bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of sleep disorders in children with Congenital Zika Syndrome
Authors: Tavares Carolina Santos Souza , Marques Raquel Souza , Santos Victor Santana , Santos Hudson P , Reis Monique Carla da Silva , Martins-Filho Paulo Ricardo
Published: October 2023

Studies have reported that children with Congenital Zika Syndrome (CZS) experience changes in their sleep patterns, which can result in mood disturbances, behavioral issues and delays in growth and development. This systematic review synthesized the available evidence on the prevalence of sleep disorders in children with CZS. Eligible studies were those with an observational design that reported sleep disorders in children with CZS using validated questionnaires, polysomnography/electroencephalographic recording or parent/caregiver reports. Searches were conducted in PubMed, Web of Science, SCOPUS and Embase, as well as a gray literature search using Google Scholar. The Freeman-Tukey double-arcsine transformation with a random-effects model was used to estimate the pooled prevalence of sleep disorders with a 95% confidence interval (CI). Five studies were included and data from 340 Brazilian children with CZS were analyzed. The overall prevalence of sleep disorders was 27.4% (95% CI 16.7–39.4), without differences among studies using validated questionnaires (29.4%, 95% CI 21.4–37.8) or report from parents and caregivers (27.4%, 95% CI 11.5–47.0). Sleep disorders are prevalent in children with CZS, impacting their development and quality of life. It is critical to examine the quality of sleep in these children to develop appropriate interventions that can mitigate these issues.
Primary healthcare service delivery for older people with progressive multimorbidity in low- and middle-income countries: a systematic review
Authors: Kwaitana Duncan , Chisoni Felix , van Breevoort Dorothee , Mildestvedt Thomas , Meland Eivind , Bates Jane , Umar Eric
Published: October 2023

Ensuring primary healthcare (PHC) accessibility to older people with multimorbidity is vital in preventing unnecessary health deterioration. However, older people ≥50 y of age in low- and middle-income countries (LMICs) face challenges in effectively accessing and utilizing PHC. A systematic review was conducted adopting the Andersen–Newman theoretical framework for health services utilization to assess evidence on factors that affect access to PHC by older people. This framework predicts that a series of factors (predisposing, enabling and need factors) influence the utilization of health services by people in general. Seven publications were identified and a narrative analytical method revealed limited research in this area. Facilitating factors included family support, closeness to the PHC facility, friendly service providers and improved functional status of the older people. Barriers included long distance and disjointed PHC services, fewer health professionals and a lack of person-centred care. The following needs were identified: increasing the number of health professionals, provision of PHC services under one roof and regular screening services. There is a need for more investment in infrastructure development, coordination of service delivery and capacity building of service providers in LMICs to improve access and utilization of PHC services for older people.
UFMylation of HRD1 regulates endoplasmic reticulum homeostasis
Authors: Luo Hui , Jiao Qi‐Bin , Shen Chuan‐Bin , Gong Wen‐Yan , Yuan Jing‐Hua , Liu Ying‐Ying , Chen Zhen , Liu Jiang , Xu Xiao‐Ling , Cong Yu‐Sheng , Zhang Xing‐Wei
Published: October 2023

Ubiquitin fold modifier 1 is a small ubiquitin‐like protein modifier that is essential for embryonic development of metazoans. Although UFMylation has been connected to endoplasmic reticulum homeostasis, the underlying mechanisms and the relevant cellular targets are largely unknown. Here, we show that HRD1, a ubiquitin ligase of ER‐associated protein degradation (ERAD), is a novel substrate of UFM1 conjugation. HRD1 interacts with UFMylation components UFL1 and DDRGK1 and is UFMylated at Lys610 residue. In UFL1‐depleted cells, the stability of HRD1 is increased and its ubiquitination modification is reduced. In the event of ER stress, the UFMylation and ubiquitination modification of HRD1 is gradually inhibited over time. Alteration of HRD1 Lys610 residue to arginine impairs its ability to degrade unfolded or misfolded proteins to disturb protein processing in ER. These results suggest that UFMylation of HRD1 facilitates ERAD function to maintain ER homeostasis.
Association of Parity and Previous Birth Outcome With Brachial Plexus Birth Injury Risk
Authors: Manske M. Claire , Wilson Machelle D. , Wise Barton L. , James Michelle A. , Melnikow Joy , Hedriana Herman L. , Tancredi Daniel J.
Published: October 2023

OBJECTIVE:

To evaluate the association of maternal delivery history with a brachial plexus birth injury risk in subsequent deliveries and to estimate the effect of subsequent delivery method on brachial plexus birth injury risk.

METHODS:

We conducted a retrospective cohort study of all live-birth deliveries occurring in California-licensed hospitals from 1996 to 2012. The primary outcome was recurrent brachial plexus birth injury in a subsequent pregnancy. The exposure was delivery history (parity, shoulder dystocia in a previous delivery, or previously delivering a neonate with brachial plexus birth injury). Multiple logistic regression was used to model adjusted associations of delivery history with brachial plexus birth injury in a subsequent pregnancy. The adjusted risk and adjusted risk difference for brachial plexus birth injury between vaginal and cesarean deliveries in subsequent pregnancies were determined, stratified by delivery history, and the number of cesarean deliveries needed to prevent one brachial plexus birth injury was determined.

RESULTS:

Of 6,286,324 neonates delivered by 4,104,825 individuals, 7,762 (0.12%) were diagnosed with a brachial plexus birth injury. Higher parity was associated with a 5.7% decrease in brachial plexus birth injury risk with each subsequent delivery (adjusted odds ratio [aOR] 0.94, 95% CI 0.92–0.97). Shoulder dystocia or brachial plexus birth injury in a previous delivery was associated with fivefold (0.58% vs 0.11%, aOR 5.39, 95% CI 4.10–7.08) and 17-fold (1.58% vs 0.11%, aOR 17.22, 95% CI 13.31–22.27) increases in brachial plexus birth injury risk, respectively. Among individuals with a history of delivering a neonate with a brachial plexus birth injury, cesarean delivery was associated with a 73.0% decrease in brachial plexus birth injury risk (0.60% vs 2.21%, aOR 0.27, 95% CI 0.13–0.55) compared with an 87.9% decrease in brachial plexus birth injury risk (0.02% vs 0.15%, aOR 0.12, 95% CI 0.10–0.15) in individuals without this history. Among individuals with a history of brachial plexus birth injury, 48.1 cesarean deliveries are needed to prevent one brachial plexus birth injury.

CONCLUSIONS:

Parity, previous shoulder dystocia, and previously delivering a neonate with brachial plexus birth injury are associated with future brachial plexus birth injury risk. These factors are identifiable prenatally and can inform discussions with pregnant individuals regarding brachial plexus birth injury risk and planned mode of delivery.
Genomic approaches to explore susceptibility and pathogenesis of alcohol use disorder and alcohol-associated liver disease
Authors: Norden-Krichmar Trina M. , Rotroff Daniel , Schwantes-An Tae-Hwi , Bataller Ramon , Goldman David , Nagy Laura E. , Liangpunsakul Suthat
Published: October 2023

Excessive alcohol use is a major risk factor for the development of an alcohol use disorder (AUD) and contributes to a wide variety of other medical illnesses, including alcohol-associated liver disease (ALD). Both AUD and ALD are complex and causally interrelated diseases, and multiple factors other than alcohol consumption are implicated in the disease pathogenesis. While the underlying pathophysiology of AUD and ALD is complex, there is substantial evidence for a genetic susceptibility of both diseases. Current genome-wide association studies indicate that the genes associated with clinical AUD only poorly overlap with the genes identified for heavy drinking and, in turn, neither overlap with the genes identified for ALD. Uncovering the main genetic factors will enable us to identify molecular drivers underlying the pathogenesis, discover potential targets for therapy, and implement patient care early in disease progression. In this review, we described multiple genomic approaches and their implications to investigate the susceptibility and pathogenesis of both AUD and ALD. We concluded our review with a discussion of the knowledge gaps and future research on genomic studies in these 2 diseases.
Association of blood pressure and heart rate with carotid markers of vascular remodeling in the young: a case for early prevention
Authors: Büschges Julia C. , Schmidt-Trucksäss Arno , Neuhauser Hannelore
Published: October 2023

Objective:

The association of childhood blood pressure (BP) and heart rate (HR) with intermediate markers of cardiovascular disease several decades later has been shown, but studies on more short-term outcomes are scarce. Using population-based data, this study investigates the association of four BP parameters and HR in childhood with three carotid markers for vascular remodeling one decade later.

Methods:

At the 11-year follow–up, 4607 participants of the nationwide KiGGS cohort aged 14 to 28 years had semi-automated sonographic carotid intima media thickness (CIMT) measurements. We investigated associations of baseline (age 3–17 years) and follow-up SBP, DBP, mean arterial pressure (MAP), pulse pressure (PP) and resting heart rate (RHR), with CIMT and lumen diameter at or above the 90th percentile and distensibility coefficient at or below the tenth percentile in logistic regressions. Analyses were further adjusted using a composite cardiovascular risk (CVR) score of BMI, triglycerides, total/HDL-cholesterol-ratio and HbA1c.

Results:

SBP, DBP, MAP and RHR were significantly and similarly associated with all carotid measures 11 years later, for example an odds ratio (OR) of 1.17 [confidence interval (CI) 1.06–1.29] for one standard deviation SBP increase with elevated CIMT when adjusting for sex, age and CVR score. Cross–sectionally, the strongest association was found for MAP with reduced distensibility coefficient (OR 1.76; CI 1.59–1.94).

Conclusion:

This population-based cohort study shows robust and consistent associations between childhood BP and RHR and three carotid measures of vascular remodeling only one decade later, clearly underscoring the potential importance of preventing high BP already early in the life course.
Pleural effusion due to lymphangiomatosis and the role of sirolimus: A case report
Authors: Riazuddin Muhammad , Farouk Noha I. , Ali Saad S. , Butt Muhammad I. , Arabi Tarek Z. , Sabbah Belal N. , Ali Maha S. , Alkattan Khaled
Published: October 2023

Introduction:

Lymphangiomatosis is a rare abnormal proliferation of lymphatic vessels involving multiple organs like the brain, lung, heart, spleen, liver, and bones. Lymphangiomas constitute 5.6% of all benign tumors in infancy and adulthood.

Case presentation:

We report a case of a young lady who presented with constitutional symptoms and progressive dyspnea. Her medical history is significant for muco-cutaneous albinism, diffuse hemangiomas of the bone and viscera, and consumptive coagulopathy status post-splenectomy. After initial investigations, she was found to have right-sided pleural effusion. Pleural fluid analysis indicated chylothorax. She had multiple drainages of the pleural fluid done, and afterward, ligation of the right thoracic duct was performed with a trial of sirolimus, which improved her chylothorax.

Clinical discussion:

Several case reports have reported positive outcomes with sirolimus in the treatment of lymphangiomatosis. However, larger controlled studies are needed to confirm these findings.

Conclusion:

Sirolimus is promising as a medical treatment for diffuse pulmonary lymphangiomatosis.
Clinicopathologic Analysis and Molecular Profiling of Ovarian Steroid Cell Tumors
Authors: Mendoza Rachelle P. , Wang Peng , Smith Heather L. , Fitzpatrick Carrie A. , Haridas Rishikesh , Wanjari Pankhuri , Briese Renee , Shahid Anum , McCluggage W. Glenn , Bennett Jennifer A.
Published: October 2023

Ovarian steroid and Leydig cell tumors (SCT and LCT, respectively) are rare stromal tumors, with aggressive behavior described in approximately one third of SCTs. Previously reported features potentially predictive of malignancy include size ≥7 cm, gross hemorrhage, necrosis, grade 2 or 3 nuclear atypia, and mitoses ≥2/10 HPFs; however, no subsequent studies have corroborated these findings. Herein, we evaluated a series of 25 tumors (21 SCT, 4 LCT) to explore their clinicopathologic and molecular features. Patients ranged from 16 to 79 years (median: 53 y) and all tumors were FIGO stage I. Recurrences occurred in 3 patients, all of whom died from disease. At least 1 atypical feature was identified in 63% of SCT/LCT and included hemorrhage (n=9), grade 2 or 3 atypia (n=7), mitoses≥2/10 HPFs (n=7), size≥7.0 cm (n=6), and necrosis (n=2); only malignant SCTs demonstrated 4 or 5 atypical features. Next-generation sequencing revealed malignant SCTs were genomically unstable, with uncommon and nonrecurring gene-level alterations (MDM2/CDK4 coamplification, ATRX rearrangement, BAP1 mutation). One SCT with limited follow-up harbored FH and TP53 mutations and occasional arm-level copy number alterations, while all other sequenced tumors (n=7) were genomically stable; 1 had a CTNNB1 mutation and another a CASP10 mutation. In summary, the presence of at least 1 atypical feature is common in SCT/LCT, but most patients demonstrate a benign clinical course. Genomic alterations are infrequent but occur in malignant SCTs as well as a subset of benign SCTs. Molecular analysis of additional malignant SCTs is necessary to identify recurring and/or potentially actionable targets.
Hepatocellular Carcinoma Genetic Classification
Authors: Lominadze Zurabi , Shaik Mohammed Rifat , Choi Dabin , Zaffar Duha , Mishra Lopa , Shetty Kirti
Published: October 2023

Hepatocellular carcinoma (HCC) represents a significant global burden, with management complicated by its heterogeneity, varying presentation, and relative resistance to therapy. Recent advances in the understanding of the genetic, molecular, and immunological underpinnings of HCC have allowed a detailed classification of these tumors, with resultant implications for diagnosis, prognostication, and selection of appropriate treatments. Through the correlation of genomic features with histopathology and clinical outcomes, we are moving toward a comprehensive and unifying framework to guide our diagnostic and therapeutic approach to HCC.
Syphilis Mimicking Malignant Pulmonary Tumor With Nodal and Bone Metastasis on 18F-FDG PET/CT
Authors: Bronte Viedma Angela , Menendez-Sanchez Sandra , Bastidas Tamayo Juan Fernando , Lajusticia Andrés Héctor , García-Velloso Maria José
Published: October 2023

A 52-year-old man suffering left pleuritic pain underwent a chest CT showing a subpleural pulmonary nodule in the left upper lobe. Because of the possibility of a lung tumor, he was referred for 18F-FDG PET/CT. The scan revealed FDG uptake in the pulmonary nodule, in an upper right paratracheal lymph node, and at 4 destructive bone lesions. Pathologic examination after pulmonary biopsy manifested only the presence of inflammatory cells. Further clinical history research proved risky sexual behavior with a positive syphilis serology test. A follow-up PET/CT 7 months after penicillin therapy showed a complete metabolic response of all the lesions.
Locally Low-Rank Denoising of Multi-Echo Functional MRI Data With Application in Resting-State Analysis
Authors: Meyer Nolan K. , Kang Daehun , Ahmed Zaki , In Myung-Ho , Shu Yunhong , Huston John , Bernstein Matt A. , Trzasko Joshua D.
Published: October 2023

Objectives:

Locally low-rank (LLR) denoising of functional magnetic resonance imaging (fMRI) time series image data is extended to multi-echo (ME) data. The proposed method extends the capabilities of non-physiologic noise suppression beyond single-echo applications with a dedicated ME algorithm.

Materials and Methods:

Following an institutional review board (IRB) approved protocol, resting-state fMRI data were acquired in 7 healthy subjects. A compact 3T scanner enabled whole-brain acquisition of multiband ME fMRI data at high spatial resolution (1.4 × 1.4 × 2.8 mm3) with a 1810 ms repetition time (TR). Image data were denoised with ME-LLR preceding functional processing. The results of connectivity maps generated from denoised data were compared with maps generated with equivalent processing of non-denoised images. To assess ME-LLR as a method to reduce scan time, comparisons were made between maps computed from image data with full and retrospectively truncated durations. Assessments were completed with seed-based connectivity analyses using echo-combined image data. In a feasibility assessment, nondenoised and denoised full-duration echo-combined data were equivalently processed with independent component analysis (ICA) and compared.

Results:

ME-LLR denoising yielded strengthened resting-state network connectivity maps after nuisance regression and seed-based connectivity analysis. In assessing ME-LLR as a scan reduction mechanism, maps generated from denoised data at half scan time showed comparable quality with maps generated from full-duration, non-denoised data, at both single subject and group levels. ME-LLR substantially increased temporal signal-to-noise ratio (tSNR) for image data respective to each individual echo and for image data after nuisance regression. Among echo-specific image volumes, increases in tSNR yielded by ME-LLR were most pronounced for image data with the longest echo time and thereby lowest SNR. ICA showed resting-state networks consistently identified between non-denoised and denoised data, with clearer demarcation of networks for ME-LLR.

Conclusions:

ME-LLR is demonstrated to suppress non-physiologic noise, enhance functional connectivity map quality, and could potentially facilitate scan time reduction in ME-fMRI.
Data Requirement for Animal-Derived Wound Care Devices: Limitations of the 510(k) Regulatory Pathway
Authors: DeLong Michael R , Wells Michael W , Chang Irene A , Vardanian Andrew J , Harris Hobart
Published: October 2023

BACKGROUND:

Device classification and preclinical data requirements for animal-derived wound care products were recently reviewed by the FDA. Given the possible performance differences for these products, we evaluated the FDA data requirements as well as the published literature for all animal-derived wound care products ever cleared through the FDA.

STUDY DESIGN:

The publicly available online database was queried for all animal-derived wound products; premarket data requirements for each product were recorded. A PubMed search was conducted to determine the number of published clinical studies for each product, and manufacturer websites were accessed to obtain the price for each product.

RESULTS:

A total of 132 animal-derived wound products have been cleared by the FDA since the Center for Devices and Radiological Health was established in 1976. Of these, 114 had a publicly available clearance statement online. Preclinical biocompatibility testing was performed in 85 products (74.6%) and referenced in 10 (8.8%). Preclinical animal wound healing testing took place in 17 (14.9%). Only 9 products (7.9%) had clinical safety testing, and no products had clinical effectiveness data. We found no published peer-reviewed clinical data for 97 products (73%). Cost was infrequently available but ranged from $4.79 to $2,178 per unit.

CONCLUSIONS:

Although the current pathway is appropriate for efficiently clearing new wound care products, clinical effectiveness is not included in the regulatory review process. Wound care products are primarily evaluated by the FDA for safety and biocompatibility. Thus, any claims of clinical effectiveness require independent validation, which is often lacking.
Identification of secondary metabolites containing a diketopiperazine core in extracts from myxobacterial strains with growth inhibition activity against a range of prey species
Authors: Radford Emily J. , Whitworth David E. , Allison Gordon
Published: October 2023

Myxobacteria produce a variety of bioactive secondary metabolites, and with a wealth of under-researched species they hold vast potential for undiscovered compounds. With the ever-increasing need for new antibiotics, the development of novel therapeutics is vitally important. Therefore, this study aimed to extract and elucidate antimicrobial metabolites from the following myxobacteria:

Myxococcus xanthus

CA010 and AB022;

Corallococcus exiguus

DSM 14696T;

Myxococcus stipitatus

DSM 14675T; and

Corallococcus aberystwythensis

AB050AT. Metabolite mixtures were extracted in acetone from XAD-16 resin incubated in liquid cultures and analysed using GC-MS. Bioactivity was identified using a growth inhibition assay against a panel of clinically relevant prey species including Gram-positive and Gram-negative bacteria and a fungus. Growth of

Klebsiella pneumoniae

and

Enterococcus faecalis

was most affected by the metabolite mixtures and the mixtures from AB022 and AB050AT were effective against the most prey. GC-MS analysis revealed metabolites with roles in the synthesis and degradation of amino acids and fatty acids, but also identified compounds A and B with a diketopiperazine (DKP) core. With previously confirmed bioactivity of compound A, it is suggested that these DKP compounds are contributing to the antimicrobial activity observed. Furthermore, many compounds could not be identified and so these unknowns present further potential for novel bioactive compounds.
Pan-Cancer Drug Response Prediction Using Integrative Principal Component Regression
Authors: Liu Qingzhi , Li Gen , Baladandayuthapani Veerabhadran
Published: October 2023

The pursuit of precision oncology heavily relies on large-scale genomic and pharmacological data garnered from preclinical cancer model systems such as cell lines. While cell lines are instrumental in understanding the interplay between genomic programs and drug response, it well-established that they are not fully representative of patient tumors. Development of integrative methods that can systematically assess the commonalities between patient tumors and cell-lines can help bridge this gap. To this end, we introduce the Integrative Principal Component Regression (iPCR) model which uncovers both joint and model-specific structured variations in the genomic data of cell lines and patient tumors through matrix decompositions. The extracted joint variation is then used to predict patient drug responses based on the pharmacological data from preclinical models. Moreover, the interpretability of our model allows for the identification of key driver genes and pathways associated with the treatment-specific response in patients across multiple cancers. We demonstrate that the outputs of the iPCR model can assist in inferring both model-specific and shared co-expression networks between cell lines and patients. We show that iPCR performs favorably compared to competing approaches in predicting patient drug responses, in both simulation studies and real-world applications, in addition to identifying key genomic drivers of cancer drug responses.
The archerfish uses motor adaptation in shooting to correct for changing physical conditions
Authors: Volotsky Svetlana , Donchin Opher , Segev Ronen
Published: October 2023

The archerfish is unique in its ability to hunt by shooting a jet of water from its mouth that hits insects situated above the water’s surface. To aim accurately, the fish needs to overcome physical factors including changes in light refraction at the air-water interface. Nevertheless, archerfish can still hit the target with a high success rate under changing conditions. One possible explanation for this extraordinary ability is that it is learned by trial and error through a motor adaptation process. We tested this possibility by characterizing the ability of the archerfish to adapt to perturbations in the environment to make appropriate adjustments to its shots. We introduced a perturbing airflow above the water tank of archerfish trained to shoot at a target. For each trial shot, we measured the error; i.e., the distance between the center of the target and the center of the water jet produced by the fish. Immediately after the airflow perturbation, there was an increase in shot error. Then, over the course of several trials, the error was reduced and eventually plateaued. After the removal of the perturbation, there was an aftereffect, where the error was in the opposite direction but washed out after several trials. These results indicate that archerfish can adapt to the airflow perturbation. Testing the fish with two opposite airflow directions indicated that adaptation took place within an egocentric frame of reference. These results thus suggest that the archerfish is capable of motor adaptation, as indicated by data showing that the fish produced motor commands that anticipated the perturbation.
Predictable sequential structure augments auditory sensitivity at threshold
Authors: Marin Nadège , Gérenton Grégory , Jean Hadrien , Paraouty Nihaad , Wallaert Nicolas , Lazard Diane S. , Doelling Keith B. , Arnal Luc H.
Published: October 2023

Human hearing is highly sensitive and allows us to detect acoustic events at low levels. However, sensitivity is not only a function of the integrity of cochlear transduction mechanisms, but also constrained by central processes such as attention and expectation. While the effects of distraction and attentional orienting are generally acknowledged, the extent to which probabilistic expectations influence sensitivity at threshold is not clear. Classical audiometric tests, commonly used to assess hearing thresholds, do not distinguish between bottom-up sensitivity and top-down processes. In this study, we aim to decipher the influence of various types of expectations on hearing thresholds and how this information can be used to improve the assessment of hearing sensitivity. Our results raise important questions regarding the conventional assessment of hearing thresholds, both in fundamental research and in audiological clinical assessment.
Bacteriophage in combination with ciprofloxacin againstPseudomonas aeruginosainfections in diabetic foot ulcer patients
Authors: Liu Sha , Goonetilleke Shenoi , Hon Karen , Burdon Isabella Amy , Bouras George Spyro , McMillan Neil , Psaltis Alkis J , Wormald Peter-John , Fitridge Robert , Vreugde Sarah
Published: October 2023

Background

In diabetic foot ulcer (DFU) patients,Pseudomonas aeruginosa(P. aeruginosa) infections are linked to poor wound healing. The ineffectiveness of antibiotics against these infections promotes the emergence of multidrug-resistant (MDR) strains. Bacteriophage (phage) therapy has recently gained popularity as an alternative to antibiotics.

Methodology

Bacterial and viral swabs and tissue were obtained from DFU infections (DFI). Bacteria were cultured followed by MALDI-TOF MS for identification. 16S rRNA long-read sequencing was used to identify the microbiota. Bacteriophages were isolated and underwent transmission electron microscopy, genomic sequencing, and stability testing. The antimicrobial activity of phages alone and in combination with ciprofloxacin againstP. aeruginosaplanktonic cells and biofilm grownin vitroand inex vivotissue was tested by measuring the optical density (OD), crystal violet assays and live/dead staining with visualisation using confocal scanning laser microscopy respectively.

Results

A total of 34 DFI patients were recruited from which microbiota were analysed for 25 patients.P. aeruginosawas the most prevalent pathogen cultured and was one of the top 6 most prevalent and abundant species in the microbiota analysis. Phage APTC-PA18 was isolated from DFIs, belonged to themyoviridaefamily and was strictly lytic. PA18 was stable between 4 and 70 degrees Celsius and between pH 3 and 11. Seven of eightP. aeruginosaclinical isolates were sensitive to APTC-PA18, and when APTC-PA18 was combined with ciprofloxacin against planktonic and biofilm ofP. aeruginosa, synergistic effects were observedin vitroand in DFI tissue samples.

Conclusion

Phage APTC-PA18, when combined with ciprofloxacin, has the ability to killP. aeruginosaclinical isolates bothin vitroandex vivoand is a promising treatment option forP. aeruginosainfections in DFUs.
Using claims data to predict pre-operative BMI among bariatric surgery patients: development of the BMI Before Bariatric Surgery Scoring System (B3S3)
Authors: Wong Jenna , Li Xiaojuan , Arterburn David E. , Li Dongdong , Messenger-Jones Elizabeth , Wang Rui , Toh Sengwee
Published: October 2023

Background

Lack of body mass index (BMI) measurements limits the utility of claims data for bariatric surgery research, but pre-operative BMI may be imputed due to existence of weight-related diagnosis codes and BMI-related reimbursements requirements. We used a machine learning pipeline to create a claims-based scoring system to predict pre-operative BMI, as documented in the electronic health record (EHR), among patients undergoing a new bariatric surgery.

Methods

Using the Optum Labs Data Warehouse, containing linked de-identified claims and EHR data for commercial or Medicare Advantage enrollees, we identified adults undergoing a new bariatric surgery between January 2011 and June 2018 with a BMI measurement in linked EHR data ≤30 days before the index surgery (n=3,226). We constructed predictors from claims data and applied a machine learning pipeline to create a scoring system for pre-operative BMI, the B3S3. We evaluated the B3S3 and a simple linear regression model (benchmark) in test patients whose index surgery occurred concurrent (2011-2017) or prospective (2018) to the training data.

Results

The machine learning pipeline yielded a final scoring system that included weight-related diagnosis codes, age, and number of days hospitalized and distinct drugs dispensed in the past 6 months. In concurrent test data, the B3S3 had excellent performance (R20.862, 95% confidence interval [CI] 0.815-0.898) and calibration. The benchmark algorithm had good performance (R20.750, 95% CI 0.686-0.799) and calibration but both aspects were inferior to the B3S3. Findings in prospective test data were similar.

Conclusions

The B3S3 is an accessible tool researchers can use with claims data to obtain granular and accurate predicted values of pre-operative BMI, which may enhance confounding control and investigation of effect modification by baseline obesity levels in bariatric surgery studies utilizing claims data.
Sensorimotor mechanisms selective to numerosity derived from individual differences
Authors: Anobile Giovanni , Petrizzo Irene , Paiardini Daisy , Burr David C. , Cicchini Guido Marco
Published: October 2023

We have previously shown that after few seconds of adaptation by finger-tapping, the perceived numerosity of spatial arrays and temporal sequences of visual objects displayed near the tapping region is increased or decreased, implying the existence of asensorimotor numerosity system(Anobile et al., 2016). To date, this mechanism has been evidenced only by adaptation. Here we extend our finding by leveraging on a well-established covariance technique, used to unveil and characterize “channels” for basic visual features such as colour, motion, contrast, and spatial frequency. Participants were required to press rapidly a key a specific number of times, without counting. We then correlated the precision of reproduction for various target number presses between participants. The results showed high positive correlations for nearby target numbers, scaling down with numerical distance, implying tuning selectivity. Factor analysis identified two factors, one for low and the other for higher numbers. Principal component analysis revealed two bell-shaped covariance channels, peaking at different numerical values. Two control experiments ruled out the role of non-numerical strategies based on tapping frequency and response duration. These results reinforce our previous reports based on adaptation, and further suggest the existence of at least two sensori-motor number channels responsible for translating symbolic numbers into action sequences.
What makes a temperate phage an effective bacterial weapon?
Authors: Thomas M. J. N. , Brockhurst M. A. , Coyte K. Z.
Published: October 2023

Temperate bacteriophages (phages) are common features of bacterial genomes and can act as self-amplifying biological weapons, killing susceptible competitors and thus increasing the fitness of their bacterial hosts (lysogens). Despite their prevalence, however, the key characteristics of an effective temperate phage weapon remain unclear. Here we use systematic mathematical analyses coupled with experimental tests to understand what makes an effective temperate phage weapon. We find that effectiveness is controlled by phage life history traits – in particular, the probability of lysis, and induction rate – but that the optimal combination of traits varies with the initial frequency of a lysogen within a population. As a consequence, certain phage weapons can be detrimental when their hosts are rare, yet beneficial when their hosts are common, while subtle changes in individual life history traits can completely reverse the impact of an individual phage weapon on lysogen fitness. We confirm key predictions of our model experimentally, using temperate phages isolated from the clinically relevant Liverpool Epidemic Strain ofPseudomonas aeruginosa. Through these experiments, we further demonstrate that nutrient availability can also play a critical role in driving frequency-dependent patterns in phage-mediated competition. Together, these findings highlight the complex and context-dependent nature of temperate phage weapons, and highlight the importance of both ecological and evolutionary processes in shaping microbial community dynamics more broadly.

Importance

Temperate bacteriophage – viruses that integrate within bacterial DNA – are incredibly common within bacterial genomes. These phages are thought to act as powerful self-amplifying weapons, allowing their bacterial hosts to kill nearby competitors and thus gain a fitness advantage within a given niche. But what makes an effective phage weapon? Here we first use a simple mathematical model to explore the factors determining phage weapon utility. Our models suggest that phage weapons are nuanced and context-dependent: an individual phage may be beneficial or costly depending upon tiny changes to how it behaves, or to the bacterial community in which it resides. We then confirm these mathematical predictions experimentally, using phage isolated from Cystic Fibrosis patients. But, in doing so, we also find that another factor – nutrient availability – plays a key role in shaping phage-mediated competition. Together our results provide new insights into how temperate phage modulate bacterial communities.
mtx-COBRA: Subcellular localization prediction for bacterial proteins
Authors: Arora Isha , Kummer Arkadij , Zhou Hao , Gadjeva Mihaela , Ma Eric , Chuang Gwo-Yu , Ong Edison
Published: October 2023

Background

Bacteria can have beneficial effects on our health and environment; however, many are responsible for serious infectious diseases, warranting the need for vaccines against such pathogens. Bioinformatic and experimental technologies are crucial for the development of vaccines. The vaccine design pipeline requires identification of bacteria-specific antigens that can be recognized and induce a response by the immune system upon infection. Immune system recognition is influenced by the location of a protein. Methods have been developed to determine the subcellular localization (SCL) of proteins in prokaryotes and eukaryotes. Bioinformatic tools such as PSORTb can be employed to determine SCL of proteins, which would be tedious to perform experimentally. Unfortunately, PSORTb often predicts many proteins as having an “Unknown” SCL, reducing the number of antigens to evaluate as potential vaccine targets.

Method

We present a new pipeline called subCellular lOcalization prediction forBacteRiAl Proteins (mtx-COBRA). mtx-COBRA uses Meta’s protein language model, Evolutionary Scale Modeling, combined with an Extreme Gradient Boosting machine learning model to identify SCL of bacterial proteins based on amino acid sequence. This pipeline is trained on a curated dataset that combines data from UniProt and the publicly available ePSORTdb dataset.

Results

Using benchmarking analyses, nested 5-fold cross-validation, and leave-one-pathogen-out methods, followed by testing on the held-out dataset, we show that our pipeline predicts the SCL of bacterial proteins more accurately than PSORTb.

Conclusions

mtx-COBRA provides an accessible pipeline with greater efficiency to classify bacterial proteins with currently “Unknown” SCLs than existing bioinformatic and experimental methods.
Thymine DNA glycosylase combines sliding, hopping, and nucleosome interactions to efficiently search for 5-formylcytosine
Authors: Schnable Brittani L. , Schaich Matthew A. , Roginskaya Vera , Leary Liam P. , Weaver Tyler M. , Freudenthal Bret D. , Drohat Alexander C. , Houten Bennett Van
Published: October 2023

Base excision repair is the main pathway involved in active DNA demethylation. 5-formylctyosine and 5-carboxylcytosine, two oxidized moieties of methylated cytosine, are recognized and removed by thymine DNA glycosylase (TDG) to generate an abasic site. Using single molecule fluorescence experiments, we studied TDG in the presence and absence of 5-formylctyosine. TDG exhibits multiple modes of linear diffusion, including hopping and sliding, in search of a lesion. We probed TDG active site variants and truncated N-terminus revealing how these variants alter the lesion search and recognition mechanism of TDG. On DNA containing an undamaged nucleosome, TDG was found to either bypass, colocalize with, or encounter but not bypass the nucleosome. However, truncating the N-terminus reduced the number of interactions with the nucleosome. Our findings provide unprecedented mechanistic insights into how TDG searches for DNA lesions in chromatin.
Effects of benzothiazinone and ethambutol on the integrity of the corynebacterial cell envelope
Authors: Meyer Fabian M. , Repnik Urska , Karnaukhova Ekaterina , Schubert Karin , Bramkamp Marc
Published: October 2023

The mycomembrane (MM) is a hydrophobic layer formed by mycolic acids covering the surface ofMycobacteriaand related species. This group includes important pathogens such asMycobacterium tuberculosis,Corynebacterium diphtheriae, but also the biotechnologically important strainCorynebacterium glutamicum. The MM contributes to the impermeability of the cell envelope and thereby also protects bacteria from antibiotics. This makes biosynthesis of the MM an attractive target for antibiotic intervention. The first line anti-tuberculosis drug ethambutol (EMB) interferes with the synthesis of the arabinogalactan (AG), which is a structural scaffold for covalently attached mycolic acids that form the inner leaflet of the MM. Similarly, the new drug candidate, benzothiazinone 043 (BTZ) affects the synthesis of the AG component of the cell wall. We previously showed thatC. glutamicumcells treated with a sublethal concentration of EMB lose the integrity of the MM. In this study we examined the effects of a sublethal concentration of BTZ. Our work shows that 1 µg ml−1BTZ efficiently blocks the apical growth machinery and reduces cell proliferation, however the integrity of the MM is largely preserved and the effects of β-lactam antibiotics are only additive, not synergistic. Transmission electron microscopy (TEM) analysis revealed a distinct middle layer in the septum of control cells considered to be the inner leaflet of the MM covalently attached to the AG. It functions as a greasy slide for the lateral flow of mycolic acids in the outer leaflet. This layer was not detectable in the septa of BTZ or EMB treated cells, which suggests that the greasy slide is impaired and the confluency of the MM is thereby reduced. In addition, we observed that EMB treated cells have a thicker and less electron dense peptidoglycan (PG) layer consistent with the report that EMB also inhibits the glutamate racemase MurI. We conclude that EMB and BTZ have distinct differences in their modes of action. While EMB and BTZ both effectively block elongation growth, BTZ also strongly reduces septal cell wall synthesis. This renders BTZ treated cells likely more tolerant to antibiotics that act on growing bacteria.
Conjoint specification of action by neocortex and striatum
Authors: Park Junchol , Polidoro Peter , Fortunato Catia , Arnold Jon , Mensh Brett , Gallego Juan A. , Dudman Joshua T.
Published: October 2023

The interplay between two major forebrain structures - cortex and subcortical striatum - is critical for flexible, goal-directed action. Traditionally, it has been proposed that striatum is critical for selecting what type of action is initiated while the primary motor cortex is involved in the online control of movement execution. Recent data indicates that striatum may also be critical for specifying movement execution. These alternatives have been difficult to reconcile because when comparing very distinct actions, as in the vast majority of work to date, they make essentially indistinguishable predictions. Here, we develop quantitative models to reveal a somewhat paradoxical insight: only comparing neural activity during similar actions makes strongly distinguishing predictions. We thus developed a novel reach-to-pull task in which mice reliably selected between two similar, but distinct reach targets and pull forces. Simultaneous cortical and subcortical recordings were uniquely consistent with a model in which cortex and striatum jointly specify flexible parameters of action during movement execution.

One sentence summary

Motor cortex and subcortical striatum act in concert to specify the movement parameters of a reach-to-pull action in mice.
Deciphering D4Z4 CpG methylation gradients in fascioscapulohumeral muscular dystrophy using nanopore sequencing
Authors: Butterfield Russell J. , Dunn Diane M. , Duval Brett , Moldt Sarah , Weiss Robert B.
Published: October 2023

Fascioscapulohumeral muscular dystrophy (FSHD) is caused by a unique genetic mechanism that relies on contraction and hypomethylation of the D4Z4 macrosatellite array on the Chromosome 4q telomere allowing ectopic expression of theDUX4gene in skeletal muscle. Genetic analysis is difficult because of the large size and repetitive nature of the array, a nearly identical array on the 10q telomere, and the presence of divergent D4Z4 arrays scattered throughout the genome. Here, we combine nanopore long-read sequencing with Cas9-targeted enrichment of 4q and 10q D4Z4 arrays for comprehensive genetic analysis including determination of the length of the 4q and 10q D4Z4 arrays with base-pair resolution. In the same assay, we differentiate 4q from 10q telomeric sequences, determine A/B haplotype, identify paralogous D4Z4 sequences elsewhere in the genome, and estimate methylation for all CpGs in the array. Asymmetric, length-dependent methylation gradients were observed in the 4q and 10q D4Z4 arrays that reach a hypermethylation point at approximately 10 D4Z4 repeat units, consistent with the known threshold of pathogenic D4Z4 contractions. High resolution analysis of individual D4Z4 repeat methylation revealed areas of low methylation near the CTCF/insulator region and areas of high methylation immediately preceding theDUX4transcriptional start site. Within theDUX4exons, we observed a waxing/waning methylation pattern with a 180-nucleotide periodicity, consistent with phased nucleosomes. Targeted nanopore sequencing complements recently developed molecular combing and optical mapping approaches to genetic analysis for FSHD by adding precision of the length measurement, base-pair resolution sequencing, and quantitative methylation analysis.
Crystal structure of dibenzylammonium hydrogen (4-aminophenyl)arsonate monohydrate
Authors: Traoré Bocar , Diallo Waly , Sidibé Mamadou , Diop Libasse , Plasseraud Laurent , Cattey Hélène
Published: October 2023

The title salt, C14H16N+·C6H7AsNO3
−·H2O or [(C6H5CH2)2NH2][H2NC6H4As(OH)O2]·H2O, (I), was synthesized by mixing an aqueous solution of (4-aminophenyl)arsonic acid with an ethanolic solution of dibenzylamine at room temperature. Compound I crystallizes in the monoclinic P21/c space group. The three components forming I are linked via N—H...O and O—H...O intermolecular hydrogen bonds, resulting in the propagation of an infinite zigzag chain. Additional weak interactions between neighbouring chains, such as π–π and N—H...O contacts, involving phenyl rings, –NH2 and –As(OH)O3 functions, and H2O, respectively, lead to a three-dimensional network.
Synthesis, crystal structure and in vitro anti-proliferative activity of 2-[(4-acetylphenyl)carbamoyl]phenyl acetate
Authors: Mohamed-Ezzat Reham A. , Kariuki Benson M. , Srour Aladdin M.
Published: October 2023

2-[(4-Acetylphenyl)carbamoyl]phenyl acetate, C17H15NO4, has been synthesized and structurally characterized. In the structure, N—H...O hydrogen-bonding interactions form chains of molecules aligned along the [101] direction. The chains are linked by π–π and C—H...π interactions, forming a three dimensional network. The compound has been screened for in vitro anti-proliferative activity revealing considerable activity.
Synthesis, crystal structure and Hirshfeld analysis of trans-bis{(2E)-N-phenyl-2-[(2E)-3-phenyl-2-propen-1-ylidene]hydrazinecarbothioamidato-κ2
N
1,S}palladium(II)
Authors: Melo Ana Paula Lopes de , Martins Bianca Barreto , Bresolin Leandro , Tirloni Bárbara , Oliveira Adriano Bof de
Published: October 2023

The reaction of (2E)-N-phenyl-2-[(2E)-3-phenyl-2-propen-1-ylidene]hydrazinecarbothioamide (common name: cinnamaldehyde-4-phenylthiosemicarbazone) deprotonated with NaOH in ethanol with an ethanolic suspension of PdII chloride in a 2:1 molar ratio yielded the title compound, [Pd(C16H14N3S)2]. The anionic ligands act as metal chelators, κ2
N
1
S-donors, forming five-membered rings with a trans-configuration. The PdII ion is fourfold coordinated in a slightly distorted square-planar geometry. For each ligand, one H...S and one H...N intramolecular interactions are observed, with S(5) and S(6) graph-set motifs. Concerning the H...S interactions, the coordination sphere resembles a hydrogen-bonded macrocyclic environment-type. In the crystal, the complexes are linked via pairs of H...S interactions, with graph-set motif R
2
2(8), and building a mono-periodic hydrogen-bonded ribbon along [001]. The Hirshfeld surface analysis indicates that the major contributions for the crystal cohesion are: H...H (45.3%), H...C/C...H (28.0%), H...S/S...H (8.0%) and H...N/N...H (7.4%).