bluuebunny/crossref_metadata_2025 huggingface dataset:
Preanalytical Errors in Clinical Biochemistry Laboratory and Relationship With Hospital Departments and Staff: A Record-Based Study
Authors: Dundar Cihad , Bahadir Ozkan
Published: February 2023

Objective

Despite many efforts to improve the overall quality of clinical laboratory service, errors that compromise patient safety and increase healthcare costs continue to occur even infrequently. We aimed to determine the causes of preanalytical errors and related factors by evaluating the laboratory records of a tertiary hospital.

Methods

In this retrospective study, 7,762,981 requests that were registered in the biochemistry laboratory records of Ondokuz Mayıs University Health Practice and Research Center during 2019 were examined. All rejected samples were analyzed according to the department where they were collected and the reasons for rejection.

Results

Of the total sample rejections, 99,561 (74.8%) were preanalytical and 33,474 (25.2%) belonged to the analytical phase. The preanalytical rejection rate was 1.28%, with the highest rejection rate in the inpatients (2.26%) and the lowest in the outpatients (0.02%). Insufficient sample (43.7%), clotted sample (35.1%), and inappropriate sample (11.1%) were the first 3 rows of rejection reasons. It was determined that sample rejection rates were low during routine working hours and high during nonworking hours.

Conclusions

Preanalytical errors were most common in inpatient wards and were most likely due to incorrect phlebotomy techniques. Education of health personnel on good laboratory practices, systematic monitoring of errors, and the development of quality indicators will play an important role in reducing the vulnerability of the preanalytical phase.
Clinical evidence supporting ceftaroline fosamil and ceftobiprole for complicated skin and soft tissue infections
Authors: Leventogiannis Konstantinos , Mouktaroudi Maria , Giamarellos-Bourboulis Evangelos J.
Published: February 2023

Purpose of review

Ceftaroline and ceftobiprole are advanced generation cephalosporins with activity against methicillin-resistant Staphylococcus aureus (MRSA). This review summarizes their clinical efficacy for complicated skin and soft tissue infections (cSSTIs).

Recent findings

Both these agents retain excellent in vitro activity against both MRSA and Gram-negative isolates from patients with CSSTIs. Both these agents are registered for the management of cSSTIs based on the results of large scale phase III noninferiority trials. Ceftaroline and ceftobiprole are noninferior to the combination of vancomycin and aztreonam as this was assessed by their clinical cure rate at the test-of-cure visits. Furthermore, ceftobiprole is noninferior to comparators for the achievement of early clinical success at 72 h. Ceftaroline achieves 81% clinical cure against diabetic foot infections.

Ceftaroline and ceftobiprole can be used as monotherapy for the treatment of cSSTIs.
How to manage skin and soft-tissue infections in the emergency department
Authors: Bouza Emilio , Burillo Almudena , Muñoz Patricia
Published: February 2023

Purpose of review

Our purpose is to review the state-of-the-art on the management of skin and soft tissue infections (SSTI) in emergency departments (ED).

Although the information is scarce, SSTI may account for 3–30% of all cases presenting to an ED, of which 25–40% require hospital admission.

SSTI include very different entities in aetiology, location, pathogenesis, extension, and severity. Therefore, no single management can be applied to them all. A simple approach is to classify them as non-purulent, purulent, and necrotising, to which a severity scale based on their systemic repercussions (mild, moderate, and severe) must be added.

The initial approach to many SSTIs often requires no other means than anamnesis and physical examination, but imaging tests are an indispensable complement in many other circumstances (ultrasound, computerized tomography, magnetic resonance imaging…). In our opinion, an attempt at etiological filiation should be made in severe cases or where there is suspicion of a causality other than the usual one, with tests based not only on cultures of the local lesion but also molecular tests and blood cultures.

Recent findings

Recent contributions of interest include the value of bedside ultrasound and the potential usefulness of biomarkers such as thrombomodulin to differentiate in early stages the presence of necrotising lesions not yet explicit.

New antimicrobials will allow the treatment of many of these infections, including severe ones, with oral drugs with good bioavailability and for shorter periods.

The ED has an essential role in managing SSTIs, in their classification, in decisions on when and where to administer antimicrobial treatment, and in the rapid convening of multidisciplinary teams that can deal with the most complex situations.
Integrative polygenic risk score improves the prediction accuracy of complex traits and diseases
Authors: Truong Buu , Hull Leland E. , Ruan Yunfeng , Huang Qin Qin , Hornsby Whitney , Martin Hilary , van Heel David A. , Wang Ying , Martin Alicia R. , Lee S. Hong , Natarajan Pradeep
Published: February 2023

Polygenic risk scores (PRS) are an emerging tool to predict the clinical phenotypes and outcomes of individuals. Validation and transferability of existing PRS across independent datasets and diverse ancestries are limited, which hinders the practical utility and exacerbates health disparities. We propose PRSmix, a framework that evaluates and leverages the PRS corpus of a target trait to improve prediction accuracy, and PRSmix+, which incorporates genetically correlated traits to better capture the human genetic architecture. We applied PRSmix to 47 and 32 diseases/traits in European and South Asian ancestries, respectively. PRSmix demonstrated a mean prediction accuracy improvement of 1.20-fold (95% CI: [1.10; 1.3]; P-value = 9.17 × 10−5) and 1.19-fold (95% CI: [1.11; 1.27]; P-value = 1.92 × 10−6), and PRSmix+ improved the prediction accuracy by 1.72-fold (95% CI: [1.40; 2.04]; P-value = 7.58 × 10−6) and 1.42-fold (95% CI: [1.25; 1.59]; P-value = 8.01 × 10−7) in European and South Asian ancestries, respectively. Compared to the previously established cross-trait-combination method with scores from pre-defined correlated traits, we demonstrated that our method can improve prediction accuracy for coronary artery disease up to 3.27-fold (95% CI: [2.1; 4.44]; P-value after FDR correction = 2.6 × 10−4). Our method provides a comprehensive framework to benchmark and leverage the combined power of PRS for maximal performance in a desired target population.
Baseline Clinical, Hormonal and Molecular Markers Associated with Clinical Response to IL-23 Antagonism in Hidradenitis Suppurativa: A Prospective Cohort Study
Authors: Flora A , Kozera EK , Jepsen R , Gill K , Xu J , Frew JW
Published: February 2023

Background

Hidradenitis Suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL-23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated.

Objectives

To assess whether baseline clinical, hormonal, or molecular markers are associated with clinical response to IL-23 antagonism with Risankizumab in Hidradenitis Suppurativa.

Methods

26 individuals with Hurley Stage 2/3 disease were administered Risankizumab 150mg Week 0,4,12. Baseline sex hormones and skin biopsies were taken. Clinical response at Week 16 assessed by the HiSCR, and differences between responders and non-responders assessed.

Results

18 of 26 participants achieved HiSCR50 at week 16 (69.2%). Clinical response to IL-23 antagonism was associated with male gender, elevated total serum testosterone, and decreased levels of FSH. Stratification by clinical responders/non responders identified differentially expressed genes includingPLPP4andMAPK10. Immunohistochemistry identified elevated numbers of CD11c, IL-17A and IL-17F positive cells compared to non-responders. CD11c+ cells significantly correlated with serum levels of total testosterone and inversely correlated with serum FSH.

Conclusions

Clinical response to IL-23 antagonism in HS is associated with serum sex hormones, Th17 polarized inflammation in lesional tissue and CD11c+ cells. These potential therapeutic biomarkers require further validation in larger cohorts but may suggest potential targeted HS therapy.
Alternative analysis of mpox vaccine effectiveness data from Israel
Authors: Boyer Christopher B. , Lipsitch Marc
Published: February 2023

The authors have withdrawn their manuscript owing to a misunderstanding about the nature of the time-dependent analysis conducted by Wolff Sagy et al. Specifically, in an exchange the authors clarified that they did not reset the time variable in their analysis of person-time among the vaccinated, but split the observation at the time of vaccination and introduced a time-dependent indicator of vaccination. The authors stand by the general point that observational studies of vaccination during an outbreak should be aware of the potential confounding effects of calendar time and immortal time bias. However, the authors do not wish this work to be cited as specific comment on the analysis of Wolff Sagy et al. If you have any questions, please contact the corresponding author.
Comparing human and artificial intelligence in writing for health journals: an exploratory study
Authors: Haq Zaeem ul , Naeem Huzaifa , Naeem Ayesha , Iqbal Faisal , Zaeem Durayya
Published: February 2023

Aim and objectives

The aim was to contribute to the editorial principles on the possible use of Artificial Intelligence (AI)- based tools for scientific writing.

The objectives included

Enlist the inclusion and exclusion criteria to test ChatGPT use in scientific writing

Develop evaluation criteria to assess the quality of articles written by human authors and ChatGPT

Compare prospectively written manuscripts by human authors and ChatGPT

Design

Prospective exploratory study

Intervention

Human authors and ChatGPT were asked to write short journal articles on three topics: 1) Promotion of early childhood development in Pakistan 2) Interventions to improve gender-responsive health services in low-and-middle-income countries, and 3) The pitfalls in risk communication for COVID-19. We content analyzed the articles using an evaluation matrix.

Outcome measures

The completeness, credibility, and scientific content of an article. Completeness meant that structure (IMRaD) and organization was maintained. Credibility required that others work is duly cited, with an accurate bibliography. Scientific content required specificity, data accuracy, cohesion, inclusivity, confidentiality, limitations, readability, and time efficiency.

Results

The articles by human authors scored better than ChatGPT in completeness and credibility. Similarly, human-written articles scored better for most of the items in scientific content except for time efficiency where ChatGPT scored better. The methods section was absent in ChatGPT articles, and a majority of references in its bibliography were unverifiable.

Conclusions

ChatGPT generates content that is believable but may not be true. The creators of this powerful model must step up and provide solutions to manage its glitches and potential misuse. In parallel, the academic departments, editors, and publishers must expect a growing utilization of ChatGPT and similar tools. Disallowing ChatGPT as a co-author may not be enough on their part. They must adapt the editorial policies, use measures to detect AI-based writing, and stop its likely implications for human health and life.

STRENGTHS AND LIMITATIONS

First study that examines the scientific writing of ChatGPT by comparing it with human-written articles.

Explains how ChatGPT generates believable content that may not be true.

Indicates that the creators of ChatGPT must step up to address its misuse and potential hazards.

An initial exploration, based on limited data—larger studies are needed for generalizable conclusions.
Ultra fast oscillations in the human brain and their functional significance
Authors: Brázdil Milan , Worrell Gregory A. , Trávníček Vojtěch , Pail Martin , Roman Robert , Plešinger Filip , Klimeš Petr , Cimbálník Jan , Stacey William , Jurák Pavel
Published: February 2023

Human brain cellular assemblies generate emergent oscillations up to very high frequencies that can exceed the known firing rates of individual neurons. Using advanced intracranial microEEG recordings in a cohort of patients with epilepsy, we identified short-lasting local field oscillations with frequencies between 2 and 8 kHz. These ultra fast oscillations were consistently and locally detected in epileptic hippocampi but were extremely rare in normal brain tissue. The observed ultra high frequency oscillations may reflect local circuit hyperexcitability and we use a simple model to demonstrate the feasibility that these local fields are emergent oscillations representing the crest of collective high frequency neuronal unit activity.
IFT74variants cause skeletal ciliopathy and motile cilia defects in mice and humans
Authors: Bakey Zeineb , Cabrera Oscar A. , Hoefele Julia , Antony Dinu , Wu Kaman , Stuck Michael W. , Micha Dimitra , Eguether Thibaut , Smith Abigail O. , van der Wel Nicole N. , Wagner Matias , Strittmatter Lara , Beales Philip L. , Jonassen Julie A. , Thiffault Isabelle , Cadieux-Dion Maxime , Boyes Laura , Sharif Saba , Tüysüz Beyhan , Dunstheimer Desiree , Niessen Hans W.M. , Devine William , Lo Cecilia W , Mitchison Hannah M. , Schmidts Miriam , Pazour Gregory J.
Published: February 2023

Motile and non-motile cilia are critical to mammalian development and health. Assembly of these organelles depends on proteins synthesized in the cell body and transported into the cilium by intraflagellar transport (IFT). A series of human and mouseIFT74variants were studied to understand the function of this IFT subunit. Humans missing exon 2, which codes for the first 40 residues, presented an unusual combination of ciliary chondrodysplasia and mucociliary clearance disorders while individuals carrying biallelic splice site variants developed a lethal skeletal chondrodysplasia. In mice, variants thought to remove all Ift74 function, completely block ciliary assembly and result in midgestational lethality. A mouse allele that removes the first 40 amino acids, analogous to the human exon 2 deletion, results in a motile cilia phenotype with mild skeletal abnormalities.In vitrostudies suggest that the first 40 amino acids of IFT74 are dispensable for binding of other IFT subunits but are important for tubulin binding. Higher demands on tubulin transport in motile cilia compared to primary cilia could account for the motile cilia phenotype observed in human and mice.
Next-generation sequencing of pancreatic cyst wall specimens obtained using Moray micro-forceps for improving diagnostic accuracy
Authors: Astbury Stuart , Baskar Aishwarya , Grove Jane I , Kaye Philip , Aravinthan Aloysious D , James Martin W , Clarke Christopher , Aithal Guruprasad P , Venkatachalapathy Suresh Vasan
Published: February 2023

Background and study aims

Pancreatic cysts are common incidental findings, with an estimated prevalence of 13-15% in imaging done for other reasons. It is difficult to identify cysts with malignant potential. Diagnosis often relies on collection of cyst fluid, but tissue sampling using micro-forceps may allow for a more reliable diagnosis and higher yield of DNA for next-generation sequencing (NGS).

Patients and methods

24 patients referred for endoscopic ultrasound were recruited. Biopsies were taken using micro-forceps and the AmpliSeq Cancer Hotspot panel was used for NGS, a PCR assay targeting several hotspots within 50 genes, including GNAS, KRAS and VHL.

Results

The concentration of DNA extracted from 24 cyst wall samples was significantly higher than in the 9/24 available matched cyst fluid samples. Cyst wall biopsy was able to diagnose 19/24 cysts (5 high risk, 6 intraductal papillary mucinous neoplasm and 4 benign). The sensitivity, specificity and diagnostic accuracy for standard of care was 66.6%, 50% and 63.1% respectively and for standard of care with NGS was 100%, 50% and 89.4% respectively.

Conclusions

Cyst wall biopsy performs well in diagnosing cysts but was inadequate in 5/24 patients. NGS data correlates well with histology and may aid in diagnosis and risk stratification of pancreatic cysts.
Caregivers and Coping: Well-being and coping styles among caregivers of young adults with developmental disabilities
Authors: Singer Hannah , Clarke Elaine , Schiltz Hillary , Lord Catherine
Published: February 2023

Little research examines well-being in caregivers of individuals with developmental disabilities (DDs) during their child’s adulthood. Drawing from a longitudinal cohort of caregivers of adults with autism spectrum disorder (ASD) and other DDs (n= 134), this study examined change in caregiver well-being over ten years (young adults ages 18-28) and predictors of well-being, such as coping. Lower caregiver education and high young adult externalizing symptoms were related to lower caregiver well-being. Notably, caregiver coping style predicted degree of change in well-being over time. Effects of coping were moderated by demographic (i.e., parental education) and young adult characteristics (i.e., externalizing symptoms). In line with strengths-based approaches, these results illustrate the importance of coping styles in promoting caregiver well-being.
A leptin-responsive hypothalamic circuit inputs to the circadian feeding network
Authors: Tang Qijun , Godschall Elizabeth , Brennan Charles D. , Zhang Qi , Abraham-Fan Ruei-Jen , Williams Sydney P. , Güngül Taha Buğra , Onoharigho Roberta , Buyukaksakal Aleyna , Salinas Ricardo , Olivieri Joey J. , Deppmann Christopher D. , Campbell John N. , Podyma Brandon , Güler Ali D.
Published: February 2023

Salient cues, such as the rising sun or the availability of food, play a crucial role in entraining biological clocks, allowing for effective behavioral adaptation and ultimately, survival. While the light-dependent entrainment of the central circadian pacemaker (suprachiasmatic nucleus, SCN) is relatively well defined, the molecular and neural mechanisms underlying entrainment associated with food availability remains elusive. Using single nucleus RNA sequencing during scheduled feeding (SF), we identified a leptin receptor (LepR) expressing neuron population in the dorsomedial hypothalamus (DMH) that upregulates circadian entrainment genes and exhibits rhythmic calcium activity prior to an anticipated meal. We found that disrupting DMHLepRneuron activity had a profound impact on both molecular and behavioral food entrainment. Specifically, silencing DMHLepRneurons, mis-timed exogenous leptin administration, or mis-timed chemogenetic stimulation of these neurons all interfered with the development of food entrainment. In a state of energy abundance, repetitive activation of DMHLepRneurons led to the partitioning of a secondary bout of circadian locomotor activity that was in phase with the stimulation and dependent on an intact SCN. Lastly, we discovered that a subpopulation of DMHLepRneurons project to the SCN with the capacity to influence the phase of the circadian clock. This leptin regulated circuit serves as a point of integration between the metabolic and circadian systems, facilitating the anticipation of meal times.
Outer hair cell receptor potentials reveal a local resonance in the mammalian cochlea
Authors: Lukashkin Andrei N , Russell Ian J , Rybdylova Oyuna
Published: February 2023

Sensory hair cells, including the sensorimotor outer hair cells, which enable the sensitive, sharply tuned responses of the mammalian cochlea, are excited by radial shear between the organ of Corti and the overlying tectorial membrane. It is not currently possible to measure directlyin vivomechanical responses in the narrow cleft between the tectorial membrane and organ of Corti over a wide range of stimulus frequencies and intensities. The mechanical responses can, however, be derived by measuring hair cell receptor potentials. We demonstrate that the seemingly complex frequency and intensity dependent behaviour of outer hair cell receptor potentials could be qualitatively explained by a two-degrees of freedom system with a local cochlear partition and tectorial membrane resonances strongly coupled by the outer hair cell stereocilia. A local minimum in the receptor potential below the characteristic frequency is always observed at the tectorial membrane resonance frequency which, however, might shift with stimulus intensity.
Function of the bacteriophage P2 baseplate central spike Apex domain in the infection process
Authors: Miller John-Mark , Knyazhanskaya Ekaterina S. , Buth Sergii A. , Prokhorov Nikolai S. , Leiman Petr G.
Published: February 2023

The contractile tail of bacteriophage P2 functions to drive the tail tube across the outer membrane of its host bacterium, a prerequisite event for subsequent translocation of phage genomic DNA into the host cell. The tube is equipped with a spike-shaped protein (product of P2 geneV, gpV or Spike) that contains a membrane-attacking Apex domain carrying a centrally positioned Fe ion. The ion is enclosed in a histidine cage that is formed by three symmetry-related copies of a conserved HxH (histidine, any residue, histidine) sequence motif. Here, we used solution biophysics and X-ray crystallography to characterize the structure and properties of Spike mutants in which the Apex domain was either deleted or its histidine cage was either destroyed or replaced with a hydrophobic core. We found that the Apex domain is not required for the folding of full-length gpV or its middle intertwined β-helical domain. Furthermore, despite its high conservation, the Apex domain is dispensable for infection in laboratory conditions. Collectively, our results show that the diameter of the Spike but not the nature of its Apex domain determines the efficiency of infection, which further strengthens the earlier hypothesis of a drill bit-like function of the Spike in host envelope disruption.
Cell-type-specific regulation of APOE levels in human neurons by the Alzheimer’s disease risk gene SORL1
Authors: Lee Hyo , Aylward Aimee J. , Pearse Richard V. , Hsieh Yi-Chen , Augur Zachary M. , Benoit Courtney R. , Chou Vicky , Knupp Allison , Pan Cheryl , Goberdhan Srilakshmi , Duong Duc M. , Seyfried Nicholas T. , Bennett David A. , Klein Hans-Ulrich , De Jager Philip L. , Menon Vilas , Young Jessica E. , Young-Pearse Tracy L.
Published: February 2023

SORL1 is strongly implicated in the pathogenesis of Alzheimer’s disease (AD) through human genetic studies that point to an association of reduced SORL1 levels with higher risk for AD. To interrogate the role(s) of SORL1 in human brain cells, SORL1 null iPSCs were generated, followed by differentiation to neuron, astrocyte, microglia, and endothelial cell fates. Loss of SORL1 led to alterations in both overlapping and distinct pathways across cell types, with the greatest effects in neurons and astrocytes. Intriguingly, SORL1 loss led to a dramatic neuron-specific reduction in APOE levels. Further, analyses of iPSCs derived from a human aging cohort revealed a neuron-specific linear correlation between SORL1 and APOE RNA and protein levels, a finding validated in human post-mortem brain. Pathway analysis implicated intracellular transport pathways and TGF- β/SMAD signaling in the function of SORL1 in neurons. In accord, enhancement of retromer-mediated trafficking and autophagy rescued elevated phospho-tau observed in SORL1 null neurons but did not rescue APOE levels, suggesting that these phenotypes are separable. Stimulation and inhibition of SMAD signaling modulated APOE RNA levels in a SORL1-dependent manner. These studies provide a mechanistic link between two of the strongest genetic risk factors for AD.
Active zone protein SYD-2/Liprin-α acts downstream of LRK-1/LRRK2 to regulate polarized trafficking of synaptic vesicle precursors through clathrin adaptor protein complexes
Authors: Nadiminti Sravanthi S P , Dixit Shirley B , Ratnakaran Neena , Hegde Sneha , Swords Sierra , Grant Barth D , Koushika Sandhya P
Published: February 2023

Synaptic vesicle proteins (SVps) are thought to travel in heterogeneous carriers dependent on the motor UNC-104/KIF1A. InC. elegansneurons, we found that some SVps are transported along with lysosomal proteins by the motor UNC-104/KIF1A. LRK-1/LRRK2 and the clathrin adaptor protein complex AP-3 are critical for the separation of lysosomal proteins from SVp transport carriers. Inlrk-1mutants, both SVp carriers and SVp carriers containing lysosomal proteins are independent of UNC-104, suggesting that LRK-1 plays a key role in ensuring UNC-104-dependent transport of SVps. Additionally, LRK-1 likely acts upstream of the AP-3 complex and regulates the membrane localization of AP-3. The action of AP-3 is necessary for the active zone protein SYD-2/Liprin-α to facilitate the transport of SVp carriers. In the absence of the AP-3 complex, SYD-2/Liprin-α acts with UNC-104 to instead facilitate the transport of SVp carriers containing lysosomal proteins. We further show that the mistrafficking of SVps into the dendrite inlrk-1andapb-3mutants depends on SYD-2, likely by regulating the recruitment of the AP-1/UNC-101. We propose that SYD-2 acts in concert with both the AP-1 and AP-3 complexes to ensure polarized trafficking of SVps.
Stromal depletion by TALEN-edited universal hypoimmunogenic FAP-CAR T cells enables infiltration and anti-tumor cytotoxicity of tumor antigen-targeted CAR-T immunotherapy
Authors: Das Shipra , Valton Julien , Duchateau Philippe , Poirot Laurent
Published: February 2023

Adoptive cell therapy based on chimeric antigen receptor-engineered T (CAR-T) cells has proven to be lifesaving for many cancer patients. However, its therapeutic efficacy has so far been restricted to only a few malignancies, with solid tumors proving to be especially recalcitrant to efficient therapy. Poor intra-tumor infiltration by T cells and T cell dysfunction due to a desmoplastic, immunosuppressive microenvironment are key barriers for CAR T-cell success against solid tumors.

Cancer-associated fibroblasts (CAFs) are critical components of the tumor stroma, evolving specifically within the tumor microenvironment in response to tumor cell cues. The CAF secretome is a significant contributor to the extracellular matrix and a plethora of cytokines and growth factors that induce immune suppression. Together they form a physical and chemical barrier which induces a T cell-excluding ‘cold’ TME. CAF depletion in stroma rich solid tumors can thus provide an opportunity to convert immune evasive tumors susceptible to tumor-antigen CAR T-cell cytotoxicity.

Using our TALEN-based gene editing platform we engineered non-alloreactive, immune evasive CAR T-cells (termed UCAR T-cells) targeting the unique CAF marker Fibroblast Activation Protein, alpha (FAP). In an orthotopic mouse model of triple-negative breast cancer (TNBC) composed of patient derived-CAFs and tumor cells, we demonstrate the efficacy of our engineered FAP UCAR T-cells in CAF depletion, reduction of desmoplasia and successful tumor infiltration. Furthermore, while previously resistant, pre-treatment with FAP UCAR T-cells now sensitized these tumors to Mesothelin (Meso) UCAR T-cell infiltration and anti-tumor cytotoxicity. Combination therapy of FAP UCAR, Meso UCAR T cells and the checkpoint inhibitor anti-PD-1 significantly reduced tumor burden and prolonged mice survival. Our study thus proposes a novel treatment paradigm for successful CAR-T immunotherapy against stroma-rich solid tumors.
Local administration of a novel siRNA modality into the CNS extends survival and improves motor function in the SOD1G93Amouse model for ALS
Authors: Duan Chunling , Kang Moorim , Pan Xiaojie , Gan Zubao , Huang Vera , Li Guanlin , Place Robert F. , Li Long-Cheng
Published: February 2023

Antisense oligonucleotides (ASOs) were the first modality to pioneer targeted gene knockdown in the treatment of ALS caused by mutant superoxide dismutase 1 (SOD1). RNA interference (RNAi) is another mechanism of gene silencing with historically superior potency in which short interfering RNAs (siRNAs) guide the RNA-induced silencing complex (RISC) to cleave complementary transcripts. However, delivery to extrahepatic tissues like the central nerve system (CNS) has been a bottleneck in the clinical development of RNAi. Herein, we identify potent siRNA duplexes for the knockdown of human SOD1 (hSOD1) in which medicinal chemistry and conjugation to an accessory oligonucleotide (ACO) enables durable and potent activity in CNS tissues. Local delivery via intracerebroventricular (ICV) or intrathecal (IT) injection into SOD1G93Amice delayed disease progression and extended animal survival with superior efficacy compared to an ASO compound resembling Tofersen in sequence and chemistry. Treatment also prevented disease-related declines in motor function including improvements in animal mobility, muscle strength, and coordination. The ACO itself does not target any specific complementary nucleic acid sequence; rather, it imparts benefits conducive to bioavailability and delivery through its chemistry. The complete conjugate (i.e., siRNA-ACO) represents a novel modality for delivery of RNAi to the CNS in which we aim to pursue ALS as an exemplary indication for clinical development.
Finite-element simulation for crystals with surface undulations based on Takagi–Taupin theory
Authors: Wang Yu-Hang , Li Ming , Kang Le , Jia Quan-Jie
Published: February 2023

A finite-element method based on a weak formulation of the Takagi–Taupin equations was adopted to study the X-ray diffraction of crystals with surface undulations. A general diffraction geometry was simulated to investigate the diffraction features caused by the surface undulations. The numerical results reveal that the effects of surface undulations on Bragg diffraction are local for those limited in the low-frequency range and physically result from the refractive effect, brought on by the variation of the local asymmetry angle. Thus, a formula based on the local perfect flat crystal approximation was introduced to efficiently evaluate the change in the direction of the diffracted wave caused by surface undulations.
Using social media to analyze consumers' attitude toward natural food products
Authors: Fatemi Hajar , Kao Erica , Schillo R. Sandra , Li Wanyu , Du Pan , Jian-Yun Nie , Dube Laurette
Published: February 2023

Purpose

This paper examines user generated social media content bearing on consumers’ attitude and belief systems taking the domain of natural food product as illustrative case. This research sheds light on how consumers think and talk about natural food within the context of food well-being and health.

Design/methodology/approach

The authors used a keyword-based approach to extract user generated content from Twitter and used both food as well-being and food as health frameworks for analysis of more than two million tweets.

Findings

The authors found that consumers mostly discuss food marketing and less frequently discuss food policy. Their results show that tweets regarding naturalness were significantly less frequent in food categories that feature naturalness to an extent, e.g. fruits and vegetables, compared to food categories dominated by technologies, processing and man-made innovation, such as proteins, seasonings and snacks.

Research limitations/implications

This paper provides numerous implications and contributions to the literature on consumer behavior, marketing and public policy in the domain of natural food.

Practical implications

The authors’ exploratory findings can be used to guide food system stakeholders, farmers and food processors to obtain insights into consumers' mindset on food products, novel concepts, systems and diets through social media analytics.

Originality/value

The authors’ results contribute to the literature on the use of social media in food marketing on understanding consumers' attitudes and beliefs toward natural food, food as the well-being literature and food as the health literature, by examining the way consumers think about natural (versus man-made) food using user generated content of Twitter, which has not been previously used.
Macro investigation on China's engineering insurance industry: based on industrial organization theories
Authors: Zhou Xiaowei , Wang Yousong , Zhang Yangbing , Liu Fangfang
Published: February 2023

Purpose

In China, engineering insurance has been questioned as not being beneficial as expected. This paper seeks to further understand how China's engineering insurance industry functions and to provide a macro perspective explanation for engineering insurance's underdevelopment.

Design/methodology/approach

Three industrial organization hypotheses were extended to the engineering insurance context: structure conduct performance (SCP), relative market power (RMP) and efficiency structure (ES) hypotheses. This paper employed the Generalized Method of Moments (GMM) and Data Envelopment Analysis (DEA) bootstrap to test the hypotheses using panel data from 2008 to 2017.

Findings

The results suggest that the SCP paradigm is validated in China's engineering insurance market, indicating a concentrated market where the welfare of consumers (e.g. owners, contractors and designers) may be eroded. Several factors are identified to have significant impacts on engineering insurers' performance, such as the investment return, percentage of engineering business, the ratio of outstanding claims, the number of large contractors, market rivalry and entry barriers.

Originality/value

Despite the sheer size of China's construction industry and the urgent need to improve risk management, the insurance industry that serves construction firms engineering insurance is underdeveloped. Engineering insurance is yet to be understood from a macro perspective, which may reveal the underlying reasons for engineering insurance's underdevelopment. The industrial organization theories provided a theoretical framework to test the functioning of this specific industry. The disaggregated data (engineering line specific) is employed to ensure effective regulation and policymaking.
When is research and development more effective in times of crisis? The role of environmental policies
Authors: Petti Claudio , Lepore Dominique , Liakh Olena , Elia Gianluca
Published: February 2023

Purpose

In times of crisis, innovation management and specifically Research and Development (R&D) investments are critical to temper company losses and stimulate higher revenues. Environmental policies, for their potential to stimulate environmental innovations and efficient management of resources, may hold a magnifying role in this relationship. By relying on the distinction between regulatory policies and institutional incentives, this paper argues about the moderating role of environmental policies between a firm's R&D expenses and its performance.

Design/methodology/approach

Hypotheses are tested on data collected from a sample of small and medium-sized Chinese enterprises after the 2008 financial crisis.

Findings

Findings reveal positive moderating effects of both regulatory pressures and institutional incentives, with a more significant effect of government support. The highest impact is reached when both these types of policies are present.

Originality/value

The theoretical and methodological relevance of this distinction, the importance of an appropriate mix of environmental policies in policymaking and their resilience building role in stimulating environmental innovations in the aftermath of crises are discussed.
The impact of innovation orientation and knowledge management on business services performance moderated by technological readiness
Authors: Borodako Krzysztof , Berbeka Jadwiga , Rudnicki Michał , Łapczyński Mariusz
Published: February 2023

Purpose

This work aims to determine how innovation orientation (IO), built from six dimensions (strategic, structural-process, human resources, technological, organizational culture and market) affects organizational performance (OP) with the inclusion of knowledge management (KM) as a mediator and technological readiness (TR) as a moderator in the model.

Design/methodology/approach

Questionnaires completed by business service companies were analyzed using multiple regression analysis (path analysis), including the mediating variable (KM) and moderating variable (TR). The construct was validated with positive outcomes.

Findings

Of the eight hypotheses, six were supported. The study results show that strategic, technological, organizational culture and market dimensions of IO positively influence KM. On the other hand, KM plays an important role as a mediator in supporting the relationship between the four dimensions of IO and performance. Moreover, TR, as a moderator, positively affects the relationship between KM and OP.

Originality/value

The study is the first to explore the relationship between six dimensions of IO and KM in business service sector. Furthermore, this study provides evidence that TR can be beneficial for companies with respect to effective KM, which leads to the better performance.
Research trends on guest experience with service robots in the hospitality industry: a bibliometric analysis
Authors: Yörük Tayfun , Akar Nuray , Özmen Neslihan Verda
Published: February 2023

Purpose

The purpose of this study is to reveal the research trends in guest experiences of service robots in the hospitality industry.

Design/methodology/approach

In this study, a review was carried out on the Web of Science (WoS) database with the assistance of bibliometric analysis techniques. Cluster analysis was also employed for this to group important data to determine the relationships and to visualize the areas in which the studies are concentrated. The thematic content analysis method was used to reveal on which customer experiences and on which methods the focuses were.

Findings

On the subject of experiences of service robots, the greatest number of publications was in 2021. In terms of country, China has come to the fore in the distribution of publications. As a result of thematic content analysis, it was determined that the leading factor was the main dimension of emotional experience. In terms of sub-dimensions, social interactions attracted more attention. Most of the studies discussed were not based on any theory. Apart from these, the Technology Acceptance Model (TAM), the Service Quality Model (SERVQUAL) and Perceived Value Theory (PVT) were featured more prominently among other studies.

Research limitations/implications

In this study, only the WoS database was reviewed. In future studies, it would be possible to make contextual comparisons by scanning other databases. In addition to quantitative research designs, social dimensions may be examined in depth following qualitative research methods. Thus, various comparisons can be made on the subject with mixed-method research designs. Experimental research designs can also be applied to where customers have experienced human-robot interactions (HRIs).

Originality/value

In the hospitality industry, it is critical to uncover every dimension of guests' robot acceptance. This study, which presents the current situation on this basis, guides future projections for the development of guest experiences regarding service robots in the hospitality industry.
AEC/FM performance in adaptive reuse projects: investigation of challenges and development of practical guidelines
Authors: Hassanain Mohammad A. , Hamida Mohammad B.
Published: February 2023

Purpose

This paper aims to provide architecture, engineering, construction and facilities management (AEC/FM) practitioners with a guiding tool for overcoming the challenges affecting their performance in adaptive reuse project.

Design/methodology/approach

Literature review was conducted to comprehend the challenges affecting the AEC/FM performance during the implementation of adaptive reuse projects. A case study was conducted on an adaptively reused building, located in Saudi Arabia. The case study building was converted from a bookstore into an amusement center. Document review of the as-built drawings, and a structured interview with the project manager were conducted. The study concluded with the development of AEC/FM practical guidelines, pertaining to the different involved domains.

Findings

This study indicated that the potential challenges are interrelated among the three domains. These challenges pertained to the spatial, legislative, technical, administrative and operational aspects. The findings emphasized the vital role of the integration among the AEC/FM domains, at the early project planning phases. Based on the findings, three sets of AEC/FM guidelines were developed.

Research limitations/implications

Theoretically, to the best of the authors’ knowledge, this is the first study that provides a case-specific investigation of the challenges affecting the AEC/FM performance in adaptive reuse projects.

Practical implications

The developed practical guidelines could potentially enhance the AEC/FM performance in future adaptive reuse projects.

Originality/value

This study contributes to the practice of adaptive reuse projects through providing practical guidelines for mitigating the challenges that affect the AEC/FM performance in these projects.
An energy performance baseline scenario for 19thC listed dwellings in the UK
Authors: Menconi Michela , Painting Noel , Piroozfar Poorang
Published: February 2023

Purpose

The inclusion of heritage dwellings in the UK decarbonization policies can contribute to cut operational carbon emissions from the building stock; this needs to be made a priority if net zero carbon targets are to be achieved. However, the energy and carbon savings potential of suitable retrofit interventions on this part of the stock is extremely variable and strictly intertwined with the range of baseline conditions of such dwellings. This study aims to propose a framework for interventions in traditional listed dwellings (TLDs) to improve their energy performance utilizing dynamic energy simulation (DES) of selected case studies (CSs) in the city of Brighton and Hove (South-East England).

Design/methodology/approach

To achieve this aim, the study established a baseline scenario which provides a basis for the assessment of energy performance and thermo-hygrometric behaviour pre- and post-interventions and allows for comparison between different CSs under comparable conditions.

Findings

Presenting a brief overview of the methodology adopted in this study, the paper describes the approach devised to generate such baseline scenario. The paper then compares the results obtained from simulation of normalized and baseline models with the status-quo energy consumption of the dwellings investigated (based on meter readings).

Originality/value

This analysis finally allows to highlight some key physical determinants of the baseline HEC which, in the following stage of research, proved to have a considerable effect also on the amount of energy and carbon savings achievable post retrofit interventions.
Achievement to adaptive reuse strategies of industrial heritage: learning from Iranian cases
Authors: Porkar Mohammad Javad , Khakzand Mehdi , Mardanlou Nima
Published: February 2023

Purpose

The adaptability of multi-functional industrial buildings can be an important factor in their reuse. This utility requires the evaluation of factors that are effective apart from physical interventions. Therefore, this study used a combined method to investigate the factors affecting the reuse of the case studies of Iran and their adaptation to the theories proposed in the field of industrial heritage. This study aims to achieve effective strategies in adaptive reuse of industrial heritage buildings.

Design/methodology/approach

Hence, six factors in the economic, social, technological, environmental and legal sectors were analyzed based on PESTEL analysis and the interactions of the proposed matrix factors were evaluated. The results from this evaluation were integrated based on conceptual similarities and examined by SWOT technique as the main factors. Finally the criteria obtained from SWOT analysis has been approved by a Delphi survey.

Findings

Consequently, the interaction of the findings to determine the strategy was multiplied in a matrix and the resulting concepts were identified. Finally, 23 strategies were extracted as the factors affecting the reuse of industrial heritage buildings and dealing with future issues. According to the results, the most important strategies are government policies and interventions. Also, the determination of the status of ownership, supervision by the Ministry of Cultural Heritage over the preservation and revitalization of industrial heritage buildings and intervention policies for defining the uses related to an industrial building fall into this category.

Originality/value

The findings of this study indicate that an adaptive view of the above strategies and the indicators of each factor could affect the adaptive reuse of the industrial heritage.
The relations between resilience and self-efficacy among healthcare practitioners in context of the COVID-19 pandemic – a rapid review
Authors: Baluszek Joanna Barbara , Brønnick Kolbjørn Kallesten , Wiig Siri
Published: February 2023

Purpose

The purpose of this rapid review was to present current evidence on relations between resilience and self-efficacy among healthcare practitioners in the context of COVID-19 pandemic.

Design/methodology/approach

Literature searches were conducted in February/2022 in the online database MEDLINE EBSCO and not date/time limited. Eligibility criteria were as follows: population – healthcare practitioners, interest – relations between resilience and self-efficacy and context – COVID-19.

Findings

Six eligible studies from Italy, China, United Kingdom, India, Pakistan and Spain, published between 2020 and 2021 were included in the review. All studies used quantitative methods. The relations between resilience and self-efficacy were identified in contexts of resilience programs, measuring mental health of frontline nurses, measuring nurses' and nursing students' perception of psychological preparedness for pandemic management, perception of COVID-19 severity and mediating roles of self-efficacy and resilience between stress and both physical and mental quality of life. Findings indicated limited research on this topic and a need for more research.

Practical implications

Broader understanding of the relations between resilience and self-efficacy may help healthcare organizations' leaders/managers aiming to support resilience of their employers under challenging circumstances such as future pandemic.

Originality/value

The latest COVID-19 pandemic presented the opportunity to research relations between resilience and self-efficacy and enrich existed research in a new and extraordinary context.