bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring the turnover kinetics of G protein-coupled receptors
Authors: Edwardson J Michael
Published: November 2023

G protein-coupled receptors are found predominantly at the plasma membrane in unstimulated cells (1). Following agonist stimulation, the receptors are usually efficiently endocytosed and delivered to intracellular compartments, from where they may be either recycled to the plasma membrane or transported to lysosomes for degradation. This intracellular transport is known to play an important role in the regulation of receptor function. Consequently, a complete characterization of the processes of receptor endocytosis and recycling is crucial to our understanding of cellular responses to agonists. The quantitation of receptor trafficking is best achieved by the use of radioligand binding. In intact cells, a non-polar, membrane-permeant radioligand will detect the total population of receptors, whereas a polar, membrane-impermeant radioligand will detect only receptors present at the cell surface. The transport of receptors into and out of the plasma membrane can therefore be measured through changes in the binding of a membrane-impermeant radioligand. In response to agonist stimulation, the binding of such a radioligand typically falls rapidly, with a half-time of a few minutes, reaching a value of 40-60% of the binding to unstimulated cells after about 30 minutes (2, 3). During this 30 minute period there is no significant reduction in the total number ofreceptors, measured through the binding of a membrane-permeant radioligand (2, 3). If the agonist is removed after a short time, the density of receptors at the surface is restored almost to the original value, by receptor recycling (2, 3). In fact, the redistribution of receptors in response to agonist stimulation, usually termed internalization, represents a ‘snap-shot’ of a new steady-state, in which at any instant there are fewer receptors at the cell surface and more in internal compartments.
Real time receptor function in vitro: microphysiometry and the fluorometric imaging plate reader (FLIPR)
Authors: Wood Martyn , Smart Darren
Published: November 2023

The recent application of molecular biological techniques to the cloning of receptors has greatly increased our understanding of their function and regulation. This has enabled the study of the direct interaction of the ligand with a single receptor essentially free of many of the complications experienced with in vitro studies in native receptors, although the use of recombinant expression systems has introduced new problems such as overexpression and lack of, or incorrect, coupling mechanisms. However, for receptors with 7-transmembrane domains, the use of heterologous expression systems has resulted in a limited ability to study receptor function in real time. Instead of measuring contractile or secretory responses directly, receptor function is studied using biochemical techniques such as changes in the concentration of cAMP, changes in the activity of adenylyl cyclase, or accumulation of inositol phosphates. However, these changes are not measured in real time but use ‘before’ and ‘after’ or ‘end-point’ measurements. Here, we describe the use of two techniques which enable the real time assessment of receptor function using cloned receptors expressed in cell lines, with special reference to the family of 7-transmembrane spanning receptors.
In vivo gene transfer of antisense to receptors: methods for antisense delivery with adeno-associated virus
Authors: Phillips M Ian , Qian Keping , Mohuczy Dagmara
Published: November 2023

Ligand receptor binding is a critically important step in the process of many diseases. Over-production of a ligand can be as pathogenic as under-production or lack of a ligand and up-regulation of receptors can produce the same defect as over-production of a ligand. Likewise, down-regulation of receptors can result in the same effects as under-production of the ligand. For example, drugs used to treat hypertension, a chronic disease affecting millions, have included p-adrenergic receptor blockers, ot-adrenergic receptor blockers and, more recently, angiotensin type 1 receptor (ATrR) blockers and Ca2+ channel blockers. All are aimed at reducing the ligand receptor binding interaction by drug receptor antagonism.
Intracameral injection of triamcinolone acetonide to treat macular edema in pseudophakia
Authors: Hwang Jin Young , Eom Youngsub , Kim Hyo Myung , Song Jong Suk
Published: November 2023

The study aimed to evaluate the effectiveness of intracameral injection of triamcinolone acetonide (TA) on macular edema before and after cataract surgery. Intracameral injection of TA was performed at the end of cataract surgery in patients with macular edema before cataract surgery. We also performed intracameral injection of TA to treat macular edema in other pseudophakic eyes. In the patient receiving intracameral injection of TA during cataract surgery, central macular thickness decreased from 351 to 272 μm at 1 month after cataract surgery. In 2 patients who had secondary intraocular lens (IOL) implantation using retropupillary fixation of the iris claw IOL, intracameral TA injection successfully reduced central macular thickness, although 1 patient was refractory to intravitreal TA injection. Intracameral injection of TA seems to be more familiar to cataract surgeons and is an effective treatment for macular edema in pseudophakic eyes.
Factors Associated With Sinoatrial Reinnervation After Heart Transplantation
Authors: Christensen Anders H. , Wyller Vegard B.B. , Nygaard Sissel , Rolid Katrine , Nytrøen Kari , Gullestad Lars , Fiane Arnt , Thaulow Erik , Saul J. Philip , Døhlen Gaute
Published: November 2023

Background.

Factors associated with sympathetic and parasympathetic sinoatrial reinnervation after heart transplantation (HTx) are inadequately studied.

Methods.

Fifty transplant recipients were examined at 7 to 12 wk (index visit), 6, 12, 24, and 36 mo after HTx. Supine rest heart rate variability in the low-frequency (LF) domain (sympathetic and parasympathetic sinoatrial reinnervation) and the high-frequency (HF) domain (parasympathetic sinoatrial reinnervation) were measured repeatedly and related to selected recipient, donor, and perisurgical characteristics. We primarily aimed to identify index visit factors that affect the sinoatrial reinnervation process. Secondarily, we examined overall associations between indices of reinnervation and repeatedly measured recipient characteristics to generate new hypotheses regarding the consequences of reinnervation.

Results.

LF and HF variability increased time dependently. In multivariate modeling, a pretransplant diagnosis of nonischemic cardiomyopathy (P = 0.038) and higher index visit handgrip strength (P = 0.028) predicted improved LF variability. Recipient age, early episodes of rejection, and duration of extracorporeal circulation were not associated with indices of reinnervation. Study average handgrip strength was positively associated with LF and HF variability (respectively, P = 0.005 and P = 0.029), whereas study average C-reactive protein was negatively associated (respectively, P = 0.015 and P = 0.008).

Conclusions.

Indices of both sympathetic and parasympathetic sinoatrial reinnervation increased with time after HTx. A pretransplant diagnosis of nonischemic cardiomyopathy and higher index visit handgrip strength predicted higher indices of mainly sympathetic reinnervation, whereas age, rejection episodes, and duration of extracorporeal circulation had no association. HTx recipients with higher indices of reinnervation had higher average handgrip strength, suggesting a link between reinnervation and improved frailty. The more reinnervated participants had lower average C-reactive protein, suggesting an inhibitory effect of reinnervation on inflammation, possibly through enhanced function of the inflammatory reflex. These potential effects of reinnervation may affect long-term morbidity in HTx patients and should be scrutinized in future research.
Lacibacter sediminis sp. nov., isolated from contaminated freshwater sediment
Authors: Zhuo Ye , Jin Chun-Zhi , Jin Feng-Jie , Oh Hee-Mock , Lee Hyung-Gwan , Li Taihua , Jin Long
Published: November 2023

Two Gram-stain-negative bacterial strains, S13-6-6 and S13-6-22T, were isolated from sediment sample collected at a water depth of 4 m from Lake Hongze, Jiangsu Province, PR China. The cells of strains S13-6-6 and S13-6-22T were non-spore-forming, aerobic, non-motile and formed orange colonies on R2A agar. Comparative 16S rRNA gene sequence studies revealed a clear affiliation of the two strains with he phylum

Bacteroidota

, and revealed the highest pairwise sequence similarities with

Lacibacter daechungensis

H32-4T (97.8 %),

Lacibacter cauensis

NJ-8T (97.8 %),

Lacibacter luteus

TTM-7T (97.4 %) and

Lacibacter nakdongensis

SS2-56T (97.4 %). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that the strains formed a clear phylogenetic lineage with the genus

Lacibacter

. The major fatty acids were identified as iso-C15 : 1G, iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) (>10 %), and the respiratory quinone was identified as menaquinone MK-7. The polar lipids consisted of phosphatidylethanolamine, two unidentified aminolipids, an unidentified phospholipid and six unidentified lipids. The genomic DNA G+C content was determined to be 40.2 mol% (HPLC) for strain S13-6-6 and 40.3 % (genome) for strain S13-6-22T. The combined genotypic and phenotypic data indicated that strains S13-6-6 and S13-6-22T represent a novel species of the genus

Lacibacter

, for which the name Lacibacter sediminis sp. nov. is proposed. The type strain is S13-6-22T (=CGMCC 1.17450T =JCM 35802T).
Motivational drivers of heavy work investment: intercultural comparison between USA and Egypt
Authors: Garas Lydia , Aziz Shahnaz , Wuensch Karl , Waterwall Brian
Published: November 2023

Purpose

The purpose is to identify the underlying motives of heavy work investment (HWI) types (i.e. workaholism and work engagement) based on self-determination theory, while controlling for job demands and resources. The role of four cultural differences (i.e. individualism, power distance, uncertainty avoidance and masculinity) in moderating the motivational correlated relationships is also explored using data retrieved from two distinct cultures (i.e. the USA and Egypt).

Design/methodology/approach

Full-time employees (N = 595) in the USA and Egypt were surveyed. Multiple regression analyses were used to test the associations between the two HWI types and four types of motivation (i.e. intrinsic, extrinsic, introjected and identified motivations). Furthermore, moderation analyses were conducted to explore potential effects of four cultural dimensions (i.e. individualism, power distance, uncertainty avoidance and masculinity) on the motivationalcorrelated relationships.

Findings

Workaholism positively relates to the controlled types of motivation (i.e. extrinsic and introjected regulation), while work engagement positively relates to the autonomous ones (i.e. intrinsic and identified regulation) and negatively associates with extrinsic motivation. Moreover, cultural masculinity moderated the relationship between work engagement and extrinsic motivation, as well as the association between workaholism and extrinsic motivation.

Practical implications

A clear differentiation of motivation behind both types of HWI is required by occupational health practitioners to design interventions that stimulate employee engagement rather than fuel workaholism. Multinational organizations could also benefit from understanding the interaction between cultural dimensions, motives and HWI, thereby planning more effective work engagement strategies among different cultures.

Originality/value

This is the first study to investigate the motivational correlates of HWI types across two contrasting cultures.
Mitochondrial dysfunction is associated with hypertrophic cardiomyopathy in Pompe disease‐specific induced pluripotent stem cell‐derived cardiomyocytes
Authors: Huang Wenjun , Zhou Rui , Jiang Congshan , Wang Jie , Zhou Yafei , Xu Xiaoyan , Wang Tao , Li Anmao , Zhang Yanmin
Published: November 2023

Pompe disease (PD) is a rare autosomal recessive disorder that presents with progressive hypertrophic cardiomyopathy. However, the detailed mechanism remains clarified. Herein, PD patient‐specific induced pluripotent stem cells were differentiated into cardiomyocytes (PD‐iCMs) that exhibited cardiomyopathic features of PD, including decreased acid alpha‐glucosidase activity, lysosomal glycogen accumulation and hypertrophy. The defective mitochondria were involved in the cardiac pathology as shown by the significantly decreased number of mitochondria and impaired respiratory function and ATP production in PD‐iCMs, which was partially due to elevated levels of intracellular reactive oxygen species produced from depolarized mitochondria. Further analysis showed that impaired fusion and autophagy of mitochondria and declined expression of mitochondrial complexes underlies the mechanism of dysfunctional mitochondria. This was alleviated by supplementation with recombinant human acid alpha‐glucosidase that improved the mitochondrial function and concomitantly mitigated the cardiac pathology. Therefore, this study suggests that defective mitochondria underlie the pathogenesis of cardiomyopathy in patients with PD.
Use of simulated data to explore the application of optical coherence tomography for classifying middle-ear pathologies
Authors: Golabbakhsh Marzieh , Funnell W. Robert J.
Published: November 2023

Optical coherence tomography (OCT) vibrometry is a non-invasive tool for functional imaging of the middle ear. It provides spatially resolved vibrational responses and also anatomical images of the same ear. Our objective here was to explore the potential of OCT vibration measurements at the incus, as well as at the umbo, to distinguish among middle-ear disorders. Our approach was to build finite-element models of normal and pathological ears, generate large amounts of synthetic data, and then classify the simulated data into normal and pathological groups using a decision tree based on features extracted from simulated vibration magnitudes. We could distinguish between normal ears and ears with incudomallear joint (IMJ) disarticulation or stapes fixation, with the sensitivity and specificity both being 1.0; distinguish between stapes fixation and IMJ disarticulation with a sensitivity of 0.900 and a specificity of 0.889; and distinguish ears with ISJ disarticulation from normal ears with a sensitivity of 0.784 and a specificity of 0.872. Less extreme pathologies were also simulated. The results suggest that the vibration measurements within the middle ear that can be provided by OCT (e.g., at the incus) may be very valuable for diagnosis.
Sirtuin 2 promotes human cytomegalovirus replication by regulating cell cycle progression
Authors: Betsinger Cora N. , Justice Joshua L. , Tyl Matthew D. , Edgar Julia E. , Budayeva Hanna G. , Abu Yaa F. , Cristea Ileana M.
Published: November 2023

The ability to modulate host cell cycle progression is a requirement of many human viruses in order to facilitate their replication and propagation. Nuclear-replicating DNA viruses frequently stall the host cell cycle in G1 to avoid competition with host DNA replication. Among these viruses is human cytomegalovirus (HCMV), a prevalent beta-herpesvirus. Here, we discover a pro-viral mechanism that employs the deacetylase activity of the human enzyme sirtuin 2 (SIRT2) for HCMV-mediated cell cycle dysregulation. First, we show that the SIRT2 deacetylase activity supports an early stage of HCMV replication. Focusing on these early infection time points, we next define temporal SIRT2 protein interactions and deacetylation substrates by using mass spectrometry-based interactome and acetylome analyses. We find that SIRT2 interacts with and modulates the acetylation level of cell cycle proteins during infection, including the cyclin-dependent kinase 2 (CDK2). Using flow cytometry, cell sorting, and functional assays, we demonstrate that SIRT2 regulates CDK2 K6 acetylation and the G1- to S-phase transition in a manner that supports HCMV replication. Altogether, our findings expand the understanding of mechanisms underlying HCMV-induced cell cycle dysregulation and point toward regulatory feedback between SIRT2 and CDK2 that can have implications in other viral infections and human diseases.

IMPORTANCE

This study expands the growing understanding that protein acetylation is a highly regulated molecular toggle of protein function in both host anti-viral defense and viral replication. We describe a pro-viral role for the human enzyme SIRT2, showing that its deacetylase activity supports HCMV replication. By integrating quantitative proteomics, flow cytometry cell cycle assays, microscopy, and functional virology assays, we investigate the temporality of SIRT2 functions and substrates. We identify a pro-viral role for the SIRT2 deacetylase activity via regulation of CDK2 K6 acetylation and the G1-S cell cycle transition. These findings highlight a link between viral infection, protein acetylation, and cell cycle progression.
Supplemental Material: Sustained deformation across the Sub-Himalayas since 200 ka
Authors: Bouscary Chloé , al. et
Published: November 2023

Sample selection and methods, Tables S1–S11, and Figures S1–S5.  
Atraumatic splenic rupture associated with COVID-19
Authors: Smaadahl Nils , Rüber Fabienne , Bosbach Simon , Martig Franz
Published: November 2023

Atraumatic splenic rupture (ASR) is a rare but life-threatening condition. Several underlying pathologies have been associated with a splenic rupture in the absence of trauma, most often malignant-haematological disorders, viral infections or local inflammatory disorders. The management of ASR is similar to traumatic splenic rupture and includes early risk stratification of patients to determine those eligible for non-operative treatment versus those who need immediate surgical intervention. In this report, we discuss a rare case of a non-operatively managed ASR in an otherwise healthy young patient with SARS-CoV-2 as the likely aetiology. The multisystemic nature of the ongoing novel COVID-19 is evident, but not all manifestations are yet known. This case report underlines the challenge for physicians in terms of recognising and treating emergent complications of this new disease.
A narrative review of challenges related to healthcare worker rights, roles and responsibilities in the provision of sexual and reproductive services in health facilities
Authors: Schaaf Marta , Lavelanet Antonella , Codjia Laurence , Nihlén Åsa , Rehnstrom Loi Ulrika
Published: November 2023

Introduction

This paper identifies and summarises tensions and challenges related to healthcare worker rights and responsibilities and describes how they affect healthcare worker roles in the provision of sexual and reproductive health (SRH) care in health facilities.

Method

The review was undertaken in a two-phase process, namely: (1) development of a list of core constructs and concepts relating to healthcare worker rights, roles and responsibilities to guide the review and (2) literature review.

Result

A total of 110 papers addressing a variety of SRH areas and geographical locations met our inclusion criteria. These papers addressed challenges to healthcare worker rights, roles and responsibilities, including conflicting laws, policies and guidelines; pressure to achieve coverage and quality; violations of the rights and professionalism of healthcare workers, undercutting their ability and motivation to fulfil their responsibilities; inadequate stewardship of the private sector; competing paradigms for decision-making—such as religious beliefs—that are inconsistent with professional responsibilities; donor conditionalities and fragmentation; and, the persistence of embedded practical norms that are at odds with healthcare worker rights and responsibilities. The tensions lead to a host of undesirable outcomes, ranging from professional frustration to the provision of a narrower range of services or of poor-quality services.

Conclusion

Social mores relating to gender and sexuality and other contested domains that relate to social norms, provider religious identity and other deeply held beliefs complicate the terrain for SRH in particular. Despite the particularities of SRH, a whole of systems response may be best suited to address embedded challenges.
Addressing the challenges of establishing quality wastewater or non-sewered sanitation-based surveillance, including laboratory and epidemiological considerations, in Malawi
Authors: Holm Rochelle H , Nyirenda Ruth , Smith Ted , Chigwechokha Petros
Published: November 2023

Learning from clinical laboratories, wastewater or environmental (including non-sewered sanitation) environmental microbiology laboratories can be established in resource-limited settings that focus on pathogen detection and pandemic prevention. Transparent discussions on the laboratory challenges and adaptations required for this can help meet the future requirements of health research and surveillance. This report aims to describe the challenges encountered when setting up a wastewater or environmental laboratory for multipathogen surveillance in Malawi, a resource-limited setting, as well as the lessons learnt. We identified nine unifying themes: what to monitor, human resource capacity, indicators of data quality, equipment availability, supply of consumable goods, ongoing operation and maintenance of the laboratory, application of localised guidelines for laboratory operations, lack of real-time clinical correlation for calibration and localised ethical considerations. Over our 6-month timeline, onlySalmonellatyphi,Vibrio choleraeand severe acute respiratory syndrome coronavirus 2 analyses were set-up. However, we were unable to set-up measles and tuberculosis analyses owing largely to supply delays. By establishing this system at a public higher education academic laboratory in Malawi, we have ensured that ongoing capacity building and piloting of public health work is conducted in the country, rather than relying on non-governmental organisations or reference laboratory support beyond national borders. This work is not intended to replace clinical testing but rather demonstrates the potential for adapting higher education academic laboratory infrastructure to add wastewater or environmental (including non-sewered sanitation) samples, where appropriate, as additive epidemiological data for better pandemic preparedness.
Single-nucleus transcriptome profiling of prefrontal cortex induced by
chronic methamphetamine treatment
Authors: Zeng Kuan , Yu Xuan , Wei Zhen , Wu Yong , Wang Jianzhi , Liu Rong , Li Yi , Wang Xiaochuan
Published: November 2023

Background

Methamphetamine (METH) addiction causes a huge burden on society.
The prefrontal cortex (PFC), associated with emotion and cognitive
behaviours, is also involved in addiction neurocircuitry. Although bulk
RNA sequencing has shown METH-induced gene alterations in the mouse PFC,
the impact on different cell types remains unknown.

Aims

To clarify the effects of METH treatment on different cell types of
the PFC and the potential pathways involved in METH-related
disorders.

Methods

We performed single-nucleus RNA sequencing (snRNA-seq) to examine
the transcriptomes of 20 465 nuclei isolated from the PFC of chronic
METH-treated and control mice. Main cell types and differentially
expressed genes (DEGs) were identified and confirmed by RNA fluorescence
in situ hybridization(FISH).

Results

Six main cell types were identified depending on the single-cell
nucleus sequencing; of particular interest were the mature
oligodendrocytes in the PFC. The DEGs of mature oligodendrocytes were
enriched in the myelin sheath, adenosine triphosphate (ATP) metabolic
process, mitochondrial function and components, and so on. The messenger
RNA levels of Aldoc and
Atp5l (FISH) and the protein level of the
mitochondrial membrane pore subunit TOM40 (immunofluorescence) decreased
in the mature oligodendrocytes. Fast blue staining and transmission
electron microscopy image indicated myelin damage, and the myelin
thickness decreased in METH brains.

Conclusions

snRNA-seq reveals altered transcriptomes of different cell types in
mouse PFC induced by chronic METH treatment, underscoring potential
relationships with psychiatric disorders.
Aortic valve perivascular adipose tissue computed tomography attenuation in patients with aortic stenosis
Authors: Botezatu Simona B , Yu Xinming , Meah Mohammed N , Williams Michelle C , Dey Damini , Newby David E , Tzolos Evangelos , Dweck Marc R
Published: November 2023

Objective

Aortic stenosis (AS) shares pathophysiological similarities with atherosclerosis including active inflammation. CT attenuation of perivascular adipose tissue provides a measure of vascular inflammation that is linked to prognosis and has the potential to be applied to the aortic valve. We investigated perivascular adipose tissue attenuation around the aortic valve in patients with AS.

Methods

CT attenuation was measured in the perivascular adipose tissue extending 3 mm radially and 10 mm longitudinally around the aortic valve in patients with and without AS. Associations between perivascular adipose tissue attenuation and AS disease severity, activity and progression were investigated.

Results

Perivascular adipose tissue attenuation around the aortic valve demonstrated good intraobserver and interobserver repeatability (interobserver: intraclass correlation coefficient 0.977 (95% CI: 0.94, 0.99)) but was similar between patients with AS (n=120) and control subjects (n=80) (−62.4 (−68.7, −56.5) Hounsfield units (HU) vs −61.2 (−65.3, −55.6) HU, p=0.099). There were no differences between perivascular adipose tissue attenuation in patients with mild (−60.2 (−66.9, −55.1) HU), moderate (−62.8 (−69.6, −56.80) HU) or severe (−62.3 (−69.3, −55.4) HU) AS (all p>0.05), and perivascular adipose tissue attenuation did not demonstrate an association with AS severity as assessed by echocardiography or CT calcium scoring, nor with disease activity assessed by18F-sodium fluoride positron emission tomography. Moreover, there was no association between baseline aortic valve perivascular adipose tissue attenuation and subsequent AS progression (annualised change in peak velocity: r=0.072, p=0.458). Similar results were found using five other image analysis methods.

Conclusions

CT-derived aortic valve perivascular adipose tissue attenuation is not associated with AS disease severity, activity or progression suggesting that it has no value in the investigation and management of patients with AS.
Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis
Authors: Bella Ángela , Arrizabalaga Leire , Di Trani Claudia Augusta , Gonzalez-Gomariz Jose , Gomar Celia , Russo-Cabrera Joan Salvador , Olivera Irene , Cirella Assunta , Fernandez-Sendin Myriam , Alvarez Maite , Teijeira Alvaro , Atay Cigdem , Medina-Echeverz José , Hinterberger Maria , Hochrein Hubertus , Melero Ignacio , Berraondo Pedro , Aranda Fernando
Published: November 2023

Background

Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses.

Methods

MVA encoding scIL-12 (MVA.scIL-12) was evaluated against peritoneal carcinomatosis models based on intraperitoneal engraftment of tumor cells. CD8-mediated immune responses, elucidated antitumor efficacy, and safety were evaluated following intravenous, intratumoral, or intraperitoneal administration of the viral vector. The immune response was measured by ELISpot (enzyme-linked immunosorbent spot), RNA sequencing, flow cytometry, intravital microscopy, and depletion of lymphocyte subsets with monoclonal antibodies. Safety was assessed by body-weight follow-up and blood testing. Tissue tropism on intravenous or intraperitoneal administration was assessed by bioluminescence analysis using a reporter MVA encoding luciferase.

Results

Intraperitoneal or locoregional administration, but not other routes of administration, resulted in a potent immune response characterized by increased levels of tumor-specific CD8+T lymphocytes with the ability to produce both interferon-γ and tumor necrosis factor-α. The antitumor immune response was detectable not only in the peritoneal cavity but also systemically. As a result of intraperitoneal treatment, a single administration of MVA.scIL-12 encoding scIL-12 completely eradicated MC38 tumors implanted in the peritoneal cavity and also protected cured mice from subsequent subcutaneous rechallenges. Bioluminescence imaging using an MVA encoding luciferase revealed that intraperitoneal administration targets transgene to the omentum. The omentum is considered a key tissue in immune protection of the peritoneal cavity. The safety profile of intraperitoneal administration was also better than that following intravenous administration since no weight loss or hematological toxicity was observed when the vector was locally delivered into the peritoneal cavity.

Conclusion

Intraperitoneal administration of MVA vectors encoding scIL-12 targets the omentum, which is the tissue where peritoneal carcinomatosis usually begins. MVA.scIL-12 induces a potent tumor-specific immune response that often leads to the eradication of experimental tumors disseminated to the peritoneal cavity.
Characterization of anadromous Arctic char winter habitat and egg incubation areas in collaboration with Inuit fishers
Authors: Dubos Véronique , St-Hilaire André , Laurion Isabelle , Bergeron Normand E.
Published: November 2023

In Nunavik, anadromous Arctic char spend more than 6 months under ice-covered habitats, mainly in lakes. Their winter habitats in this region have been scarcely studied due to the challenging logistics in the Arctic. In this study, we worked with Inuit fishers to characterize the winter habitat and incubation areas used by Arctic chars in five overwintering lakes and one lentic river reach. The collaborating fishers determined char occupancy of certain areas related to fishing sites (presence, absence, and spawning) and conducted measurements to characterize the sites while performing their fishing activities. The data showed that incubation areas were associated with significantly shallower depths and warmer (albeit not statistically significant) lake bottom temperatures than sites where no spawning occurs, which is beneficial for egg maturation. The productivity of these areas is also beneficial for fry that hatch during winter. Adult and post-smolt habitats tended to be associated with cold littoral zone, but their habitat did not show any other distinct characteristics. This exploratory study adds insights into the cryptic characteristics of the Arctic char winter habitat use, thanks to the Inuit fishers’ knowledge of fish habitats and movements, and the experience and expertise they have acquired working in the local environment.
Kùzu: A Database Management System For "Beyond Relational" Workloads
Authors: Salihoglu Semih
Published: November 2023

I would like to share my opinions on the following question: how should a modern graph DBMS (GDBMS) be architected? This is the motivating research question we are addressing in the K`uzu project at University of Waterloo [4, 5].1 I will argue that a modern GDBMS should optimize for a set of what I will call, for lack of a better term, "beyond relational" workloads. As a background, let me start with a brief overview of GDBMSs.
Study of Adsorption Kinetics of Fe Metal in Batik Cual Waste using Chitosan of Rice Crab Shells
Authors: Fadillah Ramadhani  , Widodo Budi Kurniawan  , Aldila Widodo Budi Kurniawan
Published: November 2023

Fe metal is one of the heavy metal composition contained in cual batik waste. The content of these metal has potency as pollutan and can increase the risk of chemical substance stored in various aquatic biota and very dangerous for human consumption because it is toxic in the long term. In this research, batik waste treatment has been carried out by decadarizing Fe metal using adsorbent agent based from citosan. Paddy crab shell was extracted through demineralization, deproteination, decolorization, and deacetylation to become chitosan powder. Chitosan powder becomes an adsorbent in the adsorption process with adsorption data collection patterns for various contact times of 30, 60, 90, 120, 150, 180, 210, and 240 minutes. The adsorption results were kinetic modeled using the kinetic model of first order, second order, and BMG. From that three models obtained the R2 value that is closest to 1 is the BMG kinetic model, which is 0.999602. In addition, this model has the advantage that is it can find out the magnitude of the decolorization decay constant and the rate of decolorization of Fe metal.
Os personagens de O terceiro assassinato (Sandome no satsujin), de Hirokazu Koreeda
Authors: Sugai Mari
Published: November 2023

O presente trabalho tem como finalidade realizar uma investigação na participação e no papel desenvolvido por um dos elementos essenciais nos enredos cinematográficos, no caso específico desse trabalho, os personagens presentes na trama do longa-metragem de produção japonesa, O terceiro assassinato (Sandome no satsujin, 2018), de Hirokazu Koreeda, pertencente ao gênero de suspense. Essa categoria específica apresenta uma estrutura narrativa que demanda uma série de etapas pelas quais, tanto o protagonista, quanto o antagonista precisam se submeter para que a narrativa se desenvolva e avance. Para o desenvolvimento textual, a base teórica faz uso das obras de Luís Nogueira (2010), Doc Comparato (1995) e Flávio de Campos (2007).
Dossiê “Pensando o cinema amador”
Authors: Foster Lila
Published: November 2023

A nova edição da Revista Laika traz cinco textos dedicados à experiência amadora em quatro países diferentes: Brasil, Escócia, Estados Unidos e França. As perspectivas teóricas também são múltiplas, apontando para a riqueza da prática amadora, um universo que pode ser pensado a partir de matrizes conceituais das mais diversas: o lugar do filme doméstico em arquivos institucionais, a apropriação desses filmes como fontes históricas e material para análise visual, a relação entre memória e novas tecnologias, as particularidades e as preocupações estéticas de grupos amadores no passado e no presente. Considerando o conjunto de pesquisas desenvolvidas neste campo específico, a coleção de textos aqui apresentada concentra-se em dois temas que mereceram especial atenção nos últimos anos: a reapropriação do filme/vídeo doméstico como patrimônio, fonte histórica ou matéria de criação e a caracterização das atividades de grupos amadores.
Report, de Bruce Conner: contestando Camelot
Authors: Jenkins Bruce
Published: November 2023

Once again, as he had been forced to do in making A Movie five years earlier, Bruce Conner began creating his “report” with stock footage and appropriated sound. Report was worked, reworked, and reworked again by Conner for more than three years, and he created eight different versions of the film. As the artist confessed in 1968 at a session devoted to his work at the Robert Flaherty Film Seminar, “I was obsessed... I didn’t want to stop the changes”. It was in the end less a question of getting the film right than of finally accepting the original intention of the project: coming to terms with President Kennedy’s death.
Mosaïque ou Broderie
Authors: Fontaine Cécile
Published: November 2023

Além de alguns títulos, meus filmes são montagens curtas com duração máxima de dez minutos, misturando fitas de conteúdo variado, em diversos formatos (8mm, super-8, 16 e 35mm); eles usam filme e fotografia, colorido e preto e branco, filme mudo e filme sonoro. Constituem verdadeiros repertórios: coleções de planos escolhidos e entrelaçados, após sua “mistura” muito física e primitiva. Com exceção da parte preto e branco do Home Movie, meu trabalho não está de forma alguma relacionado à reprodução por impressora ótica ou ao uso de qualquer outro equipamento sofisticado que permita transplantar – tirar uma imagem ou um som.
Propuesta para una dimensión social de la Globalización en tiempos de pandemia: ¿Podemos contribuir a un desarrollo del proceso de Globalización que sea más ético y socialmente sostenible?
Authors: Ursua Nicanor
Published: November 2023

Se trata de ofrecer una conceptualización del proceso de la globalización contemporánea, bajo la perspectiva de una reflexión teórico-práctica, a saber, desde valores universalmente aceptados y compartidos, que conduzcan, a su vez, a un desarrollo de la globalización socialmente robusto y a la buena “gobernanza” de la globalización centrada no en utopías, sino en la resolución de los problemas reales de las personas mediante acuerdos y contratos. Se expone también el nuevo concepto de “desglobalización” y cómo la pandemia del covid-19, que está “globalizada,” está teniendo unas consecuencias sanitarias, económicas y sociales, llenas de incertidumbre como nunca se había experimentado y que nos plantea grandes retos globales.
A role of point-of-care ultrasound in the emergency department diagnosis of vision loss due to traumatic cataract
Authors: Tagle Christian A. , Chen Joe W. , Mistry Jamshid , Fernandez Danny , Neeki Cameron C. , Dong Fanglong , Neeki Michael M.
Published: November 2023

Background

Ocular complaints, including acute or subacute vision loss, are commonly encountered in emergency departments (ED). These potentially time-sensitive complaints are difficult to diagnose and evaluate without adequate, specialized equipment and expertise. Additionally, a thorough evaluation often requires a more extensive and specialized physical exam, imaging, and ophthalmologic consultation, all of which may not be readily available in the acute setting.

Case presentation

This case report presented a patient in the emergency department with the chief complaint of vision loss. Point-of-care ultrasound (POCUS) using the 10-MHz-linear-array probe, in the ocular setting, demonstrated calcification of the lens, a finding consistent with cataract in the right eye.

Conclusions

The use of POCUS can expedite the accurate identification of vision threatening pathology, such as cataracts, and streamline ED disposition and plan of care.
Attack rate, case fatality rate and determinants of measles infection during a measles outbreak in Ethiopia: systematic review and meta-analysis
Authors: Tariku Mengistie Kassahun , Worede Daniel Tarekegn , Belete Abebe Habtamu , Bante Simachew Animen , Misikir Sewnet Wongiel
Published: November 2023

Background

Although Ethiopia is working towards measles elimination, a recurrent measles outbreak has occurred. To take appropriate measures, previously, many fragmented and inconsistent outbreak investigations were done, but there is no consolidated evidence on attack rate, case fatality rate, and determinants of measles infection during the measles outbreak. This systematic review and meta-analysis aimed to identify cumulative evidence on attack rate, case fatality rate, and determinants of measles infection during the outbreak.

Methods

A systematic literature review and Meta-analysis was used. We searched Google Scholar, Medline/PubMed, Cochrane/Wiley Library, EMBASE, Science Direct, and African Journals Online databases using different terms. Investigations that applied any study design, data collection- and analysis methods related to the measles outbreak investigation were included. Data were extracted in an Excel spreadsheet and imported into STATA version 17 software for meta-analysis. The I2 statistics were used to test heterogeneity, and ‘Begg’s and ‘Egger’s tests were used to assess publication bias. The odds ratio (OR) with a 95% confidence interval (CI) was presented using forest plots.

Results

Eight measles outbreak investigations with 3004 measles cases and 33 deaths were included in this study. The pooled attack rate (A.R.) and case fatality rate were 34.51/10,000 [95% CI; 21.33–47.70/10,000] population and 2.21% [95% CI; 0.07-2.08%], respectively. Subgroup analysis revealed the highest attack rate of outbreaks in the Oromia region (63.05 per 10,000 population) and the lowest in the Amhara region (17.77 per 10,000 population). Associated factors with the measles outbreak were being unvaccinated (OR = 5.96; 95% CI: 3.28–10.82) and contact history (OR = 3.90; 95% CI: 2.47–6.15).

Conclusion

Our analysis revealed compelling evidence within the outbreak descriptions, highlighting elevated attack and case fatality rates. Measles infection was notably linked to being unvaccinated and having a contact history. Strengthening routine vaccination practices and enhancing contact tracing measures are vital strategies moving forward.
Estimating productivity levels in primary medical services across clinical commissioning groups in England and the impact of the COVID-19 pandemic: a data envelopment analysis
Authors: Williams Kate , Croft Stacey , Mohammed Mohammed A. , Wyatt Steven
Published: November 2023

Objectives

To assess the relative productivity of primary medical services in England and the impact of the COVID-19 pandemic on productivity levels.

Setting

Primary medical services for 59 million patients (98% of the population in England), in 101 clinical commissioning groups (CCGs), across two time periods: period 1, pre-pandemic, April to December 2019 and period 2, pandemic, April to December 2020.

Methods

We use data envelopment analysis (DEA) to assess relative productivity with four input measures (the number of full-time equivalent general practitioners, nurses, other direct patient contact staff and administrators), and five output measures (face-to-face appointments, remote consultations, home visits, referrals to secondary care and prescriptions). Our units of analysis were CCGs. DEA assigns an efficiency score to a CCG, taking a value between 0 and 100%, by benchmarking it against the most productive CCGs. We use Tobit regression to examine the association between productivity and other factors.

Results

The mean bias-corrected efficiency score of primary medical services in CCGs was 92.9% (interquartile range 92.0% to 95.7%) in period 1, falling to 90.6% (interquartile range 86.8% to 95.2%) in period 2. In period 1, CCGs with a higher proportion of registered patients aged over 65 years, higher levels of deprivation, lower levels of disease prevalence, higher nurse to GP ratios and higher GP to other direct patient contact staff ratios, achieved statistically significantly higher general practice efficiency scores (p < 0.05). In period 2, only the ratio of GP to other direct patient contact staff was associated with efficiency scores (p > 0.05).

Conclusions

Our analysis indicates only modest geographic variation in productivity of primary medical services when measured at the level of clinical commissioning groups and a small reduction in productivity during the pandemic. Further work to establish relative productivity of individual GP practices is warranted once sufficient data on appointment rates by GP practice is available.
The efficacy and safety assessment of oncolytic virotherapies in the treatment of advanced melanoma: a systematic review and meta-analysis
Authors: Wang Changyuan , Lu Nanxiao , Yan Lin , Li Yang
Published: November 2023

Background

The efficacy and safety of oncolytic virotherapies in the treatment of advanced melanoma still remains controversal. It is necessary to conduct quantitative evaluation on the basis of preclinical trial reports.

Methods

Publicly available databases (PubMed, Embase, Medline, Web of Science and Cochrane Library.) and register (Clinicaltrials.gov) were searched to collect treatment outcomes of oncolytic virotherapies (including herpes simplex virus type 1 (HSV), coxsackievirus A21 (CVA21), adenovirus, poxvirus and reovirus) for advanced/unresectable melanoma. Comparisons of treatment response, adverse events (AEs) and survival analyses for different virotherapies were performed by R software based on the extracted data from eligible studies.

Results

Finally, thirty-four eligible studies were analysed and HSV virotherapy had the highest average complete response (CR, 24.8%) and HSV had a slightly higher average overall response rate (ORR) than CVA21 (43.8% vs 42.6%). In the pooled results of comparing talimogene laherparepve (T-VEC) with or without GM-CSF/ICIs (immune checkpoint inhibitors) to GM-CSF/ICIs monotherapy suggested virotherapy was more efficient in subgroups CR (RR = 1.80, 95% CI [1.30; 2.51], P < 0.01), ORR (RR = 1.17, 95% CI [1.02; 1.34], P < 0.05), and DCR (RR = 1.27, 95% CI [1.15; 1.40], P < 0.01). In patients treated with T-VEC+ICIs, 2-year overall survival (12.1 ± 6.9 months) and progression-free survival (9.9 ± 6.9) were significantly longer than those treated with T-VEC alone. Furthermore, we found that AEs occurred frequently in virotherapy but decreased in a large cohort of enrolled patients, some of which, such as abdominal distension/pain, injection site pain and pruritus, were found to be positively associated with disease progression in patients treated with T-VEC monotherapy.

Conclusion

Given the relative safety and tolerability of oncolytic viruses, and the lack of reports of dose-limiting-dependent toxicities, more patients treated with T-VEC with or without ICIs should be added to future assessment analyses. There is still a long way to go before it can be used as a first-line therapy for patients with advanced or unresectable melanoma.