bluuebunny/crossref_metadata_2025 huggingface dataset:
THE SOCIAL COST OF MODIFIABLE RISK FACTORS IN SINGAPORE
Authors: Tan Vanessa , Ma Stefan , Chen Cynthia
Published: December 2022

Close to half of total disease burdens are attributable to modifiable risk factors, indicating that many illnesses are preventable by modifying behaviours such as increasing physical activity levels or maintaining a healthy diet. This study measures the social costs attributable to modifiable risks in Singapore, one of the most rapidly ageing populations in the world. Measuring the social cost of modifiable risk factors can help public health policymakers prioritise public health programmes and allocate resources. Our study builds on the comparative risk assessment framework from the Global Burden of Disease study. We used a prevalence-based cost-of-illness approach to estimate the social cost attributable to modifiable risk factors. We included healthcare costs from inpatient hospitalisation and productivity losses from absenteeism and premature mortality. Our results found that metabolic risks had the highest social cost of S$2.20 billion in 2019, followed by lifestyle risks of S$1.98 billion and substance risks of S$1.56 billion. Across the risk factors, the social costs were largely driven by productivity losses, heavily skewed towards the older working-age group. For metabolic risks, approximately 80% of the total cost (S$1.82 billion) was from those aged above 45 years old. This study provides evidence of the high social cost of modifiable risks and highlights the importance of developing holistic public health promotion programmes. Our findings suggest that implementing effective population-based programmes targeting multiple modifiable risks would have a strong potential to manage rising disease burdens and healthcare costs, especially with an ageing population.
IFIT3 GENE EXPRESSION AND FUNCTION CONTRIBUTE TO HAND PATHOLOGY EVEN WITH ANTIRETROVIRAL THERAPIES (CARTS)
Authors: Das Ranjit Kumar , Roy Deepa , Sahoo Nirakar , Roy Upal
Published: December 2022

The advent of cART has revolutionized the management of HIV-1 infection and saved the lives of millions of people worldwide. Yet, HIV-Associated Neurocognitive Disorder (HAND) continues to be clinically relevant with aging people with HIV-1 (PWH). The underlying mechanism of HAND remains poorly understood. In this regard Signal transducer and activator of transcription 1(STAT1) and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) genes have been shown to induce neuroinflammation and neuronal cell death. However, the role of IFIT3 in HAND pathology has not been well established. Therefore, the present work investigated the significant role of IFIT3 gene in the development of HAND. In the current study, we used an in-vitro model to expose the neuroblastoma cell-line SH-SY5Y with clinically relevant cARTs drug and HIV Tat protein to observe the STAT1 and IFIT3 genes dysregulation. Furthermore, study also investigates the STAT1 and IFIT3 protein dysregulation through immunocytochemistry and western blot assay. Overall observation indicated that HIV-Tat protein upregulated gene expression whereas with the cART exposure there was a downregulation of STAT1 and IFIT3 genes. We next aim to investigate the role of STAT1 and IFIT3 genes in HIV-induced neuroinflammation. The current study has established IFIT3 as a biomarker marker for the detection of HAND.
AGING DRAG QUEENS: RISKS, REWARDS, EXPRESSION AND PERFORMANCE
Authors: Donorfio Laura , Chapman Brian , Henneberry Kathleen
Published: December 2022

This poster presentation will share the exploratory findings of a qualitative research study examining the lived experiences of older drag queens, age 50+. Drag queens are an understudied and underrepresented population in the social science literature (Knutson, Koch, Sneed, Lee, & Chung, 2020; O’Brien, 2018). Older drag queens have yet to be studied in the social science literature. “Drag Queens possess unique characteristics as a subpopulation of the lesbian, gay, bisexual, and transgender (LGBT) community that warrant exploration” (Knutson, Koch, Sneed, & Lee, 2018). A comprehensive literature review identified approximately a dozen research driven articles from 2004 to the present, studying such areas as motivations, obstacles and stressors in becoming and being a drag queen (Hopkins, 2004; Knutson et al., 2021), depression, substance abuse, and resilience (Knutson et al., 2019; Tillewein & Kruse-Diehr, 2021) and the role gender plays via sexuality identities (Taylor & Rupp, 2004, Levitt et al. 2017). This research seeks to better understand how drag expression is integrated with one’s persona and how it interfaces with dragism, coping, and if drag expression can be used as a tool to foster resilience. Using a semi-structured interview protocol and thematic analysis, many themes emerged including the risks and rewards associated with drag expression, the relationship between aging and being a drag performer, and the shift in traditional versus 21st century drag. Lastly, we highlight the implications for gender and LGBTQIA+ theory and plans for future research.
PASSING THE TORCH: EXPLORING THE SUSTAINABILITY OF AN INTERPROFESSIONAL GERIATRICS FACULTY DEVELOPMENT PROGRAM
Authors: Davis Kimberly , Marrs Sarah , Williams Ishan , Zimmerman Kristin , Coogle Constance , Parsons Pamela , Slattum Patricia , Waters Leland
Published: December 2022

Faculty development programs (FDPs) are an effective, evidence-based method of promoting the knowledge, skills and self-efficacy of faculty. However, the implementation and sustainability of curricula are rarely reported. Furthermore, the challenges to sustaining programmatic implementation of interprofessional FDP curricula in academic and clinical settings over time have yet to be extensively evaluated. Using dynamic sustainability as a framework, we aimed to assess the evolving barriers and facilitators that influence the implementation and sustainability of the geriatrics curriculum Capstone projects designed by faculty scholars in our FDP. We planned to report on projects that were and weren't successful. A survey, sent to 115 faculty scholars from eight different cohorts who completed our 10-month FDP, recruited faculty participants and set the stage for qualitative data collection to help us better understand the sustained impact of the program. Thematic analysis of virtual interviews with 17 Scholars revealed several key factors facilitating and hindering the implementation and dynamic sustainability of curricular projects. Three major themes and sub-themes were identified as follows: Project Implementation (Supportive Factors, Hindering Factors and Filling in Gaps in the Field); Pedagogical Development (Enhancement of Skills and Culture Change); and Sustainability Impact (Project Sustainability, Career Development and Passing the Torch). Supporting these factors through skills development may favorably impact project sustainability and thus the aspects of workforce development that catalyze practice change. Implementation of geriatrics-focused FDPs provides an evidence-based approach to sustainability. Further study of the ongoing barriers and facilitators to sustainability is encouraged.
A COMPARISON OF SUBJECTIVE COGNITIVE DECLINE AND RELATED LIMITATIONS AMONG TRANSGENDER COMMUNITIES IN THE US
Authors: Cicero Ethan , Goodman Michael , Barnes Lisa , Perkins Molly , Flatt Jason , Tangpricha Vin
Published: December 2022

Background

The transgender population is composed of subgroups that are diverse in gender identity (e.g., transgender women[TW], transgender men[TM], nonbinary[NB] individuals). Compared to cisgender adults, transgender adults are more likely to report subjective cognitive decline (SCD). It remains unclear if SCD prevalence and related limitations vary by transgender subgroups.

Methods

2015-2020 Behavioral Risk Factor Surveillance System data, representing 38 U.S. states that assessed SCD (confusion/memory loss happening more often/getting work over previous 12months) and gender identity were used to examine differences in SCD prevalence and SCD-related limitations by transgender subgroups, TW(n=442), TM(n=298), and NB(n=183). Age-adjusted odds ratios (OR) along with 95% confidence intervals (CI) were calculated to investigate group differences in SCD prevalence. Separate analyses compared SCD-related limitations, demographics, and health across groups among participants reporting SCD.

Results

SCD prevalence was highest among NB(21.3%), followed by TW(16.3%) and TM(14.1%). After accounting for age, subgroup differences remained; odds of SCD were 1.6x higher among TW compared to TM (CI:1.1–2.4, p=0.012). Among those with SCD, TW were less likely to receive help they needed with day-to-day activities when compared to TM (OR=7.9; CI:0.1–0.2, p< 0.001) and NB (OR=5.0; CI:0.1–0.4, p=0.001); and TW were more likely to be deaf (OR=4.2; CI:1.7–10.1, p=0.002) and have asthma (OR=2.8; CI:1.4–5.7, p=0.005) when compared to NB adults. No other differences were found.

Conclusion

Health and social inequities are not uniformly experienced across transgender subgroups, and it is important to understand how these factors impact the brain health of TW, TM, and NB adults.
Predicting serum hormone concentration by estimation of urinary hormones through a home-use device
Authors: Pattnaik Siddharth , Das Dipankar , Venkatesan Varun Akur , Rai Aayush
Published: December 2022

STUDY QUESTION

Can a home-use device be used to predict serum hormone levels?

SUMMARY ANSWER

A home-use device can predict urinary hormone values which are well-correlated to serum concentrations of respective hormones and hence can be used as a proxy for serum measurements.

WHAT IS KNOWN ALREADY

Home-use devices that predict ovulation are calibrated against the actual day of ovulation. However, the correlation of any quantitative system to serum hormone concentrations has not been established.

STUDY DESIGN, SIZE, DURATION

A total of 73 data points obtained from 20 participants across different phases of the menstrual cycle, i.e. bleeding days, follicular phase and luteal phase were used to establish the correlation between serum hormones and urinary metabolite values. Single data points from 20 random users were used to assess the correlation established.

PARTICIPANTS/MATERIALS, SETTING, METHODS

Participants were women in the fertile age groups and only current users of the home-use device. Selection was done based on inclusion and exclusion criteria. Blood hormones were tested using chemiluminescent immunoassays and urinary measurements were taken on the home-use device at home.

MAIN RESULTS AND THE ROLE OF CHANCE

Serum estradiol (E2), progesterone (P4) and LH were correlated with urinary estrone-3-glucuronide (E3G), pregnanediol glucuronide (PdG) and LH with an R2 of 0.96, 0.95 and 0.98, respectively. Repredicted serum concentration obtained by using the correlation equation had a correlation of 0.92, 0.94 and 0.93 in unknown samples.

LIMITATIONS, REASONS FOR CAUTION

The study was designed to include women who have normal cycle lengths regularly; therefore, the values obtained were in the normal range. Certain infertility conditions may cause the values to be higher and correlation in such cases needs to be established.

WIDER IMPLICATIONS OF THE FINDINGS

The results of this study imply a new tool that can be used by fertility specialists as a proxy for blood tests whenever required. Extended study on this system can enable its use in assisted reproductive techniques as well.

STUDY FUNDING/COMPETING INTEREST(S)

No funding was received for this study. S.P. and D.D. are employees of the research and development division of Samplytics Technologies Pvt. Ltd. which is a forwarder for Inito Inc., USA. A.R. and V.A.V. are co-founders of Inito Inc., USA.

TRIAL REGISTRATION NUMBER

The trial was registered at the International Standard Randomised Controlled Trial Number (ISRCTN) registry (Identifier: ISRCTN15534557).
The Production of Souls in International Relations
Authors: Forough Mohammadbagher
Published: December 2022

Global politics is exceedingly soulful, but the field of international relations (IR) astonishingly soulless. The world order is undergoing tectonic shifts: the “Western” unipolar moment is receding, China is rising, and geographies of “(Afro-)EurAsia” and the “Indo-Pacific” are emerging. To align with such shifts and remap the international geography, global actors are increasingly (re)producing narratives of civilizational “souls.” Putin views Ukraine as part of the “Russian world,” imbued with the “Russian soul.” Xi's “Thought,” instilled in China's schools and constitution, intends to “engineer” the country's soul as a “civilizational state.” Von der Leyen advocates strengthening the European Union's “soul.” Biden and Trump vied for “America's soul.” But what is even a soul? I define a collective soul as a historical–spiritual space, constructed materially and ideationally, and construed as a vital force that permeates, orders, and embodies—or transubstantiates—a body politic, and engraves in it a mythical Ursprung (origin) and telos. Adopting a critical geography approach, I map out several soul-making narratives by unpacking how they “graph” their (internal, regional, or global) “geo” through “space-framing assumptions” and “space-producing practices.” They include (1) “civilizational states,” focused on China and geographies of “Sinosphere” and “Afro-EurAsia”; (2) “civilizational crossroads,” focused on the “Iranosphere”; (3) the US-led “rules-based order,” as the latest iteration of the “liberal civilization” regraphing its soul onto the “Indo-Pacific”; and (4) two European soul-producing narratives: the far-right's “Judeo-Christianism” and the mainstream “European strategic autonomy.” Finally, I discuss the implications of soulcraft—as an indispensable yet unacknowledged component of statecraft—for IR theory.
Pre-Existing Population Immunity and severe acute respiratory syndrome coronavirus 2 Variant Establishment and Dominance Dynamics in the United States: An Ecological Study
Authors: Ankomah Pierre O , Siedner Mark J , Bhattacharyya Roby P
Published: December 2022

We conducted an ecological analysis of the dynamics of Delta and Omicron establishment and dominance in US states. Omicron became the dominant circulating variant later in states with higher population-level immunity. By contrast, population immunity did not impact the maximum rate of takeover by Delta or Omicron from prior variants.
Recognizing Facial Identity
Authors: Matthews Claire M. , Maurer Daphne , Mondloch Catherine J.
Published: December 2022

Adults recognize hundreds of familiar faces at a glance: a neighbor both at the gym and in wedding photos; actors in numerous movies, despite dramatic variability in their appearance; a high school classmate at a twenty-fifth reunion—despite physical changes associated with aging. What makes this ability so remarkable is that faces are a homogeneous class of stimuli—increasing both the challenge of telling faces apart and of recognizing someone despite changes in appearance. Here we focus on the development of the ability to recognize facial identity, underlying mechanisms, and the role of experience. We focus on behavioral development but sample the neuroscience literature when doing so is helpful. We begin with a brief synopsis of adults’ abilities, followed by a discussion of changes in these abilities during infancy and childhood.
Encountering Ostomies in Acute Care: Peristomal Skin Changes
Authors: Paul Julia C. , Zimnicki Katherine , Pieper Barbara A.
Published: December 2022

Up to 80% of individuals with an ostomy experience a peristomal skin complication, which can result in significant healthcare issues. All clinicians working with patients with stomas need to be aware of the signs and symptoms of peristomal skin complications and basic strategies to address the most common cause of skin complications: leakage of stool or other effluent onto the skin. Use of an evidence-based, standardized instrument to guide peristomal assessment and selection of appropriate interventions can improve patient outcomes and increase meaningful collaboration between all members of the healthcare team. This case study addresses dilemmas of care during a non-ostomy-related hospitalization.
A Scoping Review and Field Guide of Theoretical Approaches and Recommendations to Studying the Decision to Adopt Hearing Aids
Authors: Iankilevitch Maria , Singh Gurjit , Russo Frank A.
Published: December 2022

Objectives:

Given the low rates of hearing aid adoption among individuals with hearing loss, it is imperative to better understand the decision-making processes leading to greater hearing aid uptake. A careful analysis of the existing literature on theoretical approaches to studying these processes is needed to help researchers frame hypotheses and methodology in studies on audiology. Therefore, we conducted a scoping review with two aims. First, we examine theories that have been used to study research on hearing aid adoption. Second, we propose additional theories from the behavioral sciences that have not yet been used to examine hearing aid uptake but that can inform future research.

Design:

We identified peer-reviewed publications whose research was driven by one or more theoretical approaches by searching through PubMed, ProQuest PsycINFO, CINHAL Plus, Web of Science, Scopus, and OVID Medline/Embase/PsycINFO. The publications were examined by two researchers for eligibility.

Results:

Twenty-three papers were included in the analysis. The most common theoretical approaches studied include the Health Belief Model, the Transtheoretical Model of Behavior Change, Self-Determination Theory, and the COM-B Model. Seven other theoretical frameworks based on cognitive psychology and behavioral economics have also appeared in the literature. In addition, we propose considering nudge theory, framing effect, prospect theory, social learning theory, social identity theory, dual process theories, and affective-based theories of decision making when studying hearing aid adoption.

Conclusions:

We conclude that, although a number of theories have been considered in research on hearing aid uptake, there are considerable methodological limitations to their use. Furthermore, the field can benefit greatly from the inclusion of novel theoretical approaches drawn from outside of audiology.
A novel risk model to predict all-cause mortality in patients undergoing percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy
Authors: Pan Jianyuan , Liu Ming , Su Huimin , Ma Likun
Published: December 2022

Background and purpose:

Hypertrophic obstructive cardiomyopathy (HOCM) is a global genetic myocardial disease. In clinical practice, an indicator that could be used to identify suitable patients for percutaneous transluminal septal myocardial ablation (PTSMA) and assess their long-term prognosis is important for cardiologists. HOCM patients undergoing PTSMA, poor long-term prognosis has been associated with higher left ventricular outflow tract gradient (LVOTG) and interventricular septal thickness (IVST). In this retrospective, multicenter study, we aimed to investigate the association between TG (TG = IVS thickness × LVOT gradient) index and acute- or long-term outcomes of HOCM patients after PTSMA and further investigate the interaction effects of LVOTG and IVST.

Methods:

The study design is based on four tertiary centers from Mid-China, and a total of 284 HOCM patients (132 males, average age 54.80 ± 11.98 years) were treated with PTSMA. A new clinic index (TG = IVS thickness × LVOT gradient) was designed. Both 30-day major cardiovascular adverse events and all-cause mortality of the HOCM patients were analyzed. Cox proportional hazards regression model adjusting for potential risk factors was applied to explore the hazard ratio (HR) for all-cause mortality.

Results:

Total alcohol injection volume was 2.201 ± 1.025 mL. LVOTG and IVST were reduced to 40.11 ± 24.44 mmHg and 17.68 ± 4.07 mm at the last clinical check-up, respectively. Patients with low IVST (≤20 mm) or low TG index (≤1,683) had a higher rate of PTSMA-contributable complications and a higher need for a permanent pacemaker. Within the 903 patient-years follow-up, a total of 21 (9.8%) deaths occurred. The number of deaths per 100 patient-years was 0.65 and 4.06 in the high versus low TG index groups. The 8-year OS rate was 48.95% (95% CI = 39.07%–57.75%) versus 82.63% (95% CI = 74.99%–86.66%) in the high versus low TG groups, respectively (log-rank P < 0.001). The patients with both high LVOTG (>82 mmHg) and high IVST had the highest risk of all-cause mortality (HR: 18.63 vs low LVOTG, 95% CI = 1.09–319.15).

Conclusions:

The 8-year OS rate was markedly higher in patients with a low TG index (≤1,683) (48.95%) versus in patients with a high TG index (>1,683 group) (82.63%). The TG index could be a useful tool in the evaluation of HOCM patients for suitability for PTSMA.
How Far Is Too Far? Cost-Effectiveness Analysis of Regionalized Rectal Cancer Surgery
Authors: Leeds Ira L. , Xu Zhaomin , Loria Anthony , Pantel Haddon J. , Mongiu Anne K. , Longo Walter L. , Reddy Vikram
Published: December 2022

BACKGROUND:

Regionalized rectal cancer surgery may decrease postoperative and long-term cancer-related mortality. However, the regionalization of care may be an undue burden on patients.

OBJECTIVE:

To assess the cost-effectiveness of regionalized rectal cancer surgery.

DESIGN:

Tree-based decision analysis.

PATIENTS:

Patients with stage II/III rectal cancer anatomically suitable for low anterior resection.

SETTING:

Rectal cancer surgery performed at a high-volume regional center rather than the closest hospital available.

MAIN OUTCOME MEASURES:

Incremental costs ($) and effectiveness (quality-adjusted life year) reflected a societal perspective and were time-discounted at 3%. Costs and benefits were combined to produce the incremental cost-effectiveness ratio ($ per quality-adjusted life year). Multivariable probabilistic sensitivity analysis modeled uncertainty in probabilities, costs, and effectiveness.

RESULTS:

Regionalized surgery economically dominated local surgery. Regionalized rectal cancer surgery was both less expensive on average ($50,406 versus $65,430 in present-day costs) and produced better long-term outcomes (10.36 versus 9.51 quality-adjusted life years). The total costs and inconvenience of traveling to a regional high-volume center would need to exceed $15,024 per patient to achieve economic breakeven alone or $112,476 per patient to satisfy conventional cost-effectiveness standards. These results were robust on sensitivity analysis and maintained in 94.6% of scenario testing.

LIMITATIONS:

Decision analysis models are limited to policy-level rather than individualized decision-making.

CONCLUSIONS:

Regionalized rectal cancer surgery improves clinical outcomes and reduces total societal costs compared to local surgical care. Prescriptive measures and patient inducements may be needed to expand the role of regionalized surgery for rectal cancer. See Video Abstract at http://links.lww.com/DCR/C83.
Halomonas binhaiensis sp. nov., isolated from saline-alkali soil
Authors: Li Xiaoyan , Lu Hegang , Wang Qian , Yang Haixia , Yang Hongpeng , Wu Jiang , Huang Haidong
Published: December 2022

A Gram-stain-negative, aerobic and rod-shaped bacterium, strain Y2R2T, was isolated from a saline–alkali soil sample collected from Binhai New Area, Tianjin, PR China. Growth of strain Y2R2T was observed at 10–45 °C (optimum, 30 °C), at pH 6.0–11.0 (optimum, pH 9.0) and in the presence of 0–15 % (w/v) NaCl (optimum, 9.0 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain Y2R2T was affiliated with the genus

Halomonas

and showed the highest similarity to

Halomonas huangheensis

BJGMM-B45T (99.0%) and

Halomonas cupida

DSM 4740T (98.4%). The digital DNA–DNA hybridization and average nucleotide identity values of 21.0–22.8 % and 73.3–75.7 % with the closely related species

H. huangheensis

BJGMM-B45T,

H. cupida

DSM 4740T,

H. ventosae

AL12T,

H. stenophila

N12T and

H. litopenaei

SYSU ZJ2214T were lower than the threshold recommended for species discrimination.

The major respiratory quinone of strain Y2R2T was Q-9 and the major cellular fatty acids consisted of C16 : 0, C19 : 0 cyclo ω8c and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The DNA G+C content of strain Y2R2T was 57.0 mol%. On the basis of this polyphasic taxonomic study, strain Y2R2T is considered to represent a novel species of the genus

Halomonas

, for which the name Halomonas binhaiensis sp. nov. is proposed. The type strain is Y2R2T (=CGMCC 1.16974T=KCTC 72578T).
Mucilaginibacter aurantiaciroseus sp. nov. and Mucilaginibacter flavidus sp. nov., isolated from Renlongba glacier on the Tibetan Plateau
Authors: Yang Lei-Lei , Pang Yu , Liu Hong-Can , Xin Yu-Hua , Liu Qing
Published: December 2022

Strains RB4R14T and RT5R15T, two Gram-stain-negative, aerobic, rod-shaped, non-motile bacteria, were isolated from ice and cryoconite of Renlongba glacier, respectively, on the Tibetan Plateau, PR China. The results of phylogenetic analysis based on 16S rRNA genes indicated that strains RB4R14T and RT5R15T belonged to the genus

Mucilaginibacter

with the highest similarities to

Mucilaginibacter rigui

WPCB133T (98.78 %) and

Mucilaginibacter xinganensis

BJC16-A31T (97.64 %), respectively. The genomic DNA G+C contents of strains RB4R14T and RT5R15T were 42.8 and 43.1 mol%, respectively. The digital DNA–DNA hybridization values between strains RB4R14T, RT5R15T and their close relatives were below 31.9 and 17.4 %, respectively. The average nucleotide identity values between the two novel strains and their close relatives were 79.5–82.0 and 77.9–79.3 % respectively, indicating the novelty of the two isolates at a species level. The two novel strains contained MK-7 as the major menaquinone, and summed feature 3 (comprising C16 : 1
 ω7c and/or C16 : 1
 ω6c), iso-C15 : 0 and iso-C17 : 0-3OH as the major fatty acids. The major polar lipid of the two novel strains were phosphatidylethanolamine. Based on phenotypic, chemotaxonomic and phylogenetic results, we propose two novel species, Mucilaginibacter aurantiaciroseus sp. nov. (RB4R14T=CGMCC 1.11911T=NBRC 114020T) and Mucilaginibacter flavidus sp. nov. (RT5R15T=CGMCC 1.23117T=NBRC 113930T).
Backtracking: Improved methods for identifying the source of a deliberate release ofBacillus anthracisfrom the temporal and spatial distribution of cases
Authors: Shingleton Joseph , Mustard David , Dyke Steven , Finnie Thomas , Williams Hannah , Bennett Emma
Published: December 2022

Reverse epidemiology is a mathematical modelling tool used to ascertain information about the source of a pathogen, given the spatial and temporal distribution of cases, hospitalisations and deaths. In the context of a deliberately released pathogen, such asBacillus anthracis(the disease-causing organism of anthrax), this can allow responders to quickly identify the location and timing of the release, as well as other factors such as the strength of the release, and the realized wind speed and direction at release. These estimates can then be used to parameterise a predictive mechanistic model, allowing for estimation of the potential scale of the release, and to optimise the distribution of prophylaxis.

In this paper we present two novel approaches to reverse epidemiology, and demonstrate their utility in responding to a simulated deliberate release ofB. anthracisin ten locations in the UK and compare these to the standard grid-search approach. The two methods - a modified MCMC and a Recurrent Convolutional Neural Network - are able to identify the source location and timing of the release with significantly better accuracy compared to the grid-search approach. Further, the neural network method is able to do inference on new data significantly quicker than either the grid-search or novel MCMC methods, allowing for rapid deployment in time-sensitive outbreaks.

Author summary

In this paper we demonstrate three methods for estimating the source location and timing of a deliberate release ofBacillus anthracisbased on the temporal and spatial distribution of cases. Two of our proposed methods, a modified MCMC approach and a neural network based approach, provide significant improvements over previous methods by directly addressing the problematic parameter-likelihood surface, and, in the case of the neural network approach, addressing the slow deployment speeds of existing methods. Our results represent a major step forward in the accuracy and speed of epidemiological back-calculation.
Genetic Underpinnings and Audiological Characteristics in Children with Unilateral Sensorineural Hearing Loss
Authors: Lee Chen-Yu , Lin Pei-Hsuan , Chiang Yu-Ting , Tsai Cheng-Yu , Yang Shu-Yu , Chen You-Mei , Li Chao-Hsuan , Lu Chun-Yi , Liu Tien-Chen , Hsu Chuan-Jen , Chen Pei-Lung , Hsu Jacob Shujui , Wu Chen-Chi
Published: December 2022

Objective

Unilateral sensorineural hearing loss is a condition commonly encountered in otolaryngology clinics. However, its molecular pathogenesis remains unclear. This study aimed to investigate the genetic underpinnings of childhood unilateral sensorineural hearing loss and analyze the associated audiological features.

Study Design

Retrospective analysis of a prospectively recruited cohort Setting: Tertiary referral center Methods: We enrolled 38 children with unilateral sensorineural hearing loss and performed physical, audiological, imaging, and congenital cytomegalovirus examinations as well as genetic testing using next-generation sequencing targeting 30 deafness genes. The audiological results were compared across different etiologies.

Results

Causative genetic variants were identified in eight (21.1%) patients, including five withGJB2variants, two withPAX3variants, and one withEDNRBvariant.GJB2variants were associated with mild-to-moderate unilateral sensorineural hearing loss in various audiogram configurations, whereasPAX3andEDNRBvariants were associated with profound unilateral sensorineural hearing loss in flat audiogram configurations. In addition, whole genome sequencing and extended next-generation sequencing targeting 213 deafness genes were performed in two multiplex families compatible with autosomal recessive inheritance; yet no definite causative variants were identified. Cochlear nerve deficiency and congenital cytomegalovirus infection were observed in nine and two patients without definite genetic diagnoses.

Conclusion

Genetic underpinnings can contribute to approximately 20% of childhood unilateral sensorineural hearing loss, and different genotypes are associated with various audiological features. These findings highlight the utility of genetic examinations in guiding the diagnosis, counseling, and treatment of unilateral sensorineural hearing loss in children.
Modeling of the chest wall response to prolonged bracing in pectus carinatum
Authors: Sargent Brandon , Varela Katie , Eggett Dennis , McKenna Emily , Bates Christina , Brown Rebeccah , Garcia Victor , Howell Larry
Published: December 2022

Pectus carinatum is a chest wall deformity that is often treated through the wearing of an external brace. The treatment of the deformity could benefit from a greater understanding of chest wall characteristics under prolonged loading. These characteristics are difficult to model directly but empirical studies can be used to create statistical models. 185 patients from 2018-2020 received bracing treatment. Data on the severity of the deformity, treatment pressures, and time of wear were recorded at the first fitting and all subsequent follow-up visits. This data was analyzed using a statistical mixed effects model to identify significant measures and trends in treatment. These models were designed to help quantify changes in chest wall characteristics through prolonged bracing. Two statistical models were created. The first model predicts the change in the amount of pressure to correct the deformity after bracing for a given time and pressure. The second model predicts the change in pressure response by the body on the brace after bracing for a given time and pressure. These models show a high significance in the amount of pressure and time to the changes in the chest wall response. Initial deformity severity is also significant in changes to the deformity. The statistical models predict general trends in pectus carinatum brace treatment and can assist in creating treatment plans, motivating patient compliance, and can inform the design of future treatment systems.
Root-associated Fungi in Orchidaceae: Diversity, Phylogeny, Ecology, and Outstanding Questions
Authors: Wang Deyi , Lerou Jun , Nuytinck Jorinde , Gomes Sofia I.F. , Jacquemyn Hans , Merckx Vincent S.F.T.
Published: December 2022

Mycorrhizal fungi form ubiquitous symbiotic associations with almost all land plants and are of key interest to evolutionary biologists and ecologists because this ancient symbiosis was essential for the colonization of land by plants – a major turning point in the evolutionary history of the earth – and the subsequent development and functioning of the terrestrial ecosystems. Within the orchid family (Orchidaceae), plants establish unique interactions with specific orchid mycorrhizal fungi. These fungal symbionts are essential for the development of orchids as they provide carbon and soil nutrients to germinating orchid seeds and the nutritional supply continues for adult orchids to different degrees. Fueled by the development of DNA sequencing techniques, the diversity of mycorrhizal and other root-associated fungi in orchid roots has been extensively reported in evolutionary and ecophysiological studies. However, the full taxonomic range of orchid-associated fungi remains to be investigated in a broad phylogenetic framework, hampering a further understanding of the evolution and ecological adaptation of orchid mycorrhizal interactions. In this study, we used the most complete DNA dataset to date to map the phylogenetic distribution and ecological lifestyles of root-associated fungi in Orchidaceae by phylogenetic reconstructions at the fungal order level. We found that a broad taxonomic range of fungi (clustered into 1898 operational taxonomic units) resided in orchid roots, belonging to at least 150 families in 28 orders inBasidiomycotaandAscomycota. These fungi were assigned to diverse ecological lifestyles including typical orchid mycorrhizal fungi (‘rhizoctonia’), ectomycorrhizal fungi, wood- or litter-decaying saprotrophic fungi, and other endophytes/pathogens/saprotrophs. This overview reveals that among the four different mycorrhizal types, the orchid mycorrhizal symbiosis probably involves the highest diversity of fungal taxa. We hope that our newly reconstructed phylogenetic framework of orchid-associated fungi and the assessment of their potential mycorrhizal status will benefit future ecological and evolutionary studies on orchid-fungal interactions.
Morphine-induced mechanical hypersensitivity in mice requires δ receptors, β-arrestin2 and c-Src activity
Authors: Singleton Samuel , Hales Tim G.
Published: December 2022

Background

Morphine diminishes acute pain, but long-term use is compromised by tolerance and hyperalgesia. Studies implicate δ receptors, β-arrestin2 and Src kinase in tolerance. We examined whether these proteins are also involved in morphine-induced hypersensitivity (MIH). A common pathway for tolerance and hypersensitivity may provide a single target to guide improved analgesic approaches.

Methods

We examined mechanical sensitivity using automated von Frey in wild type (WT) and transgenic male and female C57Bl/6 mice before and after hind paw inflammation by complete Freund’s adjuvant (CFA). We explored the expression of opioid genes in the spinal cord using quantitative RT-PCR.

Results

CFA-evoked hypersensitivity ceased on day 7 in WT mice but persisted in μ-/-mice. Recovery was delayed until day 13 in δ-/-mice. Restoration to basal sensitivity in WT mice occurred with increased δ expression. By contrast, κ expression was reduced, while μ remained unchanged. Daily morphine reduced hypersensitivity in WT mice on day 3 compared to controls, however hypersensitivity recurred on day 9 and beyond. By contrast, WT mice had no recurrence of hypersensitivity in the absence of daily morphine. We used β-arrestin2-/-, δ-/-and Src inhibition by dasatinib in WT mice to establish whether these approaches, which diminish tolerance, also attenuate MIH. While none of these approaches affected CFA-evoked inflammation or acute hypersensitivity, all caused sustained morphine anti-hypersensitivity, abolishing MIH.

Conclusions

Like morphine tolerance, MIH in this model requires δ receptors, β-arrestin2 and Src activity. Our findings suggest that MIH is caused by a tolerance-induced reduction in endogenous opioid signalling.
Interleukin-17 signaling influences CD8+T cell immunity and tumor progression according to the IL-17 receptor subunit expression pattern in cancer cells
Authors: Rodriguez Constanza , Araujo Furlan Cintia L. , Boari Jimena Tosello , Bossio Sabrina N. , Boccardo Santiago , Fozzatti Laura , Canale Fernando P. , Beccaria Cristian G. , Nuñez Nicolás G. , Ceschin Danilo G. , Piaggio Eliane , Gruppi Adriana , Montes Carolina L. , Acosta Rodríguez Eva V.
Published: December 2022

The role of IL-17 mediated immune responses in cancer is conflicting as pre-clinical and clinical results show tumor-promoting as wel as tumor-repressing functions. Herein, we used syngeneic tumor models from different tissue origins as a tool to evaluate the role of IL-17 signaling in cancer progression, dissecting the effects in cancer cell growth and tumor immunity. We show that absence of IL-17RA or IL-17A/F expression in the host has contrasting effects in thein vivogrowth of different tumor types. We observed that lack of IL-17A/F-IL-17RA signaling in host cells changed the expression pattern of several mediators within the tumor microenvironment in a cancer-type specific manner. Deficiencies in host IL-17RA or IL-17A/F expression resulted in reduced antitumor CD8+ T cell immunity in all cancer models and in tumor-specific changes in several lymphoid cell populations. These findings were associated to particular patterns of expression of cytokines (IL-17A and IL-17F) and receptor subunits (IL-17RA, IL-17RC and IL-17RD) of the IL-17 family in the injected tumor cell lines that, in turn, dictated tumor cell responsiveness to IL-17. We identified IL-17RC as an important determinant of the IL-17-mediated transcriptional response in tumor cells and; consequently, as a predictive biomarker of the overall effect of IL-17 signaling in tumor progression. Our findings contribute to unraveling the molecular mechanisms underlying the divergent activities of IL-17 in cancer and provide rational targets for immunotherapies based on personalized approaches.
Fatecode: Cell fate regulator prediction using classification autoencoder perturbation
Authors: Sadria Mehrshad , Layton Anita , Goyal Sidharta , Bader Gary D.
Published: December 2022

Cell reprogramming, which guides the conversion between cell states, is a promising technology for tissue repair and regeneration. Typically, a group of key genes, or master regulators, are manipulated to control cell fate, with the ultimate goal of accelerating recovery from diseases or injuries. Of importance is the ability to correctly identify the master regulators from single-cell transcriptomics datasets. To accomplish that goal, we propose Fatecode, a computational method that combines in silico perturbation experiments with cell trajectory modeling using deep learning to predict master regulators and key pathways controlling cell fate. Fatecode uses only scRNA-seq data from wild-type samples to learn and predict how cell type distribution changes following a perturbation. We assessed Fatecode’s performance using simulations from a mechanistic gene regulatory network model and diverse gene expression profiles covering blood and brain development. Our results suggest that Fatecode can detect known master regulators of cell fate from single-cell transcriptomics datasets. That capability points to Fatecode’s potential in accelerating the discovery of cell fate regulators that can be used to engineer and grow cells for therapeutic use in regenerative medicine applications.
A phylogenetic approach to studying the roles of within-host evolution and between-host transmission of resistance for clinicalEscherichia coliinfections
Authors: van Nouhuijs Florentine , Antony MaryGracy Arakkal , Orcales Faye , Gozashti Landen , Roy Scott W. , Ogbunugafor C. Brandon , Pennings Pleuni S.
Published: December 2022

Bacterial antibiotic resistance represents a public health concern that will remain relevant for the foreseeable future. Antibiotic resistant bacterial infections can occur in two ways: (1) a host is infected by a resistant bacterial strain (due to between-host transmission of resistance), or (2) a host is infected infection by a susceptible strain, followed by the de novo evolution or acquisition of resistance (due to within-host evolution of resistance). While both are critical to understanding how the evolution of resistance happens in natural settings, the relative rate at which they occur is unclear. Here, we employ phylogenetic comparative methods to examine the evolutionary dynamics of resistance inEscherichia colifor multiple common antibiotics. We report evolutionary patterns consistent with commonde novoevolution of resistance for some antibiotics and sustained transmission of resistant strains for others. For example, we observe 79 putativede novoresistance evolution events for resistance to Cefuroxime but only 31 for resistance to Ciprofloxacin, despite similar numbers of observed infections (239 and 267 respectively). We find that clusters of resistance are generally larger for Ciprofloxacin, Ceftazidima and AmoxiClav, which suggests that for these drugs, resistance is often transmitted from patient to patient. In contrast, we find that cluster sizes for resistance are generally smaller for PipTaz, Cefuroxime and Gentamicin, suggesting that resistance to these drugs is less often transmitted from patient to patient and instead evolvesde novo. In addition to differences between drugs, we also find that cluster sizes were generally larger in phylogroup B2 compared to the other phylogroups, suggesting that transmission of resistant strains is more common in this phylogroup compared to the others. Our study proposes new approaches for determining the importance ofde novoevolution or acquisition (within-host evolution) from resistance from infection with an already resistant strain (between-host transmission). Significantly, this work also bridges an important gap between evolutionary genomics and epidemiology, opening up a range of opportunities for studying the evolutionary dynamics of bacterial antibiotic resistance.
Effect of image registration on the estimation of pharmacokinetic parameters from DCE-MRI of patients with esophageal cancer
Authors: Lee Joonsang , Ma Jingfei , Carter Brett , Court Laurence E. , Lin Steven H.
Published: December 2022

We investigated the effectiveness of the most commonly used registration methods (deformable and rigid-body registrations) with different reference images on pharmacokinetic parameters estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of esophageal cancer patients. We obtained DCE-MRI images from 10 patients with esophageal cancer. Both rigid-body and deformable registrations of the images were performed on DCE-MRI images at different time points as reference images before the pharmacokinetic parameters were estimated. The deformable registration used non-rigid B-spline transforms in a multi-resolution scheme, and Euler transform were used for the rigid body registration. A nonparametric statistical test and the intra-class correlation coefficient assessed the consistency and reproducibility of the pharmacokinetic parameters estimated with both registration methods and using images acquired at different time points. Kruskal-Wallis testing demonstrated significant differences (p < 0.05) in all the estimated parameters for deformable registration but no significant differences (p > 0.78) for rigid-body registration. The intra-class correlation coefficient for rigid-body registration was higher than that for deformable registration for each pharmacokinetic parameter, indicating that, for rigid-body registration, the parameter values from different reference images of one patient tended to be similar to each other. In contrast, the values for deformable registration were more variable. In conclusion, the choice of the reference image of deformable registration significantly affected the estimates of pharmacokinetic parameters, and rigid-body registration showed small variations in pharmacokinetic parameters over the choice of the reference images for small motion artifacts of small distal esophageal cancer on DCE-MRI.
CD4+ T cells regulate sickness-induced anorexia and fat wasting during a chronic parasitic infection
Authors: Redford Samuel E. , Varanasi Siva Karthik , Sanchez Karina K. , Ayres Janelle S.
Published: December 2022

Catabolic responses of lean and fat energy stores are a component of the host response to infection. Cachexia is an extreme catabolic state characterized by unintentional weight loss and muscle loss, that can include fat loss. Whether cachexia plays any role in host defense or is a maladaptive consequence of host-pathogen interactions remains unknown. Traditionally studies have focused on understanding how inflammatory mediators and cells of the innate immune system contribute to the pathogenesis of cachexia and the depletion of energy stores. The cells of the adaptive immune system that regulate infection-induced cachexia remain elusive. In the present study, we examined the role of the adaptive immune response in cachexia pathogenesis using a murine model of the chronic parasitic infectionTrypanosoma brucei, the causative agent of sleeping sickness. We found that the cachectic response occurs in two phases with the first stage occurring early in the infection and involved a loss of body fat mass associated with anorexia, and the second stage occurring later in the infection and involved a sustained loss of fat mass that was accompanied by lean mass wasting. CD4+ T cells were necessary for the development of the sickness-induced anorexic response during stage 1 of the infection, which led to adipose triglyceride lipase dependent lipolysis in adipocytes and the resulting fat wasting. Adipose tissue wasting had no impact on host resistance defenses or survival of infection, both of which were antibody-mediated and independent ofCD4+ T cell responses. Our work reveals a new mechanism for infection induced cachexia involving CD4+ T cell regulation of host feeding behavior and an unexpected decoupling of adaptive immune mediated resistance from the cachectic response during infection.
Transposon-derived transcription factors across metazoans
Authors: Mukherjee Krishanu , Moroz Leonid L.
Published: December 2022

Transposable elements (TE) could serve as sources of new transcription factors (TFs) in plants and some other model species, but such evidence is lacking for most animal lineages. Here, we discovered multiple independent co-options of TEs to generate 788 TFs across Metazoa, including all early-branching animal lineages. Six out of ten super-families of known TEs (ZBED, CENPB, FHY3, HTH-Psq, THAP, and FLYWCH) were recruited as representatives of nine phyla. The most extensive convergent domestication of TE-derived TFs occurred in the hydroid polyps, polychaete worms, cephalopods, oysters, and sea slugs. Phylogenetic reconstructions showed species-specific clustering and lineage-specific expansion; none of the identified TE-derived TFs revealed homologs in their closest neighbors. Together, our study established a framework for categorizing TE-derived TFs and informing the origins of novel genes across phyla.