bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning algorithm to predict anterior cruciate ligament revision demonstrates external validity
Authors: Martin R. Kyle , Wastvedt Solvejg , Pareek Ayoosh , Persson Andreas , Visnes Håvard , Fenstad Anne Marie , Moatshe Gilbert , Wolfson Julian , Lind Martin , Engebretsen Lars 
Published: January 2022

Abstract
Purpose
External validation of machine learning predictive models is achieved through evaluation of model performance on different groups of patients than were used for algorithm development. This important step is uncommonly performed, inhibiting clinical translation of newly developed models. Machine learning analysis of the Norwegian Knee Ligament Register (NKLR) recently led to the development of a tool capable of estimating the risk of anterior cruciate ligament (ACL) revision (https://swastvedt.shinyapps.io/calculator_rev/). The purpose of this study was to determine the external validity of the NKLR model by assessing algorithm performance when applied to patients from the Danish Knee Ligament Registry (DKLR).

Methods
The primary outcome measure of the NKLR model was probability of revision ACL reconstruction within 1, 2, and/or 5 years. For external validation, all DKLR patients with complete data for the five variables required for NKLR prediction were included. The five variables included graft choice, femur fixation device, KOOS QOL score at surgery, years from injury to surgery, and age at surgery. Predicted revision probabilities were calculated for all DKLR patients. The model performance was assessed using the same metrics as the NKLR study: concordance and calibration.

Results
In total, 10,922 DKLR patients were included for analysis. Average follow-up time or time-to-revision was 8.4 (± 4.3) years and overall revision rate was 6.9%. Surgical technique trends (i.e., graft choice and fixation devices) and injury characteristics (i.e., concomitant meniscus and cartilage pathology) were dissimilar between registries. The model produced similar concordance when applied to the DKLR population compared to the original NKLR test data (DKLR: 0.68; NKLR: 0.68–0.69). Calibration was poorer for the DKLR population at one and five years post primary surgery but similar to the NKLR at two years.

Conclusion
The NKLR machine learning algorithm demonstrated similar performance when applied to patients from the DKLR, suggesting that it is valid for application outside of the initial patient population. This represents the first machine learning model for predicting revision ACL reconstruction that has been externally validated. Clinicians can use this in-clinic calculator to estimate revision risk at a patient specific level when discussing outcome expectations pre-operatively. While encouraging, it should be noted that the performance of the model on patients undergoing ACL reconstruction outside of Scandinavia remains unknown.

Level of evidence
III.
Pharmacological inhibition of MERTK induces in vivo retinal degeneration: a multimodal imaging ocular safety assessment
Authors: Hamm Gregory , Maglennon Gareth , Williamson Beth , Macdonald Ruth , Doherty Ann , Jones Stewart , Harris Jayne , Blades James , Harmer Alexander R. , Barton Peter , Rawlins Philip B. , Smith Paul , Winter-Holt Jon , McMurray Lindsay , Johansson Julia , Fitzpatrick Paul , McCoull William , Coen Muireann 
Published: January 2022

AbstractThe receptor tyrosine kinase, MERTK, plays an essential role in homeostasis of the retina via efferocytosis of shed outer nuclear segments of photoreceptors. The Royal College of Surgeons rat model of retinal degeneration has been linked to loss-of-function of MERTK, and together with the MERTK knock-out mouse, phenocopy retinitis pigmentosa in humans with MERTK mutations. Given recent efforts and interest in MERTK as a potential immuno-oncology target, development of a strategy to assess ocular safety at an early pre-clinical stage is critical. We have applied a state-of-the-art, multi-modal imaging platform to assess the in vivo effects of pharmacological inhibition of MERTK in mice. This involved the application of mass spectrometry imaging (MSI) to characterize the ocular spatial distribution of our highly selective MERTK inhibitor; AZ14145845, together with histopathology and transmission electron microscopy to characterize pathological and ultra-structural change in response to MERTK inhibition. In addition, we assessed the utility of a human retinal in vitro cell model to identify perturbation of phagocytosis post MERTK inhibition. We identified high localized total compound concentrations in the retinal pigment epithelium (RPE) and retinal lesions following 28 days of treatment with AZ14145845. These lesions were present in 4 of 8 treated animals, and were characterized by a thinning of the outer nuclear layer, loss of photoreceptors (PR) and accumulation of photoreceptor outer segments at the interface of the RPE and PRs. Furthermore, the lesions were very similar to that shown in the RCS rat and MERTK knock-out mouse, suggesting a MERTK-induced mechanism of PR cell death. This was further supported by the observation of reduced phagocytosis in the human retinal cell model following treatment with AZ14145845. Our study provides a viable, translational strategy to investigate the pre-clinical toxicity of MERTK inhibitors but is equally transferrable to novel chemotypes.
Prevalence of Paediatric Surgical Conditions in Eastern Uganda: A Cross‐Sectional Study
Authors: Ajiko Mary Margaret , Weidman Viking , Nordin Pär , Wladis Andreas , Löfgren Jenny 
Published: January 2022

AbstractBackgroundThe role of surgery in global health has gained greater attention in recent years. Approximately 1.8 billion children below 15 years live in low‐ and middle‐income countries (LMIC). Many surgical conditions affect children. Therefore, paediatric surgery requires specific emphasis. Left unattended, the consequences can be dire. Despite this, there is a paucity of data regarding prevalence of surgical conditions in children in LMIC. The present objective was to investigate the prevalence of paediatric surgical conditions in children in a defined geographical area in Eastern Uganda.MethodA cross‐sectional study was carried out in the Iganga‐Mayuge Health and Demographic Surveillance Site located in Eastern Uganda. Through a two‐stage, cluster‐based sampling process, 490 households from 49 villages were randomly selected, generating a study population of 1581 children. The children's caregivers were interviewed, and the children were physically examined by two medical doctors to identify any surgical conditions.ResultsThe interview was performed with 1581 children, and 1054 were physically examined. Among these, the overall prevalence of any surgical condition was 16.0 per cent (n = 169). Of these, 39 per cent had an unmet surgical need (66 of 169). This is equivalent to a 6.3 per cent prevalence of current unmet surgical need. The most common groups of surgical condition were congenital anomalies and trauma‐related conditions.ConclusionSurgical conditions in children are common in eastern Uganda. The unmet need for surgery is high. With a growing population, the need for paediatric surgical capacity will increase even further. The health care system must be reinforced to provide services for children with surgical conditions if United Nations Sustainability Development Goal 3 is to be achieved by 2030.
The burden of illness in patients with paroxysmal nocturnal hemoglobinuria receiving treatment with the C5-inhibitors eculizumab or ravulizumab: results from a US patient survey
Authors: Dingli David , Matos Joana E. , Lehrhaupt Kerri , Krishnan Sangeeta , Yeh Michael , Fishman Jesse , Sarda Sujata P. , Baver Scott B. 
Published: January 2022

Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening disease with symptoms of hemolysis and thrombosis. Current therapies for this complement-mediated disease rely predominantly on inhibition of the C5 complement protein. However, data on treatment responses and quality of life in C5-inhibitor (C5i)-treated PNH patients are scarce. The objective of this study was to determine C5i treatment effects on clinical parameters, PNH symptoms, quality of life, and resource use for PNH patients. This cross-sectional study surveyed 122 individuals in the USA receiving treatment for PNH with C5-targeted monoclonal antibodies, eculizumab (ECU) or ravulizumab (RAV). Despite most patients receiving C5i therapy for ≥ 3 months (ECU 100%, n = 35; RAV 95.4%, n = 83), many patients remained anemic with hemoglobin levels ≤ 12 g/dL in 87.5% (n = 28/32) and 82.9% (n = 68/82) of ECU and RAV recipients, respectively. A majority of patients on ECU (88.6%; n = 31/35) and RAV (74.7%; n = 65/87) reported fatigue symptoms. Among PNH patients receiving C5i therapy for ≥ 12 months, some still reported thrombotic events (ECU, 10.0%, n = 1/10; RAV, 23.5%, n = 4/17) and required transfusions within the past year (ECU, 52.2%, n = 12/23; RAV, 22.6%, n = 7/31). Other patient-reported PNH symptoms included breakthrough hemolysis, shortness of breath, and headaches. Patients reported scores below the average population norms on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scales. Overall, this study found that PNH patients receiving ECU or RAV therapy demonstrated a significant burden of illness, highlighting the need for improved PNH therapies.
Validation of an automatic tool for the rapid measurement of brain atrophy and white matter hyperintensity: QyScore®
Authors: Cavedo Enrica , Tran Philippe , Thoprakarn Urielle , Martini Jean-Baptiste , Movschin Antoine , Delmaire Christine , Gariel Florent , Heidelberg Damien , Pyatigorskaya Nadya , Ströer Sébastian , Krolak-Salmon Pierre , Cotton Francois , dos Santos Clarisse Longo , Dormont Didier 
Published: January 2022

Abstract
Objectives
QyScore® is an imaging analysis tool certified in Europe (CE marked) and the US (FDA cleared) for the automatic volumetry of grey and white matter (GM and WM respectively), hippocampus (HP), amygdala (AM), and white matter hyperintensity (WMH). Here we compare QyScore® performances with the consensus of expert neuroradiologists.

Methods
Dice similarity coefficient (DSC) and the relative volume difference (RVD) for GM, WM volumes were calculated on 50 3DT1 images. DSC and the F1 metrics were calculated for WMH on 130 3DT1 and FLAIR images. For each index, we identified thresholds of reliability based on current literature review results. We hypothesized that DSC/F1 scores obtained using QyScore® markers would be higher than the threshold. In contrast, RVD scores would be lower. Regression analysis and Bland–Altman plots were obtained to evaluate QyScore® performance in comparison to the consensus of three expert neuroradiologists.

Results
The lower bound of the DSC/F1 confidence intervals was higher than the threshold for the GM, WM, HP, AM, and WMH, and the higher bounds of the RVD confidence interval were below the threshold for the WM, GM, HP, and AM. QyScore®, compared with the consensus of three expert neuroradiologists, provides reliable performance for the automatic segmentation of the GM and WM volumes, and HP and AM volumes, as well as WMH volumes.

Conclusions
QyScore® represents a reliable medical device in comparison with the consensus of expert neuroradiologists. Therefore, QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases.

Key Points
• QyScore® provides reliable automatic segmentation of brain structures in comparison with the consensus of three expert neuroradiologists.
• QyScore® automatic segmentation could be performed on MRI images using different vendors and protocols of acquisition. In addition, the fast segmentation process saves time over manual and semi-automatic methods.
• QyScore® could be implemented in clinical trials and clinical routine to support the diagnosis and longitudinal monitoring of neurological diseases.
Drivers and physical processes of drought events over the State of São Paulo, Brazil
Authors: Abatan Abayomi A. , Tett Simon F. B. , Dong Buwen , Cunningham Christopher , Rudorff Conrado M. , Klingaman Nicholas P. , de Abreu Rafael C. 
Published: January 2022

AbstractThe State of São Paulo, Brazil (SSP) was impacted by severe water shortages during the intense austral summer drought of 2013/2014 and 2014/2015 (1415SD). This study seeks to understand the features and physical processes associated with these summer droughts in the context of other droughts over the region during 1961–2010. Thus, this study examines the spatio-temporal characteristics of anomalously low precipitation over SSP and the associated large-scale dynamics at seasonal timescales, using an observation-based dataset from the Climatic Research Unit (CRU) and model simulation outputs from the Met Office Hadley Centre Global Environment Model (HadGEM3-GA6 at N216 resolution). The study analyzes Historical and Natural simulations from the model to examine the role of human-induced climate forcing on droughts over SSP. Composites of large-scale fields associated with droughts are derived from ERA-20C and ERA-Interim reanalysis and the model simulations. HadGEM3-GA6 simulations capture the observed interannual variability of normalized precipitation anomalies over SSP, but with biases. Drought events over SSP are related to subsidence over the region. This is associated with reduced atmospheric moisture over the region as indicated by the analysis of the vertically integrated moisture flux convergence, which is dominated by reduced moisture flux convergence. The Historical simulations simulate the subsidence associated with droughts, but there are magnitude and location biases. The similarities between the circulation features of the severe 1415SD and other drought events over the region show that understanding of the dynamics of the past drought events over SSP could guide assessment of changes in risk of future droughts and improvements of model performance. The study highlights the merits and limitations of the HadGEM3-GA6 simulations. The model possesses the skills in simulating the large-scale atmospheric circulations modulating precipitation variability, leading to drought conditions over SSP.
Assessment of thoron contribution to indoor radon exposure in Canada
Authors: Chen Jing 
Published: January 2022

AbstractFrom 2007 to 2013, simultaneous radon (222Rn) and thoron (220Rn) measurements were conducted in a total of 3534 residential homes in 34 metropolitan areas covering 71% of the Canadian population. While radon levels were above the detector’s detection limit in almost all homes, thoron concentrations were measurable in only 1738 homes. When analysis was limited to homes where thoron concentrations exceeded the detection limit, a pooled analysis confirmed that thoron is log-normally distributed in the indoor environment, and the distribution was characterized by a population-weighted geometric mean of 13 Bq/m3 and a geometric standard deviation of 1.89. Thoron contribution to indoor radon dose varied widely, ranging from 1.3 to 32% geographically. This study indicated that on average, thoron contributes 4% of the radiation dose due to total indoor radon exposure (222Rn and 220Rn) in Canada.
Pre-emptive active drainage of reflux (PARD) in Ivor-Lewis oesophagectomy with negative pressure and simultaneous enteral nutrition using a double-lumen open-pore film drain (dOFD)
Authors: Loske Gunnar , Müller Johannes , Schulze Wolfgang , Riefel Burkhard , Müller Christian Theodor 
Published: January 2022

Abstract
Background
Postoperative reflux can compromise anastomotic healing after Ivor-Lewis oesophagectomy (ILE). We report on Pre-emptive Active Reflux Drainage (PARD) using a new double-lumen open-pore film drain (dOFD) with negative pressure to protect the anastomosis.

Methods
To prepare a dOFD, the gastric channel of a triluminal tube (Freka®Trelumina, Fresenius) is coated with a double-layered open-pore film (Suprasorb®CNP drainage film, Lohmann & Rauscher) over 25 cm. The ventilation channel is blocked. The filmcoated segment is placed in the stomach and the intestinal feeding tube in the duodenum. Negative pressure is applied with an electronic vacuum pump (− 125 mmHg, continuous suction) to the gastric channel. Depending on the findings in the endoscopic control, PARD will either be continued or terminated.

Results
PARD was used in 24 patients with ILE and started intraoperatively. Healing was observed in all the anastomoses. The median duration of PARD was 8 days (range 4–21). In 10 of 24 patients (40%) there were issues with anastomotic healing which we defined as “at-risk anastomosis”. No additional endoscopic procedures or surgical revisions to the anastomoses were required.

Conclusions
PARD with dOFD contributes to the protection of anastomosis after ILE. Negative pressure applied to the dOFD (a nasogastric tube) enables enteral nutrition to be delivered simultaneously with permanent evacuation and decompression.
A convolution neural network approach for fall detection based on adaptive channel selection of UWB radar signals
Authors: Wang Ping , Li Qimeng , Yin Peng , Wang Zhonghao , Ling Yu , Gravina Raffaele , Li Ye 
Published: January 2022

AbstractAccording to the World Health Organization and other authorities, falls are one of the main causes of accidental injuries among the elderly population. Therefore, it is essential to detect and predict the fall activities of older persons in indoor environments such as homes, nursing, senior residential centers, and care facilities. Due to non-contact and signal confidentiality characteristics, radar equipment is widely used in indoor care, detection, and rescue. This paper proposes an adaptive channel selection algorithm to separate the activity signals from the background using an ultra-wideband radar and to generalize fused features of frequency- and time-domain images which will be sent to a lightweight convolutional neural network to detect and recognize fall activities. The experimental results show that the method is able to distinguish three types of fall activities (i.e., stand to fall, bow to fall, and squat to fall) and obtain a high recognition accuracy up to 95.7%.
Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials
Authors: Jones Robyn R. , Freeman Marlene P. , Kornstein Susan G. , Cooper Kimberly , Daly Ella J. , Canuso Carla M. , Nicholson Susan 
Published: January 2022

AbstractThe objective of this analysis was to determine if there are sex differences with esketamine for treatment-resistant depression (TRD). Post hoc analyses of three randomized, controlled studies of esketamine in patients with TRD (TRANSFORM-1, TRANSFORM-2 [18–64 years], TRANSFORM-3 [≥ 65 years]) were performed. In each 4-week study, adults with TRD were randomized to esketamine or placebo nasal spray, each with a newly initiated oral antidepressant. Change from baseline to day 28 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was assessed by sex in pooled data from TRANSFORM-1/TRANSFORM-2 and separately in data from TRANSFORM-3 using a mixed-effects model for repeated measures. Use of hormonal therapy was assessed in all women, and menopausal status was assessed in women in TRANSFORM-1/TRANSFORM-2. Altogether, 702 adults (464 women) received ≥ 1 dose of intranasal study drug and antidepressant. Mean MADRS total score (SD) decreased from baseline to day 28, more so among patients treated with esketamine/antidepressant vs. antidepressant/placebo in both women and men: TRANSFORM-1/TRANSFORM-2 women—esketamine/antidepressant -20.3 (13.19) vs. antidepressant/placebo -15.8 (14.67), men—esketamine/antidepressant -18.3 (14.08) vs. antidepressant/placebo -16.0 (14.30); TRANSFORM-3 women—esketamine/antidepressant -9.9 (13.34) vs. antidepressant/placebo -6.9 (9.65), men—esketamine/antidepressant -10.3 (11.96) vs. antidepressant/placebo -5.5 (7.64). There was no significant sex effect or treatment-by-sex interaction (p > 0.35). The most common adverse events in esketamine-treated patients were nausea, dissociation, dizziness, and vertigo, each reported at a rate higher in women than men. The analyses support antidepressant efficacy and overall safety of esketamine nasal spray are similar between women and men with TRD. The TRANSFORM studies are registered at clinicaltrials.gov (identifiers: NCT02417064 (first posted 15 April 2015; last updated 4 May 2020), NCT02418585 (first posted 16 April 2015; last updated 2 June 2020), and NCT02422186 (first posted 21 April 2015; last updated 29 September 2021)).
Biophysical Determinants of Shifting Tundra Vegetation Productivity in the Beaufort Delta Region of Canada
Authors: Seider Jordan H. , Lantz Trevor C. , Hermosilla Txomin , Wulder Michael A. , Wang Jonathan A. 
Published: January 2022

AbstractTemperature increases across the circumpolar north have driven rapid increases in vegetation productivity, often described as ‘greening’. These changes have been widespread, but spatial variation in their pattern and magnitude suggests that biophysical factors also influence the response of tundra vegetation to climate warming. In this study, we used field sampling of soils and vegetation and random forests modeling to identify the determinants of trends in Landsat-derived Enhanced Vegetation Index, a surrogate for productivity, in the Beaufort Delta region of Canada between 1984 and 2016. This region has experienced notable change, with over 71% of the Tuktoyaktuk Coastlands and over 66% of the Yukon North Slope exhibiting statistically significant greening. Using both classification and regression random forests analyses, we show that increases in productivity have been more widespread and rapid at low-to-moderate elevations and in areas dominated by till blanket and glaciofluvial deposits, suggesting that nutrient and moisture availability mediate the impact of climate warming on tundra vegetation. Rapid greening in shrub-dominated vegetation types and observed increases in the cover of low and tall shrub cover (4.8% and 6.0%) also indicate that regional changes have been driven by shifts in the abundance of these functional groups. Our findings demonstrate the utility of random forests models for identifying regional drivers of tundra vegetation change. To obtain additional fine-grained insights on drivers of increased tundra productivity, we recommend future research combine spatially comprehensive time series satellite data (as used herein) with samples of high spatial resolution imagery and integrated field investigations.
Binary optimal control by trust-region steepest descent
Authors: Hahn Mirko , Leyffer Sven , Sager Sebastian 
Published: January 2022

AbstractWe present a trust-region steepest descent method for dynamic optimal control problems with binary-valued integrable control functions. Our method interprets the control function as an indicator function of a measurable set and makes set-valued adjustments derived from the sublevel sets of a topological gradient function. By combining this type of update with a trust-region framework, we are able to show by theoretical argument that our method achieves asymptotic stationarity despite possible discretization errors and truncation errors during step determination. To demonstrate the practical applicability of our method, we solve two optimal control problems constrained by ordinary and partial differential equations, respectively, and one topological optimization problem.