bluuebunny/crossref_metadata_2025 huggingface dataset:
The emancipatory potential of the Yugoslav socialist narratives of the Second World War
Authors: Mandić Asja
Published: June 2022

This article discusses the Yugoslav socialist narratives and memory culture of the heroic, antifascist Partisan resistance during the Second World War and their suppression with the emergence of contested accounts of history, rise of nationalism and right-wing ideologies. The outcome of the post-communist transition in Yugoslavia was not only the disintegration of the common state, but wars, atrocities and genocide in Bosnia and Herzegovina. In multi-ethnic Bosnia and Herzegovina, ravaged by nationalism and religion-based conflicts, the return of the progressive socialist narratives of unity and social cohesion can have emancipatory potential. Such potential is explored in the Treasures of Socialism exhibition, the project in which I participated as one of the curators; thus, it is presented from my experience of working with this subversive material and institutional constraints involved in its presentation and interpretation.
Refracting implication: The question of silence in (A)pollonia
Authors: Twitchin Mischa
Published: June 2022

Addressing the work (or, indeed, the lessons) of Memory Studies, Ann Rigney has suggested that the creative arts play a particular role as ‘catalysts’ in the cultural understanding of the past. Contrasting an example of contemporary theatre repertoire with an officially legislated ‘theatre’ of remembrance, this essay reflects on differences between the cultural politics of a creative performance produced by Warsaw’s Nowy Teatr – (A)pollonia – and those of commemorative ‘performance’ mandated by the state concerning specifically the citation of ‘Righteous among the nations’. In a context where memory wars over ‘the good name’ of Poland include recourse to the law intervening in both scholarly and artistic research, how might this theatre production offer a form of counter-memorability to claims about national ‘tradition’, especially with respect to remembering the Shoah?
Improving the tolerability of osimertinib by identifying its toxic limit
Authors: Agema Bram C. , Veerman G. D. Marijn , Steendam Christi M. J. , Lanser Daan A. C. , Preijers Tim , van der Leest Cor , Koch Birgit C. P. , Dingemans Anne-Marie C. , Mathijssen Ron H. J. , Koolen Stijn L. W.
Published: June 2022

Background:

Osimertinib is the cornerstone in the treatment of epidermal growth factor receptor-mutated non-small cell lung cancer (NSCLC). Nonetheless, ±25% of patients experience severe treatment-related toxicities. Currently, it is impossible to identify patients at risk of severe toxicity beforehand. Therefore, we aimed to study the relationship between osimertinib exposure and severe toxicity and to identify a safe toxic limit for a preventive dose reduction.

Methods:

In this real-life prospective cohort study, patients with NSCLC treated with osimertinib were followed for severe toxicity (grade ⩾3 toxicity, dose reduction or discontinuation, hospital admission, or treatment termination). Blood for pharmacokinetic analyses was withdrawn during every out-patient visit. Primary endpoint was the correlation between osimertinib clearance (exposure) and severe toxicity. Secondary endpoint was the exposure–efficacy relationship, defined as progression-free survival (PFS) and overall survival (OS).

Results:

In total, 819 samples from 159 patients were included in the analysis. Multivariate competing risk analysis showed osimertinib clearance ( c.q. exposure) to be significantly correlated with severe toxicity (hazard ratio 0.93, 95% CI: 0.88–0.99). An relative operating characteristic curve showed the optimal toxic limit to be 259 ng/mL osimertinib. A 50% dose reduction in the high-exposure group, that is 25.8% of the total cohort, would reduce the risk of severe toxicity by 53%. Osimertinib exposure was not associated with PFS nor OS.

Conclusion:

Osimertinib exposure is highly correlated with the occurrence of severe toxicity. To optimize tolerability, patients above the toxic limit concentration of 259 ng/mL could benefit from a preventive dose reduction, without fear for diminished effectiveness.
Single Incidents or Patterns of Control? Researcher-Practitioner Differences in Screening for Intimate Partner Violence
Authors: Levine Ethan C. , Dickenson Jessica
Published: June 2022

Intimate partner violence (IPV) has long been recognized as a pervasive and urgent problem. Yet, there is no consensus on what constitutes IPV, and screening practices vary widely across professional domains. Whereas many researchers approach IPV as potentially bidirectional, and assessment tools in research and emergency healthcare often categorize any violence within a romantic partnership as IPV, antiviolence advocates tend to conceptualize IPV as a pattern of controlling behaviors. We engage Karen Barad’s theory of agential realism to explore the complexity of IPV and how professionals screening for “the same” phenomenon may classify individuals (participants, patients, or clients) and relationships differently. This variation is particularly important for applied researchers. Those who conceptualize IPV as being potentially bidirectional may classify some individuals as “victim-perpetrators” who would otherwise be classified solely as “survivors” or “perpetrators” by antiviolence advocates. Those who conceptualize any incident of violence as constituting IPV may classify a number of individuals as victims or perpetrators, and a number of relationships as abusive, that would screen as non-IPV in many advocacy contexts. This limits the capacity of research to substantively inform practitioners’ efforts to address what they conceptualize and subsequently operationalize as IPV.
Geographies of ruralisation or ruralities? The death and life of a category
Authors: Parsons Laurie , Lawreniuk Sabina
Published: June 2022

The rural sphere has suffered from underrepresentation in recent years in part due to growing interest in the urban. A perhaps equally important aspect of the decline has been the troubling of the spatial boundaries that define the rural and urban among scholars of mobilities and translocality. Exploring the decline of the rural in relation to these literary works, this commentary interrogates current geographical thinking on spatial categories, positing the concept of ruralities as a means to reinvigorate rural space on its own terms.
Assessments of a novel digital follow-up tool Rehabkompassen® to identify rehabilitation needs among stroke patients in an outpatient setting
Authors: Hu Xiaolei , Jonzén Karolina , Karlsson Marcus , Lindahl Olof A
Published: June 2022

Introduction

It remains a huge challenge to identify individual rehabilitation needs in a time-efficient manner for providing patient-tailored rehabilitation during the continuum of stroke care. We have recently demonstrated the usefulness of a paper-version Rehab-Compass as a follow-up tool. The aim of the current study was to develop a digital version of the Rehab-Compass and evaluate its usability and feasibility.

Methods

The novel digital tool Rehabkompassen® was developed by an iterative and participatory design process. Patients’ rehabilitation needs were visualized by the tool and used before, during, and after the consultation. The usability and feasibility of the tool was assessed by task completion rate, the System Usability Scale, and satisfaction questionnaires among 2 physicians and 24 adult stroke patients in an outpatient clinical setting.

Results

Rehabkompassen® identified and graphically visualized a panoramic view of the stroke patients’ multidimensional needs in individual- and group levels. The instrument appeared to be feasible and time efficient in clinical use with a 100% overall task completion rate for both patients and physicians. A majority of the patients reported that it was very easy or fairly easy to answer the digital questionnaires and to understand their own digital Rehab-Compass graph. Two physicians reported a high mean score on the System Usability Scale (95/100) and were positive about using the tool in the future.

Conclusions

The current results indicated that Rehabkompassen® was a feasible, useful, and time-saving follow-up tool for the identification of rehabilitation needs among stroke survivors in the post-acute continuum of care after stroke. Further research is needed to evaluate the efficacy of the digital instrument among stroke patients.
On the “Basketball Africa League”: Framing Analysis of the Broadcast Commentary of an African Professional Basketball League
Authors: Slater Kelsey , Burch Lauren M. , Zimmerman Matthew H.
Published: June 2022

The inaugural season of the National Basketball Association–supported Basketball Africa League (BAL) featured 12 teams from the African continent, competing in a Champions League-style competition. This brand-new professional endeavor featured player rosters mandated to feature a certain number of players from each of the countries in which the individual teams were based, with rosters also including a small number of foreign players. Proceeding from a Framing Theory paradigm, two coders examined the broadcasts of the BAL competition, analyzing for descriptors including physicality, intelligence, nationality, and experience. Most descriptors pertained to athlete success or failure, with significant findings for most descriptors between nationalities. Ideas for future research are also discussed.
Disparities in Elective Spine Surgery for Medicaid Beneficiaries: A Systematic Review
Authors: Badin Daniel , Ortiz-Babilonia Carlos , Musharbash Farah N. , Jain Amit
Published: June 2022

Study Design

Systematic review

Objectives

We sought to synthesize the literature investigating the disparities that Medicaid patients sustain with regards to 2 types of elective spine surgery, lumbar fusion (LF) and anterior cervical discectomy and fusion (ACDF).

Methods

Our review was constructed in accordance with Preferred Reporting Items and Meta-analyses (PRISMA) guidelines and protocol. We systematically searched PubMed, Embase, Scopus, CINAHL, and Web of Science databases. We included studies comparing Medicaid beneficiaries to other payer categories with regards to rates of LF and ACDF, costs/reimbursement, and health outcomes.

Results

A total of 573 articles were assessed. Twenty-five articles were included in the analysis. We found that the literature is consistent with regards to Medicaid disparities. Medicaid was strongly associated with decreased access to LF and ACDF, lower reimbursement rates, and worse health outcomes (such as higher rates of readmission and emergency department utilization) compared to other insurance categories.

Conclusions

In adult patients undergoing elective spine surgery, Medicaid insurance is associated with wide disparities with regards to access to care and health outcomes. Efforts should focus on identifying causes and interventions for such disparities in this vulnerable population.
Outcomes and Return-to-Sport Rates for Elite Athletes With Femoral Retroversion Undergoing Hip Arthroscopy: A Propensity-Matched Analysis With Minimum 2-Year Follow-up
Authors: Owens Jade S. , Jimenez Andrew E. , Lee Michael S. , Maldonado David R. , Lall Ajay C. , Domb Benjamin G.
Published: June 2022

Background:

Return to sports (RTS) and patient-reported outcomes (PROs) for elite athletes with femoral version abnormalities undergoing hip arthroscopy have not been well established.

Purposes:

To (1) report minimum 2-year PROs and RTS rates in elite athletes with femoral retroversion who underwent primary hip arthroscopy and (2) compare clinical results to those of a propensity-matched control group of elite athletes with normal femoral version who underwent primary hip arthroscopy.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Data were prospectively collected and retrospectively reviewed for elite (professional and collegiate) athletes with femoral version <5°, as measured on magnetic resonance imaging scans, who underwent hip arthroscopy for femoroacetabular impingement syndrome between March 2010 and April 2018. Inclusion criteria were preoperative and minimum 2-year follow-up PROs for the modified Harris Hip Score, Nonarthritic Hip Score, Hip Outcome Score–Sports Specific Subscale (HOS-SSS), and visual analog scale for pain. Exclusion criteria were Tönnis grade >1, hip dysplasia, and previous ipsilateral hip surgery or conditions. Rates of achieving the minimal clinically important difference (MCID), Patient Acceptable Symptom State (PASS), and maximum outcome improvement satisfaction threshold were recorded in addition to RTS. Athletes with retroversion were propensity matched in a 1:2 ratio to elite athletes with normal femoral version (5°-20°) for comparison.

Results:

A total of 33 elite athletes (33 hips) with femoral retroversion who underwent hip arthroscopy met the inclusion criteria, and follow-up was available for 30 hips in 30 athletes (90.9%) at an average of 36.1 ± 25.6 months. Elite athletes with femoral retroversion demonstrated significant improvements in all recorded PROs, achieved the MCID and PASS for the HOS-SSS at high rates (86.7%), and returned to sports at a rate of 83.3%. PROs, rates of achieving MCID and PASS for the HOS-SSS, and RTS rates were similar between the study and propensity-matched control group.

Conclusion:

Elite athletes with femoral retroversion undergoing primary hip arthroscopy demonstrated favorable PROs and high RTS rates at a minimum 2-year follow-up. These results were comparable with those of a propensity-matched control group of elite athletes with normal femoral version.
Sex-Based Differences in Athletes Undergoing Primary Hip Arthroscopy With Labral Reconstruction: A Propensity-Matched Analysis With Minimum 2-Year Follow-up
Authors: Owens Jade S. , Lee Michael S. , Jimenez Andrew E. , Maldonado David R. , Paraschos Olivia A. , Domb Benjamin G.
Published: June 2022

Background:

There is a paucity of literature comparing sex-based outcome differences in athletes after primary hip arthroscopy with labral reconstruction for femoroacetabular impingement syndrome (FAIS) and irreparable labral tears.

Purpose:

To report sex-based differences in clinical characteristics, patient-reported outcome (PRO) scores, and return-to-sports (RTS) rates in athlete who underwent primary hip arthroscopy with labral reconstruction.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Data were reviewed for recreational, organized amateur, high school, collegiate, and professional athletes who underwent primary hip arthroscopy with labral reconstruction for FAIS and irreparable labral tears between July 2014 and May 2019. Inclusion criteria included preoperative and minimum 2-year postoperative PRO scores (modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome Score–Sports Specific Subscale, International Hip Outcome Tool [iHOT-12], and visual analog scale [VAS] for pain). Exclusion criteria were Tönnis grade >1, hip dysplasia (lateral center-edge angle, <18°), or prior ipsilateral hip surgery/conditions. Patients were divided into groups by sex and were propensity-matched in a 1:1 ratio by age, body mass index, graft type, labral tear size, and sports level.

Results:

A total of 101 hips were eligible, and 94 hips (93.1%) had a minimum 2-year follow-up. Twenty-nine female athlete hips were propensity-matched to 29 male athlete hips. Female athletes underwent higher rates of capsular repair (79.3% vs 24.1% for men; P < .001) and lower rates of acetabular microfracture (0.0% vs 20.7% for men; P = .024). Both female and male athletes experienced significant improvement on all PRO scores ( P < .001 for all), high RTS rates (women, 84% vs men, 80.8%), and high rates of achieving the minimal clinically important difference for the iHOT-12 and VAS pain (women, 88.5% vs men, 71.4% for both) and achieving the patient acceptable symptom state for the iHOT-12 (women, 88.5% vs men, 71.4%), with no significant difference between the sexes.

Conclusion:

Despite different clinical characteristics and surgical procedures, both female and male athletes undergoing primary hip arthroscopy with labral reconstruction had significant improvements in all PROs at the minimum 2-year follow-up, high RTS rates, and similar rates of achieving the minimal clinically important difference and patient acceptable symptom state.
Social Return on Investment of Home Exercise and Community Referral for People With Early Dementia
Authors: Hartfiel Ned , Gladman John , Harwood Rowan , Tudor Edwards Rhiannon
Published: June 2022

Exercise can improve physical function and slow the progression of dementia. However, uncertainty exists around the costeffectiveness of exercise programmes for people with early dementia. The aim of this study was to determine whether a home-based supervised exercise programme (PrAISED – promoting activity, independence, and stability in early dementia) could generate a positive social return on investment (SROI). SROI analysis was conducted as part of a randomised controlled feasibility trial comparing PrAISED with usual care. Wellbeing valuation was used to compare the costs of the programme with the monetised benefits to participants, carers, and healthcare service providers. The PrAISED programme generated SROI ratios ranging from £3.46 to £5.94 for every £1 invested. Social value was created from improved physical activity, increased confidence, more social connection and PrAISED participants using healthcare services less often than usual care. This study found that home-based supervised exercise programmes could generate a positive SROI for people with early dementia. Trial registration: ClinicalTrials.gov: NCT02874300 (first posted 22 August 2016), ISRCTN: 10,550,694 (date assigned 31 August 2016).
For You? Using TikTok® to Teach Key Content
Authors: Middleton Stuart
Published: June 2022

As management educators grapple with the challenges of educating Gen Z cohorts (born 1997–2015) in and beyond an online COVID-19 environment, social media platforms represent potential teaching tools. TikTok® is one of the most popular global social media technologies with people aged under 25 and therefore has strong appeal for students. TikTok allows users to view and create short video content of 3 minutes or less for a range of purposes, including education. This review details how TikTok was used to complement other teaching approaches in an undergraduate Strategic Management course. The educational characteristics of TikTok are outlined, including its advantages and disadvantages as a management education tool.
Endoscope-Assisted Sutureless Intrascleral Haptic Fixation of a Posterior Chamber Intraocular Lens
Authors: Tandias Rachel , Lemire Colin A. , Yu Gina , Seto Brendan , Arroyo Jorge G.
Published: June 2022

Purpose:

In eyes with compromised capsule support, sutureless scleral fixation is a popular method of placing a posterior chamber intraocular lens (PCIOL). We describe an endoscope-assisted sutureless technique for intrascleral fixation of a 3-piece PCIOL.

Methods:

Eyes of patients who had endoscope-assisted scleral-fixated intraocular lens (SFIOL) implantation were examined retrospectively. The technique comprised direct capture of the IOL haptic with a forceps through a pars plana sclerotomy with subsequent haptic fixation into scleral tunnels created with a 26-gauge needle. The endoscope was used to visualize haptic positioning under the iris and ensure proper centration of the IOL.

Results:

Thirteen eyes of 13 patients were examined. The mean age of the patients was 68.2 years (range, 38-87 years), and the mean follow-up was 13.6 months (range, 5-23 months). The indications for surgery were a subluxated IOL (6 eyes), postoperative aphakia (5 eyes), and a subluxated cataract (2 eyes). The mean best-corrected visual acuity ± SD improved significantly from 1.2 ± 0.6 logMAR preoperatively to 0.6 ± 0.7 logMAR at last the follow-up (paired Welch t test; t10 = 2.69; P = .023). IOL stability and centration were maintained in all patients.

Conclusions:

Endoscopic visualization during sutureless SFIOL implantation helped improve haptic localization, minimize intraoperative complications, and achieve excellent IOL centration.
Hemolysis, free hemoglobin toxicity, and scavenger protein therapeutics
Authors: Vallelian Florence , Buehler Paul W. , Schaer Dominik J.
Published: June 2022

During hemolysis, erythrophagocytes dispose damaged red blood cells. This prevents the extracellular release of hemoglobin, detoxifies heme, and recycles iron in a linked metabolic pathway. Complementary to this process, haptoglobin and hemopexin scavenge and shuttle the red blood cell toxins hemoglobin and heme to cellular clearance. Pathological hemolysis outpaces macrophage capacity and scavenger synthesis across a diversity of diseases. This imbalance leads to hemoglobin-driven disease progression. To meet a void in treatment options, scavenger protein-based therapeutics are in clinical development.
UBE2S promotes the development of ovarian cancer by promoting PI3K/AKT/mTOR signaling pathway to regulate cell cycle and apoptosis
Authors: Zhang Mengjun , Liu Yuan , Yin Yue , Sun Zhenxing , Wang Yan , Zhang Zexue , Li Fei , Chen Xiuwei
Published: June 2022

Background

Ovarian cancer is one of the important factors that seriously threaten women's health and its morbidity and mortality ranks eighth among female cancers in the world. It is critical to identify potential and promising biomarkers for prognostic evaluation and molecular therapy of OV. Ubiquitin-conjugating enzyme E2S (UBE2S), a potential oncogene, regulates the malignant progression of various tumors; however, its role in OV is still unclear.

Methods

The expression and prognostic significance of UBE2S at the pan-cancer level were investigated through high-throughput gene expression analysis and clinical prognostic data from TCGA, GEPIA, and GEO databases. 181 patients with OV were included in this study. Cell culture and cell transfection were performed on OV cell lines (SKOV3 and A2780) and a normal ovarian cell line (IOSE80). The expression level and prognostic significance of UBE2S in OV were verified by western blot, immunohistochemistry, and Kaplan–Meier survival analysis. Through cell transfection, CCK-8, Ki-67 immunofluorescence, wound healing, Transwell, clonogenic, and flow cytometry assays, the effect and detailed mechanism of UBE2S knockdown on the malignant biological behavior of OV cells were explored.

Results

UBE2S exhibited abnormally high expression at the pan-cancer level. The results of RT-qPCR and Western blotting indicated that UBE2S was significantly overexpressed in ovarian cancer cell lines compared with normal cell lines (P < 0.05). Kaplan–Meier survival analysis and Immunohistochemistry indicated that overexpression of UBE2S was related to poor prognosis of OV (HR > 1, P < 0.05). Results of in vitro experiments indicated that UBE2S gene knockdown might inhibit the proliferation, invasion, and prognosis of OV cells by inhibiting the PI3K/AKT/mTOR signaling pathway, thereby blocking the cell cycle and promoting apoptosis (P < 0.05).

Conclusion

UBE2S is a potential oncogene strongly associated with a poor prognosis of OV patients. Knockdown of UBE2S could block the cell cycle and promote apoptosis by inhibiting the PI3K/AKT/mTOR pathway and ultimately inhibit the proliferation, migration and prognosis of ovarian cancer, which suggested that UBE2S might be used for molecular therapy and prognostic evaluation of ovarian cancer.
Modeling binding specificities of transcription factor pairs with random forests
Authors: Antikainen Anni A. , Heinonen Markus , Lähdesmäki Harri
Published: June 2022

Background

Transcription factors (TFs) bind regulatory DNA regions with sequence specificity, form complexes and regulate gene expression. In cooperative TF-TF binding, two transcription factors bind onto a shared DNA binding site as a pair. Previous work has demonstrated pairwise TF-TF-DNA interactions with position weight matrices (PWMs), which may however not sufficiently take into account the complexity and flexibility of pairwise binding.

Results

We propose two random forest (RF) methods for joint TF-TF binding site prediction: and . We train models with previously published large-scale CAP-SELEX DNA libraries, which comprise DNA sequences enriched for binding of a selected TF pair. builds a random forest with sub-sequences selected from CAP-SELEX DNA reads with previously proposed pairwise PWM. outperforms (area under receiver operating characteristics curve, AUROC, 0.75) the current state-of-the-art method i.e. orientation and spacing specific pairwise PWMs (AUROC 0.59). Thus, may be utilized to improve prediction accuracy for pre-determined binding preferences. However, pairwise TF binding is currently considered flexible; a pair may bind DNA with different orientations and amounts of dinucleotide gaps or overlap between the two motifs. Thus, we developed , which utilizes random forests by considering simultaneously multiple orientations and spacings of the two factors. Our approach outperforms (AUROC 0.78) PWMs, as well as (p<0.00195). provides an approach for predicting TF-TF binding sites without prior knowledge on pairwise binding preferences. However, more research is needed to assess eligibility for practical applications.

Conclusions

Random forest is well suited for modeling pairwise TF-TF-DNA binding specificities, and provides an improvement to pairwise binding site prediction accuracy.
Ancillary polymorphic floral traits between two morphs adaptive to hawkmoth pollination in distylous plant Tirpitzia sinensis (Linaceae)
Authors: Wang Xiaoyue , Hu Demei , Chen Yan , Xiang Mengda , Tang Hanqing , Yi Yin , Tang Xiaoxin
Published: June 2022

Background

Floral morphs are characterized differentiations in reciprocal positions of sexual organs and ancillary floral traits in heterostylous plants. However, it remains unclear how differential floral morphs ensure reproductive success between morphs using the same pollinator.

Results

Measurements of floral traits in white-flowered Tirpitzia sinensis with long corolla tubes indicated that it is typically distylous, long-styled (L-) morph producing more but smaller pollen grains per flower than short-styled (S-) morph. Both morphs secreted more nectar volume at night than in the day and the sugar composition was rich in sucrose, potentially adaptive to pollination by hawkmoths (Macroglossum spp.) which were active at dusk. A bumblebee species functioned as the nectar robber in both morphs and a honeybee as the pollen feeder in the S-morph. The L-morph secreted more nectar volume but relatively lower sucrose/hexose ratio than the S-morph. Floral visitation rate by hawkmoths was higher but its pollination efficiency was lower in the S-morph than the L-morph. Hand pollination treatments indicated self-incompatibility in T. sinensis and seed set of open-pollinated flowers did not differ between morphs.

Conclusions

Our findings suggest that the two morphs differ with respect to traits relevant to pollination. The L-morph, with its exserted stigma, has more pollen grains per anther and a greater volume of nectar, which may prolong the foraging time and increase the pollination efficiency of hawkmoths. The S-morph has a higher sucrose/hexose ratio in its nectar which can be more attractive to hawkmoths and increase the visit rates. Ancillary polymorphic floral traits between two morphs are adaptive to hawkmoth and ensure reproductive success in distylous plant T. sinensis.
Bayesian mendelian randomization with study heterogeneity and data partitioning for large studies
Authors: Zou Linyi , Guo Hui , Berzuini Carlo
Published: June 2022

Background

Mendelian randomization (MR) is a useful approach to causal inference from observational studies when randomised controlled trials are not feasible. However, study heterogeneity of two association studies required in MR is often overlooked. When dealing with large studies, recently developed Bayesian MR can be computationally challenging, and sometimes even prohibitive.

Methods

We addressed study heterogeneity by proposing a random effect Bayesian MR model with multiple exposures and outcomes. For large studies, we adopted a subset posterior aggregation method to overcome the problem of computational expensiveness of Markov chain Monte Carlo. In particular, we divided data into subsets and combined estimated causal effects obtained from the subsets. The performance of our method was evaluated by a number of simulations, in which exposure data was partly missing.

Results

Random effect Bayesian MR outperformed conventional inverse-variance weighted estimation, whether the true causal effects were zero or non-zero. Data partitioning of large studies had little impact on variations of the estimated causal effects, whereas it notably affected unbiasedness of the estimates with weak instruments and high missing rate of data. For the cases being simulated in our study, the results have indicated that the “divide (data) and combine (estimated subset causal effects)” can help improve computational efficiency, for an acceptable cost in terms of bias in the causal effect estimates, as long as the size of the subsets is reasonably large.

Conclusions

We further elaborated our Bayesian MR method to explicitly account for study heterogeneity. We also adopted a subset posterior aggregation method to ease computational burden, which is important especially when dealing with large studies. Despite the simplicity of the model we have used in the simulations, we hope the present work would effectively point to MR studies that allow modelling flexibility, especially in relation to the integration of heterogeneous studies and computational practicality.
Management of esophageal perforations in infants by endoscopic vacuum therapy: a single center case series
Authors: Kaczmarek Dominik J. , Heling Dominik J. , Strassburg Christian P. , Katzer David , Düker Gesche , Strohm Joanna , Müller Andreas , Heydweiller Andreas , Weismüller Tobias J.
Published: June 2022

Background

Endoscopic vacuum therapy (EVT) has become a standard treatment method for esophageal perforations in adults. However, experience with EVT in infants is scarce. In this retrospective case series, we report on four very young infants who were successfully treated with EVT for esophageal perforations of different etiology.

Methods

Four infants were diagnosed with esophageal perforations on day 7, 32, 35 and 159 of life, respectively. The youngest one was prematurely born in the 31st week of pregnancy weighing 980 g only. Three infants had perforations due to foreign body insertion (nasogastric tube or pulling through of percutaneous endoscopic gastrostomy (PEG) tube through the esophagus). One child had an anastomotic dehiscence after Foker’s surgery for atresia. In three children EVT was applied as first-line therapy for perforation, in one child EVT was a rescue therapy due to persisting leakage after surgical closure involving thoracotomy. Depending on the esophageal diameter, either an open-pore drainage film or polyurethane sponge was attached to a single-lumen 8 Fr suction catheter, endoscopically (or fluoroscopically by wire-guidance) placed into the esophagus (intraluminal EVT) and supplied with continuous negative pressure (ranging between 75 and 150 mmHg). The EVT system was exchanged twice per week.

Results

Complete closure of the perforation/leakage could be achieved in all four infants (100%) after 22 days of continuous EVT (median value; range 7–39) and 4.5 EVT exchanges (median value; range 1–12). No serious adverse events occurred.

Conclusions

EVT is an effective and safe addition to our therapeutic armamentarium in the management of esophageal perforations irrespective of its etiology. Here we prove the feasibility of EVT even in very young infants. The use of an extra thin vacuum open-pore drainage film is helpful to cope with the small esophageal diameter. EVT settings and exchange rates similar to those known from adult treatment were used.
Establishment of MELD-lactate clearance scoring system in predicting death risk of critically ill cirrhotic patients
Authors: Li Xin , Gong Man , Fu Shuangnan , Zhang Jingjing , Wu Shanbin
Published: June 2022

Background

To develop a scoring system related to the lactate clearance (ΔLA) to predict the mortality risk (MELD-ΔLA) for critically ill cirrhotic patients.

Methods

In this retrospective cohort study, 881 critically ill cirrhotic patients from the Medical Information Mart for Intensive Care (MIMIC-III) database were included eventually. The outcomes of our study were defined as ICU death, 28-day, 90-day and 1-year mortality. Predictors were identified by multivariate Cox analysis to develop the predictive scoring system. The C-index and area under the curve (AUC) of receiver operator characteristic curve (ROC) were used to identify the predicting performance of the MELD-ΔLA, sequential organ failure assessment (SOFA), chronic liver failure-sequential organ failure assessment (CLIF-SOFA), the model for end-stage liver disease (MELD), Child–Pugh, chronic liver failure consortium acute-on-chronic liver failure (CLIF-C ACLF), chronic liver failure consortium-acute decompensation (CLIF-C AD) and MELD-Na scoring systems. Additionally, subgroup analysis was also performed based on whether critically ill cirrhotic patients underwent liver transplantation.

Results

Creatinine, bilirubin, international normalized ratio (INR), lactate first, ΔLA and vasopressors were closely associated with ICU death of liver critically ill cirrhotic patients. The C-index of the MELD-ΔLA in ICU death was 0.768 (95% CI 0.736–0.799) and the AUC for the MELD-ΔLA scoring system in predicting 28-day, 90-day, and 1-year mortality were 0.774 (95% CI 0.743–0.804), 0.765 (95% CI 0.735–0.796), and 0.757 (95% CI 0.726–0.788), suggested that MELD-ΔLA scoring system has a good predictive value than SOFA, CLIF-SOFA, MELD, Child–Pugh, CLIF-C ACLF, CLIF-C AD) and MELD-Na scoring systems. Additionally, the study also confirmed the good predictive value of MELD-ΔLA scoring system for critically ill cirrhotic patients regardless of undergoing liver transplantation.

Conclusion

The developed MELD-ΔLA score is a simple scoring system in predicting the risk of ICU death, 28-day, 90-day and 1-year mortality for critically ill cirrhotic patients, which may have a good predictive performance.
Prevalence and factors associated with fatigue in patients with ulcerative colitis in China: a cross-sectional study
Authors: Xu Feng , Hu Jingyi , Yang Qian , Ji Yuejin , Cheng Cheng , Zhu Lei , Shen Hong
Published: June 2022

Background

Fatigue is one of the most common symptoms reported by patients with ulcerative colitis (UC), while it has not been fully recognized and taken seriously in clinical practice. We aimed to investigate the prevalence of fatigue in patients with UC and identify the factors associated with fatigue and its severity in China.

Methods

A cross-sectional study was conducted in Affiliated Hospital of Nanjing University of Chinese Medicine from May 2020 to February 2021. Demographic and clinical characteristics were collected. Fatigue was evaluated with the Fatigue Severity Scale and the Multidimensional Fatigue Inventory. The Hospital Anxiety and Depression Scale, the Pittsburgh Sleep Index Scale and the Malnutrition Universal Screening Tool were respectively used to evaluate the anxiety, depression, sleep disturbance and nutritional risk of patients with UC.

Results

A total of 220 UC patients were enrolled in this study. The prevalence of fatigue in patients was 61.8%, of which in patients with disease activity was 68.2%, and in patients in remission was 40.0%. Univariate analysis indicated that the Montreal classification, disease activity, anemia, anxiety, depression, sleep disturbance and high nutritional risk were the factors associated with fatigue in Patients with UC. Multivariate logistic regression analysis showed that the Montreal classification (E3: E1, OR = 2.665, 95% CI = 1.134–6.216), disease activity (OR = 2.157, 95% CI = 1.055–4.410) and anxiety (OR = 2.867, 95% CI = 1.154–7.126) were related to an increased risk of fatigue. Disease activity (RC = 0.240, 95% CI = 0.193–0.674) and anxiety (RC = 0.181, 95% CI = 0.000–0.151) were associated with severity of fatigue.

Conclusions

This study demonstrated that the prevalence of fatigue among UC patients in China. The Montreal classification, disease activity and anxiety are associated with an increased risk of fatigue.
SEB genotyping: SmartAmp-Eprimer binary code genotyping for complex, highly variable targets applied to HBV
Authors: Delobel Diane , Furutani Yutaka , Nagoshi Sumiko , Tsubota Akihito , Miyasaka Akio , Watashi Koichi , Wakita Takaji , Matsuura Tomokazu , Usui Kengo
Published: June 2022

Background

SmartAmp-Eprimer Binary code (SEB) Genotyping is a novel isothermal amplification method for rapid genotyping of any variable target of interest.

Methods

After in silico alignment of a large number of sequences and computational analysis to determine the smallest number of regions to be targeted by SEB Genotyping, SmartAmp primer sets were designed to obtain a binary code of On/Off fluorescence signals, each code corresponding to a unique genotype.

Results

Applied to HBV, we selected 4 targets for which fluorescence amplification signals produce a specific binary code unique to each of the 8 main genotypes (A–H) found in patients worldwide.

Conclusions

We present here the proof of concept of a new genotyping method specifically designed for complex and highly variable targets. Applied here to HBV, SEB Genotyping can be adapted to any other pathogen or disease carrying multiple known mutations. Using simple preparation steps, SEB Genotyping provides accurate results quickly and will enable physicians to choose the best adapted treatment for each of their patients.
Uncontrolled pain in critically ill patients and acute kidney injury: a hypothesis-generating cohort study
Authors: Herranz Prinz Laura , de Castro Isac , de Cesar Pontes Azevedo Luciano , Mauro Vieira Jose
Published: June 2022

Background

In critically ill patients, acute pain occurs frequently, causes sympathetic activation, release of inflammatory mediators, and potential organ dysfunction, with the kidneys potentially sensitive to inflammation-mediated injury. This study aimed to explore the association between acute pain in critically ill patients and the occurrence of acute kidney injury (AKI).

Methods

Data from a retrospective cohort of adult patients admitted between June 2013 and June 2016 to the Intensive Care Unit (ICU) of a tertiary hospital in São Paulo, Brazil, were analyzed. The main exclusion criteria were ICU length of stay < 48 h, coma, and prior kidney dysfunction. The outcome (AKI) was defined as an elevation in the baseline serum creatinine level of ≥ 0.3 mg/dl and/or > 50% at any time after the first 48 h in the ICU. Multivariable logistic regression and hierarchical cluster analysis were performed.

Results

The isolated incidence of pain was 23.6%, and the incidence of pain duration > 5 days was 10.6%. AKI occurred in 31.7% of the cohort. In multivariable logistic analysis, duration of pain > 5 days (OR 5.25 CI 2.19–12.57 p < 0.01) and mechanical ventilation (MV) ≥ 3 days (OR 5.5 CI 2.3–13.5 p < 0.01) were the variables with positive association with AKI. The hierarchical cluster analysis reinforced the relation between AKI, MV and duration of pain.

Conclusions

Pain is an especially important issue in critically ill patients and in this exploratory study it appears to be associated with AKI development. The search for more rigorous pain control in ICU is crucial and can influence organ dysfunction.

Graphical Abstract
Expression relationship and significance of NEAT1 and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer’s disease
Authors: He Lijie , Chen Zongnan , Wang Jing , Feng Heqiang
Published: June 2022

Objective

To explore the expression relationship and significance of long chain non-coding RNA nuclear-enriched abundant transcript 1 (LncRNA NEAT1) and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer’s disease (AD).

Methods

Sixty-six AD patients received by the Department of Neurology of our hospital from October 2019 to September 2021 were gathered, according to the Clinical Dementia Rating Scale (CDR) score, they were grouped into mild group (≤1 point, n = 41) and moderate-to-severe group (> 1 point, n = 25). Another 32 cases of serum and cerebrospinal fluid samples from outpatient physical examination personnel were regarded as the control group. The general materials on all subjects was recorded and cognition was assessed;real-time quantitative PCR was performed to measure the expression levels of miR-27a-3p and NEAT1 in serum and cerebrospinal fluid;enzyme-linked immunosorbent assay was performed to measure the protein levels of β-amyloid precursor protein cleaving enzyme 1 (BACE1), β-amyloid (Aβ) 40 and Aβ42 in cerebrospinal fluid;Spearman’s method was performed to analyze the correlation of serum miR-27a-3p and NEAT1 levels with MMSE and MoCA scores;Pearson method was performed to analyze the correlation between serum miR-27a-3p and NEAT1 levels and Aβ deposition standard uptake value ratio (SUVR) and cerebrospinal fluid miR-27a-3p, NEAT1, BACE1, Aβ42 and Aβ40 levels.

Results

The MMSE score, MoCA score, serum miR-27a-3p level, cerebrospinal fluid miR-27a-3p, Aβ42 levels and Aβ42/Aβ40 ratio of AD patients in mild group and moderate-to-severe group were all lower than those in the control group, and the moderate-to-severe group were lower than the mild group (all P < 0.05);the serum NEAT1 level, SUVR, and cerebrospinal fluid NEAT1 and BACE1 levels were higher than those in the control group, and the moderate-to-severe group were higher than the mild group (all P < 0.05). Serum NEAT1 level in AD patients was positively correlated with SUVR, cerebrospinal fluid NEAT1 and BACE1 (r = 0.350, 0.606, 0.341, all P < 0.05);serum miR-27a-3p level was positively correlated with cerebrospinal fluid miR-27a-3p level (r = 0.695, P < 0.05), and negatively correlated with SUVR and cerebrospinal fluid BACE1 level (r = − 0.521, − 0.447, both P < 0.05).

Conclusions

The expression trends of NEAT1 and miR-27a-3p in the serum and cerebrospinal fluid of AD patients are consistent, the level of NEAT1 is increased, and the level of miR-27a-3p is decreased. The levels of the two are negatively correlated, which is related to the degree of Aβ deposition in the brain of AD patients and is involved in the progression of AD.
Prognostic factors for patients with anal cancer treated with conformal radiotherapy—a systematic review
Authors: Theophanous Stelios , Samuel Robert , Lilley John , Henry Ann , Sebag-Montefiore David , Gilbert Alexandra , Appelt Ane L.
Published: June 2022

Aims

Anal cancer is primarily treated using concurrent chemoradiotherapy (CRT), with conformal techniques such as intensity modulated radiotherapy (IMRT) and volumetric arc therapy (VMAT) now being the standard techniques utilised across the world. Despite this, there is still very limited consensus on prognostic factors for outcome following conformal CRT. This systematic review aims to evaluate the existing literature to identify prognostic factors for a variety of oncological outcomes in anal cancer, focusing on patients treated with curative intent using contemporary conformal radiotherapy techniques.

Materials and methods

A literature search was conducted using Medline and Embase to identify studies reporting on prognostic factors for survival and cancer-related outcomes after conformal CRT for anal cancer. The prognostic factors which were identified as significant in univariable and multivariable analysis, along with their respective factor effects (where available) were extracted. Only factors reported as prognostic in more than one study were included in the final results.

Results

The results from 19 studies were analysed. In both univariable and multivariable analysis, N stage, T stage, and sex were found to be the most prevalent and reliable clinical prognostic factors for the majority of outcomes explored. Only a few biomarkers have been identified as prognostic by more than one study – pre-treatment biopsy HPV load, as well as the presence of leukocytosis, neutrophilia and anaemia at baseline measurement. The results also highlight the lack of studies with large cohorts exploring the prognostic significance of imaging factors.

Conclusion

Establishing a set of prognostic and potentially predictive factors for anal cancer outcomes can guide the risk stratification of patients, aiding the design of future clinical trials. Such trials will in turn provide us with greater insight into how to effectively treat this disease using a more personalised approach.
Axial length shortening after orthokeratology and its relationship with myopic control
Authors: Wang Anken , Yang Chenhao , Shen Li , Wang Jiaying , Zhang Zhehuan , Yang Weiming
Published: June 2022

Purpose

To determine the pattern of axial variation in subjects with initial shortened axial length during the entire period of orthokeratology and to discuss the possibility of shortened AL after one month of orthokeratology becoming a predictor of myopia control.

Method

This study retrospectively included 106 children with myopia aged 8 to 14 wearing OK lenses. Fifty-four eyes with shortened axial length (AL) at the first-month visit were enrolled in the axial length shortening (ALS) group, and fifty-two eyes without shortened AL were enrolled in the no axial length shortening (NALS) group. Axial length and refractive error at baseline and within the entire period of orthokeratology (20 months), including fitting, washout period and re-wear, were measured. Eighty-five children who started wearing single vision spectacle were also included as a control group.

Results

In the ALS group, AL became longer after shortening and slowly exceeded baseline; afterward, AL experienced a rebound during the washout period and shortened again if OK lenses were re-worn. After washout period, significant difference in AL (ALS:0.28 ± 0.19 mm, NALS: 0.52 ± 0.17 mm) and spherical equivalent (ALS:-0.43 ± 0.44D, NALS:-0.91 ± 0.40D) between the two groups were found(P<0.05). The changes in AL and SE were both significantly correlated with the changes in AL at the first-month visit (P<0.05).

Conclusion

After AL is shortened in the initial stage of orthokeratology, it will experience a rapid rebound during the washout period, and the shortening can reappear when re-wearing OK lenses. Hence, the evaluation of orthokeratology will be more objective and accurate after the wash-out period. In addition, the existence and degree of axial shortening can be used as a predictor of long-term myopia development.
Swept-source optical coherence tomography angiography of retinal occlusive vasculitis following brolucizumab administration: a case report
Authors: Lee Eun Kyoung , Oh Baek-Lok , Yoon Chang Ki , Park Un Chul
Published: June 2022

Background

We present a case of retinal occlusive vasculitis following brolucizumab administration and the first report of optical coherence tomography angiography (OCTA) findings after treatment.

Case presentation

A 71-year-old man complained of vision loss in the left eye 6 weeks after brolucizumab injection. His visual acuity was counting fingers, and examination revealed 1 + anterior chamber cells with 2 + vitreous cells. Fundus examination demonstrated vitreous haze, retinal whitening, and vascular sheathing. Fluorescein angiography revealed filling defects in the retinal arteries and veins, and OCTA showed extensive capillary nonperfusion. Under the diagnosis of brolucizumab-associated intraocular inflammation (IOI) and retinal occlusive vasculitis, topical, sub-Tenon, and systemic corticosteroids were administered. After the treatment, visual acuity improved to 20/200, and OCTA revealed gradual improvement in capillary dropout; however, with the limited improvement of reperfusion in the perifoveal areas.

Conclusions

Prompt evaluation and intensive corticosteroid treatments are required for brolucizumab-associated IOI. OCTA imaging provides detailed information on microvascular changes in the retinal vascular plexuses in brolucizumab-associated retinal occlusive vasculitis.