bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between absolute counts of lymphocyte subsets and clinical features in patients with pulmonary tuberculosis
Authors: An Hui‐Ru , Bai Xue‐Juan , Liang Jian‐Qin , Wang Tao , Wang Zhong‐Yuan , Xue Yong , Liu Yin‐Ping , Wang Lan , Wu Xue‐Qiong
Published: May 2022

Background

The aim of the present study is to investigate the clinical value and characteristics of peripheral blood lymphocyte subsets in patients with pulmonary tuberculosis (PTB) using flow cytometry.

Methods

The absolute counts of T, CD4+T, CD8+T, natural killer (NK), NKT and B lymphocytes in 217 cases of PTB were detected, and the variations in lymphocyte subset counts between different ages and genders and between aetiological detection results and chest radiography results were analysed.

Results

In 75.3% of the patients with PTB, six subset counts were lower than the normal reference range, and 44% showed lower‐than‐normal CD4+T lymphocyte levels. The counts of T, CD4+T, CD8+T and B lymphocytes were significantly lower in patients aged >60 years, and the NKT cell counts were significantly lower in female patients than in male patients. Among the patients with positive aetiological results, 40.8% had reduced CD8+T counts; these were significantly lower than those in patients with negative aetiological results (P = 0.0295). The cell counts of T, CD4+T, CD8+T and B lymphocytes reduced as lesion lobe numbers increased. The counts of T, CD4+T and CD8+T lymphocytes were significantly higher in the group with lesions affecting one lobe than in the groups with two to three lobes or four to five lobes, and the counts of B lymphocytes were significantly higher in the group with one lobe and the group with two to three lobes than in the group with four to five lobes. The counts of CD4+T and CD8+T lymphocytes were highest in the no cavity group and showed a downward trend with the increase in cavities; the T lymphocyte count was significantly higher in the no cavity group than in the group with five or more cavities (P = 0.014), and the CD8+T lymphocyte count was significantly higher in the no cavity group than in the group with one to two cavities and the group with five or more cavities (P = 0.001 and 0.01, respectively).

Conclusions

In most patients with tuberculosis, immune function is impaired. The absolute counts of peripheral blood lymphocyte subsets are closely related to the aetiological results and lesion severity in patients with PTB; this could be used as evidence for immune intervention and monitoring curative effects.
Construction and validation of prognostic nomograms for elderly patients with metastatic non‐small cell lung cancer
Authors: Sun Haishuang , Liu Min , Yang Xiaoyan , Ren Yanhong , Dai Huaping , Wang Chen
Published: May 2022

Background

Metastatic non‐small cell lung cancer (NSCLC) is mostly seen in older patients and is associated with poor prognosis. There is no reliable method to predict the prognosis of elderly patients (≥60 years old) with metastatic NSCLC. The aim of our study was to develop and validate nomograms which accurately predict survival in this group of patients.

Methods

NSCLC patients diagnosed between 2010 and 2015 were all identified from the Surveillance, Epidemiology, and End Results (SEER) database. Nomograms were constructed by significant clinicopathological variables (p < 0.05) selected in multivariate Cox analysis regression.

Results

A total of 9584 patients met the inclusion criteria and were randomly allocated in the training (n = 6712) and validation (n = 2872) cohorts. In training cohort, independent prognostic factors included age, gender, race, grade, tumor site, pathology, T stage, N stage, radiotherapy, surgery, chemotherapy, and metastatic site (p < 0.05) for lung cancer‐specific survival (LCSS) and overall survival (OS) were identified by the Cox regression. Nomograms for predicting 1‐, 2‐, and 3‐years LCSS and OS were established and showed excellent predictive performance with a higher C‐index than that of the 7th TNM staging system (LCSS: training cohort: 0.712 vs. 0.534; p < 0.001; validation cohort: 0.707 vs. 0.528; p < 0.001; OS: training cohort: 0.713 vs. 0.531; p < 0.001; validation cohort: 0.710 vs. 0.528; p < 0.001). The calibration plots showed good consistency from the predicted to actual survival probabilities both in training cohort and validation cohort. Moreover, the decision curve analysis (DCA) achieved better net clinical benefit compared with TNM staging models.

Conclusions

We established and validated novel nomograms for predicting LCSS and OS in elderly patients with metastatic NSCLC with desirable discrimination and calibration ability. These nomograms could provide personalized risk assessment for these patients and assist in clinical decision.
Effect of inhaled corticosteroids on microbiome and microbial correlations in asthma over a 9‐month period
Authors: Huang Chunrong , Ni Yingmeng , Du Wei , Shi Guochao
Published: May 2022

The effect of inhaled corticosteroids (ICS) on the airway microbiome requires longitudinal research for corroboration. Asthma patients, not undergoing ICS treatment (baseline), were enrolled and prescribed ICS; all these patients were followed up with regular visits at 3 months (visit 1) and 9 months (visit 2). Induced sputum was collected, and fungal microbiota (mycobiome) and bacterial microbiota (bacteriome) were estimated using 16S rRNA and internal transcribed spacer (ITS) sequencing. Bacterial α diversity indices were not significantly different between baseline, visit 1, and visit 2. Visit 1 showed lower fungal evenness than the baseline, and visit 2 showed lower fungal diversity and evenness than the baseline. Fungal, but not bacterial, community compositions differed significantly between the baseline, visit 1, and visit 2. The most abundant bacterial phyla and genera did not differ significantly between the baseline, visit 1, and visit 2. Compared with the baseline, visit 1 showed significantly increased frequency of the fungal phylum Ascomycota and lower frequency of Basidiomycota. We found sharply decreased fungal genera Wallemia, Cladosporium, Penicillium, and Alternaria at visit 1 and visit 2 compared with the baseline, although the differences were not statistically significant. We also found the proportion of Basidiomycota was positively correlated with percentages of sputum eosinophils and neutrophils. The proportions of Saccharomyces, Wallemia, and Aplosporella were positively correlated with percentage of sputum eosinophils. Moreover, we identified distinct inter‐ and intra‐kingdom interactions in baseline, visit 1, and visit 2. Therefore, ICS use altered the airway microbial diversity, evenness, community composition, and microbial connections.
Influence of CYP2D6 genetic variation on adverse events with propafenone in the pediatric and young adult population
Authors: Sunthankar Sudeep D. , Kannankeril Prince J. , Gaedigk Andrea , Radbill Andrew E. , Fish Frank A. , Van Driest Sara L.
Published: May 2022

Propafenone is an antiarrhythmic drug metabolized primarily by cytochrome P450 2D6 (CYP2D6). In adults, propafenone adverse events (AEs) are associated with CYP2D6 poor metabolizer status; however, pediatric data are lacking. Subjects were tested for 10 CYP2D6 allelic variants and copy number status, and activity scores assigned to each genotype. Seventy‐six individuals (median 0.3 [range 0–26] years old) were included. Propafenone AEs occurred in 29 (38%); 14 (18%) required drug discontinuation due to AE. The most common AEs were QRS (n = 10) and QTc (n = 6) prolongation. Those with AEs were older at the time of propafenone initiation (1.58 [0.13–9.92] vs. 0.20 [0.08–2.01] years old; p = 0.042). CYP2D6 activity scores were not associated with presence of an AE (odds ratio [OR] 0.48 [0.22–1.03]; p = 0.055) but with the total number of AE (β1 = −0.31 [−0.60, −0.03]; p = 0.029), systemic AEs (OR 0.33 [0.13–0.88]; p = 0.022), and drug discontinuation for systemic AEs (OR 0.28 [0.09–0.83]; p = 0.017). Awareness of CYP2D6 activity score and patient age may aid in determining an individual's risk for an AE with propafenone administration.
Protease‐activated receptor‐mediated platelet aggregation in patients with type 2 diabetes on potent P2Y12 inhibitors
Authors: Panzer Benjamin , Wadowski Patricia P. , Huber Kurt , Panzer Simon , Gremmel Thomas
Published: May 2022

Background

Antiplatelet therapy is a cornerstone in the secondary prevention of ischemic events following percutaneous coronary intervention (PCI). The new P2Y12 receptor inhibitors prasugrel and ticagrelor have been shown to improve patients' outcomes. Whether or not these drugs have equal efficacy in individuals with or without diabetes is disputed. Furthermore, platelets can be activated by thrombin, which is, at least in part, independent of P2Y12‐mediated platelet activation. Protease‐activated receptor (PAR)‐1 and −4 are thrombin receptors on human platelets. We sought to compare the in vitro efficacy of prasugrel (n = 121) and ticagrelor (n = 99) to inhibit PAR‐mediated platelet aggregation in individuals with type 2 diabetes (prasugrel n = 26, ticagrelor n = 29).

Materials and Methods

We compared P2Y12‐, PAR‐1‐ and PAR‐4‐mediated platelet aggregation as assessed by multiple electrode platelet aggregometry between prasugrel‐ and ticagrelor‐treated patients without and with type 2 diabetes who underwent acute PCI.

Results

Overall, there were no differences of P2Y12‐, PAR‐1‐ and PAR‐4‐mediated platelet aggregation between prasugrel‐ and ticagrelor‐treated patients. However, both drugs inhibited P2Y12‐mediated platelet aggregation stronger, and thereby to a similar extent in patients with type 2 diabetes than in those without diabetes. There was no correlation between either P2Y12‐, or PAR‐1‐ or PAR‐4‐mediated platelet aggregation and levels of HbA1c or the body mass index (BMI). However, we observed patients with high residual platelet reactivity in response to PAR‐1 and PAR‐4 stimulation in all cohorts.

Conclusion

Prasugrel and ticagrelor inhibit P2Y12‐ and PAR‐mediated platelet aggregation in individuals with diabetes to a similar extent, irrespective of HbA1c levels and BMI.
Dynamics of public opinion and policy response under proportional and plurality elections
Authors: McGann Anthony J. , Dellepiane‐Avellaneda Sebastian , Bartle John
Published: May 2022

We compare the patterns of adjustment of government policy to changes in public opinion in the Netherlands and the United Kingdom. These countries are similar in many ways, except that the United Kingdom has plurality elections and single‐party government, while the Netherlands has proportional representation (PR) and coalition government. This provides the first application of the Macro Polity approach to a country with PR elections. We find that government policy in the Netherlands is highly responsive to public opinion. This cannot be the result of alternation of government, but instead must be the result of some other process, such as coalition bargaining. In the United Kingdom, however, the dynamic of adjustment is far more complex. Alternation of government does not produce responsiveness, but rather seems to get in the way of it. This leads to an over‐correction dynamic in which policy can be out of line with public opinion for long periods of time.
Natural history and burden of Huntington's disease in the UK: A population‐based cohort study
Authors: Furby Hannah , Siadimas Athanasios , Rutten‐Jacobs Loes , Rodrigues Filipe B. , Wild Edward J.
Published: May 2022

Background

Huntington's disease (HD) is a rare neurodegenerative disease that presents with progressive psychological, cognitive and motor impairment. These diverse symptoms place a high burden on the patient, families and the healthcare systems they rely on. This study aimed to describe the epidemiology and clinical burden in individuals with HD compared with controls from the general population.

Methods

This cohort study utilised data from general practitioner medical records to estimate the prevalence and incidence of HD between January 2000 and December 2018. A cohort of incident HD cases were matched 1:3 to controls from the general population, in whom common clinical diagnoses, medications and healthcare interventions were compared at the time of first recorded diagnosis and at a time close to death. Incidence rates of common diagnoses and mortality were compared with matched controls in the time following HD diagnosis.

Results

Prevalence of HD increased between 2000 and 2018, whilst incidence remained stable. Prevalence of psychiatric diagnoses and symptomatic treatments were higher in HD cases than controls. A higher relative risk of psychotic disorders, depression, insomnia, dementia, weight loss, pneumonia and falls was observed in HD cases. Risk of death was >4 times higher in HD, with a median survival of ~12 years from first recorded diagnosis.

Conclusions

This study demonstrates the significant and progressive clinical burden in individuals with HD up to 18 years after first recorded diagnosis.
Conditioned serum in vitro treatment of chondrocyte pellets and osteoarthritic explants
Authors: Löfgren Maria , Ekman Stina , Ekholm Josefine , Engström Mona , Fjordbakk Cathrine T. , Svala Emilia , Holm Forsström Karin , Lindahl Anders , Skiöldebrand Eva
Published: May 2022

Background

Autologous conditioned serum (ACS) is used to treat osteoarthritis in horses, although its effects are not fully investigated.

Objectives

To investigate the effects of equine serum and conditioned serum on chondrocytes stimulated with interleukin (IL)‐1β and cartilage explants with mild osteoarthritis.

Study design

In vitro experimental study.

Methods

The effect of three different serum preparations (unincubated control [PS], serum incubated 24 h [PS24h] and serum incubated 24 h in ACS containers [PCS]) pooled from lame horses were tested in two in vitro models. IL‐1β and IL‐1 receptor antagonist (IL‐1Ra) concentrations were measured in all sera. In model 1, chondrocyte pellet cultures were stimulated with IL‐1β prior to treatment with the serum preparations for 2 and 48 h. Microarray, polymerase chain reaction, and matrix metallopeptidase‐13 analyses were performed. In model 2, cartilage explants from horses with structural osteoarthritis were treated with PS or PCS on days 0, 6 and 12, or left untreated, and evaluated at day 24 using the OARSI grading scale for histological evaluation of articular cartilage.

Results

The IL‐1Ra concentration in PS24h and PCS was significantly higher than in PS. In model 1, inflammation‐ and cartilage matrix degradation‐related genes were upregulated after 48 h in all treatment groups versus untreated controls. Cartilage matrix molecules, aggrecan and collagens, were downregulated in PS24h‐ and PCS‐treated pellets versus untreated controls. Growth factor signalling genes were upregulated—FGF7 in all treatment groups, BMP2 in PS24h‐, and INHBA in PCS‐treated—compared with untreated controls. In model 2, the OARSI score at day 24 was not significantly different between treatment groups.

Main limitations

Results from in vitro models cannot be directly translated to in vivo situations.

Conclusions

In vitro treatment with conditioned serum did not alleviate IL‐1β‐induced responses in chondrocyte pellets or lead to morphological improvement in osteoarthritic cartilage explants.
Modulation of mitochondrial dynamics rescues cognitive function in rats with ‘doxorubicin‐induced chemobrain’ via mitigation of mitochondrial dysfunction and neuroinflammation
Authors: Ongnok Benjamin , Maneechote Chayodom , Chunchai Titikorn , Pantiya Patcharapong , Arunsak Busarin , Nawara Wichwara , Chattipakorn Nipon , Chattipakorn Siriporn C.
Published: May 2022

Doxorubicin (DOX), an effective, extensively used chemotherapeutic drug, can cause cognitive deterioration in cancer patients. The associated debilitating neurological sequelae are referred to as chemobrain. Our recent work demonstrated that Dox treatment resulted in an imbalance in mitochondrial dynamics, ultimately culminating in cognitive decline in rats. Therefore, in this study, we aim to explore the therapeutic efficacy of a pharmacological intervention, which modulates mitochondrial dynamics using a potent mitochondrial fission inhibitor (Mdivi‐1) and mitochondrial fusion promoter (M1) against Dox‐induced chemobrain. In the study, male Wistar rats were randomly assigned to receive either normal saline solution or six doses of Dox (3 mg·kg−1) via intraperitoneal injection. Then, the Dox‐treated rats were intraperitoneally given either 1% DMSO as the vehicle, Mdivi‐1 (1.2 mg·kg−1), M1 (2 mg·kg−1), or a combined treatment of Mdivi‐1 and M1 for 30 consecutive days. Long‐term learning and memory were evaluated using the novel object location task and novel object recognition task. Following euthanasia, the rat brains were dissected to enable further molecular investigation. We demonstrated that long‐term treatment with mitochondrial dynamic modulators suppressed mitochondrial fission in the hippocampus following Dox treatment, leading to an improvement in brain homeostasis. Mitochondrial dynamic modulator treatments restored cognitive function in Dox‐treated rats by attenuating neuroinflammation, decreasing oxidative stress, preserving synaptic integrity, reducing potential Alzheimer's related lesions, and mitigating both apoptosis and necroptosis following Dox administration. Together, our findings suggested that mitochondrial dynamics modulators protected against Dox‐induced cognitive impairment by rebalancing mitochondrial homeostasis and attenuating both oxidative and inflammatory insults.
Inclusion orientation dependent flaking process in rolling contact fatigue observed by laminography using ultrabright synchrotron radiation X‐ray
Authors: Nakai Yoshikazu , Shiozawa Daiki , Kikuchi Shoichi , Saito Hitoshi , Nishina Takashi , Kobayashi Hiroshi , Makino Taizo , Neishi Yutaka
Published: May 2022

The formation and propagation of cracks in rolling contact fatigue were observed by synchrotron radiation computed laminography, and the effect of stringer‐type inclusion orientation was examined. For longitudinal inclusions, cracks started forming at their tips. After cracks propagated toward the rolling direction, a longitudinal crack was kinked simultaneously at both its tips, and propagated toward the direction perpendicular to the rolling direction to form lateral cracks. After kinking, horizontal cracks were formed from the deepest point of a lateral crack, leading to flaking. On the other hand, for specimens with lateral inclusions, cracks propagated to the lateral direction without the formation of longitudinal cracks. Since the propagation life of lateral cracks and that of horizontal cracks were unrelated to the inclusion orientation, the rolling contact fatigue life of specimens with longitudinal inclusions was considerably longer than that of specimens with lateral inclusions.
Proficiency development and smartphone usage in study abroad: Microgenetic longitudinal case studies of French learners
Authors: Mroz Aurore P. , Thrasher Tricia
Published: May 2022

This longitudinal study explores how the language proficiency of eight (N = 8) US‐affiliated university students developed relative to their smartphone usage during study abroad (SA) in Paris. Phone usage was tracked daily withSpace, proficiency weekly using NCSSFL‐ACTFL Can‐Do statements, and language use monthly via a Language Engagement Questionnaire. Adopting a Complex Dynamic Systems Theory (CDST) framework and following a microgenetic approach to case studies, the trajectories of each participant's phone consumption and Can‐Do statements were established, allowing to visualize floors, ceilings, and probes in proficiency development. Spearman's correlations served to determine whether and how phone usage related to fluctuations in proficiency, and Kendall's tau‐b its link with language used. Findings revealed that these relationships varied widely across participants, types of phone usage, and phone applications, with students displaying positive, mixed, or negative relationships, thus suggesting that there is no one‐size‐fits‐all model to proficiency/smartphone management, but idiosyncratic complex cases.
Gene therapy – are we ready now?
Authors: Kaczmarek Radoslaw
Published: May 2022

Introduction

Haemophilia therapy has evolved from rudimentary transfusion‐based approaches to an unprecedented level of innovation with glimmers of functional cure brought by gene therapy. After decades of misfires, gene therapy has normalized factor (F)VIII and factor (F)IX levels in some individuals in the long term. Several clinical programmes testing adeno‐associated viral (AAV) vector gene therapy are approaching completion with imminent regulatory approvals.

Discussion

Phase 3 studies along with multiyear follow‐up in earlier phase investigations raised questions about efficacy as well as short‐ and long‐term safety, prompting a reappraisal of AAV vector gene therapy. Liver toxicities, albeit mostly low‐grade, occur in the first year in at least some individuals in all haemophilia A and B trials and are poorly understood. Extreme variability and unpredictability of outcome, as well as a slow decline in factor expression (seemingly unique to FVIII gene therapy), are vexing because immune responses to AAV vectors preclude repeat dosing, which could increase suboptimal or restore declining expression, while overexpression may result in phenotoxicity. The long‐term safety will need lifelong monitoring because AAV vectors, contrary to conventional wisdom, integrate into chromosomes at the rate that calls for vigilance.

Conclusions

AAV transduction and transgene expression engage the host immune system, cellular DNA processing, transcription and translation machineries in ways that have been only cursorily studied in the clinic. Delineating those mechanisms will be key to finding mitigants and solutions to the remaining problems, and including individuals who cannot avail of gene therapy at this time.
von Willebrand disease and von Willebrand factor
Authors: Sadler Brooke , Castaman Giancarlo , O'Donnell James S.
Published: May 2022

Progress in both basic and translational research into the molecular mechanisms of VWD can be seen in multiple fields.

Genetics of VWD

In the past several decades, knowledge of the underlying pathogenesis of von Willebrand disease (VWD) has increased tremendously, thanks in no small part to detailed genetic mapping of the von Willebrand Factor (VWF) gene and advances in genetic and bioinformatic technology. However, these advances do not always easily translate into improved management for patients with VWD and low‐VWF levels.

VWD and pregnancy

For example, the treatment of pregnant women with VWD both pre‐ and postpartum can be complicated. While knowledge of the VWF genotype at some amino acid positions can aid in knowledge of who may be at increased risk of thrombocytopenia or insufficient increase in VWF levels during pregnancy, in many cases, VWF levels and bleeding severity is highly heterogeneous, making monitoring recommended during pregnancy to optimize treatment strategies.

VWF and COVID‐19

New challenges related to the consequences of dysregulation of hemostasis continue to be discovered. The ongoing COVID‐19 pandemic has highlighted that VWF has additional biological roles in the regulation of inflammatory disorders and angiogenesis, disruption of which may contribute to COVID‐19 induced vasculopathy. Increased endothelial cell activation and Weibel‐Palade body exocytosis in severe COVID‐19 lead to markedly increased plasma VWF levels. Coupled with impairment of normal ADAMTS13 multimer regulation, these data suggest a role for VWF in the pathogenesis underlying pulmonary microvascular angiopathy in severe COVID‐19.

Conclusion

With the increased affordability and availability of next‐generation sequencing techniques, as well as a push towards a multi‐omic approach and personalized medicine in human genetics, there is hope that translational research will improve VWD patient outcomes.
The relation of climate change denial with benevolent and hostile sexism
Authors: Nicol Adelheid A. M. , De France Kalee , Mayrand Nicol Ariane
Published: May 2022

Ecofeminism purports that sexist ideology and climate change denial are related, as prejudice, and its desire for power and nonuniversalism, create a disregard for both. In three studies we examined the associations between hostile and benevolent sexism with climate change denial. The first study (n = 270) demonstrated that hostile sexism explained unique variance in climate change denial over and above two strong predictors of prejudice and climate change denial, social dominance orientation and right‐wing authoritarianism. The second study (n = 294) reports on the significant indirect effects of willingness to make sacrifices for the environment on the relation between hostile/benevolent sexism and climate change denial. The third and final study (n = 514) found significant indirect effects of hostile and benevolent sexism, as well as willingness to make sacrifices for the environment, on the relation between power and climate change denial. Universalism demonstrated direct effects with climate change denial when benevolent sexism and willingness to make sacrifices for the environment were taken into account; direct and indirect effects were found when hostile sexism and willingness to make sacrifices for the environment were considered. Our findings provide support for a strong relation between hostile sexism and climate change denial and suggest underlying psychological processes that may represent paths through which climate change attitudes could be indirectly modified.
BMAT's predictive validity for medical school performance: A retrospective cohort study
Authors: Davies Daniel J. , Sam Amir H. , Murphy Kevin G. , Khan Shahid A. , Choe Ruth , Cleland Jennifer
Published: May 2022

Background

Although used widely, there is limited evidence of the BioMedical Admissions Test's (BMAT) predictive validity and incremental validity over prior educational attainment (PEA). We investigated BMAT's predictive and incremental validity for performance in two undergraduate medical schools, Imperial College School of Medicine (ICSM), UK, and Lee Kong Chian School of Medicine (LKCMedicine), Singapore. Our secondary goal was to compare the evidence collected with published evidence relating to comparable tools.

Methods

This was a retrospective cohort study of four ICSM (1188 students, entering 2010–2013) and three LKCMedicine cohorts (222 students, 2013–2015). We investigated associations between BMAT Section 1 (‘Thinking Skills’), Section 2 (‘Scientific Knowledge and Applications’) and Section 3a (‘Writing Task’) scores, with written and clinical assessment performance across all programme years. Incremental validity was investigated over PEA (A‐levels) in a subset of ICSM students.

Results

When BMAT sections were investigated independently, Section 2 scores predicted performance on all written assessments in both institutions with mainly small effect sizes (standardised coefficient ranges: ICSM: 0.08–0.19; LKCMedicine: 0.22–0.36). Section 1 scores predicted Years 5 and 6 written assessment performance at ICSM (0.09–0.14) but nothing at LKCMedicine. Section 3a scores only predicted Year 5 clinical assessment performance at ICSM with a coefficient <0.1. There were no positive associations with standardised coefficients >0.1 between BMAT performance and clinical assessment performance. Multivariable regressions confirmed that Section 2 scores were the most predictive. We found no clear evidence of incremental validity for any BMAT section scores over A‐level grades.

Discussion

Schools who wish to assess scientific knowledge independently of A‐levels may find BMAT Section 2 useful. Comparison with previous studies indicates that, overall, BMAT seems less useful than comparable tools. Larger scale studies are needed. Broader questions regarding why institutions adopt certain admissions tests, including those with little evidence, need consideration.
Temporal variation of high‐level pyrethroid resistance in the major malaria vector Anopheles gambiae s.l. in Yaoundé, Cameroon, is mediated by target‐site and metabolic resistance
Authors: Tene‐Fossog Billy , Fotso‐Toguem Yvan Gaetan , Amvongo‐Adjia Nathalie , Ranson Hilary , Wondji Charles S.
Published: May 2022

Constant assessment of insecticide resistance levels is mandatory to implement adequate malaria control tools, but little information is available on the annual dynamics of resistance. We, therefore, monitored variations in resistance in Anopheles gambiae s.l. over four seasons during 2 years in two localities of Yaoundé: urban Etoa‐Meki and peri‐urban Nkolondom. Mosquitoes were collected seasonally at larval stage and reared to adults for insecticide susceptibility tests and molecular analysis of resistance mechanisms. Anopheles coluzzii was found in Etoa‐Meki and An. gambiae in Nkolondom. Low mortalities to pyrethroids were observed (permethrin <10%, deltamethrin <21%), and resistance extended to 5× and 10× diagnostic doses, revealing a marked increase compared to previous studies. A seasonal variation in resistance was observed with the highest levels within dry seasons in Etoa‐Meki and rainy seasons in Nkolondom. The 1014F kdr allele shows a high frequency (0.9), associated with overexpression of metabolic genes (Cyp6M2, Cyp6P4, Cyp9K1, Cyp6Z1, and Cyp6Z2) varying significantly seasonally. This study reveals an escalation in resistance to pyrethroids in Yaoundé's malaria vectors with seasonal variations. An adequate choice of the implementation period of punctual vector control actions according to the resistance profile will help to potentiate the desired effect and thus improve its efficiency.
The common triggers of urticaria in children admitted to the pediatric emergency room
Authors: Bezirganoglu Handan , Arik Yilmaz Ebru , Sahiner Umit M. , Soyer Ozge , Sekerel Bulent E. , Teksam Ozlem , Buyuktiryaki Betul , Sackesen Cansin
Published: May 2022

Background

Urticaria frequently causes pediatric emergency department (PED) admissions. Children with urticaria may unnecessarily avoid suspected allergens. We aimed to investigate the possible and exact triggers of urticaria in children admitted to the PED.

Methods

Medical records of children admitted to the PED within a 1‐year period were evaluated for the International Classification of Diseases 10 (ICD‐10) L50 urticaria code, noting symptoms, and possible triggers of urticaria. We performed telephone interviews to complete the missing data and further diagnostic tests for IgE‐mediated allergies to identify the exact triggers of urticaria.

Results

Among 60,142 children, 462 (0.8%) with the L50 code were evaluated. Possible triggers based on the history and physical examination could be identified in 46%: infections (18%), drugs (11%), foods (8%), infections and drugs (3%), insects (3%), pollen (1%), blood products (0.4%), and vaccines (0.4%). The most frequent infections related to urticaria were upper respiratory tract infections (74.5%), urinary tract infections (13.2%), gastroenteritis (8.2%), and otitis media (4.1%). After a diagnostic workup, IgE‐mediated allergic diseases were diagnosed in 6% of patients. Twenty‐two percent of the patients had multiple PED admission for the same urticaria flare. Urticaria severity was found to be the most important risk factor for readmissions to the PED (odds ratio: 3.86; 95% confidence interval: 2.39–6.23; p < .001). No relationship between urticaria severity, duration, and the triggers was present.

Conclusions

Despite detailed diagnostic tests, IgE‐mediated allergic triggers were rarely the cause of urticaria in children admitted to the PED. Infections are the most frequent trigger. Severe urticaria causes more frequent readmissions to the PED.
Genomic full‐length sequence of the HLA‐A*02:406 allele was identified by full‐length group‐specific sequencing
Authors: An Run , Hu Bin , Jiao Shuxian , Pang Shutao
Published: May 2022

Genomic full‐length sequence of HLA‐A*02:406 was identified by group‐specific sequencing in a Chinese individual.
Dynamically expressed small RNAs, substantially driven by genomic structural variants, contribute to transcriptomic changes during tomato domestication
Authors: Qing You , Zheng Yi , Mlotshwa Sizolwenkosi , Smith Heather N. , Wang Xin , Zhai Xuyang , van der Knaap Esther , Wang Ying , Fei Zhangjun
Published: May 2022

Tomato has undergone extensive selections during domestication. Recent progress has shown that genomic structural variants (SVs) have contributed to gene expression dynamics during tomato domestication, resulting in changes of important traits. Here, we performed comprehensive analyses of small RNAs (sRNAs) from nine representative tomato accessions. We demonstrate that SVs substantially contribute to the dynamic expression of the three major classes of plant sRNAs: microRNAs (miRNAs), phased secondary short interfering RNAs (phasiRNAs), and 24‐nucleotide heterochromatic siRNAs (hc‐siRNAs). Changes in the abundance of phasiRNAs and 24‐nucleotide hc‐siRNAs likely contribute to the alteration of mRNA gene expression in cis during tomato domestication, particularly for genes associated with biotic and abiotic stress tolerance. We also observe that miRNA expression dynamics are associated with imprecise processing, alternative miRNA‐miRNA* selections, and SVs. SVs mainly affect the expression of less‐conserved miRNAs that do not have established regulatory functions or low abundant members in highly expressed miRNA families. Our data highlight different selection pressures on miRNAs compared to phasiRNAs and 24‐nucleotide hc‐siRNAs. Our findings provide insights into plant sRNA evolution as well as SV‐based gene regulation during crop domestication. Furthermore, our dataset provides a rich resource for mining the sRNA regulatory network in tomato.
Platelet transfusions in a murine model of neonatal polymicrobial sepsis: Divergent effects on inflammation and mortality
Authors: Davenport Patricia , Fan Hsuan‐Hao , Nolton Emily , Feldman Henry A. , Lorenz Viola , Canas Jorge , Acosta‐Zaldívar Maikel , Yakah William , Arthur Connie , Martin Camilia , Stowell Sean , Koehler Julia , Mager Donald , Sola‐Visner Martha
Published: May 2022

Background

Platelet transfusions (PTxs) are often given to septic preterm neonates at high platelet count thresholds in an attempt to reduce bleeding risk. However, the largest randomized controlled trial (RCT) of neonatal transfusion thresholds found higher mortality and/or major bleeding in infants transfused at higher thresholds. Using a murine model, we investigated the effects of adult PTx on neonatal sepsis‐induced mortality, systemic inflammation, and platelet consumption.

Study design and methods

Polymicrobial sepsis was induced via intraperitoneal injection of cecal slurry preparations (CS1, 2, 3) into P10 pups. Two hours after infection, pups were transfused with washed adult Green Flourescent Protein (GFP+) platelets or control. Weights, platelet counts, and GFP% were measured before 4 and 24 h post‐infection. At 24 h, blood was collected for quantification of plasma cytokines.

Results

The CS batches varied in 24 h mortality (11%, 73%, and 30% in CS1, 2, and 3, respectively), due to differences in bacterial composition. PTx had differential effects on sepsis‐induced mortality and systemic inflammatory cytokines, increasing both in mice infected with CS1 (low mortality) and decreasing both in mice infected with CS2 and 3. In a mathematical model of platelet kinetics, the consumption of transfused adult platelets was higher than that of endogenous neonatal platelets, regardless of CS batch.

Discussion

Our findings support the hypothesis that transfused adult platelets are consumed faster than endogenous neonatal platelets in sepsis and demonstrate that PTx can enhance or attenuate neonatal inflammation and mortality in a model of murine polymicrobial sepsis, depending on the composition of the inoculum and/or the severity of sepsis.
Material Selection and Corrosion Studies of Candidate Bearing Materials for Use in Molten Chloride Salt
Authors: Keiser James R. , He Xin , Sulejmanovic Dino , Qu Jun , Robb Kevin R. , Oldinski Keith
Published: May 2022

Molten chloride salts are being given strong consideration for use in heat transfer and storage in concentrating solar power (CSP) systems as well as in some nuclear reactor applications. Containment of the molten salt, particularly at the highest temperatures, is a major material concern and has received considerable study. Another material issue is the pumps that will be required to move the molten salt along with the bearing materials that will be required to have sufficient corrosion resistance as well as wear resistance in the high temperature salt. A pair of coordinated studies in our laboratory has addressed the corrosion, and the wear issues of candidate bearing materials including the selection of candidate materials as well as their performance in a molten sodium chloride-potassium chloride-magnesium chloride salt environment. This article addresses the selection of candidate materials and their chemical compatibility with the molten salt. The studies have identified material pairs that have suitable properties for use as bearings that would be immersed in molten chloride salt.
Molecular characterization of trichlorfon resistance in bovine ticks Boophilus microplus collected from two ecological zones of Khyber Pakhtunkhwa, Pakistan
Authors: Qasim Muhammad , Abdul Hafeez Mian , Ahmad Nisar , Ahmad Anjum Aftab , Oneeb Muhammad
Published: May 2022

Boophilus microplus, an ectoparasite of bovines has immense importance in South Asian countries like Pakistan. These are cosmopolitans and affect cattle herds drastically worldwide and are involved in direct and indirect harm to the bovine species. In this regard, trichlorfon is widely used to control ticks in bovines along with its sprays to control different pests, which leads to resistance in ticks against these acaricides in different parts of the world. Therefore, the present study aims to investigate the resistance and prevailing genomic mutations in Boophilus microplus ticks against trichlorfon. Molecular characterization was carried out and heterozygous mutations were observed in the adult tick samples collected from two different zones of the Khyber Pakhtunkhwa (KPK) province of Pakistan. After the identification of ticks, in vitro studies were performed which showed resistance in ticks against trichlorfon drug. To assess genomic mutation in the samples, DNA was extracted through a kit, and PCR was performed to evaluate the mutation in the samples. After in-vitro studies, almost 104 (54%) ticks samples were found resistant and run through PCR in which 3 and 4 samples from zone-I and zone-II, were identified mutated while the remaining samples were found non-mutated. Boophilus microplus acetylcholinesterase genes were sequenced and compared with the control group. All these findings suggest a continuous monitoring of heterozygous mutations in the Boophilus microplus ticks and the strategic application of trichlorfon against Boophilus microplus ticks, to enable improvement in drug efficacy and tick control strategies.
Early sum frequency generation vibrational spectroscopic studies on peptides and proteins at interfaces
Authors: Chen Zhan
Published: May 2022

This paper summarizes the early research results on studying proteins and peptides at interfaces using sum frequency generation (SFG) vibrational spectroscopy. SFG studies in the C—H stretching frequency region to examine the protein side-chain behavior and in the amide I frequency region to investigate the orientation and conformation of interfacial peptides/proteins are presented. The early chiral SFG research and SFG isotope labeling studies on interfacial peptides/proteins are also discussed. These early SFG studies demonstrate the feasibility of using SFG to elucidate interfacial molecular structures of peptides and proteins in situ, which built a foundation for later SFG investigations on peptides and proteins at interfaces.
Real-time atmospheric effects on sound propagation for a simulated outdoor concert
Authors: Woolworth David s.
Published: May 2022

Outdoor live sound is best controlled at the sound source; computer simulation tools are available to estimate impact of concerts on nearby communities using methods such as NORD 2000, ISO 9613-2, and CNOSSOS. These methods utilize generalized temperature gradients and wind speed profiles up to 100 m and can be useful and somewhat accurate up to 3 miles, after which higher level atmospheric effects takeover. This paper will provide some examples of long rang propagation due to higher level atmospheric effects, compare 3 mile radius modeling to real-time measurements and examine some of the fluctuations over a 2-h simulated concert with changing weather conditions and programming.
Development of deep neural networks for marine mammal call detection using an open-source, user friendly tool
Authors: Ferguson Elizabeth L. , Sugarman Peter , Coffey Kevin R. , Pettis Schallert Jennifer , Alongi Gabriela C.
Published: May 2022

As the collection of large acoustic datasets used to monitor marine mammals increases, so too does the need for expedited and reliable detection of accurately classified bioacoustic signals. Deep learning methods of detection and classification are increasingly proposed as a means of addressing this processing need. These image recognition and classification methods include the use of a neural networks that independently determine important features of bioacoustic signals from spectrograms. Recent marine mammal call detection studies report consistent performance even when used with datasets that were not included in the network training. We present here the use of DeepSqueak, a novel open-source tool originally developed to detect and classify ultrasonic vocalizations from rodents in a low-noise, laboratory setting. We have trained networks in DeepSqueak to detect marine mammal vocalizations in comparatively noisy, natural acoustic environments. DeepSqueak utilizes a regional convolutional neural network architecture within an intuitive graphical user interface that provides automated detection results independent of acoustician expertise. Using passive acoustic data from two hydrophones on the Ocean Observatories Initiative’s Coastal Endurance Array, we developed networks for humpback whales, delphinids, and fin whales. We report performance and limitations for use of this detection method for each species.
INSTINCT: The infrastructure for noise and soundscape tolerant investigation of nonspecific call types
Authors: Woodrich Daniel F.
Published: May 2022

INSTINCT is open-source, command line software for custom data pipelines, developed by the NOAA’s Alaska Fisheries Science Center to formalize AI workflows for passive acoustic monitoring (PAM) of sounds produced by marine mammals and to provide a framework for new algorithm development. INSTINCT is built in Python over the Luigi framework and was designed to be lightweight and Window/Linux compatible. To promote collaboration, the software is partitioned into a core module and organization-governed submodules. The original INSTINCT detection and classification algorithm has been applied to various Alaska region cetacean species and presents a powerful CPU-based approach for those seeking to train, evaluate, and deploy a generalized detector. Furthermore, INSTINCT pipelines are in development to train and deploy GPU-based algorithms, structure annotation workflows, and pioneer complex workflows. Case studies will be presented to highlight the existing capabilities of the software and new workflows that are currently being explored. This talk will also cover design philosophy, technical specifications, and instructions for implementation. Although INSTINCT continues to progress at AFSC, it will benefit greatly from a larger network of collaborators, and ideally, will give back to the community via innovation of new AI approaches in PAM.
Parselmouth for bioacoustics: Integrating Praat into the Python scientific ecosystem
Authors: Jadoul Yannick , Duengen Diandra , Ravignani Andrea
Published: May 2022

As collected datasets become larger and computational analyses become ever more complex, the efficient processing of bioacoustical data is a crucial problem to tackle. Often, during data exploration and analysis, different research software packages need to be flexibly combined in a script. A typical example of such a multi-faceted workflow is the extraction of acoustic parameters from a recording, which are then plotted and tested for statistical significance. Parselmouth is an open-source Python library for Praat, a widely used acoustics and phonetics software package implementing acoustic algorithms and analyses regularly adopted in bioacoustics research. Parselmouth's goal is to provide a full-fledged Python library that integrates efficiently into the larger Python ecosystem. This way, it not only simplifies the application of Praat’s functionality within a typical data analysis workflow but also enables the creation of new experimental tools. Parselmouth’s contribution to bioacoustics research can be highlighted through concrete examples of studies we have conducted, e.g., on vocal flexibility in seals. Moreover, the integration of Praat’s functionality into a general-purpose programming language allows for novel, more complex experimental setups: for example, the integration of Parselmouth into a custom-created software tool permits live-monitoring and instantly evaluating the vocal development during animal training.
Parselmouth for bioacoustics: Analysis pipelines for seal vocalizations
Authors: Ravignani Andrea , Torres Borda Laura , Rasilo Heikki , Salazar Casals Anna , Jadoul Yannick
Published: May 2022

Every empirical research project includes bottlenecks at various levels. In bioacoustics, one of these time-consuming bottlenecks corresponds to the step of transforming a long stream of audio into acoustic properties of specific sounds. Here, we describe a data-extraction pipeline which integrates manual annotation with Parselmouth’s powerful computational analyses. This semi-supervised method allows extracting a large volume of sound features with limited repetitive human “point and click.” We illustrate this using recently published empirical research, where we focused on vocal production learning and plasticity in pinnipeds. Faced with a species capable of imitating sounds, fully automatic methods may misclassify individuals (because of imitation), while the large number of calls make fully manual approaches suboptimal and error-prone. Focusing on early vocal development, we tested 1–3 weeks-old harbor seal pups (Phoca vitulina). Noise playbacks served to induce seal pups to shift their fundamental frequency. Pups' spontaneous calls were recorded while exposed to bandpass-filtered noise, which spanned and masked the animals’ fundamental frequency range. After a summary manual annotation of calls’ boundaries, Parselmouth identified these boundaries in the files, and automatically extracted multiple sound parameters. Based on this, we found that pups modified their vocalizations by lowering their fundamental frequency in response to noise.