Machine learning models for abstract screening task - A systematic literature review application for health economics and outcome research.

OBJECTIVE: Systematic literature reviews (SLRs) are critical for life-science research. However, the manual selection and retrieval of relevant publications can be a time-consuming process. This study aims to (1) develop two disease-specific annotated corpora, one for human papillomavirus (HPV) associated diseases and the other for pneumococcal-associated pediatric diseases (PAPD), and (2) optimize machine- and deep-learning models to facilitate automation of the SLR abstract screening. METHODS: This study constructed two disease-specific SLR screening corpora for HPV and PAPD, which contained citation metadata and corresponding abstracts. Performance was evaluated using precision, recall, accuracy, and F1-score of multiple combinations of machine- and deep-learning algorithms and features such as keywords and MeSH terms. RESULTS AND CONCLUSIONS: The HPV corpus contained 1697 entries, with 538 relevant and 1159 irrelevant articles. The PAPD corpus included 2865 entries, with 711 relevant and 2154 irrelevant articles. Adding additional features beyond title and abstract improved the performance (measured in Accuracy) of machine learning models by 3% for HPV corpus and 2% for PAPD corpus. Transformer-based deep learning models that consistently outperformed conventional machine learning algorithms, highlighting the strength of domain-specific pre-trained language models for SLR abstract screening. This study provides a foundation for the development of more intelligent SLR systems.

Prognosis and conditional survival among women with newly diagnosed ovarian cancer.

OBJECTIVE: An important question in determining long-term prognosis for women with ovarian cancer is whether risk of death changes the longer a woman lives. Large real-world datasets permit assessment of conditional survival (CS) given both prior overall survival (OS) and real-world progression-free survival (rwPFS). METHODS: Using a longitudinal dataset from US oncology centers, this study included 6778 women with ovarian cancer. We calculated CS rates as the Kaplan-Meier probability of surviving an additional 1 or 5 years, given no mortality (OS) or disease progression (rwPFS) event in the previous 0.5-5 years since first-line chemotherapy initiation, adjusted for factors associated with OS based on multivariable Cox regression. RESULTS: Median study follow-up was 9 years (range, 1-44) from first-line initiation to data cutoff (17-Feb-2021). Median OS was 58.0 months (95% CI, 54.9-60.8); median rwPFS was 18.4 months (17.4-19.4). The adjusted 1-year CS rate (ie, rate of 1 year additional survival) did not vary based on time alive, whereas the adjusted 5-year CS rate increased from 48.5% (47.0%-50.1%) for women who had already survived 6 months to 66.4% (63.3%-69.6%) for those already surviving 5 years (thus surviving 10 years total). The adjusted 1-year CS rate increased from 90.4% (89.5%-91.4%) with no rwPFS event at 6 months to 97.6% (96.4%-98.8%) with no rwPFS event at 5 years; adjusted 5-year CS rate increased from 53.7% (52.0%-55.5%) to 85.0% (81.2%-88.9%), respectively. CONCLUSIONS: This analysis extends the concept of CS by also conditioning on time progression-free. Patients with longer rwPFS experience longer survival than patients with shorter rwPFS.

Corrigendum to "Adjuvant and first line chemotherapy use for endometrial cancer" [Gynecol. Oncol. Rep. 41 (2022) 101002].

[This corrects the article DOI: 10.1016/j.gore.2022.101002.].

Pembrolizumab-combination therapy for previously untreated metastatic nonsquamous NSCLC: Real-world outcomes at US oncology practices.

Objectives: The availability of immunotherapies has expanded the options for treating metastatic NSCLC, but information is needed regarding outcomes of immunotherapy for patients treated outside of clinical trials. The aim of this retrospective study was to evaluate the outcomes of therapy with first-line pembrolizumab plus pemetrexed and carboplatin (pembrolizumab-combination) for patients with metastatic nonsquamous NSCLC in the real-world setting of oncology clinics in the United States (US). Methods: Using deidentified, longitudinal patient records from a nationwide, electronic health record-derived US database, we identified patients with metastatic nonsquamous NSCLC, without EGFR/ALK/ROS1 genomic alterations, who had received no previous systemic anticancer therapy. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and initiated first-line pembrolizumab-combination therapy from 11-May-2017 to 31-January-2019; data cutoff was 31-August-2020. Patients treated in a clinical trial were excluded. Manual chart review supplemented technology-enabled abstraction to identify disease progression and tumor response. Time-to-event endpoints from initiation of pembrolizumab-combination therapy were determined using Kaplan-Meier. Results: Of 377 patients with metastatic nonsquamous NSCLC, 105 (28%), 104 (28%), and 103 (27%) had programmed death-ligand 1 (PD-L1) expression ≥50%, 1-49%, and <1%, respectively; PD-L1 expression was not documented for 65 patients (17%). Median age was 66 years, and 227 patients (60%) were men. Median follow-up time from first-line therapy initiation to data cutoff was 31.2 months (range, 19.0-39.6 months). Median pembrolizumab real-world time on treatment (rwToT) was 5.8 months (95% CI, 5.0-6.7); 12- and 24-month on-treatment rates for pembrolizumab were 28.0% and 14.9%, respectively. Median overall survival (OS) was 17.2 months (95% CI, 13.6-19.9). For patients in PD-L1 expression ≥50%, 1-49%, <1%, and unknown cohorts, the 12-month survival rates were 66.0%, 58.5%, 54.5%, and 58.3%, respectively, and 24-month survival rates were 43.1%, 37.2%, 35.6%, and 42.0%, respectively. Median real-world progression-free survival was 6.2 months (95% CI, 5.5-7.1); and the real-world response rate was 39.3%, with median duration of response of 13.1 months (95% CI, 10.5-16.8). Conclusions: These findings demonstrate the benefits of first-line pembrolizumab-combination therapy for patients with EGFR/ALK-wild-type, metastatic nonsquamous NSCLC and good performance status who are treated at US community oncology clinics.

Relative importance of individual insurance status and hospital payer mix on survival for women with cervical cancer.

OBJECTIVE: To assess the relative contributions of individual insurance status and hospital payer mix (safety net status) to quality of care and survival for patients with cervical cancer. METHODS: We used the National Cancer Database to identify patients with cervical cancer diagnosed from 2004 to 2017. Patients were classified by insurance (uninsured/Medicaid/private/Medicare/other) and hospitals were grouped into quartiles based on the proportion of uninsured/Medicaid patients (payer mix) (top quartile defined as safety-net hospital (SNHs) and lowest as Q1 hospitals). Quality-of-care was assessed by adherence to evidence-based metrics. Individual contributions of insurance status and payer mix to survival was assessed with a proportional hazards Cox model. RESULTS: A total of 124,339 patients including 11,338 uninsured (9.1%) and 27,281 Medicaid (21.9%) recipients treated at 1156 hospitals were identified. Quality-of-care was not significantly different across hospital quartiles. Adjusting for patients' clinical/demographic characteristics, treatment at a SNH was associated with a 14% higher mortality (HR = 1.14; 95% CL, 1.08-1.20) than at Q1 hospitals. Testing for individual insurance, uninsured patients had 32% increased mortality (HR = 1.32; 95% CI,1.26-1.38) and Medicaid recipients 40% increased (HR = 1.40; 95%CI,1.35-1.44) compared to privately insured patients. Examining both payer mix and insurance, only individual insurance retained a significant impact on mortality. CONCLUSIONS: Individual insurance may be a more important predictor of survival than site-of-care and hospital payer mix for women with cervical cancer. There is substantial variation in outcomes within hospitals based on individual insurance, regardless of hospital payer mix.

Adjuvant and first line chemotherapy use for endometrial cancer.

Objective: The objective of this study was to describe patterns of utilization of cytotoxic, hormonal, and immunotherapy in patients with endometrial cancer in the adjuvant setting and at the time of first recurrence. Methods: We identified patients in the IBM MarketScan database with endometrial cancer who underwent hysterectomy from 2011 to 2019. The use of clinically relevant therapeutic agents and combination regimens was determined in the adjuvant setting and at the time of first recurrence. Results: A total of 22,632 patients were identified. Of these, 7,147 patients (31.6%) received adjuvant radiation and 4,381 (19.4%) received adjuvant chemotherapy following surgery. Of those who received adjuvant chemotherapy, the most commonly utilized agents were carboplatin (90.3%), paclitaxel (85.8%), cisplatin (9.4%), docetaxel (9.3%), gemcitabine (3.8%), and doxorubicin (2.0%), while bevacizumab was utilized in 1.5% of patients. A combination of platinum and a taxane were utilized as adjuvant therapy in 88.8% of women. Of the cohort, 1,825 patients (8.1%) recurred, of whom 1,017 patients had already received adjuvant chemotherapy. The median time from hysterectomy to initiation of chemotherapy for recurrence was 13.3 months (IQR: 7.6-23.1 months). Overall, platinum and taxane combination therapy was used in 788 (46.8%) of patients with recurrent disease, platinum alone or with other drugs in 194 (11.5%), taxanes alone or with other drugs in 145 (8.6%), and non-platinum and non-taxane based therapy in 31.3%. Conclusions: Among patients with endometrial cancer who underwent hysterectomy, platinum-taxane combination chemotherapy was used in almost 90% of patients who received adjuvant chemotherapy while nearly 70% of patients who recurred were treated with platinum or taxane based therapy at first recurrence.

Real-World Time on Treatment with First-Line Pembrolizumab Monotherapy for Advanced NSCLC with PD-L1 Expression ≥ 50%: 3-Year Follow-Up Data.

Our aim was to evaluate real-world time on treatment (rwToT), overall and by KRAS mutation status, with first-line pembrolizumab monotherapy for advanced non-small cell lung cancer (NSCLC) in real-world oncology practice in the US. rwToT is a readily available, intermediate-range endpoint that is moderately to highly correlated with overall survival in clinical trials and real-world data. Using deidentified electronic medical record data, we studied patients with ECOG performance status (PS) of 0-2 who initiated pembrolizumab (1 November 2016 to 31 March 2020) for advanced NSCLC with programmed death-ligand 1 (PD-L1) expression ≥ 50% and without EGFR/ALK/ROS1 genomic alterations. The data cutoff was 31 March 2021, and the median study follow-up was 34 months. The Kaplan-Meier median rwToT with first-line pembrolizumab monotherapy was 7.4 months (95% CI, 6.3-8.1) for 807 patients with PS 0-1, which was consistent with the median treatment duration in the KEYNOTE-024 trial (7.9 months). The median rwToT for 237 patients with PS 2 was 2.1 months (95% CI, 1.4-2.8). For those with KRAS-mutated and KRAS wild-type nonsquamous NSCLC and PS 0-1, the median rwToT was 7.6 months and 7.0 months, respectively. Our findings suggest long-term benefit of first-line pembrolizumab monotherapy for advanced NSCLC with PD-L1 expression ≥ 50% in real-world settings in the US, particularly for patients with good performance status at the start of therapy, irrespective of KRAS status.

Synergy of Porous Structure and Microstructure in Piezoresistive Material for High-Performance and Flexible Pressure Sensors.

A porous and microstructure piezoresistive material composed of polydimethylsiloxane (PDMS) and multiwalled carbon nanotubes (MWCNTs) was designed and prepared for a flexible and highly sensitive pressure sensor over a wide detection range. The microstructure was patterned on the surface of the partially cured PDMS/MWCNTs/NaCl mixture by imprinting a nonwoven fabric. After curing and dissolving the NaCl powders, the porous and surface microstructure PDMS/MWCNT film was obtained. Two PDMS/MWCNT films were stacked together and sandwiched between two copper foil electrodes, in which the two microstructure surfaces were in contact with the electrodes. Due to the synergistic effects of the combination of the porous structure and surface microstructure, the flexible sensor had highly sensitive response over a wide pressure range from 1 Pa to 100 kPa. Under the small pressure, the high sensitivity was achieved by the change in contact areas between the electrodes and the surface microstructures; at high pressure up to 100 kPa, the sensor retained its high sensitivity because of the porous structure of the piezoresistive PDMS/MWCNT material. Additionally, the sensor had fast response speed and good durability. The piezoresistive pressure sensors based on the porous and microstructure PDMS/MWCNTs were demonstrated in detection of sound, monitoring of human activities, and array mapping of the spatial pressure distribution.

Assessment of pelvic morphology using 3D imaging and analysis in unilateral Crowe-IV developmental dysplasia of the hip.

AIMS: Morphological abnormalities are present in patients with developmental dysplasia of the hip (DDH). We studied and compared the pelvic anatomy and morphology between the affected hemipelvis with the unaffected side in patients with unilateral Crowe type IV DDH using 3D imaging and analysis. METHODS: A total of 20 patients with unilateral Crowe-IV DDH were included in the study. The contralateral side was considered normal in all patients. A coordinate system based on the sacral base (SB) in a reconstructed pelvic model was established. The pelvic orientations (tilt, rotation, and obliquity) of the affected side were assessed by establishing a virtual anterior pelvic plane (APP). The bilateral coordinates of the anterior superior iliac spine (ASIS) and the centres of hip rotation were established, and parameters concerning size and volume were compared for both sides of the pelvis. RESULTS: The ASIS on the dislocated side was located inferiorly and anteriorly compared to the healthy side (coordinates on the y-axis and z-axis; p = 0.001; p = 0.031). The centre of hip rotation on the dislocated side was located inferiorly and medially compared to the healthy side (coordinates on the x-axis and the y-axis; p < 0.001; p = 0.003). The affected hemipelvis tilted anteriorly in the sagittal plane (mean 8.05° (SD 3.57°)), anteriorly rotated in the transverse plane (mean 3.31° (SD 1.41°)), and tilted obliquely and caudally in the coronal plane (mean 2.04° (SD 0.81°)) relative to the healthy hemipelvis. The affected hemipelvis was significantly smaller in the length, width, height, and volume than the healthy counterpart. (p = 0.014; p = 0.009; p = 0.035; p = 0.002). CONCLUSION: Asymmetric abnormalities were identified on the affected hemipelvis in patients with the unilateral Crowe-IV DDH using 3D imaging techniques. Improved understanding of the morphological changes may influence the positioning of the acetabular component at THA. Acetabular component malpositioning errors caused by anterior tilt of the affected hemi pelvis and the abnormal position of the affected side centre of rotation should be considered by orthopaedic surgeons when undertaking THA in patients with Crowe-IV DDH. Cite this article: Bone Joint J 2020;102-B(10):1311-1318.

Metabolic Score for Insulin Resistance Is Correlated to Adipokine Disorder and Inflammatory Activity in Female Knee Osteoarthritis Patients in a Chinese Population.

PURPOSE: This study was to evaluate the metabolic score for insulin resistance (METS-IR) in female knee osteoarthritis (KOA) patients in a Chinese population. The associations between METS-IR and adipokines, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were investigated. PATIENTS AND METHODS: This study included 4686 women from the 2011 China Health and Retirement Longitudinal Study (CHARLS) and 108 women who underwent arthroplasty of KOA at a university hospital. The clinical data were collected, and adipokines were evaluated. METS-IR was calculated in the KOA patients and compared with the national baseline. Logistic regression analyses were applied to explore the associations of METS-IR with adipokines, ESR, and CRP. RESULTS: Receiver operating characteristic curve analysis of METS-IR and metabolic syndrome (MetS) in national baseline showed an area under the curve value of 0.851, with sensitivity of 0.777 and specificity of 0.772. The METS-IR of KOA was higher than the national baseline level (40.29 ± 6.98 vs 36.20 ± 8.50, P < 0.01), even after adjusting age. In addition, the METS-IR was higher in patients with KOA who had MetS than in those without metabolic syndrome (nMetS), even after adjusting body mass index (BMI). After adjusting for age and BMI, METS-IR was associated with CRP (OR 1.238, 95% confidence interval (CI) 1.088, 1.409, P < 0.01), ESR (OR 1.124, 95% CI 1.008, 1.254, P = 0.036), plasma leptin (OR 1.123, 95% CI 1.052, 1.199, P < 0.01), plasma resistin (OR 1.134, 95% CI 1.011, 1.271, P = 0.031), and plasma adiponectin (OR 0.865, 95% CI 0.771, 0.971, P = 0.014). CONCLUSION: METS-IR in female KOA was higher than that of the national baseline. The METS-IR was related to adipokine disorder and inflammatory activity. These findings suggest that METS-IR can be used to evaluate the degree of involvement of MetS in KOA.

An update on the association between metabolic syndrome and osteoarthritis and on the potential role of leptin in osteoarthritis.

Metabolic syndrome (MetS) has been associated with osteoarthritis (OA). Leptin, which is one of the markers of MetS, has been associated with OA pathophysiology. This study aimed to provide an update on the association between MetS and OA and on the potential role of leptin in OA. In this review, we summarized the current knowledge of the association between MetS and OA and updated the evidence on the potential role of leptin in OA. Clinical studies have investigated the epidemiologic association between MetS or its components and OA. Results suggested strong epidemiologic associations between MetS and OA, especially in the Asian population. Animal studies also indicated that metabolic dysregulation may lead to OA pathogenesis. The systemic role of MetS in OA pathophysiology is associated with obesity-related inflammation, the beneficial role of n-3 polyunsaturated fatty acids and deleterious role of cholesterol, physical inactivity, hypertension-induced subchondral ischemia, dyslipidemia-induced ectopic lipid deposition in chondrocytes, hyperglycemia-induced local effects of oxidative stress and advanced glycation end-products, low-grade systemic inflammation, and obesity-related adipokines by inducing the expression of proinflammtory factors. Leptin levels in serum/plasma and synovial fluid were associated with joint pain, radiographic progression, bone formation biomarkers, cartilage volume, knee OA incidence, and total joint arthroplasty in OA patients. Elevated leptin expression and increased effect of leptin on infrapatellar fat pad, synovium, articular cartilage, and bone were also involved in the pathogenesis of OA. Current knowledge indicates a convincing epidemiologic association between MetS and OA, especially in the Asian population. Animal studies have also shown that metabolic dysregulation may lead to OA pathogenesis. Accumulating evidence suggests that leptin may play a potential role in OA pathogenesis. Therefore, leptin and its receptor may be an emerging target for intervention in metabolic-associated OA.

Finite-element analysis of the proximal tibial sclerotic bone and different alignment in total knee arthroplasty.

BACKGROUND: Despite potential for improving patient outcomes, studies using three-dimensional measurements to quantify proximal tibial sclerotic bone and its effects on prosthesis stability after total knee arthroplasty (TKA) are lacking. Therefore, this study aimed to determine: (1) the distribution range of tibial sclerotic bone in patients with severe genu varum using three-dimensional measurements, (2) the effect of the proximal tibial sclerotic bone thickness on prosthesis stability according to finite-element modelling of TKA with kinematic alignment (KA), mechanical alignment (MA), and 3° valgus alignment, and (3) the effect of short extension stem augment utilization on prosthesis stability. METHODS: The sclerotic bone in the medial tibial plateau of 116 patients with severe genu varum was measured and classified according to its position and thickness. Based on these cases, finite-element models were established to simulate 3 different tibial cut alignments with 4 different thicknesses of the sclerotic bone to measure the stress distribution of the tibia and tibial prosthesis, the relative micromotion beneath the stem, and the influence of the short extension stem on stability. RESULTS: The distribution range of proximal tibial sclerotic bone was at the anteromedial tibial plateau. The models were divided into four types according to the thickness of the sclerotic bone: 15 mm, 10 mm, 5 mm, and 0 mm. The relative micromotion under maximum stress was smallest after MA with no sclerotic bone (3241 µm) and largest after KA with 15 mm sclerotic bone (4467 µm). Relative micromotion was largest with KA and smallest with MA in sclerotic models with the same thickness. Relative micromotion increased as thickness of the sclerotic bone increased with KA and MA (R = 0.937, P = 0.03 and R = 0.756, P = 0.07, respectively). Relative micromotion decreased with short extension stem augment in the KA model when there was proximal tibial sclerotic bone. CONCLUSIONS: The influence of proximal tibial sclerotic bone on prosthesis's stability is significant, especially with KA tibial cut. Tibial component's short extension stem augment can improve stability.

JASPer controls interphase histone H3S10 phosphorylation by chromosomal kinase JIL-1 in Drosophila.

In flies, the chromosomal kinase JIL-1 is responsible for most interphase histone H3S10 phosphorylation and has been proposed to protect active chromatin from acquiring heterochromatic marks, such as dimethylated histone H3K9 (H3K9me2) and HP1. Here, we show that JIL-1's targeting to chromatin depends on a PWWP domain-containing protein JASPer (JIL-1 Anchoring and Stabilizing Protein). JASPer-JIL-1 (JJ)-complex is the major form of kinase in vivo and is targeted to active genes and telomeric transposons via binding of the PWWP domain of JASPer to H3K36me3 nucleosomes, to modulate transcriptional output. JIL-1 and JJ-complex depletion in cycling cells lead to small changes in H3K9me2 distribution at active genes and telomeric transposons. Finally, we identify interactors of the endogenous JJ-complex and propose that JIL-1 not only prevents heterochromatin formation but also coordinates chromatin-based regulation in the transcribed part of the genome.

Tunable Water Delivery in Carbon-Coated Fabrics for High-Efficiency Solar Vapor Generation.

Solar vapor generation by localized heating and evaporation has potential to be a viable and "green" way to produce fresh water. This work reports a carbon black-coated cotton fabric with a tunable water delivery property for high-efficiency solar vapor generation under 1 sun. The fabric is prepared by an electrospray of poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP) on one-side of the fabric followed by dip-coating of the fabric with carbon black as a photothermal absorber. Depending on the duration of electrospray, the roughness gradient generated by the PVDF-HFP layer in the fabric leads to guided and continuous one-way water transport from the electrosprayed hydrophobic side to the hydrophilic side with a tunable delivery rate. The tunable water delivery capability of the fabric regulates the amount of water supplied to the vicinity of the photothermal absorber. Additionally, the fabric shows excellent broadband absorption and low thermal conductivity. In comparison with the carbon black-coated fabric without a roughness gradient, the regulation of water improves the solar vapor conversion efficiency, owing to reduced heat loss and better heat allocation. Under optimal conditions, a solar vapor conversion efficiency of 88.9% and a stable water evaporation rate of 1.33 kg (m2·h)-1 under 1 sun are achieved.

Analysis of the effect of tibial torsion on tibial osteotomy in knee arthroplasty using a three-dimensional computed tomography-based modelling technique.

BACKGROUND: Extramedullary systems are commonly used in knee arthroplasty, with the rod location being determined from the tibial torsion line during surgery. The traditional method for tibial torsion measurement is not in accordance with clinical practice. This study aimed to evaluate proximal and distal tibial torsion using 3-dimensional (3D) computed technology to establish a new evaluation method, as well as to investigate the association between tibial torsion and postoperative alignment deviation. METHODS: Fifty-five osteoarthritis tibias with >10°varus preoperatively were divided into valgus, neutral, and varus groups based on their postoperative alignment deviation. A new method based on clinical practice was built using a 3D tibial model. Proximal and distal tibial torsions were measured by both the new and traditional methods. In addition, tibial osteotomy that followed the intramedullary osteotomy system was simulated on the 3D model in the varus and valgus groups to investigate the association between tibial torsion and alignment deviation. RESULTS: Proximal tibial torsion was smaller and distal torsion was greater in the valgus group than the other two groups, according to the new method (p = 0.03 and p = 0.02, respectively). No significant difference was found when comparing these torsions by the traditional method (p = 0.782 and p = 0.753, respectively). In the valgus group, the postoperative alignment deviation improved after simulated osteotomy guided by the intramedullary system, while no significant improvement was found in the varus group. CONCLUSION: According to this new tibial-rotation evaluation method, valgus deviation in knee arthroplasty was identified as the main cause for knees in which the proximal tibial internal torsion is too small and the distal external torsion is too great. The use of an intramedullary system may help reduce this deviation. TRIAL REGISTRATION: Prospectively registered.

Evidence for a role of spindle matrix formation in cell cycle progression by antibody perturbation.

In Drosophila it has recently been demonstrated that a spindle matrix in the form of a membrane-less macromolecular assembly embeds the microtubule-based spindle apparatus. In addition, two of its constituents, Megator and Chromator, were shown to function as spatial regulators of spindle checkpoint proteins. However, whether the spindle matrix plays a wider functional role in spatially regulating cell cycle progression factors was unknown. Here using a live imaging approach we provide evidence that a number of key cell cycle proteins such as Cyclin B, Polo, and Ran co-localize with the spindle matrix during mitosis. Furthermore, prevention of spindle matrix formation by injection of a function blocking antibody against the spindle matrix protein Chromator results in cell cycle arrest prior to nuclear envelope breakdown. In such embryos the spatial dynamics of Polo and Cyclin B enrichment at the nuclear rim and kinetochores is abrogated and Polo is not imported into the nucleus. This is in contrast to colchicine-arrested embryos where the wild-type dynamics of these proteins are maintained. Taken together these results suggest that spindle matrix formation may be a general requirement for the localization and proper dynamics of cell cycle factors promoting signaling events leading to cell cycle progression.

Behind the scenes: A medical natural language processing project.

Advancement of Artificial Intelligence (AI) capabilities in medicine can help address many pressing problems in healthcare. However, AI research endeavors in healthcare may not be clinically relevant, may have unrealistic expectations, or may not be explicit enough about their limitations. A diverse and well-functioning multidisciplinary team (MDT) can help identify appropriate and achievable AI research agendas in healthcare, and advance medical AI technologies by developing AI algorithms as well as addressing the shortage of appropriately labeled datasets for machine learning. In this paper, our team of engineers, clinicians and machine learning experts share their experience and lessons learned from their two-year-long collaboration on a natural language processing (NLP) research project. We highlight specific challenges encountered in cross-disciplinary teamwork, dataset creation for NLP research, and expectation setting for current medical AI technologies.

Comparing deep learning and concept extraction based methods for patient phenotyping from clinical narratives.

In secondary analysis of electronic health records, a crucial task consists in correctly identifying the patient cohort under investigation. In many cases, the most valuable and relevant information for an accurate classification of medical conditions exist only in clinical narratives. Therefore, it is necessary to use natural language processing (NLP) techniques to extract and evaluate these narratives. The most commonly used approach to this problem relies on extracting a number of clinician-defined medical concepts from text and using machine learning techniques to identify whether a particular patient has a certain condition. However, recent advances in deep learning and NLP enable models to learn a rich representation of (medical) language. Convolutional neural networks (CNN) for text classification can augment the existing techniques by leveraging the representation of language to learn which phrases in a text are relevant for a given medical condition. In this work, we compare concept extraction based methods with CNNs and other commonly used models in NLP in ten phenotyping tasks using 1,610 discharge summaries from the MIMIC-III database. We show that CNNs outperform concept extraction based methods in almost all of the tasks, with an improvement in F1-score of up to 26 and up to 7 percentage points in area under the ROC curve (AUC). We additionally assess the interpretability of both approaches by presenting and evaluating methods that calculate and extract the most salient phrases for a prediction. The results indicate that CNNs are a valid alternative to existing approaches in patient phenotyping and cohort identification, and should be further investigated. Moreover, the deep learning approach presented in this paper can be used to assist clinicians during chart review or support the extraction of billing codes from text by identifying and highlighting relevant phrases for various medical conditions.

Determinants of satisfaction following total hip arthroplasty in patients with ankylosing spondylitis.

BACKGROUND: The aim was to explore the factors contributing to a high degree of satisfaction following total hip arthroplasty in patients with ankylosing spondylitis and hip joint fusion. METHODS: From January 2001 to June 2015, 43 patients with ankylosing spondylitis were treated with total hip arthroplasty. The patients were divided into two groups, including 20 patients in non-fusion groups, with 25 cases of hip non-fusion, and 23 patients in fusion groups, with 40 cases of hip fusion. Patients were followed for an average of 27 months. Harris hip scores (HHSs) and Barthel scores were recorded pre-operatively and post-operatively. The improvement rates of both groups were calculated, and the data were compared and analyzed. The Self-Administered Patient Satisfaction Scale (SAPS) was used to assess the degree of satisfaction in each group. RESULTS: The post-operative HHS and Barthel scores of two groups both significantly improved. In non-fusion groups compared with fusion groups, there were significant differences in the pre-operative HHSs, the improvement of the HHSs, the pre-operative Barthel score, the improvement of the Barthel score, and the satisfaction score. However, there were no significant differences in the post-operative HHSs and Barthel scores. CONCLUSION: Patients in the hip fusion group had higher satisfaction scores. The improvements in joint function and self-care ability after total hip arthroplasty are the decisive factors in determining patient satisfaction for patients with ankylosing spondylitis combined with hip fusion.

H2Av facilitates H3S10 phosphorylation but is not required for heat shock-induced chromatin decondensation or transcriptional elongation.

A model has been proposed in which JIL-1 kinase-mediated H3S10 and H2Av phosphorylation is required for transcriptional elongation and heat shock-induced chromatin decondensation. However, here we show that although H3S10 phosphorylation is indeed compromised in the H2Av null mutant, chromatin decondensation at heat shock loci is unaffected in the absence of JIL-1 as well as of H2Av and that there is no discernable decrease in the elongating form of RNA polymerase II in either mutant. Furthermore, mRNA for the major heat shock protein Hsp70 is transcribed at robust levels in both H2Av and JIL-1 null mutants. Using a different chromatin remodeling paradigm that is JIL-1 dependent, we provide evidence that ectopic tethering of JIL-1 and subsequent H3S10 phosphorylation recruits PARP-1 to the remodeling site independently of H2Av phosphorylation. These data strongly suggest that H2Av or H3S10 phosphorylation by JIL-1 is not required for chromatin decondensation or transcriptional elongation in Drosophila.