bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empowering the discovery of novel target-disease associations via machine learning approaches in the open targets platform
Authors: Han Yingnan , Klinger Katherine , Rajpal Deepak K. , Zhu Cheng , Teeple Erin 
Published: June 2022

Abstract
Background
The Open Targets (OT) Platform integrates a wide range of data sources on target-disease associations to facilitate identification of potential therapeutic drug targets to treat human diseases. However, due to the complexity that targets are usually functionally pleiotropic and efficacious for multiple indications, challenges in identifying novel target to indication associations remain. Specifically, persistent need exists for new methods for integration of novel target-disease association evidence and biological knowledge bases via advanced computational methods. These offer promise for increasing power for identification of the most promising target-disease pairs for therapeutic development. Here we introduce a novel approach by integrating additional target-disease features with machine learning models to further uncover druggable disease to target indications.

Results
We derived novel target-disease associations as supplemental features to OT platform-based associations using three data sources: (1) target tissue specificity from GTEx expression profiles; (2) target semantic similarities based on gene ontology; and (3) functional interactions among targets by embedding them from protein–protein interaction (PPI) networks. Machine learning models were applied to evaluate feature importance and performance benchmarks for predicting targets with known drug indications. The evaluation results show the newly integrated features demonstrate higher importance than current features in OT. In addition, these also show superior performance over association benchmarks and may support discovery of novel therapeutic indications for highly pursued targets.

Conclusion
Our newly generated features can be used to represent additional underlying biological relatedness among targets and diseases to further empower improved performance for predicting novel indications for drug targets through advanced machine learning models. The proposed methodology enables a powerful new approach for systematic evaluation of drug targets with novel indications.
On the effect of inheritance of microbes in commensal microbiomes
Authors: Zapién-Campos Román , Bansept Florence , Sieber Michael , Traulsen Arne 
Published: June 2022

Abstract
Background
Our current view of nature depicts a world where macroorganisms dwell in a landscape full of microbes. Some of these microbes not only transit but establish themselves in or on hosts. Although hosts might be occupied by microbes for most of their lives, a microbe-free stage during their prenatal development seems to be the rule for many hosts. The questions of who the first colonizers of a newborn host are and to what extent these are obtained from the parents follow naturally.

Results
We have developed a mathematical model to study the effect of the transfer of microbes from parents to offspring. Even without selection, we observe that microbial inheritance is particularly effective in modifying the microbiome of hosts with a short lifespan or limited colonization from the environment, for example by favouring the acquisition of rare microbes.

Conclusion
By modelling the inheritance of commensal microbes to newborns, our results suggest that, in an eco-evolutionary context, the impact of microbial inheritance is of particular importance for some specific life histories.
A pragmatic effectiveness-implementation study comparing trial evidence with routinely collected outcome data for patients receiving the REACH-HF home-based cardiac rehabilitation programme
Authors: Daw Paulina , Harrison Alexander , Doherty Patrick J. , van Zanten Jet J. C. S. Veldhuijzen , Dalal Hasnain M. , Taylor Rod S. , van Beurden Samantha B. , McDonagh Sinéad T. J. , Greaves Colin J. 
Published: June 2022

Abstract
Background
Cardiac rehabilitation for heart failure continues to be greatly underused worldwide despite being a Class I recommendation in international clinical guidelines and uptake is low in women and patients with mental health comorbidities.

Methods
Rehabilitation EnAblement in CHronic Heart Failure (REACH-HF) programme was implemented in four UK National Health Service early adopter sites (‘Beacon Sites’) between June 2019 and June 2020. Implementation and patient-reported outcome data were collected across sites as part of the National Audit of Cardiac Rehabilitation. The change in key outcomes before and after the supervised period of REACH-HF intervention across the Beacon Sites was assessed and compared to those of the intervention arm of the REACH-HF multicentre trial.

Results
Compared to the REACH-HF multicentre trial, patients treated at the Beacon Site were more likely to be female (33.8% vs 22.9%), older (75.6 vs 70.1), had a more severe classification of heart failure (26.5% vs 17.7%), had poorer baseline health-related quality of life (MLHFQ score 36.1 vs 31.4), were more depressed (HADS score 6.4 vs 4.1) and anxious (HADS score 7.2 vs 4.7), and had lower exercise capacity (ISWT distance 190 m vs 274.7 m). There appeared to be a substantial heterogeneity in the implementation process across the four Beacon Sites as evidenced by the variation in levels of patient recruitment, operationalisation of the REACH-HF intervention and patient outcomes. Overall lower improvements in patient-reported outcomes at the Beacon Sites compared to the trial may reflect differences in the population studied (having higher morbidity at baseline) as well as the marked challenges in intervention delivery during the COVID-19 pandemic.

Conclusion
The results of this study illustrate the challenges in consistently implementing an intervention (shown to be clinically effective and cost-effective in a multicentre trial) into real-world practice, especially in the midst of a global pandemic. Further research is needed to establish the real-world effectiveness of the REACH-HF intervention in different populations.
Portable stroke detection devices: a systematic scoping review of prehospital applications
Authors: Chennareddy Susmita , Kalagara Roshini , Smith Colton , Matsoukas Stavros , Bhimani Abhiraj , Liang John , Shapiro Steven , De Leacy Reade , Mokin Maxim , Fifi Johanna T. , Mocco J , Kellner Christopher P. 
Published: June 2022

Abstract
Background
The worldwide burden of stroke remains high, with increasing time-to-treatment correlated with worse outcomes. Yet stroke subtype determination, most importantly between stroke/non-stroke and ischemic/hemorrhagic stroke, is not confirmed until hospital CT diagnosis, resulting in suboptimal prehospital triage and delayed treatment. In this study, we survey portable, non-invasive diagnostic technologies that could streamline triage by making this initial determination of stroke type, thereby reducing time-to-treatment.

Methods
Following PRISMA guidelines, we performed a scoping review of portable stroke diagnostic devices. The search was executed in PubMed and Scopus, and all studies testing technology for the detection of stroke or intracranial hemorrhage were eligible for inclusion. Extracted data included type of technology, location, feasibility, time to results, and diagnostic accuracy.

Results
After a screening of 296 studies, 16 papers were selected for inclusion. Studied devices utilized various types of diagnostic technology, including near-infrared spectroscopy (6), ultrasound (4), electroencephalography (4), microwave technology (1), and volumetric impedance spectroscopy (1). Three devices were tested prior to hospital arrival, 6 were tested in the emergency department, and 7 were tested in unspecified hospital settings. Median measurement time was 3 minutes (IQR: 3 minutes to 5.6 minutes). Several technologies showed high diagnostic accuracy in severe stroke and intracranial hematoma detection.

Conclusion
Numerous emerging portable technologies have been reported to detect and stratify stroke to potentially improve prehospital triage. However, the majority of these current technologies are still in development and utilize a variety of accuracy metrics, making inter-technology comparisons difficult. Standardizing evaluation of diagnostic accuracy may be helpful in further optimizing portable stroke detection technology for clinical use.
Stimulated phosphorylation of ERK in mouse kidney mesangial cells is dependent upon expression of Cav3.1
Authors: Pandi Sudha Priya Soundara , Shattock Michael J. , Hendry Bruce M. , Sharpe Claire C. 
Published: June 2022

Abstract
Background
T-type calcium channels (TTCC) are low voltage activated channels that are widely expressed in the heart, smooth muscle and neurons. They are known to impact on cell cycle progression in cancer and smooth muscle cells and more recently, have been implicated in rat and human mesangial cell proliferation. The aim of this study was to investigate the roles of the different isoforms of TTCC in mouse mesangial cells to establish which may be the best therapeutic target for treating mesangioproliferative kidney diseases.

Methods
In this study, we generated single and double knockout (SKO and DKO) clones of the TTCC isoforms CaV3.1 and CaV3.2 in mouse mesangial cells using CRISPR-cas9 gene editing. The downstream signals linked to this channel activity were studied by ERK1/2 phosphorylation assays in serum, PDGF and TGF-β1 stimulated cells. We also examined their proliferative responses in the presence of the TTCC inhibitors mibefradil and TH1177.

Results
We demonstrate a complete loss of ERK1/2 phosphorylation in response to multiple stimuli (serum, PDGF, TGF-β1) in CaV3.1 SKO clone, whereas the CaV3.2 SKO clone retained these phospho-ERK1/2 responses. Stimulated cell proliferation was not profoundly impacted in either SKO clone and both clones remained sensitive to non-selective TTCC blockers, suggesting a role for more than one TTCC isoform in cell cycle progression. Deletion of both the isoforms resulted in cell death.

Conclusion
This study confirms that TTCC are expressed in mouse mesangial cells and that they play a role in cell proliferation. Whereas the CaV3.1 isoform is required for stimulated phosphorylation of ERK1/2, the Ca V3.2 isoform is not. Our data also suggest that neither isoform is necessary for cell proliferation and that the anti-proliferative effects of mibefradil and TH1177 are not isoform-specific. These findings are consistent with data from in vivo rat mesangial proliferation Thy1 models and support the future use of genetic mouse models to test the therapeutic actions of TTCC inhibitors.
Pregnant at the start of the pandemic: a content analysis of COVID-19-related posts on online pregnancy discussion boards
Authors: Choi Rebekah , Nagappan Ashwini , Kopyto Deena , Wexler Anna 
Published: June 2022

Abstract
Background
A growing body of evidence indicates that the COVID-19 pandemic has had detrimental mental health effects for pregnant women. However, little is known about the specific stressors that increased anxiety for pregnant women at the start of the pandemic. The present study aimed to better understand the concerns of pregnant women during the beginning COVID-19 pandemic by analyzing content posted during the month of March 2020 on online pregnancy message boards hosted on WhatToExpect.com.

Methods
All posts published between March 1–31, 2020 on nine different due-date specific WhatToExpect.com message boards were reviewed for COVID-19 relevance. Posts mentioning COVID-19 or its direct effects (e.g., “quarantine” or “stay-at-home order”) were included in our final sample. Data were coded by three authors according to a codebook developed inductively by all four authors. Posts were analyzed by overall frequency of appearance, by trimester, and temporally across the month of March 2020.

Results
Across the 5,541 posts included in our final sample, the most common topics were fear of COVID-19 exposure, concerns with labor and delivery, navigating social interactions, and disruptions to prenatal care. The most dominant topics by trimester were disruptions to prenatal care (first trimester), fear of COVID-19 exposure (second trimester), and concerns about labor and delivery (third trimester).

Conclusion
Our findings add to prior literature by demonstrating the salience of social concerns, which was the third largest COVID-19 topic in our sample. Emotional distress was most salient with regard to restrictions on birthing partners, but was apparent in everything from disruptions to pregnancy announcements, to cancelled baby showers, and limitations on newborn visitors. Given that anxiety during pregnancy is associated with worse maternal–fetal health outcomes, in the early stages of future pandemics healthcare providers should focus not only on strictly health-related concerns expressed by pregnant women, but also more broadly on other sources of anxiety that may be impacting the well-being and mental health of their patients.
Isolated steroid-resistant nephrotic syndrome in a Chinese child carrying a de novo mutation in WT1 gene:a case report and literature review
Authors: Li Yiyang , Tian Chuan , Wang Yajun , Ma Guoda , Chen Riling 
Published: June 2022

Abstract
Background
Isolated steroid-resistant nephrotic syndrome (ISRNS) is caused by mutations in the Wilms’ tumor-1 (WT1) gene, which encodes glomerular podocytes and podocyte slit diaphragm.We report a novel 8-year-old female patient with ISRNS carrying a de novo missense mutation in WT1 gene and presenting a new type of pathology, have never been reported.We also systematically review previous reports of ISRNS in Chinese children.

Case presentation
A 8-year-old Chinese patient who had steroid-resistant nephrotic syndrome,responded poorly to immunosuppressant, and had no extrarenal manifestations. The patient had a female phenotype and karyotype of 46, XX. A new type of renal pathology, proliferative sclerosing glomerulonephritis (PSG),and a de novo missense mutation in WT1 gene, c.748C > T (p.R250W),which have not yet been reported, were identified. She was diagnosed with ISRNS.The patient progressed to end-stage renal disease at the age of 10 years,underwent dialysis and kidney transplant. Renal function and urine protein were normal during 4-year follow-up.

Conclusions
WT1 gene testing should be performed to guide treatment for patients with steroid-resistant nephrotic syndrome, especially for isolated cases and female patients.
Interactive effects of maternal exposure to chemical fertilizer and socio-economic status on the risk of low birth weight
Authors: Lin Shiqi , Li Jiajia , Wu Jilei , Yang Fan , Pei Lijun , Shang Xuejun 
Published: June 2022

Abstract
Background
Maternal exposure to chemical fertilizer and disadvantaged maternal socio-economic status (SES) have been found to associate with increased risk of low birth weight (LBW). However, whether the two factors would interact to elevate the risk of LBW remains unknown. The present study aimed to explore the interactive effects of maternal exposure to chemical fertilizer during pregnancy and low SES on the risk of term LBW (tLBW).

Methods
In this population-based case–control study, 179 tLBW cases (birthweight < 2500 g and gestational age ≥ 37 weeks) and 204 controls (birthweight ≥ 2500 g and gestational age ≥ 37 weeks) were chosen from the Perinatal Health Care Surveillance System of Pingding County, Shanxi Province, China between 2007 and 2012. Data on basic socio-demographic, dietary and lifestyle characteristics and environmental exposure were directly extracted from the system. Maternal exposure to chemical fertilizer was measured at both household level and village level. Household-level exposure was indicated by household chemical fertilizer use in farming during pregnancy and the data was collected by trained healthcare workers after the selection of cases and controls in 2013. Village-level exposure was indicated by annual amount of village chemical fertilizer consumption per acre and the data came from the Annals of National Economics Statistics of Pingding County in 2010. Interactions between maternal exposure to chemical fertilizer and SES were assessed in logistic regressions using relative excess risk due to interaction (RERI), which indicates an additive interaction if larger than 0.

Results
The combination of low maternal SES and high exposure to village-level chemical fertilizer consumption was associated with increased risk of tLBW (aOR = 2.62, 95%CI: 1.44 ~ 4.77); The combination of low maternal SES and exposure to household chemical fertilizer use was associated with elevated risk of tLBW (aOR = 2.18, 95%CI: 1.24 ~ 3.83). Additive interactions were detected between high exposure to village-level chemical fertilizer consumption and low maternal SES (RERI:1.79, P < 0.001) and between exposure to household chemical fertilizer use and low maternal SES (RERI:0.77, P < 0.05).

Conclusions
Our study suggested negative impacts of potential agricultural pollutants on adverse pregnancy outcomes, especially in disadvantaged socio-economic populations.
Understanding the journeys of patients with an asthma exacerbation requiring urgent therapy at a primary care clinic
Authors: Quek Jing Sheng , Tang Wern Ee , Chen Elya , Smith Helen Elizabeth 
Published: June 2022

Abstract
Background
Asthma is a significant health issue in primary care. We examined the journeys of patients with asthma exacerbations requiring urgent therapy at a primary care clinic in Singapore.

Methods
Face-to-face semi-structured interviews were conducted with patients who received urgent therapy for asthma exacerbation at a primary care clinic. Data collected was used to construct themes.

Results
Fifteen multi-ethnic adult patients were recruited. Participants cited treatment cost, underuse of preventer medication, difficulties attending routine asthma care due to work, and stigma as barriers to asthma control. Reasons for delay in seeking urgent care for asthma were: inability to access medical care out of hours, competing priorities, perception that an exacerbation was ‘not serious enough’, difficulty recognizing symptoms of asthma exacerbation, and being tired or despondent. Participants were triggered to seek care due to failure of reliever inhalers, duration of symptoms, sleep disturbance, inability to work, or advice from others. During an exacerbation, participants often initiated other self-management measures besides using reliever medication. This included over-the-counter medications and non-pharmacological interventions (e.g. drinking water). Of the 15 patients interviewed, only one stepped up preventer inhaler adequately, according to their Asthma Action Plan (AAP).

Conclusions
In caring for patients with asthma, primary care providers should address patients’ asthma self-management skills, such as recognizing symptoms of asthma exacerbations and regular preventer use, and provide clear instructions on how to respond to asthma symptoms (AAP). Minimizing direct (medication and consultation fees) and indirect costs (loss of earnings and adverse impact on employment prospects) are also important considerations.
Lung disease burden assessment by oscillometry in a systematically disadvantaged urban population experiencing homelessness or at-risk for homelessness in Ottawa, Canada from a prospective observational study
Authors: Pakhale Smita , Visentin Carly , Tariq Saania , Kaur Tina , Florence Kelly , Bignell Ted , Jama Sadia , Huynh Nina , Boyd Robert , Haddad Joanne , Alvarez Gonzalo G. 
Published: June 2022

Abstract
Rationale
Oscillometry is an emerging technique that offers some advantages over spirometry as it does not require forced exhalation and may detect early changes in respiratory pathology. Obstructive lung disease disproportionately impacts people experiencing homelessness with a high symptoms burden, yet oscillometry is not studied in this population.

Objectives
To assess lung disease and symptom burden using oscillometry in people experiencing homelessness or at-risk of homelessness using a community-based participatory action research approach (The Bridge Model™).

Methods
Of 80 recruited, 55 completed baseline oscillometry, 64 completed spirometry, and all completed patient-reported outcomes with demographics, health, and respiratory symptom related questionnaires in the Participatory Research in Ottawa: Management and Point-of-Care for Tobacco Dependence project. Using a two-tail t-test, we compared mean oscillometry values for airway resistance (R5–20), reactance area under the curve (Ax) and reactance at 5 Hz (X5) amongst individuals with fixed-ratio method (FEV1/FVC ratio < 0.70) and LLN (FEV1/FVC ratio ≤ LLN) spirometry diagnosed chronic obstructive pulmonary disease (COPD). We compared mean oscillometry parameters based on participants’ COPD assessment test (CAT) scores using ANOVA test.

Results
There was no significant difference between the pre- and post- bronchodilator values of R5–20 and Ax for the fixed ratio method (p = 0.63 and 0.43) and the LLN method (p = 0.45 and 0.36). There was a significant difference in all three of the oscillometry parameters, R5–20, Ax and X5, based on CAT score (p = 0.009, 0.007 and 0.05, respectively). There was a significant difference in R5–20 and Ax based on the presence of phlegm (p = 0.03 and 0.02, respectively) and the presence of wheeze (p = 0.05 and 0.01, respectively). Oscillometry data did not correlate with spirometry data, but it was associated with CAT scores and correlated with the presence of self-reported symptoms of phlegm and wheeze in this population.

Conclusions
Oscillometry is associated with respiratory symptom burden and highlights the need for future studies to generate more robust data regarding the use of oscillometry in systematically disadvantaged populations where disease burden is disproportionately higher than the general population.
TrialRegistration: ClinicalTrails.gov—NCT03626064, Retrospective registered: August 2018, https://clinicaltrials.gov/ct2/show/NCT03626064