bluuebunny/crossref_metadata_2025 huggingface dataset:
An International Survey of the Management of Atrial Fibrillation in Critically Unwell Patients
Authors: Johnston Brian W. , Udy Andrew A. , McAuley Daniel F. , Mogk Martin , Welters Ingeborg D. , Sibley Stephanie
Published: March 2024

OBJECTIVES:

To evaluate the current management of new-onset atrial fibrillation and compare differences in practice regionally.

DESIGN:

Cross-sectional survey.

SETTING:

United States, Canada, United Kingdom, Europe, Australia, and New Zealand.

SUBJECTS:

Critical care attending physicians/consultants and fellows.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A total of 386 surveys were included in our analysis. Rate control was the preferred treatment approach for hemodynamically stable patients (69.1%), and amiodarone was the most used antiarrhythmic medication (70.9%). For hemodynamically unstable patients, a strategy of electrolyte supplementation and antiarrhythmic therapy was most common (54.7%). Physicians responding to the survey distributed by the Society of Critical Care Medicine were more likely to prescribe beta-blockers as a first-line antiarrhythmic medication (38.4%), use more transthoracic echocardiography than respondents from other regions (82.4%), and more likely to refer patients who survive their ICU stay for cardiology follow-up if they had new-onset atrial fibrillation (57.2%). The majority of survey respondents (83.0%) were interested in participating in future studies of atrial fibrillation in critically ill patients.

CONCLUSIONS:

Significant variation exists in the management of new-onset atrial fibrillation in critically ill patients, as well as geographic variation. Further research is necessary to inform guidelines in this population and establish if differences in practice impact long-term outcomes.
Early Physiologic Numerical and Waveform Characteristics of Simulated Hemorrhagic Events With Healthy Volunteers Donating Blood
Authors: Yoon Joo Heung , Kim Jueun , Lagattuta Theodore , Pinsky Michael R. , Hravnak Marilyn , Clermont Gilles
Published: March 2024

OBJECTIVES:

Early signs of bleeding are often masked by the physiologic compensatory responses delaying its identification. We sought to describe early physiologic signatures of bleeding during the blood donation process.

SETTING:

Waveform-level vital sign data including electrocardiography, photoplethysmography (PPG), continuous noninvasive arterial pressure, and respiratory waveforms were collected before, during, and after bleeding.

SUBJECTS:

Fifty-five healthy volunteers visited blood donation center to donate whole blood.

INTERVENTION:

After obtaining the informed consent, 3 minutes of resting time was given to each subject. Then 3 minutes of orthostasis was done, followed by another 3 minutes of resting before the blood donation. After the completion of donating blood, another 3 minutes of postbleeding resting time, followed by 3 minutes of orthostasis period again.

MEASUREMENTS AND MAIN RESULTS:

From 55 subjects, waveform signals as well as numerical vital signs (heart rate [HR], respiratory rate, blood pressure) and clinical characteristics were collected, and data from 51 subjects were analyzable. Any adverse events (AEs; dizziness, lightheadedness, nausea) were documented. Statistical and physiologic features including HR variability (HRV) metrics and other waveform morphologic parameters were modeled. Feature trends for all participants across the study protocol were analyzed. No significant changes in HR, blood pressure, or estimated cardiac output were seen during bleeding. Both orthostatic challenges and bleeding significantly decreased time domain and high-frequency domain HRV, and PPG amplitude, whereas increasing PPG amplitude variation. During bleeding, time-domain HRV feature trends were most sensitive to the first 100 mL of blood loss, and incremental changes of different HRV parameters (from 300 mL of blood loss), as well as a PPG morphologic feature (from 400 mL of blood loss), were shown with statistical significance. The AE group (n= 6) showed decreased sample entropy compared with the non-AE group during postbleed orthostatic challenge (p= 0.003). No significant other trend differences were observed during bleeding between AE and non-AE groups.

CONCLUSIONS:

Various HRV-related features were changed during rapid bleeding seen within the first minute. Subjects with AE during postbleeding orthostasis showed decreased sample entropy. These findings could be leveraged toward earlier identification of donors at risk for AE, and more broadly building a data-driven hemorrhage model for the early treatment of critical bleeding.
Validation of Adult Sepsis Event and Epidemiologic Analysis of Sepsis Prevalence and Mortality Using Adult Sepsis Event’s Electronic Health Records-Based Sequential Organ Failure Assessment Criteria: A Single-Center Study in South Korea*
Authors: Lee Su Yeon , Park Mi Hyeon , Oh Dong Kyu , Lim Chae-Man
Published: March 2024

OBJECTIVES:

In 2018, the Centers for Disease Control and Prevention introduced the Adult Sepsis Event (ASE) definition, using electronic health records (EHRs) data for surveillance and sepsis quality improvement. However, data regarding ASE outside the United States remain limited. We therefore aimed to validate the diagnostic accuracy of the ASE and to assess the prevalence and mortality of sepsis using ASE.

DESIGN:

Retrospective cohort study.

SETTING:

A single center in South Korea, with 2732 beds including 221 ICU beds.

PATIENTS:

During the validation phase, adult patients who were hospitalized or visiting the emergency department between November 5 and November 11, 2019, were included. In the subsequent phase of epidemiologic analysis, we included adult patients who were admitted from January to December 2020.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

ASE had a sensitivity of 91.6%, a specificity of 98.3%, a positive predictive value (PPV) of 57.4%, and a negative predictive value of 99.8% when compared with the Sepsis-3 definition. Of 126,998 adult patient hospitalizations in 2020, 6,872 cases were diagnosed with sepsis based on the ASE (5.4% per year), and 893 patients were identified as having sepsis according to the International Classification of Diseases, 10th Edition (ICD-10) (0.7% per year). Hospital mortality rates were 16.6% (ASE) and 23.5% (ICD-10-coded sepsis). Monthly sepsis prevalence and hospital mortality exhibited less variation when diagnosed using ASE compared with ICD-10 coding (coefficient of variation [CV] for sepsis prevalence: 0.051 vs. 0.163, Miller test p < 0.001; CV for hospital mortality: 0.087 vs. 0.261, p = 0.001).

CONCLUSIONS:

ASE demonstrated high sensitivity and a moderate PPV compared with the Sepsis-3 criteria in a Korean population. The prevalence of sepsis, as defined by ASE, was 5.4% per year and was similar to U.S. estimates. The prevalence of sepsis by ASE was eight times higher and exhibited less monthly variability compared with that based on the ICD-10 code.
Chemical Peels for Melasma: A Systematic Review
Authors: Sarkar Rashmi , Lakhani Ridhima
Published: March 2024

BACKGROUND

Melasma is a common chronic, relapsing pigmentary disorder that causes psychological impact. Chemical peels are a well-known therapeutic modality used for accelerating the treatment of melasma.

OBJECTIVE

To review the published evidence on the efficacy and safety of chemical peels in the treatment of melasma.

METHODS

A systematic review was done. A meta-analysis could not be done due to the heterogeneity of data.

RESULT

The authors conducted a PubMed search and included prospective case series of more than 10 cases and randomized controlled trials (RCTs) that have studied the safety and/or efficacy of chemical peel in melasma. Out of 24 studies, 9 were clinical/comparative trials and 15 were RCTs. The total sample size was 1,075. The duration of the study varied from 8 to 36 weeks. Only 8 studies were split face. All studies used self-assessment, physician global assessment, and Melasma Area and Severity Index (MASI) for quantifying the results. Glycolic acid was found to be the most safe and effective in melasma.

CONCLUSION

Chemical peels were found to be safe and effective in the management of melasma.
Characterizing Health Literacy and Its Correlates Among Individuals With Traumatic Brain Injury (TBI): A TBI Model Systems Study
Authors: Sander Angelle M. , Pappadis Monique R. , Juengst Shannon B. , Leon-Novelo Luis , Ngan Esther , Corrigan John D. , Dreer Laura E. , Driver Simon , Lequerica Anthony H.
Published: March 2024

Objective:

To characterize health literacy among individuals with traumatic brain injury (TBI) at least a year postinjury and to explore its relationship to sociodemographic variables, injury severity, and cognition.

Setting:

Community following discharge from inpatient rehabilitation.

Participants:

In total, 205 individuals with complicated mild to severe TBI who completed follow-up as part of a national longitudinal study of TBI and completed a web-based health literacy measure.

Design:

Multicenter, cross-sectional, observational study.

Main Measures:

Health Literacy Assessment Using Talking Touchscreen Technology.

Results:

Thirty-one percent of the sample demonstrated marginal/inadequate health literacy; 69% demonstrated adequate health literacy. A higher proportion of non-Hispanic White adults had adequate health literacy than non-Hispanic Black and Hispanic adults. Individuals with greater than a high school education were more likely to have adequate health literacy than those with a high school education or less. Better executive functioning performance was related to adequate health literacy. Better episodic memory performance was related to adequate health literacy, but only for those with complicated mild to moderate injury.

Conclusions:

A substantial proportion of individuals with TBI have marginal/inadequate health literacy, which may impact their understanding, appreciation, and use of health-related information and recommendations. While low health literacy may be preexisting, directly related to TBI, or a combination of both, it should be screened and considered by professionals when communicating with persons with TBI. Healthcare providers should tailor their communication approaches and presentation of health information, particularly for those with low health literacy.
Foveal Phenotypes in Choroideremia on Adaptive Optics Scanning Light Ophthalmoscopy
Authors: Wynne Niamh , Jiang Yu You , Aleman Tomas S , Morgan Jessica IW
Published: March 2024

Purpose:

Choroideremia is an X-linked inherited retinal degeneration involving the choriocapillaris, retinal pigment epithelium and photoreceptors. Adaptive optics scanning light ophthalmoscopy allows visualization of retinal structure at the level of individual cells and is well poised to provide insight into the pathophysiological mechanisms underpinning the retinal degeneration in choroideremia.

Methods:

Foveal adaptive optics scanning light ophthalmoscopy images of 102 eyes of 54 individuals with choroideremia were analyzed. Measures were compared to those from standard clinical imaging. Visual acuity was also measured and compared to quantitative foveal metrics.

Results:

The 3 distinct phenotypes observed were: relatively normal (5 eyes, 4 individuals), spiderweb (9 eyes, 7 individuals) and salt and pepper (87 eyes, 47 individuals). Peak cone density (86 eyes of 51 individuals) was significantly lower in choroideremia than in healthy retinas (p<0.0001, range: 29,382-157,717 cones/mm2). Peak cone density was significantly related to extent of retained ellipsoid zone on en face OCT (r2=0.47, p=0.0009) and inversely related to visual acuity (r2=0.20, p=0.001).

Conclusions:

Distinct phenotypes can be observed on adaptive optics scanning light ophthalmoscopy imaging in choroideremia that cannot always be discerned on standard clinical imaging. Quantitative measures on adaptive optics imaging are related to the structural and functional severity of disease.
Epidemiology and Prognostic Nomogram for Predicting Long-Term Disease-Specific Survival in Patients With Pancreatic Carcinoid Tumor
Authors: Lin Hai , Li Yufang , Chen Yutong , Zeng Linjuan , Li Bixiang , Chen Shili
Published: March 2024

Objectives

Pancreatic carcinoid tumor (PCT) is described as a malignant form of carcinoid tumors. However, the epidemiology and prognostic factors for PCT are poorly understood.

Materials and Methods

The data of 2447 PCT patients were included in this study from the Surveillance, Epidemiology, and End Results database and randomly divided into a training cohort (1959) and a validation cohort (488). The epidemiology of PCT was calculated, and independent prognostic factors were identified to construct a prognostic nomogram for predicting long-term disease-specific survival (DSS) among PCT patients.

Results

The incidence of PCT increased remarkably from 2000 to 2018. The 1-, 5-, and 10-year DSS rates were 96.4%, 90.3%, and 86.5%, respectively. Age at diagnosis, stage, surgery, radiotherapy, and chemotherapy were identified as independent prognostic factors to construct a prognostic nomogram. The C-indices; area under the receiver operating characteristic curves for predicting 1-, 5-, and 10-year DSS, and calibration plots of the nomogram in both cohorts indicated a high discriminatory accuracy, preferable survival predictive ability, and optimal concordances, respectively.

Conclusions

The incidence of PCT has increased rapidly since 2000. In addition, we established a practical, effective, and accurate prognostic nomogram for predicting the long-term DSS of PCT patients.
Establishment and Diagnostic Value of an Early Prediction Model for Acute Pancreatitis Complicated With Acute Kidney Injury
Authors: Chi Cheng , Song Xiaojing , Ma Yong , Wang Chunyu , Zhu Jihong
Published: March 2024

Objectives

To establish an early prediction model for acute pancreatitis (AP) complicated with acute kidney injury (AKI) and evaluate its diagnostic value.

Method

AP patients were recruited from the Emergency Department at Peking University People's Hospital in 2021 and stratified into AKI and control (no AKI) groups. Their clinical data were analyzed. The risk for AKI development was determined using logistic analyses to establish a risk prediction model, whose diagnostic value was analyzed using a receiver operating characteristic curve.

Results

There was no significant difference in the basic renal function between the AKI (n = 79) and control (n = 179) groups. The increased triglyceride glucose index (odds ratio [OR], 2.613; 95% confidence interval [CI], 1.324–5.158; P = 0.006), age (OR, 1.076; 95% CI, 1.016–1.140; P = 0.013), and procalcitonin (OR, 1.377; 95% CI, 1.096–1.730, P = 0.006) were associated with AKI development. A model was established for prediction of AKI (sensitivity 79.75%, specificity 96.65%). The area under the receiver operating characteristic curve was 0.856 which was superior to the Ranson, Bedside Index for Severity in AP, and Acute Physiology and Chronic Health Evaluation II scores (0.856 vs 0.691 vs 0.745 vs 0.705).

Conclusions

The prediction model based on age, triglyceride glucose, and procalcitonin is valuable for the prediction of AP-related AKI.
Exosomes Derived From Cerulein-Stimulated Pancreatic Acinar Cells Mediate Peritoneal Macrophage M1 Polarization and Pyroptosis via an miR-24-3p/MARCH3/NLRP3 Axis in Acute Pancreatitis
Authors: Su Xiao-ju , Chen Yan , Zhang Qi-chen , Peng Xiao-bo , Liu Ya-ping , Wang Lei , Du Yi-qi
Published: March 2024

Objectives

Acute pancreatitis (AP) has a high incidence of hospitalizations, morbidity, and mortality worldwide. A growing number of studies on AP pathogenesis are based on cerulein-induced experimental model, which simulates human AP in vivo. It has been demonstrated that both pancreatic acinar cells and peritoneal macrophages are involved in pancreatic inflammation and damage. However, their connection has not been well understood.

Methods

A cerulein-induced AP model was established on the pancreatic acinar cell line AR42J. Rat macrophages were isolated from the peritoneal cavity. The effects of cerulein-induced pancreatic exosomes on the peritoneal macrophage and pancreas in vivo and in vitro were examined. The underlying molecular mechanism was investigated by exploring the regulatory role of downstream molecules.

Results

We found that exosomes derived from cerulein-treated AR42J cells induced rat peritoneal macrophage M1 polarization and pyroptosis. miR-24-3p was upregulated in cerulein-stimulated exosomes, whereas the miR-24-3p inhibitor counteracted the effect of pancreatic exosomes on peritoneal macrophage M1 polarization and pyroptosis. Furthermore, miR-24-3p inhibited March3 expression, whereas MARCH3 mediated NLRP3 ubiquitination in rat peritoneal macrophages, which, in turn, contributed to the apoptosis, reactive oxygen species production, and inflammation in AR42J cells.

Conclusions

Exosomes derived from cerulein-stimulated pancreatic acinar cells mediate peritoneal macrophage M1 polarization and pyroptosis via an miR-24-3p/MARCH3/NLRP3 axis in AP.
Poly (Adp-Ribose) Polymerase-1 (PARP-1) Is a Good Prognostic Marker for Pancreatic/Periampullary Cancers
Authors: Yim Kwangil , Seo Kyung Jin , Abdul-Ghafar Jamshid , Alam Mohammad Rizwan , Paik Kwang Yeol , Chong Yosep , Shin Ok Ran
Published: March 2024

Background

Periampullary cancer (PAC) is highly aggressive with no effective adjuvant therapy or prognostic markers. Recently, poly (ADP-ribose) polymerase-1 (PARP-1) has emerged as a target in solid cancers, and its relationship with epithelial-mesenchymal transition (EMT) has been observed. However, the relationship between PARP-1 and EMT in PAC has not explored well.

Materials and Methods

We assessed the prognostic significance of PARP-1 in 190 PACs patients and correlated it with EMT markers, including FGF8, FGFR4, MMP2, MMP3, Snail, and ZEB1. Immunohistochemistry for PARP-1 and EMT markers was performed using a tissue microarray.

Results

PARP-1 and FGF8 expression were associated with better survival unlike other solid cancers (P = 0.006 and P = 0.003), and MMP3 and ZEB1 expression were associated with poor prognosis in multivariate and survival analyses (P = 0.009 and P < 0.001). In addition, PARP-1 is related negatively to Snail but not related with other EMT markers, implying an independent mechanism between PARP-1 and EMT in PACs. PARP-1 and FGF8 are independent good survival markers in PACs unlike other solid cancers.

Conclusions

PARP-1 and FGF8 in PACs could not be related to the EMT pathway but must be rather understood in light of similar cancer-protective roles. Further studies are required on EMT-associated immune markers in PACs.
Enhancing Overhead Throwing Ball Velocity After Core Muscle Training in Athletes
Authors: Lin Long-Huei , Lin Ting-Yu , Chang Ke-Vin , Wu Wei-Ting , Özçakar Levent
Published: March 2024

Objective

This systematic review and meta-analysis aimed to evaluate the influence of core muscle training on throwing ball velocity among overhead throwing athletes.

Design

A literature search was performed from inception to July 2023 for randomized controlled trials investigating the effects of core muscle training on overhead throwing ball velocity. The primary outcome was the change in standing throwing ball velocity. The secondary outcome focused on the enhancement of step/jump throwing ball velocity.

Results

Ten randomized controlled trials were included, revealing a significant improvement in standing throwing ball velocity in the group undergoing core muscle training (Hedges’ g = 0.701, 95% confidence interval = 0.339 to 1.063, P < 0.001). Longer treatment duration and a higher frequency of core muscle training sessions per week contributed to improved standing throwing ball velocity. However, core muscle training did not show significant benefits for step (Hedge’s g = 0.463, 95% confidence interval = −0.058 to 0.985, P = 0.082) and jump throwing ball velocity (Hedges’ g = 0.550, 95% confidence interval = −0.051 to 1.152, P = 0.073).

Conclusions

Core muscle training significantly enhanced standing ball throwing velocity. However, its effect on step/jump throwing ball velocity was less certain. Further research is needed to explore the impact of core muscle training (especially its long-term effects) on throwing ball velocity.
Predictors of a Preference for Telemedicine Virtual Visits in Patients Undergoing Cancer Rehabilitation
Authors: Ng Amy H. , Tennison Jegy , Fu Jack B. , Gupta Ekta , Lu Zhanni , Bruera Eduardo
Published: March 2024

The purpose of this retrospective study was to examine the use of virtual visits (telemedicine) at our cancer rehabilitation outpatient clinics from March 2020 to August 2021, when virtual visits became more widely available, and to identify any demographic and clinical variables making patients more likely to favor virtual over in-person visits. There were 3971 outpatient encounters (2020 virtual and 1951 in-person visits from a total of 1638 patients) in our cancer rehabilitation outpatient clinics during this time frame. Significant findings in both the univariate and multivariate analyses were race (P < 0.001 and P = 0.006, respectively), cancer type (P < 0.001 for both), and distance to the clinic (P < 0.001 for both). Our research showed that virtual visits were accepted by patients with cancer, and that younger age (62 compared to 65), non-White race/ethnicity, solid tumor, and shorter distance to the clinic were associated with a preference for virtual over in-person visits.
Association of Weight Indicators, Dietary Habits, and Physical Activity With Common Benign Breast Diseases
Authors: Rastad Hadith , Saberi Azin , Ghanaei Mahsa , Alipour Sadaf
Published: March 2024

Benign breast diseases (BBDs) are 10 times more common than breast cancer, and fibroadenoma (FA) and fibrocystic disease (FCD) are the most frequent. The association of BBD with physical activity (PA), weight indicators, and diet was investigated. Eligible women were entered in the FA, non-FA, FCD, and non-FCD groups. A PA and a food questionnaire were completed and anthropometric measures were taken and 779 women were studied. There was no significant difference regarding weight indicators and PA between the groups. Contrary to the general assumption, chocolate, tea, and coffee do not increase BBD, while chicken may elevate the risk.
Testing a Prioritization Tool to Identify Older Adults in Need of Home-Delivered Meals and Nutrition-Related Services
Authors: Mendez Izabelle , Vaudin Anna M. , Simon Judy R. , Cruz-Cano Raul , Sahyoun Nadine R.
Published: March 2024

The Expanded Food Security Screener (FSS-Exp) determines food insecurity risk based on physical, economic, and social access to food. It categorizes individuals into 5 priorities based on need for a home-delivered meal. Concurrent and construct validity were applied to the tool. For concurrent validity, partial correlations between FSS-Exp and health- and food-related measures were significant and ranged between 0.20 and 0.33. For construct validity, analysis of variance was used to examine scores of the health- and food-related tools by priority level. The 2 highest priority levels had significantly lower mean scores for all the health variables except for dietary intake. The FSS-Exp tool effectively identifies those most in need of meal services.
Mobile Apps for Hypertension Management
Authors: DiFilippo Kristen N. , Chapman-Novakofski Karen M.
Published: March 2024

Mobile applications (apps) show promise for managing hypertension; however, more evidence is needed to understand how dietitians use apps in hypertension care. Dietitians (n = 191) completed an online survey assessing app use in hypertension care. Most dietitians agreed that apps support behavior change, diet tracking, and goal setting. Apps are recommended for diet tracking more often than online programs or websites (P < .001), but not more than pen and paper. Dietitians generally recommended apps to some or most of their patients (40% and 25%, respectively); however, the majority (64%) do not recommend apps specific to hypertension (64%). Future work should examine barriers to app use for patients with hypertension.
The Effect of Oxandrolone on Weight Loss and Muscle Mass in Acute Spinal Cord Injury Patients
Authors: Pelekhaty Stacy L. , Pajoumand Mehrnaz , Scarboro Maureen , Kozar Rosemary
Published: March 2024

To investigate the impact of oxandrolone on weight and lean body mass (LBM) loss after acute spinal cord injury (aSCI), this observational study compared patients who received oxandrolone with historical controls. Age, sex, injury level, admission and discharge anthropometrics, nutrition interventions, length of stay, liver function tests, sternocleidomastoid muscle area (SMA) indexed to height on admission, and follow-up computed tomography scans were collected. Twenty patients receiving oxandrolone and 20 controls were included. Oxandrolone patients lost less weight; however, no differences were observed in SMA. Oxandrolone reduced weight loss following aSCI, but larger studies are needed to assess its impact on LBM.
Body Composition Analyses in Older Adults May Vary Significantly Depending on the Bioelectrical Impedance Analyzer Modality
Authors: Yildirim Borazan Funda , Citar Dazıroglu Merve Esra , Erdogan Gövez Nazlıcan , Acar-Tek Nilüfer , Göker Berna , Varan Hacer Dogan
Published: March 2024

This study aimed to investigate the effects of aging on body composition analyses detected by a single-frequency (SF-BIA) and a multifrequency bioelectrical impedance analyzer (MF-BIA). Forty older patients and 42 young subjects were included in the study. Body composition was measured using an SF-BIA and an MF-BIA consecutively. Significant differences were found between the analyses of SF-BIA and MF-BIA in older patients. Handgrip strength values were found to correlate more strongly with the skeletal muscle mass index detected by MF-BIA. MF-BIA may be preferable to SF-BIA in older adults due to its higher correlation coefficient with handgrip strength.
The influence of flocculation upon global gene transcription in a yeast CYC8 mutant
Authors: Lee Brenda , Hokamp Karsten , Alhussain Mohamed M. , Bamagoos Atif A. , Fleming Alastair B.
Published: March 2024

The transcriptome from a Saccharomyces cerevisiae tup1 deletion mutant was one of the first comprehensive yeast transcriptomes published. Subsequent transcriptomes from tup1 and cyc8 mutants firmly established the Tup1-Cyc8 complex as predominantly acting as a repressor of gene transcription. However, transcriptomes from tup1/cyc8 gene deletion or conditional mutants would all have been influenced by the striking flocculation phenotypes that these mutants display. In this study, we have separated the impact of flocculation from the transcriptome in a cyc8 conditional mutant to reveal those genes (i) subject solely to Cyc8p-dependent regulation, (ii) regulated by flocculation only and (iii) regulated by Cyc8p and further influenced by flocculation. We reveal a more accurate list of Cyc8p-regulated genes that includes newly identified Cyc8p-regulated genes that were masked by the flocculation phenotype and excludes genes which were indirectly influenced by flocculation and not regulated by Cyc8p. Furthermore, we show evidence that flocculation exerts a complex and potentially dynamic influence upon global gene transcription. These data should be of interest to future studies into the mechanism of action of the Tup1-Cyc8 complex and to studies involved in understanding the development of flocculation and its impact upon cell function.
Noise Reduction and Localization Accuracy in a Mobile Magnetoencephalography System
Authors: Bardouille Timothy , Smith Vanessa , Vajda Elias , Leslie Carson Drake , Holmes Niall
Published: March 2024

Magnetoencephalography (MEG) non-invasively provides important information about human brain electrophysiology. The growing use of optically pumped magnetometers (OPM) for MEG, as opposed to fixed arrays of cryogenic sensors, has opened the door for innovation in system design and use cases. For example, cryogenic MEG systems are housed in large shielded rooms to provide sufficient space for the system dewar. Here, we investigate the performance of OPM recordings inside of a cylindrical shield with a 1×2 m2footprint. The efficacy of shielding was measured in terms of field attenuation and isotropy, and the value of post hoc noise reduction algorithms was also investigated. Localization accuracy was quantified for 104 OPM sensors mounted on a fixed helmet array based on simulations and recordings from a bespoke current dipole phantom. Passive shielding attenuated direct current (DC) and power line (60 Hz) fields by approximately 60 dB, and all other frequencies by 80-90 dB. Post hoc noise reduction provided an additional 5-15 dB attenuation. Substantial field anisotropy remained in the volume encompassing the sensor array. The consistency of the anisotropy over months suggests that a field nulling solution could be readily applied. A current dipole phantom generating source activity at an appropriate magnitude for the human brain generated field fluctuations on the order of 0.5-1 pT. Phantom signals were localized with 3 mm localization accuracy and no significant bias in localization was observed, which is in line with performance for cryogenic and OPM MEG systems. This validation of the performance of a small footprint MEG system opens the door for lower cost MEG installations in terms of raw materials and facility space, as well as mobile imaging systems (e.g., truck-based). Such implementations are relevant for global adoption of MEG outside of highly resourced research and clinical institutions.
PreTSA: computationally efficient modeling of temporal and spatial gene expression patterns
Authors: Zhuang Haotian , Ji Zhicheng
Published: March 2024

Modeling temporal and spatial gene expression patterns in large-scale single-cell and spatial transcriptomics data is a computationally intensive task. We present PreTSA, a method that offers computational efficiency in modeling these patterns and is applicable to single-cell and spatial transcriptomics data comprising millions of cells. PreTSA consistently matches the results of state-of-the-art methods while significantly reducing computational time. PreTSA provides a unique solution for studying gene expression patterns in extremely large datasets.
Unveiling the genetic blueprint of a desert scorpion: A chromosome-level genome ofHadrurus arizonensisprovides the first reference for Parvorder Iurida
Authors: Bryant Meridia Jane , Coello Asher M. , Glendening Adam M. , Hilliman Samuel A. , Jara Carolina Fernanda , Pring Samuel S. , Rivera Aviel Rodriguez , Santiago Membreño Jennifer , Nigro Lisa , Pauloski Nicole , Graham Matthew R. , King Teisha , Jockusch Elizabeth L. , O’Neill Rachel J. , Wegrzyn Jill L. , Santibáñez-López Carlos E. , Webster Cynthia N.
Published: March 2024

Over 400 million years old, scorpions represent an ancient group of arachnids and one of the first animals to adapt to life on land. Presently, the lack of available genomes within scorpions hinders research on their evolution. This study leverages ultra-long nanopore sequencing and Pore-C to generate the first chromosome level assembly and annotation for the desert hairy scorpion,Hadrurus arizonensis. The assembled genome is 2.23 Gb in size with an N50 of 280 Mb. Pore-C scaffolding re-oriented 99.6% of bases into nine chromosomes and BUSCO identified 998 (98.6%) complete arthropod single copy orthologs. Repetitive elements represent 54.69% of the assembled bases, including 872,874 (29.39%) LINE elements. A total of 18,996 protein-coding genes and 75,256 transcripts were predicted, and extracted protein sequences yielded a BUSCO score of 97.2%. This is the first genome assembled and annotated within the family Hadruridae, representing a crucial resource for closing gaps in genomic knowledge of scorpions, resolving arachnid phylogeny, and advancing studies in comparative and functional genomics.

Significance

Genomic resources for the study of arachnids are limited. To date, only four scorpion genomes have been published; none of these are chromosome-level assemblies, and all four belong to a single family, Buthidae. In this study, we assembled the first chromosome-level, annotated genome for a non-buthid species (Hadrurus arizonensis). This high quality reference will provide a critical resource for comparative and functional genomics and contribute to the understanding of arachnid evolution.
Generative Adversarial Networks Accurately Reconstruct Pan-Cancer Histology from Pathologic, Genomic, and Radiographic Latent Features
Authors: Howard Frederick M. , Hieromnimon Hanna M. , Ramesh Siddhi , Dolezal James , Kochanny Sara , Zhang Qianchen , Feiger Brad , Peterson Joseph , Fan Cheng , Perou Charles M. , Vickery Jasmine , Sullivan Megan , Cole Kimberly , Khramtsova Galina , Pearson Alexander T.
Published: March 2024

Artificial intelligence models have been increasingly used in the analysis of tumor histology to perform tasks ranging from routine classification to identification of novel molecular features. These approaches distill cancer histologic images into high-level features which are used in predictions, but understanding the biologic meaning of such features remains challenging. We present and validate a custom generative adversarial network – HistoXGAN – capable of reconstructing representative histology using feature vectors produced by common feature extractors. We evaluate HistoXGAN across 29 cancer subtypes and demonstrate that reconstructed images retain information regarding tumor grade, histologic subtype, and gene expression patterns. We leverage HistoXGAN to illustrate the underlying histologic features for deep learning models for actionable mutations, identify model reliance on histologic batch effect in predictions, and demonstrate accurate reconstruction of tumor histology from radiographic imaging for a ‘virtual biopsy’.
Data-driven prioritization of genetic disorders for global genomic newborn screening programs
Authors: Minten Thomas , Gold Nina B. , Bick Sarah , Adelson Sophia , Gehlenborg Nils , Amendola Laura M. , Boemer François , Coffey Alison J. , Encina Nicolas , Ferlini Alessandra , Kirschner Janbernd , Russell Bianca E. , Servais Laurent , Sund Kristen L. , Taft Ryan J. , Tsipouras Petros , Zouk Hana ,   ICoNS Gene List Contributors, Bick David , Green Robert C. ,   the International Consortium on Newborn Sequencing (ICoNS)
Published: March 2024

Genomic sequencing is poised to expand newborn screening for treatable childhood-onset disorders. Over 30 international research studies and companies are exploring its use, collectively aiming to screen more than 500,000 infants. A key challenge is determining which genes to include in screening. Among 27 newborn sequencing programs, the number of genes analyzed ranged from 134 to 4,299, with only 74 genes included by over 80% of programs. To understand this variability, we assembled a dataset with 25 characteristics of 4,389 genes included in any program and used a multivariate regression analysis to identify characteristics associated with inclusion across programs. These characteristics included presence on the US Recommended Uniform Screening panel, evidence regarding the natural history of disease, and efficacy of treatment. We then used a machine learning model to generate a ranked list of genes, offering a data-driven approach to the future prioritization of disorders for public health newborn screening efforts.
Long-Term Trajectories of Posttraumatic Stress Disorder Symptoms: A 20-Year Longitudinal Study of World Trade Center Responders
Authors: Mann Frank D. , Waszczuk Monika A. , Clouston Sean A.P. , Feltman Scott , Ruggero Camilo J. , Marx Brian P. , Schwartz Joseph E. , Bromet Evelyn J. , Luft Benjamin J. , Kotov Roman
Published: March 2024

Objective

The present study examined the 20-year course of posttraumatic stress disorder (PTSD) in World Trade Center (WTC) responders to address four questions: (1) How stable are symptoms of PTSD? (2) What is the average symptom trajectory? (3) How much do responders differ from the average trend? (4) How quickly do PTSD symptoms improve or worsen?

Methods

Data include 81,298 observations fromn= 12,822 responders, spanning from July 2002 to December 2022. Fourteen percent meet PTSD criteria. PTSD symptoms were measured using the PCL-17. Retest correlations were calculated to estimate stability, growth curve models to estimate individual trajectories, and Kaplan-Meier curves to estimate the rate of clinically significant change.

Results

Retest correlations were high overall (range =.49, .84), lower in PTSD cases (range =.21, .78), and decreased as a function of time between assessments. The best-fitting growth model represented trajectories continuously rather than multiple classes. Symptom burden peaked in 2011 and declined modestly by 2022 (Cohen’s d = -0.28 and -0.59 in all responders and PTSD cases, respectively). Median time before clinically significant improvement in responders with PTSD was 8.88 years (95% CI = 8.01, 9.79).

Conclusions

In the longest and largest study of PTSD symptoms tracked continuously since exposure, illness course was characterized to find that, while symptoms were highly stable in the short term, symptoms changed significantly over two decades. Most responders experienced clinical improvement after nine years, but 10% had poor course and should be the focus of public health efforts.
DPR-MEDIATED H2O2RESISTANCE CONTRIBUTES TO STREPTOCOCCI SURVIVAL IN A CYSTIC FIBROSIS AIRWAY MODEL SYSTEM
Authors: Rogers Rendi R. , Kesthely Christopher A. , Jean-Pierre Fabrice , Hafi Bassam El , O’Toole George A.
Published: March 2024

The cystic fibrosis (CF) lung environment is conducive to the colonization of bacteria as polymicrobial biofilms, which are associated with poor clinical outcomes for persons with CF (pwCF).Streptococcusspp. is highly prevalent in the CF airway, but its role in the CF lung microbiome is poorly understood. Some studies have shownStreptococcusspp. to be associated with better clinical outcomes for pwCF, while others show that high abundance ofStreptococcusspp. is correlated with exacerbations. Our lab previously reported a polymicrobial culture system consisting of four CF-relevant pathogens that can be used to study microbial behavior in a more clinically relevant setting. Here, we use this model system to identify genetic pathways that are important forStreptococcus sanguinissurvival in the context of the polymicrobial community. We identified genes related to reactive oxygen species (ROS) as differentially expressed inS. sanguinismonoculture versus growth of this microbe in the mixed community. Genetic studies identified Dpr as important forS. sanguinissurvival in the community. We show that Dpr, a DNA binding ferritin-like protein, and PerR, a peroxide-responsive transcriptional regulator of Dpr, are important for protectingS. sanguinisfrom phenazine-mediated toxicity in co-culture withP. aeruginosaand when exposed to ROS, both of which mimic the CF lung environment. Characterizing such interactions in a clinically relevant model system contributes to our understanding of microbial behavior in the context of polymicrobial biofilm infections.

IMPORTANCE

Streptococcusspp. is recognized as a highly prevalent pathogen in CF airway infections. However, its role in clinical outcomes for pwCF is poorly understood. Here, we leverage a polymicrobial community system previously developed by our group to model CF airway infections as a tool to investigate aPseudomonas-Streptococcusinteraction involving ROS. We show that protection against ROS is required forS. sanguinissurvival in a clinically relevant polymicrobial system. Using this model system to study interspecies interactions contributes to our broader understanding of the complex role ofStreptococcusspp. in the CF lung.
Have AI-Generated Texts from LLM Infiltrated the Realm of Scientific Writing? A Large-Scale Analysis of Preprint Platforms
Authors: Cheng Huzi , Sheng Bin , Lee Aaron , Chaudary Varun , Atanasov Atanas G. , Liu Nan , Qiu Yue , Wong Tien Yin , Tham Yih-Chung , Zheng Yingfeng
Published: March 2024

Since the release of ChatGPT in 2022, AI-generated texts have inevitably permeated various types of writing, sparking debates about the quality and quantity of content produced by such large language models (LLM). This study investigates a critical question: Have AI-generated texts from LLM infiltrated the realm of scientific writing, and if so, to what extent and in what setting? By analyzing a dataset comprised of preprint manuscripts uploaded to arXiv, bioRxiv, and medRxiv over the past two years, we confirmed and quantified the widespread influence of AI-generated texts in scientific publications using the latest LLM-text detection technique, the Binoculars LLM-detector. Further analyses with this tool reveal that: (1) the AI influence correlates with the trend of ChatGPT web searches; (2) it is widespread across many scientific domains but exhibits distinct impacts within them (highest: computer science, engineering sciences); (3) the influence varies with authors who have different language speaking backgrounds and geographic regions according to the location of their affiliations (Italy, China, etc.); (4) AI-generated texts are used in various content types in manuscripts (most significant: hypothesis formulation, conclusion summarization); (5) AI usage has a positive influence on paper’s impact, measured by its citation numbers. Based on these findings, suggestions about the advantages and regulation of AI-augmented scientific writing are discussed.
Model for the cyclonic bias of convective vortices in a rotating system
Authors: Dingwall Jenny , Taylor John R.
Published: March 2024

In convective fluids, small vortices develop between neighboring convective cells. Familiar in the atmosphere in the form of dust devils and water spouts, these convective vortices have been seen in simulations of oceanic convection where the vortices exhibit an unexplained bias towards cyclonic rotation despite having a large Rossby number. Here we use large eddy simulations (LES) of an idealized oceanic convective mixed layer and vary independently the Coriolis acceleration and the surface buoyancy flux to investigate the development of the cyclonic bias of convective vortices. While large convective vortices are biased for sufficiently large values of the Coriolis parameter, small convective vortices do not exhibit a clear bias. Using Lagrangian particles, we find that the large convective vortices develop through the merger of many small convective vortices. We propose a statistical theory to predict the cyclonic bias of large convective vortices composed of many small unbiased convective vortices and test the theory using LES results. We apply the theory to typical convective conditions and find that convective vortices in upper ocean mixed layers are expected to exhibit a bias, while convective vortices in the terrestrial and Martian atmospheres are expected to be largely unbiased.

Published by the American Physical Society
2024
Robust image descriptor for machine learning based data reduction in serial crystallography
Authors: Rahmani Vahid , Nawaz Shah , Pennicard David , Graafsma Heinz
Published: March 2024

Serial crystallography experiments at synchrotron and X-ray free-electron laser (XFEL) sources are producing crystallographic data sets of ever-increasing volume. While these experiments have large data sets and high-frame-rate detectors (around 3520 frames per second), only a small percentage of the data are useful for downstream analysis. Thus, an efficient and real-time data classification pipeline is essential to differentiate reliably between useful and non-useful images, typically known as `hit' and `miss', respectively, and keep only hit images on disk for further analysis such as peak finding and indexing. While feature-point extraction is a key component of modern approaches to image classification, existing approaches require computationally expensive patch preprocessing to handle perspective distortion. This paper proposes a pipeline to categorize the data, consisting of a real-time feature extraction algorithm called modified and parallelized FAST (MP-FAST), an image descriptor and a machine learning classifier. For parallelizing the primary operations of the proposed pipeline, central processing units, graphics processing units and field-programmable gate arrays are implemented and their performances compared. Finally, MP-FAST-based image classification is evaluated using a multi-layer perceptron on various data sets, including both synthetic and experimental data. This approach demonstrates superior performance compared with other feature extractors and classifiers.
FLEXRGUI: a graphical user interface for multi-conformer modeling of proteins
Authors: Stachowski Timothy R. , Fischer Marcus
Published: March 2024

Proteins are well known `shapeshifters' which change conformation to function. In crystallography, multiple conformational states are often present within the crystal and the resulting electron-density map. Yet, explicitly incorporating alternative states into models to disentangle multi-conformer ensembles is challenging. We previously reported the toolFLEXR, which, within a few minutes, automatically separates conformational signal from noise and builds the corresponding, often missing, structural features into a multi-conformer model. To make the method widely accessible for routine multi-conformer building as part of the computational toolkit for macromolecular crystallography, we present a graphical user interface (GUI) forFLEXR, designed as a plugin forCoot 1. The GUI implementation seamlessly connectsFLEXRmodels with the existing suite of validation and modeling tools available inCoot. We envision thatFLEXRwill aid crystallographers by increasing access to a multi-conformer modeling method that will ultimately lead to a better representation of protein conformational heterogeneity in the Protein Data Bank. In turn, deeper insights into the protein conformational landscape may inform biology or provide new opportunities for ligand design. The code is open source and freely available on GitHub at https://github.com/TheFischerLab/FLEXR-GUI.
From solution to structure: empowering inclusive cryo-EM with a pre-characterization pipeline for biological samples
Authors: Mueller-Dieckmann Christoph , Grinzato Alessandro , Effantin Grégory , Fenel Daphna , Flot David , Schoehn Guy , Leonard Gordon , Kandiah Eaazhisai
Published: March 2024

In addressing the challenges faced by laboratories and universities with limited (or no) cryo-electron microscopy (cryo-EM) infrastructure, the ESRF, in collaboration with the Grenoble Institute for Structural Biology (IBS), has implemented the cryo-EM Solution-to-Structure (SOS) pipeline. This inclusive process, spanning grid preparation to high-resolution data collection, covers single-particle analysis and cryo-electron tomography (cryo-ET). Accessible through a rolling access route, proposals undergo scientific merit and technical feasibility evaluations. Stringent feasibility criteria demand robust evidence of sample homogeneity. Two distinct entry points are offered: users can either submit purified protein samples for comprehensive processing or initiate the pipeline with already vitrified cryo-EM grids. The SOS pipeline integrates negative stain imaging (exclusive to protein samples) as a first quality step, followed by cryo-EM grid preparation, grid screening and preliminary data collection for single-particle analysis, or only the first two steps for cryo-ET. In both cases, if the screening steps are successfully completed, high-resolution data collection will be carried out using a Titan Krios microscope equipped with a latest-generation direct electron counting detector coupled to an energy filter. The SOS pipeline thus emerges as a comprehensive and efficient solution, further democratizing access to cryo-EM research.