bluuebunny/crossref_metadata_2025 huggingface dataset:
Women’s experiences of indignity in immigration detention and beyond
Authors: Gerlach Alice
Published: June 2022

In this article, I set out to define dignity in immigration detention and beyond. Throughout this piece, I will examine the role of dignity in detention, and the way in which the existence of ‘dignity’ in detention impacts on people when they are in detention and after they leave. Based on interviews and research with women who have experienced immigration detention in the United Kingdom, it is clear that this experience of indignity has had a lasting impact on women, causing them distress both in detention and after they leave. The key themes emerging out of this research into violations of dignity include vilification, lack of autonomy and ‘diminishment’. In light of this, I suggest that immigration detention is incompatible with the concept of dignity that has been defined by the women in this study.
Single-cell multiomics reveal the scale of multilayered adaptations enabling CLL relapse during venetoclax therapy
Authors: Thijssen Rachel , Tian Luyi , Anderson Mary Ann , Flensburg Christoffer , Jarratt Andrew , Garnham Alexandra L. , Jabbari Jafar S. , Peng Hongke , Lew Thomas E. , Teh Charis E. , Gouil Quentin , Georgiou Angela , Tan Tania , Djajawi Tirta M. , Tam Constantine S. , Seymour John F. , Blombery Piers , Gray Daniel H. D. , Majewski Ian J. , Ritchie Matthew E. , Roberts Andrew W. , Huang David C. S.
Published: June 2022

Venetoclax (VEN) inhibits the prosurvival protein BCL2 to induce apoptosis and is a standard therapy for chronic lymphocytic leukemia (CLL), delivering high complete remission rates and prolonged progression-free survival in relapsed CLL but with eventual loss of efficacy. A spectrum of subclonal genetic changes associated with VEN resistance has now been described. To fully understand clinical resistance to VEN, we combined single-cell short- and long-read RNA-sequencing to reveal the previously unappreciated scale of genetic and epigenetic changes underpinning acquired VEN resistance. These appear to be multilayered. One layer comprises changes in the BCL2 family of apoptosis regulators, especially the prosurvival family members. This includes previously described mutations in BCL2 and amplification of the MCL1 gene but is heterogeneous across and within individual patient leukemias. Changes in the proapoptotic genes are notably uncommon, except for single cases with subclonal losses of BAX or NOXA. Much more prominent was universal MCL1 gene upregulation. This was driven by an overlying layer of emergent NF-κB (nuclear factor kappa B) activation, which persisted in circulating cells during VEN therapy. We discovered that MCL1 could be a direct transcriptional target of NF-κB. Both the switch to alternative prosurvival factors and NF-κB activation largely dissipate following VEN discontinuation. Our studies reveal the extent of plasticity of CLL cells in their ability to evade VEN-induced apoptosis. Importantly, these findings pinpoint new approaches to circumvent VEN resistance and provide a specific biological justification for the strategy of VEN discontinuation once a maximal response is achieved rather than maintaining long-term selective pressure with the drug.
European Respiratory Society guidelines on transbronchial lung cryobiopsy in the diagnosis of interstitial lung diseases
Authors: Korevaar Daniël A. , Colella Sara , Fally Markus , Camuset Juliette , Colby Thomas V. , Hagmeyer Lars , Hetzel Juergen , Maldonado Fabien , Morais Antonio , Ravaglia Claudia , Spijker René , Tomassetti Sara , Troy Lauren K. , Verschakelen Johny A. , Wells Athol U. , Tonia Thomy , Annema Jouke T. , Poletti Venerino
Published: June 2022

Background

In patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD.

Methods

The ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied.

Results

In patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required.

Conclusions

TBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly “very low”.
Impact of wait times for treatment on clinical outcomes in patients with obstructive sleep apnoea: protocol for a randomised controlled trial
Authors: Thornton Christina S. , Povitz Marcus , Tsai Willis H. , Loewen Andrea H. , Ip-Buting Ada , Kendzerska Tetyana , Flemons W. Ward , Fraser Kristin L. , Hanly Patrick J. , Pendharkar Sachin R.
Published: June 2022

Background

Obstructive sleep apnoea (OSA) is a common chronic condition that is associated with significant morbidity and economic cost. Prolonged wait times are increasingly being recognised as a barrier to diagnosis and treatment of many chronic diseases; however, no study to date has prospectively evaluated the impact of wait times on health outcomes in OSA.

Objective

The purpose of this study is to determine whether treatment outcomes for individuals with OSA differ between patients managed using an expeditedversusstandard pathway.

Methods

A pragmatic randomised controlled trial design will be used with a target sample size of 200 adults. Participants with clinically significant uncomplicated OSA will be recruited through referrals to a large tertiary care sleep centre (Calgary, AB, Canada) and randomised to either early management (within 1 month) or usual care (∼6 months) with a 1:1 allocation using a concealed computer-generated randomisation sequence. The primary outcome will be adherence to positive airway pressure (PAP) therapy at 3 months after treatment initiation. Secondary outcomes will include change in sleepiness, quality of life, patient satisfaction, and patient engagement with therapy from baseline to 3 months after PAP initiation, measured using validated questionnaires and qualitative methods.

Anticipated results

This study will determine whether expedited care for OSA leads to differences in PAP adherence and/or patient-reported outcomes. More broadly, the findings of this study may improve the understanding of how wait time reductions impact health outcomes for other chronic diseases.
Real-life burden of hospitalisations due to COPD exacerbations in Spain
Authors: Izquierdo José Luis , Rodríguez José Miguel , Almonacid Carlos , Benavent María , Arroyo-Espliguero Ramón , Agustí Alvar
Published: June 2022

Background

Patients with chronic obstructive pulmonary disease (COPD) often suffer episodes of exacerbation of symptoms (ECOPD) that may eventually require hospitalisation due to several, often overlapping, causes. We aimed to analyse the characteristics of patients hospitalised because of ECOPD in a real-life setting using a “big data” approach.

Methods

The study population included all patients over 40 years old with a diagnosis of COPD (n=69 359; prevalence 3.72%) registered from 1 January 2011 to 1 March 2020 in the database of the public healthcare service (SESCAM) of Castilla-La Mancha (Spain) (n=1 863 759 subjects). We used natural language processing (Savana Manager version 3.0) to identify those who were hospitalised during this period for any cause, including ECOPD.

Results

During the study 26 453 COPD patients (38.1%) were hospitalised (at least once). Main diagnoses at discharge were respiratory infection (51%), heart failure (38%) or pneumonia (19%). ECOPD was the main diagnosis at discharge (or hospital death) in 8331 patients (12.0% of the entire COPD population and 31.5% of those hospitalised). In-hospital ECOPD-related mortality rate was 3.11%. These patients were hospitalised 2.36 times per patient, with a mean hospital stay of 6.1 days. Heart failure was the most frequent comorbidity in patients hospitalised because of ECOPD (52.6%).

Conclusions

This analysis shows that, in a real-life setting, ECOPD hospitalisations are prevalent, complex (particularly in relation to heart failure), repetitive and associated with significant in-hospital mortality.
Trends and predictors of specialist assessments in oral corticosteroid treated asthma among young adults
Authors: Skov Inge Raadal , Madsen Hanne , Andersen Jacob Harbo , Pottegård Anton , Davidsen Jesper Rømhild
Published: June 2022

Background

Repeated oral corticosteroid use indicates uncontrolled disease among asthma patients, and referral for asthma specialist assessment is recommended. We aimed to describe trends and predictors associated with specialist contacts among young adults with asthma and repeated oral corticosteroid use.

Methods

Individuals aged 18–45 years with two or more dispensed asthma medication prescriptions and two dispended oral corticosteroid prescriptions (including short-term and long-term treatments) within 12 months during 1999–2018 were identified by use of Danish healthcare registers. The frequency of specialist contacts within 1 year of follow-up was assessed among individuals without previous specialist contacts within 5 years of inclusion. Factors associated with specialist contact were identified using logistic regression models. Furthermore, oral corticosteroid prescriber sources were assessed.

Results

For the 11 223 individuals included, 2444 (22%) had previous specialist-contact care within 5 years prior of inclusion, and additionally 926 (8.3%) within 1 year of follow-up. Among those without previous specialist contacts (n=8779), the frequency of incident specialist contacts within 1 year of follow-up increased from 6.3% in 1999 to 18% in 2017. Factors associated with incident specialist contacts included dispensing ≥12 short-acting β-agonist canisters and previous asthma-related emergency department visits and hospitalisations. The majority of oral corticosteroid prescriptions at baseline (71%) were prescribed by general practitioners, although with decreasing proportions from 1999 to 2018.

Conclusions

The majority (70%) of young adults with asthma and repeated oral corticosteroid use do not seem to receive specialist assessment in Denmark. This highlights a potential room for improvement in the patient referral pathway for at-risk asthma patients.
Increased monocyte level is a risk factor for radiological progression in patients with early fibrotic interstitial lung abnormality
Authors: Achaiah Andrew , Lyon Paul , Fraser Emily , Saunders Peter , Hoyles Rachel , Benamore Rachel , Ho Ling-Pei
Published: June 2022

Background

Interstitial lung abnormalities (ILA) are specific spatial patterns on computed tomography (CT) scan potentially compatible with early interstitial lung disease. A proportion will progress; management involves risk stratification and surveillance. Elevated blood monocyte levels have been shown to associate with progression of idiopathic pulmonary fibrosis. The aims of the present study were: 1) to estimate the proportion of “early fibrotic” (EF)-ILAs (reticular±ground-glass opacities, excluding traction bronchiectasis and honeycombing) on CT scans of patients attending all-indications thoracic CTs, and proportion demonstrating radiological progression; and 2) to explore association between peripheral blood leukocyte levels and ILA progression.

Methods

We analysed all thoracic CT reports in individuals aged 45–75 years performed between January 2015 and December 2020 in one large teaching hospital (Oxford, UK) to identify patient CT reports consistent with EF-ILA. CT-contemporaneous blood leukocyte counts were examined to explore contribution to progression and all-cause mortality, using multivariate Cox regression.

Results

40 711 patients underwent thoracic CT imaging during this period. 1259 (3.1%) demonstrated the EF-ILA pattern (mean±sdage 65.4±7.32 years; 735 (47.8%) male). EF-ILA was significantly associated with all-cause mortality (hazard ratio 1.87, 95% CI 1.25–2.78; p=0.002). 362 cases underwent at least one follow-on CT. Radiological progression was observed in 157 (43.4%) cases: increase in reticulation n=51, new traction bronchiectasis n=84, honeycombing n=22. Monocyte count, neutrophil count, monocyte:lymphocyte ratio, neutrophil:lymphocyte ratio and “systemic inflammatory response index” were significantly associated with radiological progression.

Conclusion

3.1% of subjects requiring thoracic CT during a 6-year period demonstrated EF-ILA. Monocyte levels and blood leukocyte-derived indexes were associated with radiological progression and could indicate which patients may require closer follow-up.
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

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

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

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

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

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

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

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

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

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

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
Long-term postoperative outcomes of Roux-en-Y cholangiojejunostomy in patients with benign biliary stricture
Authors: Shalayiadang Paizula , Yasen Aimaiti , Abulizi Abduaini , Ahan Ayifuhan , Jiang Tiemin , Ran Bo , Zhang Ruiqing , Guo Qiang , Wen Hao , Shao Yingmei , Aji Tuerganaili
Published: June 2022

Background

Although there are common postoperative complications, Roux-en-Y cholangiojejunostomy is still broadly used as a standard surgical procedure for patients with biliary stricture. This study aimed to explore long-term risk factors of cholangiojejunostomy in patients with biliary stricture who underwent revisional cholangiojejunostomy.

Methods

Clinical data of 61 patients with biliary stricture undergoing revisional cholangiojejunostomy were retrospectively analyzed. These patients were classified into two groups (patients with traumatic biliary stricture and non-traumatic biliary stricture). Postoperative complications and survival time were successfully followed up.

Results

Among the patients, 34 underwent revisional cholangiojejunostomy due to traumatic biliary stricture, and 27 underwent revisional cholangiojejunostomy due to non-traumatic biliary surgery. Although there was no statistical difference in most clinical data between two groups, biliary dilation or not during the first surgery, cholelithiasis or not during the first surgery, long-term complications after first surgery, cholelithiasis or not during the second surgery, identifying abnormalities during the second surgery and long-term complications after second surgery were significantly different. All patients were successfully followed up and average follow-up time for patients with traumatic and non-traumatic biliary stricture was (88.44 ± 35.67) months and (69.48 ± 36.61) months respectively. Survival analysis indicated that there was no statistical difference in overall survival between two groups. Additionally, cox proportional hazard analysis demonstrated that first preoperative bilirubin level, short-term complication after first surgery and identifying abnormalities during the second surgery were independent risk factors that may have significant effects on patients' overall survival and long-term prognosis after cholangiojejunostomy. Among the intraoperative abnormal findings, residual lesions after the first operation had significant effects on the patients overall survival in the earlier stage. Relatively, anastomotic stoma stricture and biliary output loop problems had obvious effects on patients' overall survival at later stages.

Conclusion

First preoperative bilirubin level, short-term complication after first surgery and abnormal findings during the second surgery were independent risk factors of revisional cholangiojejunostomy, which may affect patients' long-term survival. Therefore, surgeons should minimize incidence of postoperative complications through fully evaluating optimal operative time and standardizing surgical procedures.
A systematic scoping review moral distress amongst medical students
Authors: Ong Rui Song Ryan , Wong Ruth Si Man , Chee Ryan Choon Hoe , Quek Chrystie Wan Ning , Burla Neha , Loh Caitlin Yuen Ling , Wong Yu An , Chok Amanda Kay-Lyn , Teo Andrea York Tiang , Panda Aiswarya , Chan Sarah Wye Kit , Shen Grace Shen , Teoh Ning , Chin Annelissa Mien Chew , Krishna Lalit Kumar Radha
Published: June 2022

Background

Characterised by feelings of helplessness in the face of clinical, organization and societal demands, medical students are especially prone to moral distress (MD). Despite risks of disillusionment and burnout, efforts to support them have been limited by a dearth of data and understanding of MD in medical students. Yet, new data on how healthcare professionals confront difficult care situations suggest that MD could be better understood through the lens of the Ring Theory of Personhood (RToP). A systematic scoping review (SSR) guided by the RToP is proposed to evaluate the present understanding of MD amongst medical students.

Methods

The Systematic Evidence-Based Approach (SEBA) is adopted to map prevailing accounts of MD in medical students. To enhance the transparency and reproducibility, the SEBA methodology employs a structured search approach, concurrent and independent thematic analysis and directed content analysis (Split Approach), the Jigsaw Perspective that combines complementary themes and categories, and the Funnelling Process that compares the results of the Jigsaw Perspective with tabulated summaries to ensure the accountability of these findings. The domains created guide the discussion.

Results

Two thousand six hundred seventy-one abstracts were identified from eight databases, 316 articles were reviewed, and 20 articles were included. The four domains identified include definitions, sources, recognition and, interventions for MD.

Conclusions

MD in medical students may be explained as conflicts between the values, duties, and principles contained within the different aspects of their identity. These conflicts which are characterised as disharmony (within) and dyssynchrony (between) the rings of RToP underline the need for personalised and longitudinal evaluations and support of medical students throughout their training. This longitudinal oversight and support should be supported by the host organization that must also ensure access to trained faculty, a nurturing and safe environment for medical students to facilitate speak-up culture, anonymous reporting, feedback opportunities and supplementing positive role modelling and mentoring within the training program.
Comparison between machine learning methods for mortality prediction for sepsis patients with different social determinants
Authors: Wang Hanyin , Li Yikuan , Naidech Andrew , Luo Yuan
Published: June 2022

Background

Sepsis is one of the most life-threatening circumstances for critically ill patients in the United States, while diagnosis of sepsis is challenging as a standardized criteria for sepsis identification is still under development. Disparities in social determinants of sepsis patients can interfere with the risk prediction performances using machine learning.

Methods

We analyzed a cohort of critical care patients from the Medical Information Mart for Intensive Care (MIMIC)-III database. Disparities in social determinants, including race, sex, marital status, insurance types and languages, among patients identified by six available sepsis criteria were revealed by forest plots with 95% confidence intervals. Sepsis patients were then identified by the Sepsis-3 criteria. Sixteen machine learning classifiers were trained to predict in-hospital mortality for sepsis patients on a training set constructed by random selection. The performance was measured by area under the receiver operating characteristic curve (AUC). The performance of the trained model was tested on the entire randomly conducted test set and each sub-population built based on each of the following social determinants: race, sex, marital status, insurance type, and language. The fluctuations in performances were further examined by permutation tests.

Results

We analyzed a total of 11,791 critical care patients from the MIMIC-III database. Within the population identified by each sepsis identification method, significant differences were observed among sub-populations regarding race, marital status, insurance type, and language. On the 5783 sepsis patients identified by the Sepsis-3 criteria statistically significant performance decreases for mortality prediction were observed when applying the trained machine learning model on Asian and Hispanic patients, as well as the Spanish-speaking patients. With pairwise comparison, we detected performance discrepancies in mortality prediction between Asian and White patients, Asians and patients of other races, as well as English-speaking and Spanish-speaking patients.

Conclusions

Disparities in proportions of patients identified by various sepsis criteria were detected among the different social determinant groups. The performances of mortality prediction for sepsis patients can be compromised when applying a universally trained model for each subpopulation. To achieve accurate diagnosis, a versatile diagnostic system for sepsis is needed to overcome the social determinant disparities of patients.
HBV genome-enriched single cell sequencing revealed heterogeneity in HBV-driven hepatocellular carcinoma (HCC)
Authors: Wang Wenhui , Chen Yan , Wu Liang , Zhang Yi , Yoo Seungyeul , Chen Quan , Liu Shiping , Hou Yong , Chen Xiao-ping , Chen Qian , Zhu Jun
Published: June 2022

Background

Hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) is heterogeneous and frequently contains multifocal tumors, but how the multifocal tumors relate to each other in terms of HBV integration and other genomic patterns is not clear.

Methods

To interrogate heterogeneity of HBV-HCC, we developed a HBV genome enriched single cell sequencing (HGE-scSeq) procedure and a computational method to identify HBV integration sites and infer DNA copy number variations (CNVs).

Results

We performed HGE-scSeq on 269 cells from four tumor sites and two tumor thrombi of a HBV-HCC patient. HBV integrations were identified in 142 out of 269 (53%) cells sequenced, and were enriched in two HBV integration hotspots chr1:34,397,059 (CSMD2) and chr8:118,557,327 (MED30/EXT1). There were also 162 rare integration sites. HBV integration sites were enriched in DNA fragile sites and sequences around HBV integration sites were enriched for microhomologous sequences between human and HBV genomes. CNVs were inferred for each individual cell and cells were grouped into four clonal groups based on their CNVs. Cells in different clonal groups had different degrees of HBV integration heterogeneity. All of 269 cells carried chromosome 1q amplification, a recurrent feature of HCC tumors, suggesting that 1q amplification occurred before HBV integration events in this case study. Further, we performed simulation studies to demonstrate that the sequential events (HBV infecting transformed cells) could result in the observed phenotype with biologically reasonable parameters.

Conclusion

Our HGE-scSeq data reveals high heterogeneity of HCC tumor cells in terms of both HBV integrations and CNVs. There were two HBV integration hotspots across cells, and cells from multiple tumor sites shared some HBV integration and CNV patterns.
Gastrointestinal bleeding caused by metastatic testicular choriocarcinoma: a case report and literature review
Authors: Zhang Pengliang , Wang Yu , Xiong Lishou
Published: June 2022

Background

Testicular tumor is one of the common solid tumors in young men. Testicular choriocarcinoma is a non-spermatogonial germ cell tumor, which is the rarest of all testicular cancers. Choriocarcinoma usually shows bleeding at the metastatic site, while gastrointestinal involvement is rare.

Methods

Here, we report a case of testicular choriocarcinoma with gastrointestinal bleeding as the first diagnosis and summarize the similar cases all over the world in recent 20 years.

Results

A 28-year-old male was treated with repeated melena for 2 months. No bleeding foci of the stomach, duodenum, colon, and rectum were found in endoscopy, and no bleeding foci of digestive tract was found in selective angiography, but a space occupying lesions of the lung, liver, and upper jejunum were found in chest and abdominal CT. Considering the possibility of a metastatic tumor and the ineffectiveness of medical treatment, the patient was converted to surgical treatment. The postoperative pathology was consistent with testicular choriocarcinoma. The patient received a chemotherapy regimen of paclitaxel, ifosfamide, and cisplatin. At present, the chemotherapy regimen is well tolerated.

Conclusions

The case report confirmed that even if we cannot find the logical relationship between clinical manifestations and genital examination, genital examination should also be part of the patient’s systematic examination.