bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignancies in Immunoglobulin G4-related ophthalmic disease
Authors: Lai Kenneth K.H. , Li Emmy Y.M. , Chan Regine Y.C. , Wong Kenneth C.W. , Yu Jimmy K.S. , Cheuk W. , Hui Y.H. , Cheng Andy C.O. , Chin Joyce K.Y. , Ip S. K. , Chan W. H. , Kwok Jeremy S.W. , Lam W. C. , Io Ida Y. F. , Mak Theresa S.T. , Li Kenneth K.W. , Lam N. M. , Yip Wilson W. K. , Young Alvin L. , Chan Edwin , Ko Callie K.L. , Ko Simon T. C. , Yuen Hunter K.L. , Tham Clement C.Y. , Pang Chi Pui , Chong Kelvin K.L. 
Published: June 2022

Purpose Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the patterns of affecting organs have different risks of malignancies. We attempt to determine the association of malignancies with IgG4-related ophthalmic disease (IgG4-ROD). Design Retrospective cohort study. Methods Review of medical records, orbital images and histopathology reports in a territory-wide cohort of biopsy proven IgG4-ROD patients from 2005–2019. Findings Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n = 108), orbital mass (n = 30), infiltrated orbital fat (n = 10), conjunctiva (n = 2) or extraocular muscles (n = 3), 13% (16/122) developed malignancies over 73 ± 48months’ follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs = 10.0, 95%CI = 4.5–17.6) while that of extra-orbital malignancies was similar. The SIRs was highest within the first year (SIR = 46.7, 95%CI = 18.5–87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients at IgG4-ROD diagnosis (64.9 ± 7.1, 68.3 ± 8.5 versus 55.2 ± 15.0 years, P < 0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%) were associated with OAL (all P < 0.05). Pre-treatment serum IgG4 level or extra-orbital IgG4-RD involvement was similar among patients with or without malignancies. Conclusion In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.
Low estimated glomerular filtration rate explains the association between hyperhomocysteinemia and in-hospital mortality among patients with ischemic stroke/transient ischemic attack or intracerebral hemorrhage: Results from the Chinese Stroke Center Alliance
Authors: Liu Wei , Ma Xue-Lian , Gu Hong-Qiu , Li Hao , Li Zi-Xiao , Wang Yong-Jun 
Published: June 2022

Objectives: To investigate the association between hyperhomocysteinemia (HHcy) and in-hospital mortality following ischemic stroke (IS), transient ischemic attack (TIA), or intracerebral hemorrhage (ICH). Methods: Data on patients with ischemic cerebrovascular disease (IS/TIA) or ICH enrolled in the Chinese Stroke Center Alliance (CSCA) from 2015 to 2019 were extracted. Patient characteristics and in-hospital mortality were analyzed and multiple adjusted logistic regression analyses performed to investigate the association between blood tHcy (total homocysteine) and in-hospital mortality in patients with HHcy (tHcy ⩾ 15 µmol) and patients with normohomocysteinemia (nHcy) (tHcy < 15 µmol). Results: A total of 823,622 participants were included. Mean (SD) age was 65.9 (12.1), and 62.5% (n = 514,888) were male. A total of 379,807 (46.0%) patients were identified as having HHcy, and 70,364 (8.5%) patients had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. An eGFR < 60 mL/min/1.73 m2 was the strongest independent risk factor for HHcy in both patients with IS/TIA (adjusted odds ratio (aOR) 2.67, 95% confidence interval (CI): 2.49–2.86), and those with ICH (2.94, 2.46–3.50). On multivariable logistic regression, after adjusting for potential confounding factors, HHcy was associated with in-hospital mortality (aOR: 1.25, 95% CI: 1.13–1.37 for patients with IS/TIA; aOR: 1.40, 95% CI: 1.12–1.76 for patients with ICH). However, after additionally adjusting for eGFR, this association disappeared among patients with both IS/TIA (aOR: 1.09, 95% CI: 0.99–1.20) and those with ICH (aOR: 1.17, 9% CI: 0.96–1.43). Conclusion: HHcy was associated with in-hospital mortality among the patients with IS/TIA or ICH but this association disappeared after controlling for eGFR, suggesting HHcy was acting as a marker of poor renal function which itself was the predictor of poor outcome. Our results suggest the prevention and management of renal impairment may be an important measure in the reduction of mortality in patients with HHcy after IS/TIA or ICH.
Neural Networks With Gated Recurrent Units Reduce Glucose Forecasting Error Due to Changes in Sensor Location
Authors: Tucker Aaron P. , Erdman Arthur G. , Schreiner Pamela J. , Ma Sisi , Chow Lisa S. 
Published: June 2022

Background: Continuous glucose monitors (CGMs) have become important tools for providing estimates of glucose to patients with diabetes. Recently, neural networks (NNs) have become a common method for forecasting glucose values using data from CGMs. One method of forecasting glucose values is a time-delay feedforward (FF) NN, but a change in the CGM location on a participant can increase forecast error in a FF NN. Methods: In response, we examined a NN with gated recurrent units (GRUs) as a method of reducing forecast error due to changes in sensor location. Results: We observed that for 13 participants with type 2 diabetes wearing blinded CGMs on both arms for 12 weeks (FreeStyle Libre Pro—Abbott), GRU NNs did not produce significantly different errors in glucose prediction due to sensor location changes ( P < .05). Conclusion: We observe that GRU NNs can mitigate error in glucose prediction due to differences in CGM location.
Personalized Offloading Treatments for Healing Plantar Diabetic Foot Ulcers
Authors: Jarl Gustav , Rusaw David F. , Terrill Alexander J. , Barnett Cleveland T. , Woodruff Maria A. , Lazzarini Peter A. 
Published: June 2022

Background: Non-removable knee-high devices are the gold-standard offloading treatments to heal plantar diabetic foot ulcers (DFUs). These devices are underused in practice for a variety of reasons. Recommending these devices for all patients, regardless of their circumstances and preferences influencing their ability to tolerate the devices, does not seem a fruitful approach. Purpose: The aim of this article is to explore the potential implications of a more personalized approach to offloading DFUs and suggest avenues for future research and development. Methods: Non-removable knee-high devices effectively heal plantar DFUs by reducing plantar pressure and shear at the DFU, reducing weight-bearing activity and enforcing high adherence. We propose that future offloading devices should be developed that aim to optimize these mechanisms according to each individual’s needs. We suggest three different approaches may be developed to achieve such personalized offloading treatment. First, we suggest modular devices, where different mechanical features (rocker-bottom sole, knee-high cast walls/struts, etc.) can be added or removed from the device to accommodate different patients’ needs and the evolving needs of the patient throughout the treatment period. Second, advanced manufacturing techniques and novel materials could be used to personalize the design of their devices, thereby improving common hindrances to their use, such as devices being heavy, bulky, and hot. Third, sensors could be used to provide real-time feedback to patients and clinicians on plantar pressures, shear, weight-bearing activity, and adherence. Conclusions: By the use of these approaches, we could provide patients with personalized devices to optimize plantar tissue stress, thereby improving clinical outcomes.
Mothers’ Perspectives on a Mother/Infant Dyad Postpartum Primary Care Program Following Gestational Diabetes Mellitus: A Qualitative Pilot Study
Authors: Brown Jordyn A. , Leonard Melissa , Clinton Tiffany , Bower Julie K. , Gillespie Shannon L. , Fareed Naleef , Thomas Nikki , Prater Laura , Lorenz Allison , May Sara , Voisin Christiane , Thung Stephen , Oza-Frank Reena , Bose Brill Seuli 
Published: June 2022

Purpose: The purpose of this study is to characterize mothers’ experiences within a mother/infant dyad postpartum primary care program (Dyad) following gestational diabetes mellitus (GDM) to inform improvements in the delivery of care. Methods: A qualitative pilot study of women (n = 10) enrolled in a mother/infant Dyad program was conducted in a primary care practice at a large, urban academic medical center. Respondents were asked a series of open-ended questions about their experience with GDM, the Dyad program, and health behaviors. Interviews were audio-recorded, transcribed verbatim, and analyzed using ground theory with NVivo 12 Plus software. Results: Three key themes emerged: (1) Dyad program experience, (2) implementation of health behavior changes, and (3) acknowledgment of future GDM and type 2 diabetes mellitus (T2DM) health risks. Respondents felt that the program conveniently served mother and infant health care needs in a single appointment. Respondents also valued support from primary care providers when implementing health behavior changes. The Dyad program provided an opportunity for respondents to understand their current and future risk for developing GDM and T2DM. Conclusions: Postpartum women enrolled in the Dyad program received highly personalized primary care services. The results of our study will help integrate patient-centered strategies into models for GDM care to maintain patient engagement in postpartum clinical services.
Linked-read whole-genome sequencing resolves common and private structural variants in multiple myeloma
Authors: Peña-Pérez Lucía , Frengen Nicolai , Hauenstein Julia , Gran Charlotte , Gustafsson Charlotte , Eisfeldt Jesper , Kierczak Marcin , Taborsak-Lines Fanny , Olsen Remi-André , Wallblom Ann , Krstic Aleksandra , Ewels Philip , Lindstrand Anna , Månsson Robert 
Published: June 2022

Abstract
Multiple myeloma (MM) is an incurable and aggressive plasma cell malignancy characterized by a complex karyotype with multiple structural variants (SVs) and copy-number variations (CNVs). Linked-read whole-genome sequencing (lrWGS) allows for refined detection and reconstruction of SVs by providing long-range genetic information from standard short-read sequencing. This makes lrWGS an attractive solution for capturing the full genomic complexity of MM. Here we show that high-quality lrWGS data can be generated from low numbers of cells subjected to fluorescence-activated cell sorting (FACS) without DNA purification. Using this protocol, we analyzed MM cells after FACS from 37 patients with MM using lrWGS. We found high concordance between lrWGS and fluorescence in situ hybridization (FISH) for the detection of recurrent translocations and CNVs. Outside of the regions investigated by FISH, we identified &gt;150 additional SVs and CNVs across the cohort. Analysis of the lrWGS data allowed for resolution of the structure of diverse SVs affecting the MYC and t(11;14) loci, causing the duplication of genes and gene regulatory elements. In addition, we identified private SVs causing the dysregulation of genes recurrently involved in translocations with the IGH locus and show that these can alter the molecular classification of MM. Overall, we conclude that lrWGS allows for the detection of aberrations critical for MM prognostics and provides a feasible route for providing comprehensive genetics. Implementing lrWGS could provide more accurate clinical prognostics, facilitate genomic medicine initiatives, and greatly improve the stratification of patients included in clinical trials.
A glimpse into the past: phylogenesis and protein domain analysis of the group XIV of C-type lectins in vertebrates
Authors: Barbera Stefano , Cucini Claudio 
Published: June 2022

Abstract
Background
The group XIV of C-type lectin domain-containing proteins (CTLDcps) is one of the seventeen groups of CTLDcps discovered in mammals and composed by four members: CD93, Clec14A, CD248 and Thrombomodulin, which have shown to be important players in cancer and vascular biology. Although these proteins belong to the same family, their phylogenetic relationship has never been dissected. To resolve their evolution and characterize their protein domain composition we investigated CTLDcp genes in gnathostomes and cyclostomes and, by means of phylogenetic approaches as well as synteny analyses, we inferred an evolutionary scheme that attempts to unravel their evolution in modern vertebrates.

Results
Here, we evidenced the paralogy of the group XIV of CTLDcps in gnathostomes and discovered that a gene loss of CD248 and Clec14A occurred in different vertebrate groups, with CD248 being lost due to chromosome disruption in birds, while Clec14A loss in monotremes and marsupials did not involve chromosome rearrangements. Moreover, employing genome annotations of different lampreys as well as one hagfish species, we investigated the origin and evolution of modern group XIV of CTLDcps. Furthermore, we carefully retrieved and annotated gnathostome CTLDcp domains, pointed out important differences in domain composition between gnathostome classes, and assessed codon substitution rate of each domain by analyzing nonsynonymous (Ka) over synonymous (Ks) substitutions using one representative species per gnathostome order.

Conclusions
CTLDcps appeared with the advent of early vertebrates after a whole genome duplication followed by a sporadic tandem duplication. These duplication events gave rise to three CTLDcps in the ancestral vertebrate that underwent further duplications caused by the independent polyploidizations that characterized the evolution of cyclostomes and gnathostomes. Importantly, our analyses of CTLDcps in gnathostomes revealed critical inter-class differences in both extracellular and intracellular domains, which might help the interpretation of experimental results and the understanding of differences between animal models.
The correlation of EZH2 expression with the progression and prognosis of hepatocellular carcinoma
Authors: Wu Shi-yi , Xie Zhao-yu , Yan Lu-yu , Liu Xiao-fang , Zhang Yue , Wang Da-an , Dong Jie , Sun Hong-tao 
Published: June 2022

Abstract
Background
Enhancer of Zeste homologue 2 (EZH2) is a polycomb group gene and an epigenetic regulator that inhibits transcription, a modification associated with gene silencing. EZH2 plays an essential role in humoral and cell-mediated adaptive immunity. The purpose of the current study is to investigate the prognostic potential of EZH2 and to comprehensively analyse the correlation between EZH2 and immune infiltration in multiple cancer cases, especially liver hepatocellular carcinoma.

Methods
EZH2 expression across cancers was explored through Oncomine, HPA, and GEPIA2. Additionally, the prognostic value of EZH2 analysis across cancers was based on the GEPIA2, TCGA portal, Kaplan–Meier Plotter, and LOGpc databases. Based on GO and KEGG analyses, GSEA helped demonstrate the biological processes through which EZH2 might lead to HCC development. GEPIA and TIMER were adopted to detect the possible relationship of EZH2 expression with tumour-infiltrating immune cells (TIICs).

Results
EZH2 overexpression levels were associated with poor prognosis of cancer, especially hepatocellular carcinoma. A high EZH2 expression level is related to a poor prognosis of HCC, especially in disease histology and stage III. The EZH2 expression level was positively correlated with critical gene markers of TAMs, M2 macrophages, M1 macrophages, and monocytes. Further analysis revealed that EZH2 genes were mainly related to DNA recombination, mitotic cell cycle phase transition, and chromosome segregation.

Conclusion
EZH2 plays an essential role in the immune microenvironment and is a potential prognostic marker and immunotherapy target for hepatocellular carcinoma.
Clinical and cost-effectiveness of a personalised health promotion intervention enabling independence in older people with mild frailty (‘HomeHealth’) compared to treatment as usual: study protocol for a randomised controlled trial
Authors: Frost Rachael , Avgerinou Christina , Goodman Claire , Clegg Andrew , Hopkins Jane , Gould Rebecca L. , Gardner Benjamin , Marston Louise , Hunter Rachael , Manthorpe Jill , Cooper Claudia , Skelton Dawn A. , Drennan Vari M. , Logan Pip , Walters Kate 
Published: June 2022

Abstract
Background
Frailty is clinically associated with multiple adverse outcomes, including reduced quality of life and functioning, falls, hospitalisations, moves to long-term care and mortality. Health services commonly focus on the frailest, with highest levels of need. However, evidence suggests that frailty is likely to be more reversible in people who are less frail. Evidence is emerging on what interventions may help prevent or reduce frailty, such as resistance exercises and multi-component interventions, but few interventions are based on behaviour change theory. There is little evidence of cost-effectiveness.
Previously, we co-designed a new behaviour change health promotion intervention (“HomeHealth”) to support people with mild frailty. HomeHealth is delivered by trained voluntary sector support workers over six months who support older people to work on self-identified goals to maintain their independence, such as strength and balance exercises, nutrition, mood and enhancing social engagement. The service was well received in our feasibility randomised controlled trial and showed promising effects upon outcomes.

Aim
To test the clinical and cost-effectiveness of the HomeHealth intervention on maintaining independence in older people with mild frailty in comparison to treatment as usual (TAU).

Methods
Single-blind individually randomised controlled trial comparing the HomeHealth intervention to TAU. We will recruit 386 participants from general practices and the community across three English regions. Participants are included if they are community-dwelling, aged 65 + , with mild frailty according to the Clinical Frailty Scale. Participants will be randomised 1:1 to receive HomeHealth or TAU for 6 months. The primary outcome is independence in activities of daily living (modified Barthel Index) at 12 months. Secondary outcomes include instrumental activities of daily living, quality of life, frailty, wellbeing, psychological distress, loneliness, cognition, capability, falls, carer burden, service use, costs and mortality. Outcomes will be analysed using linear mixed models, controlling for baseline Barthel score and site. A health economic analysis and embedded mixed-methods process evaluation will be conducted.

Discussion
This trial will provide definitive evidence on the effectiveness and cost-effectiveness of a home-based, individualised intervention to maintain independence in older people with mild frailty in comparison to TAU, that could be implemented at scale if effective.

Trial registration
ISRCTN, ISRCTN54268283. Registered 06/04/2020.
Falls, healthcare resources and costs in older adults with insomnia treated with zolpidem, trazodone, or benzodiazepines
Authors: Amari Diana T. , Juday Timothy , Frech Feride H. , Wang Weiying , Wu Zheng , Atkins Norman , Wickwire Emerson M. 
Published: June 2022

AbstractBackgroundFalls are the leading cause of injury-related death among older Americans. While some research has found that insomnia heightens falls, health care resource utilization (HCRU) and costs, the impact of insomnia treatments on fall risk, mortality, HCRU and costs in the elderly population, which could be of substantial interest to payers, has not been fully elucidated. This study evaluated the risk of falls and related consequences among adults ≥ 65 years of age treated with common prescription medications for insomnia compared with non-sleep disordered controls.MethodsThis was a retrospective cohort analysis of deidentified Medicare claims from January 2011 through December 2017. Medicare beneficiaries treated for insomnia receiving zolpidem extended-release, zolpidem immediate-release, trazodone, or benzodiazepines were matched with non-sleep disordered controls. The main outcomes were falls, mortality, healthcare resource utilization (HCRU), and medical costs during the 12 months following the earliest fill date for the insomnia medication of interest. Generalized linear models controlled for several key covariates, including age, race, sex, geographic region and Charlson Comorbidity Index score.ResultsThe study included 1,699,913 Medicare beneficiaries (59.9% female, mean age 75 years). Relative to controls, adjusted analyses showed that beneficiaries receiving insomnia medication experienced over twice as many falls (odds ratio [OR] = 2.34, 95% CI: 2.31–2.36). In adjusted analyses, patients receiving benzodiazepines or trazodone had the greatest risk. Crude all-cause mortality rates were 15-times as high for the insomnia-treated as controls. Compared with controls, beneficiaries receiving insomnia treatment demonstrated higher estimated adjusted mean number of inpatient, outpatient, and emergency department visits and longer length of inpatient stay. All-cause total adjusted mean costs were higher among insomnia treated patients ($967 vs $454).ConclusionsIndividuals receiving insomnia treatment had an increased risk of falls and mortality and higher HCRU and costs compared with matched beneficiaries without sleep disorders. Trazodone and benzodiazepines were associated with the greatest risk of falls. This analysis suggests that significant risks are associated with common, older generation insomnia medication treatments in the elderly. Nonetheless, these results should be interpreted with caution as the use of these medications may be indicative of underlying morbidity with potential for residual confounding.
Acute percheron infarction: a precision learning
Authors: Zhang Bei , Wang Xiaoxun , Gang Chen , Wang Jiping 
Published: June 2022

Abstract
Background
So far, the diagnosis of acute artery of percheron (AOP) infarction is uncommon. In this study, patients with acute AOP infarction were studied to explore the relationship of imaging findings, clinical manifestations and prognosis of acute AOP infarction.

Materials
A total of 23 patients with acute AOP infarction in our institution from 2014 to 2019 were reviewed retrospectively. All cases were evaluated by computed tomography (CT) and magnetic resonance imaging (MRI). The modified Rankin scale (MRS), blood examination, electrocardiogram and transthoracic echocardiography were used for detailed clinical and prognostic evaluation. All standard risk factors for these patients were recorded. The MRS scores were performed 90 days after discharge.

Results
Four different types of acute AOP infarction were identified: (a) bilateral paramedian thalamic infarction (BPTI, 52%); (b) bilateral paramedian thalamic with rostral midbrain infarction (BPTRMI, 30%), (c) bilateral paramedian and anterior thalamic infarction (BPATI, 13%), and (d) bilateral paramedian thalamic with red nuclei infarction (BPTRNI, 4%). These patients had consciousness disorder, memory dysfunctions, vertical gaze paresis and mesencephalothalamic syndrome. The 65% of patients with BPTI and BPATI experienced relatively good functional recovery and could carry out daily life activities (MRS score ≤ 2). However, patients with BPTRMI may have an unfavorable outcome.

Conclusions
Although the clinical features are variable, DWI or ADC map can improve the diagnosis of acute AOP infarction patterns. Acute AOP occlusion requires immediate diagnosis and treatment to obtain more favorable outcome and avoid additional unnecessary procedures.