bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Media and Website Use: The Experiences of Parents and Carers Accessing Care at the Oxford Craniofacial Unit
Authors: Kilcoyne Sarah , Overton Sarah , Brockbank Sally , Lloyd-White Samuel , Samuel Rosanna , Hotton Matthew , Cropper Jennifer , Thomas Gregory P.L. , Ching C. Rosanna , Johnson David
Published: November 2023

Introduction:

Historically, medical professionals have been the providers of specialist information about rare medical conditions. Now, increasingly, patients and the public are using the internet to access and generate information about medical diagnoses. The global nature of the internet allows patients to connect across geographical borders, and to obtain and share information that would have been previously inaccessible to them. This research investigated the use of website and social media by parents of children with craniosynostosis.

Methods:

A cross-sectional survey-based design was employed. Participants were parents of children with craniosynostosis attending multidisciplinary craniofacial clinics within the Oxford Craniofacial Unit. A questionnaire was administered which assessed social media and website use adapted from the questionnaire created by Khouri and colleagues (2016) and Huggons and colleagues (2019). The surveys were administered over an 18-month period (November 2020 to May 2022).

Results:

The final sample comprised 82 parents [70 mothers; 10 fathers; 1 sister/carer and 1 parent (mother/father unspecified)]. The children were aged 11 months—16 years of age (average age 6 y and 3 mo). Children had a variety of diagnoses: 31 sagittal, 19 metopic, 14 syndromic craniosynostosis, 8 unicoronal, 6 multisuture, 3 bicoronal, and 1 unilambdoid.

Results showed that 93% (n=76/82) of parents used the internet to find out more about craniosynostosis, with 72% (n=59/82) of parents specifically using social media to find out more about craniosynostosis. The social media platforms used included: Facebook 64% (n=53/82), Instagram 24% (n=20/82), Blogs 12% (n=10/82), Twitter 4% (n= 4/82), Tik Tok 2% (n=2/82), and Snapchat 0.01% (n=1/82).

Parents reported that Facebook was the most helpful source of information about craniosynostosis (52%; n=43/82). Parents indicated the key timepoints they used social media included: when their child received a diagnosis (70%; n=58/82), before their child’s surgery (34%; n=28/82), before their first craniofacial clinic appointment (83%; n=25/30), and when child was older (17%; n=14/84). Forty percent (n=33/82) of parents said that a diagnosis of craniosynostosis made no difference to their social media use, whereas 34% (n=28/82) of parents used social media more, and 20% (n=16/82) used it less.

Conclusion:

Results highlight that parents use social media and other websites to access information relating to craniosynostosis. Future research should examine whether parental use of social media changes across their child’s lifespan and evaluate the quality of this information.
MALAT1 DEREPRESSES MIR-433-3P–MEDIATED RPTOR SUPPRESSION TO IMPAIR AUTOPHAGY AND DRIVE PYROPTOSIS IN ENDOTOXEMIA
Authors: Wu Kun , Yu Xiangyou , Wang Yi , Li Xiang , An Yuanyuan , Zhao Zuyi , Ma Long
Published: November 2023

Objective: Autophagy elevation in endotoxemia plays a protective role by negatively regulating the pyroptosis of vascular endothelial cells, but the molecular mechanisms are still poorly understood. The present study aimed to identify the mechanism underlying autophagy and pyroptosis in endotoxemia. Methods: Bioinformatics analysis and whole-gene transcriptome sequencing prediction were used to identify the endotoxemia-related lncRNA-miRNA-mRNA axis of interest. Human umbilical vein endothelial cells (HUVECs) were activated by lipopolysaccharide (LPS) to mimic the inflammatory environment encountered in endotoxemia. Autophagy and pyroptosis of LPS-treated HUVECs were assessed in response to the knockdown of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1)/miR-433-3p (miRNA-433-3p)/RPTOR (regulatory-associated protein of mTOR). The binding affinity of MALAT1, miR-433-3p, and RPTOR was detected by RNA pull-down and luciferase activity assays. The endothelial cell-specific RPTOR knockout mice were developed and rendered septic using LPS induction to verify the role of RPTOR in autophagy, pyroptosis, and inflammatory response in vivo. Results: The in vitro experiments indicated that LPS could stimulate HUVECs to highly express RPTOR, and its knockdown enhanced cellular autophagy and restricted pyroptosis to curb inflammatory responses. Mechanically, MALAT1 is competitively bound to miR-433-3p to release RPTOR expression, thereby promoting pyroptosis and aggravating endotoxemia. In vivo experiments further confirmed that the knockdown of RPTOR activated autophagy and curtailed pyroptosis in septic mice. Conclusion: MALAT1 is highly expressed in endotoxemia. MALAT1 promotes RPTOR expression by competitively absorbing miR-433-3p, inhibits LPS-activated HUVEC cell autophagy, promotes cell death, enhances LPS-induced inflammatory activation of vascular endothelial cells, and ultimately promotes the progression of endotoxemia.
IN VITRO EVALUATION OF A NOVEL AUTOMATIC INTRAOPERATIVE BLOOD LOSS MONITOR
Authors: Bai Jiangtao , Jin Qi , Zheng Qihui , Zhang LuYang , Guo Ting , Wang Guilin , Wang Zhiping
Published: November 2023

Introduction: Accurate and real-time monitoring of surgical blood loss is essential for ensuring intraoperative safety. However, there is currently no standard way to assess the amount of blood lost in patients during surgery. This study aims to evaluate the accuracy and precision of a new automatic intraoperative blood loss monitor, which can measure both free blood volume and blood content in sponges in real time. Methods: The monitor uses an integrated photoelectric probe to gauge hemoglobin levels in both free blood and blood taken from surgical sponges. These data, combined with initial hemoglobin levels, are processed using specific calculations to determine blood volume. We created 127 diverse free blood samples and 160 blood-containing sponge samples by using fresh pig blood and physiological saline. The monitor then measured these samples. We subsequently compared its measurements with actual values acquired through physical measurements, detecting both agreement and measurement errors. Repeated measurements were performed to calculate the coefficient of variation, thereby evaluating the monitor’s precision. Results: The estimated blood loss percentage error of the monitor was 5.2% for free blood, −5.7% for small sponge, −6.3% for medium sponge, and −6.6% for large sponge. The coefficient of variation of free blood with different hemoglobin concentrations measured by the monitor was less than 10%. Bland-Altman analysis showed that the limits of agreement between the monitor and the reference method were all within the acceptable clinical range. Conclusion: The new automatic intraoperative blood loss monitor is an accurate and reliable device for monitoring both free blood and surgical sponge blood, and shows high performance under various clinical simulation conditions.
Evidence for Beneficial use of the Compensatory Reserve Measurement (CRM) in Guiding Intraoperative Resuscitation: A Prospective Cohort Study of Orthotopic Liver Transplant Recipients
Authors: Ciaraglia Angelo , Osta Eri , Wang Hanzhang , Cigarroa Francisco , Thomas Elizabeth , Fritze Danielle , Nicholson Susannah , Eastridge Brian , Convertino Victor A.
Published: November 2023

Introduction

The Compensatory Reserve Measurement (CRM) is a continuous non-invasive monitoring technology that provides an assessment of the integrated capacity of all physiological mechanisms associated with responses to a hypovolemic stressor such as hemorrhagic shock. No prior studies have analyzed its use for intraoperative resuscitation guidance.

Methods

A prospective observational study was conducted of 23 patients undergoing orthotopic liver transplant (OLT). Chart review was performed to identify timing of various intraoperative events. Data were compared based on predefined thresholds for existence of hemorrhagic shock: CRM below 40% (CRM40), systolic blood pressure below 90 mmHg (SBP90), and heart rate above 100 bpm (HR100). Regression analysis was performed for predicting resuscitation events and non-linear XGBoost models were used to compare CRM to standard vital sign measures.

Results

Events where CRM dropped below 40% were 2.25 times more likely to lead to an intervention, while HR100 and SBP90 were not associated with intraoperative interventions. XGBoost prediction models showed superior discriminatory capacity of CRM alone compared to the model with SBP and HR and no difference when all three were combined (CRM + HR + SBP). All XGBoost models outperformed equivalent linear regression models.

Conclusions

Theses results demonstrate that CRM can provide an adjunctive clinical tool that can augment early and accurate of hemodynamic compromise and promote goal-directed resuscitation in the perioperative setting.
TREATMENT OF COMATOSE SURVIVORS OF IN-HOSPITAL CARDIAC ARREST WITH EXTENDED ENDOVASCULAR COOLING METHOD FOR 72 H: A PROPENSITY SCORE-MATCHED ANALYSIS
Authors: Jiang Lijun , Bian Yuan , Liu Weikang , Zheng Wen , Zheng Jiaqi , Li Chuanbao , Lv Ruijuan , Pan Yuhui , Zheng Zhaolei , Wang Mingjie , Sang Shaowei , Pan Chang , Wang Chunyi , Liu Rugang , Cheng Kai , Zhang Jianbo , Ma Jingjing , Chen Yuguo , Xu Feng
Published: November 2023

Aims: Targeted temperature management is recommended for at least 24 h in comatose survivors of in-hospital cardiac arrest (IHCA) after the return of spontaneous circulation; however, whether an extension for 72 h leads to better neurological outcomes is uncertain. Methods: We included data from the Qilu Hospital of Shandong University between July 20, 2019, and June 30, 2022. Unconscious patients who had return of spontaneous circulation lasting >20 consecutive min and received endovascular cooling (72 h) or normothermia treatment were compared in terms of survival-to-discharge and favorable neurological survival. Propensity score matching was used to formulate balanced 1:3 matched patients. Results: In total, 2,084 patients were included. Sixteen patients received extended endovascular cooling and 48 matched controls received normothermia therapy. Compared with the normothermia group, patients who received prolonged endovascular cooling had a higher survival-to-discharge rate. However, good neurological outcomes did not differ significantly. Before matching, Cox regression analysis, using mortality as the event, showed that extended endovascular cooling independently affected the survival of IHCA patients. Conclusions: Among comatose patients who had been resuscitated from IHCA, the use of endovascular cooling for 72 h might confer a benefit on survival-to-discharge.
Adenosine influences Foxp3 expression of Tregs via the A2aR/CREB pathway in a mouse model of sepsis
Authors: Zhang Teng , Fu Wei , Liu Dongjie , He Yuxin , Wang Jianyao , Ma Tao
Published: November 2023

The adenosine concentration and forkhead box protein (Foxp3) expression in T regulatory cells (Tregs) are increased during sepsis. However, the mechanism by which adenosine induces Foxp3 expression is incompletely understood. A cecal ligation and puncture (CLP) model was constructed using C57BL/J mice. The plasma adenosine concentration and Foxp3 expression in splenic Tregs were increased consistently for 15 days after sepsis onset. Analysis of the mean fluorescence intensity of Foxp3 and adenosine concentration in the same mice revealed a linear correlation. In the CLP model, adenosine 2a receptor (A2aR) blockade inhibited Foxp3 expression in Tregs. In vitro activation of A2aR promoted Foxp3 expression in Tregs and facilitated secretion of extracellular vesicles. Transcriptome sequencing revealed that A2aR blockade led to changes in cyclic adenosine monophosphate response element-binding protein (CREB) transcription in Tregs in our sepsis model. Use of adenosine or A2aR agonists promoted CREB expression, CREB phosphorylation at S133, Treg expression of Foxp3, and enhanced inhibition of proliferation of cluster of differentiation (CD)4+ lymphocytes. A2aR blockade or inhibition of CREB expression inhibited Foxp3 expression in Tregs. In the CLP model, use of CREB inhibitors could inhibit Foxp3 expression and reduce the bacterial load. In summary, adenosine in sepsis promotes CREB phosphorylation via A2aR which, in turn, upregulates Foxp3 expression in Tregs.
Distinguishing Convulsive Syncope From Seizure Induced by Repetitive Transcranial Magnetic Stimulation
Authors: Mukhtar Fahad , Feuer Elyssa , Beynel Lysianne , Jones Eudora , Regenold William T. , Lisanby Sarah H.
Published: November 2023

Repetitive transcranial magnetic stimulation (rTMS) is Food and Drug Administration cleared for clinical use in treatment-resistant depression and a growing list of other disorders. The clinical uptake of rTMS has been facilitated by its relatively benign adverse-effect profile compared with other treatment modalities. Seizure is a rare but serious adverse event that has been reported with rTMS, when dosage exceeds safety guidelines or in individuals at increased risk for seizure. Fortunately, most rTMS-induced seizures are typically transient, with no adverse sequelae, but they may lead to treatment discontinuation. Seizure is not the only cause of loss of conscious and abnormal movements induced by rTMS. Convulsive syncope, a more common adverse event that involves loss of consciousness associated with myoclonic movements, can be difficult to differentiate from an rTMS-induced seizure. We report the case of a 52-year-old man with no known seizure risk factors, enrolled in an institutional review board–approved research study who developed what appeared to be a convulsive syncopal episode lasting 10 to 15 seconds during day 2 of a 30-day rTMS protocol (10 Hz, 120% of motor threshold, 4-second pulse train, 26-second intertrain interval, 3000 pulses per session), with no adverse sequelae. The patient's history, screening, physical examination, pertinent laboratory, neurology consult, electroencephalogram, and imaging findings are discussed. This case demonstrates that distinguishing between convulsive syncope and rTMS-induced seizure can be a diagnostic challenge. Clinicians and researchers delivering rTMS should be familiar with the risk factors for rTMS-induced seizures and rTMS-induced convulsive syncope, to screen for predisposing factors and to manage these rare adverse events if they occur.
Augmenting Virtual Reality Exposure Therapy for Social and Intergroup Anxiety With Transcranial Direct Current Stimulation
Authors: McDonald Mollie A. , Meckes Samantha J. , Shires Jorja , Berryhill Marian E. , Lancaster Cynthia L.
Published: November 2023

Objectives

Exposure therapy is a cornerstone of social anxiety treatment, yet not all patients respond. Symptoms in certain social situations, including intergroup (ie, out-group) contexts, may be particularly resistant to treatment. Exposure therapy outcomes may be improved by stimulating neural areas associated with safety learning, such as the medial prefrontal cortex (mPFC). The mPFC also plays an important role in identifying others as similar to oneself. We hypothesized that targeting the mPFC during exposure therapy would reduce intergroup anxiety and social anxiety.

Methods

Participants (N = 31) with the public speaking subtype of social anxiety received active (anodal) or sham transcranial direct current stimulation (tDCS) targeting the mPFC during exposure therapy. Exposure therapy consisted of giving speeches to audiences in virtual reality. To target intergroup anxiety, half of the public speaking exposure trials were conducted with out-group audiences, defined in this study as audiences of a different ethnicity.

Results

Contrary to hypotheses, tDCS did not facilitate symptom reduction. Some evidence even suggested that tDCS temporarily increased in-group favoritism, although these effects dissipated at 1-month follow-up. In addition, collapsing across all participants, we found reductions across time for public speaking anxiety and intergroup anxiety.

Conclusions

The data provide evidence that standard exposure therapy techniques for social anxiety can be adapted to target intergroup anxiety. Transcranial direct current stimulation targeting the mPFC may boost safety signaling, but only in contexts previously conditioned to signal safety, such as an in-group context.
Hollow-fibre infection model: adaptations for the culture and assessment of fastidious organisms
Authors: Mead Andrew , Azzariti Stefano , Pelligand Ludovic
Published: November 2023

The Hollow-fibre Infection Model (HFIM) is a valuable in vitro platform for emulating antimicrobial drug (AMD) pharmacokinetic (PK) profiles. Despite its potential, standardized protocols for HFIM operation, especially concerning fastidious organisms, are lacking. This study addresses this gap by examining challenges in culturing Pasteurella multocida and Actinobacillus pleuropneumoniae, two fastidious organisms, in the HFIM.
Our findings reveal effective strategies to prevent system clogging, involving multiple freeze-thaw cycles of horse blood, centrifugation, and cell straining to enhance the clarity of the Mueller-Hinton fastidious (MH-F) medium defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI). Additionally, we demonstrate that the provision of a CO2 atmosphere, along with the utilization of gas-permeable tubing and gas vent filters, significantly facilitates the growth of fastidious organisms. Remarkably, both P. multocida and A. pleuropneumoniae were sustained for a period of up to 10 days under these optimized conditions.
This study provides crucial insights into the modifications necessary to successfully culture fastidious organisms in the HFIM, paving the way for more accurate and representative in vitro models for antimicrobial drug testing. These advancements hold promise for advancing research in the field of antimicrobial pharmacokinetics and efficacy against challenging pathogens.
Psychrobacillus antarcticus sp. nov., a psychrotolerant bioemulsifier producer isolated from King George Island, Antarctica
Authors: da Silva Mariana Barbalho Farias , da Mota Fabio Faria , Cypriano Jefferson , Abreu Fernanda , Seldin Lucy
Published: November 2023

A Gram-stain-positive rod, psychrotolerant, aerobic and bioemulsifier-producing strain, denoted as Val9T, was isolated from soil sampled at Vale Ulman, King George Island, Antarctica. The strain grew at up to 30 °C (optimum, 15 °C), at pH 6–9 (optimum, pH 8) and with up to 5 % w/v NaCl (optimum, 3 %). The strain was motile and positive for catalase, oxidase and H2S. It did not hydrolyse starch, casein or gelatin. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain Val9T belonged to the genus

Psychrobacillus

and was closely related to

Psychrobacillus psychrotolerans

DSM 11706T (99.9 % similarity),

Psychrobacillus psychrodurans

DSM 11713T (99.8 %) and

Psychrobacillus glaciei

PB01T (99.2 %). Digital DNA–DNA hybridization and average nucleotide identity values were lower than 37.3 and 85.5 %, respectively, with the closest phylogenetic neighbours. The DNA G+C content of strain Val9T calculated from the complete genome sequence was 36.6 mol%. The predominant cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 1ω11c. Menaquinone-8 was the major respiratory quinone. The peptidoglycan type was A4β l-Orn-d-glu. The novel strain contained diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol as predominant polar lipids. Based on 16S rRNA phylogenetic and multilocus sequence analyses (recA, rpoB and gyrB), as well as phylogenomic, chemotaxonomic and phenotypic tests, we demonstrate that strain Val9T represents a novel species of the genus

Psychrobacillus

, for which the name Psychrobacillus antarcticus sp. nov. is proposed. The type strain is Val9T (=DSM 115096T=CCGB 1952T=NRRL B-65674T).
Profiling of vaginal Lactobacillus jensenii isolated from preterm and full-term pregnancies reveals strain-specific factors relating to host interaction
Authors: Nori Sai Ravi Chandra , McGuire Tara K. , Lawton Elaine M. , McAuliffe Fionnuala M. , Sinderen Douwe Van , Walsh Calum J. , Cotter Paul D. , Feehily Conor
Published: November 2023

Each year, 15 million infants are born preterm (<37 weeks gestation), representing the leading cause of mortality for children under the age of five. Whilst there is no single cause, factors such as maternal genetics, environmental interactions, and the vaginal microbiome have been associated with an increased risk of preterm birth. Previous studies show that a vaginal microbiota dominated by

Lactobacillus

is, in contrast to communities containing a mixture of genera, associated with full-term birth. However, this binary principle does not fully consider more nuanced interactions between bacterial strains and the host. Here, through a combination of analyses involving genome-sequenced isolates and strain-resolved metagenomics, we identify that

L. jensenii

strains from preterm pregnancies are phylogenetically distinct from strains from full-term pregnancies. Detailed analysis reveals several genetic signatures that distinguish preterm birth strains, including genes predicted to be involved in cell wall synthesis, and lactate and acetate metabolism. Notably, we identify a distinct gene cluster involved in cell surface protein synthesis in our preterm strains, and profiling the prevalence of this gene cluster in publicly available genomes revealed it to be predominantly present in the preterm-associated clade. This study contributes to the ongoing search for molecular biomarkers linked to preterm birth and opens up new avenues for exploring strain-level variations and mechanisms that may contribute to preterm birth.
RsaM: a unique dominant regulator of AHL quorum sensing in bacteria
Authors: Venturi Vittorio , Špacapan Mihael , Ristović Nemanja , Bez Cristina
Published: November 2023

Quorum sensing (QS) in proteobacteria is a mechanism to control gene expression orchestrated by the LuxI/LuxR protein family pair, which produces and responds to N-acyl homoserine lactone (AHL) diffusible signal molecules. QS is often regarded as a cell density response via the sensing of/response to the concentrations of AHLs, which are constantly basally produced by bacterial cells. The luxI/R systems, however, undergo supra-regulation in response to external stimuli and many regulators have been implicated in controlling QS in bacteria, although it remains unclear how most of these regulators and cues contribute to the QS response. One regulator, called RsaM, has been reported in a few proteobacterial species to have a stringent role in the control of AHL QS. RsaMs are small, in the range of 140–170 aa long, and are found in several genera, principally in

Burkholderia

and

Acinetobacter

. The gene encoding RsaM is always located as an independent transcriptional unit, situated adjacent to QS luxI and/or luxR loci. One of the most remarkable aspects of RsaM is its uniqueness; it does not fall into any of the known bacterial regulatory families and it possesses a distinct and novel fold that does not exhibit binding affinity for nucleic acids or AHLs. RsaM stands out as a distinctive regulator in bacteria, as it is likely to have an important ecological role, as well as unravelling a novel way of gene regulation in bacteria.
Fatty acid oxidation drives hydrogen peroxide production by α-ketoglutarate dehydrogenase
Authors: Grayson Cathryn , Faerman Ben , Koufos Olivia , Mailloux Ryan J.
Published: November 2023

Here, we conducted the first in-depth investigation into sex effects on mitochondrial hydrogen peroxide (mH2O2) generation in hepatic tissue. Female liver mitochondria produce less mH2O2when oxidizing pyruvate, palmitoyl-carnitine, and succinate when compared to male samples. This difference was attributed to superior coupling between fuel metabolism and oxidative phosphorylation (OxPhos) in female liver mitochondria. Examination of mH2O2production by individual sites of generation revealed that KGDH was a major source in both male and female liver mitochondria oxidizing pyruvate and malate. Surprisingly, α-keto-β-methyl-n-valeric acid (KMV), a site-specific inhibitor for KGDH, nearly abolished mH2O2generation in both male and female liver mitochondria oxidizing palmitoyl-carnitine. KMV did not interfere with the fatty acid oxidation (FAO) pathway and was specific to KGDH. KMV inhibited mH2O2production in liver mitochondria from male and female mice oxidizing myristoyl, octanoyl, and butyryl-carnitine. We also supply evidence that KGDH,notcomplex I or complex III, isthemajor mH2O2generator in liver mitochondria. Together, we discovered KGDH is a major mH2O2source, regardless of sex and during FAO.
SARS-CoV-2 reinfection with Omicron BA.2.75 subvariants in Thai Adults in Thailand
Authors: Assawakosri Suvichada , Sudhinaraset Natthinee , Chansaenroj Jira , Suntronwong Nungruthai , Kanokudom Sitthichai , Nalinpakorn Natach , Tantipraphat Napat , Sethabutra Amica , Honsawek Sittisak , Poovorawan Yong
Published: November 2023

Omicron subvariants of SARS-CoV-2 may resist vaccine- or infection-induced immunity thereby increasing the risk of reinfections in previously infected persons. This study aimed to investigate the clinical severity and the average time to the onset of Omicron reinfection. This survey study collected clinical data on Omicron reinfection. Information on time of infection, reinfection interval, overall clinical presentation, and severity of infection was reported. The total prevalence of symptoms among 201 participants was significantly higher in the first infection (risk difference (RD), 9.86%; 95% CI, 7.54–12.19]) compared to the second infection, and the hospitalization rate among all participants was significantly lower for the second infection than the primary infection (odds ratio (OR), 6.25; 95% CI, 2.158−24.71). The prevalence of symptoms compared with the first infection with pre-Omicron variants was similar to that of the first infection with the Omicron variant (RD, 2.56%; 95% CI, -6.14–1.01). However, the hospitalization rate for pre-Omicron primary infection was significantly higher (OR, 6.76; 95% CI, 2.87–15.87]) than that observed with Omicron variants. The severity of the primary infection and of a pre-Omicron variant was greater than that of a secondary infection or with an Omicron variant.
ChatGPT Influence on Medical Decision-Making, Bias, and Equity: A Randomized Study of Clinicians Evaluating Clinical Vignettes
Authors: Goh Ethan , Bunning Bryan , Khoong Elaine , Gallo Robert , Milstein Arnold , Centola Damon , Chen Jonathan H
Published: November 2023

In a randomized, pre-post intervention study, we evaluated the influence of a large language model (LLM) generative AI system on accuracy of physician decision-making and bias in healthcare. 50 US-licensed physicians reviewed a video clinical vignette, featuring actors representing different demographics (a White male or a Black female) with chest pain. Participants were asked to answer clinical questions around triage, risk, and treatment based on these vignettes, then asked to reconsider after receiving advice generated by ChatGPT+ (GPT4). The primary outcome was the accuracy of clinical decisions based on pre-established evidence-based guidelines. Results showed that physicians are willing to change their initial clinical impressions given AI assistance, and that this led to a significant improvement in clinical decision-making accuracy in a chest pain evaluation scenario without introducing or exacerbating existing race or gender biases. A survey of physician participants indicates that the majority expect LLM tools to play a significant role in clinical decision making.
Convergent functional effects of antidepressants in major depressive disorder: a neuroimaging meta-analysis
Authors: Saberi Amin , Ebneabbasi Amir , Rahimi Sama , Sarebannejad Sara , Sen Zumrut Duygu , Graf Heiko , Walter Martin , Sorg Christian , Camilleri Julia A. , Laird Angela R. , Fox Peter T. , Valk Sofie L. , Eickhoff Simon B. , Tahmasian Masoud
Published: November 2023

Background

Neuroimaging studies have provided valuable insights into the macroscale impacts of antidepressants on brain functions in patients with major depressive disorder. However, the findings of individual studies are inconsistent. Here, we aimed to provide a quantitative synthesis of the literature to identify convergence of the reported findings at both regional and network levels and to examine their associations with neurotransmitter systems.

Methods

Through a comprehensive search in PubMed and Scopus databases, we reviewed 5,258 abstracts and identified 36 eligible functional neuroimaging studies on antidepressant effects in major depressive disorder. Activation likelihood estimation was used to investigate regional convergence of the reported foci of consistent antidepressant effects, followed by functional decoding and connectivity mapping of the convergent clusters. Additionally, utilizing group-averaged data from the Human Connectome Project, we assessed convergent resting-state functional connectivity patterns of the reported foci. Next, we compared the convergent circuit with the circuits targeted by transcranial magnetic stimulation (TMS) therapy. Last, we studied the association of regional and network-level convergence maps with selected neurotransmitter receptors/transporters maps.

Results

No regional convergence was found across foci of treatment-associated alterations in functional imaging. Subgroup analysis across the Treated > Untreated contrast revealed a convergent cluster in the left dorsolateral prefrontal cortex, which was associated with working memory and attention behavioral domains. Moreover, we found network-level convergence of the treatment-associated alterations in a circuit more prominent in the frontoparietal areas. This circuit was co-aligned with circuits targeted by “anti-subgenual” and “Beam F3” TMS therapy. We observed no significant correlations between our meta-analytic findings with the maps of neurotransmitter receptors/transporters.

Conclusion

Our findings highlight the importance of the frontoparietal network and the left dorsolateral prefrontal cortex in the therapeutic effects of antidepressants, which may relate to their role in improving executive functions and emotional processing.
Cell–cell adhesion drives patterning in stratified epithelia
Authors: Mai Yosuke , Kobayashi Yasuaki , Kitahata Hiroyuki , Seo Takashi , Nohara Takuma , Itamoto Sota , Mai Shoko , Kumamoto Junichi , Nagayama Masaharu , Nishie Wataru , Ujiie Hideyuki , Natsuga Ken
Published: November 2023

Epithelia consist of proliferating and differentiating cells that often display patterned arrangements. However, the mechanism regulating these spatial arrangements remains unclear. Here, we show that cell–cell adhesion dictates multicellular patterning in stratified epithelia. When cultured keratinocytes, a type of epithelial cell in the skin, are subjected to starvation, they spontaneously develop a pattern characterized by areas of high and low cell density. Pharmacological and knockout experiments show that adherens junctions are essential for patterning, whereas mathematical modeling indicates that cell–cell adhesion alone is sufficient to form regions with high/low cell density. This phenomenon, called cell–cell adhesion-induced patterning (CAIP), influences cell differentiation and proliferation through Yes-associated protein modulation. Starvation, which induces CAIP, enhances the stratification of the epithelia. These findings highlight the intrinsic self-organizing property of epithelial cells and indicate that CAIP modulation might promote wound healing in clinical settings.
A coordinated switch in sucrose and callose metabolism enables enhanced symplastic unloading in potato tubers
Authors: van den Herik Bas , Bergonzi Sara , Li Yingji , Bachem Christian W. , ten Tusscher Kirsten H.
Published: November 2023

One of the early changes upon tuber induction is the switch from apoplastic to symplastic unloading. Whether and how this change in unloading mode contributes to sink-strength has remained unclear. In addition, developing tubers also change from energy to storage-based sucrose metabolism. Here we investigated the coordination between changes in unloading mode and sucrose metabolism and their relative role in tuber sink strength by looking into callose and sucrose metabolism gene expression combined with a model of apoplastic and symplastic unloading. Decreased callose deposition in tubers is driven by decreased callose synthase activity. Furthermore, changes in callose metabolism and sucrose metabolism are strongly correlated, indicating a well-coordinated developmental switch. Modelling indicates that symplastic unloading is not the most efficient unloading mode per se. Instead, it is the concurrent metabolic switch that provides the physiological conditions necessary to potentiate symplastic transport and thereby enhance tuber sink strength.
Next-Gen Profiling of Tumor-resident Stem Cells using Machine Learning
Authors: Chowdhury Debojyoti , Neekhra Bhavesh , Priyadarshi Shreyansh , Mukherjee Swapnanil , Maity Debashruti , Gupta Debayan , Haldar Shubhasis
Published: November 2023

Tumor-resident stem cells, also known as cancer stem cells (CSCs), constitute a subgroup within tumors, play a crucial role in fostering resistance to treatment and the recurrence of tumors, and pose significant challenges for conventional therapeutic methods. Existing approaches for identifying CSCs face notable hurdles related to scalability, reproducibility, and technical consistency across different cancer types due to the adaptable nature of CSCs. In this context, we introduce OSCORP, an innovative machine-learning-driven approach. This methodology quantifies and identifies CSCs, achieving almost 99% accuracy using biopsy bulk RNAseq data. OSCORP leverages genetic similarities between normal and cancer stem cells. By categorizing CSCs into four distinct yet dynamic potency states, this approach provides insights into the differentiation landscape of CSCs, unveiling previously undisclosed facets of tumor heterogeneity. In evaluations conducted on patient samples across 22 cancer types, OSCORP revealed clinical, transcriptomic, and immunological signatures associated with each CSC state. It has emerged as a comprehensive tool for understanding and addressing the complexities of cancer stem cells. Ultimately, OSCORP opens up new possibilities for more effective personalized cancer therapies and holds the potential to serve as a clinical tool for monitoring patient-specific CSC changes during treatment or follow-up care.
Spatial characterization and stratification of colorectal adenomas by Deep Visual Proteomics
Authors: Kabatnik Sonja , Post Frederik , Drici Lylia , Snejbjerg Bartels Annette , Strauss Maximilian T , Zheng Xiang , Madsen Gunvor Iben , Mund Andreas , Rosenberger Florian A , Moreira José MA , Mann Matthias
Published: November 2023

Colorectal adenomas (CRA) are precursor lesions of the colon that may progress to adenocarcinomas, with patients currently categorized into risk groups by morphological features. We aimed to establish a molecular feature-based risk allocation framework towards improved patient stratification. Deep Visual Proteomics (DVP) is a novel approach that combines image-based artificial intelligence with automated microdissection and ultra-high sensitive mass spectrometry. Here we used DVP on formalin-fixed, paraffin-embedded (FFPE) CRA tissues from nine patients, immunohistologically stained for Caudal-type homeobox 2 (CDX2), a protein implicated in colorectal cancer, enabling the characterization of cellular heterogeneity within distinct tissue regions and across patients. DVP seamlessly integrated with current pathology workflows and equipment, identifying DMBT1, MARCKS and CD99 as correlated with disease recurrence history, making them potential markers of risk stratification. DVP uncovered a metabolic switch towards anaerobic glycolysis in areas of high dysplasia, which was specific for cells with high CDX2 expression. Our findings underscore the potential of spatial proteomics to refine early-stage detection and contribute to personalized patient management strategies and provided novel insights into metabolic reprogramming.
Genetic determinants of blood gene expression and splicing and their contribution to molecular phenotypes and health outcomes
Authors: Tokolyi Alex , Persyn Elodie , Nath Artika P. , Burnham Katie L. , Marten Jonathan , Vanderstichele Thomas , Tardaguila Manuel , Stacey David , Farr Ben , Iyer Vivek , Jiang Xilin , Lambert Samuel A. , Noell Guillaume , Quail Michael A. , Rajan Diana , Ritchie Scott C. , Sun Benjamin B. , Thurston Scott A.J. , Xu Yu , Whelan Christopher D. , Runz Heiko , Petrovski Slavé , Gaffney Daniel J. , Roberts David J. , Angelantonio Emanuele Di , Peters James E. , Soranzo Nicole , Danesh John , Butterworth Adam S. , Inouye Michael , Davenport Emma E. , Paul Dirk S.
Published: November 2023

The biological mechanisms through which most non-protein-coding genetic variants affect disease risk are unknown. To investigate the gene-regulatory cascades that ensue from these variants, we mapped blood gene expression and splicing quantitative trait loci (QTLs) through bulk RNA-sequencing in 4,732 participants, and integrated these data with protein, metabolite and lipid QTLs in the same individuals. We identifiedcis-QTLs for the expression of 17,233 genes and 29,514 splicing events (in 6,853 genes). Using colocalization analysis, we identified 3,430 proteomic and metabolomic traits with a shared association signal with either gene expression or splicing. We quantified the relative contribution of the genetic effects at loci with shared etiology through statistical mediation, observing 222 molecular phenotypes significantly mediated by gene expression or splicing. We uncovered gene-regulatory mechanisms at GWAS disease loci with therapeutic implications, such asWARS1in hypertension,IL7Rin dermatitis andIFNAR2in COVID-19. Our study provides an open-access and interactive resource of the shared genetic etiology across transcriptional phenotypes, molecular traits and health outcomes in humans (https://IntervalRNA.org.uk).
Climate change introduces threatened killer whale populations and conservation challenges to the Arctic
Authors: Garroway Colin J. , de Greef Evelien , Lefort Kyle J. , Thorstensen Matt J. , Foote Andrew D. , Matthews Cory J. D. , Higdon Jeff W. , Kucheravy Caila E. , Petersen Stephen D. , Rosing-Asvid Aqqalu , Ugarte Fernando , Dietz Rune , Ferguson Steven H.
Published: November 2023

The Arctic is the fastest-warming region on the planet, and sea ice loss has opened new habitat for sub-Arctic species such as the killer whale (Orcinus orca). As apex predators, killer whales can cause significant ecosystem-scale changes, however, we know very little about killer whales in the Arctic. Setting conservation priorities for killer whales and their Arctic prey species requires knowledge of their evolutionary history and demography. We found that there are two highly genetically distinct, non-interbreeding populations of killer whales using the eastern Canadian Arctic—one population is newly identified as globally distinct. The effective sizes of both populations recently declined, and both are vulnerable to inbreeding and reduced adaptive potential. Furthermore, we present evidence that human-caused mortalities, particularly ongoing harvest, pose an ongoing threat to these populations. The certainty of substantial environmental change in the Arctic complicates conservation and management significantly. Killer whales bring top-down pressure to Arctic food webs, however, they also merit conservation concern. The opening of the Arctic to killer whales exemplifies the magnitude of complex decisions surrounding local peoples, wildlife conservation, and resource management as the effects of climate change are realized.
RAD-seq unravels local adaptation along a latitudinal gradient for the wild riceZizania latifolia
Authors: Wagutu Godfrey Kinyori , Fan Xiangrong , Tengwer Miriam Chepkwemoi , Njeri Henry Kariuki , Li Wei , Chen Yuanyuan
Published: November 2023

The rapid climate change poses considerable threat to biodiversity by constantly alter-ing species distribution, phenotypic variation and allele frequencies. Understanding the interplay between the climate and species phenotypic and genetic variation is thus cru-cial to inform conservation strategies. In this study, we investigated local adaptation of a widespread aquatic species in China,Zizania latifolia.

We performed restriction-site associated DNA sequencing (RAD-seq) for 66 wild samples composed of 10 populations, two populations in each of the five major eco-geographical regions of China and 6 cultivated samples derived from three culti-vars found in central China. We assessed genetic diversity and structure, genetic-envi-ronmental association, and genome-wide association studies for the 60 wild samples.

Low levels of genetic variability were found in theZ. latifoliapopulations rang-ing fromHE= 0.08 toHE= 1.52. Population structure showed that samples belonged to two major groups, north and south clades, split along a temperature boundary. It was estimated that the two groups diverged during the 8.2kiloyear event and later experi-enced severe genetic bottlenecks with advancement of agriculture and increase in hu-man population some 2k years later.

Landscape analysis using SNP and trait data showed that environment was more important in shaping the genetic structure than geography, but the combined effect of environment and geography explained >90% of both genetic and morphological varia-tion. Several loci were found to be correlated with environmental variables as well as morphological traits, most of which were annotated as retrotransposons. Considering the abundance of transposable elements in theZ. latifoliagenome, differentiation and local adaptation was inferred to be partly driven by temperature-induced transposable elements activity.
Architectonic Principles of Polyproline II Helix Bundle Protein Domains
Authors: Rodríguez Cristian Segura , Laurents Douglas V.
Published: November 2023

Glycine rich polyproline II helix assemblies are an emerging class of natural domains found in several proteins with different functions and diverse origins. The distinct properties of these domains relative to those composed of α-helices and β-sheets could make glycine-rich polyproline II helix assemblies a useful building block for protein design. Whereas the high population of polyproline II conformers in disordered state ensembles could facilitate glycine-rich polyproline II helix folding, the architectonic bases of these structures are not well known. Here, we compare and analyze their structures to uncover common features. These protein domains are found to be highly tolerant of distinct flanking sequences. This speaks to the robustness of this fold and strongly suggests that glycine rich polyproline II assemblies could be grafted with other protein domains to engineer new structures and functions. These domains are also well packed with few or no cavities. Moreover, a significant trend towards antiparallel helix configuration is observed in all these domains and could provide stabilizing interactions among macrodipoles. Finally, extensive networks of Cα-H···O=C hydrogen bonds are detected in these domains. Despite their diverse evolutionary origins and activities, glycine-rich polyproline II helix assemblies share architectonic features which could help design novel proteins.
Overground walking slip perturbations induce frontal plane motion of the trunk – slips are not just a backwards but also a sideways loss of balance
Authors: Lee-Confer Jonathan S.
Published: November 2023

Slip and fall incidents are a serious health care concern globally. Previous research describes a backwards loss of balance during a slip incident, however hip fractures only occur if individuals fall on their side. Therefore, this study is investigating and quantifying the trunk motion in the sagittal and frontal plane. 13 healthy young participants’ trunk kinematics were analyzed during a slip incident. Peak trunk angle of the trunk in the sagittal and frontal plane were calculated. There was no significant difference between sagittal and frontal plane peak trunk angles suggesting that there is frontal plane motion during an overground slip incident. Our findings suggest research should investigate frontal plane mechanics during a slip incident as there is trunk frontal plane motion which if uncontrolled can result in falling on the femoral neck. Understanding and preventing falls based upon frontal plane mechanics may be more useful for preventing hip fractures from a slip incident.Lastly, the findings of this study are confirmatory results as the frontal plane trunk motion was quantified and reported in 2008.
An Exploratory study for characterIzing and predicting prostate abNormalities uSing MRI-based radiomics and arTificial intEllIgeNce (EINSTEIN)
Authors: Bouchareb Yassine , Delanerolle Gayathri , Al-Bulushi Yarab , Al-Khudhuri Ali , Sirsangandla Srinivasa Rao , Al Badaai Ghalib , Cavalini Heitor , Phiri Peter , Shetty Ashish , Shi Jian Qing
Published: November 2023

Introduction

Prostate cancer (PCa) is the fourth most prevalent cancer globally, and the most common among men. Most PCa patients in Oman are presented during the advanced stages of the disease with widespread metastatic disease reducing their overall rates of survival. Characterisation of the Omanis PCa population could be beneficial to develop a clinical profile demonstrating specific characteristics to better classify and derive radiomics signatures. These could help in developing artificial intelligence methods to assist with earlier and quicker diagnosis of possible prostate lesions.

Methods

A retrospective, cross-sectional study has been designed to determine the pathological and radiological characteristics based on multi-sequence 3-dimensional Magnetic Resonance Imaging (MRI). The MRI records are maintained within the existing electronic healthcare records of the Sultan Qaboos University Hospital’s Department of Radiology and Molecular Imaging. Data will be extracted based on a confirmed diagnosis reported between the 1stof January 2010 and October 2023. All patients included within the study will be aged between 18-99 years. A study specific data extraction template has been devised to gather demographic details, clinical parameters and radiological findings based on existing imaging reports within the HIS and PACS systems.

Ethics approval

Research Ethics approval reference for this study is (MREC #3176 REF. NO. SQU-EC/ 283\2023)

Conclusion

The data analysis will be conducted using statistical software to conduct a Joinpoint regression analysis and linear regression modelling. We will also conduct a descriptive analysis.