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Hypoxia can cause basement membrane (BM) degradation in tissues. Matrix metalloproteinase 9 (MMP-9) is involved in various human cancers as well as BM degradation by downregulating type IV collagen (COL4). This study investigated the role of MMP-9 in hypoxia-mediated BM degradation in rat bone marrow based on its regulation of collagen type IV alpha 1 chain (COL4A1). Eighty male rats were randomly divided into four groups based on exposure to hypoxic conditions at a simulated altitude of 7,000 m, control (normoxia) and 3, 7, and 10 days of hypoxia exposure. BM degradation in bone marrow was determined by transmission electron microscopy. MMP-9 levels were assessed by western blot and real-time PCR, and COL4A1 levels were assessed by western blot and immunohistochemistry. Microvessels BMs in bone marrow exposed to acute hypoxia were observed by electron microscopy. MMP-9 expression increased, COL4A1 protein expression decreased, and BM degradation occurred in the 10-, 7-, and 3-day hypoxia groups compared with that in the control group (all P < 0.05). Hypoxia increased MMP-9 levels, which in turn downregulated COL4A1, thereby increasing BM degradation. MMP-9 upregulation significantly promoted BM degradation and COL4A1 downregulation. Our results suggest that MMP-9 is related to acute hypoxia-induced BM degradation in bone marrow by regulating COL4A1.

Background Chronic rhinosinusitis (CRS) and eosinophilic esophagitis (EoE) are immune-mediated inflammatory conditions that share common histopathologic features. Once considered two separate pathologies, preliminary data has suggested that a higher prevalence of EoE may exist in patients with CRS. Objectives We aimed to expand the base of evidence across geographic regions and investigate the association between EoE and CRS, including CRS with nasal polyposis (CRSwNP). Methods Quantitative data detailing the prevalence of CRS, CRSwNP, and EoE were pooled from 6 large academic institutions spread across the United States using Epic electronic medical record system. One-way analysis of variance was then used to analyze the data. Results The mean prevalence of EoE in our general population sample of over 26 million individual records was 0.058% (range, 0.013%-0.103%). The mean prevalence of EoE in our sub-populations of individual with diagnoses of CRS and CRSwNP was 0.43% (F(1,12) = [8.194], P = .01) and 0.84% (F(1,12) = [23.61], P Conclusion This study reveals an 8-fold greater prevalence of concurrent EoE in patients with CRS. Importantly, this is the first study to describe the association of EoE and the CRSwNP subtype, and we demonstrate a 14-fold greater prevalence of EoE in patients with CRSwNP.

Background and Objective This study aims to evaluate the medicolegal trends related to 2 common orbital surgeries: orbital decompression and dacryocystorhinostomy (DCR). These procedures are performed by ophthalmologists, otolaryngologists, and multidisciplinary teams of both specialists. Methods The Westlaw database was reviewed from 1980 to 2020 for medical malpractice cases involving orbital decompression and DCR surgeries. Data were compiled on plaintiff and defendant demographics, procedure performed, legal allegation, nature of injury, and verdict or settlement awards. The Ophthalmic Mutual Insurance Company was also queried for all malpractice cases pertaining to orbital decompression and DCR from 1995 to 2021. Results The Westlaw database included 60 cases (34 orbital decompression, 26 DCR); of these, 8 orbital decompression and 6 DCR cases met inclusion criteria. Of the 7 orbital decompression cases that were tried, a verdict in favor of the plaintiff occurred in 4 cases (57%). Of the 5 DCR cases that were tried, a verdict in favor of the plaintiff occurred in 2 cases (40%). A search of all claims at OMIC yielded 31 cases (15 orbital decompression, 16 DCR). 22 of 31 cases were either dismissed or resulted in no payment. The remainder was settled out of court, with only one case being tried and the verdict supporting the defendant. Conclusion Despite several thousand orbital decompressions and DCR surgeries being performed annually in the US, very few lawsuits involving these complex surgeries have gone to trial. However, of the cases that did go to trial, a relatively high proportion of verdicts for plaintiffs was observed.

Objective/hypothesisTo investigate the clinical features, management strategies and outcomes for patients with metastatic primary skull base chordomas.Study designSystematic review.MethodsA systematic search through Pubmed/Medline, Web of Science, and EBSCOhost (CINAHL) was conducted without restriction on dates. After study screening and full-text assessment, two authors independently extracted all data using a pre-established abstraction form.ResultsForty cases were included from 38 studies. The average age (standard deviation [SD]) of the sample at presentation was 28.5 (23.3) and was equally distributed across genders. The average time (SD) between initial diagnosis to local recurrence was 40.1 (60.3) months. The average time (SD) from primary tumor detection to the diagnosis of metastatic disease was 55.2 (49.0) months. The most common subsite for metastatic spread were the lungs (32.5%). Of the 33 patients with data on outcomes, 48.5% were found to have expired by the time of publication. The median overall survival was estimated to be 84 months (95% confidence interval [CI] 62.3-105.7).ConclusionsThe most common subsites for metastatic spread of skull base chordoma were the lungs and bone. Overall survival for patients in the current cohort was a median of 84 months, with no significant differences noted when stratifying by the extent of surgery or the site of metastases.Level of evidence3a.

This retrospective case-control study evaluated the diagnostic performance of a commercially available chest radiography deep convolutional neural network (DCNN) in identifying the presence and position of central venous catheters, enteric tubes, and endotracheal tubes, in addition to a subgroup analysis of different types of lines/tubes. A held-out test dataset of 2568 studies was sourced from community radiology clinics and hospitals in Australia and the USA, and was then ground-truth labelled for the presence, position, and type of line or tube from the consensus of a thoracic specialist radiologist and an intensive care clinician. DCNN model performance for identifying and assessing the positioning of central venous catheters, enteric tubes, and endotracheal tubes over the entire dataset, as well as within each subgroup, was evaluated. The area under the receiver operating characteristic curve (AUC) was assessed. The DCNN algorithm displayed high performance in detecting the presence of lines and tubes in the test dataset with AUCs > 0.99, and good position classification performance over a subpopulation of ground truth positive cases with AUCs of 0.86–0.91. The subgroup analysis showed that model performance was robust across the various subtypes of lines or tubes, although position classification performance of peripherally inserted central catheters was relatively lower. Our findings indicated that the DCNN algorithm performed well in the detection and position classification of lines and tubes, supporting its use as an assistant for clinicians. Further work is required to evaluate performance in rarer scenarios, as well as in less common subgroups.

Accurate radiologic evaluation of the possibility of successful recanalization in symptomatic chronic ICA occlusion remains challenging. This study aimed to investigate the high-resolution MR imaging characteristics of symptomatic chronic ICA occlusion and their association with successful recanalization.Consecutive patients with symptomatic chronic ICA occlusion who underwent balloon dilation plus stent implantation were identified retrospectively and divided into 2 groups: a successful recanalization group and an unsuccessful recanalization group. Clinical and high-resolution MR imaging characteristics were compared between the groups. Univariate and multivariate analyses were used to identify the characteristics associated with successful recanalization.A total of 114 patients were included in the study. High-resolution MR imaging characteristics independently associated with unsuccessful recanalization were longer lesion length (OR, 0.41; 95% CI, 0.36-0.55;In symptomatic chronic ICA occlusion, lesion length and calcification volume (for proximal occlusion), the level of reversed distal ICA flow, and the lumen area (for distal occlusion) appear to be predictors of successful recanalization. High-resolution MR imaging can evaluate chronic ICA occlusion and help in clinical decision-making.

Steerable filter pairs that are near quadrature have many image processing applications. This paper proposes a new methodology for designing such filters. The key idea is to design steerable filters by minimizing a departure-from-quadrature function. These minimizing filter pairs are almost exactly in quadrature. The polar part of the filters is nonnegative, monotonic, and highly focused around an axis, and asymptotically the filters achieve exact quadrature. These results are established by exploiting a relation between the filters and generalized Hilbert matrices. These near-quadrature filters closely approximate three dimensional Gabor filters. We experimentally verify the asymptotic mathematical results and further demonstrate the use of these filter pairs by efficient calculation of local Fourier shell correlation of cryogenic electron microscopy.

Numerous data demonstrate that global climate change affects crop yield and quality. However, the effect of climate change on the nutritive value of forage crops remains unclear. Oat grass (Avena sativa L.) was used as a representative forage crop to understand changes in yield and chemical composition. The growth of oat grass under elevated temperature and CO

Nitryl chloride (ClNO2), an important precursor of Cl atoms, significantly affects atmospheric oxidation capacity and O3 formation. However, sources of ClNO2 in inland China have not been fully elucidated. In this work, laboratory experiments were conducted to investigate heterogeneous reactions of N2O5 with eight saline mineral dust samples collected from different regions in China, and substantial formation of ClNO2 was observed in these reactions. ClNO2 yields, φ(ClNO2), showed large variations (ranging from to ∼0.77) for different saline mineral dust samples, depending on mass fractions of particulate chloride. In addition, φ(ClNO2) could increase, decrease or show insignificant change for different saline mineral dust samples when relative humidity (RH) increased from 18 % to 75 %. We further found that current parameterizations significantly overestimated φ(ClNO2) for heterogeneous uptake of N2O5 onto saline mineral dust. In addition, assuming a uniform φ(ClNO2) value of 0.10 for N2O5 uptake onto mineral dust, we used a 3-D chemical transport model to assess the impact of this reaction on tropospheric ClNO2 in China and found that weekly mean nighttime maximum ClNO2 mixing ratios could have been increased by up to 85 pptv during a severe dust event in May 2017. Overall, our work showed that heterogeneous reaction of N2O5 with saline mineral dust could be an important source of tropospheric ClNO2 in inland China.

Purpose To investigate the dosimetric accuracy of synthetic computed tomography (sCT) images generated by a clinically-ready voxel-based MRI simulation package, and to develop a simple and feasible method to improve the accuracy. Methods 20 patients with brain tumor were selected to undergo CT and MRI simulation. sCT images were generated by a clinical MRI simulation package. The discrepancy between planning CT and sCT in CT number and body contour were evaluated. To resolve the discrepancies, an sCT specific CT-relative electron density (RED) calibration curve was used, and a layer of pseudo-skin was created on the sCT. The dosimetric impact of these discrepancies, and the improvement brought about by the modifications, were evaluated by a planning study. Volumetric modulated arc therapy (VMAT) treatment plans for each patient were created and optimized on the planning CT, which were then transferred to the original sCT and the modified-sCT for dose re-calculation. Dosimetric comparisons and gamma analysis between the calculated doses in different images were performed. Results The average gamma passing rate with 1%/1 mm criteria was only 70.8% for the comparison of dose distribution between planning CT and original sCT. The mean dose difference between the planning CT and the original sCT were −1.2% for PTV D95 and −1.7% for PTV Dmax, while the mean dose difference was within 0.7 Gy for all relevant OARs. After applying the modifications on the sCT, the average gamma passing rate was increased to 92.2%. Mean dose difference in PTV D95 and Dmax were reduced to −0.1% and −0.3% respectively. The mean dose difference was within 0.2 Gy for all OAR structures and no statistically significant difference were found. Conclusions The modified-sCT demonstrated improved dosimetric agreement with the planning CT. These results indicated the overall dosimetric accuracy and practicality of this improved MR-based treatment planning method.

The major objective of this review was to compare the diagnostic accuracy of ultrasound in confirming tracheal intubation to the standard methods of confirmation in the intensive care unit (ICU).This systematic review and meta-analysis of observational studies was conducted from inception to July 2022. We included studies that compared the diagnostic accuracy of ultrasound-detected tracheal intubation to that of the gold standard diagnostic technique performed in adult patients who underwent tracheal intubation as part of any procedure. We searched the following electronic databases for published studies: PubMed, EMBASE, Cochrane Central, and Web of Science. Risk of bias was assessed using a standard procedure based on the Quality Assessment of Diagnostic Accuracy Studies-2 criteria. The results were analyzed using the RevMan or Meta-Disc software to determine the adequacy and conclusiveness of the available evidence.Five studies that included 344 patients met the inclusion criteria. Pooled sensitivity was 0.96 (95% confidence interval (CI) (0.92-0.98) and 1.00 (95% CI: 0.97-1.00), respectively. Furthermore, the diagnostic odds ratio of ultrasonography was 311.25 (95% CI: 63.77-1,519.22), which was confirmed by a summary receiver operating characteristic curve with an area under the curve of 0.98.Ultrasonography has high sensitivity and specificity, is a valuable adjunct for confirming tracheal intubation in the ICU and should be performed when capnography is unavailable or unreliable.

We introduce here SOIL-WATERGRIDS, a new dataset of dynamic changes in soil moisture and depth of water table over 45 years from 1970 to 2014 globally resolved at 0.25 × 0.25 degree resolution (about 30 × 30 km at the equator) along a 56 m deep soil profile. SOIL-WATERGRIDS estimates were obtained using the BRTSim model instructed with globally gridded soil physical and hydraulic properties, land cover and use characteristics, and hydrometeorological variables to account for precipitation, ecosystem-specific evapotranspiration, snowmelt, surface runoff, and irrigation. We validate our estimates against independent observations and re-analyses of the soil moisture, water table depth, wetland occurrence, and runoff. SOIL-WATERGRIDS brings into a single product the monthly mean water saturation at three depths in the root zone and the depth of the highest and lowest water tables throughout the reference period, their long-term monthly averages, and data quality. SOIL-WATERGRIDS can therefore be used to analyse trends in water availability for agricultural abstraction, assess the water balance under historical weather patterns, and identify water stress in sensitive managed and unmanaged ecosystems., Measurement(s)volumetric water content • water table depthTechnology Type(s)computational modeling techniqueFactor Type(s)hydrometeorology • soil properties • land useSample Characteristic - Environmentsoil Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.15982578

The amygdala is a medial temporal lobe structure known to be involved in processing emotional conflict. However, its role in processing non-emotional conflict is not well understood. Previous studies have utilized the Stroop Task to examine brain modulation of humans under the color-word conflict scenario, which is non-emotional conflict processing, and found hippocampal theta-band (4-7 Hz) modulation. This study aims to survey amygdaloid theta power changes during non-emotional conflict processing using intracranial depth electrodes in nine epileptic patients (3 female; age 20-62). All patients were asked to perform a modified Stroop task. During task performance, local field potential (LFP) data was recorded from macro contacts sampled at 2 K Hz and used for analysis. Mean theta power change from baseline was compared between the incongruent and congruent task condition groups using a paired sample t-test. Seven patients were available for analysis after artifact exclusion. In five out of seven patients, statistically significant increases in theta-band power from baseline were noted during the incongruent task condition (paired sample t-test p 0.001), including one patient exhibiting theta power increases in both task conditions. Average response time was 1.07 s (failure trials) and 1.04 s (success trials). No speed-accuracy tradeoff was noted in this analysis. These findings indicate that human amygdaloid theta-band modulation may play a role in processing non-emotional conflict. It builds directly upon work suggesting that the amygdala processes emotional conflict and provides a neurophysiological mechanism for non-emotional conflict processing as well.

Objective: Coherence between the hippocampus and other brain structures has been shown with the theta frequency (3–8 Hz). Cortical decreases in theta coherence are believed to reflect response accuracy efficiency. However, the role of theta coherence during conflict resolution is poorly understood in noncortical areas. In this study, coherence between the hippocampus and orbitofrontal cortex (OFC) was measured during a conflict resolution task. Although both brain areas have been previously implicated in the Stroop task, their interactions are not well understood. Methods: Nine patients were implanted with stereotactic electroencephalography contacts in the hippocampus and OFC. Local field potential data were sampled throughout discrete phases of a Stroop task. Coherence was calculated for hippocampal and OFC contact pairs, and coherence spectrograms were constructed for congruent and incongruent conditions. Coherence changes during cue processing were identified using a nonparametric cluster-permutation t test. Group analysis was conducted to compare overall theta coherence changes among conditions. Results: In 6 of 9 patients, decreased theta coherence was observed only during the incongruent condition (P < 0.05). Congruent theta coherence did not change from baseline. Group analysis showed lower theta coherence for the incongruent condition compared with the congruent condition (P < 0.05). Conclusions: Theta coherence between the hippocampus and OFC decreased during conflict. This finding supports existing theories that theta coherence desynchronization contributes to improved response accuracy and processing efficiency during conflict resolution. The underlying theta coherence observed between the hippocampus and OFC during conflict may be distinct from its previously observed role in memory.

Acute respiratory distress syndrome (ARDS) is a critical disease commonly found in many clinical cases, with a mortality rate of approximately 50%. Early diagnosis and intervention are important for improving ARDS prognosis. In this study, the applications of lung ultrasound in ARDS diagnosis and assessment are reviewed to clarify its key clinical values and application prospects.According to the standard diagnosis of ARDS based on the Berlin definition, CXR or CT examination should be conducted. However, both the blurred images of the former, as well as the inconvenience and high risks of the latter, impose restrictions on their application in critically ill patients.Lung ultrasound was shown to improve safety, effectiveness, lacked radiation, can be performed bedside, and offers dynamic functionality.It may be a suitable approach to replace or complement traditional imaging examinations with lung ultrasound.

This study aimed at reviewing the diagnostic accuracy of ultrasonography for detecting correct nasogastric tube placement compared with X-ray imaging as the reference standard.This was a systematic review and meta-analysis of observational studies published between 1961 and 2022. We included studies that compared the diagnostic accuracy of ultrasound detection for nasogastric tube placement with that of X-ray imaging in adult patients who were undergoing nasogastric tube placement for any reason. We searched for published studies in the following electronic databases: Cochrane Library, PubMed, EMBASE, and Web of Science. The risk of bias was assessed using a standard procedure according to the Quality Assessment of Diagnostic Accuracy Studies-2 criteria. The results were analyzed using RevMan or Meta-Disc software to determine the adequacy and conclusiveness of the available evidence.Fourteen studies met our inclusion criteria. Overall, 1,812 patients were included in these studies. The results included a pooled sensitivity of 0.96 (95% confidence interval [CI] 0.94-0.97), specificity of 0.91 (95% CI 0.85-0.96), positive likelihood ratio of 5.08 (95% CI 1.49-17.39), and negative likelihood ratio of 0.08 (95% CI 0.06-0.10). This was confirmed through a summary receiver operating characteristic curve, which showed that the area under the curve was 0.96.We found evidence about validity of ultrasound as an efficient method for verifying nasogastric tube placement, although there is insufficient evidence to suggest that it can be used as a diagnostic tool for incorrect gastric tube placement.

OBJECTIVES Cerebrospinal fluid (CSF) leaks and meningoencephaloceles originating in the lateral recess of the sphenoid sinus can be challenging. The traditional transpterygoid approach through the pterygopalatine fossa (PPF) is time consuming and places important structures at risk, which can lead to significant morbidity. We report a multi-institutional experience using a simplified, endoscopic modified transpterygoid approach (MTPA), which spares the PPF contents in the management of lateral sphenoid sinus meningoencephaloceles and CSF leaks. STUDY DESIGN Multi-Institutional, Retrospective Case Series. METHODS Patients with lateral sphenoid recess CSF leaks and meningoencephaloceles between 2014 and 2020 who underwent the MTPA at two academic medical centers were identified. Repair techniques and outcomes were evaluated. RESULTS Thirty-three patients underwent the MTPA for management. Skull base reconstruction was performed using a free mucosal graft (24/33, 72.7%), nasoseptal flap (4/33, 12.1%), bone grafts (3/33, 9.1%), and abdominal fat grafts (2/33, 6.1%). Lumbar drains and perioperative intracranial pressure measurements were routinely employed. Postoperative complications were uncommon and included three patients (9.7%) with temporary V2 anesthesia, one patient (3.2%) with prolonged V2 anesthesia, and one patient (3.2%) with subjective dry eye, all of which resolved at 9 months postoperatively. There were no recurrent CSF leaks resulting in a 100% success rate. Average follow-up was 13 months. CONCLUSION The MTPA reduces morbidity and greatly simplifies access to the lateral sphenoid sinus for the management of CSF leaks and meningoencephaloceles, without compromising exposure. This technique avoids the need for extensive PPF dissection and should be considered for the management of benign lesions involving the lateral sphenoid sinus. LEVEL OF EVIDENCE 4 Laryngoscope, 131:2224-2230, 2021.

Background Post-traumatic Stress Disorder (PTSD) often does not respond to available treatments. Memories are vulnerable to disruption during reconsolidation, and electroconvulsive therapy (ECT) has amnestic effects Objective/hypothesis To test the use of ECT to disrupt the reconsolidation of traumatic memories as a potential treatment for PTSD Methods Participants were adults from the civilian population and were referred for ECT treatment for severe depression with comorbid PTSD symptoms. Twenty-eight participants were randomly assigned to reactivation of a traumatic or non-traumatic memory using audio script driven imagery prior to each ECT treatment. Primary outcomes were change in scores on the Modified PTSD Symptom Scale - Self Report (MPSS-SR) and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Secondary outcomes included a comparison of the change in heart rate while listening to the script Results Twenty-five female patients who completed a post-ECT assessment were included in the analysis. No significant group differences were found in the MPSS-SR or CAPS-5 scores from pre-ECT to post-ECT or 3-month follow-ups. However, both groups improved at post-ECT and 3-month follow up. Partial eta squared estimates of effect size showed large effect sizes for all outcomes (η2 > 0.13). Changes in heart rate were not significantly different between groups or over time Conclusions ECT paired with pre-treatment traumatic memory reactivation was not more effective for treating PTSD symptoms than ECT with non-traumatic memory reactivation. While our primary hypothesis was not supported, our data provides further support for the efficacy of ECT for improving symptoms of PTSD with comorbid depression. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04027452 . Identifier NCT04027452.

Pesticides are widely used to protect food production and meet global food demand but are also ubiquitous environmental pollutants, causing adverse effects on water quality, biodiversity and human health. Here we use a global database of pesticide applications and a spatially explicit environmental model to estimate the world geography of environmental pollution risk caused by 92 active ingredients in 168 countries. We considered a region to be at risk of pollution if pesticide residues in the environment exceeded the no-effect concentrations, and to be at high risk if residues exceeded this by three orders of magnitude. We find that 64% of global agricultural land (approximately 24.5 million km2) is at risk of pesticide pollution by more than one active ingredient, and 31% is at high risk. Among the high-risk areas, about 34% are in high-biodiversity regions, 5% in water-scarce areas and 19% in low- and lower-middle-income nations. We identify watersheds in South Africa, China, India, Australia and Argentina as high-concern regions because they have high pesticide pollution risk, bear high biodiversity and suffer from water scarcity. Our study expands earlier pesticide risk assessments as it accounts for multiple active ingredients and integrates risks in different environmental compartments at a global scale. Pesticide pollution is a risk for two-thirds of agriculture land. A third of high-risk areas are in high-biodiversity regions and a fifth are in low- and lower-middle-income areas, according to environmental modelling combined with pesticide application data.

Summary Background The vertical rectus abdominis myocutaneous (VRAM) flap is an established technique employed to reconstruct pelvic and perineal defects not amenable to primary closure. The aim of this study was to systematically review the morbidity of VRAM flap reconstruction following exenterative pelvic surgery. Materials and methods A systematic literature search was conducted by using Medline, EMBASE, and Cochrane databases. Abstracts of all studies published from inception to November 2019 were identified. Search terms used included ‘vertical rectus abdominis myocutaneous’, ‘vertical rectus abdominis musculocutaneous’ and ‘VRAM’. Only studies that described outcomes when a VRAM flap was used during exenterative pelvic surgery were included; case reports were excluded. The primary outcome measure was VRAM flap morbidity. Secondary outcome measures included donor site morbidity and hospital length of stay. Results Sixty-five studies with a total of 1827 patients were identified and included. Perineal reconstruction was most commonly performed following abdominal perineal excision of the rectum (APER) (n = 636 and 34.8%). Median patient age at surgery ranged from 38 to 78 years. Mean perineal flap morbidity was 27%, with a complete flap loss rate of 1.8% and a perineal hernia rate of 0.2%. Mean donor site morbidity was 15%, with an abdominal dehiscence rate of 5.5% and an incisional hernia rate of 3.3%. Conclusions While overall morbidity after VRAM flap reconstruction in pelvic visceral surgery is high; the risk of major complications remains low. These data are important when counselling patients for surgery.

The manuscript presents the importance of integrating mathematical methods for the determination of due date optimization parameter for maturity optimization in evolutionary computation (EC) methods in multi-objective flexible job shop scheduling problem (FJSSP). The use of mathematical modelling methods of due date optimization with slack (SLK) for low and total work content (TWK) for medium and high dimensional problems was presented with the integration into the multi-objective heuristic Kalman algorithm (MOHKA). The multi-objective optimization results of makespan, machine utilization and due date scheduling with the MOHKA algorithm were compared with two comparative multi-objective algorithms. The high capability and dominance of the EC method results in scheduling jobs for FJSSP production was demonstrated by comparing the optimization results with the results of scheduling according to conventional priority rules. The obtained results of randomly generated datasets proved the high level of job scheduling importance with respect to the interdependence of the optimization parameters. The ability to apply the presented method to the real-world environment was demonstrated by using a real-world manufacturing system dataset applied in Simio simulation and scheduling software. The optimization results prove the importance of the due date optimization parameter in highly dynamic FJSSP when it comes to achieving low numbers of tardy jobs, short job tardiness and potentially lower tardy jobs costs in relation to short makespan of orders with highly utilized production capacities. The main findings prove that multi-objective optimization of FJSSP planning and scheduling, taking into account the optimization parameter due date, is the key to achieving a financially and timely sustainable production system that is competitive in the global market.

Thyroid carcinoma (THCA) is the most prevalent tumor in the endocrine system with an increasing incidence. Recent studies have underscored the function of microRNAs (miRNAs) in THCA. Nevertheless, knowledge regarding the effects of exosomal miRNAs in THCA is still limited. This report intended to probe the regulatory effects of exosomal miR-152 on THCA and the underlying mechanism. The expression profile of miR-152 was studied in clinical samples as well as B-CPAP and TPC-1 cells. Transwell, CCK-8, and flow cytometric assays were performed to investigate the roles of miR-152 on invasion, migration, proliferation, and apoptosis in B-CPAP and TPC-1 cells. The putative target of miR-152 was predicted using the bioinformatic analysis, and the targeting relationship was confirmed verified subsequently. Afterward, exosomes were isolated from bone marrow mesenchymal stem cells (BM-MSCs) and co-cultured with B-CPAP and TPC-1 cells to explore the function of exosomal miR-152 on THCA cells. miR-152 was reduced in THCA tissues and cells. Restoration of miR-152 inhibited proliferation, invasion and migration of B-CPAP and TPC-1 cells, but promoted cell apoptosis. Dipeptidyl dipeptidase 4 (DPP4), a target of miR-152, was found to promote THCA cell invasion and migration. miR-152 ferried by BM-MSCs-derived exosomes repressed THCA cell invasion and migration, and pcDNA-DPP4 weakened the repression effect. Exosomal miR-152 inhibited proliferation, migration and invasion of THCA cells by binding with DPP4, which may represent a novel target for the treatment of THCA.

Objectives Diabetes mellitus (DM) is a serious public health issue worldwide, and DM patients have higher risk of cardiovascular diseases (CVDs), which is the leading cause of DM-related deaths. China has the largest DM population, yet a robust model to predict CVDs in Chinese DM patients is still lacking. This systematic review is carried out to summarize existing models and identify potentially important predictors for CVDs in Chinese DM patients. Study design Systematic review. Methods Medline and Embase were searched for data from April 1st, 2011 to May 31st, 2018. A study was eligible if it developed CVD (defined as total CVD or any major cardiovascular component) risk prediction models or explored potential predictors of CVD specifically for Chinese people with type 2 DM. Standardized forms were utilized to extract information, appraise applicability, risk of bias, and availabilities. Results Five models and 29 studies focusing on potential predictors were identified. Models for a primary care setting, or to predict total CVD, are rare. A number of common predictors (e.g. age, sex, diabetes duration, smoking status, glycated hemoglobin (HbA1c), blood pressure, lipid profile, and treatment modalities) were observed in existing models, in which urine albumin:creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) are highly recommended for the Chinese population. Variability of blood pressure (BP) and HbA1c should be included in prediction model development as novel factors. Meanwhile, interactions between age, sex, and risk factors should also be considered. Conclusions A 10-year prediction model for CVD risk in Chinese type 2 DM patients is lacking and urgently needed. There is insufficient evidence to support the inclusion of other novel predictors in CVDs risk prediction functions for routine clinical use.

To revisit the population norms of health-related quality of life (HRQoL) and health utility for the Hong Kong general population, compare these scores over past health surveys, and assess the association of scores with non-communicable diseases (NCDs) and their risk factors. HRQoL data measured by the standard Short Form 12 Health Survey-version 2 (SF-12v2) were extracted from the surveys in 1998, 2003/2004, 2008/2009 and 2014/2015. SF-12v2 data were mapped to the Short-form 6-dimension (SF-6D) preference-based measure to generate the health utility scores. Population weighting based on the sex and age in the second quarter of 2015 was applied when generating population normative values. Linear regression models were fitted to assess the effect of the number of NCDs and modifiable lifestyle factors on HRQoL and health utility. The general population mean scores of SF-12v2 domains and SF-6D in 2014/15 were higher compared to past surveys. Linear increases in General Health, Vitality and Mental Health domains were observed from 1998 to 2014/15. More doctor-diagnosed NCDs, insufficient physical activity and fruit/vegetable consumption, poor sleep quality and insufficient or excessive amount of sleep (

Treatment of tendon injuries is challenging. To develop means to augment tendon regeneration, we have previously prepared a soluble, low immunogenic (DNA-free), tendon extracellular matrix fraction (tECM) by urea extraction of juvenile bovine tendons, which is capable of enhancing transforming growth factor-β (TGF-β) mediated tenogenesis in human adipose-derived stem cells (hASCs). Here, we aimed to elucidate the mechanism of tECM-driven hASC tenogenic differentiation in vitro, focusing on the integrin and TGF-β/SMAD pathways. Our results showed that tECM promoted hASC proliferation and tenogenic differentiation in vitro based on tenogenesis-associated markers. tECM also induced higher expression of several integrin subunits and TGF-β receptors, and nuclear translocation of p-SMAD2 in hASCs. Pharmacological inhibition of integrin-ECM binding, focal adhesion kinase (FAK) signaling, or TGF-β signaling independently led to compromised pro-tenogenic effects of tECM and actin fiber polymerization. Additionally, integrin blockade inhibited tECM-driven TGFBR2 expression, while inhibiting TGF-β signaling decreased tECM-mediated expression of integrin α1, α2, and β1 in hASCs. Together, these findings suggest that the strong pro-tenogenic bioactivity of tECM is regulated via integrin/TGF-β signaling crosstalk. Understanding how integrins interact with signaling by TGF-β and/or other growth factors (GFs) within the tendon ECM microenvironment will provide a rational basis for an ECM-based approach for tendon repair.

Background Gonorrhea, caused by the bacterium Neisseria gonorrhoeae, is a globally prevalent sexually transmitted infection. The dynamics of gonococcal population biology have been poorly defined due to a lack of resolution in strain typing methods. Methods In this study, we assess how the core genome can be used to improve our understanding of gonococcal population structure compared with current typing schemes. Results A total of 1668 loci were identified as core to the gonococcal genome. These were organized into a core genome multilocus sequence typing scheme (N gonorrhoeae cgMLST v1.0). A clustering algorithm using a threshold of 400 allelic differences between isolates resolved gonococci into discrete and stable core genome groups, some of which persisted for multiple decades. These groups were associated with antimicrobial genotypes and non-overlapping NG-STAR and NG-MAST sequence types. The MLST-STs were more widely distributed among core genome groups. Conclusions Clustering with cgMLST identified globally distributed, persistent, gonococcal lineages improving understanding of the population biology of gonococci and revealing its population structure. These findings have implications for the emergence of antimicrobial resistance in gonococci and how this is associated with lineages, some of which are more predisposed to developing antimicrobial resistance than others.

Background The relationship between good early control of thyroid hormone levels after thyroidectomy for Graves’ disease (GD) and subsequent risks of mortality and morbidities is not well known. The aim of this study was to examine the association between thyroid hormone levels within a short interval after surgery and long-term mortality and morbidity risks from a population-based database. Methods Patients with GD who underwent complete/total thyroidectomy between 2006 and 2018 were selected from the Hong Kong Hospital Authority clinical management system. All patients were classified into three groups (euthyroidism, hypothyroidism, and hyperthyroidism) according to their thyroid hormone levels at 6, 12, and 24 months after surgery. Cox proportional hazards models were performed to compare the risks of all-cause mortality, cardiovascular disease (CVD), Graves’ ophthalmopathy, and cancer. Results Over a median follow-up of 68 months with 5709 person-years, 949 patients were included for analysis (euthyroidism, n = 540; hypothyroidism, n = 282; and hyperthyroidism, n = 127). The hypothyroidism group had an increased risk of CVD (HR = 4.20, 95 per cent c.i. 2.37 to 7.44, P Conclusions This study showed a higher risk of CVD in postsurgical hypothyroidism and a higher risk of cancer in hyperthyroidism compared with achieving euthyroidism early after thyroidectomy. Patients who were euthyroid at 6 months and 12 months had better outcomes than those achieving euthyroidism only at 6 months or 12 months. Attaining biochemical euthyroidism early after thyroidectomy should become a priority.

Introduction Older people in care homes living with frailty are less likely to benefit from tight glycaemic control in the management of type 2 diabetes with increased risk of adverse effects for example hypoglycaemia, falls and hospital admission. We wished to ascertain the scale of the problem and reduce overtreatment. We defined overtreatment based on American Diabetes Association guidelines as being on an agent that can cause hypoglycaemia and having an HBA1C of ≤53 mmol/mol or, an HbA1c 53–64 mmol/mol with either three or more co-morbidities. Methods In 2016, we audited the management of type 2 diabetes in older people discharged from LTHT to care homes. We discussed our concerns with diabetes and geriatric medicine colleagues across medical, nursing and pharmacy disciplines. We engaged the support of the citywide diabetes network which comprises secondary care colleagues, general practitioners and pharmacists. We presented the findings of our initial audit to colleagues within primary and secondary care through departmental meetings and citywide network meetings. We wrote a new guideline, specifically for frail older people that was disseminated citywide through these networks. We re-audited in 2020. Results In total, 113 cases were reviewed in 2016 and 105 cases in 2020. In 2020, only 6% (6 patients) were overtreated compared to 38% (43 patients) in 2016. Conclusions There has been a marked reduction in overtreatment which should result in less adverse events. We believe the reasons for success lie in wide engagement of relevant stakeholder groups around an issue that is important, large in scale and meaningful to both patient and clinician. There are potential cost savings from reducing medications and reducing harm.

Among the dairy sector's current concerns, the as-sessment of global animal health status is a complex challenge. Its multidimensionality means that global monitoring tools are rarely considered. Instead, specific disease detection is often studied separately and, due to financial and ethical issues, uses small-scale data sets focusing on few biomarkers. Several studies have already been conducted using milk Fourier transform mid-infrared (FT-MIR) spectroscopy to detect mastitis and lameness or to quantify health-related biomarkers in milk or blood. Those studies are relevant but they focus mainly on one biomarker or disease. To solve this issue and the small-scale data set, in this study, we proposed a holistic approach using big data obtained from milk recording, including milk yield, somatic cell count, and 27 FT-MIR-based predictors related to milk composition and animal health status. Using 740,454 records collected from 114,536 first-parity Holstein cows in southern Belgium, we performed repeated unsupervised learning algorithms based on Ward's agglomerative hierarchical clustering method to find potential interesting patterns. A divide-and-conquer approach was used to overcome the limitation of computational resources in clustering a relatively large data set. Five groups of records were identified. Differences observed in the fourth group suggested a relationship to metabolic disorders. The fifth group seemed to be related to mastitis. In a second step, we performed a partial least squares discriminant analysis (PLS-DA) to predict the probability of belonging to those specific groups for the entire data set. The obtained global ac-curacy was 0.77 and the balanced accuracy (i.e., the mean between sensitivity and specificity) of discrimi-nating the fourth and fifth groups was 0.88 and 0.96, respectively. Then, a validation of the interpretation of those groups was performed using 204 milk and blood reference records. The predicted probability associated with the metabolic disorders issue had significant cor-relations of 0.54 with blood beta-hydroxybutyrate, 0.44 with blood nonesterified fatty acids, -0.32 with blood glucose, -0.23 with milk glucose-6-phosphate, and 0.38 with milk isocitrate. In contrast, the predicted prob-ability of belonging to the mastitis group had correla-tions of 0.69 with milk lactate dehydrogenase, 0.46 with milk N-acetyl-beta-D-glucosaminidase, -0.18 with milk free glucose, and 0.16 with milk glucose-6-phosphate. Consequently, these results suggest that the obtained quantitative traits indirectly reflect some of the main health disorders in dairy farming and could be used to monitor dairy cows on a large scale. By using unsuper-vised learning on large-scale milk recording data and then validating the pattern using reference laboratory measures, we propose a new approach to quickly assess dairy cow health status.

Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin loss—notably within muscles and the central neurons system. DMD presents as cognitive weakness, progressive skeletal and cardiac muscle degeneration until pre-mature death from cardiac or respiratory failure. Innovative therapies have improved life expectancy; however, this is accompanied by increased late-onset heart failure and emergent cognitive degeneration. Thus, better assessment of dystrophic heart and brain pathophysiology is needed. Chronic inflammation is strongly associated with skeletal and cardiac muscle degeneration; however, neuroinflammation’s role is largely unknown in DMD despite being prevalent in other neurodegenerative diseases. Here, we present an inflammatory marker translocator protein (TSPO) positron emission tomography (PET) protocol for in vivo concomitant assessment of immune cell response in hearts and brains of a dystrophin-deficient mouse model [mdx:utrn(+/−)]. Preliminary analysis of whole-body PET imaging using the TSPO radiotracer, [18F]FEPPA in four mdx:utrn(+/−) and six wildtype mice are presented with ex vivo TSPO-immunofluorescence tissue staining. The mdx:utrn(+/−) mice showed significant elevations in heart and brain [18F]FEPPA activity, which correlated with increased ex vivo fluorescence intensity, highlighting the potential of TSPO-PET to simultaneously assess presence of cardiac and neuroinflammation in dystrophic heart and brain, as well as in several organs within a DMD model.

Limitations of the chest X-ray (CXR) have resulted in attempts to create machine learning systems to assist clinicians and improve interpretation accuracy. An understanding of the capabilities and limitations of modern machine learning systems is necessary for clinicians as these tools begin to permeate practice. This systematic review aimed to provide an overview of machine learning applications designed to facilitate CXR interpretation. A systematic search strategy was executed to identify research into machine learning algorithms capable of detecting >2 radiographic findings on CXRs published between January 2020 and September 2022. Model details and study characteristics, including risk of bias and quality, were summarized. Initially, 2248 articles were retrieved, with 46 included in the final review. Published models demonstrated strong standalone performance and were typically as accurate, or more accurate, than radiologists or non-radiologist clinicians. Multiple studies demonstrated an improvement in the clinical finding classification performance of clinicians when models acted as a diagnostic assistance device. Device performance was compared with that of clinicians in 30% of studies, while effects on clinical perception and diagnosis were evaluated in 19%. Only one study was prospectively run. On average, 128,662 images were used to train and validate models. Most classified less than eight clinical findings, while the three most comprehensive models classified 54, 72, and 124 findings. This review suggests that machine learning devices designed to facilitate CXR interpretation perform strongly, improve the detection performance of clinicians, and improve the efficiency of radiology workflow. Several limitations were identified, and clinician involvement and expertise will be key to driving the safe implementation of quality CXR machine learning systems.

Shigella sonnei is a major cause of bacillary dysentery and an increasing concern due to the spread of multidrug resistance. S. sonnei harbors pINV, an;210 kb plasmid that encodes a type III secretion system (T3SS), which is essential for virulence. During growth in the laboratory, avirulence arises spontaneously in S. sonnei at high frequency, hampering studies on and vaccine development against this important pathogen. Here, we investigated the molecular basis for the emergence of avirulence in S. sonnei and showed that avirulence mainly results from pINV loss, which is consistent with previous findings. Ancestral deletions have led to the loss from S. sonnei pINV of two toxin-antitoxin (TA) systems involved in plasmid maintenance, CcdAB and GmvAT, which are found on pINV in Shigella flexneri. We showed that the introduction of these TA systems into S. sonnei pINV reduced but did not eliminate pINV loss, while the single amino acid polymorphisms found in the S. sonnei VapBC TA system compared with S. flexneri VapBC also contributed to pINV loss. Avirulence also resulted from deletions of T3SS-associated genes in pINV through recombination between insertion sequences (ISs) on the plasmid. These events differed from those observed in S. flexneri due to the different distribution and repertoire of ISs. Our findings demonstrated that TA systems and ISs influenced plasmid dynamics and loss in S. sonnei and could be exploited for the design and evaluation of vaccines.

Science, technology, engineering and mathematics (STEM) education is a globalized trend of equipping students to facilitate technological and scientific developments. Among STEM education, technology education (TE) plays a significant role in teaching applied knowledge and skills to create and add value to systems and products. In higher education, the learning effectiveness of the TE assisted by the immersive technologies is an active research area to enhance the teaching quality and learning performance. In this study, a taught subject of radio frequency identification (RFID) assisted by using mixed reality technologies in a higher education institution was examined, while the soft systems methodology (SSM) was incorporated to evaluate the changes in learning performance. Under the framework of SSM, stakeholders’ perceptions toward immersive learning and RFID education are structured. Thus, a rich picture for teaching activities is established for subject control, monitoring, and evaluation. Subsequently, the design of TE does not only satisfy the students’ needs but also requirements from teachers, industries, and market trends. Finally, it is found that SSM is an effective approach in designing courses regarding hands-on technologies, and the use of immersive technologies improves the learning performance for acquiring fundamental knowledge and application know-how.

Plantar flexor functional deficits measured using joint dynamometry are associated with poor outcomes in patients following Achilles tendon rupture. In this study, we developed a small animal dynamometer to quantify functional deficits in a rat Achilles tendon rupture model. Like our reported plantar flexor deficits in patients recovering from Achilles tendon ruptures, we found in our small animal model functional deficits across the ankle range of motion, resulting in an average 34% less positive work being done compared to the uninjured contralateral limb. These functional deficits are similar to 38% less plantar flexor work done by patients who were treated non-surgically in our prior research. Further, these deficits were greater in plantar flexion than dorsiflexion, which agree with clinical complaints of limited function during tasks like jumping and hiking. These findings highlight the impact of muscle-tendon loading during early tendon healing on long-term plantar flexor function and serve as compelling evidence that our Sprague Dawley rat model of an Achilles tendon rupture recapitulates the human disease. We provide thorough documentation for other groups to build their own dynamometers, which can be modified to meet unique experimental criteria.SIGNIFIGANCEPreclinical models are critical tools for translating knowledge discovery to clinical decision making. We developed a low-cost and flexible joint dynamometer that quantifies joint function in small animals. Here, we used a rat model to test the implications of Achilles tendon ruptures not surgically repaired on plantar flexor function. We found that Achilles tendon ruptures in a rodent model closely resemble the functional deficits our group has observed in patients.

Shigella is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low–middle income countries. Shigella sonnei prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant strains have emerged, as a significant public health concern. One strategy to combat drug resistance in S. sonnei is the development of effective vaccines. There is no licensed vaccine against Shigella, and development has been hindered by the lack of an effective small-animal model. In this work, we used human enteroids, for the first time, as a model system to evaluate a plasmid-stabilized S. sonnei live attenuated vaccine strain, CVD 1233-SP, and a multivalent derivative, CVD 1233-SP::CS2-CS3, which expresses antigens from enterotoxigenic Escherichia coli. The strains were also tested for immunogenicity and protective capacity in the guinea pig model, demonstrating their ability to elicit serum and mucosal antibody responses as well as protection against challenge with wild-type S. sonnei. These promising results highlight the utility of enteroids as an innovative preclinical model to evaluate Shigella vaccine candidates, constituting a significant advance for the development of preventative strategies against this important human pathogen.

Background Aneurysmal subarachnoid hemorrhage (aSAH) requires complex multidisciplinary care. After initial treatment (index hospital), readmission to a different hospital (nonindex) can compromise quality of care, resulting in increased morbidity. We aimed to evaluate factors associated with nonindex readmission and evaluate association of nonindex hospital readmission on outcomes in patients with ruptured aneurysm. Methods Readmissions within 90 days after aSAH treatment were identified in the 2010–2014 Nationwide Readmissions Database. Multivariable logistic regression identified patient and hospital characteristics associated with nonindex readmission. Separate multivariable models determined increased morbidity or risk of second readmission for nonindex readmissions. Results A total of 9254 patients who underwent treatment of ruptured aneurysms from 2010 to 2014 were identified. Of these, 1985 (21.5%) were readmitted within 90 days. Three hundred and fifty-five of these readmissions (17.9%) occurred to nonindex hospitals. Patients that were discharged to a skilled nursing or other facility (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.27–2.28]) had higher odds of nonindex readmission, whereas patients with private insurance were associated with lower odds of nonindex readmission (OR, 0.65; 95% CI, 0.46–0.92). Patients readmitted to a nonindex (vs. index) hospital were associated with increased likelihood of major complications (OR, 1.71; 95% CI, 1.18–2.48) and second readmissions (OR, 1.51; 95% CI, 1.17–1.96). Conclusions After treatment of a ruptured cerebral aneurysm, 17.9% of readmissions occurred at a nonindex hospital. These patients were at increased risk for major complications or subsequent readmissions, which may be because of care fragmentation. Interventions aimed at improving continuity of care may reduce higher morbidity associated with nonindex readmission.