bluuebunny/crossref_metadata_2025_split 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

Abstract
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

RationaleNontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear.ObjectivesWe aimed to identify host susceptibility loci forMycobacterium aviumcomplex (MAC), the most common NTM pathogen.MethodsThis 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.ResultsThe 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.ConclusionsWe 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.
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 objectivesProne 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.Methods27 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 resultsOxygen 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.ConclusionsSelf-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

Abstract
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

Abstract
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.