (95.8% 21/24;p=0.23); HCN (91.6%; 22/24;p=0.036),; date and senior doctor (100% as before); time (87.5%; 21/24;p=0.55); signature (100%; 24/24), and printed name/GMC/bleep (87.5%; 21/24;p=0.022).

Conclusions

This closed loop audit demonstrates an overall improvement in the quality of surgical documentation at ward rounds with a very simple intervention. Additionally, a statistically significant improvement was noted in recording HCN and printed name/GMC/bleep.
1434 An Audit of Surgical Consent Standards in Patients Undergoing Elective ENT Surgery
Authors: Shivabalendran T , Ahmed U , Eweiss A , Kaddour H
Published: October 2021

Aim

Good Surgical Practice (RCS England) and GMC guidelines inform a surgeon’s practice in the consent process for an operation. Since the Covid-19 pandemic, many surgical departments have converted from face-to-face to telephonic consultations. The clinic letter is of increased importance given that it forms a key part of the medical record which the patient should receive to ensure sufficient time and information to make an informed decision.

Method

Clinic letters of patients undergoing elective ENT surgery at our trust over a four-week period were examined in this retrospective audit of compliance with RCSEng and GMC guidelines. Additional data was collected on clinician grade and proportion of letters sent to patients. Patients rated satisfaction with consultation on a five-point Likert scale.

Results

135 eligible patients were included in our audit and the majority were listed by a consultant (57%). In all domains, consultant letters were more likely to be comprehensive as compared to registrars. Overall quality of clinic letters was highly variable regarding documentation of diagnosis (52%), surgical risks (50%), discussion of alternative or no treatment (30%) and registrar discussion with consultant (31%). There was also a stark difference between registrars and consultants sending patients copies of clinic letters (10% vs 47%). Only 10% of patients received a leaflet on their condition. 90% of patients were either satisfied or very satisfied with their clinic consultation.

Conclusions

Refresher sessions on consent, updated template letters and increased provision of patient information leaflets will be introduced to the ENT department, and improvements monitored with further re-audit.
1469 Audit of Clinical Notes Filing in Vascular Surgery
Authors: Griffiths M , Perusseau-Lambert A , Bush A , Mittapalli D
Published: October 2021

Aim

Assess the correctness of patient's notes filing following the Royal College of Physicians, Record Keeping Standards, and the General Medical Council, Good Medical Practice, guidance: medical notes must be filed in the correct section, in a chronological order, three key identifiers on each page.

Method

Over 3 months, the general surgical wards, using case notes and those using folders for the current admission were assessed to identify loose notes. The vascular surgery patients’ notes were reviewed for the following criteria: not loose, filed in the correct section, in chronological order, and had three key identifiers.

Results

Surgical wards using case notes had 28.6% of the notes filed (n = 21) compared with 78.9% filed on wards with admission folders (n = 57). Within vascular surgery (n = 15), 13.3% had all notes filed, 20% were in chronological order, 6.7% had notes filed in the correct section, and 20% had key identifiers on every page.

Conclusions

The filing of case notes on the vascular ward resulted in loose notes more than other wards that use admission folders. To resolve this, “Admission Folders” were introduced (alongside full case notes) to assist with filing and label sheets used to assist with fast identification of current admission documents. After implementation of Admission Folders, the staff found notes easier to access and follow, according to the staff surveys, and notes were correctly filed and given identifiers, ensuring continued quality care for the patients.
1470 Consenting for a Bedside Procedure: A Prospective Observational Analysis of Consenting Practice in the Surgical Emergency Admissions Unit of a District General Hospital
Authors: Davis H , Mishra S , Balakumar C , Shrestha A
Published: October 2021

Aim

Consent is necessary to enable patient autonomy, and it is vital that it is voluntary, informed and, where possible, the patient has valid mental capacity to give consent. Recent case law has grown around consent and practice guidance has evolved.

This was a prospective observational study investigating the quality of consenting practice for incision and drainage procedures performed within the surgical emergency admissions unit (SEAU) at a district general hospital.

Method

A prospective study was conducted on consent documentation for a study period from August to September 2020, for patients undergoing bedside incision and drainage (I&D) procedures within the SEAU. Documentation was reviewed and data collected for quality of consent. Further data into the quality of this documentation was also collected; including legibility, risk and benefit discussions, local anaesthetic used, operation note documentation and discussion of the procedure. This was compared against GMC standards.

Results

Of 20 cases (n = 20), 1 case had written consent and 15 cases had verbal consent documented. 4 cases had no documentation of consent. No cases had benefit documentation, and 4 out of the 20 cases had risks documented. 4 cases had documentation of procedure discussion. 13 cases had an operation note included.

Conclusions

This study highlights a deviation from recommended practice, and results have been communicated at a departmental level. Recommendations have been offered in an attempt to improve compliance, including the display of posters in the SEAU. We shall re-audit practice within the coming months after these changes have been implemented.
1512 A Service Evaluation of Transoral Laser Resection Procedures for Oral Cancer and Dysplasia
Authors: Amin A , Twigg J , Bowe C , Ho M
Published: October 2021

Aim

The use of the diode laser is a frequently employed treatment modality in primary surgical excision, especially for early oral cancer. This is due to advantages offered in precision of excision, and potential reduced post-operative pain compared to other excision methods. Additionally, haemostasis can often be obtained simultaneous to excision. Despite frequent use of laser excision for oral cancer/dysplasia, there is limited information on the incidence of postoperative complications.

Method

Data was collected retrospectively by review of electronic healthcare records for a 5-year period (Jan 2015-Jan 2020) for patients who underwent transoral laser excision of oral dysplasia in a major UK teaching hospital. The number of short (<30 days) and longer-term complications was evaluated and categorised using the Clavien-Dindo classification.

Results

A total 260 patients received diode laser resection for oral cancer/dysplasia in this period. Approximately one third of patients had the diagnosis of SCC and 52% of patients were treated on a day case basis. Approximately one third of patients experienced postoperative complications.; including positive or close resection margins (16%), bleeding (8%), superficial infection (6%) and significant postoperative pain (2%). A total of 16% of patients required further treatment in theatre (Clavien-Dindo IIIb).

Conclusions

The use of lasers for excision of oral tumours and dysplastic lesions is a frequently employed modality, offering advantages to the operating surgeon (improved haemostasis, excellent manoeuvrability) and patients (reduced pain and scarring). Complications are largely predictable in nature, but the surgical team should be aware of potential issues to ensure safe, effective patient care.
MUC1-C dictates neuroendocrine lineage specification in pancreatic ductal adenocarcinomas
Authors: Luan Zhou , Morimoto Yoshihiro , Fushimi Atsushi , Yamashita Nami , Suo Wenhao , Bhattacharya Atrayee , Hagiwara Masayuki , Jin Caining , Kufe Donald
Published: October 2021

Pancreatic ductal adenocarcinomas (PDAC) and poorly differentiated pancreatic neuroendocrine (NE) carcinomas are KRAS mutant malignancies with a potential common cell of origin. PDAC ductal, but not NE, lineage traits have been associated with cell-intrinsic activation of interferon (IFN) pathways. The present studies demonstrate that the MUC1 C-terminal subunit (MUC1-C), which evolved to protect mammalian epithelia from loss of homeostasis, is aberrantly overexpressed in KRAS mutant PDAC tumors and cell lines. We show that MUC1-C is necessary for activation of the type I and II IFN pathways and for expression of the Yamanaka OCT4, SOX2, KLF4 and MYC (OSKM) pluripotency factors. Our results demonstrate that MUC1-C integrates IFN signaling and pluripotency with NE dedifferentiation by forming a complex with MYC and driving the (i) achaete-scute homolog 1 and BRN2/POU3F2 neural, and (ii) NOTCH1/2 stemness transcription factors. Of translational relevance, targeting MUC1-C genetically and pharmacologically in PDAC cells (i) suppresses OSKM, NE dedifferentiation and NOTCH1/2, and (ii) inhibits self-renewal capacity and tumorigenicity. In PDAC tumors, we show that MUC1 significantly associates with activation of IFN signaling, MYC and NOTCH, and that upregulation of the MUC1-C → MYC pathway confers a poor prognosis. These findings indicate that MUC1-C dictates PDAC NE lineage specification and is a potential target for the treatment of recalcitrant pancreatic carcinomas with NE dedifferentiation.
GNA14’s interaction with RACK1 inhibits hepatocellular carcinoma progression through reducing MAPK/JNK and PI3K/AKT signaling pathway
Authors: Xu Cong , Li Yi-Ming , Sun Bo , Zhong Fang-Jing , Yang Lian-Yue
Published: October 2021

Gαq subfamily proteins play critical roles in many biological functions including cardiovascular development, angiogenesis, and tumorigenesis of melanoma. However, the understanding of G Protein Subunit Alpha 14 (GNA14) in diseases, especially in cancers is limited. Here, we revealed that GNA14 was significantly low expression in Human hepatocellular carcinoma (HCC) samples. Low GNA14 expression was correlated with aggressive clinicopathological features. Moreover, the overall survival (OS) and disease-free survival (DFS) of high GNA14 expression HCC patients were much better than low GNA14 expression group. Lentivirus-mediated GNA14 knockdown significantly promoted the growth of liver cancer in vitro and in vivo. However, opposing results were observed when GNA14 is upregulated. Mechanistically, We identified receptor for activated C kinase 1 (RACK1) as a binding partner of GNA14 by co-immunoprecipitation and mass spectrometry (MS). Glutathione-S-transferase (GST) pull-down assay further verified the direct interaction between GNA14 and RACK1. RNA-Seq and loss- and gain-of-function assays also confirmed that GNA14 reduced the activity of both MAPK/JNK and PI3K/AKT signaling pathways through RACK1. GNA14 synergized with U73122 (PLC inhibitor) to enhance this effect. Further studies suggested that GNA14 potentially competed with protein kinase C (PKC) to bind with RACK1, consequently reducing the stability of PKC. Moreover, we also showed that GNA14’supression of p-AKT protein level depended on sufficient RACK1 expression. In conclusion, we indicated a different role of GNA14, which acted as a suppressor inhibiting liver cancer progression through MAPK/JNK and PI3K/AKT signaling pathways. Due to this, GNA14 served as a potentially valuable prognostic biomarker for liver cancer.
Developmental age and biological sex influence muscarinic receptor function and neuron morphology within layer VI of the medial prefrontal cortex
Authors: Patel Ashutosh V , Codeluppi Sierra A , Ervin Kelsy S J , St-Denis Myles B , Choleris Elena , Bailey Craig D C
Published: October 2021

Acetylcholine (ACh) neurotransmission within the medial prefrontal cortex (mPFC) plays an important modulatory role to support mPFC-dependent cognitive functions. This role is mediated by ACh activation of its nicotinic (nAChR) and muscarinic (mAChR) classes of receptors, which are both present on mPFC layer VI pyramidal neurons. While the expression and function of nAChRs have been characterized thoroughly for rodent mPFC layer VI neurons during postnatal development, mAChRs have not been characterized in detail. We employed whole-cell electrophysiology with biocytin filling to demonstrate that mAChR function is greater during the juvenile period of development than in adulthood for both sexes. Pharmacological experiments suggest that each of the M1, M2, and M3 mAChR subtypes contributes to ACh responses in these neurons in a sex-dependent manner. Analysis of dendrite morphology identified effects of age more often in males, as the amount of dendrite matter was greatest during the juvenile period. Interestingly, a number of positive correlations were identified between the magnitude of ACh/mAChR responses and dendrite morphology in juvenile mice that were not present in adulthood. To our knowledge, this work describes the first detailed characterization of mAChR function and its correlation with neuron morphology within layer VI of the mPFC.
Reframing urban and regional ‘development’ for ‘left behind’ places
Authors: MacKinnon Danny , Kempton Louise , O’Brien Peter , Ormerod Emma , Pike Andy , Tomaney John
Published: October 2021

The recent wave of populism has focused attention on ‘left behind’ places as hotspots of discontent. Seeking to remedy their neglect in urban and regional studies, the aim of this paper is to engage with the problems of ‘left behind’ places and to stimulate fresh thinking about alternative approaches. Reflecting the complex and inter-connected issues facing such places, it argues that a new conception is required to address issues of belonging and attachment. The paper outlines the basis of an expanded neo-endogenous development approach, identifying the foundational economy, income and livelihoods, social infrastructures and social innovation as key policy concerns.
Early and late acute kidney injury: temporal profile in the critically ill pediatric patient
Authors: Ruth Amanda , Basu Rajit K , Gillespie Scott , Morgan Catherine , Zaritsky Joshua , Selewski David T , Arikan Ayse Akcan
Published: October 2021

Background

Increasing AKI diagnosis precision to refine the understanding of associated epidemiology and outcomes is a focus of recent critical care nephrology research. Timing of onset of acute kidney injury (AKI) during pediatric critical illness and impact on outcomes has not been fully explored.

Methods

This was a secondary analysis of the Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) database. AKI was defined as per Kidney Disease: Improving Global Outcomes criteria. Early AKI was defined as diagnosed at ≤48 h after intensive care unit (ICU) admission, with any diagnosis >48 h denoted as late AKI. Transient AKI was defined as return to baseline serum creatinine ≤48 h of onset, and those without recovery fell into the persistent category. A second incidence of AKI ≥48 h after recovery was denoted as recurrent. Patients were subsequently sorted into distinct phenotypes as early-transient, late-transient, early-persistent, late-persistent and recurrent. Primary outcome was major adverse kidney events (MAKE) at 28 days (MAKE28) or at study exit, with secondary outcomes including AKI-free days, ICU length of stay and inpatient renal replacement therapy.

Results

A total of 1262 patients had AKI and were included. Overall mortality rate was 6.4% (n = 81), with 34.2% (n = 432) fulfilling at least one MAKE28 criteria. The majority of patients fell in the early-transient cohort (n = 704, 55.8%). The early-persistent phenotype had the highest odds of MAKE28 (odds ratio 7.84, 95% confidence interval 5.45–11.3), and the highest mortality rate (18.8%). Oncologic and nephrologic/urologic comorbidities at AKI diagnosis were associated with MAKE28.

Conclusion

Temporal nature and trajectory of AKI during a critical care course are significantly associated with patient outcomes, with several subtypes at higher risk for poorer outcomes. Stratification of pediatric critical care-associated AKI into distinct phenotypes is possible and may become an important prognostic tool.
Urine metabolic risk factors and outcomes of patients with kidney transplant nephrolithiasis
Authors: Bolen Erin , Stern Karen , Humphreys Mitchell , Brady Alexandra , Leavitt Todd , Zhang Nan , Keddis Mira
Published: October 2021

Background

Nephrolithiasis in allograft kidneys is rare, but this diagnosis may lead to allograft complications and patient morbidity. Previous studies that have evaluated nephrolithiasis posttransplant have focused on surgical stone management, with limited data on urine metabolic risk factors and the presence of stones after follow-up.

Methods

We retrospectively evaluated kidney transplant recipients who were diagnosed with transplant nephrolithiasis between 2009 and 2019. Computed tomography and ultrasound imaging were used to confirm stone presence.

Results

The incidence of allograft kidney stone formation was 0.86% of 6548 kidney transplant recipients. Of the 56 cases identified, 17 (30%) had a pretransplant history of nephrolithiasis. Only four (7%) patients received a known kidney stone at the time of allograft implantation. Of the 56 cases, 34 had a 24-h supersaturation study. The urine supersaturation study showed 32 patients (94%) had a urine citrate of <450 mg excreted in 24 h (median 124.5 mg/24 h, reference range >500 mg/24 h), along with 22 patients (61%) having a urine oxalate excretion of ≥30 mg in 24 h (median 34.4 mg/24 h, reference range <30 mg/24 h). Calcium oxalate composition was most common (91% with >1 supersaturation for calcium oxalate crystals), with normal median urine calcium levels (median urine calcium 103.5 mg/24 h, reference range <200 mg/24 h). After a 4-year follow-up, 50% (n = 28) required surgical intervention and 43 (77%) patients continued to have evidence of transplant nephrolithiasis on imaging.

Conclusions

This is the largest study of transplant nephrolithiasis confirming that hypocitraturia and hyperoxaluria were the most significant urine metabolic risk factors associated with allograft nephrolithiasis and that hyperoxaluria was the most prevalent driver for calcium oxalate stone composition. Our study is first to show low stone-free rates at the last follow-up and a significant proportion requiring surgical intervention.
Use of nephrotoxic medications in adults with chronic kidney disease in Swedish and US routine care
Authors: Bosi Alessandro , Xu Yunwen , Gasparini Alessandro , Wettermark Björn , Barany Peter , Bellocco Rino , Inker Lesley A , Chang Alex R , McAdams-DeMarco Mara , Grams Morgan E , Shin Jung-Im , Carrero Juan J
Published: October 2021

Background

To characterize the use of nephrotoxic medications in patients with chronic kidney disease (CKD) Stages G3–5 in routine care.

Methods

We studied cohorts of adults with confirmed CKD G3–5 undergoing routine care from 1 January 2016 through 31 December 2018 in two health systems [Stockholm CREAtinine Measurements (SCREAM), Stockholm, Sweden (N = 57 880) and Geisinger, PA, USA (N = 16 255)]. We evaluated the proportion of patients receiving nephrotoxic medications within 1 year overall and by baseline kidney function, ranked main contributors and examined the association between receipt of nephrotoxic medication and age, sex, CKD G-stages comorbidities and provider awareness of the patient's CKD using multivariable logistic regression.

Results

During a 1-year period, 20% (SCREAM) and 17% (Geisinger) of patients with CKD received at least one nephrotoxic medication. Among the top nephrotoxic medications identified in both cohorts were non-steroidal anti-inflammatory drugs (given to 11% and 9% of patients in SCREAM and Geisinger, respectively), antivirals (2.5% and 2.0%) and immunosuppressants (2.7% and 1.5%). Bisphosphonate use was common in SCREAM (3.3%) and fenofibrates in Geisinger (3.6%). Patients <65 years of age, women and those with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts. Notably, provider awareness of a patient's CKD was associated with lower odds of nephrotoxic medication use {odds ratios [OR] 0.85[95% confidence interval (CI) 0.80–0.90] in SCREAM and OR 0.80 [95% CI 0.72–0.89] in Geisinger}.

Conclusions

One in five patients with CKD received nephrotoxic medications in two distinct health systems. Strategies to increase physician's awareness of patients’ CKD and knowledge of drug nephrotoxicity may reduce prescribing nephrotoxic medications and prevent iatrogenic kidney injury.
Blockade of IL-23: What is in the Pipeline?
Authors: Parigi Tommaso Lorenzo , Iacucci Marietta , Ghosh Subrata
Published: October 2021

Interleukin 23 [IL-23] plays a key role in the pathogenesis of both Crohn’s disease [CD] and ulcerative colitis [UC], promoting a Th17 cell-related immune response. The combined blockade of IL-23 and IL-12 with ustekinumab has been demonstrated to be safe and effective in the treatment of inflammatory bowel disease [IBD]. Studies on preclinical models and observations of other immune-mediated diseases, such as psoriasis, suggest that the selective inhibition of IL-23 could be beneficial in IBD. Four monoclonal antibodies [risankizumab, mirikizumab, brazikumab and guselkumab] are currently in advance clinical trials for either CD or UC. In this review, we provide an overview of the main results from published studies of selective anti IL-23 agents.
Myocardial efficiency in patients with different aetiologies and stages of heart failure
Authors: Hansen Kristoffer Berg , Sörensen Jens , Hansson Nils Henrik , Nielsen Roni , Larsen Anders Hostrup , Frøkiær Jørgen , Tolbod Lars Poulsen , Gormsen Lars Christian , Harms Hendrik Johannes , Wiggers Henrik
Published: October 2021

Aims

Myocardial external efficiency (MEE) is the ratio of cardiac work in relation with energy expenditure. We studied MEE in patients with different aetiologies and stages of heart failure (HF) to discover the role and causes of deranged MEE. In addition, we explored the impact of patient characteristics such as sex, body mass index (BMI), and age on myocardial energetics.

Methods and results

Cardiac energetic profiles were assessed with 11C-acetate positron emission tomography (PET) and left ventricular ejection fraction (LVEF) was acquired with echocardiography. MEE was studied in 121 participants: healthy controls (n = 20); HF patients with reduced (HFrEF; n = 25) and mildly reduced (HFmrEF; n = 23) LVEF; and patients with asymptomatic (AS-asymp; n = 38) and symptomatic (AS-symp; n = 15) aortic stenosis (AS). Reduced MEE coincided with symptoms of HF irrespective of aetiology and declined in tandem with deteriorating LVEF. Patients with AS-symp and HFmrEF had reduced MEE as compared with controls (22.2 ± 4.9%, P = 0.041 and 20.0 ± 4.2%, P < 0.001 vs. 26.1 ± 5.8% in controls) and a further decline was observed in patients with HFrEF (14.7 ± 6.3%, P < 0.001). Disproportionate left ventricular hypertrophy was a major cause of reduced MEE. Female sex (P < 0.001), a lower BMI (P = 0.001), and advanced age (P = 0.03) were associated with a lower MEE.

Conclusion

MEE was reduced in patients with HFrEF, HFmrEF, and HF due to pressure overload and MEE may therefore constitute a treatment target in HF. Patients with LVH, advanced age, female sex, and low BMI had more pronounced reduction in MEE and personalized treatment within these patient subgroups could be relevant.