bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing characteristics of populations seen at Commission on Cancer facilities using Pennsylvania linked data
Authors: Reed Kristine G , Sun Zhaojun , Yabes Jonathan G , Drake Coleman , Ober Nicole , Jacobs Bruce , van Londen G J , Bradley Cathy J , Sabik Lindsay M
Published: October 2023

Commission on Cancer (CoC) accreditation certifies facilities provide quality care. We assessed differences among patients who do and do not visit CoC facilities using Pennsylvania Cancer Registry data linked to facility records for patients diagnosed with cancer between 2018 and 2019 (n = 87 472). Predicted probabilities from multivariable logistic regression indicated patients in the most advantaged Area Deprivation Index quartiles were more likely to visit CoC facilities (78.0%, 95% confidence interval [CI] = 77.5% to 78.6%) compared with other quartiles. Urban patients (74.1%, 95% CI = 73.8% to 74.4%) were more likely than rural to be seen at a CoC facility (62.7%, 95% CI = 61.2% to 64.2%) as were Hispanic patients (88.0%, 95% CI = 86.7% to 89.3%) and non-Hispanic Black patients (79.1%, 95% CI = 78.1% to 80.0%) compared with White patients (72.0%, 95% CI = 71.7% to 72.4%). Differences in demographics suggest CoC data may underrepresent some groups, including low-income and rural patients.
Predicting the impact of feedback on matter clustering with machine learning in CAMELS
Authors: Delgado Ana Maria , Anglés-Alcázar Daniel , Thiele Leander , Pandey Shivam , Lehman Kai , Somerville Rachel S , Ntampaka Michelle , Genel Shy , Villaescusa-Navarro Francisco , Hernquist Lars
Published: October 2023

Extracting information from the total matter power spectrum with the precision needed for upcoming cosmological surveys requires unraveling the complex effects of galaxy formation processes on the distribution of matter. We investigate the impact of baryonic physics on matter clustering at z = 0 using a library of power spectra from the Cosmology and Astrophysics with MachinE Learning Simulations project, containing thousands of $(25\, h^{-1}\, {\rm Mpc})^3$ volume realizations with varying cosmology, initial random field, stellar and active galactic nucleus (AGN) feedback strength and subgrid model implementation methods. We show that baryonic physics affects matter clustering on scales $k \gtrsim 0.4\, h\, \mathrm{Mpc}^{-1}$ and the magnitude of this effect is dependent on the details of the galaxy formation implementation and variations of cosmological and astrophysical parameters. Increasing AGN feedback strength decreases halo baryon fractions and yields stronger suppression of power relative to N-body simulations, while stronger stellar feedback often results in weaker effects by suppressing black hole growth and therefore the impact of AGN feedback. We find a broad correlation between mean baryon fraction of massive haloes (M200c > 1013.5 M⊙) and suppression of matter clustering but with significant scatter compared to previous work owing to wider exploration of feedback parameters and cosmic variance effects. We show that a random forest regressor trained on the baryon content and abundance of haloes across the full mass range 1010 ≤ Mhalo/M⊙<1015 can predict the effect of galaxy formation on the matter power spectrum on scales k = 1.0–20.0 $h\, \mathrm{Mpc}^{-1}$.
Anal Cancers in Previously Screened Versus Unscreened Patients: Tumor Stage and Treatment Outcomes
Authors: Walker Richard J.B. , Easson Alexandra M. , Hosni Ali , Kim John , Weiss Edward , Santiago Anna Theresa , Chesney Tyler R. , Salit Irving E.
Published: October 2023

BACKGROUND:

Targeted screening programs for patients at high risk for anal squamous cell carcinoma have been proposed; however, the evidence in support of screening remains unclear.

OBJECTIVE:

This study aimed to determine whether screening high-risk patients (predominantly those living with HIV) detected squamous cell carcinoma at an earlier stage compared to the routine practice of not screening.

DESIGN:

This is a cohort study.

SETTINGS:

This study was conducted at a quaternary care center in Canada.

PATIENTS:

Included patients were at least 18 years old with a pathologic diagnosis of invasive anal squamous cell carcinoma between 2002 and 2022.

INTERVENTIONS:

Patients diagnosed through a high-risk screening program were compared to those who did not undergo screening.

MAIN OUTCOME MEASURES:

The primary outcome was clinical stage at presentation, categorized as T1N0M0 vs. other. Secondary outcomes included treatments received, treatment failure, and overall survival.

RESULTS:

A total of 612 anal squamous cell carcinoma patients were included, with 26 of those patients diagnosed through a screening program. Patients with screen-detected cancers had greater odds of presenting with T1N0M0 tumors compared to unscreened patients (18 [69.2%] vs. 84 [14.3%]; adjusted odds ratio 9.95; 95% confidence interval 3.95-25.08). A propensity score matched sensitivity analysis found similar results (odds ratio 11.13; 95% confidence interval 4.67-26.52; p < 0.001). Screened patients had greater odds of treatment with wide local excision alone, as opposed to any combination of chemotherapy, radiation, and surgery (3 [12.5%] vs. 18 [3.2%]; odds ratio 4.38; 95% confidence interval 1.20-16.04). There were no statistically significant differences in treatment failure or overall survival between groups.

LIMITATIONS:

The small number of screened patients limits the power of the analysis.

CONCLUSIONS:

Screening for anal squamous cell carcinoma amongst high-risk populations detects cancers at an earlier stage. Patients with screen-detected cancers also had a greater likelihood of being candidates for wide local excision alone, which may have spared them the morbidity associated with chemoradiotherapy or abdominoperineal resection.
Efficacy and Safety of Precision Cryotherapy to Treat Seborrheic Dermatitis of the Scalp
Authors: Choi Yeon Gu , Kim Sang Yeon , Kim Jin Seop , Choi Young-Jun , Kim Won-Serk
Published: October 2023

BACKGROUND

Recently, a new cryotherapy device that precisely controls skin temperature was developed. Precision cryotherapy (PC) can be a safe and alternative treatment modality for immune-related skin diseases that are difficult to treat by conventional cryotherapy because of serious adverse events.

OBJECTIVE

To evaluate the efficacy and safety of PC in scalp seborrheic dermatitis (SD).

METHODS

A single-arm, prospective trial was designed. Twenty-four patients with SD underwent 3 PC interventions 2 weeks apart. At the baseline, Week 6, and Week 8, overall improvements in Physician Global Assessment (PGA) and clinical severity scores were assessed. At each visit, the erythema index (EI) and transepidermal water loss were evaluated. The patients scored 9 subjective symptoms using a visual analog scale (VAS).

RESULTS

The itch VAS score decreased by 50.4% at Week 8. Blinded investigators reported improvement of PGA scores from 2.86 ± 0.62 to 1.66 ± 0.61 and clinical severity scores from 4.55 ± 1.30 to 2.45 ± 1.37. The average EI decreased by 19.6% at Week 8 (p < .05).

CONCLUSION

This study not only demonstrated the efficacy and safety of PC in scalp SD but it also revealed insights for PC being a promising treatment modality in immune-related skin diseases.
Feasibility of Integrating MEditatioN inTO heaRt Disease (the MENTOR Study)
Authors: Rao Angela , Zecchin Robert , Newton Phillip J. , Read Scott A. , Phillips Jane L. , DiGiacomo Michelle , Chang Sungwon , Denniss Alan Robert , Hickman Louise D.
Published: October 2023

Background

Comorbid depression and/or anxiety symptoms occur in 25% of patients attending cardiac rehabilitation (CR) programs and are associated with poorer prognosis. There is a need to evaluate psychological interventions, including meditation, that have potential to improve psychological health in CR programs.

Aims

The aim of this study was to determine the feasibility and acceptability of integrating a meditation intervention into an existing Australian CR program for the reduction of depression and anxiety symptoms.

Methods

This was a mixed-methods feasibility randomized controlled trial. Thirty-one patients with CVD and, at a minimum, mild depression and/or anxiety symptoms were randomized to meditation and standard CR or to standard CR alone. A 16-minute guided group meditation was delivered face-to-face once a week for 6 weeks, with daily self-guided meditation practice between sessions. Feasibility outcomes included screening, recruitment, and retention. Semistructured interviews of patients' (n = 10) and health professionals' (n = 18) perspectives of intervention participation and delivery were undertaken to assess acceptability. Between-group differences in depression, anxiety, stress, self-efficacy for mindfulness, and health status at 6 and 12 weeks were also assessed.

Results and Conclusion

Meditation was considered feasible, with 83% (12/15) of the intervention group completing an average of 3.13 (SD, 2.56) out of 6 group meditation sessions and 5.28 (SD, 8.50) self-guided sessions. Meditation was considered acceptable by patients, clinicians, and health managers. Between-group differences in the number of CR sessions completed favored the intervention group in per-protocol analyses (intervention group vs control group, 12 vs 9 sessions; P = .014), which suggests that meditation may be useful to improve patients' adherence to exercise-based CR program.
Extracorporeal Membrane Oxygenation Support and Critically Ill COVID-19 Patient Outcomes: A Population-Based Cohort Study
Authors: Kyu Oh Tak , Song In-Ae
Published: October 2023

We selected critically ill patients with coronavirus disease 2019 (COVID-19) who were receiving extracorporeal membrane oxygenation (ECMO) support and had been transferred to experienced centers. Thus, we aimed to evaluate factors that were associated with receiving ECMO support and factors that were associated with patient mortality. Using data from the National Health Insurance Service and Korea Disease Control and Prevention Agency in South Korea, adult patients admitted to an intensive care unit from October 8, 2020, to December 31, 2021, with a main diagnosis of COVID-19 were included. They were divided into two groups: ECMO group (n = 455) and non-ECMO group (n = 12,648). Receiving ECMO support was less associated with old age [odds ratio (OR), 0.95; 95% confidence interval (CI), 0.94–0.96; p < 0.001], underlying severe disabilities (OR, 0.49; 95% CI, 0.29–0.83; p = 0.008), and booster vaccination status (second: OR, 0.61; 95% CI, 0.39–0.94; p = 0.024; third: OR, 0.40; 95% CI, 0.25–0.65; p < 0.001). In addition, after adjusting for various variables, low mortality in patients with ECMO support was associated with having previously received a second booster vaccination (OR, 0.33; 95% CI, 0.14–0.77; p = 0.010). Vaccination and booster therapy may lower the need for ECMO support and lower mortality among critically ill patients with COVID-19 with ECMO support.
Ambulance response times and 30-day mortality: a Copenhagen (Denmark) registry study
Authors: Mills Alexander Andrew Matthew , Mills Elisabeth Helen Anna , Blomberg Stig Nikolaj Fasmer , Christensen Helle Collatz , Møller Amalie Lykkemark , Gislason Gunnar , Køber Lars , Kragholm Kristian Hay , Lippert Freddy , Folke Frederik , Andersen Mikkel Porsborg , Torp-Pedersen Christian
Published: October 2023

Background and importance

Ensuring prompt ambulance responses is complicated and costly. It is a general conception that short response times save lives, but the actual knowledge is limited.

Objective

To examine the association between the response times of ambulances with lights and sirens and 30-day mortality.

Design

A registry-based cohort study using data collected from 2014–2018.

Settings and participants

This study included 182 895 individuals who, during 2014–2018, were dispatched 266 265 ambulances in the Capital Region of Denmark.

Outcome measures and analysis

The primary outcome was 30-day mortality. Subgroup analyses were performed on out-of-hospital cardiac arrests, ambulance response priority subtypes, and caller-reported symptoms of chest pain, dyspnoea, unconsciousness, and traffic accidents. The relation between variables and 30-day mortality was examined with logistic regression.

Results

Unadjusted, short response times were associated with higher 30-day mortality rates across unadjusted response time quartiles (0–6.39 min: 9%; 6.40–8.60 min: 7.5%, 8.61–11.80 min: 6.6%, >11.80 min: 5.5%). This inverse relationship was consistent across subgroups, including chest pain, dyspnoea, unconsciousness, and response priority subtypes. For traffic accidents, no significant results were found. In the case of out-of-hospital cardiac arrests, longer response times of up to 10 min correlated with increased 30-day mortality rates (0–6.39 min: 84.1%; 6.40–8.60 min: 86.7%, 8.61–11.8 min: 87.7%, >11.80 min: 85.5%). Multivariable-adjusted logistic regression analysis showed that age, sex, Charlson comorbidity score, and call-related symptoms were associated with 30-day mortality, but response time was not (OR: 1.00 (95% CI [0.99–1.00])).

Conclusion

Longer ambulance response times were not associated with increased mortality, except for out-of-hospital cardiac arrests.
Deciphering the cell-intrinsic effect of DNMT3A clonal hematopoiesis in circulating monocytes: potential mechanistic insights into a protective role in Alzheimer’s disease
Authors: Abplanalp Wesley T. , Dimmeler Stefanie , Zeiher Andreas M.
Published: October 2023

Background

Recent evidence showed an unforeseen connection between clonal hematopoiesis (CH) and protection against Alzheimer’s disease (AD) and found mutant bone marrow-derived cells infiltrate the brain and acquire a microglial-like phenotype, correlating with reduced neuritic plaques and neurofibrillary tangles in non-AD individuals. CH, characterized by somatic mutations in hematopoietic stem cells leading to clonal expansion of immune cells, has previously been associated with the exacerbation of various age-related diseases.

Methods and Results

As the mechanism behind this protective effect remains unclear, our study introduces a novel method, MutDetect-Seq, capable of discerning cell-intrinsic effects of CH mutations. Single-cell RNA sequencing profiles in patients with DNMT3A CH mutations were assessed, hypothesizing that mutant cells might augment phagocytosis, potentially mitigating neurodegenerative processes. Indeed, DNMT3A mutant monocytes exhibited a distinct pro-phagocytic gene signature as demonstrated via upregulation of prototypical phagocytotic genes like CALR, FCGR1A, CYBA, S100A8, S100A9 and FCER1G. Upregulation was validated in vitro with DNMT3A silenced THP1 macrophages. Furthermore, upregulated gene pathways in mutant monocytes associated with phagocytosis, suggesting bone marrow-derived monocytic cells with CH DNMT3A mutations could replenish the brain’s phagocytic capacity, counteracting age-related declines in microglial phagocytosis, and thereby causatively reducing neurodegenerative processes in AD.

Conclusion

This study reveals critical phenotypic disparities between DNMT3A CH driver harboring mutant and wild-type monocytes, shedding light on a potential mechanism underlying the unexpected protective role of CH in AD progression and offering insights into the effects of different CH mutations in disease contexts.
Suppressed IgG4 class switching in dupilumab- and TNF inhibitor-treated patients after repeated SARS-CoV-2 mRNA vaccination
Authors: Valk Anika M. , Keijser Jim B.D. , van Dam Koos P.J. , Stalman Eileen W. , Wieske Luuk , Steenhuis Maurice , Kummer Laura Y.L. , Spuls Phyllis I. , Bekkenk Marcel W. , Musters Annelie H. , Post Nicoline F. , Bosma Angela L. , Horváth Barbara , Hijnen DirkJan , Schreurs Corine R.G. , van Kempen Zoé L.E. , Killestein Joep , Volkers Adriaan G. , Tas Sander W. , Boekel Laura , Wolbink Gerrit J. , Keijzer Sofie , Derksen Ninotska I.L. , van Deelen Melanie , van Mierlo Gerard , Kuijpers Taco W. , Eftimov Filip , van Ham S. Marieke , Brinke Anja ten , Rispens Theo ,   T2B! Immunity against SARS-CoV-2 study group
Published: October 2023

Background

Repeated mRNA vaccination against SARS-CoV-2 has been shown to induce class switching to IgG4, a non-inflammatory human antibody subclass linked to tolerance. Although poorly understood, prolonged antigenic stimulation and IL-4 signalling may be instrumental in IgG4 switching. We and others have previously shown that widely used immunosuppressive drugs such as methotrexate (MTX) and TNF inhibitors (TNFi) have a minor inhibitory impact on humoral SARS-CoV-2 mRNA vaccination responses. However, the impact of such immunosuppressive drugs on IgG4 switching is unknown.

Aim

To study the impact of widely used immunosuppressive drugs (TNFi, MTX, or the IL-4 receptor-blocking antibody dupilumab on IgG4 skewing upon repeated SARS-CoV-2 mRNA vaccination.

Methods

Antibody responses to the receptor-binding domain (RBD) of the spike protein upon repeated SARS-CoV-2 mRNA vaccination were measured in 604 individuals including patients with immune-mediated inflammatory diseases treated with TNFi and/or MTX, or dupilumab, as well as healthy controls and untreated patients.

Results

We observed a substantial increase in the proportion of RBD-specific IgG4 antibodies (median 21%) in healthy/untreated controls after a third mRNA vaccination. This IgG4 skewing was absent when primary vaccination was adenoviral vector-based and was profoundly reduced in both dupilumab- and TNFi-treated patients (<1%), but only moderately in patients treated with MTX (7%).

Conclusion

Our results imply a major role for both IL-4/IL-13 as well as TNF in IgG4 class switching. These novel findings advance our understanding of IgG4 class switch dynamics, and may benefit future mRNA vaccine strategies, humoral tolerance induction, as well as treatment of IgG4 pathologies.
Evaluation of Measles Surveillance System, Bono Region, Ghana
Authors: Zumah Fidelis , Asem Livingstone , Debuo Der Amanda , Sackey Samuel
Published: October 2023

Background

Measles remains a global public health problem despite the availability of a safe and effective vaccine, it is one of the leading causes of childhood morbidity and mortality. Hence, this study assessed the performance of the measles surveillance system in the Bono Region of Ghana.

Methods

A descriptive evaluation study was employed using the updated Centers for Disease Control (CDC) guideline for evaluating public health surveillance systems. The data collection methods employed were observation checklists, questionnaires, and measles records review

Results

Out of the 12 districts, 83.3% had case definitions. Three-quarters had IDSR reporting forms while 66.7% could transport measles specimens for confirmation. The performance of the supportive functions of the system was sub-optimal. The study revealed that half of the districts were not able to meet most of the standards for the support function. Moreover, timeliness of weekly and monthly reports above 90% was found in the study to be 66.7% and 25% respectively, and just about half of the districts attained over 90% timeliness. Also, the measles surveillance system was simple, flexible, useful, and acceptable despite its low positive predictive value of 1.5%.

Conclusion

The results of the study suggest that the general performance of the measles surveillance system in the Bono Region was sub-optimal. The performance of the core functions of the surveillance system is considered to be satisfactory. About half of the districts performed satisfactorily for the supportive functions. The completeness and timeliness of the reports were also satisfactory. Also, the Measles surveillance system was simple, flexible, useful, and quite acceptable despite its low positive predictive value. There is a need for capacity building on measles surveillance for surveillance officers and community volunteers, effective supportive supervision, and effective communication at all levels to improve the activities of the surveillance system and ultimately eliminate measles.
Simulation of COVID-19 Epidemic from Potential Viral Loads in Saudi Arabian Wastewater Treatment Plants
Authors: Meetei Mutum Zico , Msmali Ahmed H. , Ahmadini Abdullah Ali H. , Alshqaq Shokrya , Alna-shiri Hassien M
Published: October 2023

SARS-CoV-2 is a contagious respiratory virus that has been discovered in sewage, human waste, and wastewater treatment facilities. Wastewater surveillance has been considered one of the lowest-cost means of testing for tracking the COVID-19 outbreak in communities. This paper highlights the dynamics of the virus’s infection, persistence, and occurrence in wastewater treatment plants. Our aim is to develop and implement a mathematical model to infer the epidemic dynamics from the possible density of SARS-CoV-2 viral load in wastewater. We present a log-normal model and fractional order of susceptible-exposed-infected-recovery (SEIR) epidemic model for predicting the spread of the COVID-19 disease from the wastewater data. We study the dynamic properties of the fractional order SEIR model with respect to the fractional ordered values. The model is used to comprehend how the coronavirus spreads through wastewater treatment plants in Saudi Arabia. Our modeling approach can help with wastewater surveillance for early prediction and cost-effective monitoring of the epidemic outbreak in a situation of low testing capacity.
Cardiac atrophy, dysfunction, and metabolic impairments: a cancer-induced heart failure phenotype
Authors: Ogilvie Leslie M. , Delfinis Luca J. , Coyle-Asbil Bridget , Vudatha Vignesh , Alshamali Razan , Garlisi Bianca , Pereira Madison , Matuszewska Kathy , Garibotti Madison C. , Gandhi Shivam , Brunt Keith R. , Trevino Jose G. , Perry Christopher G.R. , Petrik Jim , Simpson Jeremy A.
Published: October 2023

Muscle atrophy and weakness are prevalent features of cancer. While extensive research has characterized skeletal muscle wasting in cancer cachexia, limited studies have investigated how cardiac structure and function are affected by therapy-naïve cancer. In cell-based models of orthotopic, syngeneic epithelial ovarian cancer (EOC) and pancreatic ductal adenocarcinoma (PDAC), and a patient-derived pancreatic xenograft model (PDX), we evaluated cardiac structure, function, and metabolism. Tumor-bearing mice showed cardiac atrophy and intrinsic systolic and diastolic dysfunction; associated with hypotension and exercise intolerance. In hearts of ovarian tumor-bearing mice, fatty acid-supported mitochondrial respiration decreased and carbohydrate-supported respiration increased, establishing a substrate shift in cardiac metabolism that is characteristic of heart failure. EOC decreased cytoskeletal and cardioprotective gene expression, which was paralleled by downregulation of transcription factors that regulate cardiomyocyte size and function. PDX tumors altered myosin heavy chain isoform expression – a molecular phenotype observed in heart failure. Markers of autophagy and ubiquitin-proteasome system were upregulated with cancer, providing evidence of catabolic signaling that promotes cardiac wasting. Together, metabolic stress, cardiac gene dysregulation, and upregulation of catabolic pathways contribute to cardiac atrophy and failure during cancer. Finally, we demonstrate that pathological cardiac remodeling is induced by human cancer, providing translational evidence of cancer-induced cardiomyopathy.
Admix-kit: An Integrated Toolkit and Pipeline for Genetic Analyses of Admixed Populations
Authors: Hou Kangcheng , Gogarten Stephanie , Kim Joohyun , Hua Xing , Dias Julie-Alexia , Sun Quan , Wang Ying , Tan Taotao ,   Polygenic Risk Methods in Diverse Populations (PRIMED) Consortium Methods Working Group, Atkinson Elizabeth G. , Martin Alicia , Shortt Jonathan , Hirbo Jibril , Li Yun , Pasaniuc Bogdan , Zhang Haoyu
Published: October 2023

Admixed populations, with their unique and diverse genetic backgrounds, are often underrepresented in genetic studies. This oversight not only limits our understanding but also exacerbates existing health disparities. One major barrier has been the lack of efficient tools tailored for the special challenges of genetic study of admixed populations. Here, we present admix-kit, an integrated toolkit and pipeline for genetic analyses of admixed populations. Admix-kit implements a suite of methods to facilitate genotype and phenotype simulation, association testing, genetic architecture inference, and polygenic scoring in admixed populations.

Availability and implementation

Admix-kit package is open-source and available athttps://github.com/KangchengHou/admix-kit. Additionally, users can use the pipeline designed for admixed genotype simulation available athttps://github.com/UW-GAC/admix-kit_workflow.
Insect hormone PTTH regulates lifespan through temporal and spatial activation of NF-κB signaling during metamorphosis
Authors: Kang Ping , Liu Peiduo , Kim Jinoh , Kumar Anku , Bolton Marie , Murzyn Wren A , Anderson Zenessa J , Frank Lexi N , Kavlock Nichola , Hoffman Elizabeth , Martin Chad C , Dorneich-Hayes Marlene K , Miao Ting , Shimell MaryJane , Chen Weihang , Hu Yanhui , Powell-Coffman JoAnne , O'Connor Michael B , Perrimon Norbert , Bai Hua
Published: October 2023

The prothoracicotropic hormone (PTTH) is a well-known neuropeptide that regulates insect metamorphosis (the juvenile-to-adult transition) by inducing the biosynthesis of steroid hormones. However, the role of PTTH in adult physiology and longevity is largely unexplored. Here, we show that Ptth loss-of-function mutants are long-lived and exhibit increased resistance to oxidative stress in Drosophila. Intriguingly, we find that loss of Ptth blunt age-dependent upregulation of NF-κB signaling specifically in fly hepatocytes (oenocytes). We further show that oenocyte-specific overexpression of Relish/NF-κB blocks the lifespan extension of Ptth mutants, suggesting that PTTH regulates lifespan through oenocyte-specific NF-κB signaling. Surprisingly, adult-specific knockdown of Ptth did not prolong lifespan, indicating that PTTH controls longevity through developmental programs. Indeed, knockdown of PTTH receptor Torso in prothoracic gland (PG) during fly development prolongs lifespan. To uncover the developmental processes underlying PTTH-regulated lifespan, we perform a developmental transcriptomic analysis and identify an unexpected activation of NF-κB signaling in developing oenocytes during fly metamorphosis, which is blocked in Ptth mutants. Importantly, knockdown of Relish/NF-κB specifically in oenocytes during early pupal stages significantly prolongs the lifespan of adult flies. Thus, our findings uncover an unexpected role of PTTH in controlling adult lifespan through temporal and spatial activation of NF-κB signaling in developing hepatocytes and highlight the vital role of developmental NF-κB signaling in shaping adult physiology.
The neuronal chromatin landscape in adult schizophrenia brains is linked to early fetal development
Authors: Girdhar Kiran , Bendl Jaroslav , Baumgartner Andrew , Therrien Karen , Venkatesh Sanan , Mathur Deepika , Dong Pengfei , Rahman Samir , Kleopoulos Steven P. , Misir Ruth , Reach Sarah M. , Auluck Pavan K. , Marenco Stefano , Lewis David A. , Haroutunian Vahram , Funk Cory , Voloudakis Georgios , Hoffman Gabriel E. , Fullard John F. , Roussos Panos
Published: October 2023

Non-coding variants increase risk of neuropsychiatric disease. However, our understanding of the cell-type specific role of the non-coding genome in disease is incomplete. We performed population scale (N=1,393) chromatin accessibility profiling of neurons and non-neurons from two neocortical brain regions: the anterior cingulate cortex and dorsolateral prefrontal cortex. Across both regions, we observed notable differences in neuronal chromatin accessibility between schizophrenia cases and controls. A per-sample disease pseudotime was positively associated with genetic liability for schizophrenia. Organizing chromatin intocis- andtrans-regulatory domains, identified a prominent neuronaltrans-regulatory domain (TRD1) active in immature glutamatergic neurons during fetal development. Polygenic risk score analysis using genetic variants within chromatin accessibility of TRD1 successfully predicted susceptibility to schizophrenia in the Million Veteran Program cohort. Overall, we present the most extensive resource to date of chromatin accessibility in the human cortex, yielding insights into the cell-type specific etiology of schizophrenia.
Walking Pace, Sport Genes, and the Lung Cancer
Authors: Wang Mengying , Meng Xiangqi , Tian Weiliang , Sun Ruinan , Wang Siyue , Qin Yilei , Ranson Janice M. , Peng Hexiang , Napolioni Valerio , Lau Patrick W. C. , Wu Tao , Huang Jie
Published: October 2023

Background

To investigate the association between walking pace and lung cancer risk, and explore whether any association is modified by endurance and power-related genes.

Methods

We followed up 449,890 UK Biobank participants free of cancer at baseline. Data on self-reported walking pace were collected by touchscreen questionnaire at baseline. Blood samples were obtained for genotyping. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for lung cancer incidence and mortality, with slow walking pace as the reference.

Findings

4,087 lung cancer incident cases and 2,245 lung cancer deaths were identified during a median follow-up period of 12.1 and 12.7 years, respectively. For incident lung cancer, HR (95% CI) were 0.71 (0.65- 0.78) and 0.55 (0.49-0.61) among participants with steady and brisk walking pace, respectively. For lung cancer mortality, steady and brisk walking paces were associated with 32% and 48% lower risks, respectively. Associations of walking pace with risks of lung cancer occurrence and mortality were modified by rs1815739 inACTN3and rs7191721 inRBFOX1. The protective effect of faster walking pace was more evident among participants carrying a higher number of T allele for rs1815739 inACTN3(Pinteraction=0.04 for both lung cancer incidence and mortality) and A allele for rs7191721 inRBFOX1(Pinteraction=0.01 for lung cancer incidence,Pinteraction=0.004 for lung cancer mortality).

Interpretation

Faster walking pace is associated with lower risks of both lung cancer occurrence and mortality, and this protective effect is modulated by polymorphisms in endurance geneRBFOX1and in power gene (ACTN3).

Funding

This work was supported by grants from the China Postdoctoral Science Foundation (Grant No. BX2021021, 2022M710249), Fujian Provincial Health Technology Project (Grant No. 2020CXB009), and the Natural Science Foundation of Fujian Province, China (Grant No. 2021J01352).
A Large Language Model-Based Generative Natural Language Processing Framework Finetuned on Clinical Notes Accurately Extracts Headache Frequency from Electronic Health Records
Authors: Chiang Chia-Chun , Luo Man , Dumkrieger Gina , Trivedi Shubham , Chen Yi-Chieh , Chao Chieh-Ju , Schwedt Todd J. , Sarker Abeed , Banerjee Imon
Published: October 2023

Background

Headache frequency, defined as the number of days with any headache in a month (or four weeks), remains a key parameter in the evaluation of treatment response to migraine preventive medications. However, due to the variations and inconsistencies in documentation by clinicians, significant challenges exist to accurately extract headache frequency from the electronic health record (EHR) by traditional natural language processing (NLP) algorithms.

Methods

This was a retrospective cross-sectional study with human subjects identified from three tertiary headache referral centers-Mayo Clinic Arizona, Florida, and Rochester. All neurology consultation notes written by more than 10 headache specialists between 2012 to 2022 were extracted and 1915 notes were used for model fine-tuning (90%) and testing (10%). We employed four different NLP frameworks: (1)ClinicalBERT (Bidirectional Encoder Representations from Transformers) regression model(2) Generative Pre-Trained Transformer-2 (GPT-2) Question Answering (QA) Model zero-shot (3) GPT-2 QA model few-shot trainingfine-tuned on Mayo Clinic notes; and(4) GPT-2 generative model few-shot trainingfine-tuned on Mayo Clinic notes to generate the answer by considering the context of included text.

Results

The GPT-2 generative model was the best-performing model with an accuracy of 0.92[0.91 – 0.93] and R2score of 0.89[0.87, 0.9], and all GPT2-based models outperformed the ClinicalBERT model in terms of the exact matching accuracy. Although the ClinicalBERT regression model had the lowest accuracy 0.27[0.26 – 0.28], it demonstrated a high R2score 0.88[0.85, 0.89], suggesting the ClinicalBERT model can reasonably predict the headache frequency within a range of ≤ ± 3 days, and the R2score was higher than the GPT-2 QA zero-shot model or GPT-2 QA model few-shot training fine-tuned model.

Conclusion

We developed a robust model based on a state-of-the-art large language model (LLM)-a GPT-2 generative model that can extract headache frequency from EHR free-text clinical notes with high accuracy and R2score. It overcame several challenges related to different ways clinicians document headache frequency that were not easily achieved by traditional NLP models. We also showed that GPT2-based frameworks outperformed ClinicalBERT in terms of accuracy in extracting headache frequency from clinical notes. To facilitate research in the field, we released the GPT-2 generative model and inference code with open-source license of community use in GitHub.
Comparing Approaches to Specimen Identification using Neotropical Freshwater Fishes in the Barra del Colorado Wildlife Refuge, Costa Rica
Authors: Perez Taegan JM , Fontenelle JP , Kolmann Matthew A. , Angulo Arturo , López-Fernández Hernán , Lovejoy Nathan R.
Published: October 2023

As global biodiversity declines continue, conservation efforts are increasingly important in megadiverse areas such as the Neotropics where biodiversity is especially imperiled. The accurate identification of specimens is critical to successful conservation plans. However, in groups such as freshwater fishes, different identification methodologies have documented challenges. Using a biodiversity survey of fishes from the Barra del Colorado Wildlife Refuge in northeastern Costa Rica, we compared: (1) morphological identifications in the field, (2) morphological identifications in the lab by experts, (3) DNA barcode-based identifications, and (4) identifications based on an integrative approach. Our results suggest that both barcode-based identifications and field morphological identifications provided fewer correct species identifications than lab identifications performed by experts using morphology. We attribute shortfalls of DNA barcoding in this case to the misidentification of reference material, the use of outdated taxonomy for references sequences, and the non-uniform representation of groups in public databases across taxa. We suggest the use of an integrative approach to identify freshwater fishes in Costa Rica and other megadiverse areas of the Neotropics where similar issues with public barcode reference libraries exist. We also recommend the creation of regional curated barcode reference libraries to aid in the identification of traditionally difficult to identify species/specimens. We also provide the most up to date species list for the ichthyofauna of the Barra del Colorado Wildlife Refuge identifying 51 species from 42 genera, 21 families, and 17 orders. Generating accurate species lists for protected areas and areas of importance will provide conservation practitioners with effective tools for tracking diversity changes over time.
Streptomycesextracellular vesicles are a broad and permissive antimicrobial packaging and delivery system
Authors: Meyer Kirsten J. , Nodwell Justin R.
Published: October 2023

Streptomycesare the primary source of bioactive specialized metabolites used in research and medicine, including many antimicrobials. These are presumed to be secreted and function as freely soluble compounds. However, increasing evidence suggests extracellular vesicles are an alternative secretion system. We assessed environmental and lab-adaptedStreptomyces(sporulating filamentous actinomycetes) and found a majority of strains produce vesicles packaging antimicrobial compounds. The cargo included actinomycins, anthracyclines, candicidin, and actinorhodin, reflecting both diverse chemical properties and diverse antibacterial and antifungal activity. The production of the antimicrobials and vesicles was linked, although vesicle production continued in the absence of antimicrobials. We demonstrated that antimicrobial-containing vesicles achieve direct delivery of the cargo to other microbes. Notably, this delivery via membrane fusion occurred to a broad range of microbes including pathogenic bacteria and yeast. Vesicle encapsulation offers a broad and permissive packaging and delivery system for antimicrobial specialized metabolites, with important implications for ecology and translation.

GRAPHICAL ABSTRACT

IMPORTANCE

Extracellular vesicle encapsulation changes our picture of how antimicrobial metabolites function in the environment, and provides an alternative translational approach for delivery of antimicrobials. We find the majority ofStreptomycesstrains are capable of releasing antimicrobial vesicles, and at least four distinct classes of compounds can be packaged, suggesting this is widespread in nature. This is a striking departure from the primary paradigm of secretion and action of specialized metabolites as soluble compounds. Importantly the vesicles deliver antimicrobial metabolites directly to other microbes via membrane fusion, including to pathogenic bacteria and yeast. This suggests future applications in which lipid-encapsulated natural product antibiotics and antifungals could be used to solve some of the most pressing problems in drug resistance.
PyDecNef: An open-source framework for fMRI-based decoded neurofeedback
Authors: Margolles Pedro , Mei Ning , Elosegi Patxi , Soto David
Published: October 2023

Real time fMRI research has suffered from inaccessible analysis pipelines, hindering collaboration and reproducibility. Here we present PyDecNef, a Python-based platform designed to advance real-time fMRI analysis and fuel exploration of close-loop neuroimaging for cognitive neuroscience studies. Creating a real-time fMRI analysis pipeline from scratch poses formidable technical challenges, involving data transfer, experimental software, and machine learning classifier preparation. Existing tools like FRIEND, Brain-Voyant, and OpenNFT demand expensive licenses or rely on proprietary software, impeding accessibility and customizability. PyDecNef offers a solution: a transparent, versatile, and open workflow for real-time fMRI decoding protocols. This open-source platform simplifies decoder construction, real-time preprocessing, decoding, and feedback signal generation. It empowers researchers to launch DecNef experiments efficiently, saving time and resources. Moreover, its openness promotes collaboration, enhancing research quality, replicability, and impact. With PyDecNef, the path to advancing DecNef studies becomes more accessible and collaborative. PyDecNef resources for real-time fMRI analysis can be found athttps://pedromargolles.github.io/pyDecNef/,. Here we also provide experimental data illustrating that PyDecNef provides more fine-grained and less binomial/overconfident neurofeedback signals compared to previous DecNef approaches that have relied on sparse multinomial logistic regression classifiers, and hence, potentially helping participants to learn better how to self-regulate their brain activity.
The macronuclear genomic landscape withinTetrahymena thermophila
Authors: Derelle Romain , Verdonck Rik , Jacob Staffan , Huet Michèle , Akerman Ildem , Philippe Hervé , Legrand Delphine
Published: October 2023

The extent of intraspecific genomic variation is key to understanding species evolutionary history, including recent adaptive shifts. Intraspecific genomic variation remains poorly explored in eukaryotic microorganisms, especially in the nuclear dimorphic ciliates, despite their fundamental role as laboratory model systems and their ecological importance in many ecosystems. We sequenced the macronuclear genome of 22 laboratory strains of the oligohymenophoranTetrahymena thermophila, a model species in both cellular biology and evolutionary ecology. We explored polymorphisms at the junctions of programmed eliminated sequences, and reveal their utility to barcode very closely related cells. As for other species of the genusTetrahymena, we confirm micronuclear centromeres as gene diversification centres inT. thermophila, but also reveal a two-speed evolution in these regions. In the rest of the genome, we highlight recent diversification of genes encoding for extracellular proteins and cell adhesion. We discuss all these findings in relation with ciliate’s ecology and cellular characteristics.

Impact Statement

This is the first study of population genomics in the ciliateTetrahymena thermophila. This bacterivore species plays an important role in aquatic trophic chains and is widely used as a model in cell and molecular biology, ecology, evolution or toxicology. As all ciliates, it contains a germline micronucleus and a somatic macronucleus. Sequencing of the macronucleus reveals that the centromeric region of the micronucleus are simultaneously a region of new gene diversification, as observed in otherTetrahymenaspecies, and a region containing highly conserved genes. The results also confirm that the formation of the macronucleus from the micronucleus is highly imprecise. Interestingly, this process generates a genomic barcode that can discriminate cells derived from a given sexual reproduction event, allowing to study more finely population dynamics/history in nature.

Data summary

All data are fully provided in Supplementary Materials. The raw data of the 22Tetrahymenagenomes have been deposited in the Sequence Read Archive (https://www-ncbi-nlm-nih-gov.inee.bib.cnrs.fr/bioproject/PRJNA1012331). Accession numbers are listed in Table S1 (available in the online version of this article).
ExoChew: An exonuclease technique to generate single-stranded DNA libraries
Authors: Patel Krishna , Lodha Chirag , Smith Christopher , Diggins Levi , Kolluru Venkata , Ross Daniel , Syed Christopher , Lewis Olivia , Daley Rachel , Mohanty Bidyut K
Published: October 2023

Although DNA in the genome is double-stranded, single-stranded DNA is generated during various processes including DNA replication and repair. Some single-stranded DNAs can form noncanonical structures. Various proteins bind to the single-stranded DNAs site-specifically and/or structure-specifically to regulate various DNA transactions. Because of the transient nature of single-stranded DNAs in the cell, currentin vivotechniques may not reveal all such sequences, structures, and protein-DNA complexes. To explore such sequences and structures genome-wide, it is necessary to generate single-stranded DNA libraries. Currentin vitromethods involve heat denaturation of libraries of double-stranded DNA fragments followed by cooling to prevent reannealing; however, a significant amount of DNA can reanneal to regenerate double-stranded DNAs. In ExoChew method, double-stranded DNA fragment libraries are enzymatically converted to single-stranded DNA libraries. Genomic DNA is sonicated to generate pools of double-stranded DNA fragments of required size. Each pool of double-stranded DNA fragments is then treated with either T7 exonuclease orE. coliexonuclease III. which recognize and cleave double-stranded DNA from 5’ ends or 3’ ends, generating single-stranded DNA pools, respectively. The enzymatically generated single-stranded DNA pools can be used for genome-wide studies of protein-DNA interactions and structural studies of DNA.
Antimicrobial use in laboratory rodent facilities in Australia and New Zealand- a cross-sectional survey of veterinarians and facility managers
Authors: Wilcox Rebbecca S. , Marenda Marc S. , Devlin Joanne M. , Wilks Colin R.
Published: October 2023

This cross-sectional study surveyed veterinarians and facility managers to characterise the use of antimicrobials in laboratory rodent facilities within Australia and New Zealand. Most facilities (71%) reported routine administration of antimicrobials. The indications for antibiotic use reflected those described in publications and differed significantly to reasons for use in non-laboratory animals. Antimicrobials used include those of critical importance to human health, and access to these drugs is unregulated, as prescription-only classes are ordered through research catalogues, without human or veterinary physician prescriptions.

The ways in which antimicrobials are used in Australian and New Zealand rodent facilities are likely contributing to antimicrobial resistance within rodent populations, particularly as they are largely administered in drinking water, risking subtherapeutic dosing. Much antimicrobial use reported is unnecessary and could be replaced with changes to husbandry and handling. The generation of resistance in both pathogenic and commensal microbes may also represent a work health and safety issue for humans working with these animals.

Reported disposal of antimicrobials included discharge into wastewater, without inactivation, and some respondents reported disposal of substrate, or soiled bedding, nesting material, and disposable enrichment items, from treated animals and medicated feed into landfill, without prior inactivation. Environmental contamination with resistant microbes and antimicrobials is a significant driver of antimicrobial resistance. As such, significant opportunities exist to implement judicious and responsible use of antimicrobials within research rodent facilities in Australia and New Zealand, with a particular focus on instituting aseptic surgery, optimising dosing regimens, and inactivation of medicated water and substrate before disposal.
BMP signaling maintains auricular chondrocyte identity and prevents microtia development by inhibiting protein kinase A
Authors: Yang Ruichen , Chu Hongshang , Yue Hua , Mishina Yuji , Zhang Zhenlin , Liu Huijuan , Li Baojie
Published: October 2023

Elastic cartilage constitutes a major component of the external ear, which functions to guide sound to the middle and inner ears. Defects in auricle development cause congenital microtia, which affects hearing and appearance in patients. Mutations in several genes have been implicated in microtia development, yet, the pathogenesis of this disorder remains incompletely understood. Here, we show thatPrrx1genetically marks auricular chondrocytes in adult mice. Interestingly, BMP-Smad1/5/9 signaling in chondrocytes is increasingly activated from the proximal to distal segments of the ear, which is associated with a decrease in chondrocyte regenerative activity. Ablation ofBmpr1ain auricular chondrocytes led to chondrocyte atrophy and microtia development at the distal part. Transcriptome analysis revealed thatBmpr1adeficiency caused a switch from the chondrogenic program to the osteogenic program, accompanied by enhanced protein kinase A activation, likely through increased expression ofAdcy5/8. Inhibition of PKA blocked chondrocyte-to-osteoblast transformation and microtia development. Moreover, analysis of single-cell RNA-seq of human microtia samples uncovered enriched gene expression in the PKA pathway and chondrocyte-to-osteoblast transformation process. These findings suggest that auricle cartilage is actively maintained by BMP signaling, which maintains chondrocyte identity by suppressing osteogenic differentiation.