bluuebunny/crossref_metadata_2025 huggingface dataset:
Post‐amputation pain: Comparing pain presentations between adults with and without increased amputated‐region sensitivity
Authors: Beisheim‐Ryan Emma Haldane , Pohlig Ryan Todd , Hicks Gregory Evan , Horne John Robert , Sions Jaclyn Megan
Published: October 2022

Objective

Among adults with persistent post‐amputation pain, increased amputated‐region pain sensitivity may reflect peripheral sensitization or indicate underlying central sensitization. To determine whether underlying central sensitization may contribute to increased pain sensitivity in this population, this study compared clinical signs and symptoms associated with central sensitization between adults with post‐amputation pain who demonstrate or lack increased amputated‐region sensitivity (as compared to reference data).

Design

Cross‐sectional.

Subjects

Ninety‐nine adults (60 with a unilateral, transtibial amputation and post‐amputation pain, 39 pain‐free controls with intact limbs).

Methods

Participants underwent pain‐pressure threshold testing of amputated‐region and secondary (non‐amputated region) sites and completed outcome measures assessing central sensitization symptoms (Patient‐Reported Outcomes Measurement Information System® pain intensity and interference domains, Central Sensitization Inventory). Among the full sample, the presence and frequency of specific central sensitization symptoms were evaluated. Participants with post‐amputation pain were then grouped based on whether normalized, amputated‐region pain‐pressure thresholds fell below (i.e., sensitive) or above (i.e., non‐sensitive) the 25th percentile of sex‐specific reference data. Between‐group differences in normalized secondary‐site sensitivity were evaluated using a multivariate analysis of variance; central sensitization symptom scores were compared using a Kruskal–Wallis test.

Results

Noteworthy symptoms associated with central sensitization (e.g., fatigue, sleep disturbance, cognitive difficulty) were reported by 33%–62% of participants. Secondary‐site pain sensitivity was greater among individuals with increased amputated‐region sensitivity (n = 24) compared to peers without increased amputated‐region sensitivity ([n = 36], mean difference > 1.33 standard deviation [SD], p < 0.001). Central sensitization symptom scores, however, were similar between groups (p > 0.187).

Conclusions

Participants with increased amputated‐region sensitivity demonstrate generalized, secondary‐site pain hypersensitivity, potentially indicating underlying central sensitization. Central sensitization symptom scores, however, were similar between groups, suggesting differences in physiological pain sensitivity may not manifest in subjective post‐amputation pain descriptions.
Long‐term impact of tobacco exposure during pregnancy on children's psychomotor development
Authors: Saliaj Aurela , Zahaj Majlinda , Vasilika Prifti , Mechili Enkeleint‐Aggelos
Published: October 2022

Background

Both active and second‐hand smoking (SHS) can cause complications during pregnancy and after delivery. This study aimed to assess how tobacco exposure (active and passive) during the fetal period could impact the psychomotor development of children when they attain the age of 3–6 years.

Methods

The study included 160 mothers and their 3–6 year‐old children. Two research groups were set up of children born to active or SHS mothers during the period when they were pregnant and a control group of children of non‐smoking mothers. The parameters of the psychomotor development of the children were measured using the Age & Stage Questionnaires 3® (ASQ‐3).

Results

Children, whose mothers were smokers themselves or who were exposed to SHS during the period of pregnancy had an average psychomotor development score of 221 points versus 243.5 points in the control group. Twenty‐six percent had delays (near or under the cut‐off scores) in one of the assessed psychomotor areas and 60% had two or more psychomotor delays; 36% of children whose mothers were not exposed to smoking during pregnancy had normal psychomotor development and only 34% presented multiple psychomotor delays.

Conclusions

Fetuses exposed to tobacco are more likely to achieve a psychomotor development in the ‘monitor’ and ‘fail’ areas compared to the non‐exposed control group. The children exposed to smoking during their fetal development should be considered as a group at risk of developmental delays, therefore they should be closely monitored and supported by caregivers and developmental pediatricians.
Coping during the COVID‐19 pandemic among young adults experiencing homelessness and unstable housing: A qualitative study
Authors: Gibbs Karen DiValerio , Jones Jennifer Torres , LaMark Whitney , Abdulmooti Sarah , Bretz Lauren , Kearney Kelly D. , Narendorf Sarah Carter , Santa Maria Diane M.
Published: October 2022

Background

Young adults experiencing homelessness (YAEH) experience more stressors compared to housed peers, yet little is known about the impact of the COVID‐19 pandemic on these youth. The purpose of this qualitative study was to explore how YAEH perceived the pandemic's impact on their well‐being and coping.

Methods

YAEH were recruited from those participating in an HIV prevention study. Semi‐structured interviews were conducted and analysis was guided by Lazarus and Folkman's transactional theory of stress and coping.

Results

Four major themes were identified from interviews with 40 youth: (1) ongoing harms, (2) COVID‐19 as a stressor, (3) mental health impacts, and (4) coping strategies. Participants described unmet basic needs, emotions of frustration and anxiety, and several coping strategies including substance use.

Conclusion

Many YAEH reported experiencing continued challenges that were compounded by the stressors related to the COVID‐19 pandemic. Special considerations are needed to address pandemic‐related exacerbations of mental health symptoms and substance use among YAEH.
Grass species with smoke‐released seed dormancy: A response to climate and fire regime but not photosynthetic pathway
Authors: Lamont B. B.
Published: October 2022

Both C3 and C4 photosynthetic pathways and smoke‐released seed dormancy occur among grasses. C4 species evolved from C3 species as seasonality and fire frequency increased and might therefore imply that their smoke sensitivity increased. I searched the worldwide literature for reports on germination responses among grasses, whose photosynthetic pathway was known, to treatment by smoke. Data were obtained for 217 species and 126 genera. While subfamilies tended to be C3 (Pooideae), C4 (Chloridoideae) or a mixture (Panicoideae), a beneficial smoke response was independent of their photosynthetic pathway. The only exceptions were Danthonioideae (C3, non‐smoke responsive) and Triodia (C4, smoke responsive). One third of both C3 and C4 genera were smoke responsive. Even within genera, 90% of species showed contrasting smoke responses, confirming that smoke sensitivity is rarely taxonomically constrained. Data on photosynthetic pathway, climate, fire regime and vegetation were compiled for 15 regions that formed four distinct groups: 1) In warm climates with aseasonal rainfall, C4 grasses are moderately better represented, with crown fires and limited smoke responses. 2) In cool regions, most species are C3, with surface‐crown fires and lack smoke responses. 3) In warm regions with summer rain (savannas), most species are C4, with surface fires and lack smoke responses. 4) In Mediterranean‐climate regions with summer drought, most species are C3, with crown fires and smoke‐released dormancy. Thus, even though C3 and C4 grasses are equally capable of expressing smoke sensitivity, their response depends on the region’s climate and fire regime that also dictate which photosynthetic pathway dominates.
Characterization of Xanthomonas arboricola pv. pruni from Prunus spp. orchards in Western Balkans
Authors: Iličić Renata , Jelušić Aleksandra , Milovanović Predrag , Stanković Slaviša , Zečević Katarina , Stanisavljević Rade , Popović Tatjana
Published: October 2022

The present study provides a new insight into the existing Xanthomonas arboricola pv. pruni (Xap) bacterial population originating from peach and apricot in two Western Balkans countries (Serbia and Montenegro). Multilocus sequence typing and analysis of the sequences of nine housekeeping genes revealed homology between the tested Xap strains as well as with the European population of this bacterium. The tested strains share the same haplotype (Haplotype I) with the Xap strains from Italy, France, Spain, United States, Australia and Brazil. The revealed single nucleotide change (G ↔ C) in the sequences of the gyrB1 gene differentiates Haplotype I from Haplotype II (Xap from South Korea, New Zealand, Argentina and Uruguay). The detached‐leaf bioassay results confirmed differences in virulence between strains originating from peach and apricot towards Prunus armeniaca (apricot), indicating host specialization of the apricot strain towards this host. For the first time, immunity of P. fruticosa (European ground cherry) to Xap was established. According to the AUDPC, PCA and cluster analysis, other Prunus spp. were classified as having low susceptibility (P. mahaleb, P. cerasus and P. avium), as susceptible (P. domestica) and as highly susceptible (P. persica, P. dulcis, P. cerasifera and P. spinosa). Xap strains were also found to be susceptible to 10 tested antibiotics. This study provides valuable knowledge on the Xap population from stone fruit grown in the Western Balkans region as well as the source of immunity, which could serve as a starting point for breeding Prunus cultivars and could be used as the main control strategy.
The Intergenerational Effects of Recessions
Authors: Alessandrini Diana , Diwakar Bharat
Published: October 2022

Several studies analyze the contemporaneous effects of recessions on individuals and their children. This paper shows that recessions also affect future offspring, not born yet. By linking fathers and offspring from the Panel Study of Income Dynamics, we find that a percentage‐point increase in the national unemployment rate experienced by men between ages 16 and 20 reduces their future offspring's annual wages by 4 percent, occupational prestige by 3 percent, and education by 0.2 years. We then investigate the mechanisms explaining our findings.
Shared understanding and social connection: Integrating approaches from social psychology, social network analysis, and neuroscience
Authors: Baek Elisa C. , Parkinson Carolyn
Published: October 2022

Meaningfully connecting with others is critical to the well‐being of individuals. What phenomena contribute to and stem from social connection? In this paper, we integrate emerging work that uses neuroimaging and social network analysis with theories that explore the links between shared reality and social connection. We highlight recent work suggesting that the extent to which people have aligned mental processing and shared subjective construals to those around them—as shown by neural similarity—is associated with both objective and subjective social connection. On the other hand, idiosyncrasies are linked to difficulties with social connection. We conclude by suggesting how the links between shared understanding and social connection can be productively used as a framework to study psychosocial phenomena of interest.
The room where it happened: How evangelical leaders used a Closed‐Door meeting to change sentiment for Donald J. Trump
Authors: Lemons J. Derrick
Published: October 2022

The embrace of Donald J. Trump as a presidential candidate in 2016 was not a given for evangelical voters. The thrice married, one‐time advocate for abortion, who prided himself on his ability to attract beautiful women did not seem like someone for whom evangelicals would enthusiastically show up to vote. Understanding the need to excite the tepid Evangelical base, evangelical leaders planned a meeting of 1000 pastors on 21 June 2016 in New York City. Mike Huckabee moderated this carefully planned question‐and‐answer interview with Donald J. Trump. Well‐known politically engaged evangelical pastors, including James Dobson, Franklin Graham, Jerry Falwell Jr., Tony Perkins and David Jeremiah, asked planted questions to which Donald J. Trump responded. I learned from ethnographic interviews with evangelical advisors to President Trump in 2020 that this meeting was the moment that they, and many other evangelical pastors, moved from scepticism to support of Donald J. Trump. In this article, I will analyse the 2016 meeting to understand how it helped propel Donald J. Trump into the White House. Specifically, I will use the lens of diffusion theory to understand how this meeting served as a rupture and tipping point of change for evangelical pastors' support.
Analysis of accessibility to hierarchical healthcare facilities in urban area: A case study in Shanghai
Authors: Yang Hetian , Chiu Marcus Yu Lung , Feng Qiushi , Cao Kai
Published: October 2022

The accessibility to healthcare facilities is closely linked to people's health and quality of life, which is especially evident in densely populated metropolises, such as Shanghai, China. Access to healthcare facilities is determined by various spatial and nonspatial factors, such as population, transportation modes, travel time, and the reputation of hospitals. In this research, with the consideration of all these factors mentioned above, a new approach based on the two‐step floating catchment area method and multi‐source datasets was proposed to measure the accessibility to these hierarchical healthcare facilities in Shanghai, China, including secondary hospitals and tertiary hospitals. In addition, a web mapping Application Programming Interface (API) was employed in this research to retrieve the traffic cost for different transportation modes and the analytic hierarchy process approach was also employed to help calculate the comprehensive accessibility in Shanghai considering both different types of hospitals and different modes of transportation. The results show that depending on modes of transportation, significant differences can be seen in accessibilities to different types of healthcare facilities. The calculated comprehensive accessibility reflects that the central regions in the research area have higher accessibility compared to the surrounding areas in Shanghai in general and more detailed spatial patterns could also been seen from the accessibility map. The research findings can also be utilized to support the better allocation of healthcare facilities at various levels.
Molecular phenotyping of malignant canine mammary tumours: Detection of high‐risk group and its relationship with clinicomolecular characteristics
Authors: Zamani‐Ahmadmahmudi Mohamad , Jajarmi Maziar , Talebipour Saeedeh
Published: October 2022

Canine mammary gland tumours (CMTs) constitute the most common cancer in female dogs and comprise approximately 50% of all canine cancers. With the advent of high‐throughput technologies such as microarray and next‐generation sequencing, the molecular phenotyping (classification) of various cancers has been extensively developed. The present study used a canine RNA‐sequencing dataset, namely GSE119810, to classify 113 malignant CMTs and 64 matched normal samples via an unsupervised hierarchical algorithm with a view to evaluating the association between the resulting subtypes (clusters) (n = 4) and clinical and molecular characteristics. Finally, a molecular classifier was developed, and it detected 1 high‐risk molecular subtype in the training dataset (GSE119810) and 2 independent validation datasets (GSE20718 and GSE22516). Our results revealed four molecular subtypes (C2–C5) in malignant CMTs. Furthermore, the normal samples constituted a distinct group in the clustering analysis. Marked significant associations were observed between the molecular subtypes (especially C5) and clinical/molecular features, including positive lymphatic invasion, high tumour grades, histopathology diagnoses, short survival and high TP53 mutation rates (ps <.05). The high‐risk subtype (C5) was further characterized through the development of a cell cycle‐based gene signature, which comprised 37 proliferation‐related genes according to the support vector machine algorithm. This signature identified the high‐risk group in both training and validation datasets (ps <.001). In the validation analysis, our potential classifier robustly predicted patients with positive lymphatic invasion, metastases and short survival.
Comparison of three canine nose guards for reduction of ultraviolet (UVA and UVB) solar radiation
Authors: Milich Kelsey A. , Griffin Craig E. , Dong Charli
Published: October 2022

Background

Protection from solar ultraviolet (UV) radiation is paramount for some dermatological conditions, yet there are no studies assessing UV nose guards for dogs.

Objectives

Compare the ability of three nasal guards to block solar UV radiation (UVR) from the canine nose, using two commercial products and one created by the authors.

Animals

Four fabric model dogs were used in this prospective controlled trial.

Materials and Methods

Each model had a UV dosimeter applied to the dorsal nose and anterior nasal planum. Three models had nose protectors applied: (1) a mesh hood (OutFox Field Guard, OutFox For Dogs); (2) a fabric nose shield (Nose Protector, Dog Nose Protectors); or (3) a basket muzzle with ultraviolet protection factor (UPF) 50+ fabric developed by the authors. The control had no protective device applied. All the models were placed in direct sunlight and measurements taken over nine 2 h time periods. Total cumulative UVR was analysed for each location and type of guard or control.

Results

All guards provided statistically significant UV protection compared to control at all time points (p < 0.001). The basket muzzle with UPF 50+ guard was consistent in protecting the dorsal and anterior nose, blocking 94.2% and 94.3% UVR, respectively. The fabric nose protector blocked 99.2% UVR from the dorsal and 82.9% anterior. The mesh hood blocked 72.5% of UVR dorsal and 71.4% anterior.

Conclusions and Clinical Relevance

Two guards were superior in blocking UVR; however, the choice of UV guard in a clinical setting depends on an individual's disease location and tolerance of the device.
Mining Induced Ground Motions in a Tailings Dam
Authors: Oliveira Dias Leonardo Santana de , Braga Marco Antonio da Silva , Cunha Alan De Souza , Olivier Gerrit , Machado Daniel Monteiro
Published: October 2022

Mining induced seismicity can expose tailings dams to ground motions with potential to trigger a failure, if the structure reaches a certain level of vibrations that could exceed the seismic coefficient design criteria from pseudostatic analysis. Despite the cited risk, mainly for dams that are closer to open pits, few dams in Brazil are monitored by microseismic systems, and there are no references in the literature about continuous seismic monitoring both in open pit (source) and tailings dam, which represents the motivation of this paper. A microseismic system was commissioned in Cajati Mine, São Paulo, to record seismic events continuously in an array of 16 geophones (14 Hz and 4.5 Hz), installed in boreholes near the open pit (12 sensors) and in the dam (4 sensors), has measured values of PGA (Peak Ground Acceleration) and PGV (Peak Ground Velocity) related to 2,972 induced events from rock removal in the open pit. During the period monitored, the total of 109 events have triggered sensors in both structures, producing 920 seismograms, with the highest values of PGA and PGV of 0.0135 m/s2 (0.1358% of g) and 0.0892 mm/s. The highest PGA value is 36 times lower than the vertical coefficient of 3% of g defined by Brazilian technical standard to dam design criteria, normally used in common pseudostatic analysis from geotechnical engineers. A routine microseismic monitoring brings a new set of valuable actionable data and information to support the management of geotechnical tailings dams’ risks, under the conditions of vibrations induced by mining production.
A Study on Key Disciplinary Parameters of Artificial Intelligent-Based Analysis Method for Dynamic Response Prediction of Floating Offshore Wind Turbines
Authors: Chen Peng , Hu Zhi Qiang
Published: October 2022

The dynamic performance prediction of floating offshore wind turbines (FOWTs) is a challenging task, as the existing theories might not be fully reliable for FOWTs due to the high nonlinearities and coupling effects. The artificial intelligent (AI) method gives a promising solution for this issue, and Chen and Hu proposed a novel AI-based method, named SADA (software-in-the-loop combined artificial intelligence method for dynamic response analysis of FOWTs), to overcome these challenges. This paper addresses a further and in-depth investigation of the key technologies of the key disciplinary parameters (KDPs) in the SADA method to obtain a novel and accurate analysis method for dynamic responses prediction of FOWTs. First, the categorization of KDPs is introduced, which can be divided into three categories: environmental KDPs, disciplinary KDPs, and specific KDPs. Second, two factors, the number of KDPs and boundary adjustment of KDPs, are investigated through the reinforcement learning algorithm within the SADA method. Basin experimental data of a spar-type FOWT is used for AI training. The results show that more proper KDPs set in the SADA method can lead to higher accuracy for the prediction of FOWTs. Besides, reasonable boundary conditions will also contribute to the convergence of the algorithms efficiently. Finally, the instruction on how to better choose KDPs and how to set and adjust their boundary conditions is given in the conclusion. The application of KDPs in the SADA method not only provides a deeper understanding of the dynamic response of the entire FOWTs system but also provides a promising solution to overcome the challenges of validation.
Cognitive Vulnerability to Mood Deterioration in an Exercise Cessation Paradigm
Authors: Evans Maggie , Rohan Kelly J. , Meyerhoff Jonah , Norton Richard J. , Sibold Jeremy S.
Published: October 2022

Mood deterioration in response to exercise cessation is well documented, but moderators of this effect remain unknown. This study tested the hypothesis that physically active individuals with higher levels of cognitive vulnerability (i.e., tendencies toward negative thought content and processes in response to stress or negative mood states) are at greater risk for increased anxiety and depressive symptoms when undergoing exercise cessation. Community adults meeting recommended physical activity guidelines (N = 36) participated in a 4-week prospective, longitudinal study with 2 weeks each of maintained exercise and exercise cessation. Cognitive vulnerability measures included dysfunctional attitudes, brooding rumination, and cognitive reactivity (i.e., change in dysfunctional attitudes over a dysphoric mood induction). Anxiety and depression symptoms increased during exercise cessation. Brooding emerged as a risk factor for increases in tension scores on the Profile of Mood States–Brief during exercise cessation. Future studies should explore brooding as a mediator (i.e., potential mechanism) of exercise-induced mood deterioration.
Retinoic acid inhibitors mitigate vision loss in a mouse model of retinal degeneration
Authors: Telias Michael , Sit Kevin K. , Frozenfar Daniel , Smith Benjamin , Misra Arjit , Goard Michael J. , Kramer Richard H.
Published: October 2022

Rod and cone photoreceptors degenerate in retinitis pigmentosa (RP). While downstream neurons survive, they undergo physiological changes, including accelerated spontaneous firing in retinal ganglion cells (RGCs). Retinoic acid (RA) is the molecular trigger of RGC hyperactivity, but whether this interferes with visual perception is unknown. Here, we show that inhibiting RA synthesis with disulfiram, a deterrent of human alcohol abuse, improves behavioral image detection in vision-impaired mice. In vivo Ca
2+
imaging shows that disulfiram sharpens orientation tuning of visual cortical neurons and strengthens fidelity of responses to natural scenes. An RA receptor inhibitor also reduces RGC hyperactivity, sharpens cortical representations, and improves image detection. These findings suggest that photoreceptor degeneration is not the only cause of vision loss in RP. RA-induced corruption of retinal information processing also degrades vision, pointing to RA synthesis and signaling inhibitors as potential therapeutic tools for improving sight in RP and other retinal degenerative disorders.
cART Restores Transient Responsiveness to IFN Type 1 in HIV-Infected Humanized Mice
Authors: Gruenbach Maarja , Muller Christina K. S. , Schlaepfer Erika , Baroncini Luca , Russenberger Doris , Kadzioch Nicole P. , Escher Benjamin , Schlapschy Martin , Skerra Arne , Bredl Simon , Speck Roberto F.
Published: October 2022

cART is highly efficient in suppressing HIV replication in HIV-infected patients and has resulted in a dramatic reduction in morbidity and mortality in HIV-infected people, yet it does not cure HIV infection. In addition, cART has several disadvantages.
Single Nucleotide Polymorphism-Based Real-Time PCR Screening Assay for Rapid Tracking of Bacterial Infection Clusters To Complement Whole-Genome Sequencing Efforts during Outbreak Investigations
Authors: Treffon Janina , Heppner Bianca , Eismann Julia , Bothe Julia , Omengo Birgit , Mellmann Alexander
Published: October 2022

Infection clusters of multidrug-resistant bacteria threaten medical facilities worldwide and cause immense health care costs. In recent years, whole-genome sequencing (WGS) has been increasingly applied to detect and to further control bacterial clusters.
Metabolomic markers of glucose regulation after a lifestyle intervention in prediabetes
Authors: Sevilla-Gonzalez Magdalena del Rocio , Manning Alisa K , Westerman Kenneth E , Aguilar-Salinas Carlos Alberto , Deik Amy , Clish Clary B
Published: October 2022

Introduction

Disentangling the specific factors that regulate glycemia from prediabetes to normoglycemia could improve type 2 diabetes prevention strategies. Metabolomics provides substantial insights into the biological understanding of environmental factors such as diet. This study aimed to identify metabolomic markers of regression to normoglycemia in the context of a lifestyle intervention (LSI) in individuals with prediabetes.

Research design and methods

We conducted a single-arm intervention study with 24 weeks of follow-up. Eligible study participants had at least one prediabetes criteria according to the American Diabetes Association guidelines, and body mass index between 25 and 45 kg/m2. LSI refers to a hypocaloric diet and >150 min of physical activity per week. Regression to normoglycemia (RNGR) was defined as achieving hemoglobin A1c (HbA1c) <5.5% in the final visit. Baseline and postintervention plasma metabolomic profiles were measured using liquid chromatography-tandem mass spectrometry. To select metabolites associated with RNGR, we conducted the least absolute shrinkage and selection operator-penalized regressions.

Results

The final sample was composed of 82 study participants. Changes in three metabolites were significantly associated with regression to normoglycemia; N-acetyl-D-galactosamine (OR=0.54; 95% CI 0.32 to 0.82), putrescine (OR=0.90, 95% CI 0.81 to 0.98), and 7-methylguanine (OR=1.06; 95% CI 1.02 to 1.17), independent of HbA1c and weight loss. In addition, metabolomic perturbations due to LSI displayed enrichment of taurine and hypotaurine metabolism pathway (p=0.03) compatible with biomarkers of protein consumption, lower red meat and animal fats and higher seafood and vegetables.

Conclusions

Evidence from this study suggests that specific metabolomic markers have an influence on glucose regulation in individuals with prediabetes after 24 weeks of LSI independently of other treatment effects such as weight loss.
Simplified dosing of oral azithromycin for children 1–11 months old in child survival programmes: age-based and height-based dosing protocols
Authors: Hu Huiyu , Arzika Ahmed Mamane , Sie Ali , Abdou Amza , Maliki Ramatou , Mankara Alio Karamba , Outtara Mamadou , Bountogo Mamadou , Boudo Valentin , Yago-Wienne Fanny , Bamba Issouf , Knirsch Charles , Emerson Paul , Hooper PJ , Lebas Elodie , Brogdon Jessica , Nyatigo Fanice , Oldenburg Catherine E , Lietman Thomas M , O'Brien Kieran S
Published: October 2022

Background

To facilitate mass distribution of azithromycin, trachoma control programmes use height instead of weight to determine dose for children 6 months to 15 years old. WHO has recommended azithromycin distribution to children 1–11 months old to reduce mortality in high mortality settings under carefully monitored conditions. Weight was used to determine dose in children 1–5 months old in studies of azithromycin distribution for child survival, but a simplified approach using age or height for all aged 1–11 months old could increase programme efficiency in real-world settings.

Methods

This secondary analysis used data from two cluster randomised trials of azithromycin distribution for child mortality in Niger and Burkina Faso. An exhaustive search algorithm was developed to determine the optimal dose for different age groups, using tolerance limits of 10–20 mg/kg for children 1–2 months old and 15–30 mg/kg for children 3–11 months old. Height-based dosing was evaluated against the existing trachoma dosing pole and with a similar exhaustive search.

Results

The optimal two-tiered age-based approach suggested a dose of 80 mg (2 mL) for children 1–2 months old and 160 mg (4 mL) for children 3–11 months old. Under this schedule, 89%–93% of children would have received doses within tolerance limits in both study populations. Accuracy was 93%–94% with a three-tiered approach, which resulted in doses of 80 mg (2 mL), 120 mg (3 mL) and 160 mg (4 mL) for children 1–2, 3–4 and 5–11 months old, respectively. For children 1–5 months old, the existing height pole would result in 70% of doses within tolerance limits. The optimisation identified height-based dosing options with 95% accuracy, although this would require changes to the existing dosing pole as well as additional training to measure infants lying flat.

Conclusions

Overall, an age-based approach with two age tiers resulted in high accuracy while considering both concerns about overdosing in this young population and simplicity of field operations.
Exploring variation in quality of care and clinical outcomes between neonatal units: a novel use for the UK National Neonatal Audit Programme (NNAP)
Authors: Ismail Abdul-Qader Tahir , Boyle Elaine M , Oddie Sam , Pillay Thillagavathie
Published: October 2022

Neonatology is a relatively new specialty, in which much of the practice remains non-evidence based. Variation in the quality of care delivered is recognised but measuring this is challenging. One possible indicator of this is variation in practice. For more than a decade, the National Neonatal Audit Project (NNAP) has described variation in practice between UK neonatal units in relation to its annually reviewed audit measures. These are based on evidence based national standards or developed by a consensus method and have become de facto measures defining good quality of neonatal healthcare within the UK. In this article we explore the practicality of using the NNAP to look for associations between quality of care and outcomes. This would not be to validate the measures but could help towards a better understanding of the reasons underlying recognised variation in outcomes, even between neonatal units of the same designation.
Lipoprotein(a) levels in a global population with established atherosclerotic cardiovascular disease
Authors: Nissen Steven E , Wolski Kathy , Cho Leslie , Nicholls Stephen J , Kastelein John , Leitersdorf Eran , Landmesser Ulf , Blaha Michael , Lincoff A Michael , Morishita Ryuichi , Tsimikas Sotirios , Liu Junhao , Manning Brian , Kozlovski Plamen , Lesogor Anastasia , Thuren Tom , Shibasaki Taro , Matei Florin , Silveira Fábio Serra , Meunch Andreas , Bada Aysha , Vijan Vinod , Bruun Niels Eske , Nordestgaard Borge G
Published: October 2022

Objective

Lipoprotein(a) (Lp(a)) is an important genetically determined risk factor for atherosclerotic vascular disease (ASCVD). With the development of Lp(a)-lowering therapies, this study sought to characterise patterns of Lp(a) levels in a global ASCVD population and identify racial, ethnic, regional and gender differences.

Methods

A multicentre cross-sectional epidemiological study to estimate the prevalence of elevated Lp(a) in patients with a history of myocardial infarction, ischaemic stroke or peripheral artery disease conducted at 949 sites in 48 countries in North America, Europe, Asia, South America, South Africa and Australia between April 2019 and July 2021. Low-density lipoprotein cholesterol (LDL-C) and Lp(a) levels were measured either as mass (mg/dL) or molar concentration (nmol/L).

Results

Of 48 135 enrolled patients, 13.9% had prior measurements of Lp(a). Mean age was 62.6 (SD 10.1) years and 25.9% were female. Median Lp(a) was 18.0 mg/dL (IQR 7.9–57.1) or 42.0 nmol/L (IQR 15.0–155.4). Median LDL-C was 77 mg/dL (IQR 58.4–101.0). Lp(a) in women was higher, 22.8 (IQR 9.0–73.0) mg/dL, than in men, 17.0 (IQR 7.1–52.2) mg/dL, p<0.001. Black patients had Lp(a) levels approximately threefold higher than white, Hispanic or Asian patients. Younger patients also had higher levels. 27.9% of patients had Lp(a) levels >50 mg/dL, 20.7% had levels >70 mg/dL, 12.9% were >90 mg/dL and 26.0% of patients exceeded 150 nmol/L.

Conclusions

Globally, Lp(a) is measured in a small minority of patients with ASCVD and is highest in black, younger and female patients. More than 25% of patients had levels exceeding the established threshold for increased cardiovascular risk, approximately 50 mg/dL or 125 nmol/L.

Trial registration number
Constraining the lithostratigraphic architecture of a buried bedrock valley using surface electrical resistivity and seismic refraction tomography
Authors: Conway-White Oliver , Steelman Colby M. , Arnaud Emmanuelle , Ugalde Hernan , Munn Jonathan D. , Parker Beth L.
Published: October 2022

Buried bedrock valleys are common erosional features in northern mid-latitude environments that form through glaciofluvial or paleoalluvial processes and are typically infilled by Quaternary-aged sediments. The erosional extent and geometry of the valley including a weathered interface, along with sediment infill that can contain complex sequences of unconsolidated aquifer and aquitard sediments, mean these features may act as preferential pathways to deeper bedrock aquifers. Noninvasive geophysical tools can provide rapid, high-resolution subsurface characterization of these features. This study evaluates the application of electrical resistivity and seismic refraction tomography along two transects centred over a buried bedrock valley in Elora, Ontario, Canada. Geophysical measurements were combined with existing continuous core records and an electrofacies model based on downhole geophysical logs to constrain the morphology and infilled lithostratigraphic architecture of the valley. Bedrock competency associated with lithology may act as a control on depth and width of valley incision during erosion, with resistivity measurements of the bedrock revealing a potential association between interpreted mechanical properties and variations in the resolved valley morphology. Seismic velocity corroborated these contrasting valley widths but could not assess bedrock competency variability below the bedrock interface. This study reveals the sequence of events depositing sediments in the valley, yielding a revised architectural mapping that improves on previous regional scale lithostratigraphic interpretations. Results will be of use to groundwater practitioners requiring detailed conceptualization of this buried bedrock valley and its role on preferential zones of groundwater flow. Similar approaches can be used for delineation of these common and hydrogeologically significant features.
Moving to the Right? How the Conservative Movement Has Shaped American Legal Education
Authors: Baumgardner Paul
Published: October 2022

The American legal academy has witnessed intense ideological assaults in recent decades, as political conservatives have sought to recast legal education and produce a different kind of legal professional. However, the paths by which conservatives have approached the law schools differ. Some conservative campaigns to remake American legal education have highlighted their ideological agenda, whereas other campaigns have taken steps to keep their ideological goals hidden. This review illustrates both strategies but dedicates special attention to conservative forces that have pursued the latter strategy of ideological concealment.
Molecular Dynamics Simulations of DGEBA/OSC Epoxy Composites for Improving Heat-Resistance and Elastic Modulus
Authors: Li Shuang Cui , Hao Chun Cheng
Published: October 2022

Thermal and mechanical properties of DGEBA/OSC epoxy composite polymers composed of both bisphenol A diglygde ether (DGEBA) and alicyclic epoxy resin (OSC) as co-polymerization monomers and 3,3-diaminodiphenyl sulfone (DDS) as curing agent are evaluated and investigated by molecular dynamics (MD) simulations, in which NPT ensembles and annealing cycles in a wide temperature range are utilized for modeling the thermodynamic equilibrium systems and heating processes. Glass transition and thermal-decomposition temperatures are calculated by linear fitting on the temperature dependence of elastic modulus, cohesive energy, fractional free-volume (FFV). It is verified that the two DGEBA/OSC epoxy composite can effectively improve the thermal and mechanical performances of epoxy polymer, in which DGEBA/OSC(1:1) epoxy composite are most significant of promoting mechanical stiffness and render a elevated glass transition temperature by 28 K and thermal-decomposition temperatures by 91 K, the two DGEBA/OSC epoxy composite are capable of efficiently reduce fractional free volume by 4.4% and 8.6% for DGEBA/OSC(3:1) and DGEBA/OSC(1:1) epoxy composite respectively, which is in consistent with the lower rotation amplitudes of crosslinking bonds for DGEBA/OSC composite EP polymers that vdW interaction forces between molecular-chains can be promoted by OSC co-polymeric blocks to inhibit thermal motions of EP molecular-chains.
Temporal analysis of skeletal muscle remodeling post hindlimb ischemia reveals intricate autophagy regulation
Authors: Scalabrin Mattia , Engman Viktor , Maccannell Amanda , Critchlow Annabel , Roberts Lee D. , Yuldasheva Nadira , Bowen T. Scott
Published: October 2022

Hind limb ischemia (HLI) is the most severe form of peripheral arterial disease, associated with a substantial reduction of limb blood flow that impairs skeletal muscle homeostasis to promote functional disability. The molecular regulators of HLI-induced muscle perturbations remain poorly defined. This study investigated whether changes in the molecular catabolic-autophagy signaling network were linked to temporal remodeling of skeletal muscle in HLI. HLI was induced in mice via hindlimb ischemia (femoral artery ligation) and confirmed by Doppler echocardiography. Experiments were terminated at time points defined as early- (7 days; n = 5) or late- (28 days; n = 5) stage HLI. Ischemic and nonischemic (contralateral) limb muscles were compared. Ischemic versus nonischemic muscles demonstrated overt remodeling at early-HLI but normalized at late-HLI. Early-onset fiber atrophy was associated with excessive autophagy signaling in ischemic muscle; protein expression increased for Beclin-1, LC3, and p62 ( P < 0.05) but proteasome-dependent markers were reduced ( P < 0.05). Mitophagy signaling increased in early-stage HLI that aligned with an early and sustained loss of mitochondrial content ( P < 0.05). Upstream autophagy regulators, Sestrins, showed divergent responses during early-stage HLI (Sestrin2 increased while Sestrin1 decreased; P < 0.05) in parallel to increased AMP-activated protein kinase (AMPK) phosphorylation ( P < 0.05) and lower antioxidant enzyme expression. No changes were found in markers for mechanistic target of rapamycin complex 1 signaling. These data indicate that early activation of the sestrin-AMPK signaling axis may regulate autophagy to stimulate rapid and overt muscle atrophy in HLI, which is normalized within weeks and accompanied by recovery of muscle mass. A complex interplay between Sestrins to regulate autophagy signaling during early-to-late muscle remodeling in HLI is likely.
The underappreciated role of resident epithelial cell populations in metastatic progression: contributions of the lung alveolar epithelium
Authors: Christenson Jessica L. , Williams Michelle M. , Richer Jennifer K.
Published: October 2022

Metastatic cancer is difficult to treat and is responsible for the majority of cancer-related deaths. After cancer cells initiate metastasis and successfully seed a distant site, resident cells in the tissue play a key role in determining how metastatic progression develops. The lung is the second most frequent site of metastatic spread, and the primary site of metastasis within the lung is alveoli. The most abundant cell type in the alveolar niche is the epithelium. This review will examine the potential contributions of the alveolar epithelium to metastatic progression. It will also provide insight into other ways in which alveolar epithelial cells, acting as immune sentinels within the lung, may influence metastatic progression through their various interactions with cells in the surrounding microenvironment.
Selective reduction of neurotransmitter release by cAMP-dependent pathways in mouse detrusor
Authors: Chakrabarty Basu , Drake Marcus J. , Kanai Anthony J. , Fry Christopher H.
Published: October 2022

Parasympathetic nerve-mediated contractions of detrusor smooth muscle are generated by ATP and acetylcholine (ACh) release from efferent nerve terminals. In humans, ACh is responsible for detrusor contractions in normal human bladders, whereas ATP has an additional role in overactive bladder pathologies. The ATP metabolite, adenosine, relaxes nerve-mediated contractions, with a potential action via presynaptic adenosine A1 receptor activation and subsequent suppression of neuronal ATP release. We investigated the effect of A1 receptor activation and downstream cAMP-dependent pathways on nerve-mediated ATP and ACh release, and detrusor contraction in mouse detrusor. Bladders from male C57BL/6 mice (12 wk) were used for in vitro experiments. Upon electrical field stimulation of intact preparations (detrusor and mucosal layers), ATP or ACh release was measured simultaneously with tension recordings. Activation of A1 receptors by adenosine or exogenous agonists reduced the lower frequency component of nerve-mediated contractions and neuronal ATP release. The A1 receptor antagonist abolished these effects. A1 receptor activation inhibits adenylyl cyclase (AC) activity and cAMP generation. The effect of A1 receptor activation was mimicked by a PKA antagonist but not by modulators of exchange proteins activated by cAMP, demonstrating that modulation of nerve-mediated ATP release is via PKA. Adenosine had no effect on ACh release or the higher frequency component of nerve-mediated contractions. Differential regulation of neurotransmitter release is possible at the detrusor nerve-muscle junction, as demonstrated by A1 receptor activation, and downstream inhibition of AC, cAMP generation, and PKA. The ability to specifically attenuate ATP release offers a potential to target purinergic motor pathways enhanced in overactive bladder pathologies.
Hydrogen sulfide and miR21 are suitable biomarkers of hypoxic exposure
Authors: Garcia Selina M. , Matheson Benjamin , Morales-Loredo Juan H. , Jernigan Nikki L. , Kanagy Nancy L. , Resta Thomas C. , Clark Ross M. , Shekarriz Reza , Gonzalez Bosc Laura V.
Published: October 2022

Hypoxia is the reduction of alveolar partial pressure of oxygen ([Formula: see text]). Military members and people who practice recreational activities from moderate to high altitudes are at risk for hypoxic exposure. Hypoxemia’s signs and symptoms vary from asymptomatic to severe responses, such as excessive hypoxic ventilatory responses and residual neurobehavioral impairment. Therefore, it is essential to identify hypoxia-induced biomarkers to indicate people with exposure to hypoxia. Advances have been made in understanding physiological responses to hypoxia, including elevations in circulating levels of endothelin 1 (ET-1) and microRNA 21 (miR-21) and reduction in circulating levels of hydrogen sulfide (H2S). Although the levels of these factors change upon exposure to hypoxia, it is unclear if these changes are sustained on return to normoxia. We hypothesize that hypoxia-induced ET-1 and miR-21 remain elevated, whereas hypoxia-reduction in H2S sustains after returning to normoxic conditions. To test this hypothesis, we exposed male rats to 6 h of 12% O2 and measured circulating levels of ET-1 and miR-21, pre, during, and posthypoxia. We found that ET-1 plasma levels increased in response to hypoxia but returned to normal levels within 30 min after the restoration of normoxia. miR-21 plasma levels and transdermal H2S emissions decreased in response to hypoxia, remaining decreased on return to normoxia, thus following the biomarker criteria. Therefore, this study supports a unique role for plasma miR21 and transdermal H2S as hypoxia biomarkers that could be used to identify individuals after exposure to hypoxia.
[Retracted] Serum Markers CA125, CA153, and CEA along with Inflammatory Cytokines in the Early Detection of Lung Cancer in High‐Risk Populations
Authors: Li Guangping , Zhang Hongxin , Zhang Lei , Liu Huaqun , Li Songlin , Wang Yanan , Deng Xiaoyun
Published: October 2022

Lung cancer mortality and morbidity rates are the first among malignant tumors. It is extremely crucial to pay more attention to the early diagnosis and treatment of lung cancer and to grasp and judge the progress of the patient’s condition promptly. In this study, lung cancer patients’ early diagnosis with tumor markers and inflammatory variables is examined. The general surgery department of our hospital treated 98 patients with lung cancer and 100 patients with benign pulmonary hyperplasia from January 2017 to February 2018. Additionally, 100 healthy subjects who completed physical examinations during this time period were included. Based on the findings of the pathological examination, 100 patients with benign pulmonary hyperplasia were chosen as the benign group, 100 patients with lung cancer were chosen as the malignant group, and 100 healthy individuals were chosen as the healthy group. The tumor markers carbohydrate antigen 125 (CA125), CA153, and carcinoembryonic antigen (CEA), as well as inflammatory factors such as tumor necrosis factor‐ (TNF‐) and high‐sensitivity C‐reactive protein, were measured in the venous blood of three groups of patients (hs‐CRP). There was no discernible difference in tumor marker levels between the benign and healthy groups (P > 0.05). In comparison to the benign and healthy groups, the malignant group had higher serum levels of CA153, CA125, and CEA (P 0.05). Between the benign and healthy groups, there was no discernible difference in the levels of inflammatory factors (P > 0.05). TNF‐ and hs‐CRP serum levels were observed to be higher in the malignant group compared to the benign and healthy groups (P 0.05). The combined detection of CA153 + CA125 + CEA + TNF − +hs − CRP showed the highest sensitivity and specificity, which were, respectively, 62.22 percent and 92.00 percent, when compared to single or mixed detection of tumor markers or inflammatory factors solely. Serum levels of inflammatory agents TNF‐ and hs‐CRP may be related to the pathophysiology and other functions of patients with lung cancer, as well as to the development and metastasis of the disease. These markers include CA153, CA125, and CEA. For the early detection of lung cancer and the evaluation of the disease’s severity, the detection of tumor markers in combination with inflammatory variables has a significant reference value.