bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol blunts pregnancy‐mediated insulin resistance and reduces fetal brain glucose despite elevated fetal gluconeogenesis, and these changes associate with fetal weight outcomes
Authors: Saini Nipun , Mooney Sandra M. , Smith Susan M.
Published: September 2023

Prenatal alcohol exposure (PAE) impairs fetal growth and neurodevelopment. Although alcohol is well known to alter metabolism, its impact on these processes during pregnancy is largely unexplored. Here, we investigate how alcohol affects maternal–fetal glucose metabolism using our established mouse binge model of PAE. In the dam, alcohol reduces the hepatic abundance of glucose and glycolytic intermediates, and the gluconeogenic enzymes glucose‐6‐phosphtase and phosphoenolpyruvate carboxykinase. Fasting blood glucose is also reduced. In a healthy pregnancy, elevated maternal gluconeogenesis and insulin resistance ensures glucose availability for the fetus. Glucose and insulin tolerance tests reveal that alcohol impairs the dam's ability to acquire insulin resistance. Alcohol‐exposed dams have enhanced glucose clearance (p < .05) in early gestation, after just two days of alcohol, and this persists through late term when fetal glucose needs are maximal. However, maternal plasma insulin levels, hepatic insulin signaling, and the abundance of glucose transporter proteins remain unchanged. In the PAE fetus, the expression of hepatic gluconeogenic genes is elevated, and there is a trend for elevated blood and liver glucose levels. In contrast, fetal brain and placental glucose levels remain low. This reduced maternal fasting glucose, reduced hepatic glucose, and elevated glucose clearance inversely correlated with fetal body and brain weight. Taken together, these data suggest that alcohol blunts the adaptive changes in maternal glucose metabolism that otherwise enhance fetal glucose availability. Compensatory attempts by the fetus to increase glucose pools via gluconeogenesis do not normalize brain glucose. These metabolic changes may contribute to the impaired fetal growth and brain development that typifies PAE.
Impact of Frailty and Cervical Radiographic Parameters on Postoperative Dysphagia Following Anterior Cervical Spine Surgery
Authors: Asada Tomoyuki , Singh Sumedha , Maayan Omri , Shahi Pratyush , Singh Nishtha , Subramanian Tejas , Araghi Kasra , Korsun Maximilian , Tuma Olivia , Pajak Anthony , Lu Amy , Mai Eric , Kim Yeo Eun , Dowdell James , Sheha Evan D. , Iyer Sravisht , Qureshi Sheeraz A.
Published: September 2023

Study Design.

Retrospective review of a prospectively collected registry.

Objective.

The purpose of the present study was to investigate the impact of frailty and radiographical parameters on postoperative dysphagia after anterior cervical spine surgery (ACSS).

Summary of Background Data.

There is a growing body of literature indicating an association between frailty and increased postoperative complications following various surgeries. However, few studies have investigated the relationship between frailty and postoperative dysphagia after anterior cervical spine surgery.

Materials and Methods.

Patients who underwent anterior cervical spine surgery for the treatment of degenerative cervical pathology were included. Frailty and dysphagia were assessed by the modified Frailty Index-11 (mFI-11) and Eat Assessment Tool 10 (EAT-10), respectively. We also collected clinical demographics and cervical alignment parameters previously reported as risk factors for postoperative dysphagia. Multivariable logistic regression was performed to identify the odds ratio (OR) of postoperative dysphagia at early (2–6 weeks) and late postoperative time points (1–2 years).

Results.

Ninety-five patients who underwent ACSS were included in the study. Postoperative dysphagia occurred in 31 patients (32.6%) at the early postoperative time point. Multivariable logistic regression identified higher mFI-11 score (OR, 4.03; 95% CI: 1.24–13.16; P=0.021), overcorrection of TS–CL after surgery (TS−CL, T1 slope minus C2–C7 lordosis; OR, 0.86; 95% CI: 0.79–0.95; P=0.003), and surgery at C3/C4 (OR, 12.38; 95% CI: 1.41–108.92; P=0.023) as factors associated with postoperative dysphagia.

Conclusions.

Frailty, as assessed by the mFI-11, was significantly associated with postoperative dysphagia after ACSS. Additional factors associated with postoperative dysphagia were overcorrection of TS–CL and surgery at C3/C4. These findings emphasize the importance of assessing frailty and cervical alignment in the decision-making process preceding ACSS.
Construction and Analysis of an LncRNA-miRNA-mRNA Network Based on Competitive Endogenous RNA Reveal miRNAs Potentially Involved in In-stent Restenosis After Percutaneous Coronary Intervention
Authors: Jin Xiao , Wu Bingxin , Han Li , Zhu Xiaofeng
Published: September 2023

Objective:

Percutaneous coronary intervention (PCI) is one of the most common procedures used for the invasive treatment of patients with coronary heart disease; the incidence of in-stent restenosis (ISR) after PCI is 5% to 15%. In this study, a competitive endogenous RNA (ceRNA) network was constructed to investigate potential mechanisms involved in ISR.

Methods:

The expression data for differentially expressed microRNAs (DEmiRNAs) and messenger RNAs (mRNAs) between patients with and without ISR were obtained using limma package. Long noncoding RNAs (lncRNAs) were predicted based on the DEmiRNAs using the miRDB, miRTarBase, and TargetScan databases. An ISR-specific ceRNA network was subsequently constructed and investigated. To verify the key miRNAs of ceRNA, patients with and without ISR were enrolled from Guangdong Provincial Hospital of Chinese Medicine between January 2017 and December 2018 (n = 8, respectively); plasma was collected from all enrolled patients.

Results:

Based on the raw data obtained from the Gene Expression Omnibus database, 472 DEmiRNAs and 304 differentially expressed messenger RNAs (DEmRNAs) between patients with and without ISR were identified. A ceRNA network was constructed by combining 270 lncRNAs, 3 miRNAs (miR-125, miR-140, and miR-206), and 4 mRNAs (STRADB, TKT, PCTP, and BTG2). The hub genes of the ceRNA network of ISR included the following: miR-125, miR-206, miR-140, PCDHB9, CASC2, BAK1P1, CSPG4P3Y, CSPG4P4Y, STRCP1, and GRIP2. Verification of miRNAs of ceRNA also showed that the expression of miR-206 was upregulated in patients with ISR vs. those without ISR (P < 0.05). In contrast, the expression of miR-140 and miR-125 was downregulated in patients with ISR vs. those without ISR (P < 0.05).

Conclusions:

This study constructed noncoding RNA-related ceRNA networks for ISR. The results indicated that miR-206, miR-125, and miR-140 may be biomarkers of ISR.
Positive GPNMB Immunostaining Differentiates Renal Cell Carcinoma With Fibromyomatous Stroma Associated With TSC1/2/MTOR Alterations From Others
Authors: Li Huili , Argani Pedram , Halper-Stromberg Eitan , Lotan Tamara L. , Merino Maria J. , Reuter Victor E. , Matoso Andres
Published: September 2023

Renal cell carcinoma with fibromyomatous stroma (RCCFMS) include ELOC/TCEB1-mutated renal cell carcinoma (RCC) and those with TSC1/2/MTOR alterations. Besides morphologic similarity, most of these tumors is known to be diffusely positive for carbonic anhydrase IX and cytokeratin 7 by immunohistochemistry. We previously showed strong and diffuse expression of GPNMB (glycoprotein nonmetastatic B) in translocation RCC and eosinophilic renal neoplasms with known TSC1/2/MTOR alterations. We retrospectively identified molecularly confirmed cases of TCEB1/ELOC-mutated RCC (7 tumors from 7 patients), and RCCFMS with alterations in TSC1/2/MTOR (6 tumors from 5 patients, 1 patient with tuberous sclerosis syndrome). In addition, we included 7 clear cell papillary renal cell tumors (CCPRCTs) and 8 clear cell RCC, as they can also present morphologic overlap with RCCFMS. Morphologically, RCCs with TSC1/2/MTOR alterations and those with TCEB1/ELOC mutations were indistinguishable and characterized by papillary, nested, or tubular architecture, with tumor cells with clear cytoplasm and low nuclear grade. By immunohistochemistry, cytokeratin 7 was positive in 5/7 (71%) of TCEB1/ELOC-mutated RCCs, 6/6 (100%) of RCCs with TSC1/2/mTOR alterations, and 7/7 (100%) of CCPRCTs (P=not significant). Carbonic anhydrase IX was positive in 7/7 TCEB1/ELOC-mutated RCCs, 6/6 (100%) of RCCs with TSC1/2/MTOR alterations, and 7/7 (100%) of CCPRCTs (P=NS). GPNMB was strongly and diffusely positive in all tumors with TSC1/2/MTOR alterations (6/6), while negative in all TCEB1/ELOC-mutated RCCs (0/6), or CCPRCTs (0/7) (P=0.002). Two of 8 clear cell RCC showed focal weak staining, while 6/8 were negative. In conclusion, the results support the use of GPNMB to distinguish RCCFMS with TSC1/2/MTOR alterations from others with similar morphology.
Impact of Using a Precompleted Consent Form for Procedural Sedation in the Pediatric Emergency Department
Authors: McCollum Nichole , Silva Olivia , Sigman Laura , Breslin Kristen , Kline Jaclyn
Published: September 2023

Objectives

This study aimed to compare elements discussed during the consent process for procedural sedation in the pediatric emergency department to documentation and parental recall before and after implementation of a standardized consent form.

Methods

This is a mixed-methods study combining retrospective electronic record review and cross-sectional surveys of providers and parents after consent for procedural sedation. Surveys were obtained before and after implementation of a precompleted consent form. Providers' survey responses were compared with consent documentation. Recall of consent elements discussed by linked parent-provider dyads were compared.

Results

Six hundred fifty-five encounters were reviewed. Pediatric emergency medicine fellows and pediatric emergency department-based pediatricians were more likely to document any benefit (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.0–2.4) or alternative (OR, 2.7; 95% CI, 1.8–3.9) compared with PEM attendings. Providers were more likely to report discussion of failure to complete the procedure (OR, 7.3; 95% CI, 2.3–23.3) and parents were more likely to recall discussion of this risk (OR, 5.3; 95% CI, 1.0–27.8) in the postintervention group. Based on provider recall, using the precompleted consent form was associated with providers discussing at least 2 of the 3 benefits (84.0% vs 97.2%, P < 0.01), 5 of the 5 risks (31% vs 67.7%, P < 0.01), and improved parental recall of risks (5.7% vs 22.9%, P = 0.03). More providers reported taking less than 1 minute to complete the form in the postimplementation group (12.0% vs 43.7%, P < 0.01).

Conclusions

Implementing a precompleted consent form for procedural sedation was associated with providers reporting decreased time spent completing the consent form and better alignment of key consent elements between reported provider discussion and parental recall.
Successful Outcome of Manual Testicular Detorsion Using Point-of-Care Ultrasound Guidance
Authors: Hsu Chien-Te , Chiu Po-Wei
Published: September 2023

Testicular torsion is a surgical emergency. It obstructs the blood supply to the testes, leading to testicular ischemia and necrosis. It presents with a sudden onset of severe unilateral testicular pain associated with nausea/vomiting, swollen scrotum, and high-riding testicles with an absent cremasteric reflex and negative Prehn sign. Prompt diagnosis of ischemic testicles using ultrasonography is challenging for emergency physicians. Color Doppler ultrasound may reveal a relative decrease or absence of blood flow in the affected testicle. The most specific ultrasonographic feature was the whirlpool sign of the spermatic cord. Manual detorsion should be performed as soon as possible before surgical intervention. However, manual detorsion may fail because of patient discomfort, incomplete torsion, and rotation of the testicle in a less common direction. We report a case demonstrating ultrasound-guided detorsion in a 14-year-old boy with right testicular torsion. The present case highlights the importance of incorporating ultrasound guidance into manual detorsion, which can improve the success rate of the procedure.
Middle Meningeal Artery Embolization Combined With Endoscopic Treatment for Chronic Subdural Hematoma
Authors: Guo Chong , Zhang Xinfan , Hu Zhongbo , Guo Ke , Li Zefu , Li Jianmin , Peng Jiangtao
Published: September 2023

Objective:

To explore the clinical feasibility of middle meningeal artery (MMA) embolization combined with endoscopic treatment for new or recurrent chronic subdural hematoma (CSDH).

Methods:

Twenty patients with CSDH treated in the Binzhou Medical University Hospital from June 2020 to October 2022 were analyzed retrospectively. The clinical information, prognosis, imaging results, and surgical results of the patients were collected and analyzed. The authors first performed MMA embolization, and then endoscopic treatment of CSDH was performed after successful embolization of MMA. Results: All 20 patients with CSDH were successfully treated with MMA embolization combined with endoscope-assisted evacuation. The symptoms of all patients were relieved, no surgical complications occurred, and no rebleeding and recurrence were found in follow-up computed tomography.

Conclusion:

Middle meningeal artery embolization combined with endoscopic treatment of CSDH has a good clinical effect, and it may prevent postoperative recurrence.
Monitoring Heart Failure Patients with Mobile Health Technologies: Outcomes from a 180-day Prospective Study
Authors: Mohapatra Sukanya , Issa Mirna , Ivezic Vedrana , Doherty Rose , Marks Stephanie , Lan Esther , Rozett Keith , Cullen Lauren , Reynolds Wren , Rocchio Rose , Fonarow Gregg C. , Ong Michael K. , Speier William F. , Arnold Corey W.
Published: September 2023

Mobile health (mHealth) methods have grown in popularity in preventative medicine due to their convenience, cost, and ability to acquire actionable data. At the same time, the burden of many diseases has grown due to their prevalence and high rates of morbidity and mortality. To combat this burden, mHealth can be customized to improve adherence to recommended regimens and decrease doctor or hospital visits for patients and their families. Heart failure (HF) is a disease with an especially high burden for which mHealth can be used to promote adherence to advised care plans with the goal of decreasing exacerbations and their associated urgent and emergency care visits. Our study compared adherence to different mHealth monitoring regimens that used activity trackers, scales, and a mobile app with gamification features and a financial incentive. In a prospective analysis of 111 HF patients monitored for 180 days, we found that a regimen including a mobile app with a gamified financial incentive led to significantly higher adherence to activity tracker (95% vs. 72.2%, p=0.0101) and weight (87.5% vs. 69.4%, p=0.0016) monitoring compared to a regimen that included the monitoring devices alone. Our findings indicate that mobile apps with added engagement features can be useful tools to reduce temporal adherence decline and may thus increase the impact of mHealth driven interventions.
A taxonomy of multiple stable states in complex ecological communities
Authors: Aguadé-Gorgorió Guim , Arnoldi Jean-François , Barbier Matthieu , Kéfi Sonia
Published: September 2023

Many natural and man-made systems, from financial markets to ecosystems or the human brain, are built from multiple interconnected units. This complex high-dimensionality hinders our capacity to understand and predict the dynamics, functioning and fragility of these systems. One fragility scenario, particularly relevant to ecological communities of interacting species, concerns so-called regime shifts: abrupt and unexpected transitions from healthy, species-rich communities towards states of degraded ecosystem function and services. The accepted explanation for these shifts is that they arise as abrupt transitions between alternative stable states: multiple stable configurations of a system under the same internal and external conditions. These alternative states are well-understood in low-dimensional systems, but how they upscale with system complexity remains a debated question. In the present work we investigate the emergence of multiple stable states in a number of complex system models. We find that high-dimensional models with random interactions can unfold at least four different regimes of multistability, each emerging under a specific interaction scheme. More importantly, each multistability regime leaves a distinct and quantifiable fingerprint, providing a framework to analyze experimental evidence of abrupt shifts. By bridging previous results and studying multistability regimes, their fingerprints and their correlation with empirical evidence in ecology, our study helps define a common ground to understand and classify multiple stable states in complex systems.
Brain map of aging-induced alterations in membrane ganglioside pattern
Authors: Jha Durga , Dovrtelova Gabriela , Telensky Petr , Olkowicz Seweryn , Coufalikova Katerina , Opalka Lukas , Kubicek Karel , Černá Bára , Hajek Roman , Belaskova Silvie , Klanova Jana , Hampl Ales , Damborsky Jiri , Spacil Zdenek
Published: September 2023

Recent efforts to develop comprehensive metabolome and proteome brain atlases for animal models have yielded significant progress. However, the ganglioside (GSs) profile of these models remains largely unexplored. As essential components of the brain, GSs play a crucial role in neuronal function. To address this gap in knowledge, we conducted an in-depth analysis of the young and adult rat brain, as well as its major brain regions, using ultra-high performance liquid chromatography and tandem mass spectrometry in positive and negative ion modes. We also analyzed GSs in cerebrospinal fluid (CSF) and serum from matched samples. Our findings indicate a shift in the ratio of a-series to b-series GSs with age, along with region-specific changes accompanied by aging. This could improve our understanding of brain aging and neurodegenerative diseases. Our study complements existing brain atlases of lipidome and protein expression and highlights the importance of further investigating the mechanisms underlying these GSs changes and the potential therapeutic implications of our findings.
Is the neuropeptide PEN a ligand of GPR83?
Authors: Giesecke Yvonne , Asimi Vahid , Stulberg Valentina , Kleinau Gunnar , Scheerer Patrick , Koksch Beate , Grötzinger Carsten
Published: September 2023

G protein-coupled receptor 83 (GPR83) is a class A G protein-coupled receptor with predominant expression in the cerebellum and proposed function in the regulation of food intake and in anxiety-like behavior. The neuropeptide PEN has been suggested as a specific GPR83 ligand. However, conflicting reports exist about whether PEN is indeed able to bind and activate GPR83. This study was initiated to evaluate PEN as a potential ligand of GPR83. Employing several second-messenger and other GPCR activation assays as well as a radioligand binding assay, and using multiple GPR83 plasmids and PEN peptides from different sources, no experimental evidence was found to support a role of PEN as a GPR83 ligand.
Immigration delays but does not prevent adaptation following environmental change: experimental evidence
Authors: Durkee Lily F. , Olazcuaga Laure , Melbourne Brett A. , Hufbauer Ruth A.
Published: September 2023

In today’s rapidly changing world, it is critical to examine how animal populations will respond to severe environmental change. Following events such as pollution or deforestation that cause populations to decline, extinction will occur unless populations can adapt in response to natural selection, a process called evolutionary rescue. Theory predicts that immigration can delay extinction and provide novel genetic material that can prevent inbreeding depression and facilitate adaptation. However, when potential source populations have not experienced the new environment before (i.e.,are naive), immigration can counteract selection and constrain adaptation. This study evaluated the effects of immigration of naive individuals on evolutionary rescue using the red flour beetle,Tribolium castaneum,as a model system. Small populations were exposed to a challenging environment, and three immigration rates (zero, one, or five migrants per generation) were implemented with migrants from a benign environment. Following an initial decline in population size across all treatments, populations receiving no immigration gained a higher growth rate one generation earlier than those with immigration, illustrating the constraining effects of immigration on adaptation. After seven generations, a reciprocal transplant experiment found evidence for adaptation regardless of immigration rate. Thus, while the immigration of naive individuals briefly delayed adaptation, it did not increase extinction risk or prevent adaptation following environmental change.
Intrinsic functional connectivity among memory networks does not predict individual differences in narrative recall
Authors: Kurkela Kyle , Ritchey Maureen
Published: September 2023

Individuals differ greatly in their ability to remember the details of past events, yet little is known about the brain processes that explain such individual differences in a healthy young population. Previous research suggests that episodic memory relies on functional communication among ventral regions of the default mode network ("DMN-C") that are strongly interconnected with the medial temporal lobes. In this study, we investigated whether the intrinsic functional connectivity of the DMN-C subnetwork is related to individual differences in memory ability, examining this relationship across 243 individuals (ages 18-50 years) from the openly available Cambridge Center for Aging and Neuroscience (Cam-CAN) dataset. We first estimated each participant's whole-brain intrinsic functional brain connectivity by combining data from resting-state, movie-watching, and sensorimotor task scans to increase statistical power. We then examined whether intrinsic functional connectivity predicted performance on a narrative recall task. We found no evidence that functional connectivity of the DMN-C, with itself, with other related DMN subnetworks, or with the rest of the brain, was related to narrative recall. Exploratory connectome-based predictive modeling (CBPM) analyses of the entire connectome revealed a whole-brain multivariate pattern that predicted performance, although these changes were largely outside of known memory networks. These results add to emerging evidence suggesting that individual differences in memory cannot be easily explained by brain differences in areas typically associated with episodic memory function.
Transcriptomic profiling of Schlemm’s canal cells reveals a lymphatic-biased identity and three major cell states
Authors: Balasubramanian Revathi , Kizhatil Krishnakumar , Li Taibo , Tolman Nicholas , Bhandari Aakriti , Clark Graham , Bupp-Chickering Violet , Kelly Ruth A. , Zhou Sally , Peregrin John , Simón Marina , Montgomery Christa , Stamer W Daniel , Qian Jiang , John Simon W.M.
Published: September 2023

Schlemm’s canal (SC) is central in intraocular pressure regulation but requires much characterization. It has distinct inner and outer walls, each composed of Schlemm’s canal endothelial cells (SECs) with different morphologies and functions. Recent transcriptomic studies of the anterior segment added important knowledge, but were limited in power by SEC numbers or did not focus on SC. To gain a more comprehensive understanding of SC biology, we performed bulk RNA sequencing on C57BL/6J SC, blood vessel, and lymphatic endothelial cells from limbal tissue (∼4500 SECs). We also analyzed mouse limbal tissues by single-cell and single-nucleus RNA sequencing (C57BL/6J and 129/Sj strains), successfully sequencing 903 individual SECs. Together, these datasets confirm that SC has molecular characteristics of both blood and lymphatic endothelia with a lymphatic phenotype predominating. SECs are enriched in pathways that regulate cell-cell junction formation pointing to the importance of junctions in determining SC fluid permeability. Importantly, and for the first time, our analyses characterize 3 molecular classes of SECs, molecularly distinguishing inner wall from outer wall SECs and discovering two inner wall cell states that likely result from local environmental differences. Further, and based on ligand and receptor expression patterns, we document key interactions between SECs and cells of the adjacent trabecular meshwork (TM) drainage tissue. Also, we present cell type expression for a collection of human glaucoma genes. These data provide a new molecular foundation that will enable the functional dissection of key homeostatic processes mediated by SECs as well as the development of new glaucoma therapeutics.

Significance statement

Schlemm’s canal is a critical ocular drainage structure that maintains intraocular pressure with important consequences for glaucoma. Despite this, Schlemm’s canal has been relatively understudied with the molecular process that mediate its function, maintain its health, or that are compromised in glaucoma needing much deeper characterization. This study is important as it provides the most comprehensive molecular characterization of Schlemm’s canal cells to date providing a wealth of molecular details. In addition to highlighting important biological pathways, this information will guide studies to develop new treatments against glaucoma.
Timing-dependent modulation of working memory by VTA dopamine release in medial prefrontal cortex
Authors: Ge Chaofan , Chen Zhaoqin , Sun Fangmiao , Hou Ruiqing , Fan Hongmei , Li Yulong , Li Chengyu T.
Published: September 2023

Dopamine significantly modulates working memory (WM)1–8, a fundamental cognitive function that maintains information during a brief delay period9–11. The temporal precision of dopaminergic modulation in WM and related neural mechanisms remain elusive. Here we unveiled the pivotal role of dopamine timing in WM performance with head-fixed mice engaged in learning an olfactory WM task. Through electrophysiology and optogenetics, we found that dopaminergic neurons in the ventral tegmental area (VTA) could encode WM information during the delay period, and manipulating dopaminergic neuronal activity bidirectionally modulated WM performance in an inverted U-shaped manner. Optogenetic manipulation of VTA activity also induced bidirectional changes in WM-related neural activity in the medial prefrontal cortex (mPFC). Imaging with a dopamine-sensitive GPCR-activation-based sensor (GRABDA)12,13revealed transient dopamine peaks in the mPFC specifically during the early-delay period. Optogenetic stimulation of VTA-to-mPFC dopaminergic projections during the early- and late-delay period enhanced and impaired WM performance, respectively. Manipulations outside these periods or involving the nucleus accumbens had no effect. Single-unit recordings demonstrated that optogenetic excitation of VTA-to-mPFC projections could modulate mPFC neuronal activity in a manner consistent with behavioral modulation. Thus, the timing of dopamine release is critical in modulation of neuronal activity and behavior.
Tuning apicobasal polarity and junctional recycling in the hemogenic endothelium orchestrates the morphodynamic complexity of emerging pre-hematopoietic stem cells
Authors: Torcq Léa , Majello Sara , Vivier Catherine , Schmidt Anne A.
Published: September 2023

Hematopoietic stem cells emerge in the embryo from an aortic-derived tissue called the hemogenic endothelium (HE). The HE appears to give birth to cells of different nature and fate but the molecular principles underlying this complexity are largely unknown. Here we show, in the zebrafish embryo, that two cell types emerge from the aortic floor with radically different morphodynamics. With the support of live imaging, we bring evidence suggesting that the mechanics underlying the two emergence types rely, or not, on apicobasal polarity establishment. While the first type is characterized by reinforcement of apicobasal polarity and maintenance of the apical/luminal membrane until release, the second type emerges via a dynamic process reminiscent of trans-endothelial migration. Interfering with Runx1 function suggests that the balance between the two emergence types depends on tuning apicobasal polarity at the level of the HE. In support of this and unexpectedly, we show that the zebrafish Pard3 isoform - Pard3ba - is sensitive to interference with Runx1 activity, in aortic endothelial cells. This supports the idea of a signaling cross talk controlling cell polarity and its associated features, between aortic and hemogenic cells. In addition, using new transgenic fish lines that express Junctional Adhesion Molecules and functional interference, we bring evidence for the essential role of ArhGEF11/PDZ-RhoGEF in controlling the HE-endothelial cell dynamic interface, including cell-cell intercalation, which is ultimately required for emergence completion. Overall, we highlight critical cellular and dynamic events of the endothelial-to-hematopoietic transition that support emergence complexity, with a potential impact cell fate.
SLO-MSNet: Discrimination of Multiple Sclerosis using Scanning Laser Ophthalmoscopy Images with Autoencoder-Based Feature Extraction
Authors: Arian Roya , Aghababaei Ali , Soltanipour Asieh , Iyer Shwasa B , Ashtari Fereshteh , Rabbani Hossein , Kafieh Raheleh
Published: September 2023

Background

Optical coherence tomography (OCT) studies have revealed that compared to healthy control (HC) individuals, retinal nerve fiber, ganglionic cell, and inner plexiform layers become thinner in multiple sclerosis (MS) patients. To date, a number of machine learning (ML) studies have utilized Optical coherence tomography (OCT) data for classifying MS, leading to encouraging results. Scanning laser ophthalmoscopy (SLO) uses laser light to capture high-resolution fundus images, often performed in conjunction with OCT to lock B-scans at a fixed position, removing the effects of eye motion on image quality and allowing for evaluating the disease progression at follow-up examinations. To our knowledge, no ML work has taken advantage of SLO images for automated diagnosis of MS.

Methods

In this study, SLO images were utilized for the first time with the purpose of fully automated classification of MS and healthy control (HC) cases. First, a subject-wise k-fold cross-validation data splitting approach was followed to minimize the risk of model overestimation due to data leakage between train and validation datasets. Subsequently, we used several state-of-the-art convolutional neural networks (CNNs), including VGG-16, VGG-19, ResNet-50, and InceptionV3, as well as a custom CNN architecture trained from scratch. In the next step, we designed a convolutional autoencoder (CAE) to extract semantic features from the images which are then given as the input to four conventional ML classifiers, including support vector machine (SVM), k-nearest neighbor (K-NN), random forest (RF), and multi-layer perceptron (MLP).

Results

The custom CNN model outperformed state-of-the-art models with an accuracy (ACC) of 85%, sensitivity (SE) of 85%, specificity (SP) of 87%, and AUROC of 93%; however, utilizing a combination of the CAE and MPL yields even superior results achieving an ACC of 88%, SE of 86%, SP of 91%, and AUROC of 94%, while maintaining high per-class accuracies. The best performing model was also found to be generalizable to an external dataset from an independent source, achieving an ACC of 83%, SE of 87%, and SP of 79%.

Conclusion

For the first time, we utilized SLO images to differentiate between MS and HC eyes, with promising results achieved using combination of designed CAE and MLP which we named SLO-MSNet. Should the results of the SLO-MSNet be validated in future works with larger and more diverse datasets, SLO-based diagnosis of MS can be reliably integrated into routine clinical practice.
“An explosion of alternative medicines in France!”: media-biased polyphonic epidemiology vs. evidence-based data
Authors: Berna Fabrice , Florens Nans , Verneuil Laurence , Paille François , Berna Chantal , Nizard Julien
Published: September 2023

Background

The media and several French official organizations report an “explosion” in the use of complementary and alternative medicines (CAM) in France, possibly “boosted” by the Covid-19 pandemic. In addition, the French Miviludes (Mission of Vigilance and Fight Against Sectarian Aberrations) routinely asserts in its yearly reports “a dramatic uptick” in sectarian aberrations in the health sector. However, data supporting those assertions are either scant or rarely compared with data from previous years to properly apprehend an evolution.

This paper aims to analyze existing data in this field and to examine in which domain (population-based survey, official reports, media) “increases” or “explosion” might be observed. We compared the data from France and Switzerland. In fact, no clear regulatory policy on CAM exists in France, whereas the Swiss population voted to include CAM into the Swiss Constitution in 2009.

Method

Surveys documenting the reported usage of CAM in both France and Switzerland were analyzed. Health-related sectarian aberrations were analyzed based on yearly reports of the French Miviludes and its Swiss counterpart (Inter-Cantonal Information Center on Beliefs). Then, the communication in the media on CAM was analyzed in the French media and in the scientific literature published in both countries. Three time periods were considered to apprehend the claimed boost of the Covid-19 pandemic.

Results

Our comprehensive analysis of available information sources does not suggest an “explosion” in CAM use or related sectarian misconduct. Reported CAM use in France was 39% in 2007 and later surveys did not find higher percentage. Reported CAM use increased from 24% to 28.9% between 2007 and 2017 in Switzerland. Referrals about health-related sectarian aberrations regularly increased until 2017 and then remained stable in France; they regularly decreased in Switzerland. Evidence for a pandemic boost was weak. In contrast, a steady increase was observed in the number of mentions in media of CAM.

Conclusion

Our analyses indicate a media-skewed, polyphonic epidemiology, which is not supported by available data. Health care specialists, Official organizations, journalists and politicians should become aware of biases concerning CAM and foster a more informed and balanced discourse regarding these practices.
Neonatal enteroids absorb extracellular vesicles from human milk-fed infant digestive fluid
Authors: Yung Claire , Zhang Yang , Kuhn Madeline , Armstrong Randall J. , Olyaei Amy , Aloia Molly , Scottoline Brian , Andres Sarah F.
Published: September 2023

Human milk contains extracellular vesicles (HMEVs). Pre-clinical models suggest that HMEVs may enhance intestinal function and limit inflammation; however, it is unknown if HMEVs or their cargo survive neonatal human digestion. This limits the ability to leverage HMEV cargo as additives to infant nutrition or as therapeutics. This study aimed to develop an EV isolation pipeline from small volumes of human milk and neonatal intestinal contents after milk feeding (digesta) to address the hypothesis that HMEVs survive in vivo neonatal digestion to be taken up intestinal epithelial cells (IECs). Digesta was collected from nasoduodenal sampling tubes or ostomies. EVs were isolated from raw and pasteurized human milk and digesta by density-gradient ultracentrifugation following two-step skimming, acid precipitation of caseins, and multi-step filtration. EVs were validated by electron microscopy, western blotting, nanoparticle tracking analysis, resistive pulse sensing, and super-resolution microscopy. EV uptake was tested in human neonatal enteroids. HMEVs and digesta EVs (dEVs) show typical EV morphology and are enriched in CD81 and CD9, but depleted of β-casein and lactalbumin. HMEV and some dEV fractions contain mammary gland-derived protein BTN1A1. Neonatal human enteroids rapidly take up dEVs in part via clathrin-mediated endocytosis. Our data suggest that EVs can be isolated from digestive fluid and that these dEVs can be absorbed by IECs.
Survival in macrophages induces an enhanced virulence inCryptococcus
Authors: Nielson Jacquelyn , Jezewski Andrew , Wellington Melanie , Davis J. Muse
Published: September 2023

Cryptococcusis a ubiquitous environmental fungus and frequent colonizer of human lungs. Colonization can lead to diverse outcomes, from clearance to long-term colonization, and to life-threatening meningoencephalitis. Regardless of the outcome, the process starts with an encounter with phagocytes. Using the zebrafish model of this infection, we have noted that cryptococcal cells first spend time inside macrophages before they become capable of pathogenic replication and dissemination. What ‘licensing’ process takes place during this initial encounter, and how are licensed cryptococcal cells different? To address this, we isolated cryptococcal cells after phagocytosis by cultured macrophages and found these macrophage-experienced cells to be markedly more virulent in both zebrafish and mouse models. Despite producing a thick polysaccharide capsule, they were still subject to phagocytosis by macrophages in the zebrafish. Analysis of antigenic cell wall components in these licensed cells demonstrated that components of mannose and chitin are more available to staining than they are in culture-grown cells or cells with capsule production induced in vitro.Cryptococcusis capable of exiting or transferring between macrophages in vitro, raising the likelihood that this fungus alternates between intracellular and extracellular life during growth in the lungs. Our results raise the possibility that intracellular life has its advantages over time, and phagocytosis-induced alteration in mannose and chitin exposure is one way that makes subsequent rounds of phagocytosis more beneficial to the fungus.

IMPORTANCE

Cryptococcosis begins in the lungs and can ultimately travel through the bloodstream to cause devastating infection in the central nervous system. In the zebrafish model, small amounts of cryptococcus inoculated into the bloodstream are initially phagocytosed, and become far more capable of dissemination after they exit macrophages. Similarly, survival in the mouse lung produces cryptococcal cell types with enhanced dissemination. In this study we have evaluated how phagocytosis changes the properties ofCryptococcusduring pathogenesis. Macrophage experienced cells (MECs) become ‘licensed’ for enhanced virulence. They out-disseminate culture grown cells in the fish and out-compete non-MECs in the mouse lung. Analysis of their cell surface demonstrates that MECs have increased availability of cell wall components mannose and chitin—substances involved in provoking phagocytosis. These findings suggest howCryptococcusmight tune its cell surface to induce but survive repeated phagocytosis during early pathogenesis in the lung.
Diagnosis of Pathological Speech with Efficient and Effective Features for Long Short-Term Memory Learning
Authors: Pham Tuan D. , Holmes Simon B. , Zou Lifong , Patel Mangala , Coulthard Paul
Published: September 2023

The majority of voice disorders stem from improper vocal usage. Alterations in voice quality can also serve as indicators for a broad spectrum of diseases. Particularly, the significant correlation between voice disorders and dental health underscores the need for precise diagnosis through acoustic data. This paper introduces effective and efficient features for deep learning with speech signals to distinguish between two groups: individuals with healthy voices and those with pathological voice conditions. Using a public voice database, the ten-fold test results obtained from long short-term memory networks trained on the combination of time-frequency and time-space features with a data balance strategy achieved the following metrics: accuracy = 90%, sensitivity = 93%, specificity = 87%, precision = 88%,F1score = 0.90, and area under the receiver operating characteristic curve = 0.96.
Look how sustainable I am! Effects of communication focus, individuals' differences on intention to use food waste fighting mobile applications
Authors: Sestino Andrea , Rizzo Cristian , Alam Gazi Mahabubul
Published: September 2023

Purpose

The purpose of this paper is to examine the role of digital transformation processes for food and beverage companies by investigating how the sustainability-related communication focus (low vs. high) in food waste fighting mobile applications' advertising campaigns influence consumers' intention to use such mobile app, via their environmentalism.

Design/methodology/approach

An experimental study has been conducted by using a fictitious mobile app named “Boxy Food!” among a sample of 408 randomly recruited international participants.

Findings

Findings reveal that the sustainability-related communication focus in such food waste-fighting mobile apps advertising campaigns (low vs. high) positively affects consumers' intentions to use such mobile apps through the effect of environmentalism. More interestingly, this effect increases in magnitude, becoming higher among those consumers who exhibit a high level of status consumption orientation explaining their behavior as an attempt to “be green, to be recognized from the others.”

Practical implications

This study suggests marketers and managers operating in the food and beverage sector how to design effective strategies to incentivize sustainable behavior through the use of new technologies, by leveraging consumers' individual differences, and specifically on their desire to be recognized as sustainable consumers.

Originality/value

This is the first study demonstrating how the combined effects of the sustainability-related communication focus (low vs. high) may incentivize the use of mobile applications for food waste fighting, by leveraging on consumers' looking to be recognized as green.
Big data and human resource management: paving the way toward sustainability
Authors: Gravili Ginevra , Hassan Rohail , Avram Alexandru , Schiavone Francesco
Published: September 2023

Purpose

This paper aims to examine the influence of big data (BD) on human resource management (HRM). It defines how these data can be a useful tool in the decision-making process of companies’ human resources to obtain a sustainable competitive advantage.

Design/methodology/approach

This paper emphasizes the need to develop a holistic approach to emphasize these relations. Starting from these observations, the document proposes empirical research employing Eurostat data to test the benefits of BD in HRM decisions that optimize the relationship between training, productivity, and well-being.

Findings

The findings estimate HRM decisions and their impact in a broader macroeconomic and microeconomic perspective.

Originality/value

BD research is emerging as a crucial discipline in human resources. To overcome this problem, the paper develops an analysis of the literature on cleaner production and sustainability context; it creates a conceptual framework to clarify whether the existing studies consider the growing intensity of BD on human resources.
Performance analysis of a proton exchange membrane fuel cell with the stair arrangement of obstacles in the cathode channel
Authors: Baharlou-Houreh Nasser , Masaeli Navid , Afshari Ebrahim , Mohammadzadeh Kazem
Published: September 2023

Purpose

This paper aims to investigate the effect of partially blocking the cathode channel with the stair arrangement of obstacles on the performance of a proton exchange membrane fuel cell.

Design/methodology/approach

A numerical study is conducted by developing a three-dimensional computational fluid dynamics model.

Findings

As the angle of the stair arrangement increases, the performance of the fuel cell is reduced and the pressure drop is decreased. The use of four stair obstacles with an angle of 0.17° leads to higher power density and a lower pressure drop compared to the case with three rectangular obstacles of the same size and maximum height. The use of four stair obstacles with an angle of 0.34° results in higher power density and lower pressure drop compared to the case with two rectangular obstacles of the same size and maximum height.

Originality/value

Using the stair arrangement of obstacles as an innovation of the present work, in addition to improving the fuel cell’s performance, creates a lower pressure drop than the simple arrangement of obstacles.
Factors affecting the purchase intention of over the counter products in the self care actions of consumers
Authors: Salman Unver Sevgi , Sezgin Selime , Uray Nimet
Published: September 2023

Purpose

Within the framework of the theory of planned behavior (TPB), this study aims to investigate which factors affect consumers’ purchase intention with regard to over-the-counters (OTCs), focusing on personal factors, including health consciousness and risk aversion, as well as rational factors, consisting of the level of knowledge, price consciousness and involvement in the purchase intentions.

Design/methodology/approach

Due to the necessity of finding the most crucial industry-specific indicators, it was decided to carry out two-stage research based on qualitative preliminary research and the main study. The findings obtained from the qualitative studies were integrated with insights gleaned from the literature to finalize the study’s conceptual model. The main study was based on a descriptive research design, and data were collected through an online survey. Structural equation modeling was the main technique used to test the model.

Findings

Health consciousness, level of knowledge and involvement in consumer purchase intentions affect either attitude or perceived behavioral control. Moreover, attitudes toward OTCs and perceived behavioral control were significant predictors of purchase intentions for OTC drugs. At the same time, subjective norms did not have a significant effect.

Practical implications

Knowing what influences consumer purchase intentions contributes to developing more effective marketing strategies and actions.

Originality/value

This study took an integrative approach to understanding the effect of personal and rational factors within the TPB framework for a changing tendency in consumer behavior of specific product categories.