bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual Dimorphism of Radiomic Features in the Brain
Authors: Mayerhoefer Marius E. , Shepherd Timothy M. , Weber Michael , Leithner Doris , Woo Sungmin , Pan Jullie W. , Pardoe Heath R.
Published: June 2024

Objectives

The aim of this study was to determine whether MRI radiomic features of key cerebral structures differ between women and men, and whether detection of such differences depends on the image resolution.

Materials and Methods

Ultrahigh resolution (UHR) 3D MP2RAGE (magnetization-prepared 2 rapid acquisition gradient echo) T1-weighted MR images (voxel size, 0.7 × 0.7 × 0.7 mm3) of the brain of 30 subjects (18 women and 12 men; mean age, 39.0 ± 14.8 years) without abnormal findings on MRI were retrospectively included. MRI was performed on a whole-body 7 T MR system. A convolutional neural network was used to segment the following structures: frontal cortex, frontal white matter, thalamus, putamen, globus pallidus, caudate nucleus, and corpus callosum. Eighty-seven radiomic features were extracted respectively: gray-level histogram (n = 18), co-occurrence matrix (n = 24), run-length matrix (n = 16), size-zone matrix (n = 16), and dependence matrix (n = 13). Feature extraction was performed at UHR and, additionally, also after resampling to 1.4 × 1.4 × 1.4 mm3 voxel size (standard clinical resolution). Principal components (PCs) of radiomic features were calculated, and independent samples t tests with Cohen d as effect size measure were used to assess differences in PCs between women and men for the different cerebral structures.

Results

At UHR, at least a single PC differed significantly between women and men in 6/7 cerebral structures: frontal cortex (d = −0.79, P = 0.042 and d = −1.01, P = 0.010), frontal white matter (d = −0.81, P = 0.039), thalamus (d = 1.43, P < 0.001), globus pallidus (d = 0.92, P = 0.020), caudate nucleus (d = −0.83, P = 0.039), and corpus callosum (d = −0.97, P = 0.039). At standard clinical resolution, only a single PC extracted from the corpus callosum differed between sexes (d = 1.05, P = 0.009).

Conclusions

Nonnegligible differences in radiomic features of several key structures of the brain exist between women and men, and need to be accounted for. Very high spatial resolution may be required to uncover and further investigate the sexual dimorphism of brain structures on MRI.
Application of Free Flaps in Reconstruction of Head and Neck Soft Tissue Defects With Bone Exposure
Authors: Zhang Mingjun , Fu Jile , Liu Xiaojun , Liu Bincheng , Mao Xiaoyan , Hu Zhiqi
Published: June 2024

Background

Reconstruction of head and neck soft tissue defects with bone exposure is both challenging and technically demanding for plastic surgeon. Objectives in head and neck soft tissue defects with bone exposure reconstruction are consistent restoration of functionality while also improving appearance. This study retrospectively analyzed the results of head and neck reconstructions using various types of free flaps over the past 4 years.

Methods

A retrospective analysis was conducted from June 2019 to June 2023 on 12 patients treated at our hospital for head and neck soft tissue defects with bone exposure due to various causes. These included 4 cases of trauma from car accidents, 1 burn case, and 7 postoperative malignant tumor removals. The defect sizes ranged from 4 × 6 to 15 × 45 cm. Different free flaps were used for repair based on the defect, including 6 anterolateral thigh flaps, 3 forearm flaps, 2 latissimus dorsi flaps, and 1 dorsalis pedis flap. Flaps were designed and harvested to match the defect size and transplanted via anastomosed vessels.

Results

All 12 flaps survived successfully. One patient required flap thinning surgery postoperatively. All patients were followed up for over 3 months, showing good color and texture of the transplanted flaps, satisfactory healing, and significant aesthetic improvement. Donor sites showed significant scarring without functional impairment.

Conclusion

Free flap repair for head and neck soft tissue defects with bone exposure is feasible and yields good results.
Upper Blepharoplasty through Infrabrow Skin Excision to Treat Dermatochalasis with Lateral Hooding and Medial Orbital Fat Loss in Selected Patients
Authors: Wang DaoHe , Cai TianYi , Guo FanLi , James Andrew J. , Yang JunYi , Yang YanWen
Published: June 2024

Purpose

Dermatochalasis with lateral hooding and medial orbital fat loss are common signs of aging in the upper eyelid. Removing the excess skin in this area through infrabrow skin excision can effectively lift the loose skin of the upper eyelid and minimizes visible scarring. Additionally, we have identified three compartments of orbital fat prolapse based on orbital anatomy. Transferring volume from the lateral compartment to the intermediate region can flatten the lateral upper eyelid and create medial fullness, which ultimately rejuvenates the upper eyelid. This study presents an operative method for correcting age-related changes in the upper eyelid using this technique.

Methods

A total of 34 eyelids from 17 patients underwent a surgical procedure involving infrabrow skin excision, along with repositioning and lifting of lateral orbital fat. The inclusion criteria consisted of patients with moderate to severe upper eyelid dermatochalasis, coupled with middle fat loss and lateral hooding. To correct lateral hooding and restore midfacial fullness, lateral orbital fat was repositioned to an intermediate position, and the orbicularis oculi muscle was fold-sutured to the corrugator supercilii muscle.

Results

The mean age of the patients was 55.59 ± 3.20 years, with a range of 48 to 61 years. The mean follow-up period was 9.94 ± 1.35 months, ranging from 8 to 12 months. Patients were evaluated at 1-month, 3-month, and 6-month intervals. The Strasser system was used to evaluate the surgical outcomes at 3 months. All patients achieved good surgical outcomes, expressed through satisfactory cosmetic improvements, and improved visual field. The procedure effectively corrected lateral hooding and loss of middle orbital fat through infrabrow skin excision. No complications, such as wound dehiscence, lagophthalmos, noticeable scarring, ocular dyskinesia, or sensory changes, were observed.

Conclusions

The combination of infrabrow skin excision, repositioning of lateral orbital fat, and lifting of the orbicularis oculi muscle effectively addresses moderate to severe dermatochalasis, lateral hooding, medial fat loss, and improves elasticity of the anterior wall of the upper lid in our patients. This procedure can produce satisfactory and long-lasting aesthetic results with an inconspicuous scar beneath the brow.
Surgical Intraoperative Handoff Initiative: Standardizing Operating Room Communication Using SHRIMPS
Authors: Stephens Wesley A , Anderson Madeline J , Levy Brittany E , Lantz Sherry , Harris Andrew M , Newcomb Melissa R
Published: June 2024

BACKGROUND:

Operating room (OR) handoffs are not universally standardized, although standardized sign outs have been proven to provide effective communication in other aspects of healthcare. We hypothesize that creating a standardized handoff will improve communication between OR staff.

STUDY DESIGN:

A frontline stakeholder approached our quality improvement team with concern regarding inadequate quality surgical technician handoffs during staff changes. An audit tool was created for a pilot cohort of 23 cases to evaluate surgical technician handoffs from May 2022 to November 2022. Handoffs occurred in 82.6% of cases. Elements of handoff varied significantly, with an average of 34.4% completion of critical handoff elements. Audits were reviewed with stakeholders to develop a standardized communication checklist, including domains regarding sponges, sharps, hidden items, replaced items, instruments, implants, medications, procedure overview, and specimens. An acronym of these domains, SHRIMPS, was affixed to each OR wall.

RESULTS:

In the initial Plan-Do-Study-Act cycle, piloted in urology, general surgery, and neurosurgery, 100% of the 15 observed cases included handoff, averaging 76 seconds per handoff. Additionally, 100% of cases announced a handoff to the surgeon, and all elements were addressed 99.6% of the time. Plan-Do-Study-Act cycle 2 involved implementation to all service lines. Of the 68 cases observed, 100% included handoff, averaging 69.4 seconds per handoff, with 98.2% of elements addressed, though only 97.1% of handoffs were announced.

CONCLUSIONS:

Little communication standardization exists within the OR, especially regarding intraoperative staff changes. Implementation of a standardized handoff between surgical technicians resulted in substantial improvement in critical communication during staff changes.
Resident and Fellow Performance and Supervision in Surgical Oncology Procedures
Authors: Underwood Patrick W , Balch Jeremy A , Filiberto Amanda C , Cloyd Jordan M , Pawlik Timothy M , Sarosi George A , Upchurch Gilbert R , Loftus Tyler J
Published: June 2024

BACKGROUND:

Previous research has highlighted concerns among trainees and attendings that general surgery training and fellowship are inadequately preparing trainees for practice. Providing trainees with supervision that matches their proficiency may help bridge this gap. We sought to benchmark operative performance and supervision levels among senior surgery residents (PGY-4 or -5) and fellows performing general surgical oncology procedures.

STUDY DESIGN:

Observational data were obtained from the Society for Improving Medical Procedural Learning OR application for core general surgical oncology procedures performed at 103 unique residency and fellowship programs. Procedures were divided into breast and soft tissue, endocrine, and hepatopancreatobiliary. Case evaluations completed by trainees and attendings were analyzed to benchmark trainee operative performance and level of supervision.

RESULTS:

There were 4,907 resident cases and 425 fellow cases. Practice-ready performance, as assessed by trainees and faculty, was achieved by relatively low proportions of residents and fellows for breast and soft tissue cases (residents: 38%, fellows: 48%), endocrine cases (residents: 22%, fellows: 41%), and hepatopancreatobiliary cases (residents: 10%, fellows: 40%). Among cases in which trainees did achieve practice-ready performance, supervision only was provided for low proportions of cases as rated by trainees (residents: 17%, fellows: 18%) and attendings (residents: 21%, fellows 25%).

CONCLUSIONS:

In a sample of 103 residency and fellowship programs, attending surgeons rarely provided senior residents and fellows with levels of supervision commensurate to performance for surgical oncology procedures, even for high-performing trainees. These findings suggest a critical need for surgical training programs to prioritize providing greater levels of independence to trainees that have demonstrated excellent performance.
Metamaterial applications of Tmatsolver, an easy-to-use software for simulating multiple wave scattering in two dimensions
Authors: Hawkins Stuart C. , Bennetts Luke G. , Nethercote Matthew A. , Peter Malte A. , Peterseim Daniel , Putley Henry J. , Verfürth Barbara
Published: June 2024

Multiple scattering of waves is eminent in a wide range of applications and extensive research is being undertaken into multiple scattering by ever more complicated structures, with emphasis on the design of metamaterial structures that manipulate waves in a desired fashion. Ongoing research investigates the design of structures and new solution methods for the governing partial differential equations. There is a pressing need for easy-to-use software that empowers rapid prototyping of designs and for validating other solution methods. We develop a general formulation of the multiple scattering problem that facilitates efficient application of the multipole-based method. The shape and morphology of the scatterers is not restricted, provided their T-matrices are available. The multipole method is implemented in the Tmatsolversoftware package, which uses our general formulation and the T-matrix methodology to simulate accurately multiple scattering by complex configurations with a large number of identical or non-identical scatterers that can have complex shapes and/or morphologies. This article provides a mathematical description of the algorithm and demonstrates application of the software to four contemporary metamaterial problems. It concludes with a brief overview of the object-oriented structure of the Tmatsolvercode.
“Investigating mcr Genes in CRAB Isolates during a NICU outbreak and Advancements in Colistin Sensitivity Testing"
Authors: Raza Mubashir , Khan Saadullah Jan , Masood. Muhammad Faisal , Jafri Laila , Rani Rehana , Sadiq Sara , Jamil Bushra , Ali Roomana
Published: June 2024

Purpose : Colistin-resistant Acinetobacter baumannii (CRAB) poses a growing challenge in neonatal intensive care units (NICUs) due to the emergence of plasmid-mediated Mobile Colistin Resistance (mcr) genes that can rapidly spread among neonates. This pioneering study conducted a comprehensive analysis of mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes in A. baumannii strains isolated from a Pakistani NICU. Notably, this investigation marks the first of its kind in this setting.
In addition to genotypic analyses, the study incorporated phenotypic assays to identify the most effective method for detecting colistin resistance in these A. baumannii strains. The research also encompassed the examination of A. baumannii blood isolates exhibiting low to mid-level colistin resistance during an outbreak in a tertiary care hospital.
Methods: In the genotypic investigation, DNA was extracted from strains of colistin-resistant A. baumannii, collected from the NICU of the local hospital of Islamabad, Pakistan. The specific set of primers for each mcr gene was used to detect their presence. Various phenotypic methods such as; disc diffusion, broth macro dilution, Minimum Inhibition Concentration (MIC), disc elusion and colistin agar methods were performed using predetermined calculations for phenotypic studies.
Results: The study confirms the distribution of the mcr-1 gene among the eight strains, which contributes 66 % of the total number, whereas mcr-2, 3, 4 and 5 genes were not detected in all strains. Based on phenotypic analysis, A. baumannii had shown resistance against colistin at < 2µg/mL. In contrast, MIC varies from strain to strain.
Conclusions: The horizontal transfer of the mcr-1 gene is responsible for developing resistance against colistin among A. baumannii in neonates. All phenotypic methods adopted in this study generated the same results, so the method selection depends upon individual comfort. However, we propose that the colistin agar method offers multiple advantages over other methods as it is more economical, easy to perform, multiple samples can be assessed simultaneously and fewer calculations are involved for colistin resistance determination and finding out clinical breakpoints.
A Multi-Omics Approach to Defining Target Organ Injury in Youth with Primary Hypertension
Authors: Ananthamohan Kalyani , Brady Tammy M. , Arif Mohammed , Daniels Stephen , Falkner Bonita , Ferguson Michael , Flynn Joseph T. , Hanevold Coral , Hooper Stephen R. , Ingelfinger Julie , Lande Marc , Martin Lisa J. , Meyers Kevin E. , Mitsnefes Mark , Rosner Bernard , Samuels Joshua A. , Kuffel Gina , Zilliox Michael J. , Becker Richard C. , Urbina Elaine M. , Sadayappan Sakthivel
Published: June 2024

BACKGROUND

Primary hypertension in childhood tracks into adulthood and may be associated with increased cardiovascular risk. Studies conducted in children and adolescents provide an opportunity to explore the early cardiovascular target organ injury (CV-TOI) in a population free from many of the co-morbid cardiovascular disease risk factors that confound studies in adults.

METHODS

Youths (n=132, mean age 15.8 years) were stratified by blood pressure (BP) as low, elevated, and high-BP and by left ventricular mass index (LVMI) as low- and high-LVMI. Systemic circulating RNA, miRNA, and methylation profiles in peripheral blood mononuclear cells and deep proteome profiles in serum were determined using high-throughput sequencing techniques.

RESULTS

VASH1gene expression was elevated in youths with high-BP with and without high-LVMI.VASH1expression levels positively correlated with systolic BP (r=0.3143, p=0.0034). The expression of hsa-miR-335-5p, one of theVASH1-predicted miRNAs, was downregulated in high-BP with high-LVMI youths and was inversely correlated with systolic BP (r=-0.1891, p=0.0489).GSE1hypermethylation, circulating PROZ upregulation (log2FC=0.61, p=0.0049 and log2FC=0.62, p=0.0064), and SOD3 downregulation (log2FC=-0.70, p=0.0042 and log2FC=-0.64, p=0.010) were observed in youths with elevated BP and high-BP with high-LVMI. Comparing the transcriptomic and proteomic profiles revealed elevatedHYAL1levels in youths displaying high-BP and high-LVMI.

CONCLUSIONS

The findings are compatible with a novel blood pressure-associated mechanism that may occur through impaired angiogenesis and extracellular matrix degradation through dysregulation of Vasohibin-1 and Hyaluronidase1 was identified as a possible mediator of CV-TOI in youth with high-BP and suggests strategies for ameliorating TOI in adult-onset primary hypertension.
Isolation and Genomic Analysis of Escherichia Phage AUBRB02: Implications for Phage Therapy in Lebanon
Authors: Ahmad Tasnime Abdou , Houjeiry Samar El , Abou Fayad Antoine , Kanj Souha , Matar Ghassan , Saba Esber
Published: June 2024

We obtained a new and unique Escherichia phage, AUBRB02, from sewage water in Beirut, Lebanon, as part of this research. AUBRB02 has an incubation period of around 45 minutes, a lysis period of about 10 minutes, and a burst size of around 30 plaque-forming units per cell. The phage exhibited strong biological stability over a pH range of 5.0–9.0 and temperatures ranging from 4°C to 60°C. AUBRB02 was found to have a genome size of 166,871 base pairs and a G+C content of 35.47% using whole-genome sequencing. A comparative analysis revealed that AUBRB02, a newly found phage, shares 93% intergenomic similarity to closest relative in refseq. Functional annotation revealed the presence of 10 tRNA and 262 coding sequences, out of which 123 are categorized as putative proteins. These results indicate that AUBRB02 is a highly infectious virus that belongs to theTequatrovirusgenus. This study is significant reference information that can be used in the development of phage therapy.

IMPORTANCE

Escherichia coli, a gram-negative bacterium, is a widely distributed pathogen in the natural environment and a frequent cause of illnesses. The extensive utilization of antibiotics has resulted in a rise of clinically resistant strains, posing a substantial obstacle to antimicrobial therapy. This urgent circumstance highlights the necessity for antibiotic substitutes to combatE. coliinfections. In this context, we introduce AUBRB02, a novel Escherichia phage isolated from an untreated sewage source in Beirut. Our findings indicate that AUBRB02 is highly lytic, stable against extreme culturing conditions, and has a biofilm elimination capability.
Optimizing genomic prediction for complex traits via investigating multiple factors in switchgrass
Authors: Wang Peipei , Meng Fanrui , Del Azodi Christina B , Abá Kenia Segura , Casler Michael D. , Shiu Shin-Han
Published: June 2024

Genomic prediction, the use of genetic information for predicting traits, has accelerated the breeding processes and provided mechanistic insights into the genetic bases of complex traits. While substantial efforts have been devoted to optimize genomic prediction, there remain areas that need to be further explored, including the impact of genome assemblies, genotyping approaches, variant types, allelic complexities, polyploidy levels, and population structures. Here, we assess the impact of these factors on the prediction of 20 complex traits in switchgrass (Panicum virgatumL.), a perennial biofuel feedstock. We found that short read-based genome assembly perform comparably to or even better than long read-based assembly in trait prediction; exome capture-based models have higher prediction accuracy than genotyping-by-sequencing-based models for 13 traits; bi-allelic insertion/deletions are as useful as bi-allelic single nucleotide polymorphisms in trait prediction, whereas multi-allelic variants outperform bi-allelic ones for 15 traits. Models built for tetraploids have higher prediction accuracy than those for octoploids for most traits. Traits of individuals with higher within-population genetic distances tend to have higher prediction accuracy. Finally, integrating different types of variants can improve the prediction accuracy. By exploring these factors, anthesis date prediction models built using multi-allelic insertion/deletions derived from exome capture led to the largest number of orthologs of benchmark flowering time genes compared to other models. Our study provides insights into the factors influencing genomic prediction outcomes that inform best practices for future studies and for improving agronomic traits in switchgrass and other species through selective breeding.
One-for-all gene inactivation via PAM-independent base editing in bacteria
Authors: Li Xin , Wei Ying , Wang Shu-Yan , Wang Shu-Guang , Xia Peng-Fei
Published: June 2024

Base editing is preferable for bacterial gene inactivation without generating double strand breaks, requiring homology recombination or highly efficient DNA delivery capability. However, the potential of base editing is limited by the adjoined dependence on the editing window and protospacer adjacent motif (PAM). Herein, we report an unconstrained base editing system to enable the inactivation of any genes of interests (GOIs) in bacteria. We first employed a dCas9 derivative, dSpRY, as the effector to build a base editor with activation-induced cytidine deaminase, releasing the dependence on PAM. Then, we programmed the base editor to exclude the START codon of a GOI instead of introducing STOP codons to obtain a universal approach for gene inactivation, namely XSTART, with an overall efficiency approaching 100%. By using XSTART, we successfully manipulated the amino acid metabolisms inEscherichia coli, generating glutamine, arginine, and aspartate auxotrophic strains. The effectiveness of XSTART was also demonstrated in probioticE. coliNissle 1917 and photoautotrophic cyanobacteriumSynechococcus elongatus, illustrating its potential in reprogramming clinically and industrially relevant chassis. To be noticed, we observed a relatively high frequency of off-target events as a trade-off for the efficacy and universality.
A model for accurate quantification of CRISPR effects in pooled FACS screens
Authors: Pimentel Harold , Freimer Jacob W. , Arce Maya M. , Garrido Christian M. , Marson Alexander , Pritchard Jonathan K.
Published: June 2024

CRISPR screens are powerful tools to identify key genes that underlie biological processes. One important type of screen uses fluorescence activated cell sorting (FACS) to sort perturbed cells into bins based on the expression level of marker genes, followed by guide RNA (gRNA) sequencing. Analysis of these data presents several statistical challenges due to multiple factors including the discrete nature of the bins and typically small numbers of replicate experiments. To address these challenges, we developed a robust and powerful Bayesian random effects model and software package called Waterbear. Furthermore, we used Waterbear to explore how various experimental design parameters affect statistical power to establish principled guidelines for future screens. Finally, we experimentally validated our experimental design model findings that, when using Waterbear for analysis, high power is maintained even at low cell coverage and a high multiplicity of infection. We anticipate that Waterbear will be of broad utility for analyzing FACS-based CRISPR screens.
Systems Modeling Reveals Shared Metabolic Dysregulation and Potential Treatments in ME/CFS and Long COVID
Authors: Li Gong-Hua , Han Feifei , Kalafatis Efthymios , Kong Qing-Peng , Xiao Wenzhong
Published: June 2024

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID are complex, multisystem conditions that pose significant challenges in healthcare. Accumulated research evidence suggests that ME/CFS and Long COVID exhibit overlapping metabolic symptoms, indicating potential shared metabolic dysfunctions. This study aims to systematically explore shared metabolic disturbances in the muscle tissue of patients. Utilizing genome-wide metabolic modeling, we identified key metabolic irregularities in the muscle of patients with ME/CFS, notably the downregulation of the alanine and aspartate metabolism pathway and the arginine and proline metabolism pathway. Further,in silicoknockout analyses suggested that supplementation with aspartate (ASP) or asparagine (ASN) could potentially ameliorate these metabolic deficiencies. In addition, assessments of metabolomic levels in Long COVID patients also showed the significant downregulation of ASP during post-exertional malaise (PEM) in both muscle and blood. Consequently, we propose that a combination of l-ornithine and l-aspartate (LOLA) is a potential candidate to alleviate metabolic symptoms in ME/CFS and Long COVID for future clinical trials.
The Integration of Health Equity into Policy to Reduce Disparities: Lessons from California during the COVID-19 Pandemic
Authors: Kwan Ada T. , Vargo Jason , Kurtz Caroline , Panditrao Mayuri , Hoover Christopher M. , León Tomás M. , Rocha David , Wheeler William , Jain Seema , Pan Erica S. , Shete Priya B.
Published: June 2024

Racial and ethnic minoritized groups and socioeconomically disadvantaged communities experience longstanding health-related disparities in the US and were disproportionately affected throughout the COVID-19 pandemic. How departments of public health can explicitly address these disparities and their underlying determinants remains less understood. To inform future public health responses, this paper details how California strategically placed health equity at the core of its COVID-19 reopening and response policy, known as theBlueprint for a Safer Economy. In effect from August 2020 to June 2021, “the Blueprint” employed the use of the California Healthy Places Index (HPI), a summary measure of 25 social determinants of health constructed at the census tract level, to guide activities. Using California’s approach, we categorized the state population by HPI quartiles at the state and within-county levels (HPIQ1 representing the least advantaged, HPIQ4, the most advantaged) from HPI data available to demonstrate how the state monitored COVID-19 test, case, mortality, and vaccine outcomes using equity metrics developed for the Blueprint. Notable patterns emerged. Testing disparities disappeared during the summer and winter surges but resurfaced between surges. Monthly case rate ratios (RR) peaked in May 2020 for HPIQ1 compared to HPIQ4 (RR 6.61, 95%CI: 6.41–6.81), followed by mortality RR peaking in June 2020 (RR 5.06, 95% CI: 4.34–5.91). As the pandemic wore on, case and mortality disparities between lower HPI quartiles relative to HPIQ4 reduced but remained. Utilizing an ABSM, such as HPI, enabled a data-driven approach to identify priority communities, allocate resources, and monitor outcomes based on need during a large-scale public health emergency.
Normative characterization of age-related periodic and aperiodic activity in resting-state clinical EEG recordings
Authors: Leroy Sophie , Bublitz Viktor , von Dincklage Falk , Antonenko Daria , Fleischmann Robert
Published: June 2024

Objective

Non-invasive oscillatory brain stimulation techniques target the oscillatory activity of the brain and have several potential therapeutic applications in the clinical context. The aim of these analyses from clinical routine EEG recordings was to provide normative values of physiological age-related oscillatory (periodic) and non-rhythmic (aperiodic) activity.

Methods

We analyzed 532 EEGs of patients between 8 and 92 years of age. EEG segments were preprocessed, and the power spectrum was computed using a multitaper method. We decomposed the power spectrum into periodic (peak power, frequency, and bandwidth) and aperiodic (intercept and exponent) components. Linear regression models were used to investigate age-related changes in these parameters.

Results

We observed significant global age-related changes in the periodic alpha (- 0.015 Hz/year) and gamma (+ 0.013 to + 0.031Hz/year) peak frequency as well as in the aperiodic exponent (- 0.003 to - 0.004 μV2/Hz/year). In the other parameters there were solely regional or no significant age-related changes.

Conclusions

Decomposing the power spectrum into periodic and aperiodic components allows for the characterization of age-related changes.

Significance

This study provides the first spectrum-wide normative characterization of age-related changes in periodic and aperiodic activity, relevant for non-invasive brain stimulation with alternating current targeting ongoing oscillatory activity.

Highlights

-

Alpha peak frequency decreases with age, while gamma peak frequency accelerates.

-

Age-related changes in alpha and theta power result from a flattening of the aperiodic slope, not decreased oscillatory activity

-

Decomposing the EEG spectrum into periodic and aperiodic activity is essential when characterizing ongoing oscillatory activity
The resilient brain against childhood poverty
Authors: Hu Bowen , Yang Tongxi , Hu Yuanyuan , Qin Shaozheng
Published: June 2024

Poverty remains a persistent structural issue in society, profoundly impacting children’s mental health and resilience. However, the influence of poverty on children’s resilience and its neural underpinnings is not well understood. This study investigates this impact using a nationally representative sample (N = 11878) and neuroimaging techniques to explore the heterogeneity of resilience mechanisms in poor children. Our findings reveal that poor children (living below the federal poverty threshold) experience exacerbated effects of early life adversities (ELAs) on behavioral problems, which persist into adolescence, indicating disrupted resilience. By subtyping poor children based on neural representations of self-regulation (brain activation during stop signal task), we identified two distinct subtypes: subtype-1, with heightened neural activation, exhibited significantly worse resilience; while subtype-2, with reduced activation, showed resilience levels comparable to non-poor children. Two subtypes did not differ significantly in superficial characteristics including ELA exposure and demographics. However, poor children with subtype-1 had thicker left-middle-frontal-gyrus (L-MFG) brain regions, correlating with fewer behavioral problems and weaker ELA impacts, suggesting a unique resilience mechanism. This L-MFG-based resilience mechanism is exclusive to subtype-1, and not observed in subtype-2 or non-poor children. These findings underscore the importance of understanding individual heterogeneity in resilience mechanisms among disadvantaged children. Our study emphasizes the need for future research to delve deeper into adaptation processes to ELAs and poverty, advocating for the exploration of varied resilience mechanisms to mitigate the stigma associated with poverty and guide interventions aimed at narrowing mental health gradient.
The role of socio-economic determinants in SARS-CoV-2 health outcomes: systematic review of population-based studies.
Authors: Ghattas Jinane , Makovski Tatjana , Monnier-Besnard Stephanie , Cavillot Lisa , Ambrozova Monika , Budikova Barbora , Feteira-Santos Rodrigo , Bezzegh Peter , Ponce Bollmann Felipe , Cottam James , Haneef Romana , Speybroeck Niko , Nogueira Paulo Jorge , Forjaz Maria Joao , Coste Joel , Carcaillon-bentata Laure , Devleesschauwer Brecht
Published: June 2024

Introduction: The COVID-19 pandemic has accentuated a health-wealth gradient, reminiscent of patterns observed in previous influenza pandemics. This systematic review, employing a population-based approach, aims to delve into the etiological and prognostic roles of socio-economic factors on COVID-19 outcomes during the pandemic's initial phase. Methods: Our search spanned PubMed, Embase, WHO COVID-19 Global literature, and PsycINFO databases from January 2020 to April 7, 2021, focusing on English peer-reviewed articles. We examined the impact of socio-economic determinants on SARS-CoV-2 infection, COVID-19 related hospitalization, ICU admission, mechanical ventilation, mortality, and a range of prognostic outcomes including quality of life and mental health. Results: The initial search resulted in 9,701 records after removal of duplicates. Out of hundred articles that met our review criteria, 67 discussed the etiological role of socio-economic factors, 25 addressed the prognostic role, and 8 covered both. Fifty-nine percent of the studies were from the United States of America and the United Kingdom, highlighting an increased risk of infection and severity among their Black, Asian, and Hispanic populations. Lower-income groups, crowded households, and, higher socio-economic deprivation were associated with higher COVID-19 incidence and severity. Results regarding educational status varied across different waves. Conclusion: Populations groups with disadvantaged socio-economic positions and certain ethnic and racial backgrounds face a higher risk of SARS-CoV-2 infection and poorer COVID-19 outcomes. Our findings underscore the need for incorporating social determinants into routine health surveillance and monitoring, suggesting an avenue for targeted interventions.
Long-term Public Healthcare Burden Associated with Intimate Partner Violence among Canadian Women: A Cohort Study
Authors: Dusing Gabriel John , Essue Beverley M. , O’Campo Patricia , Metheny Nicholas
Published: June 2024

Intimate partner violence (IPV) is a major global health issue, yet few studies explore its long-term public healthcare burden in countries with universal healthcare systems. This study analyzes this burden among Canadian women using data from the Neighborhood Effects on Health and Wellbeing survey and Ontario Health Insurance Plan (OHIP) records from 2009-2020. We employed inverse probability weighting with regression adjustment to estimate differences in cumulative costs and OHIP billings between those reporting exposure to IPV during the survey and those who did not. Our sample included 1,094 women, with 38.12% reporting IPV exposure via the Hurt, Insult, Threaten, Scream scale. Findings show a significant public healthcare burden due to IPV: women reporting IPV in 2009 had an average of 17% higher healthcare costs and 41 additional OHIP billings (0.1732;95% CI: 0.0578-0.2886; 41.23;95% CI: 12.63-69.82). Policies prioritizing primary prevention and integration of trauma-informed care among healthcare providers are vital to alleviate the long-term burden on public health systems.
Sex and aging signatures of proteomics in human cerebrospinal fluid identify distinct clusters linked to neurodegeneration
Authors: Seo Dahun , Lee Cheolmin Matthew , Apio Catherine , Heo Gyujin , Timsina Jigyasha , Kohlfeld Pat , Boada Merce , Orellana Adelina , Fernandez Maria Victoria , Ruiz Agustin , Morris John C. , Schindler Suzanne E. , Park Taesung , Cruchaga Carlos , Sung Yun Ju
Published: June 2024

Sex and age are major risk factors for chronic diseases. Recent studies examining age-related molecular changes in plasma provided insights into age-related disease biology. Cerebrospinal fluid (CSF) proteomics can provide additional insights into brain aging and neurodegeneration. By comprehensively examining 7,006 aptamers targeting 6,139 proteins in CSF obtained from 660 healthy individuals aged from 43 to 91 years old, we subsequently identified significant sex and aging effects on 5,097 aptamers in CSF. Many of these effects on CSF proteins had different magnitude or even opposite direction as those on plasma proteins, indicating distinctive CSF-specific signatures. Network analysis of these CSF proteins revealed not only modules associated with healthy aging but also modules showing sex differences. Through subsequent analyses, several modules were highlighted for their proteins implicated in specific diseases. Module 2 and 6 were enriched for many aging diseases including those in the circulatory systems, immune mechanisms, and neurodegeneration. Together, our findings fill a gap of current aging research and provide mechanistic understanding of proteomic changes in CSF during a healthy lifespan and insights for brain aging and diseases.
Experiences and preferences in Zambia and South Africa for delivery of HIV treatment during a client’s first six months: a cross-sectional survey
Authors: Mutanda Nyasha , Morgan Allison , Kamanga Aniset , Sande Linda , Ntjikelane Vinolia , Maskew Mhairi , Haimbe Prudence , Lumano-Mulenga Priscilla , Rosen Sydney , Scott Nancy
Published: June 2024

Background

Disengagement from antiretroviral therapy (ART) is highest in the early treatment period (≤6 months after initiation/re-initiation), but low intensity models designed to increase retention generally exclude these clients. We describe client preferences for HIV service delivery in the early treatment period.

Methods

From 9/2022-6/2023, we surveyed adult clients who were initiating or on ART for ≤6 months at primary health facilities in South Africa and Zambia. We collected data on experiences with and preferences for HIV treatment.

Results

We enrolled 1,098 participants in South Africa (72% female, median age 33) and 771 in Zambia (67% female, median age 32), 38% and 34% of whom were initiating/re-initiating ART in each country, respectively. While clients expressed varied preferences, most participants (94% in South Africa, 87% in Zambia) were not offered choices regarding service delivery. 82% of participants in South Africa and 36% in Zambia reported receiving a 1-month supply of medication at their most recent visit; however, South African participants preferred 2- or 3-month dispensing (69%), while Zambian participants preferred 3-or 6-month dispensing (85%). Many South African participants (65%) would prefer to collect medication in community settings, while Zambian participants (70%) preferred clinic-based collection. Half of participants desired more one-on-one counselling and health information. Most participants reported positive experiences with providers, but long waiting queues were reported by South African participants.

Conclusions

During the first six months on ART, many clients would prefer less frequent clinic visits, longer dispensing intervals, and frequent, high-quality counselling. Care models for the early treatment period should reflect these preferences.

Registration

Clinicaltrials.govNCT05454839,Clinicaltrials.govNCT05454852
Antipsychotic management in general practice: serial cross-sectional study (2011-2020)
Authors: Woodall Alan , Gampel Alex , Collins Huw , Walker Lauren E , Mair Frances S , Sheard Sally , Symon Pyers , Buchan Iain
Published: June 2024

Background

Long-term use of antipsychotics confers increased risk of cardiometabolic disease. Ongoing need should be reviewed regularly by psychiatrists.

Aim

To explore trends in antipsychotic management in general practice, and proportions of patients prescribed antipsychotics receiving psychiatrist review.

Design and Setting

A serial cross-sectional study using linked general practice and hospital data in Wales (2011-2020).

Method

Participants were adults (≥18 years) registered with general practices in Wales. Outcome measures were prevalence of patients receiving ≥6 antipsychotic prescriptions annually, proportion of patients prescribed antipsychotics receiving annual psychiatrist review, and proportion of patients prescribed antipsychotics registered on UK Serious Mental Illness, Depression and/or Dementia registers, or not on any of these registers.

Results

Prevalence of adults prescribed long-term antipsychotics increased from 1.06% (95%CI 1.04 to 1.07%) in 2011 to 1.45% (95%CI 1.43 to 1.46%) in 2020. The proportion receiving annual psychiatrist review decreased from 59.6% (95%CI 58.9 to 60.4%) in 2011 to 52.0% (95C%CI 51.4 to 52.7%) in 2020. The proportion of antipsychotics prescribed to patients not on the Serious Mental Illness register increased from 50% (95%CI 49 to 51%) in 2011 to 56% (95%CI 56 to 57%) by 2020.

Conclusions

Prevalence of long-term antipsychotic use is increasing. More patients are managed by general practitioners without psychiatrist review and are not on monitored disease registers; they thus may be less likely to undergo cardiometabolic monitoring and miss opportunities to optimise or deprescribe antipsychotics. These trends pose risks for patients and need to be addressed urgently.

How this fits in

Antipsychotics are effective treatments for serious mental illness, but long-term use increases the risk of cardiometabolic disease, therefore ongoing use should be reviewed regularly. There is increasing use of these medications for non-psychotic mental illness by psychiatrists who then discharge patients to sole care by GPs, often for patients who are not captured on disease registers that automate recall for cardiometabolic risk monitoring. This study demonstrates a rising burden of long-term antipsychotic prescribing in general practice, with nearly half of all adult patients not under annual psychiatrist review, and only 44% of long-term antipsychotic prescriptions being issued to patients coded on the Quality and Outcomes Framework (QOF) Serious Mental Illness register. This means many patients taking antipsychotics may be missed for cardiometabolic screening and expert review. Policy changes are required to ensure regular effective review and monitoring to prevent increasing morbidity and early mortality for patients prescribed long-term antipsychotics.
Validation of anthropometric-based weight prediction equations among Ugandan adults: A Cross-sectional study
Authors: Mukasa Zakaria , Ntuulo Juliet Mutanda , Kasirye Ronnie , Olal Emmanuel , Lwanga Christopher , Nankabirwa Victoria , Nuwaha Fred
Published: June 2024

Introduction

Proper patient management often requires accurate weight estimation. However, the appropriate weight-measuring equipment is not always available in resource-limited settings, making clinicians resort to less reliable methods like the visual estimation of weight often with negative consequences. In this study, we assess the accuracy of anthropometric-based equations in predicting weight in Ugandan adults.

Methods

A cross-sectional study was conducted at Kira Health Center IV between December 2021 and February 2022. A sample of 240 adult patients, 18 years and above, was selected by quota sampling, stratified by sex and body mass index. Demographic information was obtained and anthropometric measurements including weight, height, knee height, subscapular skin fold thickness, and circumference measurements were taken. The predicted weight was computed using the proposed equations and the accuracy of the different equations was determined using Bland Altman analysis taking the equation with the best agreement as the most accurate.

Results

Out of 240 participants, 50% were females. The mean (standard deviation) age was 32.5(11.8) years; (34.1(12.9) years for males and 30.8(10.3) years for females). The mean (standard deviation) actual weight was 66.43 (16.33) kg while the mean height was 1.64 (0.09) meters. Using Bland-Altman analysis, Rabito equation (Weight = (0.5759xMAC) + (0.5263xAC) + (1.2452xCC) - (4.8689xS)-32.9241) was found to have the best agreement with the actual weight with a mean difference (standard deviation) of 2.55(6.99) kilograms overall.

Conclusion

Equation R3 was the most accurate equation for predicting weight among Ugandan adults. Therefore, in the absence of appropriate weighing scales to weigh patients, using this anthropometric-based weight estimation equation can act as a relatively accurate alternative.
Orthosteric STING inhibition elucidates molecular correction of SAVI STING
Authors: Xie Tao , Ruzanov Max , Critton David , Merselis Leidy , Naglich Joseph , Sack Jack , Zhang Ping , Xie Chunshan , Tredup Jeffrey , Stine Laurel B. , Messier Cameron , Caceres-Cortes Janet , Mueller Luciano , Dyckman Alaric J. , Newitt John A. , Wilson Stephen C.
Published: June 2024

STING is broadly implicated in diseases ranging from cancer, autoimmune disease, neurodegeneration to rare, monogenic diseases.1Early drug discovery campaigns focused on STING activation as a promising platform for cancer immunotherapy yet failed in multiple clinical trials due to lack of efficacy thus far.2Current research and development activities concentrate on STING inhibition for treating autoimmune disease and neuroinflammation. While the progression of STING activators into the clinic has been successful, the discovery and clinical progression of STING inhibitors remain elusive. Questions persist about the molecular properties needed to distinguish between a STING activator and inhibitor, particularly within SAVI disease, a monogenic autoinflammatory disease that renders STING constitutively active.3Here we leverage an orthosteric STING activator and inhibitor from the same chemical series to discover that STING M271 is a critical residue for molecular activation. The M271CH3NMR chemical shifts reveal a unique molecular signature for pharmacological or genetically driven activation and inhibition that is not captured by x-ray crystallography. Additionally, M271 directly interacts with the most common SAVI mutation, V155M, and using an orthosteric STING inhibitor, we show partial rescue and molecular correction of STING V155M. Finally, these data present insights into therapeutic STING molecular correction for treating SAVI patients. Our results elucidate an unappreciated structural interaction critical for STING modulation that could be utilized as a molecular diagnostic tool for drug discovery. Furthermore, we demonstrate for the first time how the therapeutic requirements of a molecular corrector differ from an orthosteric STING inhibitor, and why this is important for the SAVI disease population.
Structural Basis for Substrate Binding, Catalysis and Inhibition of Breast Cancer Target Mitochondrial Creatine Kinase by Covalent Inhibitor via Cryo-EM
Authors: Demir Merve , Koepping Laura , Li Ya , Fujimoto Lynn , Bobkov Andrey , Zhao Jianhua , Hitosugi Taro , Sergienko Eduard
Published: June 2024

Mitochondrial creatine kinases are key players in maintaining energy homeostasis in cells by working in conjunction with cytosolic creatine kinases for energy transport from mitochondria to cytoplasm. High levels of MtCK observed in Her2+ breast cancer and inhibition of breast cancer cell growth by substrate analog, cyclocreatine, indicate dependence of cancer cells on the ‘energy shuttle’ for cell growth and survival. Hence, understanding the key mechanistic features of creatine kinases and their inhibition plays an important role in the development of cancer therapeutics. Herein, we present the mutational and structural investigation on understudied ubiquitous mitochondrial creatine kinase (uMtCK). Our cryo-EM structures and biochemical data on uMtCK showed closure of the loop comprising residue His61 is specific to and relies on creatine binding and the reaction mechanism of phosphoryl transfer depends on electrostatics in the active site. In addition, the previously identified covalent inhibitor CKi showed inhibition in breast cancer BT474 cells, however our biochemical and structural data indicated that CKi is not a potent inhibitor for breast cancer due to strong dependency on the covalent link formation and inability to induce conformational changes upon binding.