bluuebunny/crossref_metadata_2025_split huggingface dataset:
Completeness and accuracy of adverse drug reaction documentation in electronic medical records at a tertiary care hospital in Australia
Authors: McLachlan Gina , Broomfield Airley , Elliott Rohan 
Published: December 2021

Background: A large proportion of patients presenting to hospitals have experienced a previous adverse drug reaction (ADR). Electronic medical records (EMRs) present an opportunity to accurately document ADRs and alert clinicians against inadvertent rechallenge where there is a pre-existing reaction. However, EMR systems are imperfect and rely on the accuracy of the data entered. Objective: To ascertain the completeness of ADR documentation and the accuracy of the classification of ADRs as allergy versus intolerance in the EMR at a major metropolitan hospital in Australia. Method: Cross-sectional audit of the ADR field of the EMR for a sample of patients on four different wards over 3 weeks to ascertain the completeness of ADR documentation and the accuracy of classification of ADRs. Results: Of the 264 patients assessed, 102 (38.6%) had a total of 210 ADRs documented in the EMR. Of these, 105 (50%) were considered to have complete documentation; 63/210 (30.0%) were missing a reaction description and 88/210 (41.9%) were missing severity information. For those ADRs with a reaction description ( n = 147), 97 (66.0%) were considered to be appropriately classified as allergy or intolerance. Conclusion: Incomplete and inaccurate ADR documentation was common. These findings highlight a need for optimising ADR documentation to improve appropriate medication use in hospital. Implications: Improved EMR design and education of healthcare workers on the importance of complete and accurate documentation of reactions are needed to improve completeness and accuracy of ADR classification.
The Impact of Restrictive Family Presence Policies in Response to COVID-19 on Family Integrated Care in the NICU: A Qualitative Study
Authors: McCulloch Holly , Campbell-Yeo Marsha , Richardson Brianna , Dol Justine , Hundert Amos , Dorling Jon , Whitehead Leah , MacRae Gail , Bishop Tanya , Afifi Jehier , Earle Rebecca , Rose Annette Elliott , Foye Sarah , Inglis Darlene , Kim Theresa , Leighton Carye , Melanson Andrea , Simpson David C , Smit Mike 
Published: December 2021

Objectives: To conduct a needs assessment with families and their healthcare team to understand the impact of restrictive family presence policies in the neonatal intensive care unit (NICU) in response to COVID-19. Background: In response to the COVID-19 pandemic, significant restrictive family presence policies were instituted in most NICUs globally intended to protect infants, families, and HCPs. However, knowledge on the impact of the stress of the pandemic and policies restricting family presence in the NICU on vulnerable neonates and their families remains limited. Methods: Individuals were eligible to participate if they were a caregiver of an infant requiring NICU care or a healthcare provider (HCP) in the NICU after March 1, 2020. Semi-structured interviews were conducted using a virtual communication platform, and transcripts were analyzed using inductive thematic qualitative content analysis. Results: Twenty-three participants were interviewed (12 families and 11 HCPs). Three themes emerged: (1) successes (family-integrated care, use of technology), (2) challenges (lack of standardized messaging and family engagement, impact on parental wellbeing, institutional barriers, and virtual care), and (3) moving forward (responsive and supportive leadership). Conclusions: Our findings highlight the significant impact of family restrictions on the mental well-being of families, physical closeness with parents, and empathetic stress to HCPs. Further study of potential long-term impact is warranted.
Structural and functional markers of optic nerve damage in myelin oligodendrocyte glycoprotein antibody-associated optic neuritis
Authors: Barnes Stephanie , You Yuyi , Shen Ting , Hardy Todd A , Fraser Clare , Reddel Stephen W , Brilot Fabienne , Ramanathan Sudarshini , Klistorner Alexandr , Yiannikas Con 
Published: December 2021

Background Optic neuritis (ON) occurs in immune-mediated disorders including multiple sclerosis (MS), aquaporin-4 antibody-positive (AQP4) neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination (MOGAD). Accurate determination of aetiology is critical for appropriate treatment and prognostication. Objective To evaluate demyelination and axonal loss in MOG-ON to facilitate differentiation from MS-ON and AQP4-ON. Methods 15 MOGAD patients with previous ON (25 eyes) underwent multifocal visual evoked potential (mfVEP) recordings and optical coherence tomography scans. Comparison was made to previously reported MS patients ( n = 67, 69 eyes) and AQP4-NMOSD patients ( n = 15, 23 eyes) with prior ON and healthy controls ( n = 37, 74 eyes). Results MOG-ON patients had less retinal nerve fibre layer (RNFL) loss than AQP4-ON patients ( p < 0.05) and less mfVEP latency prolongation than MS-ON patients ( p < 0.01). Number of ON episodes in MOGAD was associated with reduced RNFL thickness (global, p = 0.07; temporal, p < 0.001) and mfVEP amplitude ( p < 0.001). There was no abnormality in non-ON eyes. Conclusions Our study demonstrated a distinct pattern of damage in MOG-ON compared to AQP4-ON and MS-ON. ON in MOGAD produces less axonal loss than AQP4-NMOSD. Damage accumulates with relapses, supporting the role of maintenance immunosuppression to induce remission. Compared to MS, MOGAD causes less demyelination.
Acute kidney injury in a mouse model of meningococcal disease
Authors: Kolbe Karin R , Sanches Talita R , Fanelli Camilla , Garnica Margoth R , Urbano de Castro Letícia , Gooch Karen , Thomas Stephen , Taylor Stephen , Gorringe Andrew , Noronha Irene de L. , Andrade Lucia 
Published: December 2021

Introduction Meningococcal disease is associated with high mortality. When acute kidney injury (AKI) occurs in patients with severe meningococcal disease, it is typically attributable to sepsis, although meningococcal disease and lipopolysaccharide release are rarely investigated. Therefore, we evaluated renal tissue in a mouse model of meningococcal disease. Methods Female BALB/c mice were induced to AKI by meningococcal challenge. Markers of renal function were evaluated in infected and control mice. Results In the infected mice, serum concentrations of tumor necrosis factor alpha, interferon gamma, interleukins (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-12), and granulocyte–macrophage colony-stimulating factor were elevated, as was renal interstitial infiltration with lymphocytes and neutrophils ( p < 0.01 for the latter). Histological analysis showed meningococcal microcolonies in the renal interstitium, without acute tubular necrosis. Infected mice also showed elevated renal expression of toll-like receptor 2, toll-like receptor 4, and Tamm–Horsfall protein. The expression of factors in the intrinsic pathway of apoptosis was equal to or lower than that observed in the control mice. Urinary sodium and potassium were also lower in infected mice, probably due to a tubular defect. Conclusion Our findings corroborate those of other studies of AKI in sepsis. To our knowledge, this is the first time that meningococci have been identified in renal interstitium and that the resulting apoptosis and inflammation have been evaluated. However, additional studies are needed in order to elucidate the mechanisms involved.
Prevalence of chronic pain in LTCs and multimorbidity: A cross-sectional study using UK Biobank
Authors: McQueenie Ross , Jani Bhautesh Dinesh , Siebert Stefan , McLoone Philip , McCowan Colin , Macdonald Sara , Mair Frances S , Nicholl Barbara I 
Published: December 2021

Objectives: Chronic pain is often experienced alongside other long-term conditions (LTCs), yet our understanding of this, particularly in relation to multimorbidity (≥2 LTCs) is poor. We aimed to examine associations between the presence/extent of chronic pain with type/number of LTCs experienced. Methods: We examined the relationship between number/type of LTCs (N = 45) in UK Biobank participants (n = 500,295) who self-reported chronic pain lasting ≥3 months in seven body sites or widespread. Relative risk ratios (RRR) for presence/extent of chronic pain sites were compared using logistic regression adjusted for sociodemographic (sex/age/socioeconomic status) and lifestyle factors (smoking/alcohol intake/BMI/physical activity). Results: 218,648 participants self-reported chronic pain. Of these, 69.1% reported ≥1 LTC and 36.2% reported ≥2 LTCs. In 31/45 LTCs examined, >50% of participants experienced chronic pain. Chronic pain was common with migraine/headache and irritable bowel syndrome where pain is a primary symptom, but also with mental health conditions and diseases of the digestive system. Participants with >4 LTCs were over three times as likely to have chronic pain (RRR 3.56, 95% confidence intervals (CIs) 3.44–3.68) and 20 times as likely to have widespread chronic pain (RRR 20.13, 95% CI 18.26–22.19) as those with no LTCs. Conclusions: Chronic pain is extremely common across a wide range of LTCs. People with multimorbidity were at higher risk of having a greater extent of chronic pain. These results show that chronic pain is a key factor for consideration in the management of patients with LTCs or multimorbidity.
Molecular features encoded in the ctDNA reveal heterogeneity and predict outcome in high-risk aggressive B-cell lymphoma
Authors: Meriranta Leo , Alkodsi Amjad , Pasanen Annika , Lepistö Maija , Mapar Parisa , Blaker Yngvild Nuvin , Jørgensen Judit , Karjalainen-Lindsberg Marja-Liisa , Fiskvik Idun , Mikalsen Lars Tore G. , Autio Matias , Björkholm Magnus , Jerkeman Mats , Fluge Øystein , Brown Peter , Jyrkkiö Sirkku , Holte Harald , Pitkänen Esa , Ellonen Pekka , Leppä Sirpa 
Published: December 2021

Abstract
Inadequate molecular and clinical stratification of the patients with high-risk diffuse large B-cell lymphoma (DLBCL) is a clinical challenge hampering the establishment of personalized therapeutic options. We studied the translational significance of liquid biopsy in a uniformly treated trial cohort. Pretreatment circulating tumor DNA (ctDNA) revealed hidden clinical and biological heterogeneity, and high ctDNA burden determined increased risk of relapse and death independently of conventional risk factors. Genomic dissection of pretreatment ctDNA revealed translationally relevant phenotypic, molecular, and prognostic information that extended beyond diagnostic tissue biopsies. During therapy, chemorefractory lymphomas exhibited diverging ctDNA kinetics, whereas end-of-therapy negativity for minimal residual disease (MRD) characterized cured patients and resolved clinical enigmas, including false residual PET positivity. Furthermore, we discovered fragmentation disparities in the cell-free DNA that characterize lymphoma-derived ctDNA and, as a proof-of-concept for their clinical application, used machine learning to show that end-of-therapy fragmentation patterns predict outcome. Altogether, we have discovered novel molecular determinants in the liquid biopsy that can noninvasively guide treatment decisions.
Awareness and knowledge of congenital cytomegalovirus infection among pregnant women and the general public: a web-based survey in Japan
Authors: Kobayashi Masayuki , Okahashi Aya , Okuyama Kotoba , Hiraishi Naomi , Morioka Ichiro 
Published: December 2021

Abstract
Background
The best approach to reduce congenital cytomegalovirus infection (cCMVi) is to practice behaviors that reduce cytomegalovirus (CMV) transmission during pregnancy. Expanding awareness and knowledge of CMV is expected to result in increased practice of preventative behaviors. To this end, it is necessary to understand current awareness and knowledge of CMV.

Methods
This web-based cross-sectional survey assessed the awareness and knowledge of cCMVi among pregnant women and the general public in Japan. Participants aged 20–45 years (pregnant and non-pregnant women, and men) were identified from a consumer panel. Study outcomes (all participants) included awareness of cCMVi and other congenital conditions. Among those aware of cCMVi, outcomes included knowledge of CMV transmission routes, long-term outcomes of cCMVi, and behaviors to prevent CMV transmission during pregnancy. Outcomes limited to pregnant women included the practice of preventative behaviors and opinion on how easy it is to implement these behaviors. The data of the pregnant group (pregnant at the time of the survey) were compared with those of the general group (non-pregnant women and men).

Results
There were 535 participants in the pregnant group and 571 in the general group. Awareness of cCMVi was generally low (pregnant, 16.1%; general, 10.2%). Pregnant participants were significantly more aware of most congenital conditions than those in the general group, including cCMVi (P = 0.004). Knowledge about CMV/cCMVi was limited; there were no significant differences between the two groups for 24 of the 26 knowledge questions. A small proportion (one third or less) of pregnant women practiced behaviors to prevent the transmission of CMV, though most (73.3–95.3%) pregnant women who were aware of cCMVi considered such behaviors easy to implement.

Conclusions
Awareness and knowledge of CMV/cCMVi is low among pregnant women in Japan; the level of knowledge is similar to that among the general public. This needs to be improved. Most pregnant women considered behaviors to prevent CMV transmission easy to perform, which indicates that effectively educating pregnant women regarding the long-term outcomes of cCMVi, CMV transmission routes, and preventative behaviors will contribute to a reduced incidence of cCMVi.

Trial registration
UMIN Clinical Trials Registry, UMIN000041260.
Sleep problems among sexual minorities: a longitudinal study on the influence of the family of origin and chosen family
Authors: Chum Antony , Nielsen Andrew , Teo Celine 
Published: December 2021

AbstractBackgroundThere is growing evidence that lesbian, gay, and bisexual (LGB) adults experience more sleep problems than the general population. As LGB individuals experience a significantly greater risk of family rejection and low family support, our study investigates the role of family support as a potential determinant of LGB sleep problems over a prolonged period, and whether friend support (i.e. chosen family) can mitigate the effect of low family support. Given the importance of sleep on mental and physical health, study results may help shed light on persistent health disparities across sexual orientations.MethodsOur sample included 1703 LGB individuals from theUK Household Longitudinal Study (UKHLS). Mixed-effect logistic regressions were used to estimate the effect of family and friend support on the development of sleep problems after 24 months while controlling for potential confounders. A modified Pittsburgh Sleep Quality Index was used to measure 1) presence of any sleep problems, 2) short sleep duration, and 3) poor sleep quality.ResultsFamily support at baseline was independently associated with all sleep problems in our study after 24-months: 1 SD increase in family support was associated with a 0.94 times lower risk of sleep problems (95% C.I = 0.90-0.98), a 0.88 times lower risk of short sleep duration (95% C.I = 0.81-0.95), and a 0.92 times lower risk of sleep quality (95% C.I = 0.93-0.98). Support from one’s chosen family (proxied by friend support) did not mitigate the effects of low family support on sleep problems.ConclusionsOur study found a consistent effect of family support across all sleep outcomes along with evidence of a persistent effect after 24 months. Our findings point to the importance of targeting family support in designing interventions aimed at reducing LGB sleep problems.
How robust are findings of pairwise and network meta-analysis in the presence of missing participant outcome data?
Authors: Spineli Loukia M. , Kalyvas Chrysostomos , Papadimitropoulou Katerina 
Published: December 2021

AbstractBackgroundTo investigate the prevalence of robust conclusions in systematic reviews addressing missing (participant) outcome data via a novel framework of sensitivity analyses and examine the agreement with the current sensitivity analysis standards.MethodsWe performed an empirical study on systematic reviews with two or more interventions. Pairwise meta-analyses (PMA) and network meta-analyses (NMA) were identified from empirical studies on the reporting and handling of missing outcome data in systematic reviews. PMAs with at least three studies and NMAs with at least three interventions on one primary outcome were considered eligible. We applied Bayesian methods to obtain the summary effect estimates whilst modelling missing outcome data under the missing-at-random assumption and different assumptions about the missingness mechanism in the compared interventions. The odds ratio in the logarithmic scale was considered for the binary outcomes and the standardised mean difference for the continuous outcomes. We calculated the proportion of primary analyses with robust and frail conclusions, quantified by our proposed metric, the robustness index (RI), and current sensitivity analysis standards. Cohen’s kappa statistic was used to measure the agreement between the conclusions derived by the RI and the current sensitivity analysis standards.ResultsOne hundred eight PMAs and 34 NMAs were considered. When studies with a substantial number of missing outcome data dominated the analyses, the number of frail conclusions increased. The RI indicated that 59% of the analyses failed to demonstrate robustness compared to 39% when the current sensitivity analysis standards were employed. Comparing the RI with the current sensitivity analysis standards revealed that two in five analyses yielded contradictory conclusions concerning the robustness of the primary analysis results.ConclusionsCompared with the current sensitivity analysis standards, the RI offers an explicit definition of similar results and does not unduly rely on statistical significance. Hence, it may safeguard against possible spurious conclusions regarding the robustness of the primary analysis results.
YY1 activates EMI2 and promotes the progression of cholangiocarcinoma through the PI3K/Akt signaling axis
Authors: Zhou Shuai , Qu Kang Lin , Li Jin Ang , Chen Shi Lei , Zhang Yi Gang , Zhu Chao , Jin Hao , Wang Yong , Pang Qing , Liu Hui Chun 
Published: December 2021

Abstract
Background
Cholangiocarcinoma (CCA) is one of the deadliest cancers of the digestive tract. The prognosis of CCA is poor and the 5-year survival rate is low. Bioinformatic analysis showed that early mitotic inhibitor 2 (EMI2) was overexpressed in CCA but the underlying mechanism is not known.

Methods
The data on bile duct carcinoma from TCGA and GEO databases were used to detect the expression of EMI2. The transcription factors of EMI2 were predicted using JASPAR and PROMO databases. Among the predicted transcription factors, YY1 has been rarely reported in cholangiocarcinoma, and was verified using the luciferase reporter gene assay. RT-PCR was performed to predict the downstream pathway of EMI2, and PI3K/Akt was suspected to be associated with it. Subsequently, in vivo and in vitro experiments were conducted to verify the effects of silencing and overexpressing EMI2 and YY1 on the proliferation, invasion, and metastasis of the bile duct cancer cells.

Results
EMI2 was highly expressed in CCA. Silencing EMI2 inhibited the proliferation, invasion, and migration of CCA cells, arrested cell cycle in the G1 phase, and promoted of apoptosis. The luciferase reporter gene assay showed that YY1 bound to the promoter region of EMI2, and after silencing YY1, the expression of EMI2 decreased and the progression of CCA was inhibited. Moreover, key proteins in the PI3K/Akt signaling pathway decreased after silencing EMI2.

Conclusion
EMI2 may be one of the direct targets of YY1 and promotes the progression of CCA through the PI3K/Akt signaling pathway.
Epithelial Wntless regulates postnatal alveologenesis
Authors: Fang Yinshan , Shao Hongxia , Wu Qi , Wong Neng Chun , Tsong Natalie , Sime Patricia J. , Que Jianwen 
Published: December 2021

ABSTRACT
Alveologenesis requires the coordinated modulation of the epithelial and mesenchymal compartments to generate mature alveolar saccules for efficient gas exchange. However, the molecular mechanisms underlying the epithelial-mesenchymal interaction during alveologenesis are poorly understood. Here, we report that Wnts produced by epithelial cells are crucial for neonatal alveologenesis. Deletion of the Wnt chaperone protein Wntless homolog (Wls) disrupts alveolar formation, resulting in enlarged saccules in Sftpc-Cre/Nkx2.1-Cre; Wlsloxp/loxp mutants. Although commitment of the alveolar epithelium is unaffected, α-SMA+ mesenchymal cells persist in the alveoli, accompanied by increased collagen deposition, and mutants exhibit exacerbated fibrosis following bleomycin challenge. Notably, α-SMA+ cells include a significant number of endothelial cells resembling endothelial to mesenchymal transition (EndMT), which is also present in Ager-CreER; Wlsloxp/loxp mutants following early postnatal Wls deletion. These findings provide initial evidence that epithelial-derived Wnts are crucial for the differentiation of the surrounding mesenchyme during early postnatal alveologenesis.
Potential use of absorbance scanning in differentiating tumor microenvironment compositions from endoscopic biopsy of colorectal cancer patients.
Authors: Abdullah Murdani , Pitarini Utari Amanda , Aziza Nursyirwan Saskia , Noor Dimas R. 
Published: December 2021

Background: The microtumor environment is an area where tumor cells are surrounded by several cells such as immune cells, stromal cells and endothelial cells as well as blood and lymphatic vessels. It is known that various cytokines and growth factors are released by various cells surrounding the tumor and affect the growth of tumor cells. Differences in chemical composition in the microtumor environment can be detected using spectrometry. The aim of this study was to examine the potential of scanning absorbance spectrometry in differentiating cells based on the chemical composition of endoscopic biopsies of colorectal cancer patients. Methods: An endoscopic biopsy of the patient from Cipto Mangunkusumo Hospital, Jakarta was collected and homogenized in phosphate buffer saline using TissueLyser. Scanning absorbance was performed using a UV-VIS spectrophotometer. The results of scanning absorbance were then processed using principal component analysis (PCA) in Orange Data-Mining version 3.28.0 software and the results were represented in a scatter plot diagram. Results: Based on the results of the analysis using PCA, three patients were identified in different quadrant regions, crc006 and crc011 obtained from patients with the differentiation status located close together while crc009 and undifferentiated were located far apart. Conclusion: This indicates the potential of scanning absorbance in differentiating the chemical composition of the tumor microenvironment from patient biopsies.