bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthropometric Analysis of the Faces of Chinese Women in Leadership Roles
Authors: Gyun Jung Sung , Wu Xiajing , Hwang Kun , Han Seung-Ho
Published: April 2024

The aim of this study was to investigate the appearance of the faces of Chinese women in leadership positions through an anthropometric analysis of Women of China from 1949 to 2022. Photographs of cover women of Women of China were gathered and a total of 380 frontal and 101 lateral photographs were collected. The photographs were divided into 3 time phases: phase I (1949–1978): from the launch of Women of China magazine, up until the time of reform and opening; phase II (1978–2010): from the time of reform and opening until when Google China was blocked; and phase III (2010–2022): to the present. The horizontal corneal diameter (11.52 mm) was set as the reference value for the frontal face. The anthropometric results showed the width of the face, midface, and lower face decreased over time. The women at phase I had larger and round faces, smaller and narrower eyes, wider noses, and thicker lips; relatively masculine and hard-working woman image, as the occupations of women were mainly described as workers, farmers, and civil servants. Phase II showed smaller but still round faces, relatively wide-set round eyes, narrower noses, and smaller lips than in phase I; neutral features as skilled workers, engineers, entrepreneurs, civil servants, and researchers. Phase III showed oval faces, almond eyes, narrower noses, smaller full lips, and wider chins, reflecting a process of feminization; working in entertainment, sports, and science. The data from this study might serve as the recommended aesthetic proportions when performing plastic surgical procedures for talented woman.
Combination of hyperoxygenation and targeted temperature management improves functional outcomes of post cardiac arrest syndrome irrespective of causes of arrest in rats
Authors: Li Jingru , Shen Yiming , Wang Jianjie , Chen Bihua , Li Yongqin
Published: April 2024

Background

The high mortality rates of patients who are resuscitated from cardiac arrest (CA) are attributed to post cardiac arrest syndrome (PCAS). This study evaluated the effect of hyperoxygenation and targeted temperature management (TTM) on PCAS in rats with different causes of CA.

Methods and Results

One hundred and sixty-eight Sprague-Dawley rats were equally divided into asphyxial and dysrhythmic groups. Animals were further randomized into four subgroups immediately after resuscitation: 1) Normoxia-normothermia (NO-NT): ventilated with 21% oxygen under normothermia; 2) Hyperoxia-normothermia (HO-NT): ventilated with 100% oxygen for 3 h under normothermia; 3) Normoxia-hypothermia (NO-HT): ventilated with 21% oxygen for 3 h under hypothermia; 4) Hyperoxia-hypothermia (HO-HT): ventilated with 100% oxygen for 3 h under hypothermia. Post resuscitation cardiac dysfunction, neurological recovery, and pathological analysis were assessed.

For asphyxial CA, HO-NT and HO-HT (68.8% and 75.0%) had significantly higher survival than NO-NT and NO-HT (31.3% and 31.3%). For dysrhythmic CA, NO-HT and HO-HT (81.3% and 87.5%) had significantly higher survival than NO-NT and HO-NT (44.0% and 50.0%). When all of the rats were considered, the survival rate was much higher in HO-HT (81.3%). Compared with NO-NT (57.7 ± 14.9% and 40.3 ± 7.8%), the collagen volume fraction and the proportion of fluoro-jade B-positive area in HO-HT (14.0 ± 5.7% and 28.0 ± 13.3%) were significantly reduced.

Conclusions

The beneficial effects of hyperoxygenation and TTM are dependent on the cause of arrest: hyperoxygenation benefits asphyxial whereas TTM benefits dysrhythmic CA. The combination of hyperoxygenation and TTM could effectively improve the functional outcome of PCAS regardless of the cause of CA.
The difficult cholecystectomy: What you need to know
Authors: Seshadri Anupamaa , Peitzman Andrew B.
Published: April 2024

This review discusses the grading of cholecystitis, the optimal timing of cholecystectomy, adopting a culture of safe cholecystectomy, understanding the common error traps that can lead to intraoperative complications, and how to avoid them.
1–28
The Tokyo Guidelines, American Association for the Surgery of Trauma, Nassar, and Parkland scoring systems are discussed. The patient factors, physiologic status, and operative findings that predict a difficult cholecystectomy or conversion from laparoscopic to open cholecystectomy are reviewed. With laparoscopic expertise and patient conditions that are not prohibitive, early laparoscopic cholecystectomy is recommended. This is ideally within 72 hours of admission but supported up to the seventh hospital day. The majority of bile duct injuries are due to misidentification of normal anatomy. Strasberg's four error traps and the zones of danger to avoid during a cholecystectomy are described. The review emphasizes the importance of a true critical view of safety for identification of the anatomy. In up to 15% of operations for acute cholecystitis, a critical view of safety cannot be achieved safely. Recognizing these conditions and changing your operative strategy are mandatory to avoid harm. The principles to follow for a safe cholecystectomy are discussed in detail. The cardinal message of this review is, “under challenging conditions, bile duct injuries can be minimized via either a subtotal cholecystectomy or top-down cholecystectomy if dissection in the hepatocystic triangle is avoided”.
21
The most severe biliary/vascular injuries usually occur after conversion from laparoscopic cholecystectomy. Indications and techniques for bailout procedures including the fenestrating and reconstituting subtotal cholecystectomy are presented. Seven percent to 10% of cholecystectomies for acute cholecystitis currently result in subtotal cholecystectomy. Level of evidence: III
Elevation of Donor-derived Cell-free DNA Before Biopsy-proven Rejection in Kidney Transplant
Authors: Bromberg Jonathan S. , Bunnapradist Suphamai , Samaniego-Picota Milagros , Anand Sanjiv , Stites Erik , Gauthier Philippe , Demko Zachary , Prewett Adam , Armer-Cabral Madeleine , Marshall Kyle , Kaur Navchetan , Bloom Michelle S. , Tabriziani Hossein , Bhorade Sangeeta , Cooper Matthew ,   on behalf of the ProActive Investigators
Published: April 2024

Background.

Standard-of-care biomarkers for renal allograft rejection are lagging indicators, signaling existing organ injury. This precludes early intervention, when immunological cascades leading to rejection are most susceptible. Donor-derived cell-free DNA (dd-cfDNA) shows promise as an early indicator of rejection, allowing earlier and possibly more effective treatment. This analysis was designed to assess this promise using real-world dd-cfDNA testing evidence.

Methods.

This retrospective analysis of the prospective, observational ProActive registry study (NCT04091984) assessed dd-cfDNA and serum creatinine levels before biopsy in 424 patients with ≥1 dd-cfDNA test (n = 1013) in the 6 mo before biopsy.

Results.

Of 4667 enrolled patients, 1631 patients had ≥18 mo of follow-up data, of which 424 had a biopsy and were included in this analysis. Twenty-six biopsies showed antibody-mediated rejection (ABMR), 62 showed T cell–mediated rejection, and 336 showed nonrejection; each from a unique patient. dd-cfDNA fractions were significantly elevated 5 mo before ABMR biopsies, and 2 mo before T cell–mediated rejection biopsies, compared with nonrejection biopsies. In contrast, serum creatinine did not discriminate between rejection and nonrejection in advance, or concurrent with biopsy. Among patients with nonrejection biopsies, estimated glomerular filtration rate was significantly lower in cases with ≥2 increased dd-cfDNA results (≥1%), compared with those with 0 or 1 increased dd-cfDNA result.

Conclusions.

These data indicate that dd-cfDNA is an early indicator of biopsy-proven rejection, especially ABMR, suggesting a greater role for dd-cfDNA in surveillance to identify patients at high risk of ongoing or future rejection, thus requiring closer monitoring, biopsy, or other management changes.
Long-Term Mortality Prediction with Pooled Cohort Equations: Implications for Lipid-Lowering Therapy
Authors: Ma Zhiyuan , Moran Lynn N. , Shirani Jamshid
Published: April 2024

Background

Current guidelines recommend primary prevention statin therapy based on 10-year risk of atherosclerotic cardiovascular disease (ASCVD) assessed by the pooled cohort equations (PCE), while assessing effectiveness through low-density lipoprotein cholesterol levels. It remains uncertain whether 10-year ASCVD risk can accurately predict the mortality impact of lipid-lowering therapy.

Methods

A retrospective analysis of National Health and Nutrition Examination Survey (NHANES) (III and 1999-2008) linked to the National Death Index was conducted with propensity score matching. The study included 6647 adults without lipid-lowering therapy and 2484 with lipid-lowering therapy. Cox regression models and C statistic were used to assess the association between 10-year ASCVD risk and mortality.

Results

In the matched cohort with 4802 individuals with similar ASCVD risks, 10-year risk of ASCVD by PCE was comparable for predicating all-cause mortality at 10 years in the lipid-lowering therapy group (area under curve [AUC], 0.75; 95% CI 0.73-0.77) and without lipid-lowering therapy (0.74; 95% CI 0.71-0.77;P= 0.50). Similarly, PCE was comparable for predicting cardiovascular mortality at 10 years in both groups (AUC, 0.75; 95% CI 0.70-0.79 versus 0.77; 95% CI 0.73-0.80;P= 0.47). Lipid-lowering therapy was significantly associated with reduced all-cause mortality (adjusted hazard ratio [HR], 0.70; 95% CI 0.61-0.82;P< 0.01) and cardiovascular mortality (adjusted HR, 0.65; 95% CI, 0.51-0.83;P< 0.01), particularly in those with a 10-year ASCVD risk of 7.5% or higher.

Conclusions

PCE provides comparable predictions of mortality in individuals with and without lipid-lowering therapy. Moreover, individuals on lipid-lowering therapy exhibited lower all-cause and cardiovascular mortality compared to those without lipid-lowering therapy but with a similar 10-year risk of ASCVD. These findings suggest that mortality risk reduction can be assessed by 10-year ASCVD risk estimated by PCE for primary prevention both prior and after treatment.
Tonotopic organization of auditory cortex in awake marmosets revealed by multi-modal wide-field optical imaging
Authors: Song Xindong , Guo Yueqi , Chen Chenggang , Lee Jong Hoon , Wang Xiaoqin
Published: April 2024

Tonotopic organization of the auditory cortex has been extensively studied in many mammalian species using various methodologies and physiological preparations. Tonotopy mapping in primates, however, is more limited due to constraints such as cortical folding, use of anesthetized subjects, and mapping methodology. Here we applied a combination of through-skull and through-window intrinsic optical signal imaging, wide-field calcium imaging, and neural probe recording techniques in awake marmosets (Callithrix jacchus), a New World monkey with most of its auditory cortex located on a flat brain surface. Coarse tonotopic gradients, including a recently described rostral-temporal (RT) to parabelt gradient, were revealed by the through-skull imaging of intrinsic optical signals and were subsequently validated by single-unit recording. Furthermore, these tonotopic gradients were observed with more details through chronically implanted cranial windows with additional verifications on the experimental design. Moreover, the tonotopy mapped by the intrinsic-signal imaging methods was verified by wide-field calcium imaging in an AAV-GCaMP labeled subject. After these validations and with the further effort to expand the field of view more anteroventrally in both windowed and through-skull subjects, an additional putative tonotopic gradient was observed more rostrally to the area RT, which has not been previously described by the standard model of tonotopic organization of the primate auditory cortex. Together, these results provide the most comprehensive data of tonotopy mapping in awake primate species with unprecedented coverage and details in the rostral proportion and supports a caudorostrally arranged mesoscale organization of at least three repeats of functional gradients in the primate auditory cortex, similar to the ventral stream of primate visual cortex.
Task-specific topology of brain networks supporting working memory and inhibition
Authors: Adamovich Timofey , Ismatullina Victoria , Chipeeva Nadezhda , Zakharov Ilya , Feklicheva Inna , Malykh Sergey
Published: April 2024

Network neuroscience investigates the brain’s connectome, revealing that cognitive functions are underpinned by dynamic neural networks. This study investigates how distinct cognitive abilities—working memory and inhibition—are supported by unique brain network configurations, which are constructed by estimating whole-brain networks through mutual information. The study involved 195 participants who completed the Sternberg Item Recognition and Flanker tasks while undergoing EEG recording. A mixed-effects linear model analyzed the influence of network metrics on cognitive performance, considering individual differences and task-specific dynamics. Results indicate that working memory and inhibition are associated with different network attributes, with working memory relying on distributed networks and inhibition on more segregated ones. Our analysis suggests that both strong and weak connections contribute to cognitive processes, as weak connections could potentially lead to a more stable and support networks of memory and inhibition. The findings indirectly support the Network Neuroscience Theory of Intelligence, suggesting different functional topology of networks inherent to various cognitive functions. Nevertheless, we propose that understanding individual variations in cognitive abilities requires recognizing both shared and unique processes within the brain’s network dynamics.

Author summary

This study analyzes how working memory and inhibition correspond to distinct neural network patterns by constructing whole-brain networks via mutual information from EEG data of 195 subjects performing cognitive tasks. Findings reveal working memory is supported by distributed connections while inhibition depends on segregated ones. The research underscores the importance of both strong and weak neural connections in cognitive function and supports the notion that cognitive functions emerge from the brain network of distinct topology. Moreover, it highlights the need to account for individual and task-specific variations to fully grasp the diverse network dynamics influencing cognitive abilities.
Resource: A Curated Database of Brain-Related Functional Gene Sets (Brain.GMT)
Authors: Hagenauer Megan H. , Sannah Yusra , Hebda-Bauer Elaine K. , Rhoads Cosette , O’Connor Angela M. , Watson Stanley J. , Akil Huda
Published: April 2024

Transcriptional profiling has become a common tool for investigating the nervous system. During analysis, differential expression results are often compared to functional ontology databases, which contain curated gene sets representing well-studied pathways. This dependence can cause neuroscience studies to be interpreted in terms of functional pathways documented in better studied tissues (e.g., liver) and topics (e.g., cancer), and systematically emphasizes well-studied genes, leaving other findings in the obscurity of the brain “ignorome”.

To address this issue, we compiled a curated database of918gene sets related to nervous system function, tissue, and cell types (“Brain.GMT”) that can be used within common analysis pipelines (GSEA, limma, edgeR) to interpret results from three species (rat, mouse, human). Brain.GMT includes brain-related gene sets curated from the Molecular Signatures Database (MSigDB) and extracted from public databases (GeneWeaver, Gemma, DropViz, BrainInABlender, HippoSeq) and published studies containing differential expression results.

Although Brain.GMT is still undergoing development and currently only represents a fraction of available brain gene sets, “brain ignorome” genes are already better represented than in traditional Gene Ontology databases. Moreover, Brain.GMT substantially improves the quantity and quality of gene sets identified as enriched with differential expression in neuroscience studies, enhancing interpretation.

Graphical abstract

Specifications table
Parameter estimation for the oral minimal model and parameter distinctions between obese and non-obese type 2 diabetes
Authors: Aravindakshan Manoja Rajalakshmi , Ghosh Devleena , Mandal Chittaranjan , Venkatesh K V , Sarkar Jit , Chakrabarti Partha , Maity Sujay K
Published: April 2024

Oral Glucose Tolerance Test (OGTT) is the primary test used to diagnose type 2 diabetes mellitus (T2DM) in a clinical setting. Analysis of OGTT data using the Oral Minimal Model (OMM) along with the rate of appearance of ingested glucose (Ra) is performed to study differences in model parameters for control and T2DM groups. The differentiation of parameters of the model gives insight into the behaviour and physiology of T2DM. The model is also studied to find parameter differences among obese and non-obese T2DM subjects and the sensitive parameters were co-related to the known physiological findings. Sensitivity analysis is performed to understand changes in parameter values with model output and to support the findings, appropriate statistical tests are done. This seems to be the first preliminary application of the OMM with obesity as a distinguishing factor in understanding T2DM from estimated parameters of insulin-glucose model and relating the statistical differences in parameters to diabetes pathophysiology.

Highlights

An established oral minimal model is used for estimation of parameters obese and non-obese type 2 diabetes.

This is a novel attempt to use oral minimal model to co-relate the parameters for different diabetic groups using oral glucose tolerance test (OGTT) data.

The data of different diabetes groups were utilised for model parameter determination and through statistical tests, distinctions in parameter distribution were identified.

It was observed that obese diabetic group are more insulin resistant compared to non-obese diabetic group.
Intermittent Cyclic Stretch of Engineered Ligaments Drives Hierarchical Collagen Fiber Maturation in a Dose- and Organizational-Dependent Manner
Authors: Troop Leia D. , Puetzer Jennifer L.
Published: April 2024

Abstract

Hierarchical collagen fibers are the primary source of strength in tendons and ligaments, however these fibers do not regenerate after injury or with repair, resulting in limited treatment options. We previously developed a culture system that guides ACL fibroblasts to produce native-sized fibers and fascicles by 6 weeks. These constructs are promising ligament replacements, but further maturation is needed. Mechanical cues are critical for developmentin vivoand in engineered tissues; however, the effect on larger fiber and fascicle formation is largely unknown. Our objective was to investigate whether intermittent cyclic stretch, mimicking rapid muscle activity, drives further maturation in our system to create stronger engineered replacements and to explore whether cyclic loading has differential effects on cells at different degrees of collagen organization to better inform engineered tissue maturation protocols. Constructs were loaded with an established intermittent cyclic loading regime at 5 or 10% strain for up to 6 weeks and compared to static controls. Cyclic loading drove cells to increase hierarchical collagen organization, collagen crimp, and tissue mechanics, ultimately producing constructs that matched or exceeded immature ACL properties. Further, the effect of loading on cells varied depending on degree of organization. Specifically, 10% load drove early improvements in mechanics and composition, while 5% load was more beneficial later in culture, suggesting a cellular threshold response and a shift in mechanotransduction. This study provides new insight into how cyclic loading affects cell-driven hierarchical fiber formation and maturation, which will help to develop better rehabilitation protocols and engineer stronger replacements.
Insulin-like Growth Factor 2 mRNA-binding protein 2 (IGF2BP2) Promotes Castration-Resistant Prostate Cancer Progression by Regulating AR-V7 mRNA Stability
Authors: Saini Taruna , Srivastava Devesh , Raut Rajnikant , Mishra Parul , Misra Ashish
Published: April 2024

The emergence of constitutively active androgen receptor (AR) splice variant AR-V7 poses a formidable challenge in treating prostate cancer, as it lacks the ligand binding region targeted by androgen deprivation therapies such as enzalutamide and abiraterone. AR-V7 is critical for castration-resistant prostate cancer (CRPC) development and progression, however the molecular mechanisms regulating its expression and biological function remain poorly understood. Here, we investigate the role of IGF2BP2 in regulating AR-V7 expression and CRPC progression. We demonstrate that IGF2BP2 silencing leads to downregulation of AR-V7 and its downstream target genes without affecting AR levels. Additionally, IGF2BP2 knockdown also enhances the sensitivity of CRPC cells to enzalutamide while overexpression increases AR-V7 expression and confers increased resistance to enzalutamide. Mechanistically, our experiments demonstrate that IGF2BP2 binds to the intronic splicing enhancer (ISE) region of AR-V7, thereby enhancing its mRNA stability Furthermore, our domain-deletion analysis pinpoints the role of KH3 and KH4 domains of IGF2BP2 in regulating AR-V7 stability and enzalutamide resistance. Taken together, our findings suggest that IGF2BP2 plays a critical role in regulating AR-V7 expression and stability, offering a novel target for developing therapeutic interventions for CRPC.
Creative tempo: Spatiotemporal dynamics of the default mode network in improvisational musicians
Authors: Watters Harrison , Fazili Abia , Daley Lauren , Belden Alex , LaGrow TJ , Bolt Taylor , Loui Psyche , Keilholz Shella
Published: April 2024

The intrinsic dynamics of human brain activity display a recurring pattern of anti-correlated activity between the default mode network (DMN), associated with internal processing and mentation, and task positive regions, associated with externally directed attention. In human functional magnetic resonance imaging (fMRI) data, this anti-correlated pattern is detectable on the infraslow timescale (<0.1 Hz) as a quasi-periodic pattern (QPP). While the DMN is implicated in creativity and musicality in traditional time-averaged functional connectivity studies, no one has yet explored how creative training may alter dynamic spatiotemporal patterns involving the DMN such as QPPs. In the present study, we compare the outputs of two QPP detection approaches, sliding window algorithm and complex principal components analysis (cPCA). We apply both methods to an existing dataset of musicians captured with resting state fMRI, grouped as either classical, improvisational, or minimally trained non-musicians. The original time-averaged functional connectivity (FC) analysis of this dataset used improvisation as a proxy for creative thinking and found that the DMN and visual networks (VIS) display higher connectivity in improvisational musicians. We expand upon this dataset’s original study and find that QPP analysis detects convergent results at the group level with both methods. In improvisational musicians, dynamic functional correlation in the group-averaged QPP was found to be increased between the DMN-VIS and DMN-FPN for both the QPP algorithm and complex principal components analysis (cPCA) methods. Additionally, we found an unexpected increase in FC in the group-averaged QPP between the dorsal attention network and amygdala in improvisational musicians; this result was not reported in the original seed-based study of this dataset. The current study represents a novel application of two dynamic FC detection methods with results that replicate and expand upon previous seed-based FC findings. The results show the robustness of both the QPP phenomenon and its detection methods. This study also demonstrates the value of dynamic FC methods in reproducing seed-based findings and their promise in detecting group-wise or individual differences that may be missed by traditional seed-based resting state fMRI studies.
Analysis of Longitudinal Change Patterns in Developing Brain Using Functional and Structural Magnetic Resonance Imaging via Multimodal Fusion
Authors: Saha Rekha , Saha Debbrata K. , Fu Zening , Duda Marlena , Silva Rogers F. , Calhoun Vince D.
Published: April 2024

Functional and structural magnetic resonance imaging (fMRI and sMRI) are complementary approaches that can be used to study longitudinal brain changes in adolescents. Each individual modality offers distinct insights into the brain. Each individual modality may overlook crucial aspects of brain analysis. By combining them, we can uncover hidden brain connections and gain a more comprehensive understanding. In previous work, we identified multivariate patterns of change in whole-brain function during adolescence. In this work, we focus on linking functional change patterns (FCPs) to brain structure. We introduce two approaches and applied them to data from the Adolescent Brain and Cognitive Development (ABCD) dataset. First, we evaluate voxelwise sMRI-FCP coupling to identify structural patterns linked to our previously identified FCPs. Our approach revealed multiple interesting patterns in functional network connectivity (FNC) and gray matter volume (GMV) data that were linked to subject level variation. FCP components 2 and 4 exhibit extensive associations between their loadings and voxel-wise GMV data. Secondly, we leveraged a symmetric multimodal fusion technique called multiset canonical correlation analysis (mCCA) + joint independent component analysis (jICA). Using this approach, we identify structured FCPs such as one showing increased connectivity between visual and sensorimotor domains and decreased connectivity between sensorimotor and cognitive control domains, linked to structural change patterns (SCPs) including alterations in the bilateral sensorimotor cortex. Interestingly, females exhibit stronger coupling between brain functional and structural changes than males, highlighting sex-related differences. The combined results from both asymmetric and symmetric multimodal fusion methods underscore the intricate sex-specific nuances in neural dynamics. By utilizing two complementary multimodal approaches, our study enhances our understanding of the dynamic nature of brain connectivity and structure during the adolescent period, shedding light on the nuanced processes underlying adolescent brain development.
Characteristic Fetal Brain MRI Abnormalities in Pyruvate Dehydrogenase Complex Deficiency
Authors: Fortin Olivier , Christoffel Kelsey , Shoaib Abdullah , Venkatesan Charu , Cilli Kate , Schroeder Jason W. , Alves Cesar , Ganetzky Rebecca D. , Fraser Jamie L.
Published: April 2024

Pyruvate dehydrogenase complex deficiency (PDCD) is a disorder of mitochondrial metabolism that is caused by pathogenic variants in multiple genes, includingPDHA1. Typical neonatal brain imaging findings in PDCD have been described, with a focus on malformative features and chronic encephaloclastic changes. However, fetal brain MRI imaging in confirmed PDCD has not been comprehensively described. We sought to demonstrate the prenatal neurological and systemic manifestations of PDCD determined by comprehensive fetal imaging and genomic sequencing.

All fetuses with a diagnosis of genetic PDCD who had undergone fetal MRI were included in the study. Medical records, imaging data, and genetic testing results were reviewed and reported descriptively.

Ten patients with diagnosis of PDCD were included. Most patients had corpus callosum dysgenesis, abnormal gyration pattern, reduced brain volumes, and periventricular cystic lesions. One patient had associated intraventricular hemorrhages. One patient had a midbrain malformation with aqueductal stenosis and severe hydrocephalus. Fetuses imaged in the second trimester were found to have enlargement of the ganglionic eminences with cystic cavitations, while those imaged in the third trimester had germinolytic cysts.

Fetuses with PDCD have similar brain MRI findings to neonates described in the literature, although some of these findings may be subtle early in pregnancy. Additional features, such as cystic cavitations of the ganglionic eminences, are noted in the second trimester in fetuses with PDCD, and these may represent a novel early diagnostic marker for PDCD. Using fetal MRI to identify these radiological hallmarks to inform prenatal diagnosis of PDCD may guide genetic counseling, pregnancy decision-making, and neonatal care planning.
Tissue informative cell-free DNA methylation sites in amyotrophic lateral sclerosis
Authors: Caggiano C. , Morselli M. , Qian X. , Celona B. , Thompson M. , Wani S. , Tosevska A. , Taraszka K. , Heuer G. , Ngo S. , Steyn F. , Nestor P. , Wallace L. , McCombe P. , Heggie S. , Thorpe K. , McElligott C. , English G. , Henders A. , Henderson R. , Lomen-Hoerth C. , Wray N. , McRae A. , Pellegrini M. , Garton F. , Zaitlen N.
Published: April 2024

Cell-free DNA (cfDNA) is increasingly recognized as a promising biomarker candidate for disease monitoring. However, its utility in neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS), remains underexplored. Existing biomarker discovery approaches are tailored to a specific disease context or are too expensive to be clinically practical. Here, we address these challenges through a new approach combining advances in molecular and computational technologies. First, we develop statistical tools to select tissue-informative DNA methylation sites relevant to a disease process of interest. We then employ a capture protocol to select these sites and perform targeted methylation sequencing. Multi-modal information about the DNA methylation patterns are then utilized in machine learning algorithms trained to predict disease status and disease progression. We applied our method to two independent cohorts of ALS patients and controls (n=192). Overall, we found that the targeted sites accurately predicted ALS status and replicated between cohorts. Additionally, we identified epigenetic features associated with ALS phenotypes, including disease severity. These findings highlight the potential of cfDNA as a non-invasive biomarker for ALS.
Pattern formation along signaling gradients driven by active droplet behaviour of cell groups
Authors: Ford Hugh Z , Celora Giulia L , Westbrook Elizabeth R , Dalwadi Mohit P , Walker Benjamin J , Baumann Hella , Weijer Cornelis J. , Pearce Philip , Chubb Jonathan R
Published: April 2024

Gradients of extracellular signals organise cells in tissues. Although there are several models for how gradients can pattern cell behaviour, it is not clear how cells react to gradients when the population is undergoing 3D morphogenesis, in which cell-cell and cell-signal interactions are continually changing.Dictyosteliumcells follow gradients of their nutritional source to feed and maintain their undifferentiated state. Using light sheet imaging to simultaneously monitor signaling, single cell and population dynamics, we show that the cells migrate towards nutritional gradients in swarms. As swarms advance, they deposit clumps of cells at the rear, triggering differentiation. Clump deposition is explained by a physical model in which cell swarms behave as active droplets: cells proliferate within the swarm, with clump shedding occurring at a critical population size, at which cells at the rear no longer perceive the gradient and are not retained by the emergent surface tension of the swarm. The droplet model predicts vortex motion of the cells within the swarm emerging from the local transfer of propulsion forces, a prediction validated by 3D tracking of single cells. This active fluid behaviour reveals a developmental mechanism we term “musical chairs” decision-making, in which the decision to proliferate or differentiate is determined by the position of a cell within the group as it bifurcates.
Microbial Analysis and Sanitization of Hydroponic Farming Facilities in Singapore
Authors: Tham Cliff An Ting , Zwe Ye Htut , Ten Michelle Mei Zhen , Ng Geraldine Shang Ya , Toh Jillinda Yi Ling , Poh Bee Ling , Zhou Weibiao , Li Dan
Published: April 2024

This study performed microbial analysis of nutrient film technique (NFT) hydroponic systems at three indoor farms in Singapore. To justify the necessity to sanitize the hydroponic systems, strong biofilm-forming bacteria were isolated from the facility and investigated with their influence onSalmonellacolonizing on polyvinyl chloride (PVC) coupons in hydroponic nutrient solutions. Last, sanitization solutions were evaluated with both laboratory-scale and field-scale tests. As a result, the microbiome composition in NFT systems was found to be highly farm-specific. Strong biofilm formersCorynebacterium tuberculostearicumC2 andPseudoxanthomonas mexicanaC3 were found to facilitate the attachment and colonization ofSalmonellaon PVC coupons. When forming dual-species biofilms, the presence of C2 and C3 also significantly promoted the growth ofSalmonella(P< 0.05). Sodium hypochlorite (NaOCl) exhibited superior efficacy in biofilm removal compared to hydrogen peroxide (H2O2) and sodium percarbonate (SPC). NaOCl at 50 ppm reduced C2 and C3 counts to < 1 log CFU/cm2within 12 h, whereas neither 3% H2O2nor 1% SPC achieved such an effect. In operational hydroponic systems, the concentration of NaOCl needed to achieve biofilm elimination increased to 500 ppm, likely due to the presence of organic matter accumulated during the crop cultivation and the higher persistence of the naturally formed multispecies biofilms. The sanitization (500 ppm NaOCl for 12 h) did not impede subsequent plant growth but chlorination by-product chlorate was detected with high levels from the hydroponic solution and plants in the sanitized systems without rinsing.

IMPORTANCE

This study’s significance lies first in its elucidation of the necessity to sanitize the hydroponic farming systems. The microbiome in hydroponic systems, although most of the times non-pathogenic, might serve as a hotbed for pathogens’ colonization and thus pose a higher risk for food safety. We thus explored sanitization solutions with both laboratory-scale and field-scale tests. Of the three tested sanitizers, NaOCl was the most effective and economical option, whereas one must note the vital importance of rinsing the hydroponic systems after sanitization with NaOCl.
Temporal Heart Rhythm Clusters and Physiomorphic Age Mapping: A Deep Learning Approach to Cardiovascular Risk Stratification
Authors: Manimaran Gouthamaan , Puthusserypady Sadasivan , Dominguez Helena , Bardram Jakob E.
Published: April 2024

Purpose

Understanding the intricate relationships between sleep quality and cardiovascular outcomes can potentially offer new avenues in risk stratification for cardiovascular diseases (CVD). This study aimed to evaluate the significance of biological age predicted through the analysis of sleep stages and nocturnal heart rhythms as a marker for cardiovascular risk.

Methods

We leveraged an unsupervised learning approach to generate time-series clusters utilizing whole-night sleep data fromN= 900 patients, focusing on identifying shifts and consistencies in nocturnal heart rhythms that may indicate variations in cardiac health. Following this, a deep learning model was applied to the time-series clusters to estimate the biological age of the individuals, thereby delineating potential relationships between predicted age, biological age, sleep patterns, and heart rhythms.

Results

In a distinct test set of 736 individuals, the predicted age based on this experiment showcased a higher association with mortality (Hazard Ratio (HR) 2.27, p<0.05) and CVD risk (HR 3.56, p<0.001). Conversely, the age estimated through only nocturnal heart rhythms demonstrated a HR of 2.29 (p<0.05) for all-cause mortality and 3.13 (p<0.01) for CVD risk.

Conclusion

Our findings underscore the high prognostic potential of sleep and electrocardiography data in predicting cardiovascular risks. The method of utilizing predicted biological age derived from sleep stages and nocturnal heart rhythms stands as a significant metric in risk stratification for CVD. Further research in this area might foster novel strategies for early interventions based on sleep quality and cardiac health markers, potentially saving numerous lives through early detection and intervention.

Author summary

This study conducted on a large database of sleep data containing physiological signals such as Electrocardiograms, Sleep Stages, anonymized patient information among others shows that the heart behaviour during sleep is indicative of future cardiovascular (CVD) risk and all-cause mortality. This study employs deep learning to predict biological age which is in turn mapped to CVD risk. Through this study, we can see that while heart rhythms during sleep and different stages of sleep (REM, light sleep, etc) does show an association with CVD risk (this exists in previous literature), the more reliable association is found in heart behaviour during specific sleep stages (which is the novelty of our work). We use deep learning to map ECG into different clusters (n=50) using self-supervised learning, and also to find correlation between these clusters and sleep stages while mapping them to their biological age.
Purine and pyrimidine synthesis differently affect the strength of the inoculum effect for aminoglycoside and β-lactam antibiotics
Authors: Hernandez Daniella M. , Marzouk Melissa , Cole Madeline , Fortoul Marla C. , Kethireddy Saipranavi Reddy , Contractor Rehan , Islam Habibul , Moulder Trent , Kalifa Ariane R. , Meneses Estefania Marin , Mendoza Maximiliano Barbosa , Thomas Ruth , Masud Saad , Pubien Sheena , Milanes Patricia , Diaz-Tang Gabriela , Lopatkin Allison J. , Smith Robert P.
Published: April 2024

The inoculum effect has been observed for nearly all antibiotics and bacterial species. However, explanations accounting for its occurrence and strength are lacking. We previously found that growth productivity, which captures the relationship between [ATP] and growth, can account for the strength of the inoculum effect for bactericidal antibiotics. However, the molecular pathway(s) underlying this relationship, and therefore determining the inoculum effect, remain undiscovered. We show that nucleotide synthesis can determine the relationship between [ATP] and growth, and thus the strength of inoculum effect in an antibiotic class-dependent manner. Specifically, and separate from activity through the tricarboxylic acid cycle, we find that transcriptional activity of genes involved in purine and pyrimidine synthesis can predict the strength of the inoculum effect for β-lactam and aminoglycosides antibiotics, respectively. Our work highlights the antibiotic class-specific effect of purine and pyrimidine synthesis on the severity of the inoculum effect and paves the way for intervention strategies to reduce the inoculum effect in the clinic.
A single particle analysis method for detecting membrane remodelling and curvature sensing
Authors: Colussi Adeline , Almeida-Souza Leonardo , McMahon Harvey T
Published: April 2024

In biology, shape and function are related. Therefore, it is important to understand how membrane shape is generated, stabilised and sensed by proteins and how this relates to organelle function. Here we present an assay that can detect curvature preference and membrane remodelling using free-floating liposomes using protein concentrations in a physiologically relevant ranges. The assay reproduced known curvature preferences of BAR domains and allowed the discovery of high curvature preference for the PH domain of AKT and the FYVE domain of HRS. In addition, our method reproduced the membrane vesiculation activity of the ENTH domain of Epsin1 and showed similar activity for the ANTH domains of PiCALM and Hip1R. Finally, we found that the curvature sensitivity of the N-BAR domain of Endophilin inversely correlates to membrane charge and that deletion of its N-terminal amphipathic helix increased its curvature specificity. Thus, our method is a generally applicable qualitative method for assessing membrane curvature sensing and remodelling by proteins.
DAB-APT: a Fluorescence-Based Assay for Determining Aminopropyl Transferase Activity and Inhibition
Authors: Singh Pallavi , Choi Jae-Yeon , Mamoun Choukri Ben
Published: April 2024

Polyamines are polycationic molecules that are crucial in a wide array of cellular functions. Their biosynthesis is mediated by aminopropyl transferases (APTs), promising targets in antimicrobial, antineoplastic and antineurodegenerative therapies. A major limitation, however, is the lack of high-throughput assays to measure their activity. We developed the first fluorescence-based assay, DAB-APT, for measurement of APT activity using 1,2-diacetyl benzene, which forms fluorescent conjugates with putrescine, spermidine and spermine with fluorescence intensity increasing with increasing carbon chain length. The assay has been validated using APT enzymes fromS. cerevisiaeandP. falciparumand is suitable for high-throughput screening of large chemical libraries. Given the importance of APTs in infectious diseases, cancer and neurobiology, our DAB-APT assay has broad applications, holding promise for advancing research and drug discovery efforts.
Hippocampal sharp wave ripples and coincident cortical ripples orchestrate human semantic networks
Authors: Mishra Akash , Akkol Serdar , Espinal Elizabeth , Markowitz Noah , Tostaeva Gelana , Freund Elisabeth , Mehta Ashesh D. , Bickel Stephan
Published: April 2024

Episodic memory function is predicated upon the precise coordination between the hippocampus and widespread cortical regions. However, our understanding of the neural mechanisms involved in this process is incomplete. In this study, human subjects undergoing intracranial electroencephalography (iEEG) monitoring performed a list learning task. We show sharp-wave ripple (SWR)-locked reactivation of specific semantic processing regions during free recall. This cortical activation consists of both broadband high frequency (non-oscillatory) and cortical ripple (oscillatory) activity. SWRs and cortical ripples in the anterior temporal lobe, a major semantic hub, co-occur and increase in rate prior to recall. Coincident hippocampal-ATL ripples are associated with a greater increase in cortical reactivation, show specificity in location based on recall content, and are preceded by cortical theta oscillations. These findings may represent a reactivation of hippocampus and cortical semantic regions orchestrated by an interplay between hippocampal SWRs, cortical ripples, and theta oscillations.
Absolute structure determination of Berkecoumarin by X-ray and electron diffraction
Authors: Decato Daniel , Palatinus Lukáš , Stierle Andrea , Stierle Donald
Published: April 2024

X-ray and electron diffraction methods independently identify the S-enantiomer of Berkecoumarin [systematic name: (S)-8-hydroxy-3-(2-hydroxypropyl)-6-methoxy-2H-chromen-2-one]. Isolated from Berkeley Pit Lake Penicillium sp., Berkecoumarin is a natural product with a light-atom composition (C13H14O5) that challenges in-house absolute structure determination by anomalous scattering. This study further demonstrates the utility of dynamical refinement of electron-diffraction data for absolute structure determination.
Fractional-order view analysis of Fisher’s and foam drainage equations within Aboodh transform
Authors: Alshehry Azzh Saad , Yasmin Humaira , Shah Rasool , Ali Amjid , Khan Imran
Published: April 2024

Purpose

The purpose of this study is to solve two unique but difficult partial differential equations: the foam drainage equation and the nonlinear time-fractional fisher’s equation. Through our methods, we aim to provide accurate solutions and gain a deeper understanding of the intricate behaviors exhibited by these systems.

Design/methodology/approach

In this study, we use a dual technique that combines the Aboodh residual power series method and the Aboodh transform iteration method, both of which are combined with the Caputo operator.

Findings

We develop exact and efficient solutions by merging these unique methodologies. Our results, presented through illustrative figures and data, demonstrate the efficacy and versatility of the Aboodh methods in tackling such complex mathematical models.

Originality/value

Owing to their fractional derivatives and nonlinear behavior, these equations are crucial in modeling complex processes and confront analytical complications in various scientific and engineering contexts.
Critical reflection on the impact of the gig economy on the hospitality workforce
Authors: Jin Dan , Liu-Lastres Bingjie
Published: April 2024

Purpose

This paper aims to provide a critical reflection on the impact of the gig economy on the hospitality workforce. The impact of the gig economy on hospitality workforce management is explored, with the paper delving into both theoretical insights and practical implications.

Design/methodology/approach

This paper offers reflections on the emerging trend of the gig economy and its impacts on the hospitality workforce, based on evidence collected from the selected literature, industry report and authors’ personal reflections. A micro-meso-macro analytical framework was also applied to assist authors in building the arguments and propositions.

Findings

The findings not only revealed the impacts of the gig economy on the hospitality workforce at micro-meso-macro levels but also underscored its close relationships with various concepts in the hospitality management literature. Both future research directions and practical implications are provided.

Practical implications

Amid the gig economy’s transformative influence, stakeholders must continually innovate for an empowering and secure work environment. A holistic approach is necessary to establish a harmonious gig ecosystem, ensuring fair treatment, benefits and protection for workers while fostering growth and well-being.

Originality/value

Throughout the paper, a critical reflection on the impact of the gig economy on the hospitality workforce is presented, along with suggestions for coping with current labor issues in hospitality and tourism. Future research directions are outlined.