bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of exhaled breath to identify critically ill patients with ventilator‐associated pneumonia
Authors: Felton T. W. , Ahmed W. , White I. R. , van Oort P. , Rattray N. J. W. , Docherty C. , Bannard‐Smith J. , Morton B. , Welters I. , McMullan R. , Roberts S. A. , Goodacre R. , Dark P. M. , Fowler S. J.
Published: April 2023

Ventilator‐associated pneumonia commonly occurs in critically ill patients. Clinical suspicion results in overuse of antibiotics, which in turn promotes antimicrobial resistance. Detection of volatile organic compounds in the exhaled breath of critically ill patients might allow earlier detection of pneumonia and avoid unnecessary antibiotic prescription. We report a proof of concept study for non‐invasive diagnosis of ventilator‐associated pneumonia in intensive care (the BRAVo study). Mechanically ventilated critically ill patients commenced on antibiotics for clinical suspicion of ventilator‐associated pneumonia were recruited within the first 24 h of treatment. Paired exhaled breath and respiratory tract samples were collected. Exhaled breath was captured on sorbent tubes and then analysed using thermal desorption gas chromatography–mass spectrometry to detect volatile organic compounds. Microbiological culture of a pathogenic bacteria in respiratory tract samples provided confirmation of ventilator‐associated pneumonia. Univariable and multivariable analyses of volatile organic compounds were performed to identify potential biomarkers for a ‘rule‐out’ test. Ninety‐six participants were enrolled in the trial, with exhaled breath available from 92. Of all compounds tested, the four highest performing candidate biomarkers were benzene, cyclohexanone, pentanol and undecanal with area under the receiver operating characteristic curve ranging from 0.67 to 0.77 and negative predictive values from 85% to 88%. Identified volatile organic compounds in the exhaled breath of mechanically ventilated critically ill patients show promise as a useful non‐invasive ‘rule‐out’ test for ventilator‐associated pneumonia.
The trajectory of pharmacometrics to support drug licensing and labelling
Authors: Dunn Allison , Gobburu Jogarao V. S.
Published: April 2023

The field of pharmacometrics has been responsible for countless advancements within the drug development space. In recent years, we have witnessed the implementation of both new and revived analytical methods to increase clinical trial success and even supplement the need for clinical trials all together. Throughout this article, we will explore the path of pharmacometrics from its inception to the present day. At this point in time, the target of drug development has been the average patient, and population approaches have primarily been utilized to support just that. The challenge we are now facing involves the translation from treating the typical patient to treating the real‐world patient. For this reason, it is our opinion that future development efforts should account more for the individual. With advanced pharmacometric methods and growing technological infrastructure, precision medicine can become a development priority rather than a clinician's burden.
Decision biases and environmental attitudes among conservation professionals
Authors: Filewod Ben , Kant Shashi , MacDonald Heather , McKenney Daniel
Published: April 2023

The importance of human behavior in biodiversity conservation is widely recognized, but there is little published evidence about how conservation professionals make decisions when conservation values are at stake. We take a behavioral economics approach, administering simplified decision problems (“choice experiments”), questions about choice‐relevant preferences and views (“elicitation questions”), and a psychometric scale (the New Ecological Paradigm scale) to a difficult‐to‐recruit sample (n = 100) of Canadian professionals involved in managing Rangifer tarandus caribou (Woodland Caribou). Our choice experiments reveal the importance of several decision biases (risk aversion, commission bias, and a bias towards fairness) in this influential group of conservation stakeholders. We then examine in‐sample differences between categories of professional affiliation (e.g., resource industry, environmental nongovernmental organization, or federal/provincial government), finding significant variation in responses to one elicitation question (reference points) and in psychometric scores. We discuss the implications of our findings for choice in conservation practice and for multistakeholder conservation policy. Comparing our findings to prior work on choice under uncertainty in nonconservation contexts suggests a possible replication problem in applying behavioral science insights to conservation problems, pointing to the need for a systematic research program. Results from development testing with a convenience sample of university students are presented for comparison throughout the study.
The dilemma of analytical method changes for soil organic carbon in long‐term experiments
Authors: Grahmann Kathrin , Zwink Mariam , Barkusky Dietmar , Verch Gernot , Sommer Michael
Published: April 2023

Long‐term experiments (LTEs) have provided data to modellers and agronomists to investigate changes and dynamics of soil organic carbon (SOC) under different cropping systems. As treatment changes have occurred due to agricultural advancements, so too have analytical soil methods. This may lead to method bias over time, which could affect the robust interpretation of data and conclusions drawn. This study aims to quantify differences in SOC due to changes in dry combustion methods over time, using soil samples of a LTE established in 1963 that focuses on mineral and organic fertilizer management in the temperate zone of Northeast Germany. For this purpose, 1059 soil samples, collected between 1976 and 2008, have been analysed twice, once with their historical laboratory method right after sampling, and a second time in 2016 when all samples were analysed using the same elementary analyser. In 9 of 11 soil sampling campaigns, a pairedt‐test provided evidence for significant differences in the historical SOC values when compared with the re‐analysed concentrations of the same LTE sample. In the sampling years 1988 and 2004, the historical analysis obtained about 0.9 g kg−1lower SOC compared with the re‐analysed one. For 1990 and 1998, this difference was about 0.4 g kg−1. Correction factors, an approach often used to correct for different analytical techniques, could only be applied for 5 of 11 sampling campaigns to account for constant and proportional systematic method error. For this particular LTE, the interpretation of SOC changes due to agronomic management (here fertilization) deviates depending on the analytical method used, which may weaken the explanatory power of the historical data. We demonstrate that analytical method changes over time present one of many challenges in the interpretation of time series data of SOC dynamics. Therefore, LTE site managers need to ensure providing all necessary protocols and data in order to retrace method changes and if necessary recalculate SOC.

Highlights

A total of 1059 LTE soil samples taken between 1976 and 2008 were re‐analysed for SOC in 2016

Several methodological changes for SOC determination led to significant different SOC concentration in the same sample

Interpretation and time series of LTE soil data suffer from consideration of analytical method changes and poor documentation of the same

Soil archive establishment, thorough method protocols and diligent proficiency testing after soil method changes ameliorate the dilemma
Neurological and (neuro)psychological sequelae in intensive care and general ward COVID‐19 survivors
Authors: Klinkhammer Simona , Horn Janneke , Duits Annelien A. , Visser‐Meily Johanna M. A. , Verwijk Esmée , Slooter Arjen J. C. , Postma Alida A. , van Heugten Caroline M. ,   NeNeSCo Study Group
Published: April 2023

Background and purpose

Coronavirus disease 2019 (COVID‐19) affects the brain, leading to long‐term complaints. Studies combining brain abnormalities with objective and subjective consequences are lacking. Long‐term structural brain abnormalities, neurological and (neuro)psychological consequences in COVID‐19 patients admitted to the intensive care unit (ICU) or general ward were investigated. The aim was to create a multidisciplinary view on the impact of severe COVID‐19 on functioning and to compare long‐term consequences between ICU and general ward patients.

Methods

This multicentre prospective cohort study assessed brain abnormalities (3 T magnetic resonance imaging), cognitive dysfunction (neuropsychological test battery), neurological symptoms, cognitive complaints, emotional distress and wellbeing (self‐report questionnaires) in ICU and general ward (non‐ICU) survivors.

Results

In al, 101 ICU and 104 non‐ICU patients participated 8–10 months post‐hospital discharge. Significantly more ICU patients exhibited cerebral microbleeds (61% vs. 32%, p < 0.001) and had higher numbers of microbleeds (p < 0.001). No group differences were found in cognitive dysfunction, neurological symptoms, cognitive complaints, emotional distress or wellbeing. The number of microbleeds did not predict cognitive dysfunction. In the complete sample, cognitive screening suggested cognitive dysfunction in 41%, and standard neuropsychological testing showed cognitive dysfunction in 12%; 62% reported ≥3 cognitive complaints. Clinically relevant scores of depression, anxiety and post‐traumatic stress were found in 15%, 19% and 12%, respectively; 28% experienced insomnia and 51% severe fatigue.

Conclusion

Coronavirus disease 2019 ICU survivors had a higher prevalence for microbleeds but not for cognitive dysfunction compared to general ward survivors. Self‐reported symptoms exceeded cognitive dysfunction. Cognitive complaints, neurological symptoms and severe fatigue were frequently reported in both groups, fitting the post‐COVID‐19 syndrome.
Microcell‐Net: A deep neural network for multi‐class classification of microscopic blood cell images
Authors: Dwivedi Karnika , Dutta Malay Kishore
Published: April 2023

Blood‐related diseases are one of the major concerns in the biomedical domain and most of the disease symptoms are reflected through the analysis of blood cells. The diagnosis by experts in laboratories is very costly and time‐consuming, thus artificial intelligence‐based systems can help in the automatic diagnosis and monitoring of an individual's health. In this study, a CNN‐based architecture Microcell‐Net is proposed which is trained on a microscopic image dataset of peripheral blood cells in eight different classes. The images have several inter‐class and intra‐class diversity with different magnification levels and the noise present in the images makes the classification task significantly challenging. Experimental results indicated that the proposed model can efficiently classify various types of microscopic blood cells with good accuracy. The experimental findings accomplished 98.76% validation accuracy and 97.65% test accuracy in complex background conditions. The performance of the model is compared with other state‐of‐the‐art models and the proposed deep neural network performs significantly better than others. The proposed model can be utilized in a real‐time diagnosis system because it is fast, automatic and efficient, which can assist in taking clinical decisions and early diagnosis of haematological disorders.
Association of vitamin D metabolites with arteriovenous fistula function in hemodialysis patients: A single center study
Authors: Chen Hong , Song Na , Li Ai‐mei , Dai Qin , Liu Yu‐ting , Yang Shi‐kun
Published: April 2023

Introduction

Arteriovenous fistula (AVF) is a primary dialysis vascular access commonly used for maintaining hemodialysis (MHD) patients. Vitamin D (VD) is a fat‐soluble steroid hormone that is closely related to vascular endothelial function. This study aimed to investigate the association between VD metabolites and AVF failure in patients undergoing HD.

Methods

This study included 443 HD patients using AVF between January 2010 and January 2020. The AVF operations in these patients were newly created by the same physician. We analyzed the AVF patency rates using the chi‐square test. Univariate and multivariate logistic regression analyses were performed to explore risk factors for AVF failure. Survival analysis was performed to explore AVF survival at different serum 25‐hydroxyvitamin D (25(OH)D) concentrations.

Results

Logistic regression analyses showed that male sex; age; BMI; serum albumin, triglyceride, phosphorus, 25(OH)D, iPTH and hemoglobin levels, history of hypertension, CHD, diabetes, stroke, and antiplatelet drug use; and smoking habits were not risk factors for AVF failure. The failure incidence rates of AVF in subjects in the VD deficiency and non VD deficiency group were not statistically significant (25.0% vs. 30.8%, p = 0.344). The AVF failure incidence rates at 1, 3, and 5 years in the patients with 25(OH)D levels more than 20 ng/mL were 26%, 29%, and 37%, respectively, and the one‐year AVF failure incidence rates were 27% in the patients with 25(OH)D levels less than 20 ng/mL. In addition, the Kaplan–Meier analysis suggested that the no significant differences were noted when calculating the cumulative survival rates of AVF between the two groups within 50 months of AVF using.

Conclusion

Our findings suggest that 25(OH)D deficiency is not associated with AVF failure incidence rates, and that 25(OH)D deficiency has no significant impact on long‐term cumulative AVF survival rate.
The use of ultrasound to detect enthesitis as a potential guide for intervention in patients with psoriasis at risk of psoriatic arthritis: a systematic review
Authors: Norden Alexandra , Oulee Aislyn , Ivanic Mirjana , Javadi Sogol Stephanie , Han George , Wu Jashin J.
Published: April 2023

Introduction

Psoriatic arthritis is estimated to develop in 2% of patients with psoriasis per year and can result in significant morbidity. Early diagnosis and treatment of psoriatic arthritis are imperative to prevent irreversible arthritic joint damage. Dermatologists play a key role in identifying patients who are at risk for or with early signs of psoriatic arthritis. Subclinical enthesopathy may be a risk factor for psoriatic arthritis or an early sign of the disease and can be detected using ultrasound.

Methods

In this systematic review, we determined the prevalence of ultrasound‐diagnosed enthesitis in psoriasis patients, as well as their risk of subsequent progression to psoriatic arthritis.

Results

We determined that the detection of enthesitis on ultrasound was associated with higher risk of future psoriatic arthritis. Systemic therapy was associated with improvement in enthesitis findings in patients with psoriasis but not in those with chronic structural damage or established psoriatic arthritis. Additionally, one study showed that ustekinumab treatment resulted in a significantly lower rate of psoriatic arthritis development.

Conclusions

These studies support the value of early detection and treatment in the prevention of progression to psoriatic arthritis, as well as the use of ultrasound for screening for risk factors in psoriasis patients. Future studies are needed to further evaluate when preventative therapy can be useful among patients with psoriasis with risk factors for psoriatic arthritis.
Parent–child communication about weight: Priorities for parental education and support
Authors: Puhl Rebecca M. , Lessard Leah M. , Foster Gary D. , Cardel Michelle I.
Published: April 2023

Background

Approximately 2/3 of parents talk about body weight with their children, which can include negative comments that have adverse health implications for youth.

Objectives

To identify ways to improve supportive parent–child communication about weight, we assessed parent and youth perspectives of barriers to weight communication, preferences for educational resources and support, and whether perspectives differ across demographic groups and weight status.

Methods

In Fall 2021, online surveys were completed by two independent, unrelated samples of parents (N = 1936) and youth (N = 2032). Participants were asked about their perceived barriers to talking about weight, and what kinds of information and support would be most useful to them in fostering supportive communication.

Results

Parent and youth‐reported barriers to weight communication included discomfort and lack of knowledge about weight, and views that weight does not need to be discussed. Most parents wanted guidance on how to navigate multiple weight‐related topics with their children, including promoting positive body image and healthy behaviours, reducing weight criticism, focusing more on health and addressing weight‐based bullying. Youth preferences for how their parents can be more supportive of their weight included avoiding weight‐related criticism and pressures, increasing sensitivity and encouragement, and emphasizing healthy behaviours rather than weight. Few differences emerged based on sex and race/ethnicity, although several differences emerged for youth engaged in weight management.

Conclusion

Parent and youth perspectives indicate a need for education to help parents engage in supportive conversations about body weight. Findings can inform efforts to reduce barriers and increase supportive weight‐related communication in families.
Efficacy of orofacial myofunctional therapy combined with myofascial release in patients with mild obstructive sleep apnoea: a randomized controlled trial
Authors: Paolucci Teresa , Ferrillo Martina , Pezzi Letizia , Agostini Francesco , Di Matteo Andrea , Prosperi Pierpaolo , Mangone Massimiliano , Bernetti Andrea , Spacone Antonella , de Sire Alessandro
Published: April 2023

Background

Obstructive sleep apnoea (OSA) is characterized by repetitive narrowing and collapse of pharyngeal airway during sleep, leading to apnoea or hypopnoea. In this context, myofunctional therapy and myofascial release might be effective, despite the literature on the combination of these approaches is still scarce.

Objectives

This randomized controlled trial aimed to assess the efficacy of oro‐facial myofunctional therapy combined with myofascial release in terms of functioning in patients with mild OSA.

Methods

Patients aged from 40 to 80 years with diagnosis of mild OSA were randomly allocated into intervention group (oro‐facial myofunctional therapy plus myofascial release) and control group (only oro‐facial myofunctional therapy). At the baseline (T0), after 4 weeks (T1), and after 8 weeks (T2), the following outcomes were assessed: apnoea/hypopnoea index (AHI), average oxygen saturation (SpO2), sleep time spent with oxygen saturation < 90% (T90), snoring index, and Pittsburgh Sleep Quality Index (PSQI).

Results

Out of the 60 patients enrolled, 28 (aged 61.46 ± 8.74 years) complete the treatment in the intervention group and 24 (aged 60.42 ± 6.61 years) in the control group. There were no significant differences in AHI between groups. A significant difference was reported for ΔT0–T1 SpO2 (p = .01), T90 (p = .030), ΔT0–T1 and ΔT0–T2 snoring index (p = .026 and <.001 respectively), and ΔT0–T1 and ΔT0–T2 Pittsburgh Sleep Quality Index (p = .003 and <.001 respectively).

Conclusion

Taken together, a combination of oro‐facial myofunctional therapy and myofascial release showed a potential treatment for sleep quality in patients with mild OSA. Future studies are necessary to better investigate the role of these interventions in OSA patients.
Rural‐urban trends in health care utilization, treatment, and mortality among US veterans with congestive heart failure: A retrospective cohort study
Authors: Aboumrad Maya , Peritz David , Friedman Scott , Zwain Gabrielle , Watts Bradley V. , Taub Cynthia
Published: April 2023

Purpose

To compare longitudinal rates of health care utilization, evidence‐based treatment, and mortality between rural and urban‐dwelling patients with congestive heart failure (CHF).

Methods

We used electronic medical record data from the Veterans Health Administration (VHA) to identify adult patients with CHF from 2012 through 2017. We stratified our cohort using left ventricular ejection fraction percentage at diagnosis (<40% = reduced ejection fraction [HFrEF]; 40%‐50% = midrange ejection fraction [HFmrEF]; >50% = preserved ejection fraction [HFpEF]). Within each ejection fraction cohort, we stratified patients into rural or urban groups. We used Poisson regression to estimate annual rates of health care utilization and CHF treatment. We used Fine and Gray regression to estimate annual hazards of CHF and non‐CHF mortality.

Findings

One‐third of patients with HFrEF (N = 37,928/109,110), HFmrEF (N = 24,447/68,398), and HFpEF (N = 39,298/109,283) resided in a rural area. Rural compared to urban patients used VHA facilities at similar or lower annual rates for outpatient specialty care across all ejection fraction cohorts. Rural patients used VHA facilities at similar or higher rates for primary care and telemedicine‐delivered specialty care. They also had lower and declining rates of VHA inpatient and urgent care use over time. There were no meaningful rural‐urban differences in treatment receipt among patients with HFrEF. On multivariable analysis, the rate of CHF and non‐CHF mortality was similar between rural and urban patients in each ejection fraction cohort.

Conclusions

Our findings suggest the VHA may have mitigated access and health outcome disparities typically observed for rural patients with CHF.
Distinct life history strategies underpin clear patterns of succession in microparasite communities infecting a wild mammalian host
Authors: Glidden Caroline K. , Karakoç Canan , Duan Chenyang , Jiang Yuan , Beechler Brianna , Jabbar Abdul , Jolles Anna E.
Published: April 2023

Individual animals in natural populations tend to host diverse parasite species concurrently over their lifetimes. In free‐living ecological communities, organismal life histories shape interactions with their environment, which ultimately forms the basis of ecological succession. However, the structure and dynamics of mammalian parasite communities have not been contextualized in terms of primary ecological succession, in part because few datasets track occupancy and abundance of multiple parasites in wild hosts starting at birth. Here, we studied community dynamics of 12 subtypes of protozoan microparasites (Theileria spp.) in a herd of African buffalo. We show that Theileria communities followed predictable patterns of succession underpinned by four different parasite life history strategies. However, in contrast to many free‐living communities, network complexity decreased with host age. Examining parasite communities through the lens of succession may better inform the effect of complex within host eco‐evolutionary dynamics on infection outcomes, including parasite co‐existence through the lifetime of the host.
A systematic review and meta‐analysis on the prevalence and clinical characteristics of dysphagia in patients with dermatomyositis
Authors: Cheng Ivy , Wong Christina Sze‐Man
Published: April 2023

Background

Dermatomyositis (DM) is a rare autoimmune disease characterized by distinctive skin rash, muscle inflammation with symmetrical and progressive muscle weakness, and elevated serum levels of muscle‐associated enzymes. DM may affect skeletal muscles involved in swallowing, leading to dysphagia, which can negatively impact individual's physical and psychosocial well‐being. Despite this, dysphagia in patients with DM remains poorly understood. This systematic review and meta‐analysis aimed to evaluate the prevalence and clinical features of dysphagia in patients with DM and juvenile DM (JDM).

Methods

Four electronic databases were systematically searched until September 2022. Studies with patients with DM or JDM and dysphagia were included. The pooled prevalence of all included studies was calculated, and the clinical characteristics of dysphagia were qualitatively analyzed.

Key Results

Thirty‐nine studies with 3335 patients were included. The overall pooled prevalence of dysphagia was 32.3% (95% CI: 0.270, 0.373) in patients with DM and 37.7% (95% CI: −0.031, 0.785) in patients with JDM. Subgroup analyses revealed that Sweden had the highest prevalence (66.7% [95% CI: 0.289, 1.044]), whereas Tunisia had the lowest prevalence (14.3% [95% CI: −0.040, 0.326]). Moreover, South America had the highest prevalence (47.0% [95% CI: 0.401, 0.538]), whereas Africa had the lowest prevalence (14.3% [95% CI: −0.040, 0.326]). Dysphagia in patients with DM and JDM was characterized by both oropharyngeal and esophageal dysfunctions, with predominant difficulties in motility.

Conclusions & Inferences

Our findings showed that dysphagia affects one in three patients with DM or JDM. However, the documentation on the diagnosis and management of dysphagia in the literature is inadequate. Our results highlighted the need to use both clinical and instrumental assessments to evaluate swallowing function in this population.
Paracrine relationship between incretin hormones and endogenous 5‐hydroxytryptamine in the small and large intestine
Authors: Tough Iain R. , Lund Mari L. , Patel Bhavik A. , Schwartz Thue W. , Cox Helen M.
Published: April 2023

Background

Enterochromaffin (EC) cell‐derived 5‐hydroxytryptamine (5‐HT) is a mediator of toxin‐induced reflexes, initiating emesis via vagal and central 5‐HT3 receptors. The amine is also involved in gastrointestinal (GI) reflexes that are prosecretory and promotile, and recently 5‐HT's roles in chemosensation in the distal bowel have been described. We set out to establish the efficacy of 5‐HT signaling, local 5‐HT levels and pharmacology in discrete regions of the mouse small and large intestine. We also investigated the inter‐relationships between incretin hormones, glucagon‐like peptide‐1 (GLP‐1) and gastric inhibitory polypeptide (GIP) and endogenous 5‐HT in mucosal and motility assays.

Methods

Adult mouse GI mucosae were mounted in Ussing chambers and area‐specific studies were performed to establish the 5‐HT3 and 5‐HT4 pharmacology, the sidedness of responses, and the inter‐relationships between incretins and endogenous 5‐HT. Natural fecal pellet transit in vitro and full‐length GI transit in vivo were also measured.

Key Results

We observed the greatest level of tonic and exogenous 5‐HT‐induced ion transport and highest levels of 5‐HT in ascending colon mucosa. Here both 5‐HT3 and 5‐HT4 receptors were involved but elsewhere in the GI tract epithelial basolateral 5‐HT4 receptors mediate 5‐HT's prosecretory effect. Exendin‐4 and GIP induced 5‐HT release in the ascending colon, while L cell‐derived PYY also contributed to GIP mucosal effects in the descending colon. Both peptides slowed colonic transit.

Conclusions & Inferences

We provide functional evidence for paracrine interplay between 5‐HT, GLP‐1 and GIP, particularly in the colonic mucosal region. Basolateral epithelial 5‐HT4 receptors mediated both 5‐HT and incretin mucosal responses in healthy colon.
Nematodes as suppressors and facilitators of plant performance
Authors: Topalović Olivera , Geisen Stefan
Published: April 2023

Plant–nematode interactions are mainly considered from the negative aspect with a focus on plant‐parasitic nematodes (PPNs), which is justified considering the agronomic losses caused by PPNs. Despite the fact that PPNs are outnumbered by nonparasitic free‐living nematodes (FLNs), the functional importance of FLNs, especially with regard to plant performance, remains largely unknown. Here, we provide a comprehensive overview and most recent insights into soil nematodes by showing direct and indirect links of both PPNs and FLNs with plant performance. We especially emphasize the knowledge gaps and potential of FLNs as important indirect players in driving plant performance such as stimulating the resistance to pests via improving the disease suppressive activity of the rhizobiome. Together, we present a holistic view of soil nematodes as positive and negative contributors to plant performance, accentuating the positive but underexplored role of FLNs.
PAX9 mutations and genetic synergism in familial tooth agenesis
Authors: Chu Kuan‐Yu , Wang Yin‐Lin , Chen Jung‐Tsu , Lin Chia‐Hui , Yao Chung‐Chen Jane , Chen Yi‐Jane , Chen Huan‐Wen , Simmer James P. , Hu Jan C.‐C. , Wang Shih‐Kai
Published: April 2023

Familial tooth agenesis (FTA) is one of the most common craniofacial anomalies in humans. Loss‐of‐function mutations in PAX9 and WNT10A have been known to cause FTA with various expressivity. In this study, we identified five FTA kindreds with novel PAX9 disease‐causing mutations: p.(Glu7Lys), p.(Val83Leu), p.(Pro118Ser), p.(Ser197Argfs*23), and c.771+4A>G. Concomitant PAX9 and WNT10A pathogenic variants found in two probands with severe phenotypes suggested an effect of mutational synergism. All overexpressed PAX9s showed proper nuclear localization, excepting the p.(Pro118Ser) mutant. Various missense mutations caused differential loss of PAX9 transcriptional ability. PAX9 overexpression in dental pulp cells upregulated LEF1 and AXIN2 expression, indicating a positive regulatory role for PAX9 in canonical Wnt signaling. Analyzing 176 cases with 63 different mutations, we observed a distinct pattern of tooth agenesis for PAX9‐associated FTA: Maxillary teeth are in general more frequently affected than mandibular ones. Along with all second molars, maxillary bicuspids and first molars are mostly involved, while maxillary lateral incisors and mandibular bicuspids are relatively less affected. Genotypically, missense mutations are associated with fewer missing teeth than frameshift and nonsense variants. This study significantly expands the phenotypic and genotypic spectrums of PAX9‐associated disorders and reveals a molecular mechanism of genetic synergism underlying FTA variable expressivity.
Food for thought: Opportunities to target carbon metabolism in antibacterial drug discovery
Authors: Tong Madeline , Brown Eric D.
Published: April 2023

Antimicrobial resistance is at an all‐time high and new drugs are required to overcome this crisis. Traditional approaches to drug discovery have failed to produce novel classes of antibiotics, with only a few currently in development. It is thought that novel classes will come from antibacterial drug discovery efforts that focus on unconventional targets. One such collection of antibacterial targets are those that comprise central carbon metabolism. Targets of this kind have been largely overlooked because conventional antibacterial testing media are ill‐suited for exploring carbon source utilization. Nevertheless, as a consequence of infection, bacteria must find a carbon source in order to survive. Here, we review what is known about the carbon sources available and used by bacteria in different host infection sites. We also look at discovery efforts targeting central carbon metabolism and evaluate how these processes can influence antibiotic efficacy.
Using Machine Learning to Create an Early Warning System for Welfare Recipients*
Authors: Sansone Dario , Zhu Anna
Published: April 2023

Using high‐quality nationwide social security data combined with machine learning tools, we develop predictive models of income support receipt intensities for any payment enrolee in the Australian social security system between 2014 and 2018. We show that machine learning algorithms can significantly improve predictive accuracy compared to simpler heuristic models or early warning systems currently in use. Specifically, the former predicts the proportion of time individuals are on income support in the subsequent 4 years with greater accuracy, by a magnitude of at least 22% (14 percentage points increase in the R‐squared), compared to the latter. This gain can be achieved at no extra cost to practitioners since the algorithms use administrative data currently available to caseworkers. Consequently, our machine learning algorithms can improve the detection of long‐term income support recipients, which can potentially enable governments and institutions to offer timely support to these at‐risk individuals.
Gingipains are the important virulence factors of Porphyromonas gingivalis downregulating B10 cells
Authors: Zou Hang , Zhou Niu , Cheng Xiao , Qiu Yi , Hou Wenhong , Sun Jianbo
Published: April 2023

Porphyromonas gingivalis is a keystone pathogen in periodontitis. Our previous study indicated that periodontitis induced by P. gingivalis increased the percentage of CD19+ B cells but decreased the ratio of IL‐10‐producing regulatory B cells (B10) in collagen‐induced arthritis (CIA) mice. It is still unclear which virulence factors of P. gingivalis are involved in these processes. Here, we compared the effects of different components of P. gingivalis on the biogenesis of B10 cells and found that the decreased proportion of B10 cells mainly resulted from the undenatured proteins other than the DNA, RNA, or lipopolysaccharides of P. gingivalis. As gingipains are enzymes and virulence factors that play a vital role in the progression in periodontitis through affecting the innate and adaptive immune system, we then compared the influence of the wild‐type (WT) strain of P. gingivalis (ATCC 33277) and its isogenic gingipain‐null mutant (∆K∆RAB) on the differentiation of splenic B cells into B10 cells. Interestingly, compared to WT strain, ∆K∆RAB treatment increased the frequency of B10 cells as well as the expression of IL‐6 in B cells. Furthermore, the acute peritonitis, an ideal model for the quick evaluation of immune effects of agents, induced by ∆K∆RAB, showed the higher IL‐6 production and proportion of B10 cells compared with WT. Finally, we performed transcriptomic analysis to better understand the effects and possible mechanisms of gingipains on B cells. Compared with WT, ∆K∆RAB upregulated the PI3K‐Akt pathway of B cells, which is important for IL‐10 production and B10 cell biogenesis, and more activated Jak‐STAT pathway, which is a classical signaling pathway mediated by IL‐6. Cumulatively, this study preliminarily revealed that gingipains of P. gingivalis are vital virulence factors downregulating B10 cells and altering immune responses.
Temporal summation in myopia and its implications for the investigation of glaucoma
Authors: Stapley Victoria , Anderson Roger S. , Redmond Tony , Saunders Kathryn , Mulholland Pádraig J.
Published: April 2023

Purpose

We have previously demonstrated the upper limit of complete spatial summation (Ricco's area) to increase in non‐pathological axial myopia compared to non‐myopic controls. This study sought to investigate whether temporal summation is also altered in axial myopia to determine if this aspect of visual function, like in glaucoma, is influenced by reductions in retinal ganglion cell (RGC) density.

Methods

Achromatic contrast thresholds were measured for a GIII‐equivalent stimulus (0.43° diameter) of six different stimulus durations (1–24 frames, 1.1–187.8 ms) in 24 participants with axial myopia (mean spherical refractive error: −4.65D, range: −1.00D to −11.25D, mean age: 34.1, range: 21–57 years) and 21 age‐similar non‐myopic controls (mean spherical refractive error: +0.87D, range: −0.25D to +2.00D, mean age: 31.0, range: 18–55 years). Measurements were performed at 10° eccentricity along the 90°, 180°, 270° and 360° meridians on an achromatic 10 cd/m2 background. The upper limit of complete temporal summation (critical duration, CD) was estimated from the data with iterative two‐phase regression analysis.

Results

There was no significant difference (p = 0.90, Mann–Whitney U‐test) in median CD between myopes (median: 44.3 ms; IQR: 26.5, 51.2) and non‐myopes (median: 41.6 ms; IQR: 27.3, 48.5). Despite RGC numbers underlying the stimulus being significantly lower in the myopic group (p < 0.001), no relationship was observed between the CD estimate and co‐localised RGC number (Pearson's r = −0.13, p = 0.43) or ocular length (Pearson's r = −0.08, p = 0.61).

Conclusions

Unlike spatial summation, temporal summation is unchanged in myopia. This contrasts with glaucoma where both temporal and spatial summation are altered. As such, perimetric methods optimised to test for anomalies of temporal summation may provide a means to differentiate between conditions causing only a reduced RGC density (e.g., myopia), and pathological processes causing both a reduced RGC density and RGC dysfunction (e.g., glaucoma).
Novel quantitative trait loci for yield and yield related traits identified in Basmati rice (Oryza sativa)
Authors: Malik Ankit , Kumar Aruna , Ellur Ranjith Kumar , Gopala Krishnan Subbaiyan , Vinod Kunnummal Kurungara , Dixit Deepshikha , Nagarajan Mariappan , Bhowmick Prolay Kumar , Bollinedi Haritha , Singh Nagendra Kumar , Singh Ashok Kumar
Published: April 2023

Increasing crop productivity is one of the prime goals of crop breeding research. Rice grain yield is a complex quantitative trait governed by polygenes. Although several QTLs governing grain yield traits have been reported and limited attempts have been made to map QTLs for grain yield parameters in Basmati rice. A population from the cross Sonasal and Pusa Basmati 1121 comprising 352 RILs was generated through the single seed descent method. A total of 12 QTLs governing yield and yield‐related traits were mapped on six chromosomes, namely, 1, 2, 3, 7, 8 and 9, of which five QTLs were novel. We identified a novel and robust epistatic QTL (qPH1.1 and qPL1.1) governing plant height and panicle length, flanked by the markers RM5336‐RM1 on chromosome 1. The gene encoding brassinosteroid insensitive 1‐associated receptor kinase 1 precursor is the putative candidate gene underlying this epistatic QTL. Another novel QTL, qNT3.1, governing tiller number was bracketed to a region of .77 Mb between the markers RM15247 and RM15281 on chromosome 3. Of the 57 annotated gene models, Os03g0437600 encoding alpha/beta‐fold hydrolase, a homologous to AtKai2 is a putative candidate gene underlying the novel QTL qNT3.1. The other QTLs such as qDFF1.1 governing days to 50% flowering co‐localizes with the gene Ghd7, QTL for plant height qPH1.2 co‐localizes with the gene sd1, the QTLs for panicle length co‐localizes with FUWA and DEP2, the QTL for tiller number co‐localizes with OsRLCK57 and QTLs for thousand‐grain weight co‐localize with the major gene GS3. The QTLs identified in the current study can be effectively used in marker‐assisted selection for developing Basmati rice varieties with a higher yield.
Policy entrepreneurs and individuals: Influence and behavior in pandemic response
Authors: Taylor Kristin , DeLeo Rob A. , Albright Elizabeth A. , Shanahan Elizabeth A. , Li Meng , Koebele Elizabeth A. , Anderson Crow Deserai , Birkland Thomas A.
Published: April 2023

Policy entrepreneurs have traditionally been recognized for their ability to influence policymakers by framing policy problems and pairing them with preferred solutions. Does their influence extend to the public? We examine this question in the context of the COVID‐19 pandemic in the United States. We analyze whether an individual's perception of a visible, national‐level policy entrepreneur, director of the National Institute of Allergy and Infectious Diseases (NIAID) Dr. Anthony Fauci, influences their perceived risk of contracting the virus and their uptake of recommended COVID‐19 risk mitigation behaviors. Findings indicate that approval of Dr. Fauci predicts individual risk perceptions and uptake of mask wearing practices, with his influence particularly strong among conservatives. However, Dr. Fauci's influence as a policy entrepreneur waned over time and was moderated by a host of factors such as an individual's worldview, perceptions of policy environment, and media consumption.
The role of peer imitation in agricultural index insurance adoption: Findings from lab‐in‐the‐field experiments in Kyrgyzstan
Authors: Moritz Laura , Kuhn Lena , Bobojonov Ihtiyor
Published: April 2023

Frequent climate shocks require farmers in developing countries to increase their resilience. Although index insurance is often discussed as a promising climate adaptation strategy, take‐up rates are still low. This study primarily explores the role of peer behavior as peer imitation in the demand for three marketable and unsubsidized crop index insurance options. Furthermore, the influence of trust and understanding is investigated. We collected data in lab‐in‐the‐field experiments among farmers in Kyrgyzstan, where index insurance is planned for imminent implementation. Applying ordered logit estimations, our results show significant and strong peer imitation effects. Imitation attitudes decrease with own insurance experience and received insurance payouts, but intensify with peer size, insurance trust and practical insurance understanding. While trust robustly increases index insurance adoption, understanding effects only gain significance in the dynamic perspective. These findings underline the importance of community‐based extension treatments and trust toward the uptake of innovative agricultural technologies in the first steps of dissemination.
Connecting simple and precise P‐values to complex and ambiguous realities (includes rejoinder to comments on “Divergence vs. decision P‐values”)
Authors: Greenland Sander
Published: April 2023

Mathematics is a limited component of solutions to real‐world problems, as it expresses only what is expected to be true if all our assumptions are correct, including implicit assumptions that are omnipresent and often incorrect. Statistical methods are rife with implicit assumptions whose violation can be life‐threatening when results from them are used to set policy. Among them are that there is human equipoise or unbiasedness in data generation, management, analysis, and reporting. These assumptions correspond to levels of cooperation, competence, neutrality, and integrity that are absent more often than we would like to believe. Given this harsh reality, we should ask what meaning, if any, we can assign to the P‐values, “statistical significance” declarations, “confidence” intervals, and posterior probabilities that are used to decide what and how to present (or spin) discussions of analyzed data. By themselves, P‐values and CI do not test any hypothesis, nor do they measure the significance of results or the confidence we should have in them. The sense otherwise is an ongoing cultural error perpetuated by large segments of the statistical and research community via misleading terminology. So‐called inferential statistics can only become contextually interpretable when derived explicitly from causal stories about the real data generator (such as randomization), and can only become reliable when those stories are based on valid and public documentation of the physical mechanisms that generated the data. Absent these assurances, traditional interpretations of statistical results become pernicious fictions that need to be replaced by far more circumspect descriptions of data and model relations.
Phylogenomics reveal extensive phylogenetic discordance due to incomplete lineage sorting following the rapid radiation of alpine butterflies (Papilionidae: Parnassius)
Authors: He Bo , Zhao Youjie , Su Chengyong , Lin Gonghua , Wang Yunliang , Li Luyan , Ma Junye , Yang Qun , Hao Jiasheng
Published: April 2023

Under rapid radiation, the earliest components of evolutionary divergence are often difficult to resolve, which were always driven by the characteristics of taxa and the limitations of alternative analytical methods. The origin and radiation of the alpine butterfly Parnassius, a high‐altitude mountainous insect group, can be attributed to the uplift of the Qinghai‐Tibet Plateau. Despite detailed phylogenetic analyses of the genus, deep phylogenetic relationships among the major subgenera remain recalcitrant. In this study, 102 individuals from 10 representative Parnassius species were sampled to resolve the phylogenetic relationships among subgenera based on nuclear and mitochondrial genome datasets. Gene‐tree/species‐tree conflicts were detected by concatenation and multispecies coalescent (MSC) approaches. We recovered a well‐supported species tree, despite these conflicts, and detected considerable phylogenetic discordance among genomic regions. The main explanation for the topological discordance among subgenera was extensive incomplete lineage sorting (ILS), whereas introgression events were not prominent. The origin and explosive radiation of Parnassius (i.e., rapid succession of speciation events) in the late Miocene associated with environmental events on the plateau led to short internal branches, thereby increasing ILS and topological conflicts, especially among closely related subgenera. Our results also suggested that MSC approaches (SNP and AFLP Package for Phylogenetic analysis [SNAPP] and SVDquartets) are accurate and superior to the concatenation approach; in particular, SVDquartets can explicitly accommodate gene‐tree/species‐tree conflicts caused by high ILS and demonstrate strong robustness. Finally, we explored the phylogenomic data by testing multiple sources of phylogenomic conflict to clarify the strengths and limitations of different approaches, while considering phylogenetic signal variation in mitochondrial loci. We anticipate that the phylogeny described here will be the backbone of future evolutionary studies of the genus and will provide insight into phylogenetic discordance due to rapid radiation.
Investigation of donor‐derived Strongyloides stercoralis infection in multiple solid organ transplant recipients—California, Michigan, Ohio, 2022
Authors: Adeyemo AdeSubomi , Montgomery Susan , Chancey Rebecca J. , Annambhotla Pallavi , Barba Lilly , Clarke Tyan , Williams Jonathan , Malilay Anne , Coyle Joseph
Published: April 2023

Background

The Centers for Disease Control and Prevention led an investigation to determine if Strongyloides infection in a right kidney recipient was an existing chronic infection, or if the infection was transmitted from an infected organ donor.

Methods

Evidence regarding the organ donor and organ recipients Strongyloides testing, treatment, and risk factors were gathered and evaluated. The case classification algorithm created by the Disease Transmission Advisory Committee was utilized.

Results

The organ donor had risk factors for Strongyloides infection; the banked donor specimen, submitted for serology testing 112 days post‐donor death, was positive. The right kidney recipient was negative for Strongyloides infection pretransplant. Strongyloides infection was diagnosed via small bowel and stomach biopsies. The left kidney recipient had risk factors for Strongyloides infection. Two posttransplant Strongyloides antibody tests were negative at 59 and 116 days posttransplant; repeat antibody tests returned positive at 158 and 190 days posttransplant.

Examination of bronchial alveolar lavage fluid collected 110 days posttransplant from the heart recipient showed a parasite morphologically consistent with Strongyloides species. She subsequently developed complications from Strongyloides infection, including hyperinfection syndrome and disseminated strongyloidiasis. Based on the evidence from our investigation, donor‐derived strongyloidiasis was suspected in one recipient and proven in two recipients.

Conclusion

The results of this investigation support the importance of preventing donor‐derived Strongyloides infections by laboratory‐based serology testing of solid organ donors. Donor positive testing results would direct the monitoring and treatment of recipients to avoid severe complications.

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