bluuebunny/crossref_metadata_2025 huggingface dataset:
Reverse Total Shoulder Arthroplasty for Treatment of 3- and 4-Part Proximal Humeral Fractures: Clinical and Radiological Analysis With Minimum Follow-Up of 2 Years
Authors: Barbosa Luis , Pires Luis , Rego Paulo , Alonso Raul
Published: March 2020

Background:

Hemiarthroplasty has been associated with inferior and unpredictable outcomes when used in the treatment of complex proximal humeral fractures in elderly patients. In this age-group, reverse shoulder arthroplasty is gaining popularity due to the promising results presented in recent evidence. Our aim is to analyze the cases of complex proximal humeral fractures treated by reverse shoulder arthroplasty, regarding functional results and complications.

Materials and Methods:

Thirty-five fractures from 33 patients with the mean age of 73.5 (65-81) years were treated with reverse shoulder arthroplasty for complex fractures of the proximal humerus. These patients were followed for a mean of 38.3 months (24-68) and analyzed regarding clinical outcomes and complications.

Results:

The average Quick-Disabilities of the Arm, Shoulder and Hand and American Shoulder and Elbow Surgeons scores were 6.8 points and 78.3%, respectively. The mean Constant score on the affected side was 64.4 points, 19.5% less than the nonoperated side. The mean active elevation was 123°, abduction 109°, external rotation 38°, and internal rotation 41°. The radiographic tuberosity healing rate was 85.7%. There were no significant differences in outcomes, between patient with healed and reabsorbed tuberosities. Inferior scapular notching was seen in 8 patients. The global complication rate was 12.8%.

Conclusion:

Reverse shoulder arthroplasty yields good and reproductive results with acceptable complication rates in selected elderly patients with complex proximal humeral fractures.
Limitations in Health-Care System Resources Affecting Adherence of Patient With Psoriasis to Topical Drugs: A Focus Group Study
Authors: Svendsen Mathias Tiedemann , Feldman Steven R. , Tiedemann Sylvia Naiga , Sørensen Anne Sofie Stochholm , Rivas Cecilie Marie Ringgaard , Andersen Klaus Ejner
Published: March 2020

Background:

Topical therapy is first-line treatment for patients with mild-to-moderate psoriasis, but low adherence to topical drugs is a barrier to treatment success. Health-care system resources are considered to have an impact on adherence of patient with psoriasis to topical drugs.

Objective:

To investigate dermatology nurses’ perception of the impact of health-care system resources on topical therapy adherence in patients with psoriasis.

Methods:

A semistructured focus group study was performed with 6 dermatology nurses and 2 student nurses. Participants were recruited from a dermatology outpatient hospital clinic. The study focused on the dermatology nurses’ perception of the effect health-care system resources (including health-care services provided to patients, how clinics are organized, and how the health-care personnel communicate) have on adherence of patients with psoriasis to topical treatment. The focus group discussion was divided into 3 areas: communication with patients and intercollegial communication, follow-up visits and admissions to consultations by other health-care professions, and how to establish consultations to support adherence of patients with psoriasis to topical drugs. Data were analyzed by a systematic text condensation method based on a phenomenological–hermeneutic approach.

Results:

Nurses identified a number of health-care system resources that may affect adherence of patients with psoriasis, primarily professional collaboration and communication, continuity of care, and the establishment of nurse consultations.

Conclusion:

Adherence may by negatively affected by contradictory information about topical drugs due to inadequate interprofessional collaboration among health-care professionals. Improving communication between health-care professionals and patients, ensuring continuity of care, and establishing nurse consultations may improve topical therapy outcomes.
Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis
Authors: Guan Wei-jie , Liang Wen-hua , Zhao Yi , Liang Heng-rui , Chen Zi-sheng , Li Yi-min , Liu Xiao-qing , Chen Ru-chong , Tang Chun-li , Wang Tao , Ou Chun-quan , Li Li , Chen Ping-yan , Sang Ling , Wang Wei , Li Jian-fu , Li Cai-chen , Ou Li-min , Cheng Bo , Xiong Shan , Ni Zheng-yi , Xiang Jie , Hu Yu , Liu Lei , Shan Hong , Lei Chun-liang , Peng Yi-xiang , Wei Li , Liu Yong , Hu Ya-hua , Peng Peng , Wang Jian-ming , Liu Ji-yang , Chen Zhong , Li Gang , Zheng Zhi-jian , Qiu Shao-qin , Luo Jie , Ye Chang-jiang , Zhu Shao-yong , Cheng Lin-ling , Ye Feng , Li Shi-yue , Zheng Jin-ping , Zhang Nuo-fu , Zhong Nan-shan , He Jian-xing
Published: March 2020

Background

The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide.

Objective

To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status.

Methods

We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities.

Results

The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424–5.048)), diabetes (1.59 (1.03–2.45)), hypertension (1.58 (1.07–2.32)) and malignancy (3.50 (1.60–7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16–2.77) among patients with at least one comorbidity and 2.59 (1.61–4.17) among patients with two or more comorbidities.

Conclusion

Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.
β2-integrin LFA1 mediates airway damage following neutrophil transepithelial migration during respiratory syncytial virus infection
Authors: Herbert Jenny Amanda , Deng Yu , Hardelid Pia , Robinson Elisabeth , Ren Luo , Moulding Dale , Smyth Rosalind Louise , Smith Claire Mary
Published: March 2020

Respiratory syncytial virus (RSV) bronchiolitis is the most common cause of infant hospital admissions, but there is limited understanding of the mechanisms of disease, and no specific antiviral treatment. Using a novelin vitroprimary transepithelial neutrophil migration model and innovative imaging methods, we show that RSV infection of nasal airway epithelium increased neutrophil transepithelial migration and adhesion to infected epithelial cells, which is associated with epithelial cell damage and reduced ciliary beat frequency, but also with a reduction in infectious viral load.

Following migration, RSV infection results in greater neutrophil activation, degranulation and release of neutrophil elastase into the airway surface media compared to neutrophils that migrated across mock-infected nasal epithelial cells. Blocking of the interaction between the ligand on neutrophils (the β2-integrin LFA-1) for intracellular adhesion molecule (ICAM)-1 on epithelial cells reduced neutrophil adherence to RSV-infected cells and epithelial cell damage to pre-infection levels, but did not reduce the numbers of neutrophils that migrated or prevent the reduction in infectious viral load.

These findings have provided important insights into the contribution of neutrophils to airway damage and viral clearance, which are relevant to the pathophysiology of RSV bronchiolitis. This model is a convenient, quantitative preclinical model that will further elucidate mechanisms that drive disease severity and has utility in antiviral drug discovery.
The role of phosphatidylserine recognition receptors in multiple biological functions
Authors: Naeini Mehri Bemani , Bianconi Vanessa , Pirro Matteo , Sahebkar Amirhossein
Published: March 2020

Apoptotic cells are rapidly engulfed and degraded by phagocytes through efferocytosis. Efferocytosis is a highly regulated process. It is triggered upon the activation of caspase-dependent apoptosis, which in turn promotes the expression of “eat me” signals on the surface of dying cells and the release of soluble “find me” signals for the recruitment of phagocytes. To date, many “eat me” signals have been recognized, including phosphatidylserine (PS), intercellular adhesion molecule-3, carbohydrates (e.g., amino sugars, mannose) and calreticulin. Among them, PS is the most studied one. PS recognition receptors are different functionally active receptors expressed by phagocytes. Various PS recognition receptors with different structure, cell type expression, and ability to bind to PS have been recognized. Although PS recognition receptors do not fall into a single classification or family of proteins due to their structural differences, they all share the common ability to activate downstream signaling pathways leading to the production of anti-inflammatory mediators. In this review, available evidence regarding molecular mechanisms underlying PS recognition receptor-regulated clearance of apoptotic cells is discussed. In addition, some efferocytosis-independent biological functions of PS recognition receptors are reviewed.
Characterisation of the gut microbial community of rhesus macaques in high-altitude environments
Authors: Wu Yuhan , Yao Yongfang , Dong Mengmeng , Xia Tianrui , Li Diyan , Xie Meng , Wu Jiayun , Wen Anxiang , Wang Qin , Zhu Guangxiang , Ni Qingyong , Zhang Mingwang , Xu Huailiang
Published: March 2020

Background

The mammal intestinal microbiota is involved in various physiological processes and plays a key role in host environment adaption. However, for non-human primates (NHPs), little is known about their gut microbial community in high-altitude environments and even less about their adaption to such habitats. We characterised the gut microbial community of rhesus macaques from multiple high-altitude environments and compared it to those of low-altitude populations.

Results

We collected faecal samples of rhesus macaques from four high-altitude populations (above 3000 m) and three low-altitude populations (below 500 m). By calculating the alpha diversity index, we found that high-altitude populations exhibited a higher diversity. Statistical analysis of beta diversity indicated significant differences between high- and low-altitude populations. Significant differences were also detected at the phylum and family levels. At the phylum level, the high-altitude gut microbial community was dominated by Firmicutes (63.42%), while at low altitudes, it was dominated by Bacteroidetes (47.4%). At the family level, the high-altitude population was dominated by Ruminococcaceae (36.2%), while the low-altitude one was dominated by Prevotellaceae (39.6%). Some families, such as Christensenellaceae and Rikenellaceae, were consistently higher abundant in all high-altitude populations. We analysed the overlap of operational taxonomic units (OTUs) in high-altitude populations and determined their core OTUs (shared by all four high-altitude populations). However, when compared with the low-altitude core OTUs, only 65% were shared, suggesting a divergence in core OTUs. Function prediction indicated a significant difference in gene copy number of 35 level-2 pathways between high- and low-altitude populations; 29 of them were higher in high altitudes, especially in membrane transport and carbohydrate metabolism.

Conclusions

The gut microbial community of high-altitude rhesus macaques was significantly distinct from that of low-altitude populations in terms of diversity, composition and function. High-altitude populations were dominated by Firmicutes and Ruminococcace, while in low-altitude populations, Bacteroidetes and Prevotellaceae were dominant. The difference in gut microbiota between these two populations may be caused by differences in host diet, environmental temperature and oxygen pressure. These differentiated gut microbial microorganisms may play a critical role in the adaptive evolution of rhesus macaques to high-altitude environments.
Dopamine response gene pathways in dorsal striatum MSNs from a gene expression viewpoint: cAMP-mediated gene networks
Authors: Babenko Vladimir N. , Galyamina Anna G. , Rogozin Igor B. , Smagin Dmitry A. , Kudryavtseva Natalia N.
Published: March 2020

Background

Medium spiny neurons (MSNs) comprise the main body (95% in mouse) of the dorsal striatum neurons and represent dopaminoceptive GABAergic neurons. The cAMP (cyclic Adenosine MonoPhosphate)—mediated cascade of excitation and inhibition responses observed in MSN intracellular signal transduction is crucial for neuroscience research due to its involvement in the motor and behavioral functions. In particular, all types of addictions are related to MSNs. Shedding the light on the mechanics of the above-mentioned cascade is of primary importance for this research domain.

Results

A mouse model of chronic social conflicts in daily agonistic interactions was used to analyze dorsal striatum neurons genes implicated in cAMP-mediated phosphorylation activation pathways specific for MSNs. Based on expression correlation analysis, we succeeded in dissecting Drd1- and Drd2-dopaminoceptive neurons (D1 and D2, correspondingly) gene pathways. We also found that D1 neurons genes clustering are split into two oppositely correlated states, passive and active ones, the latter apparently corresponding to D1 firing stage upon protein kinase A (PKA) activation.

We observed that under defeat stress in chronic social conflicts the loser mice manifest overall depression of dopamine-mediated MSNs activity resulting in previously reported reduced motor activity, while the aggressive mice with positive fighting experience (aggressive mice) feature an increase in both D1-active phase and D2 MSNs genes expression leading to hyperactive behavior pattern corresponded by us before.

Based on the alternative transcript isoforms expression analysis, it was assumed that many genes (Drd1, Adora1, Pde10, Ppp1r1b, Gnal), specifically those in D1 neurons, apparently remain transcriptionally repressed via the reversible mechanism of promoter CpG island silencing, resulting in alternative promoter usage following profound reduction in their expression rate.

Conclusion

Based on the animal stress model dorsal striatum pooled tissue RNA-Seq data restricted to cAMP related genes subset we elucidated MSNs steady states exhaustive projection for the first time. We correspond the existence of D1 active state not explicitly outlined before, and connected with dynamic dopamine neurotransmission cycles. Consequently, we were also able to indicate an oscillated postsynaptic dopamine vs glutamate action pattern in the course of the neurotransmission cycles.
Incidence and predictors of tuberculosis occurrence among adults on antiretroviral therapy at Debre Markos referral hospital, Northwest Ethiopia: retrospective follow-up study
Authors: Aemro Agazhe , Jember Abebaw , Anlay Degefaye Zelalem
Published: March 2020

Background

In resource limited settings, Tuberculosis (TB) is a major cause of morbidity and mortality among patients on antiretroviral treatment. Ethiopia is one of the 30 high TB burden countries. TB causes burden in healthcare system and challenge the effectiveness of HIV care. This study was to assess incidence and predictors of Tuberculosis among adults on antiretroviral therapy at Debre Markos Referral Hospital, Northwest Ethiopia, 2019.

Methods

Institution based retrospective follow up study was conducted among adults on ART newly enrolled from 2014 to 2018 at Debre Markos Referral Hospital. Simple random sampling technique was used to select patients chart. Data was entered to EPI- INFO version 7.2.2.6 and analyzed using Stata 14.0. Tuberculosis incidence rate was computed and described using frequency tables. Both bivariable and multivariable Cox proportional hazard models was fitted to identify predictors of TB.

Results

Out of the 536 patients chart reviewed, 494 patient records were included in the analysis. A total of 62 patients developed new TB cases during the follow up period of 1000.22 Person Years (PY); which gives an overall incidence rate of 6.19 cases per 100 PY (95% CI: 4.83–7.95). The highest rate was seen within the first year of follow up. After adjustment base line Hemoglobin < 10 g/dl (AHR = 5.25; 95% CI: 2.52–10.95), ambulatory/bedridden patients at enrolment (AHR = 2.31; 95% CI: 1.13–4.73), having fair or poor ART adherence (AHR = 3.22; 95% CI: 1.64–6.31) were associated with increased risk of tuberculosis whereas taking Isoniazid Preventive Therapy (IPT) (AHR = 0.33; 95% CI: 0.12–0.85) were protective factors of TB occurrence.

Conclusion

TB incidence was high among adults on ART especially in the first year of enrollment to ART. Low hemoglobin level, ambulatory or bedridden functional status, non-adherence to ART and IPT usage status were found to be independent predictors. Hence, continuous follow up for ART adherence and provision of IPT has a great importance to reduce the risk of TB.
Reduced bacterial contamination rates detected on silicone tourniquets compared to conventional tourniquets in clinical routine
Authors: Grohmann Marcus , Schomakers Lena , Wolschendorf Frank , Grosch Janina , Lindner Susan , Witte Anna Kristina
Published: March 2020

Background

Tourniquets used for peripheral venous vascular access such as blood sampling are regularly contaminated in clinical routine. Although most contaminations are harmless, some pose a possible risk for infection. To improve peripheral venous access infection control standards, tourniquets with no or as few as possible bacterial burden should be used. Conventional tourniquets can be reprocessed by autoclaving or by incubating in disinfectants. However, both methods are time-consuming and not suitable for immediate use between patients. In contrast, silicone tourniquets can be quickly and simply reprocessed with wipe disinfection. In vitro studies from the manufacturer have demonstrated reduced bacterial contamination on silicone tourniquets after usage compared to conventional tourniquets. This study aims to independently investigate the bacterial load on both types of tourniquets in clinical routine.

Methods

In a first trial, new conventional and silicon tourniquets were used for blood sampling in one facility with strict guidelines for reprocessing (after each patient or not at all) for 1 day and tested for bacterial contamination. In a second trial, new tourniquets were used in four facilities while the mode and frequency of tourniquets’ reprocessing was defined individually by each facility. The number of treated patients, mode and frequency of reprocessing and other relevant handling measures were documented.

Results

Under controlled conditions, with strictly specified reprocessing, slightly fewer bacteria were found on silicone than on conventional tourniquets. In routine clinical practice the reprocessing frequency was not higher for silicone tourniquets in practice. Yet, in all four facilities, there were significantly fewer bacteria found on silicone than on conventional tourniquets.

Conclusion

Although tourniquets are classified as non-critical medical devices, results show – together with benefits of faster and easier reprocessing – that silicone tourniquets can improve infection control of venous vascular access.
Group problem management plus (gPM+) in the treatment of common mental disorders in Syrian refugees in a Jordanian camp: study protocol for a randomized controlled trial
Authors:   on behalf of the STRENGTHS Consortium, Akhtar Aemal , Giardinelli Luana , Bawaneh Ahmad , Awwad Manar , Naser Hadeel , Whitney Claire , Jordans Mark J. D. , Sijbrandij Marit , Bryant Richard A.
Published: March 2020

Background

Accessing quality mental health care poses significant challenges for persons affected by adversity, especially in low- and middle-income countries where resources are scarce. To mitigate this, the World Health Organization has developed group problem management plus (gPM+), a low-intensity psychological intervention for adults experiencing psychological distress. gPM+ is a group-based intervention consisting of five-sessions, and can be delivered by non-specialist providers. This paper outlines the study protocol for a trial of gPM+ in Jordan.

Methods

We will conduct a single-blind, two-arm, randomized controlled trial in a Syrian refugee camp in Jordan. We aim to enrol 480 adults into the trial. Participants will be eligible for the trial if they screen positive for levels of psychological distress. Following screening, those eligible will be randomly assigned to receive the gPM+ intervention or enhanced treatment as usual. The primary outcome is reduction in levels of psychological distress at 3-months post-treatment. Secondary outcomes include anxiety, depression, prodromal psychotic symptoms, posttraumatic stress disorder, prolonged grief, daily functioning, economic effectiveness, and change in parenting behaviour. Secondary outcomes also include the reduction in psychological distress of the participant’s child.

Discussion

The trial aims to deliver a template for affordable and scalable psychosocial interventions that can readily be implemented in refugee settings, and that can benefit both the participant and their child.

Trial registration

Australian New Zealand Clinical Trials Registry, ACTRN12619001386123. Registered prospectively on 10/10/2019.
Barriers and facilitators for individualized rehabilitation during breast cancer treatment – a focus group study exploring health care professionals’ experiences
Authors: Olsson Möller Ulrika , Olsson Ing-Marie , Sjövall Katarina , Beck Ingela , Rydén Lisa , Malmström Marlene
Published: March 2020

Background

Breast cancer (BC) and related treatment are associated with the risk of developing a wide range of persistent disabling impairments. Despite extensive research in the field and an enhanced focus on BC rehabilitation, up to 34–43% of these patients are at risk of developing chronic distress. In addition, it is known that these patients repeatedly report unmet needs, which are strongly associated with reduced quality of life. However, despite knowledge that patients’ needs for support during BC rehabilitation varies greatly, individualized rehabilitation is often lacking. Therefore, this study aimed to explore health care professionals’ (HCPs) experiences of current rehabilitation practice and describe current barriers and facilitators for individualized rehabilitation for patients following BC treatment.

Methods

A total of 19 HCPs were included, representing various professions in BC care/rehabilitation within surgical, oncological and specialized cancer rehabilitation units at a university hospital in Sweden. Five semi structured focus group interviews were conducted and inductively analysed using conventional qualitative content analysis.

Results

Three categories were captured: (1) varying attitudes towards rehabilitation; (2) incongruence in how to identify and meet rehabilitation needs and (3) suboptimal collaboration during cancer treatment. The results showed a lack of consensus in how to optimize individualized rehabilitation. It also illuminated facilitators for individualized rehabilitation in terms of extensive competence related to long-term experience of working with patients with BC care/rehabilitation. Further, the analysis exposed barriers such as a great complexity in promoting individualized rehabilitation in a medically and treatment-driven health care system, which lacked structure and knowledge, and overarching collaboration for rehabilitation.

Conclusion

This study suggests that the cancer trajectory is medically and treatment-driven and that rehabilitation plays a marginal role in today’s BC trajectory. It also reveals that structures for systematic screening for needs, evidence-based guidelines for individualized rehabilitation interventions and structures for referring patients for advanced rehabilitation are lacking. To enable optimal and individualized recovery for BC patients’, rehabilitation needs to be an integrated part of the cancer trajectory and run in parallel with diagnostics and treatment.
Protein assembly systems in natural and synthetic biology
Authors: Chiesa Giulio , Kiriakov Szilvia , Khalil Ahmad S.
Published: March 2020

The traditional view of protein aggregation as being strictly disease-related has been challenged by many examples of cellular aggregates that regulate beneficial biological functions. When coupled with the emerging view that many regulatory proteins undergo phase separation to form dynamic cellular compartments, it has become clear that supramolecular assembly plays wide-ranging and critical roles in cellular regulation. This presents opportunities to develop new tools to probe and illuminate this biology, and to harness the unique properties of these self-assembling systems for synthetic biology for the purposeful manipulation of biological function.
Hospitalisation patterns of patients with interstitial lung disease in the light of comorbidities and medical treatment – a German claims data analysis
Authors: Wälscher Julia , Witt Sabine , Schwarzkopf Larissa , Kreuter Michael
Published: March 2020

Background

Interstitial lung disease (ILD) is a heterogeneous group of mainly chronic lung diseases differing in disease course and prognosis. For most subtypes, evidence on relevance and outcomes of hospitalisations is lacking.

Methods

Using German claims data we investigated number of hospitalisations (zero-inflated-negative-binomial models providing rate ratios (RR)) and time to first hospitalisation (Cox proportional-hazard models providing hazard ratios (RR)) for nine ILD-subtypes. Models were stratified by ILD-related and non-ILD-related hospitalisations. We adjusted for age, gender, ILD-subtype, ILD-relevant comorbidities and ILD-medication (immunosuppressive drugs, steroids, anti-fibrotic drugs).

Results

Among 36,816 ILD-patients (mean age 64.7 years, 56.2% male, mean observation period 9.3 quarters), 71.2% had non-ILD-related and 56.6% ILD-related hospitalisations. We observed more and earlier non-ILD-related hospitalisations in ILD patients other than sarcoidosis. Medical ILD-treatment was associated with increased frequency and in case of late initiation, earlier (non-)ILD-related hospitalisations. Comorbidities were associated with generally increased hospitalisation frequency except for COPD (RR = 0.90) and PH (RR = 0.94) in non-ILD-related and for lung cancer in ILD-related hospitalisations (RR = 0.89). Coronary heart disease was linked with earlier (ILD-related: HR = 1.17, non-ILD-related HR = 1.19), but most other conditions with delayed hospitalisations.

Conclusion

Hospitalisations are frequent across all ILD-subtypes. The hospitalisation risk might be reduced independently of the subtype by improved management of comorbidities and improved pharmacological and non-pharmacological ILD therapy.
A positron emission tomography imaging study to confirm target engagement in the lungs of patients with idiopathic pulmonary fibrosis following a single dose of a novel inhaled αvβ6 integrin inhibitor
Authors: Maher Toby M. , Simpson Juliet K. , Porter Joanna C. , Wilson Frederick J. , Chan Robert , Eames Rhena , Cui Yi , Siederer Sarah , Parry Simon , Kenny Julia , Slack Robert J. , Sahota Jagdeep , Paul Lyn , Saunders Peter , Molyneaux Philip L. , Lukey Pauline T. , Rizzo Gaia , Searle Graham E. , Marshall Richard P. , Saleem Azeem , Kang’ombe Arthur R. , Fairman David , Fahy William A. , Vahdati-Bolouri Mitra
Published: March 2020

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with poor prognosis and a significant unmet medical need. This study evaluated the safety, pharmacokinetics (PK) and target engagement in the lungs, of GSK3008348, a novel inhaled alpha-v beta-6 (αvβ6) integrin inhibitor, in participants with IPF.

Methods

This was a phase 1b, randomised, double-blind (sponsor unblind) study, conducted in the UK (two clinical sites, one imaging unit) between June 2017 and July 2018 (NCT03069989). Participants with a definite or probable diagnosis of IPF received a single nebulised dose of 1000 mcg GSK3008348 or placebo (ratio 5:2) in two dosing periods. In period 1, safety and PK assessments were performed up to 24 h post-dose; in period 2, after a 7-day to 28-day washout, participants underwent a total of three positron emission tomography (PET) scans: baseline, Day 1 (~ 30 min post-dosing) and Day 2 (~ 24 h post-dosing), using a radiolabelled αvβ6-specific ligand, [18F]FB-A20FMDV2. The primary endpoint was whole lung volume of distribution (VT), not corrected for air volume, at ~ 30 min post-dose compared with pre-dose. The study success criterion, determined using Bayesian analysis, was a posterior probability (true % reduction in VT > 0%) of ≥80%.

Results

Eight participants with IPF were enrolled and seven completed the study. Adjusted posterior median reduction in uncorrected VT at ~ 30 min after GSK3008348 inhalation was 20% (95% CrI: − 9 to 42%). The posterior probability that the true % reduction in VT > 0% was 93%. GSK3008348 was well tolerated with no reports of serious adverse events or clinically significant abnormalities that were attributable to study treatment. PK was successfully characterised showing rapid absorption followed by a multiphasic elimination.

Conclusions

This study demonstrated engagement of the αvβ6 integrin target in the lung following nebulised dosing with GSK3008348 to participants with IPF. To the best of our knowledge this is the first time a target-specific PET radioligand has been used to assess target engagement in the lung, not least for an inhaled drug.

Trial registration

clinicaltrials.gov: NCT03069989; date of registration: 3 March 2017.
Young people who inject drugs in Mozambique: should we emphasize them in the National Harm Reduction Plan?
Authors: Semá Baltazar Cynthia , Boothe Makini , Kellogg Timothy
Published: March 2020

Mozambique has one of the highest burdens of HIV globally, and people who inject drugs (PWID) have one of the highest HIV infection rates in Africa. After the implementation of the first Biological Behavioral Surveillance (BBS) Survey among PWID in Mozambique, the Ministry of Health started the development of a National Harm Reduction Plan. Although the findings from the BBS survey highlighted the specific needs of young PWID, the proposed Harm Reduction Plan does not explicitly focus on reducing high-risk behaviors of young PWID. We outline the importance of the inclusion of age-specific interventions focused on the needs of young PWID in Mozambique, and how a comprehensive Harm Reduction Plan can reduce the HIV epidemic in this population. There is a unique opportunity to advocate for the Harm Reduction Plan to include “youth-friendly” cost-effective and evidence-based interventions that are targeted to this important sub-group within an already vulnerable population.
The experience of polyethylene glycol (PEG) bowel preparation in adolescents undergoing colonoscopy
Authors: Örmon Karin , Bramhagen Ann-Cathrine , Sunnqvist Charlotta , Vejzovic Vedrana
Published: March 2020

Objective

The aim of this study was to describe the experience of polyethylene glycol (PEG) bowel preparation in adolescents undergoing colonoscopy.

Results

32 adolescents, 10–18 years of age self-reported a minimum of complications 1 week after colonoscopy when PEG was used for bowel preparation. 17 adolescents, 10–18 years were also interviewed about bowel preparation with PEG. Using qualitative content analysis, two categories were extracted from the data: “Being decisive makes it manageable” and “Be prepared for a horrible experience.” The adolescents reported PEG intake difficulty; the intake was, however, manageable if they received appropriate information.
Prognosis of PD-L1 in human breast cancer: protocol for a systematic review and meta-analysis
Authors: Litvin Isnard Elman , Paganella Machline Paim , Wendland Eliana Marcia , Roehe Adriana Vial
Published: March 2020

Background

Breast cancer is one of the most common malignancies in women worldwide, and one of the leading causes of cancer-related death. Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key physiologic suppressors of the cytotoxic immune reaction. Some authors advocate that PD-L1 expression may help in breast cancer prognosis.

Methods

We will conduct a systematic review of observational or interventional studies evaluating the prognostic ability of PD-L1 expression levels in predicting positive clinical outcomes in Human Breast Cancer. A sensitive search strategy will be employed in MEDLINE, EMBASE, LILACS, The Grey Literature Report, OpenGrey, OAIster, and Cochrane CENTRAL. Two reviewers will independently screen all identified references for eligibility and extract data. The outcomes evaluated will be Overall Survival, Breast Cancer-specific Survival, Disease-free Survival, Recurrence-free Survival, Positive Lymph Node, and Distant Metastasis. The outcomes will be extracted directly from the studies, if available. Methodological quality and bias of included studies will be assessed using a standardized checklist and overall quality of evidence will be assessed through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. If meta-analysis is possible, the measures of association will be calculated using bivariate random-effects models. Statistical heterogeneity will be evaluated withI2statistics and explored through sensitivity analysis.

Discussion

Immunomodulation seems to be a promising strategy in solid tumors. Breast cancer is the most common malignancies in women worldwide, and one of the leading causes of cancer death. PD-1 and PD-L1 are key physiologic suppressors of the cytotoxic immune reaction.

Trial registration

Systematic review registration:CRD42019121118(PROSPERO)
An open-source framework for neuroscience metadata management applied to digital reconstructions of neuronal morphology
Authors: Bijari Kayvan , Akram Masood A. , Ascoli Giorgio A.
Published: March 2020

Research advancements in neuroscience entail the production of a substantial amount of data requiring interpretation, analysis, and integration. The complexity and diversity of neuroscience data necessitate the development of specialized databases and associated standards and protocols. NeuroMorpho.Org is an online repository of over one hundred thousand digitally reconstructed neurons and glia shared by hundreds of laboratories worldwide. Every entry of this public resource is associated with essential metadata describing animal species, anatomical region, cell type, experimental condition, and additional information relevant to contextualize the morphological content. Until recently, the lack of a user-friendly, structured metadata annotation system relying on standardized terminologies constituted a major hindrance in this effort, limiting the data release pace. Over the past 2 years, we have transitioned the original spreadsheet-based metadata annotation system of NeuroMorpho.Org to a custom-developed, robust, web-based framework for extracting, structuring, and managing neuroscience information. Here we release the metadata portal publicly and explain its functionality to enable usage by data contributors. This framework facilitates metadata annotation, improves terminology management, and accelerates data sharing. Moreover, its open-source development provides the opportunity of adapting and extending the code base to other related research projects with similar requirements. This metadata portal is a beneficial web companion to NeuroMorpho.Org which saves time, reduces errors, and aims to minimize the barrier for direct knowledge sharing by domain experts. The underlying framework can be progressively augmented with the integration of increasingly autonomous machine intelligence components.
Predictors of contrast-induced acute kidney injury in patients with coronary artery disease receiving contrast agents twice within 30 days
Authors: Gu Chong-Huai , Wang Xiao-Zeng , Han Ya-Ling , Jing Quan-Min , Ren Li-Li , Zhang Yan , Peng Jun-Yin , Zhao Xin
Published: March 2020

Background

None of study mentioned about contrast-induced acute kidney injury (CI-AKI) in people who have received contrast agents twice within in a short period of time. This study is trying to identify the predictors.

Methods

We enrolled 607 patients between Oct. 2010 and Jul. 2015 who received contrast agents twice within 30 days in the Department of Cardiology of the General Hospital of Shenyang Military Region. The primary outcome was CI-AKI within 72 h after contrast agent exposure. Patients were divided into groups A (n = 559) and group B (n = 48) according to whether CI-AKI occurred after the second agent.

Results

Patients in group B (CI-AKI occurred after the second agent) had a more rapid heart rate and more usage of diuretics and digitalis. In group B, CI-AKI occurred more frequently after the first agent. Multivariate logistic regression showed that diuretic (P = 0.006) and intra-aortic balloon pump (IABP) usage (P = 0.012) were independent predictors of CI-AKI after the first agent. Angiotensin-converting enzyme inhibitor/Angiotensin II receptor antagonist (ACEI/ARB) usage (P = 0.039), IABP usage (P = 0.040) and CI-AKI occurring after administration of the first agent (P = 0.015) were independent predictors of CI-AKI after the second. Furthermore, dividing the patients into tertiles of the time interval between the two agents showed that CI-AKI occurred more frequently when the second agent was administered within 1–3 days after the first exposure than within 4–6 days (12.4% vs. 5.0%, P = 0.008) or ≥ 7 days (12.4% vs. 6.4%, P = 0.039).

Conclusions

Diuretic and IABP usage are independent predictors of CI-AKI following exposure to a first contrast agent. The major predictors of CI-AKI after exposure to a second agent are time since the first contrast exposure, ACEI/ARB usage, and IABP usage. More importantly, a three-day interval between the two agents is associated with a higher incidence of CI-AKI following the second administration.
Prognostic Significance of Lymphatic, Venous and Perineural Invasion After Neoadjuvant Chemotherapy in Patients with Gastric Adenocarcinoma
Authors: Woodham Benjamin L. , Chmelo Jakub , Donohoe Claire L. , Madhavan Anantha , Phillips Alexander W.
Published: March 2020

Background

The significance of perineural (PNI), lymphatic (LI) and venous invasion (VI) in gastric cancer patients who have received neoadjuvant chemotherapy is unclear. The aim of this study is to determine the incidence and prognostic significance of LI, VI and PNI in these patients.

Patients and Methods

Consecutive patients treated with neoadjuvant chemotherapy followed by gastrectomy with D2 lymphadenectomy were reviewed. Presence of LI, VI and PNI was recorded and correlated with clinical outcomes.

Results

A total of 243 patients underwent gastrectomy after neoadjuvant therapy for gastric adenocarcinoma. LI was identified in 129 (53%), VI in 107 (44%) and PNI in 116 (48%) of patients. Presence of LI (HR, 2.95, CI 1.91–4.56), VI (HR, 2.66, CI 1.78–3.98) and PNI (HR, 3.85, CI 2.49–5.95) was associated with poorer survival (all p < 0.001). Multivariable analysis revealed that ypT stage (HR, 1.35, CI 1.05–1.74), ypN stage (HR, 1.53, CI 1.28–1.83) and PNI (HR, 2.11, CI 1.31–3.42) were independent predictors of survival.

Conclusions

LI, VI and PNI are associated with poorer survival, with PNI having prognostic significance independent of lymph node status. These factors may be useful for further prognostication, in particular when multiple factors are present, and appear especially useful for prognostic stratification in patients with no nodal involvement.
Flooded Cities
Authors: Kocornik-Mina Adriana , McDermott Thomas K. J. , Michaels Guy , Rauch Ferdinand
Published: March 2020

Does economic activity move away from areas that are at high risk of recurring shocks? We examine this question in the context of floods, which displaced more than 650 million people worldwide in the last 35 years. We study large urban floods using spatially detailed inundation maps and night lights data spanning the globe’s cities. We find that low-elevation urban areas are flooded more frequently, and yet they concentrate more economic activity per square kilometer. When cities are flooded, low-elevation areas recover as rapidly as those higher up. With the exception of recently populated urban areas, we find little permanent movement of economic activity in response to floods. (JEL O18, Q54, R11, R58)
Energy Cost Pass-Through in US Manufacturing: Estimates and Implications for Carbon Taxes
Authors: Ganapati Sharat , Shapiro Joseph S. , Walker Reed
Published: March 2020

We study how changes in energy input costs for US manufacturers affect the relative welfare of manufacturing producers and consumers (i.e., incidence). We also develop a methodology to estimate the incidence of input taxes that accounts for incomplete pass-through, imperfect competition, and substitution among inputs. For the several industries we study, 70 percent of energy price-driven changes in input costs get passed through to consumers in the short to medium run. The share of the welfare cost that consumers bear is 25–75 percent smaller (and the share producers bear is larger) than models featuring complete pass-through and perfect competition would suggest. (JEL H22, H23, L60, Q48,Q54, Q58)
The Evolution of Work in the United States
Authors: Atalay Enghin , Phongthiengtham Phai , Sotelo Sebastian , Tannenbaum Daniel
Published: March 2020

Using the text from job ads, we introduce a new dataset to describe the evolution of work from 1950 to 2000. We show that the transformation of the US labor market away from routine cognitive and manual tasks and toward nonroutine interactive and analytic tasks has been larger than prior research has found, with a substantial fraction of total changes occurring within narrowly defined job titles. We provide narrative and systematic evidence on changes in task content within job titles and on the emergence and disappearance of individual job titles. (JEL E24, J21, J24, J31, N32)
Discipline-specific open access publishing practices and barriers to change: an evidence-based review
Authors: Severin Anna , Egger Matthias , Eve Martin Paul , Hürlimann Daniel
Published: March 2020

Background: Many of the discussions surrounding Open Access (OA) revolve around how it affects publishing practices across different academic disciplines. It was a long-held view that it would be only a matter of time before all disciplines fully and relatively homogeneously implemented OA. Recent large-scale bibliometric studies show, however, that the uptake of OA differs substantially across disciplines. We aimed to answer two questions: First, how do different disciplines adopt and shape OA publishing practices? Second, what discipline-specific barriers to and potentials for OA can be identified?

Methods: In a first step, we identified and synthesized relevant bibliometric studies that assessed OA prevalence and publishing patterns across disciplines. In a second step, and adopting a social shaping of technology perspective, we studied evidence on the socio-technical forces that shape OA publishing practices. We examined a variety of data sources, including, but not limited to, publisher policies and guidelines, OA mandates and policies and author surveys.

Results: Over the last three decades, scholarly publishing has experienced a shift from “closed” access to OA as the proportion of scholarly literature that is openly accessible has increased continuously. Estimated OA levels for publication years after 2010 varied between 29.4% and 66%. The shift towards OA is uneven across disciplines in two respects: first, the growth of OA has been uneven across disciplines, which manifests itself in varying OA prevalence levels. Second, disciplines use different OA publishing channels to make research outputs OA.

Conclusions: We conclude that historically rooted publishing practices differ in terms of their compatibility with OA, which is the reason why OA can be assumed to be a natural continuation of publishing cultures in some disciplines, whereas in other disciplines, the implementation of OA faces major barriers and would require a change of research culture.
Advances in the pathophysiology of adult-onset focal dystonias: recent neurophysiological and neuroimaging evidence
Authors: Conte Antonella , Defazio Giovanni , Mascia Marcello , Belvisi Daniele , Pantano Patrizia , Berardelli Alfredo
Published: March 2020

Focal dystonia is a movement disorder characterized by involuntary muscle contractions that determine abnormal postures. The traditional hypothesis that the pathophysiology of focal dystonia entails a single structural dysfunction (i.e. basal ganglia) has recently come under scrutiny. The proposed network disorder model implies that focal dystonias arise from aberrant communication between various brain areas. Based on findings from animal studies, the role of the cerebellum has attracted increased interest in the last few years. Moreover, it has been increasingly reported that focal dystonias also include nonmotor disturbances, including sensory processing abnormalities, which have begun to attract attention. Current evidence from neurophysiological and neuroimaging investigations suggests that cerebellar involvement in the network and mechanisms underlying sensory abnormalities may have a role in determining the clinical heterogeneity of focal dystonias.