bluuebunny/crossref_metadata_2025 huggingface dataset:
Rh alloimmunization in chronically transfused patients with thalassemia receiving RhD, C, E, and K matched transfusions
Authors: Waldis Sarah J. , Uter Stacey , Kavitsky Donna , Flickinger Cynthia , Vege Sunitha , Friedman David F. , Westhoff Connie M. , Chou Stella T.
Published: February 2021

Chronically transfused patients with thalassemia are at risk for red cell alloimmunization. No studies have specifically examined alloimmunization after implementation of prophylactic Rh (D, C, E) and K matched red cells in a racially diverse population of thalassemia patients and donors. This retrospective study examined Rh antibodies among 40 chronically transfused patients (Asian, White, Black, Indian, Middle Eastern) with thalassemia receiving a mean of 174 serologic prophylactic RhD, C, E, and K matched red cell units. We examined the patients’ RH genotype, as well as donor race and Rh phenotypes over 3 transfusion events preceding antibody detection. Eighteen alloantibodies were detected in 13 of 40 patients (32.5%), with an alloimmunization rate of 0.26 antibodies per 100 units transfused. Thirteen antibodies (72.2%) were directed against Rh (5 anti-D, 4 anti-C, 2 anti-E, 1 anti-e, 1 anti-V), despite donor phenotypes that confirmed lack of transfusion of D, C, or E antigens to patients lacking the corresponding antigen(s). Ten of 40 patients had an altered RH genotype, but the Rh antibodies were not associated with patients with variant RH. Black donors with a known high frequency of RH variants provided 63% of the units transfused in the 3 visits preceding unexplained anti-Rh detection. Rh alloimmunization not explained by the thalassemia patients’ RH genotype or the donors’ serologic phenotype suggests more precise matching is needed, and the role of donor RH genotypes on alloimmunization should be explored. Extending Rh D, C, and E matching to include c and e would result in better-matched units and further minimize Rh alloimmunization.
Optimising pyrazinamide for the treatment of tuberculosis
Authors: Zhang Nan , Savic Radojka M. , Boeree Martin J. , Peloquin Charles A. , Weiner Marc , Heinrich Norbert , Bliven-Sizemore Erin , Phillips Patrick P.J. , Hoelscher Michael , Whitworth William , Morlock Glenn , Posey James , Stout Jason E. , Mac Kenzie William , Aarnoutse Robert , Dooley Kelly E.
Published: February 2021

Pyrazinamide is a potent sterilising agent that shortens the treatment duration needed to cure tuberculosis. It is synergistic with novel and existing drugs for tuberculosis. The dose of pyrazinamide that optimises efficacy while remaining safe is uncertain, as is its potential role in shortening treatment duration further.

Pharmacokinetic data, sputum culture, and safety laboratory results were compiled from Tuberculosis Trials Consortium (TBTC) studies 27 and 28 and Pan-African Consortium for the Evaluation of Antituberculosis Antibiotics (PanACEA) multi-arm multi-stage tuberculosis (MAMS-TB), multi-centre phase 2 trials in which participants received rifampicin (range 10–35 mg·kg−1), pyrazinamide (range 20–30 mg·kg−1), plus two companion drugs. Pyrazinamide pharmacokinetic–pharmacodynamic (PK–PD) and pharmacokinetic-toxicity analyses were performed.

In TBTC studies (n=77), higher pyrazinamide maximum concentration (Cmax) was associated with shorter time to culture conversion (TTCC) and higher probability of 2-month culture conversion (p-value<0.001). Parametric survival analyses showed that relationships varied geographically, with steeper PK–PD relationships seen among non-African than African participants. In PanACEA MAMS-TB (n=363), TTCC decreased as pyrazinamide Cmaxincreased and varied by rifampicin area under the curve (p-value<0.01). Modelling and simulation suggested that very high doses of pyrazinamide (>4500 mg) or increasing both pyrazinamide and rifampicin would be required to reach targets associated with treatment shortening. Combining all trials, liver toxicity was rare (3.9% with grade 3 or higher liver function tests (LFT)), and no relationship was seen between pyrazinamide Cmaxand LFT levels.

Pyrazinamide's microbiological efficacy increases with increasing drug concentrations. Optimising pyrazinamide alone, though, is unlikely to be sufficient to allow tuberculosis treatment shortening; rather, rifampicin dose would need to be increased in parallel.
Genome-wide association study in patients with pulmonaryMycobacterium aviumcomplex disease
Authors: Namkoong Ho , Omae Yosuke , Asakura Takanori , Ishii Makoto , Suzuki Shoji , Morimoto Kozo , Kawai Yosuke , Emoto Katsura , Oler Andrew J. , Szymanski Eva P. , Yoshida Mitsunori , Matsuda Shuichi , Yagi Kazuma , Hase Isano , Nishimura Tomoyasu , Sasaki Yuka , Asami Takahiro , Shiomi Tetsuya , Matsubara Hiroaki , Shimada Hisato , Hamamoto Junko , Jhun Byung Woo , Kim Su-Young , Huh Hee Jae , Won Hong-Hee , Ato Manabu , Kosaki Kenjiro , Betsuyaku Tomoko , Fukunaga Koichi , Kurashima Atsuyuki , Tettelin Hervé , Yanai Hideki , Mahasirimongkol Surakameth , Olivier Kenneth N. , Hoshino Yoshihiko , Koh Won-Jung , Holland Steven M. , Tokunaga Katsushi , Hasegawa Naoki ,   the Nontuberculous Mycobacteriosis and Bronchiectasis – Japan Research Consortium (NTM-JRC)
Published: February 2021

Rationale

Nontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear.

Objectives

We aimed to identify host susceptibility loci forMycobacterium aviumcomplex (MAC), the most common NTM pathogen.

Methods

This genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping.

Results

The GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64×10−13, OR 0.54), which is in an intronic region of the calcineurin-like EF-hand protein 2 (CHP2). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. Additionally, this SNP was significantly associated with the disease in patients of Korean (p=2.18×10−12, OR 0.54) and European (p=5.12×10−03, OR 0.63) ancestry.

Conclusions

We identified rs109592 in theCHP2locus as a susceptibility marker for pulmonary MAC disease.
European Respiratory Society guidelines for the management of children and adolescents with bronchiectasis
Authors: Chang Anne B. , Fortescue Rebecca , Grimwood Keith , Alexopoulou Efthymia , Bell Leanne , Boyd Jeanette , Bush Andrew , Chalmers James D. , Hill Adam T. , Karadag Bulent , Midulla Fabio , McCallum Gabrielle B. , Powell Zena , Snijders Deborah , Song Woo-Jung , Tonia Thomy , Wilson Christine , Zacharasiewicz Angela , Kantar Ahmad
Published: February 2021

There is increasing awareness of bronchiectasis in children and adolescents, a chronic pulmonary disorder associated with poor quality of life for the child/adolescent and their parents, recurrent exacerbations, and costs to the family and health systems. Optimal treatment improves clinical outcomes. Several national guidelines exist, but there are no international guidelines.

The European Respiratory Society (ERS) Task Force for the management of paediatric bronchiectasis sought to identify evidence-based management (investigation and treatment) strategies. It used the ERS standardised methodology that included a systematic review of the literature and application of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to define the quality of the evidence and level of recommendations.

A multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, immunology, methodology, patient advocacy and parents of children/adolescents with bronchiectasis considered the most relevant clinical questions (for both clinicians and patients) related to managing paediatric bronchiectasis. 14 key clinical questions (seven PICO (Patient, Intervention, Comparison, Outcome) and seven narrative) were generated. The outcomes for each PICO were decided by voting by the panel and parent/patient advisory group.

This guideline addresses the definition, diagnostic approach and antibiotic treatment of exacerbations, pathogen eradication, long-term antibiotic therapy, asthma-type therapies (inhaled corticosteroids and bronchodilators), mucoactive drugs, airway clearance, investigation of underlying causes of bronchiectasis, disease monitoring, factors to consider before surgical treatment, and the reversibility and prevention of bronchiectasis in children/adolescents. Benchmarking quality of care for children/adolescents with bronchiectasis to improve clinical outcomes and evidence gaps for future research could be based on these recommendations.
Determinants of lung disease progression measured by lung clearance index in children with cystic fibrosis
Authors: Stanojevic Sanja , Davis Stephanie D. , Perrem Lucy , Shaw Michelle , Retsch-Bogart George , Davis Miriam , Jensen Renee , Clem Charles C. , Isaac Sarah M. , Guido Julia , Jara Sylvia , France Lisa , McDonald Nancy , Solomon Melinda , Sweezey Neil , Grasemann Hartmut , Waters Valerie , Sanders D.B. , Ratjen Felix A.
Published: February 2021

The lung clearance index (LCI) measured by the multiple breath washout (MBW) test is sensitive to early lung disease in children with cystic fibrosis. While LCI worsens during the preschool years in cystic fibrosis, there is limited evidence to clarify whether this continues during the early school age years, and whether the trajectory of disease progression as measured by LCI is modifiable.

A cohort of children (healthy and cystic fibrosis) previously studied for 12 months as preschoolers were followed during school age (5–10 years). LCI was measured every 3 months for a period of 24 months using the Exhalyzer D MBW nitrogen washout device. Linear mixed effects regression was used to model changes in LCI over time.

A total of 582 MBW measurements in 48 healthy subjects and 845 measurements in 64 cystic fibrosis subjects were available. The majority of children with cystic fibrosis had elevated LCI at the first preschool and first school age visits (57.8% (37 out of 64)), whereas all but six had normal forced expiratory volume in 1 s (FEV1) values at the first school age visit. During school age years, the course of disease was stable (−0.02 units·year−1(95% CI −0.14–0.10). LCI measured during preschool years, as well as the rate of LCI change during this time period, were important determinants of LCI and FEV1,at school age.

Preschool LCI was a major determinant of school age LCI; these findings further support that the preschool years are critical for early intervention strategies.
Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation
Authors: Busse William W. , Kraft Monica , Rabe Klaus F. , Deniz Yamo , Rowe Paul J. , Ruddy Marcella , Castro Mario
Published: February 2021

Asthma is a complex respiratory disease that varies in severity and response to treatment. Several asthma phenotypes with unique clinical and inflammatory characteristics have been identified. Endotypes, based on distinct molecular profiles, help to further elucidate the heterogeneity within asthma. Type 2 inflammation, involving both the innate (type 2 innate lymphoid cell) and adaptive (T-helper type 2 cells) immune systems, underpins the complex pathophysiology of chronic inflammation in asthma, as well as the presence of comorbid disease (e.g.chronic rhinosinusitis with nasal polyps, allergic rhinitis and atopic dermatitis). Type 2 inflammation is characterised by upregulation of the type 2 cytokines interleukin (IL)-4, IL-5 and IL-13, IgE-mediated release of immune mediators and dysfunction of epithelial or epidermal barriers. Targeting these key proximal type 2 cytokines has shown efficacy in recent studies adopting a personalised approach to treatment using targeted biologics. Elevated levels of biomarkers downstream of type 2 cytokines, including fractional exhaled nitric oxide, serum IgE and blood and sputum eosinophils, have been linked to mechanisms involved in type 2 inflammation. They have the potential to aid diagnosis, and to predict and monitor response to treatment. The objective of this review is to summarise the current understanding of the biology of type 2 inflammation in asthma, examine its influence on type 2 inflammatory comorbidities, and discuss how type 2 inflammatory biomarkers can be harnessed to further personalise treatments in the age of biologic medicines.
When things go wrong: exploring possible mechanisms driving the progressive fibrosis phenotype in interstitial lung diseases
Authors: Selman Moisés , Pardo Annie
Published: February 2021

Interstitial lung diseases (ILDs) comprise a large and heterogeneous group of disorders of known and unknown aetiology characterised by diffuse damage of the lung parenchyma. In recent years it has become evident that patients with different types of ILD are at risk of developing progressive pulmonary fibrosis, known as progressive fibrosing ILD (PF-ILD). This is a phenotype that behaves similar to idiopathic pulmonary fibrosis, the archetypical example of progressive fibrosis. PF-ILD is not a distinct clinical entity but describes a group of ILDs with similar clinical behaviour. This phenotype may occur in diseases displaying distinct aetiologies and different biopathology during their initiation and development. Importantly, these entities may have the potential for improvement or stabilisation prior to entering the progressive fibrosing phase. The crucial questions are: 1) why does a subset of patients develop a progressive and irreversible fibrotic phenotype even with appropriate treatment? and 2) what are the possible pathogenic mechanisms driving progression? Here, we provide a framework highlighting putative mechanisms underlying progression, including genetic susceptibility, ageing, epigenetics, structural fibrotic distortion, aberrant composition and stiffness of the extracellular matrix, and the emergence of distinct pro-fibrotic cell subsets. Understanding the cellular and molecular mechanisms behind PF-ILD will provide the basis for identifying risk factors and appropriate therapeutic strategies.
Nontuberculous mycobacterial pulmonary disease: an integrated approach beyond antibiotics
Authors: Faverio Paola , De Giacomi Federica , Bodini Bruno Dino , Stainer Anna , Fumagalli Alessia , Bini Francesco , Luppi Fabrizio , Aliberti Stefano
Published: February 2021

Nontuberculous mycobacterial (NTM) pulmonary disease (PD) is an emerging condition with heterogeneous manifestations from both the microbiological and the clinical point of view. Diagnostic and therapeutic guidelines are available but there are still unmet patients' and physicians' needs, including therapy-related adverse events, symptom control, management of comorbidities, risk of re-exposure to the pathogen and unfavourable outcomes.

In the present review, we provide currently available evidence for an integrated approach to NTM-PD beyond antibiotic therapy. This includes 1) avoiding exposure to environments where mycobacteria are present and careful evaluation of lifestyle and habits; 2) implementing a personalised pulmonary rehabilitation plan and airway clearance techniques to improve symptoms, exercise capacity, health-related quality of life (QoL) and functional capacity in daily living activities; 3) a nutritional evaluation and intervention to improve health-related QoL and to control gastrointestinal side-effects during antimicrobial therapy, particularly in those with low body mass index and history of weight loss; and 4) managing comorbidities that affect disease outcomes, including structural lung diseases, immune status evaluation and psychological support when appropriate.
Self-proning in COVID-19 patients on low-flow oxygen therapy: a cluster randomised controlled trial
Authors: Kharat Aileen , Dupuis-Lozeron Elise , Cantero Chloé , Marti Christophe , Grosgurin Olivier , Lolachi Sanaz , Lador Frédéric , Plojoux Jérôme , Janssens Jean-Paul , Soccal Paola M. , Adler Dan
Published: February 2021

Rationale and objectives

Prone positioning as a complement to oxygen therapy to treat hypoxaemia in coronavirus disease 2019 (COVID-19) pneumonia in spontaneously breathing patients has been widely adopted, despite a lack of evidence for its benefit. We tested the hypothesis that a simple incentive to self-prone for a maximum of 12 h per day would decrease oxygen needs in patients admitted to the ward for COVID-19 pneumonia on low-flow oxygen therapy.

Methods

27 patients with confirmed COVID-19 pneumonia admitted to Geneva University Hospitals were included in the study. 10 patients were randomised to self-prone positioning and 17 to usual care.

Measurements and main results

Oxygen needs assessed by oxygen flow on nasal cannula at inclusion were similar between groups. 24 h after starting the intervention, the median (interquartile range (IQR)) oxygen flow was 1.0 (0.1–2.9) L·min−1in the prone position group and 2.0 (0.5–3.0) L·min−1in the control group (p=0.507). Median (IQR) oxygen saturation/fraction of inspired oxygen ratio was 390 (300–432) in the prone position group and 336 (294–422) in the control group (p=0.633). One patient from the intervention group who did not self-prone was transferred to the high-dependency unit. Self-prone positioning was easy to implement. The intervention was well tolerated and only mild side-effects were reported.

Conclusions

Self-prone positioning in patients with COVID-19 pneumonia requiring low-flow oxygen therapy resulted in a clinically meaningful reduction of oxygen flow, but without reaching statistical significance.
Integrating Comprehensive Geriatric Assessment for people with COPD and frailty starting pulmonary rehabilitation: the Breathe Plus feasibility trial protocol
Authors: Brighton Lisa Jane , Evans Catherine J. , Farquhar Morag , Bristowe Katherine , Kata Aleksandra , Higman Jade , Ogden Margaret , Nolan Claire , Yi Deokhee , Gao Wei , Koulopoulou Maria , Hasan Sharmeen , Steves Claire J. , Man William D-C. , Maddocks Matthew
Published: February 2021

One in five people with COPD also lives with frailty. People living with both COPD and frailty are at increased risk of poorer health and outcomes, and face challenges to completing pulmonary rehabilitation. Integrated approaches that are adapted to the additional context of frailty are required.

The aim of the present study is to determine the feasibility of conducting a randomised controlled trial of an integrated Comprehensive Geriatric Assessment for people with COPD and frailty starting pulmonary rehabilitation.

This is a multicentre, mixed-methods, assessor-blinded, randomised, parallel group, controlled feasibility trial (“Breathe Plus”;ISRCTN13051922). We aim to recruit 60 people aged ≥50 with both COPD and frailty referred for pulmonary rehabilitation. Participants will be randomised 1:1 to receive usual pulmonary rehabilitation, or pulmonary rehabilitation with an additional Comprehensive Geriatric Assessment. Outcomes (physical, psycho-social and service use) will be measured at baseline, 90 days and 180 days. We will also collect service and trial process data, and conduct qualitative interviews with a sub-group of participants and staff. We will undertake descriptive analysis of quantitative feasibility outcomes (recruitment, retention, missing data, blinding, contamination, fidelity), and framework analysis of qualitative feasibility outcomes (intervention acceptability and theory, outcome acceptability). Recommendations on progression to a full trial will comprise integration of quantitative and qualitative data, with input from relevant stakeholders. This study has been approved by a UK Research Ethics Committee (ref.: 19/LO/1402).

This protocol describes the first study testing the feasibility of integrating a Comprehensive Geriatric Assessment alongside pulmonary rehabilitation, and testing this intervention within a mixed-methods randomised controlled trial.
Pulmonary haemodynamic response to exercise in highlandersversuslowlanders
Authors: Ulrich Silvia , Saxer Stéphanie , Furian Michael , Bader Patrick R. , Appenzeller Paula , Scheiwiller Philipp M. , Mademilov Maamed , Sheraliev Ulan , Tanner Felix , Sooronbaev Talantbek M. , Bloch Konrad E. , Lichtblau Mona
Published: February 2021

The aim of the study was to investigate the pulmonary haemodynamic response to exercise in Central Asian high- and lowlanders.

This was a cross-sectional study in Central Asian highlanders (living >2500 m) compared with lowlanders (living <800 m), assessing cardiac function, including tricuspid regurgitation pressure gradient (TRPG), cardiac index and tricuspid annular plane systolic excursion (TAPSE) by echocardiography combined with heart rate and oxygen saturation measured by pulse oximetry (SpO2) during submaximal stepwise cycle exercise (10 W increase per 3 min) at their altitude of residence (at 760 m or 3250 m, respectively).

52 highlanders (26 females; aged 47.9±10.7 years; body mass index (BMI) 26.7±4.6 kg·m−2; heart rate 75±11 beats·min−1;SpO291±5%;) and 22 lowlanders (eight females; age 42.3±8.0 years; BMI 26.9±4.1 kg·m−2; heart rate 68±7 beats·min−1;SpO296±1%) were studied. Highlanders had a lower restingSpO2compared to lowlanders but change during exercise was similar between groups (highlandersversuslowlanders −1.4±2.9%versus−0.4±1.1%, respectively, p=0.133). Highlanders had a significantly elevated TRPG and exercise-induced increase was significantly higher (13.6±10.5 mmHgversus6.1±4.8 mmHg, difference 7.5 (2.8 to 12.2) mmHg; p=0.002), whereas cardiac index increase was slightly lower in highlanders (2.02±0.89 L·min−1versus1.78±0.61 L·min−1, difference 0.24 (−0.13 to 0.61) L·min−1; p=0.206) resulting in a significantly steeper pressure–flow ratio (ΔTRPG/Δcardiac index) in highlanders 9.4±11.4 WU and lowlanders 3.0±2.4 WU (difference 6.4 (1.4 to 11.3) WU; p=0.012). Right ventricular-arterial coupling (TAPSE/TRPG) was significantly lower in highlanders but no significant difference in change with exercise in between groups was detected (−0.01 (−0.20 to 0.18); p=0.901).

In highlanders, chronic exposure to hypoxia leads to higher pulmonary artery pressure and a steeper pressure–flow relation during exercise.
Long-term exposure to high-concentration silver nanoparticles induced toxicity, fatality, bioaccumulation, and histological alteration in fish (Cyprinus carpio)
Authors: Kakakhel Mian Adnan , Wu Fasi , Sajjad Wasim , Zhang Qi , Khan Ikram , Ullah Kalim , Wang Wanfu
Published: February 2021

Background

Currently, nanotechnology and nanoparticles have quickly emerged and have gained the attention of scientists due to their massive applications in environmental sectors. However, these environmental applications of silver nanoparticles potentially cause serious effects on terrestrial and aquatic organisms. In the current study, freshwater fish C. carpio were exposed to blood-mediated silver nanoparticles for toxicity, mortality, bioaccumulation, and histological alterations. Silver nanoparticles were fabricated using animal blood serum and their toxic effect was studied against common carp fish at different concentrations levels (0.03, 0.06, and 0.09 mg/L).

Results

The findings have revealed a little influence of blood-induced silver nanoparticles on fish behavior at the highest concentration (0.09 mg/L). However, bioaccumulation of blood-mediated silver nanoparticles was reported in different organs of fish. Maximum bioaccumulation of silver nanoparticles was reported in the liver, followed by the intestine, gills, and muscles. Furthermore, the findings have shown that the bioaccumulation of silver nanoparticles led to histopathological alterations; including damaged structure of gill tissue and have caused necrosis. It is summarized that histopathological alteration in gill and intestine mostly occurred by the highest concentration of blood-induced silver nanoparticles (0.09 mg/L).

Conclusion

This study provides evidence of the silver nanoparticles influence on aquatic life; however, further systematic studies are crucial to access the effects of AgNPs on aquatic life.
Nose size indicates maximum penile length
Authors: Ikegaya Hiroshi , Suzuki Motofumi , Kondou Hiroki , Kawai Taketo , Sato Yusuke , Kitamura Tadaichi , Kume Haruki
Published: February 2021

Background

In a previous report, we investigated whether the size of male genitalia similarly exposed to serum testosterone during aging could change with age and found that penile length almost stopped increasing during adolescence and decreased in older males. In this report, to determine what factors other than age are related to penile length, we performed a multivariate analysis of the relationships between stretched penile length (SPL) and other measurements of genital organs, nose size, height and body weight in 126 adults in their 30s–50s.

Results

The most highly correlated factor with SPL was flaccid penile length (r = 0.565, P < 0.0001). The next highest correlation was nose size (r = 0.564, P < 0.0001). The penile stretched rate correlated with FPL (r = − 0.690, P < 0.0001) but not with SPL or penile circumference.

Conclusions

The fact that nose size is related to SPL indicates that penile length may not be determined by age, height or body weight but has already been determined before birth.
No evidence that selection for egg production persistency causes loss of bone quality in laying hens
Authors: Dunn Ian C. , De Koning Dirk-Jan , McCormack Heather A. , Fleming Robert H. , Wilson Peter W. , Andersson Björn , Schmutz Matthias , Benavides Cristina , Dominguez-Gasca Nazaret , Sanchez-Rodriguez Estefania , Rodriguez-Navarro Alejandro B.
Published: February 2021

Background

The physiological adaptations that have evolved for egg laying make hens susceptible to bone fractures and keel bone damage. In modern laying hen breeds, longer periods of egg laying could result in a greater risk of poor bone quality, and selection for increased egg production has frequently been stated to be a cause. However, the existing literature does not support this hypothesis. To test the hypothesis that egg production is associated with quality, breaking strength and density of bone, genetic correlations between these traits were estimated in White Leghorn and Rhode Island Red breeds. Genetic correlations of cortical and medullary bone material chemical properties with bone quality were also estimated, in order to identify methods to improve bone quality with appropriately targeted measurement of key traits.

Results

Estimates of heritability for bone quality traits were moderate (0.19–0.59) for both White Leghorn and Rhode Island Red breeds, except for the keel bone trait, which had a heritability estimate equal to zero. There was no evidence for genetic or phenotypic relationships between post-peak egg production and bone quality. In the White Leghorn breed, the estimate of the genetic correlation between pre-peak production/age at first egg and bone quality was significant and negative (− 0.7 to − 0.4). Estimates of heritability of thermogravimetric measurements of tibial medullary bone mineralisation were significant (0.18–0.41), as were estimates of their genetic correlations with tibia breaking strength and density (0.6–0.9).

Conclusions

The low genetic correlation of post-peak egg production with bone quality suggests that selection for increased persistency of egg production may not adversely affect bone quality. Onset of puberty and mineralisation of the medullary bone, which is a specialised adaptation for egg laying, were identified as important factors associated with the quality of the skeleton later during egg production. These are traits for which genetic, as well as environmental and management factors can positively impact the overall quality of the skeleton of laying hens.
Increased expression of MUSASHI1 in epithelial breast cancer cells is due to down regulation of miR-125b
Authors: Forouzanfar Mahboobeh , Lachinani Liana , Dormiani Kianoush , Nasr-Esfahani Mohammad Hossein , Ghaedi Kamran
Published: February 2021

Background

Musashi1 (MSI1) is an oncogenic protein with a crucial role in the proliferation and characteristics of the epithelial cells in breast cancer. The change in expression ofMSI1has a role in solid tumor progression. There are different factors that regulateMSI1expression in various cancer tissues including microRNAs which are considered as one of the most important of these factors. The aim of our study is identification of the molecular cause of maximal expression ofMSI1in epithelial breast cancer cell lines.

Results

Among predicted microRNAs, miR-125b, miR-637 and miR-802 were able to significantly reduce the luciferase activity. In addition, the relative expression of these three miRNAs were measured in the cancerous cell lines that results showed a significant reduction in expression of all microRNAs. On the other hand, only the overexpression of miR-125b caused a change in the expression pattern ofMSI1in breast epithelial cancer cell lines.Accordingly, our results demonstrated that the exogenous expression of miR-125b decreased not only the MSI1 protein but also expression of epithelial markers in breast cancer cells.

Conclusions

The results of luciferase reporter assay showed thatMSI1is a direct target for miR-125b in epithelial breast cancer cells. Moreover, higher amount of MSI1 in those cell lines seems due to the reduced amount of miR-125b, which is responsible for epithelial features of those kinds of cancer cells. Therefore, the modulation of miR-125b may be a potential approach to help to combat against epithelial breast tumors.
Evolutionary and demographic consequences of temperature-induced masculinization under climate warming: the effects of mate choice
Authors: Nemesházi Edina , Kövér Szilvia , Bókony Veronika
Published: February 2021

Background

One of the dangers of global climate change to wildlife is distorting sex ratios by temperature-induced sex reversals in populations where sex determination is not exclusively genetic, potentially leading to population collapse and/or sex-determination system transformation. Here we introduce a new concept on how these outcomes may be altered by mate choice if sex-chromosome-linked phenotypic traits allow females to choose between normal and sex-reversed (genetically female) males.

Results

We developed a theoretical model to investigate if an already existing autosomal allele encoding preference for sex-reversed males would spread and affect demographic and evolutionary processes under climate warming. We found that preference for sex-reversed males (1) more likely spread in ZW/ZZ than in XX/XY sex-determination systems, (2) in populations starting with ZW/ZZ system, it significantly hastened the transitions between different sex-determination systems and maintained more balanced adult sex ratio for longer compared to populations where all females preferred normal males; and (3) in ZW/ZZ systems with low but non-zero viability of WW individuals, a widespread preference for sex-reversed males saved the populations from early extinction.

Conclusions

Our results suggest that climate change may affect the evolution of mate choice, which in turn may influence the evolution of sex-determination systems, sex ratios, and thereby adaptive potential and population persistence. These findings show that preferences for sex-linked traits have special implications in species with sex reversal, highlighting the need for empirical research on the role of sex reversal in mate choice.
Oral health in adults with coronary artery disease and its risk factors: a comparative study using the Korea National Health and Nutrition Examination Survey data
Authors: Lee Sun Kyung , Hwang Seon Young
Published: February 2021

Background

This study aimed to examine the relationship between oral health status and hygiene behavior among adults and elderly with preceding chronic disease or coronary artery disease history.

Methods

Data were obtained from the Korea National Health and Nutrition Examination survey conducted from 2016 to 2017. Cardiovascular risk group was defined as adults over the age of 30 with hypertension, diabetes, dyslipidemia, previous myocardial infarction, or angina. Adult and elderly groups were separated and analyzed by 1:1 propensity score matching (PSM), and complex sample logistic regression analysis was performed using SPSS and R programs.

Results

In adults, 25.1% of healthy group and 41.9% of the risk group were diagnosed with periodontal disease by dentist. In the elderly, 40.0% of the risk group had chewing problems and 17.5% had speaking problems. After PSM, in adults (n = 1661 each), both univariate and multiple logistic regression analyzes showed that the prevalence of periodontal disease was significantly higher in the risk group than in the healthy group (Odds Ratio = 1.21, p = .028). In the elderly (n = 715 each), univariate analysis showed that the risk group had more chewing and speaking problems than the healthy group, but there was no difference in multivariate analysis.

Conclusions

Adults under the age of 65 years with cardiovascular risk require periodic evaluation and education on the importance of maintaining oral health for primary or secondary prevention. Healthcare professionals should provide patient education to help them maintain adequate oral health and oral hygiene.
Factors associated with delayed presentation to healthcare facilities for Lassa fever cases, Nigeria 2019: a retrospective cohort study
Authors: Chandra Nastassya L. , Bolt Hikaru , Dan-Nwafor Chioma , Ipadeola Oladipupo , Ilori Elsie , Namara Geoffrey , Olayinka Adebola T. , Ukponu Winifred , Iniobong Akanimo , Amedu Michael , Akano Adejoke , Akabike Kachikwulu O. , Okhuarobo Uwaifiokun , Fagbemi Stephen , Sampson Emeka , Newitt Sophie , Verlander Neville Q. , Bausch Daniel G. , le Polain de Waroux Olivier , Ihekweazu Chikwe
Published: February 2021

Background

Large outbreaks of Lassa fever (LF) occur annually in Nigeria. The case fatality rate among hospitalised cases is ~ 20%. The antiviral drug ribavirin along with supportive care and rehydration are the recommended treatments but must be administered early (within 6 days of symptom onset) for optimal results. We aimed to identify factors associated with late presentation of LF cases to a healthcare facility to inform interventions.

Methods

We undertook a retrospective cohort study of all laboratory confirmed LF cases reported in Nigeria from December 2018 to April 2019. We performed descriptive epidemiology and a univariate Cox proportional-hazards regression analysis to investigate the effect of clinical (symptom severity), epidemiological (age, sex, education, occupation, residential State) and exposure (travel, attendance at funeral, exposure to rodents or confirmed case) factors on time to presentation.

Results

Of 389 cases, median presentation time was 6 days (IQR 4–10 days), with 53% attending within 6 days. There were no differences in presentation times by sex but differences were noted by age-group; 60+ year-olds had the longest delays while 13–17 year-olds had the shortest. By sex and age, there were differences seen among the younger ages, with 0–4-year-old females presenting earlier than males (4 days and 73% vs. 10 days and 30%). For 5–12 and 13–17 year-olds, males presented sooner than females (males: 5 days, 65% and 3 days, 85% vs. females: 6 days, 50% and 5 days, 61%, respectively). Presentation times differed across occupations 4.5–9 days and 20–60%, transporters (people who drive informal public transport vehicles) had the longest delays. Other data were limited (41–95% missing). However, the Cox regression showed no factors were statistically associated with longer presentation time.

Conclusions

Whilst we observed important differences in presentation delays across factors, our sample size was insufficient to show any statistically significant differences that might exist. However, almost half of cases presented after 6 days of onset, highlighting the need for more accurate and complete surveillance data to determine if there is a systemic or specific cause for delays, so to inform, monitor and evaluate public health strategies and improve outcomes.
Comparison between nab-paclitaxel and solvent-based taxanes as neoadjuvant therapy in breast cancer: a systematic review and meta-analysis
Authors: Liu Miao , Liu Siyao , Yang Liu , Wang Shu
Published: February 2021

Background

To compare the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and solvent-based taxanes (sb-taxanes) as neoadjuvant therapy in the treatment of breast cancer.

Methods

We systematically searched the PubMed, Embase, and Cochrane Central Register databases. Randomized controlled trials (RCTs) and cohort studies, published in English, about the comparison between nab-paclitaxel and sb-taxanes as neoadjuvant therapy in patients with breast cancer were searched up to September 2019.

Results

The primary outcome was the proportion of patients with pathological complete response (pCR, defined as ypT0 ypN0 or ypT0/is ypN0). Other main outcomes included long-term survival and adverse events (AEs). Seven studies (five RCTs and two cohorts) and 2949 patients were included. Neoadjuvant nab-paclitaxel improved pCR compared with sb-taxanes (ypT0 ypN0: OR = 1.52, 95%CI: 1.27–1.83, P < 0.001; ypT0/is ypN0: OR = 1.40, 95%CI: 1.17–1.68, P < 0.001). The benefits of nab-paclitaxel on pCR were persistent in HER2-negative, hormone receptor (HR)-positive breast cancer (OR = 1.53, 95%CI: 1.07–2.19, P = 0.020), triple-negative breast cancer (weekly/every 2 weeks regimen; OR = 2.95, 95%CI: 1.54–5.67, P < 0.001), and tumors with Ki-67 > 20% (OR = 1.63, 95%CI: 1.26–2.12, P < 0.001). Patients treated with nab-paclitaxel had better event-free survival (EFS; HR = 0.69, 95%CI: 0.57–0.85, P < 0.001) than with sb-taxanes. There were no differences in most of grade > 3 AEs between nab-paclitaxel and sb-taxanes (all P > 0.05), besides of any grade hypersensitivity (OR = 0.29, 95%CI: 0.11–0.72, P = 0.008), any grade (OR = 2.10, 95%CI: 1.37–3.23, P = 0.001) and grade > 3 (OR = 4.01, 95%CI: 2.51–6.41, P < 0.001) neuropathy.

Conclusion

Nab-paclitaxel is effective for the treatment of non-metastatic breast cancer in the neoadjuvant setting. Nab-paclitaxel could improve pCR rate and EFS compared with sb-taxanes and with reasonable toxicities.
Most colitis associated carcinomas lack expression of LGR5: a preliminary study with implications for unique pathways of carcinogenesis compared to sporadic colorectal carcinoma
Authors: Iwaya Mai , Ota Hiroyoshi , Nakajima Tomoyuki , Uehara Takeshi , Riddell Robert , Conner James
Published: February 2021

Background

Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), a component of the Wnt receptor complex, is thought to lineage label gastric and intestinal stem cells. LGR5 expression is increased in colorectal carcinoma (CRC) compared to normal tissue. Colitis associated colorectal adenocarcinoma (CAC) often shows distinct morphologic and molecular phenotypes compared to sporadic cases. However, the expression profile of LGR5, and by extension the potential role of an intestinal stem cell phenotype, has not been well described in a series of human CAC.

Method

RNA in situ hybridization (ISH) for LGR5 expression on 30 CACs (12 cases with conventional morphology and 18 cases with non-conventional type morphology) from 29 inflammatory bowel disease (IBD) patients was performed and compared the expression profile to a control group of 10 sporadic CRCs. Immunohistochemistry for beta-catenin and SATB2 was performed on the 30 CACs.

Result

LGR5 was positive in 30% (9/30) of CAC cases and 90% (9/10) of sporadic CRCs (p = 0.002). A large majority (89%) of LGR5 positive CACs were of the conventional histologic type, and conventional type CAC showed a significantly higher LGR5 score (median 3.0; interquartile range 1.75–3.25) than non-conventional type CAC (median 1.5; interquartile range 1.00–2.00) (p = 0.034). CAC with conventional morphology did have a lower level of LGR5 expression than sporadic CRC. Sporadic CRCs showed a significantly higher LGR5 level score than non-conventional type CACs (p < 0.001). Nuclear translocation of beta-catenin was strongly associated with LGR5 expression (p = 0.003), however no significant association was identified between SATB2 expression and LGR5 expression status in CACs.

Conclusion

These findings suggest that the wider spectrum of tumor morphology in CAC may be associated with absence of a LGR5-expressing intestinal stem cell phenotype.
Hā Ora: secondary care barriers and enablers to early diagnosis of lung cancer for Māori communities
Authors: Kidd Jacquie , Cassim Shemana , Rolleston Anna , Chepulis Lynne , Hokowhitu Brendan , Keenan Rawiri , Wong Janice , Firth Melissa , Middleton Karen , Aitken Denise , Lawrenson Ross
Published: February 2021

Background

Lung Cancer is the leading cause of cancer deaths in Aotearoa New Zealand. Māori communities in particular have higher incidence and mortality rates from Lung Cancer. Diagnosis of lung cancer at an early stage can allow for curative treatment. This project aimed to document the barriers to early diagnosis and treatment of lung cancer in secondary care for Māori communities.

Methods

This project used a kaupapa Māori approach. Nine community hui (focus groups) and nine primary healthcare provider hui were carried out in five rural localities in the Midland region. Community hui included cancer patients, whānau (families), and other community members. Healthcare provider hui comprised staff members at the local primary healthcare centre, including General Practitioners and nurses. Hui data were thematically analysed.

Results

Barriers and enablers to early diagnosis of lung cancer were categorised into two broad themes: Specialist services and treatment, and whānau journey. The barriers and enablers that participants experienced in specialist services and treatment related to access to care, engagement with specialists, communication with specialist services and cultural values and respect, whereas barriers and enablers relating to the whānau journey focused on agency and the impact on whānau.

Conclusions

The study highlighted the need to improve communication within and across healthcare services, the importance of understanding the cultural needs of patients and whānau and a health system strategy that meets these needs. Findings also demonstrated the resilience of Māori and the active efforts of whānau as carers to foster health literacy in future generations.
Brazilian Portuguese version of the Amsterdam infant stool scale: a valid and reliable scale for evaluation of stool from children up to 120 days old
Authors: de Deus Silva Laura Cantisano , Bianchini Priscila Monaro , Ortolan Erika Veruska Paiva , Hamamoto Juliana Fattori , Fermiano Rosemary , Rego Rebeca Mayara Padilha , Lyra João César , Benninga Marc Alexander , de Arruda Lourenção Pedro Luiz Toledo
Published: February 2021

Background

For newborns and infants wearing diapers the difficulties in characterizing the appearance of the stool are significant, since the changes in consistency, quantity, and color of the stool are higher than in other age groups. The Amsterdam Infant Stool Scale (AISS) was created and validated in 2009, providing a specific tool for the evaluation of the stool of children up to 120 days old. However, to be used in clinical practice and scientific investigations in Brazil, it is mandatory to perform the translation and cross-cultural adaptation process for Brazilian Portuguese language. Thus, we aim to perform the translation and cross-cultural adaptation of AISS into Brazilian Portuguese and to evaluate the psychometric properties of the translated version.

Methods

The process of translation and cross-cultural adaptation was performed according to the internationally accepted methodology, including: translation, summary of translations, backtranslation, preparation of the pre-final version, application of the pre-test and determination of the final version. The evaluation of the psychometric properties was performed through the application of Brazilian Portuguese AISS, by five examiners (including child health field specialists and a literate adult lay on the subject), analyzing 238 stool photographs of children under 120 days old. The intra and inter-examiner agreement values were determined using kappa statistic. The validity of the criterion was investigated through correlation analysis (Kendall’s coefficient) between the classifications determined by the non-specialist examiner and the expert examiners.

Results

In all 30 tests performed between different examiners, there was an agreement considered as at least moderate (kappa values above 0.40). The intra-examiner reliability was considered as substantial (kappa> 0.6). There was a statistically significant correlation (p <  0.05) between the classifications determined by the examiners considered as specialists and the examiner considered as non-specialist.

Conclusion

The Brazilian Portuguese AISS version proved to be valid and reliable to be used by healthcare professionals and the general public in the evaluation of stool from children up to 120 days old.