bluuebunny/crossref_metadata_2025 huggingface dataset:
Do hypoallergenic skincare products contain fewer potential contact allergens?
Authors: Hiranput Siwaporn , McAllister Lucy , Hill Glenda , Yesudian Paul Devakar
Published: December 2023

Personal care products (PCPs) commonly cause allergic contact dermatitis (ACD). Skincare companies often market their products as ‘hypoallergenic’; however, this term is not regulated by industry standards. To determine whether PCPs marketed as hypoallergenic are truly less likely to precipitate ACD, we conducted a study of ingredients found in ‘hypoallergenic PCPs’ from two major UK retailers in 2022. Of 208 products meeting the inclusion criteria, 153 (73.6%) contained at least 1 allergen or related chemical from the British Society for Cutaneous Allergy baseline series, 21 (10.1%) had 2 potential allergens and 4 PCPs (1.9%) had 3 allergens. Cetearyl alcohol was the most common ­allergen identified in leave-on PCPs and parabens in rinse-off products; fragrance was the most frequent related chemical found in 85 PCPs (40.1%). A high prevalence of common allergens was found in hypoallergenic PCPs, suggesting that dermatologists and consumers should be cautious of product ingredients.
X-linked chronic granulomatous disease secondary to skewed X-chromosome inactivation in female patients
Authors: Zhang Yue , Shu Zhou , Li Yan , Piao Yurong , Sun Fei , Han Tongxin , Wang Tianyou , Mao Huawei
Published: December 2023

Background

Chronic granulomatous disease (CGD) is a heterogeneous primary immunodeficiency. X-linked (XL) CGD caused by gene defects of CYBB is the most prevalent type of CGD.

Objective

We aim to understand the clinical and molecule features of XL-CGD secondary to skewed X-chromosome inactivation (XCI) in female.

Methods

We retrospectively reviewed the medical records of a female patient diagnosed with XL-CGD. Flow cytometry was used to detect the respiratory burst function. After restriction enzyme digestion of DNA, XCI was calculated by detecting fluorescent PCR products with capillary electrophoresis. The previously published female XL-CGD cases secondary to skewed XCI was summarized.

Results

Clinical data were available for 15 female subjects. The median age of diagnosis was 16 years. Consistent with XL-CGD in males, infection was the most frequent manifestation in the female patients. Catalase-positive pathogens including Serratia marcescens and Staphylococcus aureus infections were the most common pathogens. Autoimmune/autoinflammation manifestations were observed in five patients. Dihydrorhodamine (DHR) assay showed that median %DHR+ values were 6.5% and the values varying with age were observed in 2 patients. All patients had a skewing XCI and there was no consistency between the daughter and carrier mother. Anti-infective treatment was effective in majority and there was no mortality reported in XL-CGD female patients to date.

Conclusion

XL-CGD should not be neglected in female patients manifested as CGD phenotype and it is necessary to make periodic clinical evaluation of CGD female carriers as the neutrophil oxidative function may decline with aging and increase the risk for infection.
Investigating dysregulation of TGF-β1/SMAD3 signaling in atopic dermatitis: a molecular and immunohistochemical analysis
Authors: Shafi Tabasum , Rasool Wani Roohi , Hussain Showkat , Bhat Imtiyaz A , Makhdoomi Rumana , Bashir Sheikh Adil , Hassan Iffat , Shah Zafar A
Published: December 2023

Atopic dermatitis (AD) is a persistent and recurring inflammatory condition affecting the skin. An expanding corpus of evidence indicates the potential participation of transforming growth factor-β1 (TGF-β1) in the modulation of inflammation and tissue remodeling in AD. The primary objective of this study was to examine the aberrant modulation of TGF-β1/small mothers against decapentaplegic homolog 3 (SMAD3) signaling through a comprehensive analysis of their molecular and protein expression profiles. The study encompassed an aggregate of 37 participants, which included 25 AD patients and 12 controls. The assessment of mRNA and protein levels of TGF-β1 and SMAD3 was conducted utilizing quantitative real-time PCR and immunohistochemistry (IHC), whereas serum IgE and vitamin D levels were estimated by ELISA and chemiluminescence, respectively. Quantitative analysis demonstrated a 2.5-fold upregulation of TGF-β1 mRNA expression in the lesional AD skin (P < 0.0001). IHC also exhibited a comparable augmented pattern, characterized by moderate to strong staining intensities. In addition, TGF-β1 mRNA showed an association with vitamin D deficiency in serum (P < 0.02), and its protein expression was linked with the disease severity (P < 0.01) Furthermore, a significant decrease in the expression of the SMAD3 gene was observed in the affected skin (P = 0.0004). This finding was further confirmed by evaluating the protein expression and phosphorylation of SMAD3, both of which exhibited a decrease. These findings suggest that there is a dysregulation in the TGF-β1/SMAD3 signaling pathway in AD. Furthermore, the observed augmentation in mRNA and protein expression of TGF-β1, along with its correlation with the disease severity, holds considerable clinical significance and emphasizes its potential role in AD pathogenesis.
Sicilian semi- and supercentenarians: age-related Tγδ cell immunophenotype contributes to longevity trait definition
Authors: Ligotti Mattia Emanuela , Accardi Giulia , Aiello Anna , Calabrò Anna , Caruso Calogero , Corsale Anna Maria , Dieli Francesco , Di Simone Marta , Meraviglia Serena , Candore Giuseppina
Published: December 2023

The immune system of semi- (from ≥105 to <110 years old) and supercentenarians (≥110 years old), i.e. oldest centenarians, is thought to have characteristics that allow them to reach extreme longevity in relatively healthy status. Thus, we investigated variations of the two principal subsets of Tγδ, Vδ1, and Vδ2, and their functional subsets using the markers defining Tαβ cells, i.e. CD27, CD45RA, in a cohort of 28 women and 26 men (age range 19–110 years), including 11 long-living individuals (from >90 years old to<105 years old), and eight oldest centenarians (≥105 years old), all of them were previously analysed for Tαβ and NK cell immunophenotypes on the same blood sample collected on recruitment day. Naïve Vδ1 and Vδ2 cells showed an inverse relationship with age, particularly significant for Vδ1 cells. Terminally differentiated T subsets (TEMRA) were significantly increased in Vδ1 but not in Vδ2, with higher values observed in the oldest centenarians, although a great heterogeneity was observed. Both naïve and TEMRA Vδ1 and CD8+ Tαβ cell values from our previous study correlated highly significantly, which was not the case for CD4+ and Vδ2. Our findings on γδ TEMRA suggest that these changes are not unfavourable for centenarians, including the oldest ones, supporting the hypothesis that immune ageing should be considered as a differential adaptation rather than a general immune alteration. The increase in TEMRA Vδ1 and CD8+, as well as in NK, would represent immune mechanisms by which the oldest centenarians successfully adapt to a history of insults and achieve longevity.
From Evidence to Effectiveness: Implications of the Randomized Trial to Prevent Vascular Events in HIV Study for People With HIV in Low- and Middle-Income Settings
Authors: Manne-Goehler Jennifer , Ali Mohammed K , Flood David , Marconi Vincent C , Venter Willem D F , Siedner Mark J
Published: December 2023

The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) study found a 35% reduction in major adverse cardiovascular events for people with human immunodeficiency virus who received daily pitavastatin. However, how this evidence will change practice is far from certain. Here, we outline evidence gaps and political and healthcare delivery challenges that will need to be addressed for REPRIEVE to offer public health benefits in low- and middle-income countries.
MAESTRO-Pool Enables Highly Parallel and Specific Mutation-Enrichment Sequencing for Minimal Residual Disease Detection in Cohort Studies
Authors: Blewett Timothy , Rhoades Justin , Liu Ruolin , Xiong Kan , Sridhar Sainetra , Crnjac Andjela , Cheng Ju , Lawless Aleigha R , Frederick Dennie T , Flaherty Keith T , Makrigiorgos Gerassimos Mike , Adalsteinsson Viktor A
Published: December 2023

Background

Tracing patient-specific tumor mutations in cell-free DNA (cfDNA) for minimal residual disease (MRD) detection is promising but challenging. Assaying more mutations and cfDNA stands to improve MRD detection but requires highly accurate, efficient sequencing methods and proper calibration to prevent false detection with bespoke tests.

Methods

MAESTRO (Minor Allele Enriched Sequencing Through Recognition Oligonucleotides) uses mutation-specific oligonucleotide probes to enrich cfDNA libraries for tumor mutations and enable their accurate detection with minimal sequencing. A new approach, MAESTRO-Pool, which entails pooling MAESTRO probes for all patients and applying these to all samples from all patients, was used to screen for 22 333 tumor mutations from 9 melanoma patients in 98 plasma samples. This enabled quantification of MRD detection in patient-matched samples and false detection in unmatched samples from other patients. To detect MRD, a new dynamic MRD caller was used that computes a probability for MRD detection based on the number of mutations and cfDNA molecules sequenced, thereby calibrating for variations in each bespoke test.

Results

MAESTRO-Pool enabled sensitive detection of MRD down to 0.78 parts per million (ppm), reflecting a 10- to 100-fold improvement over existing tests. Of the 8 MRD positive samples with ultra-low tumor fractions <10 ppm, 7 were either in upward-trend preceding recurrence or downward-trend aligning with response. Of 784 patient-unmatched tests, only one was found as MRD positive (tumor fraction = 2.7 ppm), suggesting high specificity.

Conclusions

MAESTRO-Pool enables massively parallel, tumor-informed MRD testing with concurrent benchmarking of bespoke MRD tests. Meanwhile, our new MRD caller enables more mutations and cfDNA molecules to be tested without compromising specificity. These improve the ability for detecting traces of MRD from blood.
Stealthy Backdoor Attacks On Deep Point Cloud Recognization Networks
Authors: Feng Le , Qian Zhenxing , Zhang Xinpeng , Li Sheng
Published: December 2023

Deep neural networks are vulnerable to backdoor attacks. Previous backdoor attacks have mainly focused on images. Unlike images composed of regular pixels, 3D point clouds are composed of irregular three-dimensional XYZ coordinates, which are widely used in areas such as autonomous driving and 3D measurement. As many deep neural networks have been developed for processing 3D point clouds, these networks also face the risk of backdoor attacks. Nevertheless, backdoor attacks on 3D point clouds have rarely been investigated. This paper proposes a stealthy backdoor attack on point clouds in the physical world, aiming to generate trainable non-rigid deformations as backdoor patterns. Instead of directly adding backdoor patterns onto the point clouds, we deform the 3D space of the point clouds to a new space, ensuring that all point clouds have the same backdoor deformation. We use point cloud alignment to overcome the inconsistency of backdoor deformation caused by shifting and scaling in the physical world. We also propose a physical transformation layer to combat the physical transformations. Additionally, we propose mask contrast learning to eliminate pseudo backdoor patterns to make the network’s backdoor property stealthier. Extensive experiments indicate that the proposed method can achieve better attack success rates and stealthiness.
GUI: A Geolocation Method for Unreachable IP
Authors: Zu Shuodi , Luo Xiangyang , Wang Liang , Zhang Fan
Published: December 2023

IP geolocation technology based on network measurement can provide IP geographic location capability without user assistance. In the case that the IP target device or intermediate route device does not respond to the detection message, the existing geolocation methods have reduced the accuracy of city-level geolocation, not to mention that the target cannot be located within the city. To solve this problem, a geolocation method for unreachable IP (called GUI) is proposed. GUI first extracts the target city metropolitan area network (MAN) topology, obtains the path to the IP target and compares it with the MAN topology to achieve the city-level geolocation of the target, and then looks for landmarks in the database that belong to the same /24 subnet and the same city-level location with the target. If the above landmarks exist, GUI uses the coordinate set corresponding to the landmarks to solve the minimum covering circle, so as to judge the location of the target. If the above landmarks do not exist, GUI searches for the intersection nodes from the target detection path and MAN topology, enumerates the connected landmarks, calculates the minimum covering circle according to the coordinates and uses it for the target’s urban internal geolocation. The experimental results of 15 cities in China and the USA show that GUI can effectively geolocate IP targets. The city-level geolocation success rate of reachable IP can reach 99.41%, that of unreachable IP can reach 89.37% and the minimum median error of urban internal unreachable IP geolocation can reach 4.99km. All indicators are significantly better than the existing typical geolocation methods, such as PoP-Based Geolocation, Street-Level Geolocation, Ranking Nodes Based Geolocation, and the existing typical IP geographic location databases such as IPIP and MaxMind.
Risankizumab Induction Therapy Achieves Early Symptom Improvements That Are Associated With Future Clinical and Endoscopic Outcomes in Crohn’s Disease: Post Hoc Analysis of the ADVANCE, MOTIVATE, and FORTIFY Phase 3 Studies
Authors: Colombel Jean-Frederic , Schreiber Stefan , D’Haens Geert , Rizzo Joanne , Kligys Kristina , Griffith Jenny , Zambrano Javier , Zhou Qian , Zhang Yafei , Kalabic Jasmina , Rieder Florian , Dubinsky Marla C , Panaccione Remo
Published: December 2023

Background and Aims

Crohn’s disease [CD] symptoms are a main driver for impaired quality of life, and fast relief is important for patient care. Stool frequency [SF] and abdominal pain score [APS] are patient-reported outcomes [PROs] measuring symptom severity, which are supported as treatment targets by the STRIDE-II consensus. This post hoc analysis examined the efficacy of risankizumab [RZB], a humanised monoclonal antibody with high specificity for interleukin-23 p19, for providing early symptom relief, along with the prognostic value of early symptom relief for achieving future clinical and endoscopic endpoints.

Methods

Individual and combined measures of SF and AP at Weeks 1, 2, and 3 were assessed in patients with moderate to severe CD who received 600 mg intravenous RZB or placebo [PBO] in the ADVANCE or MOTIVATE induction studies. Multivariate logistic regression was used to examine the predictiveness of early symptom improvement for clinical and endoscopic outcomes following RZB induction and maintenance.

Results

Higher rates of SF/APS clinical remission and enhanced clinical response were observed as early as Week 1 with RZB vs PBO. A larger proportion of patients achieved clinical endpoints with RZB vs PBO, irrespective of prior bio-failure status. Early PRO improvement was associated with a greater likelihood of achieving clinical and endoscopic improvement following 12-week induction and 52-week maintenance RZB dosing.

Conclusions

After the first intravenous RZB induction dose, significantly greater rates of symptom improvement vs PBO were achieved. Improvements could be observed as early as Week 1 and were predictive of Weeks 12 and 52 clinical and endoscopic improvement.
Artificial intelligence-enhanced electrocardiogram for arrhythmogenic right ventricular cardiomyopathy detection
Authors: Haq Ikram U , Liu Kan , Giudicessi John R , Siontis Konstantinos C , Asirvatham Samuel J , Attia Zachi I , Ackerman Michael J , Friedman Paul A , Killu Ammar M
Published: December 2023

Aims

ECG abnormalities are often the first signs of arrhythmogenic right ventricular cardiomyopathy (ARVC) and we hypothesized that an artificial intelligence (AI)-enhanced ECG could help identify patients with ARVC and serve as a valuable disease-detection tool.

Methods and results

We created a convolutional neural network to detect ARVC using a 12-lead ECG. All patients with ARVC who met the 2010 task force criteria and had disease-causative genetic variants were included. All case ECGs were randomly assigned in an 8:1:1 ratio into training, validation, and testing groups. The case ECGs were age- and sex-matched with control ECGs at our institution in a 1:100 ratio. Seventy-seven patients (51% male; mean age 47.2 ± 19.9), including 56 patients with PKP2, 7 with DSG2, 6 with DSC2, 6 with DSP, and 2 with JUP were included. The model was trained using 61 case ECGs and 5009 control ECGs; validated with 7 case ECGs and 678 control ECGs and tested in 22 case ECGs and 1256 control ECGs. The sensitivity, specificity, positive and negative predictive values of the model were 77.3, 62.9, 3.32, and 99.4%, respectively. The area under the curve for rhythm ECG and median beat ECG was 0.75 and 0.76, respectively.

Conclusion

Our study found that the model performed well in excluding ARVC and supports the concept that the AI ECG can serve as a biomarker for ARVC if a larger cohort were available for network training. A multicentre study including patients with ARVC from other centres would be the next step in refining, testing, and validating this algorithm.
Pericyte loss initiates microvascular dysfunction in the development of diastolic dysfunction
Authors: Simmonds Steven J , Grootaert Mandy O J , Cuijpers Ilona , Carai Paolo , Geuens Nadeche , Herwig Melissa , Baatsen Pieter , Hamdani Nazha , Luttun Aernout , Heymans Stephane , Jones Elizabeth A V
Published: December 2023

Aims

Microvascular dysfunction has been proposed to drive heart failure with preserved ejection fraction (HFpEF), but the initiating molecular and cellular events are largely unknown. Our objective was to determine when microvascular alterations in HFpEF begin, how they contribute to disease progression, and how pericyte dysfunction plays a role herein.

Methods and results

Microvascular dysfunction, characterized by inflammatory activation, loss of junctional barrier function, and altered pericyte–endothelial crosstalk, was assessed with respect to the development of cardiac dysfunction, in the Zucker fatty and spontaneously hypertensive (ZSF1) obese rat model of HFpEF at three time points: 6, 14, and 21 weeks of age. Pericyte loss was the earliest and strongest microvascular change, occurring before prominent echocardiographic signs of diastolic dysfunction were present. Pericytes were shown to be less proliferative and had a disrupted morphology at 14 weeks in the obese ZSF1 animals, who also exhibited an increased capillary luminal diameter and disrupted endothelial junctions. Microvascular dysfunction was also studied in a mouse model of chronic reduction in capillary pericyte coverage (PDGF-Bret/ret), which spontaneously developed many aspects of diastolic dysfunction. Pericytes exposed to oxidative stress in vitro showed downregulation of cell cycle-associated pathways and induced a pro-inflammatory state in endothelial cells upon co-culture.

Conclusion

We propose pericytes are important for maintaining endothelial cell function, where loss of pericytes enhances the reactivity of endothelial cells to inflammatory signals and promotes microvascular dysfunction, thereby accelerating the development of HFpEF.
Changes in vascular function and correlation with cardiotoxicity in women with newly diagnosed breast cancer undergoing HER2-directed therapy with and without anthracycline/cyclophosphamide
Authors: Hazim Antonious , Nhola Lara F , Kailash Vidur , Zhang Song , Sandhu Nicole P , Lerman Amir , Loprinzi Charles L , Ruddy Kathryn J , Villarraga Hector R , Lewis Bradley , Herrmann Joerg
Published: December 2023

Aims

The objective of this study was to assess the effect of HER2-directed therapy (HER2-Tx) on peripheral vasoreactivity and its correlation with cardiac function changes and the additive effects of anthracycline/cyclophosphamide (AC) therapy and baseline cardiovascular risk.

Methods and results

Single-centre, prospective cohort study of women with newly diagnosed stage 1–3 HER2-positive breast cancer undergoing HER2-Tx +/− AC. All participants underwent baseline and 3-monthly evaluations with Endo-Peripheral Arterial Tonometry (Endo-PAT), vascular biomarkers [C-type natriuretic peptide (CNP) and neuregulin-1 beta (NRG-1β)], and echocardiography. Cardiotoxicity was defined as a decrease in the left ventricular ejection fraction (LVEF) of >10% to a value <53%. Of the 47 patients enrolled, 20 (43%) received AC in addition to HER2-Tx. Deterioration of reactive hyperaemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs. 22%; P = 0.003). A decrease in CNP and log NRG-1β levels by 1 standard deviation did not differ significantly between the AC and non-AC groups (CNP: 20.0% vs. 7.4%; P = 0.20 and NRG-1β: 15% vs. 11%; P = 0.69) nor did GLS (35% vs. 37%; P = 0.89). Patients treated with AC had a significantly lower 3D LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3% (SD 3) vs. 63.8% (SD 4); P = 0.02). Reactive hyperaemia index and GLS were the only parameters correlating with LVEF change.

Conclusion

Combination therapy with AC, but not HER2-Tx alone, leads to a decline in peripheral vascular and cardiac function. Larger studies will need to define more precisely the causal correlation between vascular and cardiac function changes in cancer patients.
Evolution of flowering time due to variation in the onset of pollen dispersal among individuals
Authors: Xu Kuangyi
Published: December 2023

The evolution of flowering time is often attributed to variations in pollinator rates over time. This study proposes that flowering time can evolve through siring success variation among individuals caused by differential pollen dispersal timing (a result of flowering time variation). By building quantitative genetic models, I show that flowering time evolves to be earlier when the pollen removal rate is low and pollen deposition rate is high, and the fertilization ability of removed pollen declines slowly. Using evolutionary game theory, I show that the evolutionarily stable variance of flowering time is large when the pollen removal rate is either low or high, the pollen deposition rate is moderate, and the fertilization ability of removed pollen declines rapidly. Investigation of the coevolution of flower longevity and flowering time shows that under constant pollination rates, late flowering will be correlated with long-lived flowers due to nonrandom mating, which suggests that the observed correlation between late flowering and short-lived flowers is caused by other factors, such as declining pollination rates during late-stage flowering. I discuss how altered pollination rates under climate change will influence flowering time evolution and the importance of distinguishing between pollen removal and deposition rates.
Distinct development trajectories and symbiosis modes in vent shrimps
Authors: Methou Pierre , Guéganton Marion , Copley Jonathan T , Kayama Watanabe Hiromi , Pradillon Florence , Cambon-Bonavita Marie-Anne , Chen Chong
Published: December 2023

Most animal species have a singular developmental pathway and adult ecology, but developmental plasticity is well-known in some such as honeybees where castes display profoundly different morphology and ecology. An intriguing case is the Atlantic deep-sea hydrothermal vent shrimp pair Rimicaris hybisae and R. chacei that share dominant COI haplotypes and could represent very recently diverging lineages or even morphs of the same species. Rimicaris hybisae is symbiont-reliant with a hypertrophied head chamber (in the Mid-Cayman Spreading Centre), while R. chacei is mixotrophic with a narrow head chamber (on the Mid-Atlantic Ridge). Here, we use X-ray micro-computed tomography and fluorescence in situ hybridization to show that key anatomical shifts in both occur during the juvenile–subadult transition, when R. hybisae has fully established symbiosis but not R. chacei. On the Mid-Atlantic Ridge, the diet of R. chacei has been hypothetically linked to competition with the obligatorily symbiotic congener R. exoculata, and we find anatomical evidence that R. exoculata is indeed better adapted for symbiosis. We speculate the possibility that the distinct development trajectories in R. hybisae and R. chacei may be determined by symbiont colonization at a “critical period” before subadulthood, though further genetic studies are warranted to test this hypothesis along with the true relationship between R. hybisae and R. chacei.
Georgia and Florida Logging Businesses Persevere Through Pandemic, Rising Costs, and Uncertainty
Authors: Conrad Joseph L , Greene W Dale , Hiesl Patrick
Published: December 2023

Logging businesses in Georgia and Florida combine to harvest approximately 66 million tons of timber annually, more than 10% of the US total. Since 1987, the University of Georgia has surveyed Georgia logging business owners every 5 years. Florida logging businesses were included in 2022 to gain a better understanding of logging businesses in the region. During the first quarter of 2022, questionnaires were mailed to 503 and 132 logging businesses in Georgia and Florida, respectively. Adjusted response rates were 22% in Georgia and 25% in Florida. Logging businesses produced an average of 1,956 and 2,619 tons per week in Georgia and Florida, respectively. The median owner age was approximately 56 years in Georgia and 58 years in Florida. Nearly 40% of owners were over 60 years old in both states. More than 30% of loggers in both states expected to leave the industry within 5 years. The COVID-19 pandemic had a major impact on logging businesses, with over 80% of logging business owners reporting reduced production, employees becoming infected, and/or difficulty finding employees. Logging business owners identified fuel, labor, trucking, and insurance as their greatest challenges in 2022.

Study Implications: Rising costs, turbulent markets, and shortages of labor are stressing many logging businesses. In the short term, adjustments to logging rates are needed to respond to increased input costs. In the long term, individual logging businesses, loggers’ associations, and the forest industry should collaborate to increase the pool of qualified labor, address trucking and insurance challenges, and create succession plans for logging business owners that plan to leave the industry.
Ground penetrating radar used to detect drowning victims under ice
Authors: Giesbrecht Gordon G , Patel Mitesh , Javid Rafid , Murray Scott , Patel Vrushil , Wiens Noah , Xie Darren , Jeffrey Ian , Ferguson Philip
Published: December 2023

Every year, people drown after falling through ice on rivers and lakes. In some cases, the body of the victim floats up to the underside of the ice, making detection and recovery difficult using traditional search methods with divers. A robust and contact-less sensing system is required to locate drowning victims that does not put rescue teams at risk of falling through the ice themselves. In this paper, we demonstrate the feasibility of a ground penetrating radar (GPR) for detecting deceased drowning victims that have floated up to the underside of the ice. We placed three euthanized pigs simulating drowning victims under ice ranging in thickness from 5 to 26 cm. We dragged a GPR at 500 MHz and 1 GHz across the ice to detect the simulated victims using an autocorrelation-based detection technique. Results showed that both frequencies were able to detect the rough shape of the simulated victims at ice thicknesses up to 42 cm, with the 1-GHz data showing slightly more resolution than the 500-MHz data. These results show promise and suggest future development of an autonomous drone-based GPR detection system.

Key points
Comparison of Demirjian’s comprehensive chart with the London atlas of tooth development in children and adolescents: a pilot study
Authors: Chowdhry Aman , Kapoor Priyanka , Bhargava Deepak , Bagga Dinesh Kumar , Mehta Abhishek
Published: December 2023

Dental age estimation has its application in various subdisciplines of medicine and dentistry. New methods of dental age (DA) estimation are emerging and it is important that we compare different methods to determine which one is more closely related to the chronological age. Demirjian’s method is one of the most widely used techniques and has been tested in various ethnic populations globally. In 2016, another approach to DA estimation is the London atlas of human tooth development and eruption. No study has compared Demirjian’s comprehensive chart and London atlas method in the Indian population. Hence, in the current study, we estimated DA using Demirjian’s comprehensive chart and London atlas method for association with the known chronologic age in children and adolescent population. The study also attempted to determine if sexual dimorphism existed in DA estimated by the two methods. Estimation was performed for both methods on 100 orthopantomogram records (50 males and 50 females, aged 6–16 years) of orthodontic patients. The data were compared and analysed using paired t-tests. There was an overestimation of DA by Demirjian’s comprehensive chart on an average of +1.3 years in males and +0.5 years in females, whereas using London atlas, it was +1.4 years in males and +0.5 years in females. The mean of underestimation was −0.6 years in males and −0.8 years in females using Demirjian’s comprehensive chart, whereas it was −0.8 years in males and −0.5 years in females. A statistically significant difference (P < 0.0001) was found when mean chronological age (11.6 ± 2.6) years of the participants was compared with DA estimated using either Demirjian’s comprehensive chart (12.3 ± 2.8) years or London atlas (11.8 ± 2.9) years. The trends in this pilot study point towards more accuracy of London atlas over Demirjian’s method when done using comprehensive chart for estimating DA. In summary, the results of the current pilot study indicates greater accuracy of London atlas method over Demirjian’s comprehensive chart method for estimating DA in Indian population. This finding should be validated by conducting similar studies using larger sample, on diverse Indian ethnic populations, for applicability in pedodontic, orthodontic, and forensic domains.

Key points
A draft genome of the neritid snail Theodoxus fluviatilis
Authors: Fuchs Laura Iris Regina , Knobloch Jan , Wiesenthal Amanda Alice , Fuss Janina , Franzenburg Soeren , Torres Oliva Montserrat , Müller Christian , Wheat Christopher W , Hildebrandt Jan-Peter
Published: December 2023

The neritid snail Theodoxus fluviatilis is found across habitats differing in salinity, from shallow waters along the coast of the Baltic Sea to lakes throughout Europe. Living close to the water surface makes this species vulnerable to changes in salinity in their natural habitat, and the lack of a free-swimming larval stage limits this species’ dispersal. Together, these factors have resulted in a patchy distribution of quite isolated populations differing in their salinity tolerances. In preparation for investigating the mechanisms underlying the physiological differences in osmoregulation between populations that cannot be explained solely by phenotypic plasticity, we present here an annotated draft genome assembly for T. fluviatilis, generated using PacBio long reads, Illumina short reads, and transcriptomic data. While the total assembly size (1045 kb) is similar to those of related species, it remains highly fragmented (N scaffolds = 35,695; N50 = 74 kb) though moderately high in complete gene content (BUSCO single copy complete: 74.3%, duplicate: 2.6%, fragmented: 10.6%, missing: 12.5% using metazoa n = 954). Nevertheless, we were able to generate gene annotations of 21,220 protein-coding genes (BUSCO single copy complete: 65.1%, duplicate: 16.7%, fragmented: 9.1%, missing: 9.1% using metazoa n = 954). Not only will this genome facilitate comparative evolutionary studies across Gastropoda, as this is the first genome assembly for the basal snail family Neritidae, it will also greatly facilitate the study of salinity tolerance in this species. Additionally, we discuss the challenges of working with a species where high molecular weight DNA isolation is very difficult.
Transport of N-acetylchitooligosaccharides and fluorescent N-acetylchitooligosaccharide analogs into rat liver lysosomes
Authors: Bouzidi Younès , Bosco Michaël , Gao Haifei , Pradeau Stéphanie , Matheron Lucrèce , Chantret Isabelle , Busca Patricia , Fort Sébastien , Gravier-Pelletier Christine , Moore Stuart E H
Published: December 2023

Free polymannose-type oligosaccharides (fOS) are processed by cytosolic enzymes to generate Man5GlcNAc which is transferred to lysosomes and degraded. Lysosomal fOS import was demonstrated in vitro but is poorly characterized in part due to lack of convenient substrates. As chitooligosaccharides (COS, oligomers β1,4-linked GlcNAc) block [3H]Man5GlcNAc transport into lysosomes, we asked if COS are themselves transported and if so, can they be chemically modified to generate fluorescent substrates.

We show that COS are degraded by lysosomal hydrolases to generate GlcNAc, and robust ATP-dependent transport of [3H]COS2/4 di and tetrasaccharides into intact rat liver lysosomes was observed only after blocking lysosomal [3H]GlcNAc efflux with cytochalasin B. As oligosaccharides with unmodified reducing termini are the most efficient inhibitors of [3H]COS2/4 and [3H]Man5GlcNAc transport, the non-reducing GlcNAc residue of COS2-4 was de-N-acetylated using Sinorhizobium meliloti NodB, and the resulting amine substituted with rhodamine B (RB) to yield RB-COS2-4. The fluorescent compounds inhibit [3H]Man5GlcNAc transport and display temperature-sensitive, ATP-dependent transport into a sedimentable compartment that is ruptured with the lysosomotropic agent L-methyl methionine ester. Once in this compartment, RB-COS3 is converted to RB-COS2 further identifying it as the lysosomal compartment. RB-COS2/3 and [3H]Man5GlcNAc transports are blocked similarly by competing sugars, and are partially inhibited by the vacuolar ATPase inhibitor bafilomycin and high concentrations of the P-type ATPase inhibitor orthovanadate.

These data show that Man5GlcNAc, COS2/4 and RB-COS2/3 are transported into lysosomes by the same or closely related mechanism and demonstrate the utility of COS modified at their non-reducing terminus to study lysosomal oligosaccharide transport.
340B Contract pharmacy growth by pharmacy ownership: 2009–2022
Authors: McGlave Claire , Bruno John P , Watts Elizabeth , Nikpay Sayeh
Published: December 2023

The 340B program grants eligible health care providers (“covered entities”) access to discounted prices for outpatient prescription drugs. Covered entities frequently rely on retail pharmacies (“contract pharmacies”) to dispense discounted drugs. This analysis describes contract pharmacy participation by ownership: the top 4 chains, grocery chains, small chains, and institutional independent pharmacies. We found that 71% of pharmacies in the top 4 chains were contract pharmacies. Forty one percentage of institutional pharmacies, 38% of grocery store pharmacies, and 22% of independent pharmacies participated in 340B in 2022. The median number of contracts per pharmacy was 2 among the top 4 chains and grocery store pharmacies vs 1 for all other pharmacy types. The median farthest distance in miles from contracting covered entities was largest for the top 4 chains (19 miles) and small chains (18 miles) and smallest for independent and institutional pharmacies (10 miles). The top 4 chains held the highest proportion of contracts with core safety-net providers (75% vs 61% of institutional pharmacies).
On best p-norm approximation of discrete data by polynomials
Authors: Floater Michael S
Published: December 2023

In this note, we derive a solution to the problem of finding a polynomial of degree at most $n$ that best approximates data at $n+2$ points in the $l_{p}$ norm. Analogous to a result of de la Vallée Poussin, one can express the solution as a convex combination of the Lagrange interpolants over subsets of $n+1$ points, and the error oscillates in sign.
Mitochondrial DNA mutations in HIV-exposed uninfected infants following the cessation of triple antiretroviral drugs
Authors: Lian Yuting , Wang Ailing , Wei Lai , Yao Jun , Bulloch Gabriella , Wu Zunyou , Zhao Yan
Published: December 2023

Objectives

Mitochondrial mutations in HIV-exposed uninfected (HEU) infants after cessation of ART are rarely studied. We analysed a group of HEU newborns born to mothers with late HIV diagnosis who received three doses of ART immediately after birth. We observed mitochondrial DNA (mtDNA) mutations at different times of withdrawal.

Methods

The study was based on a clinical trial conducted from 2015 to 2020. Newborns of the intervention group who met the criteria for this study received triple antiretroviral drugs, zidovudine + lamivudine + nevirapine, within 2 h after the birth, as post-partum prophylaxis, and at 14 days were switched to zidovudine + lamivudine + lopinavir/ritonavir, which was continued until 6 weeks of age. From August to November 2019, blood samples from HEU infants were also collected after ceasing 12 months of ART, and analysed for mtDNA.

Results

Our study found that mtDNA mutations remained prevalent in HEU infants a few years after three ARTs were stopped immediately after birth. Among them, D-loop, ND1 and CYTB are the first three mutated regions during different withdrawal periods. This pattern of mutations is similar to, but not exactly consistent with, HIV-infected children receiving standard ART.

Conclusions

Further studies are needed to determine the effects of these mutations on the development of HEU infants and whether stopping ART leads to the restoration of mitochondrial function.
Effects of static magnetic field on the sulfate metabolic pathway involved in Magnetospirillum magneticum AMB-1 cell growth and magnetosome formation
Authors: Chen Haitao , Shi Hongkai , Chen Changyou , Jiao Yangkun , Wang Pingping , Chen Chuanfang , Li Jinhua , Wu Long-Fei , Song Tao
Published: December 2023

Aims

Magnetotactic bacteria (MTB) can use their unique intracellular magnetosome organelles to swim along the Earth’s magnetic field. They play important roles in the biogeochemical cycles of iron and sulfur. Previous studies have shown that the applied magnetic fields could affect the magnetosome formation and antioxidant defense systems in MTB. However, the molecular mechanisms by which magnetic fields affect MTB cells remain unclear. We aim to better understand the dark at 28°C–29°C for 20 h, as shownthe interactions between magnetic fields and cells, and the mechanism of MTB adaptation to magnetic field at molecular levels.

Methods and results

We performed microbiological, transcriptomic, and genetic experiments to analyze the effects of a weak static magnetic field (SMF) exposure on the cell growth and magnetosome formation in the MTB strain Magnetospirillum magneticum AMB-1. The results showed that a 1.5 mT SMF significantly promoted the cell growth but reduced magnetosome formation in AMB-1, compared to the geomagnetic field. Transcriptomic analysis revealed decreased expression of genes primarily involved in the sulfate reduction pathway. Consistently, knockout mutant lacking adenylyl-sulfate kinase CysC did no more react to the SMF and the differences in growth and Cmag disappeared. Together with experimental findings of increased reactive oxidative species in the SMF-treated wild-type strain, we proposed that cysC, as a key gene, can participate in the cell growth and mineralization in AMB-1 by SMF regulation.

Conclusions

This study suggests that the magnetic field exposure can trigger a bacterial oxidative stress response involved in AMB-1 growth and magnetosome mineralization by regulating the sulfur metabolism pathway. CysC may serve as a pivotal enzyme in mediating sulfur metabolism to synchronize the impact of SMF on both growth and magnetization of AMB-1.
Academic machine learning researchers’ ethical perspectives on algorithm development for health care: a qualitative study
Authors: Kasun Max , Ryan Katie , Paik Jodi , Lane-McKinley Kyle , Dunn Laura Bodin , Roberts Laura Weiss , Kim Jane Paik
Published: December 2023

Objectives

We set out to describe academic machine learning (ML) researchers’ ethical considerations regarding the development of ML tools intended for use in clinical care.

Materials and Methods

We conducted in-depth, semistructured interviews with a sample of ML researchers in medicine (N = 10) as part of a larger study investigating stakeholders’ ethical considerations in the translation of ML tools in medicine. We used a qualitative descriptive design, applying conventional qualitative content analysis in order to allow participant perspectives to emerge directly from the data.

Results

Every participant viewed their algorithm development work as holding ethical significance. While participants shared positive attitudes toward continued ML innovation, they described concerns related to data sampling and labeling (eg, limitations to mitigating bias; ensuring the validity and integrity of data), and algorithm training and testing (eg, selecting quantitative targets; assessing reproducibility). Participants perceived a need to increase interdisciplinary training across stakeholders and to envision more coordinated and embedded approaches to addressing ethics issues.

Discussion and Conclusion

Participants described key areas where increased support for ethics may be needed; technical challenges affecting clinical acceptability; and standards related to scientific integrity, beneficence, and justice that may be higher in medicine compared to other industries engaged in ML innovation. Our results help shed light on the perspectives of ML researchers in medicine regarding the range of ethical issues they encounter or anticipate in their work, including areas where more attention may be needed to support the successful development and integration of medical ML tools.
Confidence score: a data-driven measure for inclusive systematic reviews considering unpublished preprints
Authors: Tong Jiayi , Luo Chongliang , Sun Yifei , Duan Rui , Saine M Elle , Lin Lifeng , Peng Yifan , Lu Yiwen , Batra Anchita , Pan Anni , Wang Olivia , Li Ruowang , Marks-Anglin Arielle , Yang Yuchen , Zuo Xu , Liu Yulun , Bian Jiang , Kimmel Stephen E , Hamilton Keith , Cuker Adam , Hubbard Rebecca A , Xu Hua , Chen Yong
Published: December 2023

Objectives

COVID-19, since its emergence in December 2019, has globally impacted research. Over 360 000 COVID-19-related manuscripts have been published on PubMed and preprint servers like medRxiv and bioRxiv, with preprints comprising about 15% of all manuscripts. Yet, the role and impact of preprints on COVID-19 research and evidence synthesis remain uncertain.

Materials and Methods

We propose a novel data-driven method for assigning weights to individual preprints in systematic reviews and meta-analyses. This weight termed the “confidence score” is obtained using the survival cure model, also known as the survival mixture model, which takes into account the time elapsed between posting and publication of a preprint, as well as metadata such as the number of first 2-week citations, sample size, and study type.

Results

Using 146 preprints on COVID-19 therapeutics posted from the beginning of the pandemic through April 30, 2021, we validated the confidence scores, showing an area under the curve of 0.95 (95% CI, 0.92-0.98). Through a use case on the effectiveness of hydroxychloroquine, we demonstrated how these scores can be incorporated practically into meta-analyses to properly weigh preprints.

Discussion

It is important to note that our method does not aim to replace existing measures of study quality but rather serves as a supplementary measure that overcomes some limitations of current approaches.

Conclusion

Our proposed confidence score has the potential to improve systematic reviews of evidence related to COVID-19 and other clinical conditions by providing a data-driven approach to including unpublished manuscripts.
Rumen fermentation of meal-fed sheep in response to diets formulated to vary in fiber and protein degradability
Authors: Sujani Sathya , Gleason Claire B , dos Reis Barbara R , White Robin R
Published: December 2023

The concentration of volatile fatty acid (VFA) provides an imprecise view of VFA dynamics due to the confounding effects of fluid pool size and dynamics. Determination of VFA flux using isotope is expensive and a complex methodology. Therefore, a rapid and affordable approach to explore VFA dynamics may allow comprehensive characterization of VFA availability. The objective of this study was to explore the use of VFA dynamics generated by meal feeding to derive time-series rates of VFA apparent appearance and disappearance driven by different protein and fiber sources. Six ruminally cannulated wethers were fed diets containing timothy hay or beet pulp (TH and BP) and soybean meal (SBM) or heated soybean meal (HSBM). Diets were, TH + HSBM; TH + SBM; BP + HSBM; and BP + SBM and the experimental design was a partially replicated 4 × 4 Latin Square. Concentrations of VFA and polyethylene glycol (PEG) in rumen fluid samples were estimated. Concentrations of PEG were used to estimate fluid passage and volume to calculate VFA mass, and fluid-mediated exit. Maximum apparent appearance rate (mmol/h), the rate of apparent appearance decline (mmol/mmol/h), mean apparent appearance flux (mmol/h), mean apparent disappearance (mmol/h), and apparent disappearance rate (mmol/mmol/h) were estimated by deriving a 1 pool model for each VFA on a mass basis where appearance was assumed to follow an exponential decay pattern and disappearance followed mass-action kinetics. Statistical analyses were conducted using a linear mixed effect regression with fixed effects for fiber source, protein source, and their interaction, as well as random effects for animal and period. Rumen fluid volume (L) was greater in HSBM diets (P = 0.033) and fluid passage (%/h) was greater in SBM diets (P = 0.048). Concentrations (higher acetate and butyrate, P = 0.002 and 0.004, respectively) and molar proportions (higher valerate, P = 0.035) of VFA were affected only by fiber source; however, protein source and fiber source interacted to significantly influence apparent appearance rates and absorption rates of many major VFA. On a flux basis, HSBM supported significantly elevated mean disappearance of propionate (P = 0.033). This data demonstrates that time-series evaluation of fermentation dynamics, including fluid dynamics and VFA concentrations can be used to estimate apparent appearance and disappearance of VFA. Although further work is needed to confirm the alignment of these estimates with measurements of VFA supplies to the animal, this modeling approach may provide a simpler way to better understand the kinetics of rumen.