bluuebunny/crossref_metadata_2025 huggingface dataset:
Appropriateness of premature ovarian insufficiency recommendations provided by ChatGPT
Authors: Sütcüoğlu Bengü Mutlu , Güler Melike
Published: September 2023

Objective

This study aimed to evaluate the appropriateness of ChatGPT's responses to frequently asked queries regarding the prevention and treatment of premature ovarian insufficiency (POI).

Methods

A set of 25 questions covering topics related to disease risk factors, screening, symptoms, treatment, and treatment adverse effects were posed to ChatGPT, and the responses were evaluated by two experienced obstetrician/gynecologists.

Results

Of the responses given by ChatGPT, 19 of 25 (76%) were deemed appropriate, five (20%) were rated as inappropriate, and the remaining one (4%) was considered unreliable. There was no question that ChatGPT answered completely incorrectly; answers that were considered inappropriate included partially correct information.

Conclusions

The study's findings suggest that ChatGPT provides patients with mostly accurate information about the POI but might present significantly inaccurate information. However, it is important to note that further research is needed to validate the use of artificial intelligence chatbots in the context of reproductive health, especially for individuals who may be highly impacted by the emotional and psychological effects of POI. In addition, given the complexity and individuality of medical care, AI chatbots should not be considered a replacement for medical professionals but rather a supplementary tool that can help patients access reliable information and support. Overall, this study contributes to the growing body of research on AI chatbots and their potential use in reproductive health, highlighting both the benefits and limitations of these technologies.
Coronary microvascular dysfunction and heart failure with preserved ejection fraction: what are the mechanistic links?
Authors: Sinha Aish , Rahman Haseeb , Perera Divaka
Published: September 2023

Purpose of review

Heart failure with preserved ejection fraction (HFpEF) accounts for half of all heart failure presentations and is associated with a dismal prognosis. HFpEF is an umbrella term that constitutes several distinct pathophysiological entities. Coronary microvascular dysfunction (CMD), defined as the inability of the coronary vasculature to augment blood flow adequately in the absence of epicardial coronary artery disease, is highly prevalent amongst the HFpEF population and likely represents one distinct HFpEF endotype, the CMD-HFpEF endotype. This review appraises recent studies that have demonstrated an association between CMD and HFpEF with an aim to understand the pathophysiological links between the two. This is of significant clinical relevance as better understanding of the pathophysiology underlying CMD-HFpEF may result in more targeted and efficacious therapeutic options in this patient cohort.

Recent findings

There is a high prevalence of CMD, diagnosed invasively or noninvasively, in patients with HFpEF. Patients with HFpEF who have an impaired myocardial perfusion reserve (MPR) have a worse outcome than those with a normal MPR. Both MPR and coronary flow reserve (CFR) are associated with measures of left ventricular diastolic function and left ventricular filling pressures during exercise. Impaired lusitropy and subendocardial ischaemia link CMD and HFpEF mechanistically.

CMD-HFpEF is a prevalent endotype of HFpEF and one that is associated with adverse cardiovascular prognosis. Whether CMD leads to HFpEF, through subendocardial ischaemia, or whether it is secondary to the impaired lusitropy that is characteristic of HFpEF is not known. Further mechanistic work is needed to answer this pertinent question.
Lack of complete biochemical response in autoimmune hepatitis leads to adverse outcome: First report of the IAIHG retrospective registry
Authors: Slooter Charlotte D. , van den Brand Floris F. , Lleo Ana , Colapietro Francesca , Lenzi Marco , Muratori Paolo , Kerkar Nanda , Dalekos George N. , Zachou Kalliopi , Lucena M. Isabel , Robles-Díaz Mercedes , Di Zeo-Sánchez Daniel E. , Andrade Raúl J. , Montano-Loza Aldo J. , Lytvyak Ellina , Lissenberg-Witte Birgit I. , Maisonneuve Patrick , Bouma Gerd ,   Dutch AIH Study Group, Macedo Guilherme , Liberal Rodrigo , de Boer Ynto S. ,   on behalf of the International Autoimmune Hepatitis Group
Published: September 2023

Background and Aims:

The International Autoimmune Hepatitis Group retrospective registry (IAIHG-RR) is a web-based platform with subjects enrolled with a clinical diagnosis of autoimmune hepatitis (AIH). As prognostic factor studies with enough power are scarce, this study aimed to ascertain data quality and identify prognostic factors in the IAIHG-RR cohort.

Methods:

This retrospective, observational, multicenter study included all patients with a clinical diagnosis of AIH from the IAIHG-RR. The quality assessment consisted of external validation of completeness and consistency for 29 predefined variables. Cox regression was used to identify risk factors for liver-related death and liver transplantation (LT).

Results:

This analysis included 2559 patients across 7 countries. In 1700 patients, follow-up was available, with a completeness of individual data of 90% (range: 30–100). During a median follow-up period of 10 (range: 0–49) years, there were 229 deaths, of which 116 were liver-related, and 143 patients underwent LT. Non-White ethnicity (HR 4.1 95% CI: 2.3–7.1), cirrhosis (HR 3.5 95% CI: 2.3–5.5), variant syndrome with primary sclerosing cholangitis (PSC) (HR 3.1 95% CI: 1.6–6.2), and lack of complete biochemical response within 6 months (HR 5.7 95% CI: 3.4–9.6) were independent prognostic factors.

Conclusions:

The IAIHG-RR represents the world’s largest AIH cohort with moderate-to-good data quality and a relevant number of liver-related events. The registry is a suitable platform for patient selection in future studies. Lack of complete biochemical response to treatment, non-White ethnicity, cirrhosis, and PSC-AIH were associated with liver-related death and LT.
Myocilin Mutation N480K Leads to Early Onset Juvenile and Adult-onset Primary Open Angle Glaucoma in a Six Generation Family
Authors: Kader Mohideen Abdul , Devarajan Bharanidharan , Vijayan Saravanan , Ramakrishnan Rengappa , Sundaresan Periasamy , Uduman Mohammed Sithiq , Krishnadas Subbiah R. , Kuppamuthu Dharmalingam
Published: September 2023

Précis:

A pathogenic autosomal dominant MYOC mutation N480K detected in 6 generations of an Indian family is primarily responsible for juvenile open angle glaucoma (JOAG) and adult-onset primary open angle glaucoma (POAG), emphasizing the importance of screening this mutation at a younger age.

Purpose:

To screen myocilin mutations in a large South Indian family with early-onset JOAG and adult-onset POAG

Methods:

In a large South Indian family with 20 members, 8 members diagnosed as JOAG, 7 members as POAG, 4 members as JOAG suspect, and 1 member as POAG suspect were screened for myocilin (MYOC) mutations using Sanger sequencing. Whole exome sequencing was performed on clinically suspected JOAG/POAG individuals.

Results:

Myocilin gene mutation N480K (c.1440C>G) was detected in 20 family members, including proband, of whom 8 were JOAG and 7 were POAG patients, 3 were JOAG suspects, and 2 were unaffected. Among the unaffected carriers, 1 was less than 5 years old, and another was 25 years old. The earliest to develop the disease was a 10-year-old child. The penetrance of the mutation was 95% over 10 years of age. This family had JOAG/POAG suspects with no N480K MYOC mutation, and they were further screened for other mutations using whole-exome sequencing. Polymorphisms CYP1B1 L432V and MYOC R76K were detected in 3 JOAG/POAG suspects, and among these 3, one had another CYP1B1 polymorphic variant R368H. The presence of the CYP1B1 polymorphism along with an MYOC polymorphic variant among the JOAG/POAG suspects needs additional studies to explore their combined role in the onset of glaucoma.

Conclusions:

This study reveals that MYOC mutation is primarily responsible for JOAG and adult-onset POAG in a family, emphasizing the importance of screening for this mutation at a younger age for early treatment.
Participant Experience Using Novel Perimetry Tests to Monitor Glaucoma Progression
Authors: Freeman Sandra E. , De Arrigunaga Sofia , Kang Joyce , Zhao Yan , Roldán Ana M. , Lin Michael M. , Elze Tobias , Liebman Daniel , Chang Dolly S. , Friedman David S.
Published: September 2023

Précis:

Participant surveys taken after using tablet-based and smart visual function analyzer (SVFA) perimetry tests suggest that patients may prefer novel perimetry tests over traditional visual field machines.

Purpose:

Compare patient experience using the IMOvifa SVFA and the tablet-based Melbourne Rapid Fields visual field (VF) tests to the Humphrey Field 24-2 Swedish Interactive Threshold Algorithm Standard.

Patients and Methods:

Prospective observational cohort study on adult participants with diagnoses of glaucoma suspect, ocular hypertension, or glaucoma. Participants attended 2 study visits ~3 months apart. During the first visit, participants were trained to use the 2 novel perimeters, took 1 test on both new devices and the Humphrey Field Analyzer, then were surveyed. Participants received tablets and performed weekly tablet VF tests at home between study visits. At the final study visit, participants re-took the VF tests and completed the same surveys.

Results:

Eighty-one participants were surveyed twice. At the baseline survey, participants preferred the SVFA (71.7%) and tablet tests (69.2%) over the Humphrey VF. Most were willing to perform weekly monitoring at home on the SVFA (69.1%) and tablet (75.4%). Participants generally had a “very good” overall experience when testing on the SVFA (71.6%) and tablet (90.1%). At the final visit, fewer participants were willing to test on the tablet daily (23.5% to 9.9%; P = 0.02 for change) and more were willing to test monthly (18.5% to 33.3%; P = 0.03 for change).

Conclusion:

Users reported a preference for novel VF devices. Overall participant experience using these devices was positive, supporting the feasibility of home monitoring of VFs from an experience perspective.
Reliability of Intraocular Pressure Measurements in a Low-Contact Drive-Through Setting
Authors: Sun Lynn W. , Zhou Yunshu , Stein Joshua D. , Weizer Jennifer S.
Published: September 2023

Précis:

Drive-through intraocular pressure (IOP) measurement using iCare tonometry is a promising method of low-contact, high-throughput IOP monitoring. However, owing to its vulnerability to variable measurement technique and local air currents, the iCare may overestimate IOPs.

Purpose:

During the COVID-19 pandemic, a drive-through IOP measurement protocol using the iCare tonometer was established to facilitate low-contact monitoring of select glaucoma patients. As the iCare may be prone to error due to variable measurement technique and local air currents, we endeavored to assess the reliability of drive-through IOP measurements by comparing them with recent measurements taken in clinic settings.

Methods:

Inclusion criteria were patients with drive-through IOP measurements performed from April 28 to October 11, 2020; exclusion criteria were pre-drive-through IOPs >21 mmHg. Drive-through IOP measurements were compared with the closest previous and/or subsequent in-clinic IOP measurements. Data were gathered using the Sight Outcomes Research Collaborative (SOURCE) data repository.

Results:

The post-exclusion study group consisted of 314 patients receiving a total of 868 drive-through IOP measurements, all of whom had prior in-clinic measurements, and 56.8% of whom had subsequent in-clinic measurements. Drive-through IOPs were, on average, +2.4 mmHg (+14.5%; SD 4.9) higher than in-clinic IOPs. Further sub-analysis of the data showed a difference of +2.1 mmHg OD and +2.6 mmHg OS. Compared with the closest previous in-clinic visit, the difference was +2.4 mmHg OU (+2.1 mmHg OD, +2.7 mmHg OS); compared with the closest subsequent in-clinic visit, the difference was +2.3 mmHg OU (+2.1 mmHg OD, +2.5 mmHg OS). 68.6% of all drive-through IOPs were higher than corresponding in-clinic IOPs; 21.1% were lower. 25.9% of drive-through IOPs were higher by more than 5 mmHg, whereas 3.9% of drive-through IOPs were lower by more than 5 mmHg.

Discussion:

As teleophthalmology becomes an ever more important tool in glaucoma patient care, drive-through or walk-through IOP monitoring methods are likely to play an increasing role. However, our data reveals potential inaccuracies in drive-through iCare IOP measurements which tended to overestimate IOP. It is advisable to confirm large changes in IOP with in-clinic measurement before making management decisions.

Conclusion:

With better optimization of accuracy and reliability of measurements, drive-through tonometry is a promising, high-throughput, low-contact method of measuring IOP.
Diode Laser Transscleral Cyclophotocoagulation With a Novel Low-Cost Torchlight Method of Trans-Corneal Transillumination in Refractory Pediatric Glaucoma
Authors: Choudhary Sandeep , Snehi Sagarika , Singh Ashok , Thattaruthody Faisal , Pandav Surinder Singh , Kaushik Sushmita
Published: September 2023

Précis:

Trans-corneal transillumination (TI) aided transscleral cyclophotocoagulation (TSCPC) for intraocular pressure control of refractory pediatric glaucoma was found to be effective at 1 year.

Purpose:

To study 1-year outcomes of diode laser TSCPC with trans-corneal TI using a novel low-cost torchlight method in refractory pediatric glaucoma.

Methods:

This prospective interventional study included children with refractory glaucoma who underwent TSCPC with the Oculight laser system (IRIS Medical Instruments) with trans-corneal TI (TSCPC-TI) using a novel low-cost torchlight method. Children completing a minimum 1-year follow-up were analyzed. They were compared with a historical control group of children who underwent TSCPC without TI (TSCPC-No-TI) at the 1-year follow-up period. We analyzed the mean laser energy delivered, post-laser intraocular pressure reduction, number of antiglaucoma medications (AGM), the requirement of retreatment and complications of the procedure in both groups.

Results:

Forty-two eyes of 35 patients comprised the TSCPC-TI group and were compared with 31 eyes of 21 patients in the TSCPC-No-TI group. The TSCPC-TI group required lower energy than the TSCPC-No-TI group (24.7±7.8 J vs. 47.2±10.9 J, P<0.0001). Mean topical antiglaucoma drug requirement decreased from 2.9±0.08 before treatment to 0.66±0.8 at the end of 1 year in TSCPC-TI and from 2.6±1.0 before treatment to 0.6±0.77 in the TSCPC-No-TI groups, respectively (P=0.15). There was a significantly reduced dependence of oral acetazolamide in the TSCPC-TI group at 1-year follow-up [5.7% vs. 61.9%, respectively (P<0.001%)]. No adverse event of hypotony or choroidal detachment was noted in any group.

Conclusions:

TSCPC aided by TI with a low-cost torchlight for pediatric refractory glaucoma was found to be effective at 1 year in reducing intraocular pressure and the burden of medication.
Kaposi’s Sarcoma in Children After Hematopoietic Stem Cell Transplantation: Two Cases of Rare Primary Tumor Localizations in the Lungs and Lymph Node
Authors: Sidorov Il’ya Vladimirovich , Abramov Dmitriy Sergeevich , Strumila Nataliia Alekseevna , Shelihova Larisa Nikolaevna , Viktorova Ekaterina Andreevna , Konovalov Dmitry Mikhailovich
Published: September 2023

Kaposi’s sarcoma (KS) is a vascular / mesenchymal tumor with an indefinite degree of malignancy, caused by complex etiopathogenetic factors including Human Herpes Virus-8 infection of immunocompromised patients. For example, KS is more common in adult men with HIV. We describe 2 very rare cases of iatrogenic KS in children after hematopoietic stem cell transplant with isolated organ damage (case 1: lung; case 2: inguinal lymph node). KS is a potential complication of bone marrow transplant in pediatric patients and can occur in different age groups and at atypical sites.
Michael Francis Land. 12 April 1942—14 December 2020
Authors: Cronin Thomas , Nilsson Dan-Eric , Osorio Daniel
Published: September 2023

Michael (Mike) Land made lasting contributions to physiological optics of diverse animals and to understanding how animals and humans move their eyes. He combined a keen interest in natural history and evolution with elegant and accessible mathematical accounts of optics and vision. In the early part of his career he discovered focusing mechanisms based on reflection in scallops' and compound eyes, and elucidated the evolutionary and functional relationships between spatial resolution and absolute sensitivity in eyes. Starting with studies of how spiders and flies use eye and body movements to track and intercept moving targets, Land went on to apply similar principles to human visuo-motor behaviour. He described where we look during routine tasks, such as making tea, and in more exacting conditions, such as driving and playing cricket. He showed how eye movements are tailored top-down for a given task, and found that typically we foveate each location a fraction of a second before each action. Finally, he suggested how behaviour and awareness are anchored to an internal representation that incorporates egocentric and allocentric frames of reference. Land's deep curiosity about the living world led him to discover visual principles of an unexcelled diversity of creatures.
Recruitment of C4b-binding protein is not a complement evasion strategy employed by Staphylococcus aureus
Authors: Li Shuxian , Bettoni Serena , Mohlin Frida , Geoghegan Joan A. , Blom Anna M. , Laabei Maisem
Published: September 2023

Complement offers a first line of defence against infection through the opsonization of microbial pathogens, recruitment of professional phagocytes to the infection site and the coordination of inflammatory responses required for the resolution of infection.

Staphylococcus aureus

is a successful pathogen that has developed multiple mechanisms to thwart host immune responses. Understanding the precise strategies employed by

S. aureus

to bypass host immunity will be paramount for the development of vaccines and or immunotherapies designed to prevent or limit infection. To gain a better insight into the specific immune evasion mechanisms used by

S. aureus

we examined the pathogen’s interaction with the soluble complement inhibitor, C4b-binding protein (C4BP). Previous studies indicated that

S. aureus

recruits C4BP using a specific cell-wall-anchored surface protein and that bound C4BP limits complement deposition on the staphylococcal surface. Using flow-cytometric-based bacterial-protein binding assays we observed no interaction between

S. aureus

and C4BP. Moreover, we offer a precautionary warning that C4BP isolated from plasma can be co-purified with minute quantities of human IgG, which can distort binding analysis between

S. aureus

and human-derived proteins. Combined our data indicates that recruitment of C4BP is not a complement evasion strategy employed by

S. aureus

.
Supporting CIF Format of Biomolecular Structures in GROMACS
Authors: Wang Hengyue , Zhang Zhiyong
Published: September 2023

In the Protein Data Bank (PDB), the PDB format stands as the major file format for protein structures. However, there are certain intrinsic limitations in the PDB format, such as the storage of structural information in a fixed-width format that would be an issue for very large protein complexes. Therefore, the CIF (crystallographic information framework) format has been proposed, which is characterized by superior expansibility. GROMACS, a widely used software suite for molecular dynamics simulations, currently supports only the PDB format. In this study, we modified the source code of GROMACS, which enables it to support the CIF format structure files as input and subsequently generate molecular topology files. This work simplifies the preprocessing of large protein complexes for MD simulations.

Program summary

Program title: GROMACS-CIF

GitHub link to program files:https://github.com/zyzhangGroup/Gromacs-CIF

Licensing provisions: GPL-3.0 license

Programming language: C++

Nature of problem: GROMACS currently supports only the PDB format but does not support the CIF format of protein structures. For a very large protein complex, the PDB format is not suitable, and only a CIF file is available in the protein data bank. However, the latter cannot be used as a direct input of GROMACS.

Solution method: Source codes of the program “pdb2gmx” in GROMACS have been modified by adding several CIF analysis functions parallel to the PDB analysis functions.
Enhancing Neurocognitive Outcome Prediction in Congenital Heart Disease Patients: The Role of Brain Age Biomarkers and Beyond
Authors: Hussain Mohammad Arafat , Grant Ellen , Ou Yangming
Published: September 2023

This paper aimed to investigate the predictive power of combining demographic, socioeconomic, and genetic factors with a brain MRI-based quantified measure of accelerated brain aging (referred to asdeltaAGE) for neurocognitive outcomes in adolescents and young adults with Congenital Heart Disease (CHD). Our hypothesis posited that including the brain age biomarker (deltaAGE) would enhance neurocognitive outcome predictions compared to models excluding it. We conducted comprehensive analyses, including leave-one-subject-out and leave-one-group-out cross-validation techniques. Our results demonstrated that the inclusion ofdeltaAGEconsistently improved prediction performance when considering the Pearson correlation coefficient, a preferable metric for this study. Notably, thedeltaAGE-augmented models consistently outperformed those withoutdeltaAGEacross all cross-validation setups, and these correlations were statistically significant (p-value < 0.05). Therefore, our hypothesis that incorporating the brain-age biomarker alongside demographic, socioeconomic, and genetic factors enhances neurocognitive outcome predictions in adolescents and young adults with CHD is supported by the findings.
A Cholinergic Signaling Pathway underlying Cortical Circuit Regulation of Lateral Ventricle Quiescent Neural Stem Cells
Authors: Naffaa Moawiah M , Yin Henry H.
Published: September 2023

Neurogenesis and proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) are controlled by both intrinsic molecular pathways and extrinsic signaling cues, including neural circuits. One such circuit, the ACC-subep-ChAT+circuit, has been identified as a regulator of ventral SVZ neurogenesis by modulating the proliferation of LV NSCs. However, the specific neural signals that promote the proliferation activity of LV NSCs have remained largely unknown. In this study, we uncover a molecular mechanism underlying the cellular activation and proliferation of quiescent NSCs (qNSCs) in the lateral ventricle SVZ (LV-SVZ) mediated by the cortical circuit. Our findings demonstrate that postnatal and adult LV qNSCs are triggered by the cortical circuit through ChAT+neuron stimulation, consequently resulting in the activation of muscarinic 3 receptors (M3) expressed on LV qNSCs. This, in turn, triggers inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) activation, causing intracellular calcium release. Subsequently, the proliferation of LV qNSCs occurs through the downstream regulation of the calcium/calmodulin dependent protein kinase II delta (CAMK2D) and the MAPK10 signaling pathway. These findings shed light on the molecular regulatory mechanisms that govern LV qNSCs and emphasize the significant role of the cortical circuit in promoting their proliferative activation within the ventral LV-SVZ.
Multi-omics profiling reveals phenotypic and functional heterogeneity of neutrophils in COVID-19
Authors: Zhang Lin , Nishi Hafumi , Kinoshita Kengo
Published: September 2023

Background

Accumulating evidence has revealed unexpected phenotypic heterogeneity and diverse functions of neutrophils in several diseases. Coronavirus disease (COVID-19) can alter the leukocyte phenotype based on disease severity, including neutrophil activation in severe cases. However, the plasticity of neutrophil phenotypes and their relative impact on COVID-19 pathogenesis has not been well addressed. This study aimed to identify and validate the heterogeneity of neutrophils in COVID-19 and evaluate the phenotypic alterations for each subpopulation.

Methods

We analyzed public single-cell RNA-seq, bulk RNA-seq, and human plasma proteome data from healthy donors and patients with COVID-19 to investigate neutrophil subpopulations and their response to disease pathogenesis.

Results

We identified eight neutrophil subtypes, namely C1–C8, and found that they exhibited distinct features, including activation signatures and multiple enriched pathways. The neutrophil subtype C4 (DEFA1/1B/3+) associated with severe and fatal disease. Bulk RNA-seq and proteome dataset analyses using a cellular deconvolution approach validated the relative abundances of neutrophil subtypes and the expansion of C4 (DEFA1/1B/3+) in severe COVID-19 patients. Cell– cell communication analysis revealed representative ligand-receptor interactions among the identified neutrophil subtypes. Notably, the C4 (DEFA1/1B/3+) fraction showed transmembrane receptor expression of CD45 and CAP1 as well as the secretion of pro-platelet basic protein (PPBP). We further demonstrated the clinical potential of PPBP as a novel diagnostic biomarker for severe COVID-19.

Conclusion

Our work has great value in terms of both clinical and public health as it furthers our understanding of the phenotypic and functional heterogeneity of neutrophils and other cell populations in multiple diseases.
TPX2 expression promotes sensitivity to dasatinib in breast cancer by activating the YAP transcriptional signaling
Authors: Marugán Carlos , Ortigosa Beatriz , Sanz-Gómez Natalia , Monfort-Vengut Ana , Bertinetti Cristina , Teijo Ana , González Marta , Alonso de la Vega Alicia , Lallena María José , Moreno-Bueno Gema , de Cárcer Guillermo
Published: September 2023

Chromosomal instability (CIN) is a hallmark of cancer aggressiveness, providing genetic plasticity and tumor heterogeneity that allows the tumor to evolve and adapt to stress conditions. CIN is considered a cancer therapeutic biomarker because healthy cells do not exhibit CIN. Despite recent efforts to identify therapeutic strategies related to CIN, the results obtained have been very limited. CIN is characterized by a genetic signature where a collection of genes, mostly mitotic regulators, are overexpressed in CIN-positive tumors, providing aggressiveness and poor prognosis. We attempted to identify new therapeutic strategies related to CIN genes by performing a drug screen, using cells that individually express CIN-associated genes in an inducible manner. We find that the overexpression of TPX2 enhances sensitivity to the SRC inhibitor dasatinib due to activation of the YAP pathway. Furthermore, using breast cancer data from the TCGA and a cohort of cancer-derived patient samples, we find that both TPX2 expression and YAP activation are present in a significant percentage of cancer tumor samples, providing poor prognosis, being therefore putative biomarkers for dasatinib therapy.
Mechanistic implications of the ternary complex structural models for the photoenzyme protochlorophyllide oxidoreductase
Authors: Taylor Aoife , Zhang Shaowei , Johannissen Linus O. , Sakuma Michiyo , Phillips Robert S. , Green Anthony P. , Hay Sam , Heyes Derren J. , Scrutton Nigel S.
Published: September 2023

The photoenzyme protochlorophyliide oxidoreductase (POR) is an important enzyme for understanding biological H-transfer mechanisms. It uses light to catalyse the reduction of protochlorophyllide (Pchlide) to chlorophyllide, a key step in chlorophyll biosynthesis. Although a wealth of spectroscopic data have provided crucial mechanistic insight about the light-driven reaction chemistry, a structural rationale for POR photocatalysis has proved more challenging and remains hotly debated. Recent structural models of the ternary enzyme-substrate complex, derived from crystal and electron microscopy data, show differences in the orientation of the Pchlide substrate and the architecture of the POR active site that have significant implications for the catalytic mechanism of Pchlide reduction. Here, we have used a combination of computational and experimental approaches to investigate the compatibility of each of these structural models with the hypothesised reaction mechanisms and propose an alternative structural model for the cyanobacterial POR-Pchlide-NADPH ternary complex based on these findings. Through detailed site-directed mutagenesis studies we show that a strictly conserved Tyr residue, which has previously been proposed to act as the proton donor in POR photocatalysis, is not likely to be involved in this step of the reaction but is crucial for Pchlide binding. Instead, an active site Cys residue is important for both hydride and proton transfer reactions in POR and is proposed to act as the proton donor, either directly or through a water-mediated network. Moreover, a conserved Gln residue is found to be important for Pchlide binding and ensuring efficient photochemistry by tuning its electronic properties, likely by interacting with the central Mg atom of the substrate. This optimal ‘binding pose’ for the POR ternary enzyme-substrate complex illustrates how light energy can be harnessed to facilitate enzyme catalysis by this unique enzyme.
Cell of origin epigenetic priming determines susceptibility toTet2mutation
Authors: Schiroli Giulia , Kartha Vinay , Duarte Fabiana M. , Kristiansen Trine A. , Mayerhofer Christina , Shrestha Rojesh , Earl Andrew , Hu Yan , Tay Tristan , Rhee Catherine , Buenrostro Jason D. , Scadden David T.
Published: September 2023

Hematopoietic stem cell mutations can result in clonal hematopoiesis (CH) but the clinical outcomes are heterogeneous. The nature of the founder mutation and secondary mutations likely drive emergent neoplastic disease. We investigated how the state of the cell of origin where theTet2mutation occurs affects susceptibility to that commonly occurring CH mutation. Here, we provide evidence that risk is written in the epigenome of the cell of origin. By characterizing cell states that underlie myeloid differentiation and linking this information to an inducible system to assess myeloid progenitor clones, we provide evidence that epigenetic markers of the cell whereTet2mutation occurs stratifies clonal behaviors. Specifically, Sox4 fosters a global cell state of high sensitization towardsTet2KO. Using GMP and primary HSC models, we show that Sox4 promotes cell dedifferentiation, alters cell metabolism and increases the in vivo clonal output of mutant cells. Our results validate the hypothesis that epigenetic features can predispose specific clones for dominance and explain why an identical mutation can result in different outcomes.
Structural flexibility dominates over binding strength for supramolecular crystallinity
Authors: Caroprese Vincenzo , Tekin Cem , Cencen Veronika , Mosayebi Majid , Liverpool Tanniemola B. , Woolfson Derek N. , Fantner Georg , Bastings Maartje M.C.
Published: September 2023

Supramolecular crystallinity is abundantly present in nature and results from directional, weak non-covalent interactions between components. Bottom-up nanotechnology aims to exploit such phenomena to control the self-assembly of ordered networks and complex objects from rationally designed monomers. Like all crystalline materials, 2D supramolecular crystals develop from an initial nucleation site, followed by growth, based on directional interactions. Traditionally, the binding strength and directionality of interactions is thought to dictate the nucleation and crystal growth, whereas structural flexibility favours defects. Usually, macromonomers present multiple binding units with relative intramolecular flexibility that affects their intermolecular interactions. Thus far, the effects of such flexibility on supramolecular assembly have not been explored. Here we introduce the concept of “interface flexibility” and demonstrate its critical importance in the nucleation and growth of supramolecular crystalline networks. We show that tuning the interface flexibility greatly expands the available design space for synthetic supramolecular crystalline materials.
Preparing for serendipity: an illustrative analysis of participation in the field
Authors: Chapman Christopher , Kimura Asako , Sawabe Norio , Selmes-Suzuki Hiroyuki
Published: September 2023

Purpose

This paper aims to explore how researchers in general, and field researchers in particular, might respond to systems of governance of the researchers' activity in ways that can support rather than distort the quality of the research.

Design/methodology/approach

We draw upon literature on serendipity to develop a framework for engaging with the positive and negative potentials of systems of governance. We ground our analysis in discussion of participation in the field comprising two parts: first, the examination of our own activities and second, the accounts of participation found in two career-autobiographical interviews with emeritus professors of management accounting from Japan.

Findings

We highlight the potential for a productive tension between two contrasting perspectives that researchers might take on governance of their activity. A contractual perspective sees the value of targets and detailed pre-planning. A reflexive perspective sees the value of exploring the unexpected and considering many alternatives. We offer a framework for considering serendipity and the conditions that facilitate serendipity to help researchers maintain a productive tension between these perspectives.

Research limitations/implications

We build upon retrospective accounts of two successful individuals whose careers evolved in a specific context. The intention is not to set out what might be generally achievable in a research career, nor to propose specific lines of action or planning in relation to specific systems of governance, since these vary across countries and over time. Rather, the paper draws on these materials to illuminate the more general challenge of preparing for serendipity in a way that goes beyond simple opportunism.

Originality/value

We analyse how researchers' mindfulness of serendipity and the nature of contexts that facilitate serendipity can encourage a productive tension between contractual and reflexive perspectives on governance of academic activity.
Influencing factors of social media addiction: a systematic review
Authors: Liang Mengli , Duan Qingyu , Liu Jiazhen , Wang Xiaoguang , Zheng Han
Published: September 2023

Purpose

As an unhealthy dependence on social media platforms, social media addiction (SMA) has become increasingly commonplace in the digital era. The purpose of this paper is to provide a general overview of SMA research and develop a theoretical model that explains how different types of factors contribute to SMA.

Design/methodology/approach

Considering the nascent nature of this research area, this study conducted a systematic review to synthesize the burgeoning literature examining influencing factors of SMA. Based on a comprehensive literature search and screening process, 84 articles were included in the final sample.

Findings

Analyses showed that antecedents of SMA can be classified into three conceptual levels: individual, environmental and platform. The authors further proposed a theoretical framework to explain the underlying mechanisms behind the relationships amongst different types of variables.

Originality/value

The contributions of this review are two-fold. First, it used a systematic and rigorous approach to summarize the empirical landscape of SMA research, providing theoretical insights and future research directions in this area. Second, the findings could help social media service providers and health professionals propose relevant intervention strategies to mitigate SMA.
Extended electrical equivalent circuit for modelling compound DC motors
Authors: Kandemir Beser Esra
Published: September 2023

Purpose

The purpose of this study is to create an extended equivalent circuit model for a compound DC motor, consisting completely of electrical parameters and quantities.

Design/methodology/approach

The dynamic model of the compound DC motor is obtained by establishing the voltage equations for the armature and excitation circuit and the mechanical equation for the mechanical part. The mechanical parameters in the dynamic model are converted into electrical parameters with an electrical circuit proposed for the mechanical part. By combining the armature and excitation circuits with the electrical circuit created for the mechanical part, the extended equivalent circuit model of the compound DC motor is obtained. Because the proposed extended equivalent model is completely an electrical circuit, simulations can be made in the circuit simulation programme. Simulations of the proposed compound DC motor circuit were carried out, and the accuracy of the proposed circuit was verified by performing experimental studies with an existing compound motor.

Findings

When comparing speed and current profiles in experiments and simulations, it is seen that compound DC motor can be modelled with the proposed equivalent circuit including completely electrical elements in a simulation programme for the circuits. The results show that the proposed equivalent circuit satisfies the dynamic model of the compound motor.

Originality/value

In DC machine models, armature and excitation circuits are given as an electrical circuit, and mechanical part of the machine is modelled by only mechanical equations. The originality of this study is converting the dynamic model of an electrical machine consisting of electrical and mechanical equations into a completely electrical circuit. With the proposed method, the dynamic model of many motors can be converted into a completely electrical circuit. In this way, motors can be simulated as an electrical circuit in simulation programmes for the circuits, and the dynamic behaviour of motors can be obtained.
ISOMORPH: an efficient application on GPU for detecting graph isomorphism
Authors: Llanes Antonio , Imbernón Tudela Baldomero , Curado Manuel , Soto Jesús
Published: September 2023

Purpose

The authors will review the main concepts of graphs, present the implemented algorithm, as well as explain the different techniques applied to the graph, to achieve an efficient execution of the algorithm, both in terms of the use of multiple cores that the authors have available today, and the use of massive data parallelism through the parallelization of the algorithm, bringing the graph closer to the execution through CUDA on GPUs.

Design/methodology/approach

In this work, the authors approach the graphs isomorphism problem, approaching this problem from a point of view very little worked during all this time, the application of parallelism and the high-performance computing (HPC) techniques to the detection of isomorphism between graphs.

Findings

Results obtained give compelling reasons to ensure that more in-depth studies on the HPC techniques should be applied in these fields, since gains of up to 722x speedup are achieved in the most favorable scenarios, maintaining an average performance speedup of 454x.

Originality/value

The paper is new and original.
As investors sow, can they reap? Examining the moderating effect of investment opportunity on the relationship between financial literacy and investment decision
Authors: Ghosh Ratan
Published: September 2023

Purpose

This study aims to examine the investor's level of financial literacy and their attitude toward making any investment decision in the Bangladeshi capital market.

Design/methodology/approach

To measure the level of financial literacy of an individual investor, three variables have been used – financial knowledge, financial behavior and financial attitude. It also considers investment opportunity as a moderator variable to assess the effect of market-specific characteristics on financial literacy. Data have been collected through a structured questionnaire from 152 retail investors of the Dhaka Stock Exchange and Chittagong Stock Exchange. Smart-PLS 3.3 was used for analyzing the set of hypotheses for examining the relationships in the study.

Findings

Results found that financial attitude and financial behavior have a positive and significant relationship with investment decisions. Further evidence shows that investment opportunity moderates the relationship between financial attitude and financial behavior. This indicates that equity investors are suffering from market inefficiency and cannot ensure wealth maximization.

Research limitations/implications

Regulators should focus not only on financial literacy programs but also on market discipline, accountability and performance. This will encourage investors to invest their money wisely and independently.

Originality/value

The study adds value to the capital market literature in two ways. First, it investigates the success of financial literacy programs in Bangladesh to resolve the behavioral bias issue among investors, which used to affect their returns negatively. Second, the study introduces a very new and relevant variable as a moderator in the context of Bangladesh. Investment opportunity is a moderating variable developed from the efficient market hypothesis. Results reveal that investors are somehow financially literate over time, which can be a positive attribute for controlling behavioral bias. However, market inefficiency, corporate corruption, financial crime, insider trading and information asymmetry hamper the regular growth of the market. Hence, equity investors are unable to ensure wealth maximization in Bangladesh, where this kind of problem exists.
The role of social start-ups in entrepreneurial behaviour: the search for efficiency
Authors: Sanchez-Robles Manuel , Soriano Domingo Ribeiro , Puertas Rosa , Guaita Martínez José Manuel
Published: September 2023

Purpose

In a world where sustainability is a major aim at all socioeconomic levels, social entrepreneurship plays an important role in achieving the goals that have been set. The purpose of this study is to broaden the knowledge of social start-ups, social incubators and founding teams, highlighting the value of each one. The aim is to use quantitative analysis to determine the possible link between social incubators and social start-up success and identify the founding team profile of social start-ups from each sector according to a sector-based ranking.

Design/methodology/approach

Bootstrap data envelopment analysis (DEA) was used to calculate the efficiency of social incubators and social start-ups and thus quantify the impact, in terms of increased efficiency, of social incubators on social start-ups. Then, using cross-efficiency methodology, a synthetic index was used to analyse the founding team profile of social start-ups. The study is based on primary data from a survey of Spanish social incubators and social start-ups.

Findings

The study provides strong quantitative evidence of the positive effect of social incubators on the development of social start-ups. The size of this effect exceeds the know-how of start-ups. In terms of efficiency gains, this research quantifies the impact of social incubators on this entrepreneurial ecosystem. This impact exceeds 35%. The study also shows that the strongest social start-ups are in the food and information and communication technology (ICT) sectors. The founding teams in these cases have a strong business background, have a high educational level, receive subsidies and express a desire to retain control of the company.

Originality/value

There is an extensive literature dedicated to the analysis of the behaviour and characteristics of traditional incubators, accelerators and start-ups. However, despite the recent rise of social entrepreneurship, studies of social incubators and social start-ups remain scarce. This study provides two novel findings. (1) It shows the importance of creating a social start-up in a context where it receives support throughout all its development stages, providing quantitative insight into the contribution of social incubators and social start-ups. (2) It reveals the profile of founding teams in the highest-ranked business sectors.
Self-concept, self-organization and cross-border trading (CBT) behavior among females in Uganda
Authors: Sambaga Janepher Nsozi
Published: September 2023

Purpose

Women cross-border traders face impediments in their entrepreneurial work from time-to-time. To overcome these impediments, females need to take on self-concept (self-esteem, self-confidence, social roles) mediated by self-organization (adaptability, interaction, team working) in order to thrive in cross-border trading (CBT), using evidence from Uganda. So, in this paper the authors explain the behavior of a female who succeeds in CBT with interest of scaling it up to empower more female entrepreneurs.

Design/methodology/approach

This study is a correlational and cross-sectional type. A questionnaire survey of 288 females was used. The data collected were analyzed through SPSS.

Findings

The results reveal that self-concept, mediated by self-organization, controlled by tenure in business and the age of a female in CBT significantly influences CBT behavior among females in Uganda.

Research limitations/implications

This study focused on females who are involved in CBT in Uganda. Therefore, it is likely that the results may not be generalized to other settings. The results show that for females to succeed in CBT, self-concept and self-organization affect CBT behavior once they are controlled by tenure in business and the age of a female in CBT at more than 30 years of age and longer than 5 years.

Originality/value

This study provides initial evidence that self-concept, mediated by self-organization, controlled by tenure in business and age of a CBT directly affects CBT behavior, using evidence from an African developing country – Uganda.