bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilaterality, not multifocality, is an independent risk factor for recurrence in low-risk papillary thyroid cancer
Authors: Rodriguez Schaap Pedro Manuel , Lin Jia Feng , Metman Madelon J H , Dreijerink Koen M A , Links Thera P , Bonjer H Jaap , Nieveen van Dijkum Els J M , Dickhoff Chris , Kruijff Schelto , Engelsman Anton F
Published: June 2023

Background

The impact of multifocality and bilaterality on recurrence in patients with low-risk papillary thyroid cancer (PTC) is relevant when considering patients for a de-escalated treatment strategy: hemithyroidectomy instead of total thyroidectomy followed with or without radioactive iodine. This study aims to analyze contralateral tumor probability in patients treated for low-risk PTC and assess multifocality and bilaterality as possible predictors for recurrence.

Methods

Patients with low-risk PTC treated with total thyroidectomy followed with or without radioactive iodine in the Netherlands between 2005 and 2015 were included in this study. Patients were identified from the Netherlands Comprehensive Cancer Organization (IKNL) and linked with the nationwide network and registry of Pathology in the Netherlands (PALGA). Contralateral tumor probability and recurrence were assessed.

Results

Of 791 included patients, 41.8% (331 of 791) had multifocal disease, with 68.9% (228 of 331) of those patients having bilateral disease. The contralateral tumor probability after hemithyroidectomy was 24.6% (150 of 610) for patients with unifocal disease and 43.1% (78 of 181) for patients with multifocal disease. We found a higher trend of recurrence in patients with bilateral disease, regardless of multifocality: in patients with contralateral disease after precompletion diagnosed unifocal disease 7.3% (11 of 150) had recurrent disease, and patients without contralateral disease after precompletion diagnosed multifocal disease 1.9% (2 per 103) had recurrence. Cox regression analysis showed that bilaterality (hazard ratio = 3.621, 95% confidence interval = 1.548 to 8.471) was the sole statistically significant risk factor for recurrence.

Conclusion

Low recurrence rates are found in patients with either multifocal or bilateral disease with low-risk PTC. Bilaterality should be taken into account when considering these patients for de-escalated treatment strategy.
Sacubitril/valsartan cardioprotective effect against cisplatin-induced cardiotoxicity via modulation of VEGF/eNOS and TLR4/TNFα/IL6 signalling pathways
Authors: Mahmoud Refaie Marwa Monier , Ahmed Rifaai Rehab , Bayoumi Asmaa M A , Shehata Sayed
Published: June 2023

Objectives

Drug-induced cardiac injury is a potentially preventable cause of heart failure. Cisplatin (CIS) is a widely used chemotherapeutic agent complicated with cardiotoxicity that limits its clinical application so we aimed to evaluate the suspected cardioprotective effect of sacubitril/valsartan (Sac/Val) against CIS cardiotoxic injury.

Methods

Forty male rats of Wistar albino species were divided into four groups. group I received the vehicle; group II was given the vehicle plus CIS (10 mg/kg) single i.p. on fifth day; group III was given Sac/Val (30 mg/kg/d) orally for 7 days plus CIS (10 mg/kg) single i.p. on fif5th day; group IV was given the same as group III plus nitro-ω-L-arginine (L-NNA) (25 mg/kg/d) orally for 7 days.

Key findings

CIS-induced cardiotoxicity and L-NNA co-administered group showed significant increases in cardiac enzymes, toxic histopathological features, elevated heart weights, angiotensin II (Ang II), neprilysin, malondialdehyde (MDA), inflammatory mediators, blood pressure (BP) and caspase 3 expressions, but there are significant decreases in the antioxidant parameters, vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS). However, the co-administration of Sac/Val could ameliorate these changes of CIS.

Conclusion

Sac/Val has an important cardioprotective effect against CIS cardiotoxicity with the involvement of eNOS.
Improving Military Medical Retention Through Growth Counseling: A Cross-sectional Retention Survey of U.S. Army Physician Assistants
Authors: Greener Robert K , Love Ashley S , Niu Chunling , Downs Lynn T
Published: June 2023

Introduction

Although compensation is often the only factor considered with military medical retention, retention has been shown to have many other important factors. Maximizing the retention of military medical personnel not only decreases the cost of recruiting them but also maintains the institutional knowledge of military medicine needed to conduct military medical operations. This study used a recent retention survey of U.S. Army physician assistants (PAs) to understand military medical retention needs.

Materials and Methods

The study analyzed a survey created, implemented, and collected by the Statistical Cell at the U.S. Army Center of Excellence. In September 2020, all 864 active duty PAs were sent a link to the survey and 290 completed the survey, with a participation rate of 34%. The study used cross-tabulation, Pearson’s chi-square, and multivariate logistical regression to analyze the results. Institutional review board approval was obtained through the Army Medical Center of Excellence and University of the Incarnate Word.

Results

Pearson’s chi-square found that 18 questions in the survey were answered significantly different (P < .05) among those who intended to stay for 20 years in the Army. Binomial logistical regression found that each point higher on a 5-point Likert scale of the belief a PA could accomplish their career goals in Army medicine increased probability of likelihood to stay for 20 years by 74% (95% CI [0.57-0.98]). Each point higher on a 5-point Likert scale of perception Defense Health Agency control of Army medicine affected retention increased probability of likelihood to stay by 54% (95% CI [0.39-0.75]). Every decade older of age increased probability of increased likelihood to stay for 20 years by 63% (95% CI [0.40-0.98]).

Conclusions

The belief a service member can reach their career goals in the military is critical for retention. Using Army Techniques Publication 6-22.1 as a guide, leaders can help subordinates meet their career goals, and this may be the most important task a leader can accomplish to improve their unit’s retention. Strengths of this study include the high response rate of 33.6% and results demonstrating the importance of growth counseling which is already part of Army doctrine. Weaknesses include the use of secondary cross-sectional data which impair the ability to derive conclusions from the data. Future studies should explore how training programs for military leaders in growth counseling can help subordinates find their career goals in the military and the effect on military retention.
Outcome of patients with cystic fibrosis colonized byScedosporiumandLomentosporaspecies: A longitudinal cohort study
Authors: Parize Perrine , Fleury Maxime , Poupon-Bourdy Stéphanie , Persat Florence , Touzet Sandrine , Bienvenu Anne-Lise , Wallon Martine , Reix Philippe , Bouchara Jean-Philippe , Durieu Isabelle
Published: June 2023

Scedosporium and Lomentospora species rank second among the filamentous fungi colonizing the airways of cystic fibrosis (CF) patients. These fungi could be responsible for allergic bronchopulmonary mycosis (ABPM) and bronchitis before lung transplantation and invasive infections after. However, their role in CF lung disease is debated. This study aimed to identify clinical or environmental factors associated with an airway colonization by Scedosporium/Lomentospora species in patients with CF over a period of 7 years. A longitudinal cohort study was conducted from 2008 to 2014 in the CF reference centre in Lyon, France, to compare the characteristics of patients with Scedosporium/Lomentospora colonized and non-colonized patients. During the study period, 283 patients completed the clinical and microbiological follow-up. The analysis revealed that a higher number and duration of hospitalizations, an increased number of courses of parenteral antibiotic therapy, a history of ABPA, and treatment by itraconazole were significantly associated with an airway colonization by Scedosporium/Lomentospora species. The rate of decline of forced expiratory volume in the first second was not statistically different between colonized and non-colonized patients. This study provides evidence that patients colonized by Scedosporium/Lomentospora species require more medical care than non-colonized patients. Additional care could be in part explained by the management of Scedosporium/Lomentospora-related diseases such as ABPM or bronchitis. However, we did not demonstrate a faster rate of decline of respiratory function or body mass index in colonized patients, suggesting, as previously reported, that colonization of the airways by these fungi does not play a significant role in the progression of CF disease.
High-energy synchrotron flares powered by strongly radiative relativistic magnetic reconnection: 2D and 3D PIC simulations
Authors: Schoeffler K M , Grismayer T , Uzdensky D , Silva L O
Published: June 2023

The time evolution of high-energy synchrotron radiation generated in a relativistic pair plasma energized by reconnection of strong magnetic fields is investigated with 2D and 3D particle-in-cell (PIC) simulations. The simulations in this 2D/3D comparison study are conducted with the radiative PIC code OSIRIS, which self-consistently accounts for the synchrotron radiation reaction on the emitting particles, and enables us to explore the effects of synchrotron cooling. Magnetic reconnection causes compression of the plasma and magnetic field deep inside magnetic islands (plasmoids), leading to an enhancement of the flaring emission, which may help explain some astrophysical gamma-ray flare observations. Although radiative cooling weakens the emission from plasmoid cores, it facilitates additional compression there, further amplifying the magnetic field B and plasma density n, and thus partially mitigating this effect. Novel simulation diagnostics utilizing 2D histograms in the n-B space are developed and used to visualize and quantify the effects of compression. The n-B histograms are observed to be bounded by relatively sharp power-law boundaries marking clear limits on compression. Theoretical explanations for some of these compression limits are developed, rooted in radiative resistivity or 3D kinking instabilities. Systematic parameter-space studies with respect to guide magnetic field, system size, and upstream magnetization are conducted and suggest that stronger compression, brighter high-energy radiation, and perhaps significant quantum electrodynamic effects such as pair production, may occur in environments with larger reconnection-region sizes and higher magnetization, particularly when magnetic field strengths approach the critical (Schwinger) field, as found in magnetar magnetospheres.
Spectroscopic survey of faint planetary-nebula nuclei – II. The subdwarf O central star of Fr 2-30
Authors: Bond Howard E , Werner Klaus , Zeimann Gregory R , Talbot Jonathan
Published: June 2023

Fr 2-30 = PN? G126.8−15.5 is a faint emission nebula, hosting a 14th-mag central star that we identify here for the first time. Deep Hα and [O iii] images reveal a roughly elliptical nebula with dimensions of at least 22 arcmin × 14 arcmin, fading into a surrounding network of even fainter emission. Optical spectrograms of the central star show it to have a subdwarf O spectral type, with a Gaia parallax distance of 890 pc. A model-atmosphere analysis gives parameters of $T_{\rm eff}=60\, 000$ K, log g = 6.0, and a low helium content of nHe/nH = 0.0017. The location of the central star in the log g–Teff plane is inconsistent with a post-asymptotic-giant-branch evolutionary status. Two alternatives are that it is a helium-burning post-extreme-horizontal-branch object, or a hydrogen-burning post-red-giant-branch star. In either case, the evolutionary ages are so long that a detectable planetary nebula (PN) should not be present. We find evidence for a variable radial velocity (RV), suggesting that the star is a close binary. However, there are no photometric variations, and the spectral-energy distribution rules out a companion earlier than M2 V. The RVs of the star and surrounding nebula are discordant, and the nebula lacks typical PN morphology. We suggest that Fr 2-30 is a ‘PN mimic’ – the result of a chance encounter between the hot sdO star and an interstellar cloud. However, we note the puzzling fact that there are several nuclei of genuine PNe that are known to be in evolutionary states similar to that of the Fr 2-30 central star.
A thermal–kinetic subgrid model for supernova feedback in simulations of galaxy formation
Authors: Chaikin Evgenii , Schaye Joop , Schaller Matthieu , Benítez-Llambay Alejandro , Nobels Folkert S J , Ploeckinger Sylvia
Published: June 2023

We present a subgrid model for supernova feedback designed for cosmological simulations of galaxy formation that may include a cold interstellar medium (ISM). The model uses thermal and kinetic channels of energy injection, which are built upon the stochastic kinetic and thermal models for stellar feedback used in the owls and eagle simulations, respectively. In the thermal channel, the energy is distributed statistically isotropically and injected stochastically in large amounts per event, which minimizes spurious radiative energy losses. In the kinetic channel, we inject the energy in small portions by kicking gas particles in pairs in opposite directions. The implementation of kinetic feedback is designed to conserve energy, linear and angular momentum, and is statistically isotropic. To test the model, we run simulations of isolated Milky Way-mass and dwarf galaxies, in which the gas is allowed to cool down to 10 K. Using the thermal and kinetic channels together, we obtain smooth star formation histories and powerful galactic winds with realistic mass loading factors. Furthermore, the model produces spatially resolved star formation rates (SFRs) and velocity dispersions that are in agreement with observations. We vary the numerical resolution by several orders of magnitude and find excellent convergence of the global SFRs and wind mass loading. We show that large thermal energy injections generate a hot phase of the ISM and modulate the star formation by ejecting gas from the disc, while the low-energy kicks increase the turbulent velocity dispersion in the neutral ISM, which in turn helps suppress star formation.
Growing black holes through successive mergers in galactic nuclei – I. Methods and first results
Authors: Atallah Dany , Trani Alessandro A , Kremer Kyle , Weatherford Newlin C , Fragione Giacomo , Spera Mario , Rasio Frederic A
Published: June 2023

We present a novel, few-body computational framework designed to shed light on the likelihood of forming intermediate-mass (IM) and supermassive (SM) black holes (BHs) in nuclear star clusters (NSCs) through successive BH mergers, initiated with a single BH seed. Using observationally motivated NSC profiles, we find that the probability of an ${\sim }100\hbox{-}\mathrm{M}_\odot$ BH to grow beyond ${\sim }1000 \, \mathrm{M}_\odot$ through successive mergers ranges from ${\sim }0.1~{{\ \rm per\ cent}}$ in low-density, low-mass clusters to nearly 90  per cent in high-mass, high-density clusters. However, in the most massive NSCs, the growth time-scale can be very long ($\gtrsim 1\,$ Gyr); vice versa, while growth is least likely in less massive NSCs, it is faster there, requiring as little as ${\sim }0.1\,$Gyr. The increased gravitational focusing in systems with lower velocity dispersions is the primary contributor to this behaviour. We find that there is a simple ‘7-strikes-and-you’re-in’ rule governing the growth of BHs: Our results suggest that if the seed survives 7–10 successive mergers without being ejected (primarily through gravitational wave recoil kicks), the growing BH will most likely remain in the cluster and will then undergo runaway, continuous growth all the way to the formation of an SMBH (under the simplifying assumption adopted here of a fixed background NSC). Furthermore, we find that rapid mergers enforce a dynamically mediated ‘mass gap’ between about ${50\!-\!300 \, \mathrm{M}_\odot }$ in an NSC.
The evolution of radial gradients of MaNGA quiescent elliptical galaxies: inside-out quenching or outer mass growth?
Authors: Avila-Reese V , Ibarra-Medel H , Lacerna I , Rodríguez-Puebla A , Vázquez-Mata J A , Sánchez S F , Hernández-Toledo H M , Cannarozzo C
Published: June 2023

Using spatially resolved fossil record analysis on a large sample of ‘red and dead’ elliptical galaxies (classical ellipticals, CLEs) from the MaNGA/SDSS-IV DR15 survey, we reconstruct the archaeological evolution of their radial gradients in mass-to-luminosity ratio (M/L), g − r colour, and specific star formation (SF) rate. We also calculate other metrics that quantify the inside-out SF quenching and external mass growth processes. The M/L gradients, ∇Υ⋆, are approximately flat at high look-back times (tlb), but then they become negative and steeper until an epoch, when this trend reverses. These trends are shifted to later epochs the less massive the galaxies are. Colour gradients follow qualitatively similar trends. We find that these trends are mainly driven by strong inside-out quenching, without significant outer growth or structural changes overall. Our results suggest a scenario where the main progenitors of local CLE galaxies evolved quasi-passively after an early dissipative phase, but underwent radial photometric changes due to the inside-out quenching that led to the systematic decrease of ∇Υ⋆ and to an increase of the light-weighted radius. The late reversing of ∇Υ⋆, tlb≈2 − 4 Gyr, roughly coincides with the global quenching of the CLE galaxies. We have pushed archaeological inferences to the limit, but thanks to the large number of objects and an understanding of how the caveats and assumptions affect our results, we conclude that they offer an average description of evolutionary behaviours of CLE progenitors that is valid at least qualitatively.
Decoding the Fundamental Drivers of Phylodynamic Inference
Authors: Featherstone Leo A , Duchene Sebastian , Vaughan Timothy G
Published: June 2023

Despite its increasing role in the understanding of infectious disease transmission at the applied and theoretical levels, phylodynamics lacks a well-defined notion of ideal data and optimal sampling. We introduce a method to visualize and quantify the relative impact of pathogen genome sequence and sampling times—two fundamental sources of data for phylodynamics under birth–death-sampling models—to understand how each drives phylodynamic inference. Applying our method to simulated data and real-world SARS-CoV-2 and H1N1 Influenza data, we use this insight to elucidate fundamental trade-offs and guidelines for phylodynamic analyses to draw the most from sequence data. Phylodynamics promises to be a staple of future responses to infectious disease threats globally. Continuing research into the inherent requirements and trade-offs of phylodynamic data and inference will help ensure phylodynamic tools are wielded in ever more targeted and efficient ways.
Cell type deconvolution of methylated cell-free DNA at the resolution of individual reads
Authors: Keukeleire Pia , Makrodimitris Stavros , Reinders Marcel
Published: June 2023

Cell-free DNA (cfDNA) are DNA fragments originating from dying cells that are detectable in bodily fluids, such as the plasma. Accelerated cell death, for example caused by disease, induces an elevated concentration of cfDNA. As a result, determining the cell type origins of cfDNA molecules can provide information about an individual’s health. In this work, we aim to increase the sensitivity of methylation-based cell type deconvolution by adapting an existing method, CelFiE, which uses the methylation beta values of individual CpG sites to estimate cell type proportions. Our new method, CelFEER, instead differentiates cell types by the average methylation values within individual reads. We additionally improved the originally reported performance of CelFiE by using a new approach for finding marker regions that are differentially methylated between cell types. We show that CelFEER estimates cell type proportions with a higher correlation (r = 0.94 ± 0.04) than CelFiE (r = 0.86 ± 0.09) on simulated mixtures of cell types. Moreover, we show that the cell type proportion estimated by CelFEER can differentiate between ALS patients and healthy controls, between pregnant women in their first and third trimester, and between pregnant women with and without gestational diabetes.
Correction of transposase sequence bias in ATAC-seq data with rule ensemble modeling
Authors: Wolpe Jacob B , Martins André L , Guertin Michael J
Published: June 2023

Chromatin accessibility assays have revolutionized the field of transcription regulation by providing single-nucleotide resolution measurements of regulatory features such as promoters and transcription factor binding sites. ATAC-seq directly measures how well the Tn5 transposase accesses chromatinized DNA. Tn5 has a complex sequence bias that is not effectively scaled with traditional bias-correction methods. We model this complex bias using a rule ensemble machine learning approach that integrates information from many input k-mers proximal to the ATAC sequence reads. We effectively characterize and correct single-nucleotide sequence biases and regional sequence biases of the Tn5 enzyme. Correction of enzymatic sequence bias is an important step in interpreting chromatin accessibility assays that aim to infer transcription factor binding and regulatory activity of elements in the genome.
When do parts form wholes? Integrated information as the restriction on mereological composition
Authors: McQueen Kelvin J , Tsuchiya Naotsugu
Published: June 2023

Under what conditions are material objects, such as particles, parts of a whole object? This is the composition question and is a longstanding open question in philosophy. Existing attempts to specify a non-trivial restriction on composition tend to be vague and face serious counterexamples. Consequently, two extreme answers have become mainstream: composition (the forming of a whole by its parts) happens under no or all conditions. In this paper, we provide a self-contained introduction to the integrated information theory (IIT) of consciousness. We show that IIT specifies a non-trivial restriction on composition: composition happens when integrated information is maximized. We compare the IIT restriction to existing proposals and argue that the IIT restriction has significant advantages, especially in response to the problems of vagueness and counterexamples. An appendix provides an introduction to calculating parts and wholes with a simple system.
Estimating the Effectiveness of Health Warnings on Cigarette Packaging in Nigeria: A Modeling Study
Authors: Alcaraz Andrea , Adedeji Adeniran , Pichón-Riviere Andrés , Amara Ekeruche Mma , Casarini Agustín , Rodríguez Cairoli Federico , Espinola Natalia , Roberti Javier , Palacios Alfredo , Bardach Ariel
Published: June 2023

Introduction

Tobacco consumption is associated with nearly 30 000 deaths annually in Nigeria alongside other adverse health and economic effects. Our objective was to estimate the health and economic implications of the current cigarette labeling policies (text-only HWs); new health warnings policies in the country (adding graphic health warnings with up to 60% coverage), and plain packaging policy as recommended by the World Health Organization.

Aims and Methods

We used a probabilistic state-transition individual microsimulation model, considering natural history, healthcare costs, and quality-of-life losses associated with main tobacco-attributable diseases; and the potential effects of packaging and labeling policies. We used three scenarios: (1) text-only health warnings (HWs) covering 50% of the pack, (2) introduction of graphic HWs of 50% (and later increasing to 80%) of the pack, and (3) plain packaging with HWs covering 80% of the pack.

Results

A total of 748 deaths are averted in the current situation; 7478 and 14 208 deaths can be averted with the new policy and with plain packaging, respectively. The number of cardiac, cerebrovascular, and cancer events that could be averted by adopting text and graphic HWs are 3093, 5093, and 1346, respectively; increasing to 5876, 9676, and 2557, respectively, with plain packaging. Up to 251 794 years were lost because of early deaths and disability, and ₦144.6 billion (USD 469 million) in health costs could be saved with HWs covering 50% to 80% of the pack over 10 years. With plain packaging and graphic HWs covering 80% of the package 478,408 years and ₦274.7 billion (USD 895 million) would be saved.

Conclusions

The new cigarette labeling policy in Nigeria may yield significant health and economic benefits over 10 years. Moving the current policy to plain packaging can significantly improve these benefits.

Implications

The new cigarette labeling policy that Nigeria is implementing should aim to achieve 100% compliance with its current regulation and the logical next step: Plain packaging with large warnings. The present study adds evidence of the potential health effects and cost savings of these levels of implementation, which is valuable for local policymakers.
Unlocking the Potential of Genomic Data to Inform Typhoid Fever Control Policy: Supportive Resources for Genomic Data Generation, Analysis, and Visualization
Authors: Carey Megan E , Dyson Zoe A , Argimón Silvia , Cerdeira Louise , Yeats Corin , Aanensen David , Mboowa Gerald , Baker Stephen , Tessema Sofonias K , Smith Anthony M , Okeke Iruka N , Holt Kathryn E
Published: June 2023

The global response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic demonstrated the value of timely and open sharing of genomic data with standardized metadata to facilitate monitoring of the emergence and spread of new variants. Here, we make the case for the value of Salmonella Typhi (S. Typhi) genomic data and demonstrate the utility of freely available platforms and services that support the generation, analysis, and visualization of S. Typhi genomic data on the African continent and more broadly by introducing the Africa Centres for Disease Control and Prevention's Pathogen Genomics Initiative, SEQAFRICA, Typhi Pathogenwatch, TyphiNET, and the Global Typhoid Genomics Consortium.
Taking on Typhoid: Eliminating Typhoid Fever as a Global Health Problem
Authors: Chen Jessie , Long Jessica E , Vannice Kirsten , Shewchuk Tanya , Kumar Supriya , Duncan Steele A , Zaidi Anita K M
Published: June 2023

Typhoid fever is a significant global health problem that impacts people living in areas without access to clean water and sanitation. However, collaborative international partnerships and new research have improved both knowledge of the burden in countries with endemic disease and the tools for improved surveillance, including environmental surveillance. Two typhoid conjugate vaccines (TCVs) have achieved World Health Organization prequalification, with several more in the development pipeline. Despite hurdles posed by the coronavirus disease 2019 pandemic, multiple TCV efficacy trials have been conducted in high-burden countries, and data indicate that TCVs provide a high degree of protection from typhoid fever, are safe to use in young children, provide lasting protection, and have the potential to combat typhoid antimicrobial resistance. Now is the time to double down on typhoid control and elimination by sustaining progress made through water, sanitation, and hygiene improvements and accelerating TCV introduction in high-burden locations.
Nitrogen-regulated antisense transcription in the adaptation to nitrogen deficiency in Nostoc sp. PCC 7120
Authors: Brenes-Álvarez Manuel , Vioque Agustín , Muro-Pastor Alicia M
Published: June 2023

Transcriptomic analyses using high-throughput methods have revealed abundant antisense transcription in bacteria. Antisense transcription is often due to the overlap of mRNAs with long 5′ or 3′ regions that extend beyond the coding sequence. In addition, antisense RNAs that do not contain any coding sequence are also observed. Nostoc sp. PCC 7120 is a filamentous cyanobacterium that, under nitrogen limitation, behaves as a multicellular organism with division of labor among two different cell types that depend on each other, the vegetative CO2-fixing cells and the nitrogen-fixing heterocysts. The differentiation of heterocysts depends on the global nitrogen regulator NtcA and requires the specific regulator HetR. To identify antisense RNAs potentially involved in heterocyst differentiation, we assembled the Nostoc transcriptome using RNA-seq analysis of cells subjected to nitrogen limitation (9 or 24 h after nitrogen removal) in combination with a genome-wide set of transcriptional start sites and a prediction of transcriptional terminators. Our analysis resulted in the definition of a transcriptional map that includes >4,000 transcripts, 65% of which contain regions in antisense orientation to other transcripts. In addition to overlapping mRNAs, we identified nitrogen-regulated noncoding antisense RNAs transcribed from NtcA- or HetR-dependent promoters. As an example of this last category, we further analyzed an antisense (as_gltA) of the gene-encoding citrate synthase and showed that transcription of as_gltA takes place specifically in heterocysts. Since the overexpression of as_gltA reduces citrate synthase activity, this antisense RNA could eventually contribute to the metabolic remodeling that occurs during the differentiation of vegetative cells into heterocysts.
Intellectual Humility: How Recognizing the Fallibility of Our Beliefs and Owning Our Limits May Create a Better Relationship Between the Physical Therapy Profession and Disability
Authors: Schwab Sarah M , Silva Paula L
Published: June 2023

Despite the many advancements over the history of the profession, physical therapy remains in a somewhat paradoxical relationship with disability. The physical therapist profession values disability as diversity but continues to focus on the normalization of body functions as the primary means to promote functionality in people with disability. This focus, consistent with a medicalized view of disability, may prevent physical therapists from empowering individuals with disability to explore alternative, yet effective, perceptual-motor strategies to achieve their functional goals. Additionally, recent research documents implicit, negative biases of physical therapists and physical therapist assistants toward people with disability, again consistent with the medicalized view that disability is the product of an imperfectly functioning body. Dominant underlying beliefs in any profession are often difficult to counter because they are so pervasive, and those beliefs can be reinforced and made stronger when challenged. The purpose of this Perspective article is to introduce physical therapists to a rising construct in psychology—intellectual humility—that may help to facilitate the profession’s relationship with disability. Intellectual humility is predicated on recognizing the fallibility of one’s beliefs and related practices. Intellectual humility is a promising construct for physical therapy to address the disability paradox and confront implicit attitudes that have served as the basis for many dominant ideas about disability. This Perspective synthesizes views and evidence from the behavioral and social sciences, philosophy, and critical disability studies to contribute to the ongoing evolution of the profession with respect to disability.

Impact

The development of enhanced intellectual humility in physical therapy may help to challenge long-held beliefs among physical therapists about disability—many of which are unnoticed, unquestioned, and difficult to counter.
Psychometric Properties and Diagnostic Associations of the Short-Form Community Assessment of Psychic Experiences in a Population-Based Sample of 29 021 Adult Men
Authors: Birkenæs Viktoria , Refsum Bakken Nora , Frei Evgeniia , Jaholkowski Piotr , Smeland Olav B , Tesfaye Markos , Agartz Ingrid , Susser Ezra , Bresnahan Michaeline , Røysamb Espen , Nordbø Jørgensen Kjetil , Nesvåg Ragnar , Havdahl Alexandra , Andreassen Ole A , Elken Sønderby Ida
Published: June 2023

Background and Hypothesis

Around 5%–7% of the adult population are estimated to have lifetime psychotic experiences (PEs), which are associated with psychosis risk. PEs assessed with Community Assessment of Psychic Experiences (CAPE) are associated with psychosis but also non-psychotic disorders, which could be partly explained by CAPE indirectly capturing emotional symptoms. We investigated the psychometric properties of a shorter version, CAPE-9, and whether CAPE-9 scores are associated with lifetime psychotic or non-psychotic mental disorders after controlling for current anxiety and depressive symptoms.

Design

CAPE-9 questionnaire data were obtained from 29 021 men (42.4 ± 5.6 yrs.) from the Norwegian Mother, Father, and Child Cohort Study. We investigated CAPE-9 reliability and factor structure. Logistic regression was used to test effects of current anxiety and depressive symptoms (SCL-12) on associations between CAPE-9 scores and psychiatric diagnoses.

Results

CAPE-9 fit a previously reported 3-factor structure and showed good reliability. Twenty-six percent reported at least one lifetime PE. CAPE-9 scores were significantly associated with most psychiatric disorders (schizophrenia, depression, bipolar disorder, substance abuse, anxiety, trauma-related disorders, and ADHD). After controlling for concurrent emotional symptoms, only associations with schizophrenia (OR = 1.29; 95% CI = 1.18–1.38) and trauma-related disorders (OR = 1.09; CI = 1.02–1.15) remained significant.

Conclusions

CAPE-9 showed good psychometric properties in this large population-based adult male sample, and PEs were more clearly associated with psychotic disorders after controlling for current emotional symptoms. These results support the use of the short CAPE-9 as a cost-effective tool for informing public health initiatives and advancing our understanding of the dimensionality of psychosis.
Negative Symptom Trajectories in Individuals at Clinical High Risk for Psychosis: Differences Based on Deficit Syndrome, Persistence, and Transition Status
Authors: Tran Tanya , Spilka Michael J , Raugh Ian M , Strauss Gregory P , Bearden Carrie E , Cadenhead Kristin S , Cannon Tyrone D , Cornblatt Barbara A , Keshavan Matcheri , Mathalon Daniel H , McGlashan Thomas H , Perkins Diana O , Seidman Larry J , Stone William S , Tsuang Ming T , Walker Elaine F , Woods Scott W , Addington Jean M
Published: June 2023

Background and Hypothesis

Negative symptom trajectory in clinical high risk (CHR) for psychosis is ill defined. This study aimed to better characterize longitudinal patterns of change in negative symptoms, moderators of change, and differences in trajectories according to clinical subgroups. We hypothesized that negative symptom course will be nonlinear in CHR. Clinical subgroups known to be more severe variants of psychotic illness—deficit syndrome (DS), persistent negative syndrome (PNS), and acute psychosis onset—were expected to show more severe baseline symptoms, slower rates of change, and less stable rates of symptom resolution.

Study Design

Linear, curvilinear, and stepwise growth curve models, with and without moderators, were fitted to negative symptom ratings from the NAPLS-3 CHR dataset (N = 699) and within clinical subgroups.

Study Results

Negative symptoms followed a downward curvilinear trend, with marked improvement 0–6 months that subsequently stabilized (6–24 months), particularly among those with lower IQ and functioning. Clinical subgroups had higher baseline ratings, but distinct symptom courses; DS vs non-DS: more rapid initial improvement, similar stability of improvements; PNS vs non-PNS: similar rates of initial improvement and stability; transition vs no transition: slower rate of initial improvement, with greater stability of this rate.

Conclusions

Continuous, frequent monitoring of negative symptoms in CHR is justified by 2 important study implications: (1) The initial 6 months of CHR program enrollment may be a key window for improving negative symptoms as less improvement is likely afterwards, (2) Early identification of clinical subgroups may inform distinct negative symptom trajectories and treatment needs.
Quad-channel broadband compact multi-antenna GNSS down-converter for high-reliability navigation
Authors: Wang Riyan , Li Bin , He Hongyin , Yang Kunming , Feng Wei , Chen Zhijian
Published: June 2023

A high-reliability broadband high-linearity down-converter for multi-antenna global navigation satellite system (GNSS) receiver is presented in this paper. Based on direction-of-arrival estimation, the multi-antenna GNSS receiver can separate the GNSS signals from the interfering signals and suppress harmful broadband radio frequency interferences. To drive the off-chip 50 Ω resistive load and meet the stringent requirements of linearity, a quad-channel down-converter with a broadband common-gate low-noise transconductance amplifier, current-driven passive mixer and novel bridge mode transimpedance driving amplifier have been proposed to contruct the multi-antenna receiver. The operating frequency of this down-converter is from 1.15 to 1.65 GHz, covering all bands for global positioning system (GPS), Beidou navigation satellite system (BDS), global navigation satellite system (GLONASS) and Galileo. The measured results show that the proposed quad-channel down-converter achieves +38 dBm output 3rd order intercept point (OIP3) and +17 dBm OP1dB (output-referred 1 dB compression point), 9.5 dB to 12.9 dB noise figure (NF) across the variable gain of 10 dB to 27 dB and approximately 47 dB channel isolation.
RBFOX2 confers tumor growth by PI3K/AKT and MAPK signaling in gastric cancer
Authors: Xie Shuangyan , Li Zeyun , Zhong Yu , Fang Qiuyun , Ma Amin , Wang Yan , Zeng Lina , Lin Tengjiao , Xie Du
Published: June 2023

RNA-binding Fox (RBFOX)2, a member of a family of RNA-binding proteins, is well known as a regulator of alternative pre-mRNA splicing. However, its possible role in gastric cancer is unknown. In this study, we investigated the biologic role and clinical significance of RBFOX2 in gastric cancer growth and elucidated its underlying molecular mechanisms. We found that RBFOX2 was highly expressed in gastric cancer cell lines and tumor tissue compared with the adjacent nontumor tissue. We also found that RBFOX2 overexpression was correlated with poor overall survival in patients with gastric cancers. Multivariate survival analyses revealed that higher RBFOX2 expression was an independent prognostic factor for the overall survival of patients with gastric cancers. Suppression of RBFOX2 by shRNA inhibited gastric cancer cell proliferation, colony formation and induced apoptosis. Mechanism studies revealed that these effects were achieved through the simultaneous modulation of multiple signaling pathways. Knockdown of RBFOX2 expression by shRNA markedly inhibited the phosphorylation of phosphatidylinositol 3-hydroxy kinase, threonine kinase and extracellular signal-regulated kinase and Jun N-terminal kinases proteins. In contrast, the ectopic expression of RBFOX2 had the opposite effects. Moreover, RBFOX2 knockdown also induced the cleavage of caspase-3 and caspase-9 proteins. Collectively, these results demonstrate that RBFOX2 plays a critical role in regulating gastric cancer cell proliferation and survival and may be a potential prognostic biomarker and therapeutic target for gastric cancer.
Putting It All Together: An Evidence-Based Guide to High-Intensity Interval Exercise Prescription for Patients With Complex Comorbidities
Authors: Brockway Kaelee S. , Ayres Leslie , Shoemaker Michael J.
Published: June 2023

A rapidly growing body of research supports the use of high-intensity interval training across a wide range of health conditions encountered in physical therapy practice. However, most studies have included carefully selected patients without multimorbidity, significant activity limitations, or participation restrictions. In addition, much of the evidence address these patients in the outpatient setting which makes translating outcomes into clinical practice difficult for multimorbid patient populations across the continuum of care. Therefore, the present clinical perspective aims to synthesize and apply the evidence for the prescription of function-based high-intensity interval training (HIIT) programs to individuals with multiple, complex chronic diseases by (1) discussing the specific benefits of this type of exercise design for patients with multiple complex chronic health conditions; (2) highlighting the overlapping guidance for numerous conditions; (3) applying the evidence to designing individualized, functional HIIT programs to achieve functional improvement in addition to cardiorespiratory fitness; and (4) providing an example of functional HIIT program creation to demonstrate clinically relevant considerations. Clinical decision-making related to patient monitoring and safety is emphasized.
Cardiovascular and Pulmonary Research: The Year (2022) in Review
Authors: Ricard Paul E. H. , McHugh Hannah F. , Ramsey Stephen
Published: June 2023

Practitioners need access to and the ability to openly discuss advances in practice and concepts as they apply to the practice of cardiovascular and pulmonary physical therapy (PT). Lack of accessibility to research literature, limited personal time, or insufficient knowledge to adequately review the breadth of literature published each year can hinder this process. This article provides a limited overview of cardiovascular and pulmonary research published in 2022 that the authors believe most important and relevant or speaks to the volume or trend of current topics in the clinical practice of cardiovascular and pulmonary PT. Each topic area is followed by a brief overview of clinical relevance and was open to discussion with the participants present at the 2023 Combined Sections Meeting held on February 24, 2023.
Progression to cirrhosis is similar among all ages in nonalcoholic fatty liver disease, but liver-related events increase with age
Authors: Miller Matthew J. , Harding-Theobald Emily , DiBattista Jacob V. , Zhao Zhe , Wijarnpreecha Karn , Lok Anna S. , Chen Vincent L.
Published: June 2023

Background:

NAFLD is increasingly common among young people. Whether NAFLD carries a more benign course in younger adults is not known. We aimed to characterize genetic and metabolic risk factors for NAFLD and their effects on disease progression across age groups.

Methods:

We conducted a retrospective study of adults with NAFLD seen within Michigan Medicine, a tertiary care center, between 2010 and 2021. NAFLD was defined by hepatic steatosis on imaging, biopsy, or transient elastography in the absence of other chronic liver diseases. Cirrhosis was determined by validated International Classification of Diseases-9/10 codes or imaging. Fine-Gray competing risk models were generated, with incident cirrhosis and liver-related events (LREs) as the primary outcomes and death without cirrhosis or LREs as a competing risk. The primary predictor was the age category.

Results:

We included 31,505 patients with NAFLD, with 8,252 aged 18 to younger than 40, 15,035 aged 40 to younger than 60, and 8,218 aged 60 years or older years at diagnosis. Compared with older patients, young adults more often had obesity, higher ALT, and high-risk PNPLA3 alleles, and fewer had prevalent cirrhosis, hypertension, hyperlipidemia, and diabetes. The 10-year risk of incident cirrhosis was similar between ages (3.4% in age 18 to <40 vs 3.7% in age 40 to <60 vs 4.7% in age ≥60; p = 0.058). Predictors of LREs were advancing age and diabetes, with a significantly higher 10-year risk of LREs in the oldest age group (0.2% in age 18 to <40 vs 0.7% in age 40 to <60 vs 1.1% in age ≥60; p = 0.008).

Conclusions:

While the baseline prevalence of cirrhosis was higher among older adults, the rate of NAFLD progression to cirrhosis was similar in young and older adults. Older patients were more likely to have LREs.
Clinical characteristics and surgical outcomes in stage 4 macular hole with epiretinal proliferation
Authors: Uemura Akinori , Miyake Syoki , Funatsu Ryoh , Yamakiri Keita
Published: June 2023

Purpose:

To investigate the clinical characteristics and surgical outcomes of stage 4 macular holes (MHs) with epiretinal proliferation (EP) and explore the pathogenesis of MH formation.

Methods:

This retrospective study included consecutive patients who underwent pars plana vitrectomy for stage 4 MH. Patients were divided into two groups based on the presence or absence of EP. Baseline characteristics, optical coherence tomography (OCT) features of MHs, and surgical outcomes were compared between the groups.

Results:

EP was detected in 31 of 102 eyes with stage 4 MH (30%). Patients with EP were older (p = 0.044), predominantly male (p = 0.047), had a greater axial length (p = 0.008), and had better preoperative visual acuity (p < 0.001) than those without EP. On OCT, eyes with EP had more epiretinal membrane and intraretinal splitting (p = 0.002 and p < 0.001, respectively) than those without EP. The hole closure rate after primary surgery was comparable, and visual acuity at 6 months after surgery was significantly better in eyes with EP than those without EP (p = 0.036). In 9 eyes with EP, the medical record documented the presence of complete posterior vitreous detachment before MH development.

Conclusion:

Patients of stage 4 MH with EP were older, predominantly male, and had better pre- and postoperative visual acuity compared with those without EP. The differences in demographic characteristics and OCT findings suggest that the pathogenesis of stage 4 MH with EP is different from that of stage 4 MH without EP.
SUBRETINAL PHIALOPHORA ABSCESS IN CHRONIC GRANULOMATOUS DISEASE
Authors: Castillejo Becerra Clara M. , Kaplan Tyler M. , Mogil Rachel S. , Olsen Timothy W.
Published: June 2023

Purpose:

To report a rare case of a subretinal Phialophora richardsiae abscess in a patient with chronic granulomatous disease.

Methods:

A 21-year-old man with chronic granulomatous disease and a history of invasive pulmonary aspergillosis presented with progressive loss of vision and pain in his left eye. He was found to have a subretinal abscess with a macula involving serous retinal detachment. A diagnostic and therapeutic pars plana vitrectomy, subretinal biopsy with debridement, inferior retinectomy, and silicone oil tamponade were performed. Intraoperative cultures grew Pleurostoma (Phialophora) richardsiae. He was treated with systemic liposomal amphotericin B and high-dose posaconazole. However, his eye eventually required enucleation.

Results:

Preoperative visual acuity was light perception on the left eye and improved to count fingers at 4 weeks postoperative. However, VA rapidly declined to light perception, and he developed an opaque white cataract, iris neovascularization, posterior synechiae, and corectopia. The retina remained attached under silicone oil. Histopathology revealed granuloma formation and active fungal elements.

Discussion/Conclusion:

The case supports the importance of vitreoretinal surgery to determine a definitive systemic diagnosis. Treatment of Phialophora infection is surgically challenging to manage and has a poor visual prognosis in patients with chronic granulomatous disease.