bluuebunny/crossref_metadata_2025 huggingface dataset:
Photon-Counting Detector CT
Authors: Marth Adrian A. , Goller Sophia S. , Kajdi Georg W. , Marcus Roy P. , Sutter Reto
Published: January 2024

Objectives

The aim of this study was to compare the effectiveness and clinical utility of virtual monoenergetic image (VMI) reconstructions in computed tomography (CT) scans with and without tin prefiltration on a photon-counting detector (PCD) CT system to reduce metal implant artifacts in the postoperative ankle.

Materials and Methods

This retrospective study included patients with internal fixation of the ankle scanned with and without tin prefiltration (Sn) on a PCD CT scanner between March and October 2023. Virtual monoenergetic images between 60 and 190 keV were reconstructed with a 10-keV increment in a bone kernel for both acquisitions (VMISnand VMIStd, respectively). Noise measurements assessed artifact reduction in the most prominent near-metal image distortions and were compared between acquisitions modes as well as between polychromatic images and VMIs. Three readers assessed the visibility of osseous healing along with interpretability and artifact extent for 5 reconstruction levels.

Results

A total of 48 patients (21 females, 27 males; mean age, 55.1 ± 19.4 years) were included in this study. Tin-prefiltered acquisitions (n = 30) had a lower artifact level for polychromatic images and VMIs compared with non–tin-prefiltered acquisitions (n = 18;P≤ 0.043). A significant reduction of metal artifacts was observed for VMISn≥120 keV compared with polychromatic images (hyperdense artifacts: 40.2 HU [interquartile range (IQR) 39.8] vs 14.0 HU [IQR 11.1];P≤ 0.01 and hypodense artifacts: 91.2 HU [IQR 82.4] vs 29.7 HU [IQR 39.6];P≤ 0.001). For VMIStd, this applied to reconstructions ≥100 keV (hyperdense artifacts: 57.7 HU [IQR 33.4] vs 19.4 HU [IQR 27.6];P≤ 0.001 and hypodense artifacts: 106.9 HU [IQR 76.1] vs 57.4 HU [IQR 55.7];P≤ 0.021). For visibility of osseous healing, VMISnat 120 keV yielded higher ratings compared with polychromatic images (P≤ 0.001), whereas image interpretability was rated better (P= 0.023), and artifact extent was rated lower (P≤ 0.001) compared with polychromatic images.

Conclusions

Tin-prefiltered VMI at 120 keV showed a significant reduction in metal artifacts compared with polychromatic images, whereas visibility of osseous healing and image interpretability was improved. Therefore, tin-prefiltration PCD CT with VMI reconstructions may be a helpful complement to postsurgical CT imaging of the ankle in patients with metal implants.
Efficacy and Safety of Endovascular Fenestrated and Branched Grafts vs open Surgery in Thoracoabdominal Aortic Aneurysm Repair
Authors: Vigezzi Giacomo Pietro , Barbati Chiara , Blandi Lorenzo , Guddemi Annalisa , Melloni Andrea , Salvati Simone , Bertoglio Luca , Odone Anna ,   on behalf of the HTA PRO-ENDO commission investigators
Published: January 2024

Objective:

To provide an updated systematic review and meta-analysis with meta-regression of safety and efficacy of fenestrated/branched endovascular repair of thoracoabdominal aortic aneurysms (TAAAs) compared with open repair.

Summary Background Data:

Endovascular repair of TAAAs may be a promising alternative to open surgery by reducing invasiveness and expanding the eligible population, but evidence remains limited.

Methods:

We applied PRISMA to retrieve, quantitatively pool, and critically evaluate the efficacy and safety (including 30-day mortality, reintervention, spinal cord injury, SCI, and renal injury) of both approaches. Original studies were retrieved from PubMed, Embase and Cochrane Library until 20 April 2022, excluding papers reporting less than 10 patients. Pooled proportions and means were determined using a random-effects model. Heterogeneity between studies was evaluated with I2statistics.

Results:

Sixty-four studies met the pre-defined inclusion criteria. Endovascular cohort patients were older and had higher rates of comorbidities. Endovascular repair was associated with similar proportions of mortality (0.07, 95% confidence interval, CI, 0.06-0.08) compared with open repair (0.09, 95%CI 0.08-0.12;P-value=0.22), higher proportions of reintervention (0.19, 95%CI 0.13-0.26, vs. 0.06, 95%CI 0.04-0.10;P-value<0.01), similar proportions of transient SCI (0.07, 95%CI 0.05-0.09, vs. 0.06, 95%CI 0.05-0.08;P-value=0.28), lower proportions of permanent SCI (0.04, 95%CI 0.03-0.05, vs. 0.06, 95%CI 0.05-0.07;P-value<0.01) and renal injury (0.08, 95%CI 0.06-0.10, vs. 0.13, 95%CI 0.09-0.17;P-value=0.02). Results were affected by high heterogeneity and potential publication bias.

Conclusions:

Despite these limitations and the lack of randomised trials, this meta-analysis suggests that endovascular TAAA repair could be a safer alternative to the open approach.
Randomized Prospective Trial of Epidural Analgesia after Open Hepatectomy
Authors: Arslan-Carlon Vittoria , Qadan Motaz , Puttanniah Vinay , Seier Kenneth , Gönen Mithat , Yang Gloria , Fischer Mary , DeMatteo Ronald P. , Kingham T. Peter , Jarnagin William R. , D’Angelica Michael I.
Published: January 2024

Objective:

To evaluate whether patient-controlled epidural analgesia (PCEA) improves postoperative pain during ambulation following elective open hepatectomy.

Background:

Strategies to alleviate postoperative pain are a critical element of recovery after surgery. However, the optimal postoperative pain management strategy following open hepatectomy remains unclear.

Methods:

We conducted a prospective, non-blinded, randomized comparison of PCEA (intervention) vs. intravenous patient-controlled analgesia (IV PCA; control) for postoperative pain following elective open hepatectomy. The primary endpoint was pain during ambulation on postoperative day (POD) 2. The study was powered to detect a clinically significant 2-point difference on pain numeric rating scale (NRS). Secondary endpoints included pain at rest, morbidity, time to return of bowel function, and length of stay.

Results:

From 2015-2020, 231 patients were randomized (116 patients in the PCEA arm and 115 in the IV PCA arm). The incidence of epidural failure was 3% (n=4/116), with no epidural-related complications. Patients in the PCEA arm had a <2 point difference in NRS pain scores during ambulation on POD 2 vs. IV PCA (median 4.0 vs. 5.0, P<0.001). There was no difference in overall complications between the PCEA and IV PCA arms (33% vs. 40%, P=0.276). Secondary outcomes, including pain scores at rest, were similar between the study arms.

Conclusions:

PCEA was safe following open hepatectomy and was associated with a small difference in pain with activity on POD 2 that did not reach our pre-specified definition of clinical significance.
Psychometric Properties and Cutoff Value of the Turkish Overactive Bladder Symptom Score
Authors: Baran Emine , Gürşen Ceren , Ozgul Serap , Çinar Gamze Nalan , Nakip Gulbala , Üzelpasaci Esra , Ozgul Nejat , Beksaç Mehmet Sinan , Akbayrak Türkan
Published: January 2024

Importance

The Overactive Bladder Symptom Score (OABSS) measures all overactive bladder (OAB) symptoms with graded answers, evaluates urgency symptoms, and reveals the subjective bladder control. However, the Turkish version and the cutoff value of the questionnaire have not yet been studied.

Objective

The aims of this study were to determine the psychometric properties of the 7-item OABSS and to estimate the cutoff value of the scale.

Study Design

This was an observational study. The internal consistency (Cronbach α) and test-retest reliability were analyzed, and exploratory factor analysis was performed. For the criterion validity, the correlations between the OABSS, the Overactive Bladder Questionnaire, the Bristol Female Lower Urinary Tract Symptoms questionnaire, and outcomes of a bladder diary were used. The cutoff value of the OABSS was analyzed by the receiver operating characteristics curve analysis.

Results

Participants with (n = 49) and without (n = 38) OAB were included. The internal consistency was very strong (Cronbach α = 0.95). The test-retest reliability was very strong (intraclass correlation coefficients = 0.93–0.95, P = 0.001). The percentage of explanation of the total variance was calculated as 78%. There was a strong to very strong correlation between the OABSS and the Overactive Bladder Questionnaire and Bristol Female Lower Urinary Tract Symptoms scores and outcomes of the bladder diary. The cutoff value for the OABSS was determined as 10.5.

Conclusions

The Turkish OABSS was found to be a valid and reliable scale to determine OAB symptoms and severity. Those who score more than 10.5 on the questionnaire can be considered as at risk of OAB syndrome.
Barbed Versus Nonbarbed Suture for Posterior Colporrhaphy: A Randomized Controlled Trial
Authors: Merriman Amanda L. , Burrell Aletheia D. , Winn Heather , Anderson William E. , Tarr Megan E. , Myers Erinn M.
Published: January 2024

Importance

There is limited literature or even consensus on the suture material used for posterior vaginal repairs.

Objectives

This study aimed to compare outcomes of barbed versus nonbarbed delayed absorbable suture used for posterior colporrhaphy.

Study Design

This study conducted a randomized controlled trial of 72 women undergoing posterior repair using standardized technique—concurrent procedures permitted with barbed (n = 36) or nonbarbed (n = 36) suture. Standardized examinations, validated questionnaires, and a visual analog scale (VAS) were completed at baseline, 6 weeks, and 12 months, and a telephone interview was conducted at 6 months. The primary outcome was posterior compartment pain at 6 weeks, measured by a VAS.

Results

Seventy-two women enrolled, with follow-up rates 6 weeks (100%), 6 months (90.3%), and 12 months (73.6%). Demographics were similar between groups. A VAS with movement was not different between groups at 6 weeks. The odds of experiencing vaginal pain, having myofascial pain on examination, or being sexually active postoperatively were not different between the groups. There were no differences in the length of posterior colporrhaphy, surgical times, or hospital length of stay between the groups. Suture passes were lower in the nonbarbed group (median, 4 vs 7; P = <0.001), and suture burden was higher in the nonbarbed group (median, 26.9 vs 10.5 cm; P = <0.001). There was overall improvement in Pelvic Floor Distress Inventory Short Form 20 prolapse and colorectal subscores but no differences between groups. Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire Short Form 12 scores improved, and dyspareunia decreased at 6 and 12 months in both groups. In addition, there were few anatomic recurrences at 6 weeks (0%) and 12 months (3.4%) and few adverse events.

Conclusions

This study found no differences in primary or secondary outcomes; however, both suture types resulted in clinical improvements in quality-of-life measures and sexual function.
Association Between Maternal Depression and Lower Urinary Tract Symptoms in Their Primary School-Age Daughters
Authors: Cunningham Shayna D. , Lindberg Sarah , Joinson Carol , Shoham David , Chu Haitao , Newman Diane , Epperson Neill , Brubaker Linda , Low Lisa Kane , Camenga Deepa R. , LaCoursiere D. Yvette , Meister Melanie , Kenton Kimberly , Sutcliffe Siobhan , Markland Alayne D. , Gahagan Sheila , Coyne-Beasley Tamera , Berry Amanda
Published: January 2024

PURPOSE:

Although maternal depression is associated with adverse outcomes in women and children, its relationship with lower urinary tract symptoms (LUTS) in offspring is less well-characterized. We examined the association between prenatal and postpartum maternal depression and LUTS in primary school-age daughters.

DESIGN:

Observational cohort study.

SUBJECTS AND SETTING:

The sample comprised 7148 mother-daughter dyads from the Avon Longitudinal Study of Parents and Children.

METHOD:

Mothers completed questionnaires about depressive symptoms at 18 and 32 weeks' gestation and 21 months postpartum and their children's LUTS (urinary urgency, nocturia, and daytime and nighttime wetting) at 6, 7, and 9 years of age. Multivariable logistic regression models were used to estimate the association between maternal depression and LUTS in daughters.

RESULTS:

Compared to daughters of mothers without depression, those born to mothers with prenatal and postpartum depression had higher odds of LUTS, including urinary urgency (adjusted odds ratio [aOR] range = 1.99-2.50) and nocturia (aOR range = 1.67-1.97) at 6, 7, and 9 years of age. Additionally, daughters born to mothers with prenatal and postpartum depression had higher odds of daytime wetting (aOR range = 1.81-1.99) and nighttime wetting (aOR range = 1.63-1.95) at 6 and 7 years of age. Less consistent associations were observed for depression limited to the prenatal or postpartum periods only.

CONCLUSIONS:

Exposure to maternal depression in the prenatal and postpartum periods was associated with an increased likelihood of LUTS in daughters. This association may be an important opportunity for childhood LUTS prevention. Prevention strategies should reflect an understanding of potential biological and environmental mechanisms through which maternal depression may influence childhood LUTS.
Evaluation of a Skin Barrier Ring With Assisted Flow
Authors: Colwell Janice C. , Pittman Joyce , Rider Paul , Purtill Helen , Duckworth Taylor
Published: January 2024

PURPOSE:

The purpose of this study was to assess the effect of a skin barrier ring with assisted flow in preventing peristomal skin complications (PSCs) in patients with an ileostomy and to evaluate the participants' perceptions of the device.

DESIGN:

Single-group, prospective cohort study.

SUBJECTS AND SETTING:

Both inpatients and outpatients with newly created (n = 14) or established (n = 1) ileostomies were recruited from 2 clinical sites in the United States: one was an academic teaching hospital system in the Midwestern United States and the second was a teaching hospital located in the Southeastern United States.

METHODS:

Participants used the skin barrier ring with assisted flow after receiving education on its use. The pouching system was changed on a routine basis as determined by the ostomy nurse specialist. The Ostomy Skin Tool (OST) was used to assess each participant's peristomal discoloration (D), erosion (E), and tissue overgrowth (T) on admission to the study (baseline) and at final assessment (60 ± 33 days). Secondary outcomes (device handling, comfort, and discretion) were assessed through a questionnaire administered during the final data collection visit.

RESULTS:

The mean baseline DET score among the 14 participants with a new ileostomy was 2 or less, indicating no PSCs. The incidence of PSCs in this study was 40% (n = 6). Thirteen of 15 participants (86.7%) agreed that the skin barrier ring with assisted flow was easy to apply. Fourteen (93.4%) agreed that the device was comfortable and easy to remove. All 15 participants (100%) agreed it was discreet under clothing.

CONCLUSIONS:

Sixty percent of participants (n = 9) using the investigational device experienced a PSC. More than 90% of participants agreed that the device was comfortable and easy to remove, and all participants (100%) agreed it was discreet when worn under clothing.
Detecting Early-Stage Pressure Injury in Patients With Dark Skin Tones Using an Enhanced Physical Assessment Technique and Halogen Lighting
Authors: Waidley Monica , Taylor Nikki , Shever-Doletzky Leah L.
Published: January 2024

PURPOSE:

The purpose of this quality improvement project was to identify stage 1 pressure injuries (PIs) in patients with darker skin tones using an enhanced skin assessment (Skin Assessment for Dark Skin, SADS) and halogen lighting.

PARTICIPANTS AND SETTING:

This quality improvement project was conducted on 3 units at a large university teaching hospital in Southeast Michigan. The project was originally designed so that participating patients were identified by bedside nurses as having sufficient melanin to obscure blanching on the hand/forearm using regular lighting, but this goal was not met. Data analysis is based on patients who self-identified as African American or Black, Native Hawaiian or Pacific Islander, Asian, American Indian, and Native Alaskan. Bedside nurses participating in this project were also asked to complete a questionnaire describing their knowledge and experiences with this project and assessment of early-stage PI in patients with darker skin tones.

APPROACH:

The Iowa Model of Evidence-Based Practice was used to guide this quality improvement initiative. Following a trigger event, we reviewed pertinent literature and developed an enhanced technique for assessing patients with darker skin tones that involved use of halogen lighting (SADS) and documentation of findings. We selected units from our facility and taught nurses to apply the SADS approach. Data from the electronic medical record and a survey of participating nurses were used to compare findings before and after project implementation. Comparisons were based on descriptive data analysis.

OUTCOMES:

Following implementation of the enhanced physical assessment, the participating units experienced a 6% decrease in the total number of facility-acquired PIs during the implementation period.

IMPLICATIONS FOR PRACTICE:

The enhanced physical assessment, when paired with halogen lighting, enhanced identification of stage 1 PI in persons with dark skin. The assessment method was easy to teach, learn, and can be performed at the bedside as part of a shift assessment which routinely includes inspection of skin.
Determinants of Bladder Care at Night in a Subacute Ward for Aged Patients
Authors: Brown Adelle , Ferguson Laura , Castillo Jasper , Nguyen Huong Xuan Thi , Ervin Claire , Whishaw David Michael , Bower Wendy
Published: January 2024

PURPOSE:

The purpose of this study was to evaluate how bladder care at night correlates to patients' mobility status.

DESIGN:

This was an observational study.

SUBJECTS AND SETTING:

The sample comprises 63 aged care subacute patients who were observed over 3 consecutive nights in an inpatient subacute aged care ward located in Melbourne, Australia. Half of the participants were female; their mean age was 82.0 (standard deviation 8.2) years. Data were collected from December 2020 to March 2021.

METHODS:

Outcome variables included demographic and pertinent clinical characteristics, type and timing of toileting and/or bladder care provided, and mobility classification. Descriptive statistics were used to summarize the frequency of nocturnal bladder care provided each night and as a mean over the 3 nights. The relationship between the type of care units provided and other variables was explored using a 1-way analysis of variance; values ≤.05 were deemed statistically significant.

RESULTS:

Findings indicate that 27% (n = 17), 41% (n = 26), and 48% (n = 30) of participants required assistance to move in bed, sit up in bed, and stand from sitting, respectively. Care episodes for both incontinence and assistance with voiding were significantly associated with functional mobility in bed (F = 5.52, P < .001; F = 2.14, P = .02) and with ambulation independence (F = 3.52, P = .001; F = 2.04, P = .03) but not with age or ambulation distance.

CONCLUSIONS:

Care provided for urinary incontinence during the night was related to the need for physical support of ambulation and poor mobility in bed. Targeted input from a multidisciplinary team is warranted to facilitate change of practice at night.
Turtle species and ecology drive carapace microbiome diversity in three seasonally interconnected wetland habitats
Authors: Parks Matthew , Lee Jun Sheng , Camua Kassandra , Hollender Ethan
Published: January 2024

Different species of freshwater turtles exhibit primary behaviours ranging from aerial basking to benthic bottom-walking, cycle between wet and dry conditions at different time intervals, and undertake short-distance overland movements between aquatic habitats. These behaviours in turn may impact the accumulation of microbes on external shell surfaces of turtles and provide novel niches for differentiation of microbial communities. We assessed microbial diversity using 16S and 18S rRNA metabarcoding on carapace surfaces of six species of freshwater turtles residing in three adjacent and seasonally interconnected wetland habitats in southeast Oklahoma (United States). Communities were highly diverse, with nearly 4200 prokaryotic and 500 micro-eukaryotic amplicon sequence variants recovered, and included taxa previously reported as common or differentially abundant on turtle shells. The 16S rRNA alpha diversity tended to be highest for two species of benthic turtles, while 18S rRNA alpha diversity was highest for two basking and one shallow-water benthic species. Beta diversity of communities was more strongly differentiated by turtle species than by collection site, and ordination patterns were largely reflective of turtle species’ primary habits (i.e. benthic, basking, or benthic-basking). Our data support that freshwater turtles could play a role in microbial ecology and evolution in freshwater habitats and warrant additional exploration including in areas with high native turtle diversity and inter-habitat turtle movements.
Hybrid assembly improves identification of multilocus sequence types and antimicrobial resistance genes of Staphylococcus aureus isolated from Vermont dairy farms
Authors: Chakrawarti Ashma , Eckstrom Korin , Laaguiby Pheobe , Barlow John
Published: January 2024

Antimicrobial resistance (AMR) in Staphylococcus aureus is a pressing public health challenge with significant implications for the dairy industry, encompassing bovine mastitis concerns and potential zoonotic threats. To delve deeper into the resistance mechanisms of S. aureus, this study employed a hybrid whole genome assembly approach that synergized the precision of Illumina with the continuity of Oxford Nanopore. A total of 62 isolates, collected from multiple sources from Vermont dairy farms, were sequenced using the GridION Oxford Nanopore platform and the Illumina platform, and subsequently processed through our specialized bioinformatics pipeline. Our analyses showcased the hybrid-assembled genome's superior completeness compared to Oxford Nanopore-only or Illumina-only assembled genomes. Furthermore, the hybrid assembly accurately determined multilocus sequence typing (MLST) strain types across all isolates. The comprehensive probe for antibiotic resistance genes (ARGs) using databases like CARD, Resfinder, and MEGARES 2.0 characterized AMR in S. aureus isolates from Vermont dairy farms, and revealed the presence of notable resistance genes, including beta-lactam genes blaZ, blaI, and blaR. In conclusion, the hybrid assembly approach emerges as a tool for uncovering the genomic nuances of S. aureus isolates collected from multiple sources on dairy farms. Our findings offer a pathway for detecting AMR gene prevalence and shaping AMR management strategies crucial for safeguarding human and animal health.
Ramoplanin as a novel therapy for Neisseria gonorrhoeae infection: an in vitro and in vivo study in Galleria mellonella
Authors: Gestels Zina , De Baetselier Irith , Abdellati Said , Manoharan-Basil Sheeba Santhini , Kenyon Chris
Published: January 2024

Neisseria gonorrhoeae

is a bacterial pathogen that causes gonorrhoea, a sexually transmitted infection. Increasing antimicrobial resistance in

N. gonorrhoeae

is providing motivation to develop new treatment options. In this study, we investigated the effectiveness of the antibiotic ramoplanin as a treatment for

N. gonorrhoeae

infection. We tested the effectiveness of ramoplanin in vitro against 14 World Health Organization (WHO) reference strains of

N. gonorrhoeae

and found that it was active against all 14 strains tested. Furthermore, in a Galleria mellonella infection model of

N. gonorrhoeae

WHO P, we demonstrated that ramoplanin was active in vivo without any evidence of toxicity. This suggests that ramoplanin might be a new promising antibiotic treatment for gonorrhoea.
Size spectra in freshwater streams are consistent across temperature and resource supply
Authors: Gjoni Vojsava , Pomeranz Justin P. F. , Junker James R. , Wesner Jeff S.
Published: January 2024

The study explores the individual size distribution (ISD) pattern in ecological communities, characterized by a negative correlation between individual body size and abundance (N ∼ Mλ). The parameter λ denotes the rate of decline in relative abundance from small to large individuals. Despite known influences of temperature and resource availability on body size, their effects on λ remain diverse. Leveraging data from 2.4 million individual body sizes in continental freshwater streams, the research the hypothesis that λ varies as a function of temperature and resource supply. Surprisingly, despite varied environmental conditions and complete species turnover, minimal variation in λ (mean = −1.2, sd = 0.04) was observed, with no discernible impact from temperature or resource supply. The unexpected λ value of −1.2 suggests a higher-than-expected relative abundance of large individuals, challenging assumptions of metabolic scaling at 0.75 and implying large subsidy inputs to large predators. Simulation and mesocosm experiments support a metabolic scaling coefficient of ∼0.4 for freshwater macroinvertebrates. The findings underscore remarkable consistency of individual size distributions in freshwater streams, likely driven by shallow metabolic scaling and large subsidies to large consumers.
Generative modeling of biological shapes and images using a probabilisticα-shape sampler
Authors: Winn-Nuñez Emily T. , Witt Hadley , Bhaskar Dhananjay , Huang Ryan Y. , Reichner Jonathan S. , Wong Ian Y. , Crawford Lorin
Published: January 2024

Understanding morphological variation is an important task in many areas of computational biology. Recent studies have focused on developing computational tools for the task of sub-image selection which aims at identifying structural features that best describe the variation between classes of shapes. A major part in assessing the utility of these approaches is to demonstrate their performance on both simulated and real datasets. However, when creating a model for shape statistics, real data can be difficult to access and the sample sizes for these data are often small due to them being expensive to collect. Meanwhile, the current landscape of generative models for shapes has been mostly limited to approaches that use black-box inference—making it difficult to systematically assess the power and calibration of sub-image models. In this paper, we introduce theα-shape sampler: a probabilistic framework for generating realistic 2D and 3D shapes based on probability distributions which can be learned from real data. We demonstrate our framework using proof-of-concept examples and in two real applications in biology where we generate (i) 2D images of healthy and septic neutrophils and (ii) 3D computed tomography (CT) scans of primate mandibular molars. Theα-shape sampler R package is open-source and can be downloaded athttps://github.com/lcrawlab/ashapesampler.

Author Summary

Using shapes and images to understand genotypic and phenotypic variation has proven to be an effective strategy in many biological applications. Unfortunately, shape data can be expensive to collect and, as a result, sample sizes for analyses are often small. Despite methodological advancements in shape statistics and machine learning, benchmarking standards for evaluating new computational tools via data simulation is still underdeveloped. In this paper, we present a probability-based pipeline called theα-shape sampler which has the flexibility to generate new and unobserved shapes based on an input set of data. We extensively evaluate the generative capabilities of our pipeline using 2D cellular images of neutrophils and 3D mandibular molars from two different suborders of primates.
Pseudo-spectral angle mapping for automated pixel-level analysis of highly multiplexed tissue image data
Authors: Durkee Madeleine S. , Ai Junting , Casella Gabriel , Cao Thao , Chang Anthony , Halper-Stromberg Ariel , Jabri Bana , Clark Marcus R. , Giger Maryellen L.
Published: January 2024

The rapid development of highly multiplexed microscopy systems has enabled the study of cells embedded within their native tissue, which is providing exciting insights into the spatial features of human disease [1]. However, computational methods for analyzing these high-content images are still emerging, and there is a need for more robust and generalizable tools for evaluating the cellular constituents and underlying stroma captured by high-plex imaging [2]. To address this need, we have adapted spectral angle mapping – an algorithm used widely in hyperspectral image analysis – to compress the channel dimension of high-plex immunofluorescence images. As many high-plex immunofluorescence imaging experiments probe unique sets of protein markers, existing cell and pixel classification models do not typically generalize well. Pseudospectral angle mapping (pSAM) uses reference pseudospectra – or pixel vectors – to assign each pixel in an image a similarity score to several cell class reference vectors, which are defined by each unique staining panel. Here, we demonstrate that the class maps provided by pSAM can directly provide insight into the prevalence of each class defined by reference pseudospectra. In a dataset of high-plex images of colon biopsies from patients with gut autoimmune conditions, sixteen pSAM class representation maps were combined with instance segmentation of cells to provide cell class predictions. Finally, pSAM detected a diverse set of structure and immune cells when applied to a novel dataset of kidney biopsies imaged with a 43-marker panel. In summary, pSAM provides a powerful and readily generalizable method for evaluating high-plex immunofluorescence image data.

Significance Statement

Understanding the cellular constituents captured by highly multiplexed tissue imaging is a major limitation affecting the usability of these novel imaging methods. Many imaging experiments have uniquely designed staining panels, reducing the generalizability of cell classification models to new datasets. We present pseudospectral angle mapping (pSAM), which can compress high-dimensional image data into class representations. We demonstrate that the class representations generated by pSAM can be used to interpret high-plex image data and guide cell classification. Importantly, we also demonstrate that pSAM can generalize to new image datasets—collected with a different staining panel in samples from different tissues—without manual image annotation, subjective intensity gating, or re-training an algorithm.
Human Brain Mapping of Homotopic Functional Affinity
Authors: Chen Li-Zhen , Zuo Xi-Nian
Published: January 2024

Spatially corresponding areas in the left and right hemispheres of the human brain, also known as homotopic brain regions, often exhibit functional similarities, i.e., functional homotopy. To understand the principles and mechanisms of functional homotopy in human psychological behavior, this paper proposes a method for studying functional homotopy in the human brain: homotopic functional affinity. This method quantifies the functional affinity of homotopic brain regions by calculating the cosine distance of whole-brain functional connectivity patterns of homotopic regions. Using the whole-brain functional MRI database from the Human Connectome Project in the United States and China, we first mapped the homotopic functional affinity atlas with “700 milliseconds - 2 millimeters” spatiotemporal precision, assessing its test-retest reliability for individual differences. Subsequently, we located three specific areas in the human temporo-parietal junction through systematic analysis of this atlas, discovering their hemispheric lateralization patterns and revealing their functional associations with attention, language, and social cognition. Lastly, through multimodal brain atlas correlation calculations, we further explored the correlation of human brain homotopic functional affinity with genetics, evolution, structural, and functional organizational distribution. In summary, our proposed method of homotopic functional affinity provides a reliable and valid functional measurement atlas for population neuroscience research.
Efficacy of dynamic eigenvalue in anticipating and distinguishing tipping points†
Authors: Kulkarni Kaustubh , Deb Smita , Dutta Partha Sharathi
Published: January 2024

The presence of tipping points in several natural systems necessitates having improved early warning indicators to provide accurate signals of an impending transition to a contrasting state while also detecting the type of transition. Various early warning signals (EWSs) have been devised to forecast the occurrence of tipping points, also called critical transitions. Dynamic eigenvalue (DEV) is a recently proposed EWS that can not only predict the occurrence of a transition but also certain types of accompanying bifurcations. Here, we study the effectiveness and limitations of DEV as an EWS for diverse kinds of critical phenomena. We demonstrate that DEV is a powerful EWS that shows promising results in anticipating catastrophic (first-order or discontinuous) and non-catastrophic (second-order or continuous) transitions in discrete and continuous dynamical systems. However, it falls short in the case of piecewise smooth systems. Further, the ability of DEV to forecast the type of transition is limited, as it cannot differentiate saddle-node bifurcation from transcritical and pitchfork bifurcations. Despite these limitations, we show that DEV can work as a robust indicator for varying rates at which the transition is approached and with systems involving colored noise.
Analysis of the Time-Dependent Behaviors of Atrial Fibrillation with Electrographic Flow Mapping
Authors: Haines David E. , Kong Melissa H. , Ruppersberg Peter , Castellano Steven , Spitzer Stefan G. , Noelker Georg , Rillig Andreas , Szili-Torok Tamas
Published: January 2024

Background

Electrographic flow (EGF) mapping algorithms employing Horn-Schunck flow estimations can create temporospatial visualizations of atrial electrical wavefront propagations during atrial fibrillation (AF). Reproducible patterns of centrifugal EGF activation from discrete sites may represent sites of AF origin or sources. Our objectives were to assess the patterns and prevalence of AF sources using EGF mapping.

Methods

Unipolar electrograms were recorded for 1-minute with 64-pole basket catheters. Flow estimates were constructed by passing consecutive frames through an algorithm to learn and then compare typical wave direction patterns to describe flow-field evolution. During each 2-second segment, sites initiating centrifugal activation patterns were defined as AF sources. Maps of source location/activity duration were generated.

Results

The EGF method was applied to 405 prospective and retrospective patients with persistent or long-standing persistent AF. Mean age 62.5 years; mean LA size 54 mm; mean AF duration 4.6 years. EGF mapping found 6.6 ± 2.4 AF sources/patient (range 1 to 17). Distribution was 55% LA and 45% RA. Dominant sources (prevalence ≥20%) were demonstrated in 185 (45.7%) patients, but only 10.7% of all sources were dominant. While AF cycle length (CL) was not affected by source prevalence, CL variance significantly decreased as source prevalence increased.

Conclusions

Complex AF conduction patterns make ablation challenging, but EGF mapping enables detection and organization of time-dependent AF behaviors. Although many low prevalence sources are detected, they may not be clinically relevant, while higher prevalence sources seem to modulate AF. Recording durations of 1 minute facilitate source discrimination.
A cross-sectional questionnaire study: impaired awareness of hypoglycaemia remains prevalent in adults with type 1 diabetes and is associated with the risk of severe hypoglycaemia
Authors: Baxter F. , Baillie N. , Dover A. , Stimson R.H. , Gibb F. , Forbes S.
Published: January 2024

Objective

Impaired awareness of hypoglycaemia (IAH) is a risk factor for severe hypoglycaemia (SH) in type 1 diabetes (T1D). Much of the IAH prevalence data comes from older studies where participants did not have the benefit of the latest insulins and technologies. This study surveyed the prevalence of IAH and SH in a tertiary adult clinic population and investigated the associated factors.

Methods

Adults (≥18 years) attending a tertiary T1D clinic completed a questionnaire, including a Gold and Clarke score. Background information was collected from health records.

Results

189 people (56.1% female) with T1D (median [IQR] disease duration 19.3 [11.5, 29.1] years and age of 41.0 [29.0, 52.0] years) participated. 17.5% had IAH and 16.0% reported ≥1 episode of SH in the previous 12 months. Those with IAH were more likely to report SH (37.5% versus 11.7%, p=0.001) a greater number of SH episodes per person (median [IQR] 0 [0,2] versus 0 [0,0] P<0.001) and be female (72.7% versus 52.6%, p=0.036). Socio-economic deprivation was associated with IAH (p=0.032) and SH (p=0.005). Use of technology was the same between IAH vs aware groups, however, participants reporting SH were more likely to use multiple daily injections (p=0.026). Higher detectable C-peptide concentrations were associated with a reduced risk of SH (p=0.04).

Conclusion

IAH remains a risk factor for SH and is prevalent in females. Insulin pump and continuous glucose monitor use was comparable in IAH vs aware groups. Socioeconomic deprivation was associated with IAH and SH, making this an important population to target for interventions.
Primary care access and feasibility of Spatial Accessibility Index (SAI) in assessing primary care in rural Sri Lanka
Authors: Abeyrathna Parami , Agampodi Suneth Buddhika , Weerasinghe Manjula , Samaranayake Shyamalee , Pushpakumara Pahala Hangidi Gedara Janaka
Published: January 2024

Despite decades of global health efforts and policies, inequitable access to primary care in low and middle-income countries remains an ongoing challenge. This study assessed accessibility to curative sector-primary healthcare services in the Anuradhapura district of Sri Lanka in 2020 and 2021. In this study, we included both private and state-owned primary care facilities (PCF) and their corresponding primary care doctors (PCD), covering both allopathic and complementary and alternative medicine (CAM) practices. Spatial locations of private sector PCF of the entire district were collected by conducting a comprehensive road-based survey and documenting information from publicly displayed boards. Data on state PCF were collected from provincial health departments (allopathic and Ayurveda). The Spatial Accessibility Index (SAI) of 657 GND (Grama Niladhari Division: the smallest administrative division) was calculated in ARC-GIS using the 2-Steps-Floating-Catchment-Area method in 5 km and 10 km spatial-distances from a GND. The majority of the PCF were allopathic (n=318, 78%) and belonged to the private sector (n=317, 79%) whereas CAM PCD represented one-fifth of the primary care workforce. Average SAI of 4.50X 10-4and 4.67X 10-4were reported for both 5 km and 10 km spatial-distance. A statistically significant difference in mean SAI was measured between urban and rural populations. The highest SAI were observed from urban populations and it gradually declined towards the rural remotes. The national primary care coverage target of 1 allopathic PCD per 5000 population was achieved only in 64% of the population in a 5 km spatial-distance and it further depleted to 25% with only of state allopathic PCD. SAI was negatively associated with the poverty headcount indices and distance to main roads and the main town (Anuradhapura). While the private allopathic sector is the main primary care provider in this study setting, a significant proportion of the population reported limited primary care access dueto their geographic and economic status. Health policymakers need to address primary care workforce shortages in rural for the planning of human and physical resources. SAI can be recommended as a feasible method for healthcare planning and assessing service coverage in low-facility settings.
Complete absence of GLUT1 does not impair human terminal erythroid differentiation
Authors: Freire CM , King NR , Dzieciatkowska M , Stephenson D , Moura PL , Dobbe J.G.G , Streekstra GJ , D’Alessandro A , Toye AM , Satchwell TJ
Published: January 2024

The Glucose transporter 1 (GLUT1) is one of the most abundant proteins within the erythrocyte membrane and is required for glucose and dehydroascorbic acid (Vitamin C precursor) transport. It is widely recognized as a key protein for red cell structure, function, and metabolism. Previous reports highlighted the importance of GLUT1 activity within these uniquely glycolysis-dependent cells, in particular for increasing antioxidant capacity needed to avoid irreversible damage from oxidative stress in humans. However, studies of glucose transporter roles in erythroid cells are complicated by species-specific differences between humans and mice. Here, using CRISPR-mediated gene editing of immortalized erythroblasts and adult CD34+ hematopoietic progenitor cells, we generate committed human erythroid cells completely deficient in expression of GLUT1. We show that absence of GLUT1 does not impede human erythroblast proliferation, differentiation, or enucleation. This work demonstrates for the first-time generation of enucleated human reticulocytes lacking GLUT1. The GLUT1-deficient reticulocytes possess no tangible alterations to membrane composition or deformability in reticulocytes. Metabolomic analyses of GLUT1-deficient reticulocytes reveal hallmarks of reduced glucose import, downregulated metabolic processes and upregulated AMPK-signalling, alongside alterations in antioxidant metabolism, resulting in increased osmotic fragility and metabolic shifts indicative of higher oxidant stress. Despite detectable metabolic changes in GLUT1 deficient reticulocytes, the absence of developmental phenotype, detectable proteomic compensation or impaired deformability comprehensively alters our understanding of the role of GLUT1 in red blood cell structure, function and metabolism. It also provides cell biological evidence supporting clinical consensus that reduced GLUT1 expression does not cause anaemia in GLUT1 deficiency syndrome.

Key Points

GLUT1 knockout does not affect erythroid differentiation and minimally impacts reticulocyte membrane composition

Metabolic adaptation facilitates reticulocyte tolerance of GLUT1 absence
Cell-cycle dependence of bursty gene expression: insights from fitting mechanistic models to single-cell RNA-seq data
Authors: Sukys Augustinas , Grima Ramon
Published: January 2024

Bursty gene expression is characterised by two intuitive parameters, burst frequency and burst size, the cell-cycle dependence of which has not been extensively profiled at the transcriptome level. In this study, we estimate the burst parameters per allele in the G1 and G2/M cell-cycle phases for thousands of mouse genes by fitting mechanistic models of gene expression to mRNA count data, obtained by sequencing of single cells whose cell-cycle position has been inferred using a deep-learning method. We find that upon DNA replication, the median burst frequency approximately halves, while the burst size remains mostly unchanged. Genome-wide distributions of the burst parameter ratios between the G2/M and G1 phases are wide, indicating substantial heterogeneity in transcriptional regulation patterns. We also observe a significant negative correlation between the burst frequency and size ratios, suggesting that regulatory processes do not independently control the burst parameters. Finally, we argue that to accurately estimate the burst parameter ratios, mechanistic models must explicitly account for gene copy number variation and extrinsic noise due to the coupling of transcription to cell age within the cell cycle, but corrections for technical noise due to imperfect capture of RNA molecules in sequencing experiments are less critical.
The triose phosphate/phosphate translocator exports photosynthetic glyceraldehyde 3-phosphate from chloroplasts to trigger antimicrobial immunity in plants
Authors: Zuo Deng-Pan , Wang Bin , Liu Yu-Zi , Chen Zheng-Song , Hu Ru-Jian , He Meng-Jun , Zhang Zong-Ying , Wang Ying , Han Cheng-Gui
Published: January 2024

Chloroplasts play a crucial role in plant immunity against invading microbes. However, it remains poorly understood whether photosynthetic metabolites from chloroplasts participate directly in host defenses. Here, we uncoveredArabidopsis thalinanatriose phosphate/phosphate translocator (AtTPT), a known translocator for chloroplast inner membrane, plays an indispensable role in suppressing virus infection and evoking defense responses. Interestingly, overexpression of AtTPT impairs virus accumulation in plants, while loss-of-function tpt3 mutants exhibit an increased viral load. The antiviral activity of AtTPT requires its phosphate transport capacity, implying that it actually functions through its metabolite(s). To this end, we found that glyceraldehyde 3-phosphate (GAP), one of AtTPT’s translocated metabolites, can drastically enhance expression of defense-related genes and prominently induce defense signaling pathways. More excitingly, AtTPT or GAP robustly restricts the proliferation of multiple types of phytopathogens. Collectively, we propose that AtTPT exports GAP to mediate broad-spectrum resistance to pathogens, which provides new insights into the mechanism underlying the chloroplast-mediated immunity by a photosynthetic metabolite.
Hebbian activity only temporarily stabilizes synaptic transmission at CA3-CA1 synapses in the developing hippocampus
Authors: Strandberg Joakim , Gustafsson Bengt
Published: January 2024

Prolonged low frequency (0.05-1 Hz) stimulation of previously non-stimulated (naive) CA3-CA1 synapses in the developing hippocampus results in a profound synaptic depression explained by a postsynaptic AMPA silencing. It has been proposed that Hebbian activity can stabilize the synapses by preventing such depression. Using field recordings, we have examined to which extent strong repeated high frequency tetanization simulating Hebbian activity results in such prevention. The tetanization resulted within minutes in a field EPSP potentiation to 150-170% of the naive field EPSP level which remained unaltered if stimulation was suspended. If test pulse stimulation (0.2 Hz) was allowed to continue after the tetanization the field EPSP continuously decreased and was after 2700 stimuli depressed by 75% from the potentiated level. This depression did not differ in relative terms from that induced in naive synapses (by 82% from the naive level). The long-lasting component of this depression revealed by a subsequent 30 min stimulus interruption (by 59% from the potentiated level) did not differ from that of naive synapses (by 66% from the naive level). This equal relative degree of depression of tetanized and naive synapses was also observed following 2700 stimuli at 1 Hz. On the other hand, when examined at earlier time points during the test pulse stimulation (e.g. after 400-900 stimuli) tetanized synapses were less depressed than naive synapses, and the long-lasting depression after 900 stimuli at 1 Hz was only half that observed in naive synapses. This effect of tetanization was observed independently of whether the 1 Hz stimulation was commenced 15 min or 2 hours after the tetanization. In conclusion, while a strong preceding tetanization results in a partial stabilization of transmission at CA3-CA1 synapses in the developing hippocampus, this effect appears only temporary. This temporary effect is not linked to time after tetanization but to the number of low frequency stimuli given.