bluuebunny/crossref_metadata_2025_split huggingface dataset:
DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study
Authors: Doubkova Martina , Kriegova Eva , Littnerova Simona , Schneiderova Petra , Sterclova Martina , Bartos Vladimir , Plackova Martina , Zurkova Monika , Bittenglova Radka , Lostaková Vladimira , Siskova Lenka , Lisa Pavlina , Suldova Hana , Doubek Michael , Psikalova Jana , Snizek Tomas , Musilova Pavlina , Vasakova Martina 
Published: September 2021

Background: The antifibrotic drugs nintedanib and pirfenidone are used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the association of common profibrotic polymorphisms in MUC5B (mucin 5B, rs35705950) and DSP (desmoplakin, rs2076295) on antifibrotic treatment outcomes in IPF. Methods: MUC5B rs35705950 and DSP rs2076295 were assessed in IPF patients ( n = 210, 139 men/71 women) from the Czech EMPIRE registry and age- or sex-matched healthy individuals ( n = 205, 125 men/80 women). Genetic data were collated with overall survival (OS), acute exacerbation episodes, worsening lung function and antifibrotic treatment. Results: We confirmed overexpression of the MUC5B rs35705950*T allele (55.2% versus 20.9%, p < 0.001) and the DSP rs2076295*G allele (80.4% versus 68.3%, p < 0.001) in IPF compared with controls. On antifibrotic drugs, lower mortability was observed in IPF patients with DSP G* allele ( p = 0.016) and MUC5B T* allele ( p = 0.079). Carriers of the DSP rs2076295*G allele benefitted from nintedanib treatment compared with TT genotype by a longer OS [hazard ratio (HR) = 7.99; 95% confidence interval (CI) = 1.56–40.90; p = 0.013] and a slower decline in lung function (HR = 8.51; 95% CI = 1.68–43.14; p = 0.010). Patients with a TT genotype (rs2076295) benefitted from treatment with pirfenidone by prolonged OS ( p = 0.040; HR = 0.35; 95% CI = 0.13–0.95) compared with nintedanib treatment. Both associations were confirmed by cross-validation analysis. After stratifying by MUC5B rs35705950*T allele carriage, no difference in treatment outcome was observed for nintedanib or pirfenidone ( p = 0.784). In the multivariate model, smoking, age, forced vital capacity (FVC) and DLCO (diffuse lung capacity) at the IPF diagnosis were associated with survival. Conclusion: Our real-world study showed that IPF patients with MUC5B T* allele or DSP G* allele profit from antifibrotic treatment by lower mortability. Moreover, carriers of the DSP rs2076295*G allele benefit from treatment with nintedanib, and TT genotype from treatment with pirfenidone. MUC5B rs35705950 did not impact the outcome of treatment with either nintedanib or pirfenidone. Our single-registry pilot study should be confirmed with an independent patient cohort.
Combined score of C-reactive protein level and neutrophil-to-lymphocyte ratio: A novel marker in distinguishing children with exacerbated asthma
Authors: Zhu Xuming , Zhou Lina , Li Qingqing , Pan Ruilin , Zhang Jian , Cui Yubao 
Published: September 2021

Background Both C-reactive protein (CRP) level and neutrophil-to-lymphocyte ratio (NLR) are commonly elevated in patients with asthma. It is necessary to develop a novel marker, the combined score of CRP level and NLR (C-NLR score) based on cutoff points of CRP and NLR, and apply it in asthma diagnosis. The aim of this study was to explore whether C-NLR could distinguish children with exacerbated asthma. Methods Children suffering from exacerbated asthma were regarded as the asthmatic group ( n = 86), which was divided into three groups: mild ( n = 54), moderate ( n = 17), and severe ( n = 15). The control group consisted of children without any allergic disease and infection ( n = 38). To compare CRP level and NLR between the asthmatic group and control group, a receiver-operating characteristic curve was constructed to determine area under the curve (AUC) and optimal cutoff point. Thereafter, the C-NLR score was classified as follows: C-NLR score of 2 with an elevated CRP level and high NLR, a C-NLR score of 1 with one of these abnormalities, and a C-NLR score of 0 with a normal CRP level and low NLR. The C-NLR score was then compared among different asthma groups. Results In the control group, the CRP level and NLR were 1.9 (0.5–2.6) mg/L and 1.01 (0.69–1.31), respectively. In the asthmatic group, the CRP level and NLR were 7.3 (3.2–14.2) mg/L and 3.08 (1.73–5.34), respectively, which were higher than those in the control group ( p < 0.001 for CRP and p < 0.001 for NLR). The AUC of CRP was 0.86, and the optimal cutoff point was 3.6 mg/L. The AUC of NLR was 0.86, and the optimal cutoff point was 1.72. The AUC of the C-NLR score was 0.94, and the optimal cutoff point was 1. Conclusions C-NLR, a novel inflammatory marker, was applied here for the exacerbated asthma for the first time. Our study has shown C-NLR is a promising marker to distinguish children with exacerbated asthma from healthy children.
Treatment patterns in women seeking care for endometriosis at an endometriosis center
Authors: Linder Katharine E , Burnett Tatnai L , Weng Chia-Sui , Khan Zaraq , Mara Kristin , Cope Adela G 
Published: September 2021

Objective: To determine the clinical characteristics and prior medical and surgical treatments in women undergoing surgical excision of endometriosis for pelvic pain at a single institution. Methods: In this retrospective cohort study we identified 140 women with pathology-proven endometriosis who completed a preoperative standardized pain form and underwent surgery at an endometriosis center. Women were stratified into three groups for analysis: no prior surgery, 1 prior surgery, and 2+ prior surgeries. Results: The most common treatments used prior to seeking care were hormonal contraceptives (51.6%) and surgery (46.1%). More than half of women were diagnosed with pelvic floor dysfunction at time of presentation or prior to consultation. There was a significant relationship between an increasing number of surgeries (none vs 1 vs 2+) and gonadotropin-releasing hormone (GnRH) agonist use (19.0% vs 27.5% vs 56.0%, p = 0.003). Though not significant, a trend was noted between increasing surgeries and opioid use (20.6% vs 30.0% vs 40.0%, p = 0.17). There was a statistically significant relationship between multiple surgeries and illicit drug use ( p < 0.001). Conclusion: Patients with pelvic pain and endometriosis who have undergone multiple surgeries are more likely to have used GnRH agonists and report illicit drug use prior to presenting to specialized care.
Effect of Time on MRI Appearance of Graft After ACL Reconstruction: A Comparison of Autologous Hamstring and Quadriceps Tendon Grafts
Authors: Panos Joseph A. , Devitt Brian M. , Feller Julian A. , Klemm Haydn J. , Hewett Timothy E. , Webster Kate E. 
Published: September 2021

Background: After anterior cruciate ligament (ACL) reconstruction (ACLR), changes in the appearance of the ACL graft can be monitored using magnetic resonance imaging (MRI). Purpose: The purpose of this study was to evaluate and compare the MRI signal intensity (SI) of hamstring and quadriceps tendon grafts during the first postoperative year after ACLR. As a secondary aim, the relationship of SI to clinical and anatomic measurements was analyzed. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 78 patients who underwent ACLR with an autologous graft were reviewed; 55 received hamstring grafts and 23 received quadriceps tendon grafts. At 3 and 9 months postoperatively, 3-T MRI was performed using a dedicated knee coil, and the median SI of the intra-articular ACL graft was measured on sagittal-plane images. Postoperative lateral radiographs were analyzed to determine medial and lateral posterior tibial slope (PTS). Side-to-side difference in anterior knee laxity between injured and uninjured limbs was measured at 6 and 12 months postoperatively. Results: The median SI of quadriceps grafts was significantly greater than hamstring grafts at 3 months after ACLR ( P = .02). Between 3 and 9 months, the median SI of quadriceps grafts decreased ( P < .001), while that of hamstring grafts did not significantly change ( P = .55). The lateral PTS was significantly correlated with median SI measurements at 3 and 9 months such that greater lateral PTS values were associated with greater median SI. The side-to-side difference in anterior knee laxity decreased for the quadriceps group ( P = .04) between 6 and 12 months but did not change for the hamstring group ( P = .88). Conclusion: The median SI of quadriceps grafts significantly decreased on MRI between 3 and 9 months after ACLR, while the median SI of hamstring grafts did not significantly change. The change in MRI appearance of the quadriceps grafts was paralleled by a reduction in anterior knee laxity between 6 and 12 months after surgery. In the absence of standardized imaging techniques and imaging analysis methods, the role of MRI in determining graft maturation, and the implications for progression through rehabilitation to return to sport, remain uncertain.
Delayed Detection of Predominantly Pericentral Hydroxychloroquine Toxicity in a Dominican Patient
Authors: Pandit Saagar A. , Nair Archana A. , Mehta Nitish , Lee Greg D. , Freund K. Bailey , Modi Yasha S. 
Published: September 2021

Purpose: To describe delayed detection of pericentral hydroxychloroquine (HCQ) toxicity. Methods: 67-year-old Dominican woman with rheumatoid arthritis on HCQ presented for examination. Results: Spectral-domain optical coherence tomography (SD-OCT) demonstrated bilateral cystoid macular edema with parafoveal attenuation of the external limiting membrane (ELM) and the ellipsoid zone (EZ). ELM and EZ disruption was present in inferior macula. While subtle superior defects were present on 10-2 visual fields, superior pericentral defects were noted on 24-2 testing. Hyperautofluorescence along inferior arcades corresponded to SD-OCT and visual fields. Examination 2 years prior demonstrated nonspecific points of depression on 10-2 visual fields and normal central SD-OCT findings. EZ and ELM disruption was present in the perifoveal inferior macula. Conclusions: Early pericentral distribution of HCQ toxicity is not limited to Asian patients. Detecting pericentral HCQ toxicity involves reviewing entire macular cube on OCT. When OCT changes are suspected on parafoveal OCT B-scans, visual field testing with 24-2 may be more sensitive than 10-2.
Exploring the impact of workforce turnover on the sustainability of evidence-based programs: A scoping review
Authors: Pascoe Kelley M , Petrescu-Prahova Miruna , Steinman Lesley , Bacci Jennifer , Mahorter Siobhan , Belza Basia , Weiner Bryan 
Published: September 2021

Background Evidence-based programs (EBPs) are used across disciplines to integrate research into practice and improve outcomes at the individual and/or community level. Despite widespread development and implementation of EBPs, many programs are not sustained beyond the initial implementation period due to many factors, including workforce turnover. This scoping review summarizes research on the impact of workforce turnover on the sustainability of EBPs and recommendations for mitigating these impacts. Methods We searched 10 databases for articles that focused on an EBP and described an association between workforce turnover and the sustainment or sustainability of the program. We created a data abstraction tool to extract relevant information from each article and applied the data abstraction tool to all included articles to create the dataset. Data were mapped and analyzed using the program sustainability framework (PSF). Results and Discussion A total of 30 articles were included in this scoping review and mapped to the PSF. Twenty-nine articles described impacts of workforce turnover and 18 articles proposed recommendations to address the impacts. The most frequent impacts of workforce turnover included increased need for training, loss of organizational knowledge, lack of EBP fidelity, and financial stress. Recommendations to address the impact of workforce turnover included affordable and alternative training modalities, the use of champions or volunteers, increasing program alignment with organizational goals, and generating diverse funding portfolios. Conclusion The sustainment of EBPs is critical to ensure and maintain the short- and long-term benefits of the EBP for all participants and communities. Understanding the impacts of workforce turnover, a determinant of sustainability, can create awareness among EBP-implementing organizations and allow for proactive planning to increase the likelihood of program sustainability.
Murine AGM single-cell profiling identifies a continuum of hemogenic endothelium differentiation marked by ACE
Authors: Fadlullah Muhammad Zaki Hidayatullah , Neo Wen Hao , Lie-a-ling Michael , Thambyrajah Roshana , Patel Rahima , Mevel Renaud , Aksoy Irène , Do Khoa Nam , Savatier Pierre , Fontenille Laura , Baker Syed Murtuza , Rattray Magnus , Kouskoff Valerie , Lacaud Georges 
Published: September 2021

AbstractIn vitro generation and expansion of hematopoietic stem cells (HSCs) holds great promise for the treatment of any ailment that relies on bone marrow or blood transplantation. To achieve this, it is essential to resolve the molecular and cellular pathways that govern HSC formation in the embryo. HSCs first emerge in the aorta-gonad-mesonephros (AGM) region, where a rare subset of endothelial cells, hemogenic endothelium (HE), undergoes an endothelial-to-hematopoietic transition (EHT). Here, we present full-length single-cell RNA sequencing (scRNA-seq) of the EHT process with a focus on HE and dorsal aorta niche cells. By using Runx1b and Gfi1/1b transgenic reporter mouse models to isolate HE, we uncovered that the pre-HE to HE continuum is specifically marked by angiotensin-I converting enzyme (ACE) expression. We established that HE cells begin to enter the cell cycle near the time of EHT initiation when their morphology still resembles endothelial cells. We further demonstrated that RUNX1 AGM niche cells consist of vascular smooth muscle cells and PDGFRa+ mesenchymal cells and can functionally support hematopoiesis. Overall, our study provides new insights into HE differentiation toward HSC and the role of AGM RUNX1+ niche cells in this process. Our expansive scRNA-seq datasets represents a powerful resource to investigate these processes further.
How I treat AL amyloidosis
Authors: Palladini Giovanni , Merlini Giampaolo 
Published: September 2021

Abstract
The treatment of patients with systemic light chain (AL) amyloidosis is a challenge to hematologists. Despite its generally small size, the underlying clone causes a rapidly progressing, often devastating multiorgan dysfunction through the toxic light chains that form amyloid deposits. Clinical manifestations are deceitful and too often recognized at an irreversible stage. However, hematologists are in the unique position to diagnose AL amyloidosis at a presymptomatic stage, checking biomarkers of amyloid organ involvement in patients with monoclonal gammopathies at higher risk to develop the disease. Adequate technology and expertise are needed for a prompt and correct diagnosis, particularly for ruling out non-AL amyloidoses that are now also treatable. Therapy should be carefully tailored based on severity of organ involvement and clonal characteristics, and early and continual monitoring of response is critical. Three recent randomized clinical trials moved AL amyloidosis to evidence-based era. Above all, the daratumumab-bortezomib combination is a new standard-of-care for newly diagnosed patients, inducing rapid and deep responses that translate into high rates of organ response. The availability of new effective drugs allows to better personalize the therapy, reduce toxicity, and improve outcomes. Patients should be treated within clinical trials whenever possible.
Tuning the Toxicity of Reactive Oxygen Species into Advanced Tumor Therapy
Authors: Xie An , Li He , Hao Yumei , Zhang Yujia 
Published: September 2021

AbstractThe biological functions and toxic effects of reactive oxygen species (ROS) are generally entangled. A large amount of ROS may cause oxidative damage to cell biomolecules, leading to cell death. Tumor treatment can be carried out by using the toxicity of ROS, and various nanosystems related to ROS have been designed. In fact, the level of active oxygen in the biological microenvironment can be regulated in advanced therapeutics via designed nanoscale engineering, which can open up a new direction of treatment with specific simplicity. In this progress report, the authors first introduced how ROS causes cell death. Then, recent studies on converting the inherent toxicity from ROS into advanced treatment tools are highlighted.
Gene co-expression network analysis in zebrafish reveals chemical class specific modules
Authors: Shankar Prarthana , McClure Ryan S. , Waters Katrina M. , Tanguay Robyn L. 
Published: September 2021

Abstract
Background
Zebrafish is a popular animal model used for high-throughput screening of chemical hazards, however, investigations of transcriptomic mechanisms of toxicity are still needed. Here, our goal was to identify genes and biological pathways that Aryl Hydrocarbon Receptor 2 (AHR2) Activators and flame retardant chemicals (FRCs) alter in developing zebrafish. Taking advantage of a compendium of phenotypically-anchored RNA sequencing data collected from 48-h post fertilization (hpf) zebrafish, we inferred a co-expression network that grouped genes based on their transcriptional response.

Results
Genes responding to the FRCs and AHR2 Activators localized to distinct regions of the network, with FRCs inducing a broader response related to neurobehavior. AHR2 Activators centered in one region related to chemical stress responses. We also discovered several highly co-expressed genes in this module, including cyp1a, and we subsequently show that these genes are definitively within the AHR2 signaling pathway. Systematic removal of the two chemical types from the data, and analysis of network changes identified neurogenesis associated with FRCs, and regulation of vascular development associated with both chemical classes. We also identified highly connected genes responding specifically to each class that are potential biomarkers of exposure.

Conclusions
Overall, we created the first zebrafish chemical-specific gene co-expression network illuminating how chemicals alter the transcriptome relative to each other. In addition to our conclusions regarding FRCs and AHR2 Activators, our network can be leveraged by other studies investigating chemical mechanisms of toxicity.
Influence of rosuvastatin treatment on cerebral inflammation and nitro-oxidative stress in experimental lung injury in pigs
Authors: Kamuf Jens , Garcia Bardon Andreas , Ziebart Alexander , Ruemmler Robert , Schwab Johannes , Dib Mobin , Daiber Andreas , Thal Serge C. , Hartmann Erik K. 
Published: September 2021

Abstract
Background
Many patients with acute respiratory distress syndrome (ARDS) suffer from cognitive impairment after hospital discharge. Different mechanisms have been implicated as potential causes for this impairment, inter alia cerebral inflammation. A class of drugs with antioxidant and anti-inflammatory properties are β-HMG-CoA-reductase inhibitors (“statins”). We hypothesized that treatment with rosuvastatin attenuates cerebral cytokine mRNA expression and nitro-oxidative stress in an animal model of acute lung injury.

Methods
After approval of the institutional and state animal care committee, we performed this prospective randomized controlled animal study in accordance with the international guidelines for the care and use of laboratory animals. Thirty-two healthy male pigs were randomized to one of four groups: lung injury by central venous injection of oleic acid (n = 8), statin treatment before and directly after lung injury (n = 8), statin treatment after lung injury (n = 8), or ventilation-only controls (n = 8). About 18 h after lung injury and standardized treatment, the animals were euthanised, and the brains and lungs were collected for further examinations. We determined histologic lung injury and cerebral and pulmonal cytokine and 3-nitrotyrosine production.

Results
We found a significant increase in hippocampal IL-6 mRNA after lung injury (p < 0.05). Treatment with rosuvastatin before and after induction of lung injury led to a significant reduction of hippocampal IL-6 mRNA (p < 0.05). Cerebral 3-nitrotyrosine was significantly higher in lung-injured animals compared with all other groups (p < 0.05 vs. animals treated with rosuvastatin after lung injury induction; p < 0.001 vs. all other groups). 3-Nitrotyrosine was also increased in the lungs of the lung-injured pigs compared to all other groups (p < 0.05 each).

Conclusions
Our findings highlight cerebral cytokine production and nitro-oxidative stress within the first day after induction of lung injury. The treatment with rosuvastatin reduced IL-6 mRNA and 3-nitrotyrosine concentration in the brains of the animals. In earlier trials, statin treatment did not reduce mortality in ARDS patients but seemed to improve quality of life in ARDS survivors. Whether this is attributable to better cognitive function because of reduced nitro-oxidative stress and inflammation remains to be elucidated.
Increased integrated testing for HIV, hepatitis C and sexually transmitted infections in health care facilities: results from the INTEGRATE Joint Action pilots in Lithuania, Romania and Spain
Authors: Matulionytė R. , Jakobsen M. L. , Grecu V. I. , Grigaitiene J. , Raudonis T. , Stoniene L. , Olteanu M. , de la Mora L. , Raben D. , Sullivan A. K. 
Published: September 2021

Abstract
Background
Indicator condition guided HIV testing is a proven effective strategy for increasing HIV diagnosis in health care facilities. As part of the INTEGRATE Joint Action, we conducted four pilot studies, aiming to increase integrated testing for HIV/HCV/HBV and sexually transmitted infections, by introducing and expanding existing indicator condition guided HIV testing methods.

Methods
Pilot interventions included combined HIV/HCV testing in a dermatovenerology clinic and a clinic for addictive disorders in Lithuania; Increasing HIV testing rates in a tuberculosis clinic in Romania by introducing a patient information leaflet and offering testing for HIV/HCV/sexually transmitted infections to chemsex-users in Barcelona. Methods for implementing indicator condition guided HIV testing were adapted to include integrated testing. Testing data were collected retrospectively and prospectively. Staff were trained in all settings, Plan-do-study-act cycles frequently performed and barriers to implementation reported.

Results
In established indicator conditions, HIV absolute testing rates increased from 10.6 to 71% in the dermatovenerology clinic over an 18 months period. HIV testing rates improved from 67.4% at baseline to 94% in the tuberculosis clinic. HCV testing was added to all individuals in the dermatovenerology clinic, eight patients of 1701 tested positive (0.47%). HBV testing was added to individuals with sexually transmitted infections with a 0.44% positivity rate (2/452 tested positive). The Indicator condition guided HIV testing strategy was expanded to offer HIV/HCV testing to people with alcohol dependency and chemsex-users. 52% of chemsex-users tested positive for ≥ 1 sexually transmitted infection and among people with alcohol dependency 0.3 and 3.7% tested positive for HIV and HCV respectively.

Conclusions
The four pilot studies successfully increased integrated testing in health care settings, by introducing testing for HBV/HCV and sexually transmitted infections along with HIV testing for established indicator conditions and expanding the strategy to include new indicators; alcohol dependency and chemsex. HCV testing of individuals with alcohol abuse showed high positivity rates and calls for further implementation studies. Methods used for implementing indicator condition guided HIV Testing have proven transferable to implementation of integrated testing.