bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Learning Models for Predicting Hearing Thresholds Based on Swept-Tone Stimulus-Frequency Otoacoustic Emissions
Authors: Liu Yin , Gong Qin
Published: November 2023

Objectives:

This study aims to develop deep learning (DL) models for the quantitative prediction of hearing thresholds based on stimulus-frequency otoacoustic emissions (SFOAEs) evoked by swept tones.

Design:

A total of 174 ears with normal hearing and 388 ears with sensorineural hearing loss were studied. SFOAEs in the 0.3 to 4.3 kHz frequency range were recorded using linearly swept tones at a rate of 2 Hz/msec, with stimulus level changing from 40 to 60 dB SPL in 10 dB steps. Four DL models were used to predict hearing thresholds at octave frequencies from 0.5 to 4 kHz. The models—a conventional convolutional neural network (CNN), a hybrid CNN-k-nearest neighbor (KNN), a hybrid CNN-support vector machine (SVM), and a hybrid CNN-random forest (RF)—were individually built for each frequency. The input to the DL models was the measured raw SFOAE amplitude spectra and their corresponding signal to noise ratio spectra. All DL models shared a CNN-based feature self-extractor. They differed in that the conventional CNN utilized a fully connected layer to make the final regression decision, whereas the hybrid CNN-KNN, CNN-SVM, and CNN-RF models were designed by replacing the last fully connected layer of CNN model with a traditional machine learning (ML) regressor, that is, KNN, SVM, and RF, respectively. The model performance was evaluated using mean absolute error and SE averaged over 20 repetitions of 5 × 5 fold nested cross-validation. The performance of the proposed DL models was compared with two types of traditional ML models.

Results:

The proposed SFOAE-based DL models resulted in an optimal mean absolute error of 5.98, 5.22, 5.51, and 6.06 dB at 0.5, 1, 2, and 4 kHz, respectively, superior to that obtained by the traditional ML models. The produced SEs were 8.55, 7.27, 7.58, and 7.95 dB at 0.5, 1, 2, and 4 kHz, respectively. All the DL models outperformed any of the traditional ML models.

Conclusions:

The proposed swept-tone SFOAE-based DL models were capable of quantitatively predicting hearing thresholds with satisfactory performance. With DL techniques, the underlying relationship between SFOAEs and hearing thresholds at disparate frequencies was explored and captured, potentially improving the diagnostic value of SFOAEs.
15 Years of Spinal Fusion Outcomes in Children with Cerebral Palsy
Authors: Badin Daniel , Shah Suken A. , Narayanan Unni G. , Cahill Patrick J. , Marrache Majd , Samdani Amer F. , Yaszay Burt , Hunsberger Joann B. , Marks Michelle C. ,   HARMS Study Group, Sponseller Paul D.
Published: November 2023

Study Design.

Retrospective Multicenter Study

Objective.

We reviewed 15-year trends in operative factors, radiographic and quality-of-life outcomes, and complication rates in children with cerebral palsy (CP) related scoliosis who underwent spinal fusion.

Summary of Background Data.

Over the past 2 decades, significant efforts have been made to decrease complications and improve outcomes of this population.

Methods.

We retrospectively reviewed a multicenter registry of pediatric CP patients who underwent spinal fusion from 2008 to 2020. We evaluated baseline and operative, hospitalization, and complication data as well as radiographic and quality-of-life outcomes at a minimum 2-year follow-up.

Results.

Mean estimated blood loss and transfusion volume declined from 2.7±2.0 L in 2008 to 0.71±0.34 L in 2020 and 1.0±0.5 L in 2008 to 0.5±0.2 L in 2020, respectively, with a concomitant increase in antifibrinolytic use from 58% to 97% (all, P<0.01). Unit rod and pelvic fusion use declined from 33% in 2008 to 0% in 2020 and 96% in 2008 to 79% in 2020, respectively (both, P<0.05). Mean postoperative intubation time declined from 2.5±2.6 days to 0.42±0.63 days (P<0.01). No changes were observed in pre- and post-operative coronal angle and pelvic obliquity, operative time, frequency of anterior/anterior-posterior approach, and durations of hospital and intensive care unit stays. Improvements in the Caregiver Priorities and Child Health Index of Life with Disabilities postoperatively did not change significantly over the study period. Complication rates, including reoperation, superficial and deep surgical site infection, and gastrointestinal and medical complications remained stable over the study period.

Conclusions.

Over the past 15 years of CP-scoliosis surgery, surgical blood loss, transfusion volumes, duration of postoperative intubation, and pelvic fusion rates have decreased. However, the degree of radiographic correction, the rates of surgical and medical complications (including infection), and health-related quality-of-life measures have broadly remained constant.

Level of Evidence.

3
Overview of the Association between Non-Alcoholic Fatty Liver Disease and Hypertension
Authors: Kakouri Niki S. , Thomopoulos Costas G. , Siafi Eirini P. , Valatsou Angeliki E. , Dimitriadis Kyriakos S. , Mani Iliana P. , Patsilinakos Sotirios P. , Tousoulis Dimitrios M. , Tsioufis Konstantinos P.
Published: November 2023

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and its prevalence is rising. NAFLD is closely associated with metabolic syndrome, with both conditions sharing common clinical characteristics such as obesity, insulin resistance, type 2 diabetes mellitus, hypertension, and hypertriglyceridemia. Several observational studies have evaluated the relationship between NAFLD and hypertension, with the overall evidence suggesting a bidirectional relationship. It is hypothesized that activation of the sympathetic nervous and renin-angiotensin systems, observed in NAFLD with or without insulin resistance promotes the development of hypertension. In patients with hypertension, activation of these systems can lead to hepatic fibrosis and progressive inflammation through increased oxidative stress and activation of hepatic stellate cells and Kupffer cells. The present review examines the pathophysiologic and clinical evidence supporting the bidirectional association between NAFLD and hypertension.
Repeated Levosimendan Infusions in the Management of Advanced Heart Failure: Review of the Evidence and Meta-analysis of the Effect on Mortality
Authors: Silvetti Simona , Pollesello Piero , Belletti Alessandro
Published: November 2023

In the latest years, several studies described the impact of repetitive/intermittent i.v. levosimendan treatment in the management of advanced heart failure. For this updated review, we systematically searched the literature for clinical trials, registries, and real-world data and identified 31 studies that we commented in a narrative review: 3814 patients were described, of whom 1744 were treated repetitively with levosimendan. On the basis of the nature of the study protocols and of the end points, out of those studies, we further selected 9 that had characteristics, making them suitable for a meta-analysis on mortality. This short list describes data from 680 patients (of whom 399 received repeated doses of levosimendan) and 110 death events (of which 50 occurred in the levosimendan cohort). In the meta-analysis, repetitive/intermittent therapy with i.v. levosimendan was associated with a significant reduction in mortality at the longest time point available: 50 of 399 (12.5%) versus 60 of 281 (21.4%) in the control arms, with a risk ratio of 0.62 (95% confidence interval, 0.42–0.90; P < 0.01). In a sensitivity analysis, removing each trial and reanalyzing the remaining data set did not change the trend, magnitude, or significance of the results. A visual inspection of the funnel plot did not suggest publication bias. The results provide a very strong rationale for continuing to investigate the repetitive use of levosimendan in patients with advanced heart failure by properly powered regulatory clinical trials. Meanwhile, it seems that the use of repetitive/intermittent i.v. levosimendan infusions has become one of the few effective options for preserving the hemodynamic and symptomatic balance in such patients.
High Fatality Rates in Pediatric Multisystem Inflammatory Syndrome: A Multicenter Experience From the Epicenter of Brazil’s Coronavirus Pandemic
Authors: Almeida Flávia Jacqueline , Jarovsky Daniel , Almeida Farias Camila Giuliana , Ramos Nantes de Castilho Taisa Roberta , Gara Caetano Thiago , Manzoni Ribeiro Borsetto Cibele Cristina , Simões Aguiar Andressa , Serafini de Araújo Carolina , Badue Pereira Maria Fernanda , de Sousa Marques Heloisa Helena , Silva Clovis Artur , Ribeiro de Matos Tannure Andressa , Prado Rogério , Becker Mau Luciana , Andrade Alvares Paula , de Siqueira Antônio Carlos , Paro Scremin Gustavo , Otsuka Marcelo , Volpe Arnoni Mariana , Machado Rissoni Laporte Roberta , Altruda de Moraes Costa Carlesse Fabianne , Ejzenberg Fernanda , Naaman Berezin Eitan , Palazzi Sáfadi Marco Aurélio
Published: November 2023

Background:

Brazil´s case fatality rate (CFR) of pediatric multisystem inflammatory syndrome in children and adolescents (MIS-C) is among the highest worldwide. Despite these concerns, limited hospital-based and comprehensive pediatric data have been published on MIS-C in Brazilian children.

Methods:

We performed a descriptive analysis of the MIS-C scores in 16 public and private hospitals providing secondary and tertiary care in the metropolitan area of São Paulo, Brazil. Clinical and demographic information were systematically extracted from the electronic medical records of each patient. Logistic regression analysis was performed to identify the combined effects of MIS-C phenotype, disease severity and comorbidity as dependent variables.

Results:

A total of 101 patients met the MIS-C criteria and were evaluated. The median age was 67 months, 60% were male, 28.7% were black or afrodescendant and 62.3% were admitted to public hospitals. Underlying medical conditions were observed in 16.8% of patients and were associated with a longer duration of hospitalization. A Kawasaki disease-like phenotype was observed in 43.5% of patients, and they demonstrated a trend of lower median age. Children with severe MIS-C were older (median age 91 months vs. 36 months) and had a nonspecific phenotype, more cardiovascular and respiratory involvement and kidney injury; 73.3% required intensive care, 20.8% required mechanical ventilation and 35.6% required inotropic support. Four deaths occurred (CFR = 3.9%), three of which were in healthy participants.

Conclusion:

We identified a lower median age, particularly among children with Kawasaki disease-like phenotypes, those with a significant need for intensive care, and a high CFR in MIS-C. Our findings confirmed the increased severity of the disease in the selected Brazilian population.
A multiomic investigation of lung adenocarcinoma molecular subtypes
Authors: Liang Kung-Hao , Luo Yung-Hung , Wang Mong-Lien , Chiou Shih-Hwa , Chen Yuh-Min , Hsu Han-Shui
Published: November 2023

Background:

Lung adenocarcinoma—an aggressive and life-threatening malignancy—is a type of non–small-cell lung cancer. Despite medical advancements, the prognosis of lung adenocarcinoma remains unfavorable, likely because of its heterogeneous nature. Furthermore, few subtype-specific treatments are available for lung adenocarcinoma. This study was conducted to explore the molecular subtypes of lung adenocarcinoma.

Methods:

We performed a joint analysis of transcriptome and proteome data from East Asian patients with lung adenocarcinoma (nonsmokers, 86.5%).

Results:

Four novel subtypes were identified based on distinct molecular characteristics: subtypes I, II, III, and IV. In patients with subtype I lung adenocarcinoma, eukaryotic translation initiation factor 4 gamma 1 activates cell proliferation; inhibiting this factor suppresses tumor growth, and reducing its level induces autophagy. Subtype II is characterized by Kristen rat sarcoma viral oncogene homolog-activating oncogenesis; the onset age of this subtype is the lowest among all subtypes. Subtype III manifests as an advanced disease at diagnosis; it is characterized by a core serum response-related oncogenic signature, which indicates poor overall survival in Western patients with lung cancer. Subtype IV is more common in men than in women; it has astroglial characteristics. A Connectivity Map analysis revealed that the oncogenic expression patterns corresponding to subtypes I, II, III, and IV can be reversed by the inhibitors of Inhibitor of κB (IκB) kinase (eg, withaferin A), mammalian target of rapamycin (eg, everolimus), Src proto-oncogene (Src) (eg, saracatinib), and Transforming Growth Factor (TGF)-β/Smad (eg, LY-364947), respectively.

Conclusion:

This study introduced an innovative multiomics data analysis pipeline. Using this approach, we successfully identified four molecular subtypes of lung adenocarcinoma and their candidate therapeutic agents. The newly identified subtypes can be combined with the current biomarkers to generate a comprehensive roadmap for treatment decision-making.
Somatic PIK3CA Variants Are Associated With Eccrine Angiomatous Hamartomas
Authors: Bricknell Lana , Richmond Christopher M. , Das Gupta Romi , Payton Diane , Phua Yun , Kimble Roy M.
Published: November 2023

Objectives:

Eccrine angiomatous hamartoma (EAH) is a rare vascular anomaly with mixed eccrine and vascular components, typically identified in children. While benign, EAH can cause significant morbidity and be difficult to treat. The aims of this case series were to identify all patients with EAH that have been seen at the Queensland Children’s Hospital and describe their phenotypic and somatic genotypic details, in an effort to contribute to the limiting understanding and literature surrounding this condition.

Methods:

Individuals with EAH were retrospectively identified through engagement in a multidisciplinary vascular anomaly clinic in a tertiary Australian children’s hospital. All individuals had a previous histological diagnosis of EAH. High-read-depth sequencing of a panel of 27 genes known to be associated with vascular anomalies was undertaken on affected tissue. Samples were rereviewed by a senior pathologist and geneticist for this study.

Results:

Five cases of EAH were identified. All were associated with 1 of 3 somatic PIK3CA variants (c.1633G>A;p.Glu545Lys, c.1624G>A;p.Glu542Lys, and c.3140A>G;p.Histo1047Arg) in low allele fractions. These variants have previously been reported in a range of tumors and vascular anomalies, including PIK3CA-related overgrowth spectrum, but not in EAH.

Conclusion:

Occurrence of somatic PIK3CA variants in EAH provides evidence for a novel gene-disease association and is plausibly the cause of EAH in some individuals. This finding expands the phenotypic spectrum of PIK3CA, contributes to understanding of the pathophysiology of this rare condition, and may avail molecularly targeted therapy in the future.
The Perceived Intersection of Parenting and Physician Assistant Training Among Current Physician Assistant Students
Authors: Neary Stephanie , Smith Nöel E. , Henderson Derek C. , Ruggeri Mary
Published: November 2023

Introduction

Despite recent advancements in policies supporting pregnancy and parenting-related resources for physician assistant (PA) students, there remains a paucity of data on the perceptions of family planning or available resources during training. The purpose of this study was to explore the perceptions of support for, and impact on, family planning and parenting, including lactation, among PA students.

Methods

This cross-sectional study used data collected from the American Academy of Physician Associates Student Survey between January and March 2023. Descriptive and inferential statistics were performed.

Results

A total of 557 students (557/1353; 41.2%) completed the survey. Less than 15% of students (14.4%) believed their program provides resources to support parental leave, and many students (52.1%) remained unsure whether resources exist(ed). There was a significant difference for PA students (P = .005) by gender in whether family planning affected the decision to pursue PA training over another profession, with female students proportionately affected more than male students. Medical school was the most often considered aside from PA training. Most PA students (311/548; 56.8%) also felt pressure to wait until after training to have children. In addition, multiple students (26/554; 4.7%) admitted to being asked questions they believed were biased or inappropriate regarding pregnancy or parenting during the interview process for, or after beginning, PA school.

Discussion

Programs should seek opportunities to support students through all stages of family planning. Support will require both cultural and structural shifts beginning with peer stigma and extending through admissions interview question audits, faculty training, university policies, and accreditation requirements.
Self-disclosure in Adult Patients With Cancer
Authors: Lee Hyungran , Jeong Younhee
Published: November 2023

Background

Health-related self-disclosure has been studied in various aspects, as has self-disclosure of cancer patients. However, any theoretical models that comprehensively include self-disclosure events, factors associated with self-disclosure, and the outcomes of self-disclosure of cancer patients have not yet been presented.

Objective

The purpose of this study was to explore the relationships between self-disclosure, perception toward cancer, intention for self-disclosure, level and range of self-disclosure, social support, and well-being in adult patients with cancer.

Methods

Data were collected from adult cancer patients via an online survey using self-report questionnaires and analyzed using structural equation modeling. The data from 359 participants were included in the final analysis.

Results

Positive intention for self-disclosure was a significant predictor of both self-disclosure level and range, whereas negative perception toward cancer significantly decreased self-disclosure level. The self-disclosure level significantly improved both social support and well-being, whereas the self-disclosure range did not present a significant impact on social support and well-being.

Conclusion

Self-disclosure is closely associated with social support and well-being, and self-disclosure can be promoted by improving negative perceptions and positive intentions about self-disclosure. In addition, to improve the social support and well-being of cancer patients, it suggests increasing the self-disclosure depth level rather than widening the range of self-disclosure.

Implications for Practice

The results of this study can be used as evidence for the development of nursing intervention programs to reduce negative perceptions toward cancer and improve positive intentions and levels of self-disclosure among cancer patients.
Objective and subjective evaluation of walking ability with and without the use of a passive brace for hip flexor muscles in individuals with multiple sclerosis
Authors: Prada Valeria , Grange Erica , Sgarito Caterina , Pedrazzoli Elisabetta , Konrad Giovanna , Di Giovanni Rachele , Brichetto Giampaolo , Solaro Claudio
Published: November 2023

Background:

Multiple sclerosis (MS) affects the cognitive and motor domains. Muscle weakness often leads to abnormal gait. Several solutions are rising, including the use of passive exoskeletons.

Objective:

The purpose of this study is to evaluate the effect of a first-ever use of a passive exoskeleton on walking ability in people with MS.

Methods:

We recruited 50 persons with MS. All subjects were assessed using the 2-min walking test, the timed 25-foot walk test, and a two-stage rate of perceived exertion (RPE) without the exoskeleton (T0) and with the exoskeleton (T1).

Results:

The data showed a significant decrease in walking endurance while the exoskeleton is worn (2-min walking test: T0: 65.19 ± 23.37 m; T1: 59.40 ± 22.99; p < 0.0001) and a not significant difference in walking speed on a shortened distance (T0: 15.71 ± 10.30 s; T1: 15.73 ± 11.86 s; p = 0.25). No significant differences were also found for the effort perception scale (RPE: T0: 13.24 ± 3.01; T1: 13.60 ± 2.9; p = 0.3). Seventy-two percent of subjects reported a positive or neutral global perceived effect.

Conclusions:

The exoskeleton does not add any fatiguing or negative effects. Although the walking performance decreases, the overall perception of the subjects is positive. Further studies are needed to evaluate the effect of the exoskeleton on gait quality.
Radio-Guided Occult Lesion Localization With 99mTc for the Localization of Nonpalpable Melanoma and Soft Tissue Sarcoma Lesions: A Feasibility Study
Authors: Reijers Sophie J.M. , Mook Fleur J. , Groen Harald C. , Schrage Yvonne , Stokkel Marcel P.M. , Donswijk Maarten L. , van Houdt Winan J.
Published: November 2023

Purpose of the Report

Localization techniques are needed to facilitate resection of nonpalpable lesions. In this study, the feasibility of radio-guided occult lesion localization (ROLL) with99mTc is investigated for the localization of nonpalpable, small, suspicious, or proven melanoma or soft tissue sarcoma lesions at various locations throughout the body.

Patients and Methods

Patients with nonpalpable, suspicious, or proven melanoma or soft tissue sarcoma lesions were selected for this study. Within 24 hours before surgery, a median dose of 33.92 MBq99mTc-labeled human albumin particles (99mTc-NA or99mTc-MAA) was injected in the lesion under ultrasound guidance. A hand-held gamma probe was used to detect the radioactive signal and guidance during surgery.

Results

In this study, 20 patients with a total of 25 lesions were included and analyzed. The median size of the lesions was 1.8 cm (interquartile range [IQR], 1.8–4.0 cm), of which 44% were intramuscular located and 36% were subcutaneous, and 20% consisted of suspicious lymph nodes, mostly in the lower extremity. At median 4 hours (IQR, 3–6 hours) postinjection,99mTc ROLL showed a 100% intraoperative identification rate with proper signal identification with the gamma probe in all patients. With a median surgery time of 76 minutes (IQR, 45–157 minutes), all targeted lesions could be resected without99mTc-related complications, resulting in 88% microscopically margin-negative resection. No reoperations were needed for the same lesion.

Conclusions

The99mTc ROLL procedure is feasible for the localization and excision of small, nonpalpable melanoma and soft tissue sarcoma lesions at various locations in the body.
Morphometric Assessment of Alveolar Antral Artery Using Medical Computed Tomography
Authors: Mustakim Kezia Rachellea , Jung Sung Young , Eo Mi Young , Seo Mi Hyun , Kim Soung Min
Published: November 2023

This study aimed to investigate the prevalence, diameter, and position of the alveolar antral artery (AAA) in paranasal sinus computed tomography (CT) images and to correlate the location of the AAA with tooth position, the presence of teeth, and residual alveolar bone height (ABH). A retrospective study was conducted at the Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, from November 2016 to October 2021. CT images of 100 maxillary sinuses from 50 patients managed for modified endoscopic sinus surgery and sinus lifting by a single surgeon were selected and obtained from the Infinitt picture archiving and communication system radiology system (Infinitt Healthcare Co., Seoul, Korea). The location of the AAA in the lateral wall of the maxillary sinus was evaluated in correlation with the area of the first and second molars (M1 and M2), the presence of teeth, and the residual ABH. In this study, we found that the intraosseous type is the most common type of AAA. Furthermore, the location and distance of the AAA are significantly affected by tooth position, an edentulous state in the case of the first molar, and residual ABH. Pre-evaluation of the diameter, position, and distance to the AAA using CT images is essential to help prevent hemorrhage. The existence and wide range of the AAA distances based on the tooth position, edentulous state, and residual ABH should be considered even if CT imaging cannot locate the AAA.
Molecular dynamics simulation of the interaction between palmitic acid and high pressure CO
2
Authors: Li Fei , Sun Fayu , Li Zirui , Zheng Zihao , Wang Weiqiang
Published: November 2023

In this study, molecular dynamics simulation was used to explore the interaction characteristics of palmitic acid and CO
2
, and the effects of temperature and pressure on the solubility of palmitic acid in CO
2
were investigated. In the range of 293–353 K and 5–30 MPa, the snapshot of palmitic acid distribution in CO
2
shows that the molecular chain of palmitic acid in high-density CO
2
system is more straight and more dispersed than that in low-density CO
2
system. The radial distribution function further clearly shows that the solubility of palmitic acid in CO
2
decreases with the increase of temperature and increases with the increase of pressure, which is consistent with the fatty acid solubility data reported in the literature and the setting rules of supercritical CO
2
extraction process conditions. As the temperature decreases and the pressure increases, the interaction energy between palmitic acid and CO
2
increases, which is conducive to overcoming the intermolecular force of palmitic acid and promoting dissolution. The solubility parameters of palmitic acid and CO
2
can better reflect the trend of palmitic acid solubility changing with temperature and pressure, which can play a guiding role in the determination of process conditions and even the development of new processes.
Homotopy perturbation method and its convergence analysis for nonlinear collisional fragmentation equations
Authors: Yadav Nisha , Das Ashok , Singh Mehakpreet , Singh Sukhjit , Kumar Jitendra
Published: November 2023

The exploration of collisional fragmentation pheno-mena remains largely unexplored, yet it holds considerable importance in numerous engineering and physical processes. Given the nonlinear nature of the governing equation, only a limited number of analytical solutions for the number density function corresponding to empirical kernels are available in the literature. This article introduces a semi-analytical approach using the homotopy perturbation method to obtain series solutions for the nonlinear collisional fragmentation equation. The method presented here can be readily adapted to solve both linear and nonlinear integral equations, eliminating the need for domain discretization. To gain deeper insights intothe accuracy of the proposed method, a convergence analysis is conducted. This analysis employs the concept of contractive mapping within the Banach space, a well-established technique universally acknowledged for ensuring convergence. Various collisional kernels (product and polymerization kernels), breakage distribution functions (binary and multiple breakage) and various initial particle distributions are considered to obtain the new series solutions. The obtained results are successfully compared against finite volume method [26] solutions in terms of number density functions and their moments. The error between the exact and obtained series solutions is shown in plots and tables to confirm the applicability and accuracy of the proposed method.
Bounds of the technical constants for two-dimensional anisotropic elasticity
Authors: Vannucci Paolo
Published: November 2023

The complete set of bounds for the technical constants of an elastic layer, plate or laminate is given. The bounds are valid in general, also for completely anisotropic bodies. They are obtained transforming the polar bounds previously found. These bounds complete the knowledge of classical elasticity at least in the two-dimensional case and are useful in several situations, e.g. for determining the correct feasibility domain in design problems or as necessary conditions for accepting the results of laboratory tests on anisotropic layers.
How density dependence, genetic erosion and the extinction vortex impact evolutionary rescue
Authors: Nordstrom Scott W. , Hufbauer Ruth A. , Olazcuaga Laure , Durkee Lily F. , Melbourne Brett A.
Published: November 2023

Following severe environmental change that reduces mean population fitness below replacement, populations must adapt to avoid eventual extinction, a process called evolutionary rescue. Models of evolutionary rescue demonstrate that initial size, genetic variation and degree of maladaptation influence population fates. However, many models feature populations that grow without negative density dependence or with constant genetic diversity despite precipitous population decline, assumptions likely to be violated in conservation settings. We examined the simultaneous influences of density-dependent growth and erosion of genetic diversity on populations adapting to novel environmental change using stochastic, individual-based simulations. Density dependence decreased the probability of rescue and increased the probability of extinction, especially in large and initially well-adapted populations that previously have been predicted to be at low risk. Increased extinction occurred shortly following environmental change, as populations under density dependence experienced more rapid decline and reached smaller sizes. Populations that experienced evolutionary rescue lost genetic diversity through drift and adaptation, particularly under density dependence. Populations that declined to extinction entered an extinction vortex, where small size increased drift, loss of genetic diversity and the fixation of maladaptive alleles, hindered adaptation and kept populations at small densities where they were vulnerable to extinction via demographic stochasticity.
Adaptation of perennial flowering phenology across the European range of
Arabis alpina
Authors: Wunder Jörg , Fulgione Andrea , Toräng Per , Wötzel Stefan , Herzog Michel , Obeso José Ramón , Kourmpetis Yiannis , van Ham Roeland , Odong Thomas , Bink Marco , Kemi Ulla , Ågren Jon , Coupland George
Published: November 2023

Flowering phenology is important in the adaptation of many plants to their local environment, but its adaptive value has not been extensively studied in herbaceous perennials. We used
Arabis alpina
as a model system to determine the importance of flowering phenology to fitness of a herbaceous perennial with a wide geographical range. Individual plants representative of local genetic diversity (accessions) were collected across Europe, including in Spain, the Alps and Scandinavia. The flowering behaviour of these accessions was documented in controlled conditions, in common-garden experiments at native sites and
in situ
in natural populations. Accessions from the Alps and Scandinavia varied in whether they required exposure to cold (vernalization) to induce flowering, and in the timing and duration of flowering. By contrast, all Spanish accessions obligately required vernalization and had a short duration of flowering. Using experimental gardens at native sites, we show that an obligate requirement for vernalization increases survival in Spain. Based on our analyses of genetic diversity and flowering behaviour across Europe, we propose that in the model herbaceous perennial
A. alpina
, an obligate requirement for vernalization, which is correlated with short duration of flowering, is favoured by selection in Spain where the plants experience a long growing season.
A dawn and dusk chorus will emerge if males sing in the absence of their mate
Authors: Schlicht Lotte , Schlicht Emmi , Santema Peter , Kempenaers Bart
Published: November 2023

The spring dawn and dusk chorus of birds is a widespread phenomenon, yet its origin remains puzzling. We propose that a dawn and dusk chorus will inevitably arise if two criteria are met: (1) females leave their roost later in the morning and go to roost earlier in the evening than their mate, and (2) males sing more when separated from their mate. Previous studies on blue tits (
Cyanistes caeruleus
) support the first criterion. We here report that males sing at a higher rate whenever they are separated from their mate and that song rate increases with the duration of female absence. These findings can explain the existence of the dawn and dusk chorus in blue tits, and they can explain why the dawn chorus is more pronounced than the dusk chorus, as is typically observed. An exhaustive literature search provides support for both criteria of the ‘absent mate’ hypothesis in several passerine birds. We found no evidence contradicting the hypothesis. The new hypothesis is not inconsistent with many of the existing hypotheses about dawn singing, but may be a more general explanation for the occurrence of a dawn and dusk chorus. We describe how the ‘absent mate’ hypothesis leads to testable predictions about daily and seasonal variation in song output.
Performance of CHROMagar ESBL media for the surveillance of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) from rectal swabs in Botswana
Authors: Mannathoko Naledi , Lautenbach Ebbing , Mosepele Mosepele , Otukile Dimpho , Sewawa Kgotlaetsile , Glaser Laurel , Cressman Leigh , Cowden Laura , Alby Kevin , Jaskowiak-Barr Anne , Gross Robert , Mokomane Margaret , Paganotti Giacomo M. , Styczynski Ashley , Smith Rachel M. , Snitkin Evan , Wan Tiffany , Bilker Warren B. , Richard-Greenblatt Melissa
Published: November 2023

Introduction. Lack of laboratory capacity hampers consistent national antimicrobial resistance (AMR) surveillance. Chromogenic media may provide a practical screening tool for detection of individuals colonized by extended-spectrum beta-lactamase (ESBL)-producing organisms.

Hypothesis. CHROMagar ESBL media represent an adequate screening method for the detection of extended-spectrum cephalosporin-resistant

Enterobacterales

(ESCrE), isolated from rectal swabs.

Aim. To evaluate the performance of CHROMagar ESBL media to accurately identify ESCrE isolates from rectal swab samples attained from hospitalized and community participants.

Methodology. All participants provided informed consent prior to enrolment. Rectal swabs from 2469 hospital and community participants were inoculated onto CHROMagar ESBL. The performance of CHROMagar ESBL to differentiate

Escherichia coli

and

Klebsiella

spp.,

Enterobacter

spp. and

Citrobacter

spp. (KEC spp.) as well as select for extended-spectrum cephalosporin resistance were compared to matrix-assisted laser desorption/ionization-time-of-flight MS (MALDI-TOF-MS) and VITEK-2 automated susceptibility testing.

Results. CHROMagar ESBL had a positive and negative agreement of 91.2 % (95 % CI, 88.4–93.3) and 86.8 % (95 % CI, 82.0–90.7) for

E. coli

and 88.1 % (95 % CI 83.2–92.1) and 87.6 % (95 % CI 84.7–90.2) for KEC spp. differentiation, respectively, when compared to species ID by MALDI-TOF-MS. When evaluated for phenotypic susceptibilities (VITEK-2), 88.1 % (714/810) of the isolates recovered on the selective agar exhibited resistance to third-generation cephalosporins.

Conclusion. The performance characteristics of CHROMagar ESBL media suggest that they may be a viable screening tool for the identification of ESCrE from hospitalized and community participants and could be used to inform infection prevention and control practices in Botswana and potentially other low-and middle-income countries (LMICs). Further studies are required to analyse the costs and the impact on time-to-result of the media in comparison with available laboratory methods for ESCrE surveillance in the country.
Correlation between COVID-19 vaccination and inflammatory musculoskeletal disorders
Authors: Park Young Hwan , Kim Min Ho , Choi Myeong Geun , Chun Eun Mi
Published: November 2023

Importance

Earlier research on COVID-19 vaccines identified a range of adverse reactions related to proinflammatory actions that can lead to an excessive immune response and sustained inflammation. However, no study has been conducted on the association between inflammatory musculoskeletal disorders and COVID-19 vaccines.

Objective

To investigate the incidence rates of inflammatory musculoskeletal disorders following COVID-19 vaccination and to compare them with those of unvaccinated individuals.

Design, Setting, and Participants

This retrospective nationwide cohort study used data from the Korean National Health Insurance Service (NHIS) database, involving 2,218,715 individuals. Data were collected from January 1, 2021, to 12 weeks after the second dose of vaccine for vaccinated individuals and 12 weeks after September 30, 2021, for unvaccinated individuals.

Exposures

Status was categorized as unvaccinated and vaccinated with mRNA vaccine, viral vector vaccine, and mixing and matching.

Main Outcomes and Measures

The primary outcome was the occurrence of inflammatory musculoskeletal disorders that were selected as plantar fasciitis (ICD code, M72.2), rotator cuff syndrome (M75.1), adhesive capsulitis (M75.0), herniated intervertebral disc (HIVD) (M50.2/M51.2), spondylosis (M47.9), bursitis (M71.9), Achilles tendinitis (M76.6), and de-Quervain tenosynovitis (M65.4). Multivariate logistic regression analysis was used to determine the risk factors of musculoskeletal disorders after adjusting for potential confounders.

Results

Among the 2,218,715 individuals, 1,882,640 (84.9%) received two doses of the COVID-19 vaccine, and 336,075 (15.1%) did not. At 12 weeks after vaccination, the incidences of plantar fasciitis (0.14-0.17%), rotator cuff syndrome (0.29-0.42%), adhesive capsulitis (0.29-0.47%), HIVD (0.18-0.23%), spondylosis (0.14-0.23%), bursitis (0.02-0.03%), Achilles tendinitis (0.0-0.05%), and de-Quervain tenosynovitis (0.04-0.05%) were higher in all three vaccinated groups (mRNA, cDNA, and mixing and matching vaccines) when compared to the unvaccinated group. All COVID-19 vaccines were identified as significant risk factors for each inflammatory musculoskeletal disorder (odds ratio, 1.404-3.730), except for mixing and matching vaccines for de-Quervain tenosynovitis.

Conclusions and Relevance

This cohort study found that individuals who received any COVID-19 vaccine were more likely to be diagnosed with inflammatory musculoskeletal disorders than those who did not. This information will be useful in clarifying the adverse reactions to COVID-19 vaccines and informing people about their potential for inflammatory musculoskeletal disorders after vaccination.
ChatGPT for assessing risk of bias of randomized trials using the RoB 2.0 tool: A methods study
Authors: Pitre Tyler , Jassal Tanvir , Talukdar Jhalok Ronjan , Shahab Mahnoor , Ling Michael , Zeraatkar Dena
Published: November 2023

Background

Internationally accepted standards for systematic reviews necessitate assessment of the risk of bias of primary studies. Assessing risk of bias, however, can be time- and resource-intensive. AI-based solutions may increase efficiency and reduce burden.

Objective

To evaluate the reliability of ChatGPT for performing risk of bias assessments of randomized trials using the revised risk of bias tool for randomized trials (RoB 2.0).

Methods

We sampled recently published Cochrane systematic reviews of medical interventions (up to October 2023) that included randomized controlled trials and assessed risk of bias using the Cochrane-endorsed revised risk of bias tool for randomized trials (RoB 2.0). From each eligible review, we collected data on the risk of bias assessments for the first three reported outcomes. Using ChatGPT-4, we assessed the risk of bias for the same outcomes using three different prompts: a minimal prompt including limited instructions, a maximal prompt with extensive instructions, and an optimized prompt that was designed to yield the best risk of bias judgements. The agreement between ChatGPT’s assessments and those of Cochrane systematic reviewers was quantified using weighted kappa statistics.

Results

We included 34 systematic reviews with 157 unique trials. We found the agreement between ChatGPT and systematic review authors for assessment of overall risk of bias to be 0.16 (95% CI: 0.01 to 0.3) for the maximal ChatGPT prompt, 0.17 (95% CI: 0.02 to 0.32) for the optimized prompt, and 0.11 (95% CI: -0.04 to 0.27) for the minimal prompt. For the optimized prompt, agreement ranged between 0.11 (95% CI: -0.11 to 0.33) to 0.29 (95% CI: 0.14 to 0.44) across risk of bias domains, with the lowest agreement for the deviations from the intended intervention domain and the highest agreement for the missing outcome data domain.

Conclusion

Our results suggest that ChatGPT and systematic reviewers only have “slight” to “fair” agreement in risk of bias judgements for randomized trials. ChatGPT is currently unable to reliably assess risk of bias of randomized trials. We advise against using ChatGPT to perform risk of bias assessments. There may be opportunities to use ChatGPT to streamline other aspects of systematic reviews, such as screening of search records or collection of data.
A mean-field model of gamma-frequency oscillations in networks of excitatory and inhibitory neurons
Authors: Tahvili Farzin , Destexhe Alain
Published: November 2023

Gamma oscillations are widely seen in the cerebral cortex in different states of the wake-sleep cycle and are thought to play a role in sensory processing and cognition. Here, we study the emergence of gamma oscillations at two levels, in networks of spiking neurons, and a mean-field model. At the network level, we consider two different mechanisms to generate gamma oscillations and show that they are best seen if one takes into account the synaptic delay between neurons. At the mean-field level, we show that, by introducing delays, the mean-field can also produce gamma oscillations. The mean-field matches the mean activity of excitatory and inhibitory populations of the spiking network, as well as their oscillation frequencies, for both mechanisms. This mean-field model of gamma oscillations should be a useful tool to investigate large-scale interactions through gamma oscillations in the brain.
Polymer-mediated oligonucleotide delivery enables construction of barcoded 3D cultures for spatial single-cell analysis
Authors: King Jessica J. , Mowla Alireza , Kretzmann Jessica A. , Norret Marck , Kadolsky Ulrich D. , Iqbal Munir , Saxena Alka , Mamsa Somayra S.A. , Amos Sebastian E. , Choi Yu Suk , Kennedy Brendan F. , Iyer K. Swaminathan , Smith Nicole M. , Evans Cameron W.
Published: November 2023

Spatial transcriptomics has been widely used to capture gene expression profiles, realised as a two-dimensional (2D) projection of RNA captured from tissue sections. Wree-dimensional (3D) cultures such as spheroids and organoids are highly promising alternatives to oversimplified and homogeneous 2D cell culture models, but existing spatial transcriptomic platforms do not currently have sufficient resolution for robust analysis of 3D cultures. We present a transfection-based method for fluorescent DNA barcoding of cell populations, and the subsequent construction of spheroidal cellular architectures using barcoded cells in a layer-by-layer approach. For the first time, changes in gene expression throughout this 3D culture architecture are interrogated using multiplex single-cell RNA sequencing in which DNA barcodes are used to encode the spatial positioning of cells. We show that transfection with fluorophore-conjugated barcode oligonucleotides enables both imaging and sequencing at single-cell resolution, providing spatial maps of gene expression and drug response. Additionally, we show that fluorophore-conjugated DNA barcodes support correlative imaging studies such as mechano-microscopy to capture information about spatially-varying mechanical heterogeneity in 3D cultures. We ability to create customised, encoded cellular assemblies is a general approach that can resolve spatial differences in gene expression in 3D cell culture models.
Decreases in purchases of energy, sodium, sugar, and saturated fat three years after implementation of the Chilean Food Labelling and Marketing Law
Authors: Taillie Lindsey Smith , Bercholz Maxime , Popkin Barry , Rebolledo Natalia , Reyes Marcela , Corvalán M. Camila
Published: November 2023

Background

In 2016, Chile implemented a multi-phase set of policies that mandated warning labels, restricted food marketing to children, and banned school sales of unhealthy foods and beverages. Chile’s law, particularly the warning label component, set the precedent for a rapid global proliferation of similar policies. While our initial evaluation showed policy-linked decreases in purchases of products carrying the warning label, a longer-term evaluation is needed, particularly as later phases of Chile’s law included stricter nutrient thresholds and introduced a daytime ban on advertising of labeled foods for all audiences. The objective is to evaluate changes in purchases of energy, sugar, sodium, and saturated fat purchased after Phase 2 implementation of the Chilean policies.

Methods and Findings

This before- and after-study used longitudinal data on monthly food and beverage purchases from 2,844 Chilean households (138,391 household-months) from July 1, 2013 until June 30, 2019. Nutrition facts panel data from food and beverage packages were linked at the product level and reviewed by nutritionists. Products were considered to carry the warning label if they contained added sugar, sodium, or saturated fat, and exceeded the final phase nutrient or calorie thresholds (thus would carry the warning label). Using correlated random-effects models and an interrupted time series design, we estimated the nutrient content of food and beverage purchases associated with Phase 1 and Phase 2 compared to a counterfactual scenario based on pre-policy trends. Compared to the counterfactual, we observed significant decreases in purchases of foods and beverages carrying the warning label during Phase 2, including a relative 36.8% reduction in sugar (−30.3 calories, 95% CI −34.5, −26.3), a 23.0% relative reduction in energy (−51.6 calories, 95% CI −60.7, −42.6), a 21.9% relative reduction in sodium (−85.8 mg, 95% CI −105.0, −66.7) and a 15.7% relative reduction in saturated fat (−6.4 calories, 95% CI −8.4, −4.3). Decreases were partially offset by increases in non-labeled purchases, but the net effect shows a significant decrease in total nutrients of concern purchased during Phase 2. Reductions in sugar and energy were driven by beverage purchases, whereas reductions in sodium and saturated fat were driven by foods. The pattern of declines in purchases was similar for households of lower vs. higher socioeconomic status. A key limitation of this study is that the data include only a portion of what Chilean households purchase that, while including important categories impacted by the law, do not cover an entire diet.

Conclusions

The Chilean policies on food labeling, marketing, and school food sales led to declines in nutrients of concern during a more complete phase of implementation, particularly from foods and drinks carrying the warning label.
Within-host virus spreading and tolerance to infection are key factors of theArabidopsis thalianaage-dependent susceptibility to viral infections
Authors: Melero Izan , Gómez-Cadenas Aurelio , González Rubén , Elena Santiago F.
Published: November 2023

Arabidopsis thalianais more susceptible to certain viruses during its later developmental stages. The reasons for this age-dependent susceptibility are not fully understood. Here we explored the possible causes by studying theA. thalianainfection response to turnip mosaic virus at three developmental stages: vegetative, bolting and flowering. We found that infected plants at later stages downregulate cell wall fortification genes and that this downregulation facilitates the viral spread and systemic infection. Despite being more susceptible to infection, infected flowering plants are more fertile (i.e., produce more viable seeds) than vegetative and bolting infected plants; that is, they have greater fitness than plants infected at these earlier developmental stages. Treatment of postbolting plants with salicylic acid increases resistance to infections at the cost of significantly reducing fertility. Together, these observations suggest a negative trade-off between viral susceptibility and plant fertility. Our findings point towards a development-dependent tolerance to infection.