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Journal and book editors in most disciplines are faced with a flood of meta-analyses, which critical reviews have shown are not always of sufficient quality. In the short run, editors could give targeted instructions to authors and make specific recommendations to reviewers to ensure that not only meta-analyses but also research syntheses more broadly, published under their watch, meet acceptable publication standards. In order to achieve satisfactory improvements in the long run, editors should foster fundamental changes in the way the publication of negative and non-significant results is handled.

Primary metastatic prostate cancer to the orbit is exceedingly rare. Benign lesions, including meningioma, have demonstrated PSMA expression and can be visualized using PSMA-based PET tracers. We report the findings of 18F-PSMA-1007 PET/CT in a 76-year-old man with progressive confusion and long-standing blindness of the left eye. PET/CT scan revealed increased uptake of PSMA in the orbital and temporal region, and other sites throughout the body. Histopathological examination after biopsy of the left orbit showed adenocarcinoma of the prostate. This case substantiates the diverse clinical and radiological presentations of metastatic prostate cancer and underscores the diagnostic significance of targeted biopsy.

Abstract Walking is a fundamental aspect of human movement, and understanding how irregular surfaces impact gait is crucial. Existing gait research often relies on laboratory settings with ideal surfaces, limiting the applicability of findings to real-world scenarios. While some irregular surface datasets exist, they are often small or lack biomechanical gait data. In this paper, we introduce a new irregular surface dataset with 134 participants walking on surfaces of varying irregularity, equipped with inertial measurement unit (IMU) sensors on the trunk and lower right limb (foot, shank, and thigh). Collected during the North American Congress on Biomechanics conference in 2022, the dataset aims to provide a valuable resource for studying biomechanical adaptations to irregular surfaces. We provide the detailed experimental protocol, as well as a technical validation in which we developed a machine learning model to predict the walking surface. The resulting model achieved an accuracy score of 95.8%, demonstrating the discriminating biomechanical characteristics of the dataset’s irregular surface gait data.

BackgroundCraniosynostosis is a type of skull deformity caused by premature ossification of cranial sutures in children. Given its variability and anatomical complexity, three-dimensional visualization is crucial for effective teaching and understanding. We developed a VR database with 3D models to depict these deformities and evaluated its impact on teaching efficiency, motivation, and memorability.MethodsWe included all craniosynostosis cases with preoperative CT imaging treated at our institution from 2012 to 2022. Preoperative CT scans were imported into SpectoVR using a transfer function to visualize bony structures. Measurements, sub-segmentation, and anatomical teaching were performed in a fully immersive 3D VR experience using a headset. Teaching sessions were conducted in group settings where students and medical personnel explored and discussed the 3D models together, guided by a host. Participants’ experiences were evaluated with a questionnaire assessing understanding, memorization, and motivation on a scale from 1 (poor) to 5 (outstanding).ResultsThe questionnaire showed high satisfaction scores (mean 4.49 ± 0.25). Participants (n = 17) found the VR models comprehensible and navigable (mean 4.47 ± 0.62), with intuitive operation (mean 4.35 ± 0.79). Understanding pathology (mean 4.29 ± 0.77) and surgical procedures (mean 4.63 ± 0.5) was very satisfactory. The models improved anatomical visualization (mean 4.71 ± 0.47) and teaching effectiveness (mean 4.76 ± 0.56), with participants reporting enhanced comprehension and memorization, leading to an efficient learning process.ConclusionEstablishing a 3D VR database for teaching craniosynostosis shows advantages in understanding and memorization and increases motivation for the study process, thereby allowing for more efficient learning. Future applications in patient consent and teaching in other medical areas should be explored.

Objectives: Nontuberculous mycobacteria (NTM) bone and joint infections (BJIs) are uncommon. We evaluated the characteristics of BJIs and identified differences according to immune status. Methods: We performed a multicenter retrospective study in France involving patients with documented NTM BJI over a 9-year period. We collected the clinical and microbiological characteristics, management, and clinical outcomes of the patients. Results: Overall, 95 patients were included, of whom 50.5% (48/95) were immunosuppressed. Tenosynovitis was more frequent in the immunocompetent group, and native arthritis more common in the immunosuppressed group. Mycobacerium marinum and M. abscessus complex were significantly more frequent in the immunocompetent group, and M. avium and M. xenopi were significantly more frequent in the immunosuppressed group. The combination of antibiotherapy with surgery tended to be more frequent in the immunocompetent than the immunosuppressed group (63.8% (30/47) vs 47.8% (22/46), respectively); of the latter, 45.7% (21/46) received antimicrobial therapy alone, a higher frequency than in the immunocompetent group (23.4%, 11/47). The median duration of antimicrobial treatment was similar in the two groups (11 months). Mortality was significantly higher in the immunosuppressed group. Conclusions: Although the clinical presentations and the NTM species involved in BJI differed according to immune status, most recovered completely after treatment.

Abstract Background Bioresorbable patient-specific additive-manufactured bone grafts, meshes, and plates are emerging as a promising alternative that can overcome the challenges associated with conventional off-the-shelf implants. The fabrication of patient-specific implants (PSIs) directly at the point-of-care (POC), such as hospitals, clinics, and surgical centers, allows for more flexible, faster, and more efficient processes, reducing the need for outsourcing to external manufacturers. We want to emphasize the potential advantages of producing bioresorbable polymer implants for cranio-maxillofacial surgery at the POC by highlighting its surgical applications, benefits, and limitations. Methods This study describes the workflow of designing and fabricating degradable polymeric PSIs using three-dimensional (3D) printing technology. The cortical bone was segmented from the patient’s computed tomography data using Materialise Mimics software, and the PSIs were designed created using Geomagic Freeform and nTopology software. The implants were finally printed via Arburg Plastic Freeforming (APF) of medical-grade poly (L-lactide-co-D, L-lactide) with 30% β-tricalcium phosphate and evaluated for fit. Results 3D printed implants using APF technology showed surfaces with highly uniform and well-connected droplets with minimal gap formation between the printed paths. For the plates and meshes, a wall thickness down to 0.8 mm could be achieved. In this study, we successfully printed plates for osteosynthesis, implants for orbital floor fractures, meshes for alveolar bone regeneration, and bone scaffolds with interconnected channels. Conclusions This study shows the feasibility of using 3D printing to create degradable polymeric PSIs seamlessly integrated into virtual surgical planning workflows. Implementing POC 3D printing of biodegradable PSI can potentially improve therapeutic outcomes, but regulatory compliance must be addressed.

In recent years, it has become increasingly clear that space weather disturbances can be triggered by transient upstream mesoscale structures (TUMS), independently of the occurrence of large-scale solar wind (SW) structures, such as interplanetary coronal mass ejections and stream interaction regions. Different types of magnetospheric pulsations, transient perturbations of the geomagnetic field and auroral structures are often observed during times when SW monitors indicate quiet conditions, and have been found to be associated to TUMS. In this mini-review we describe the space weather phenomena that have been associated with four of the largest-scale and the most energetic TUMS, namely, hot flow anomalies, foreshock bubbles, travelling foreshocks and foreshock compressional boundaries. The space weather phenomena associated with TUMS tend to be more localized and less intense compared to geomagnetic storms. However, the quiet time space weather may occur more often since, especially during solar minima, quiet SW periods prevail over the perturbed times.

Abstract Fiber optic shape sensing is an innovative technology that has enabled remarkable advances in various navigation and tracking applications. Although the state-of-the-art fiber optic shape sensing mechanisms can provide sub-millimeter spatial resolution for off-axis strain measurement and reconstruct the sensor’s shape with high tip accuracy, their overall cost is very high. The major challenge in more cost-effective fiber sensor alternatives for providing accurate shape measurement is the limited sensing resolution in detecting shape deformations. Here, we present a data-driven technique to overcome this limitation by removing strain measurement, curvature estimation, and shape reconstruction steps. We designed an end-to-end convolutional neural network that is trained to directly predict the sensor’s shape based on its spectrum. Our fiber sensor is based on easy-to-fabricate eccentric fiber Bragg gratings and can be interrogated with a simple and cost-effective readout unit in the spectral domain. We demonstrate that our deep-learning model benefits from undesired bending-induced effects (e.g., cladding mode coupling and polarization), which contain high-resolution shape deformation information. These findings are the preliminary steps toward a low-cost yet accurate fiber shape sensing solution for detecting complex multi-bend deformations.

Pneumocystis jirovecii is a fungal pathogen that causes pneumocystis pneumonia, a disease that mainly affects immunocompromised individuals. This fungus has historically been hard to study because of our inability to grow it in vitro. One of the main drug targets in P. jirovecii is its dihydrofolate reductase (PjDHFR). Here, by using functional complementation of the baker's yeast ortholog, we show that PjDHFR can be inhibited by the antifolate methotrexate in a dose-dependent manner. Using deep mutational scanning of PjDHFR, we identify mutations conferring resistance to methotrexate. Thirty-one sites spanning the protein have at least one mutation that leads to resistance, for a total of 355 high-confidence resistance mutations. Most resistance-inducing mutations are found inside the active site, and many are structurally equivalent to mutations known to lead to resistance to different antifolates in other organisms. Some sites show specific resistance mutations, where only a single substitution confers resistance, whereas others are more permissive, as several substitutions at these sites confer resistance. Surprisingly, one of the permissive sites (F199) is without direct contact to either ligand or cofactor, suggesting that it acts through an allosteric mechanism. Modeling changes in binding energy between F199 mutants and drug shows that most mutations destabilize interactions between the protein and the drug. This evidence points towards a more important role of this position in resistance than previously estimated and highlights potential unknown allosteric mechanisms of resistance to antifolate in DHFRs. Our results offer unprecedented resources for the interpretation of mutation effects in the main drug target of an uncultivable fungal pathogen.

The detection of contrast-enhancing lesions (CELs) is fundamental for the diagnosis and monitoring of patients with multiple sclerosis (MS). This task is time-consuming and suffers from high intra- and inter-rater variability in clinical practice. However, only a few studies proposed automatic approaches for CEL detection. This study aimed to develop a deep learning model that automatically detects and segments CELs in clinical Magnetic Resonance Imaging (MRI) scans. A 3D UNet-based network was trained with clinical MRI from the Swiss Multiple Sclerosis Cohort. The dataset comprised 372 scans from 280 MS patients: 162 showed at least one CEL, while 118 showed no CELs. The input dataset consisted of T1-weighted before and after gadolinium injection, and FLuid Attenuated Inversion Recovery images. The sampling strategy was based on a white matter lesion mask to confirm the existence of real contrast-enhancing lesions. To overcome the dataset imbalance, a weighted loss function was implemented. The Dice Score Coefficient and True Positive and False Positive Rates were 0.76, 0.93, and 0.02, respectively. Based on these results, the model developed in this study might well be considered for clinical decision support.

This study presents mineral composition estimates of rock and sediment samples analyzed with the CheMin X-ray diffraction instrument on board the NASA Mars Science Laboratory rover, Curiosity, in Gale crater, Mars. Mineral composition is estimated using crystal-chemically derived algorithms applied to X-ray diffraction data, specifically unit-cell parameters. The mineral groups characterized include those found in major abundance by the CheMin instrument (i.e., feldspar, olivine, pyroxene, and spinel oxide). In addition to estimating the composition of the major mineral phases observed in Gale crater, we place their compositions in a stratigraphic context and provide a comparison to that of martian meteorites. This work provides expanded insights into the mineralogy and chemistry of the martian surface.

Abstract Currently, most medical image data, such as optical coherence tomography (OCT) images, are displayed in two dimensions on a computer screen. Advances in computer information technology have contributed to the growing storage of these data in electronic form. However, the data are usually processed only locally on site. To overcome such hurdles, a cyberspace virtual reality (csVR) application was validated, in which interactive OCT data were presented simultaneously to geographically distant sites (Lucerne, London, and Barcelona) where three graders independently measured the ocular csVR OCT diameters. A total of 109 objects were measured, each three times, resulting in a total of 327 csVR measurements. A minor mean absolute difference of 5.3 µm was found among the 3 measurements of an object (standard deviation 4.2 µm, coefficient of variation 0.3% with respect to the mean object size). Despite the 5 h of online work, csVR was well tolerated and safe. Digital high-resolution OCT data can be remotely and collaboratively processed in csVR. With csVR, measurements and actions enhanced with spatial audio communication can be made consistently in near real time, even if the users are situated geographically far apart. The proposed visuo-auditory framework has the potential to further boost the convenience of digital medicine toward csVR precision and collaborative medicine.

BackgroundThe 2022 multicountry mpox outbreaks predominantly affected gay, bisexual and other men who have sex with men (GBMSM) in non-endemic countries, including in the Netherlands. We conducted a survey-based assessment of the alignment between the risk factors associated with mpox diagnosis among GBMSM in the Netherlands and the eligibility criteria used in 2022 for vaccinating this group, with the aim to refine these criteria.MethodsAn online self-report survey was conducted among adult GBMSM in the Netherlands between 29 July and 30 August 2022, corresponding to the first month of the Dutch mpox vaccination campaign. GBMSM were recruited via advertisements on social media and gay dating apps. Participants reported on their sexual behaviour, mpox diagnosis, and/or (initial) mpox vaccination since the start of the outbreak. Covariables of mpox diagnosis and vaccination were assessed using logistic regression analyses.ResultsOf the 2,460 participants, 73 (3.0%, 95% CI 2.3–3.6%) were diagnosed with mpox and 485 (19.7%, 95% CI 18.1–21.3%) had received (initial) mpox vaccination. Using sample weighting, we estimated that, of the GBMSM population aged 18–80 years in the Netherlands, 1.1% (95% CI 0.7–1.6%) had been diagnosed with mpox and 7.8% (95% CI 6.8–8.9%) had received (initial) vaccination. HIV-PrEP use, living with HIV, reporting ≥20 sex partners in the past 12 months, and sex in sex venues/parties in the past 2 months were independent risk factors for mpox diagnosis. Except for sex in sex venues/parties, these variables were also independently associated with mpox vaccination.ConclusionThis study provides novel evidence regarding the degree to which the 2022 eligibility criteria for mpox vaccination align with the risk factors for mpox among GBMSM in the Netherlands. The findings contribute to a refinement of the eligibility criteria for mpox vaccination, to which sex in sex venues/parties should be added.

AbstractThe primary goal of this study is to assess current patient information available on the internet concerning robotic colorectal surgery. Acquiring this information will aid in patients understanding of robotic colorectal surgery. Data was acquired through a web-scraping algorithm. The algorithm used two Python packages: Beautiful Soup and Selenium. The long-chain keywords incorporated into Google, Bing and Yahoo search engines were ‘Da Vinci Colon-Rectal Surgery’, ‘Colorectal Robotic Surgery’ and ‘Robotic Bowel Surgery’. 207 websites resulted, were sorted and evaluated according to the ensuring quality information for patients (EQIP) score. Of the 207 websites visited, 49 belonged to the subgroup of hospital websites (23.6%), 46 to medical centers (22.2%), 45 to practitioners (21.7%), 42 to health care systems (20,2%), 11 to news services (5.3%), 7 to web portals (3.3%), 5 to industry (2.4%), and 2 to patient groups (0.9%). Only 52 of the 207 websites received a high rating. The quality of available information on the internet concerning robotic colorectal surgery is low. The majority of information was inaccurate. Medical facilities involved in robotic colorectal surgery, robotic bowel surgery and related robotic procedures should develop websites with credible information to guide patient decisions.

In the above article [1], we found major issues with the data we used. Specifically, we received data from [2] for five distinct tissues, with ten specimens per tissue. However, upon closer examination, we realized that the data for these specimens were not unique; rather, they were scaled variations derived from a single specimen. As a result, our training, testing, and validation datasets were not independent, leading to an artificially high accuracy rate of 100%.

Background: Image guidance to assist left ventricular (LV) lead placement may improve outcome after cardiac resynchronization therapy (CRT), but previous approaches and results varied greatly, and multicenter feasibility is lacking altogether. Objective: We sought to investigate the multicenter feasibility of image guidance for periprocedural assistance of LV lead placement for CRT. Methods: In 30 patients from 3 hospitals, cardiac magnetic resonance imaging was performed within 3 months prior to CRT to identify myocardial scar and late mechanical activation (LMA). LMA was determined using radial strain, plotted over time. Segments without scar but clear LMA were classified as optimal for LV lead placement, according to an accurate 36-segment model of the whole heart. LV leads were navigated using image overlay with periprocedural fluoroscopy. After 6 months, volumetric response and super-response were defined as ≥15% or ≥30% reduction in LV end-systolic volume, respectively. Results: Periprocedural image guidance was successfully performed in all CRT patients (age 66 ± 10 years; 59% men, 62% with nonischemic cardiomyopathy, 69% with left bundle branch block). LV leads were placed as follows: within (14%), adjacent (62%), or remote (24%) from the predefined target. According to the conventional 18-segment model, a remote position occurred only once (3%). On average, 86% of patients demonstrated a volumetric response (mean LV end-systolic volume reduction 36 ± 29%), and 66% of all patients were super-responders. Conclusion: On-screen image guidance for LV lead placement in CRT was feasible in a multicenter setting. Efficacy will be further investigated in the randomized controlled ADVISE (Advanced Image Supported Lead Placement in Cardiac Resynchronization Therapy) trial (NCT05053568).

Abstract Aims ARIADNE aimed to assess the association between effects of sacubitril/valsartan and no sacubitril/valsartan treatment and clinical characteristics, functional capacity, and clinical outcomes (cause‐specific mortality and hospitalizations) in outpatients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods ARIADNE was a prospective European registry of 9069 patients with HFrEF treated by office‐based cardiologists or selected primary care physicians. Of the 8787 eligible for analysis, 4173 patients were on conventional HF treatment (non‐S/V group), whereas 4614 patients were either on sacubitril/valsartan treatment at enrolment or started sacubitril/valsartan within 1 month of enrolment (S/V group). We also generated a restricted analysis set (rS/V) including only those 2108 patients who started sacubitril/valsartan treatment within the month prior to or after enrolment. Results At the baseline, average age of patients enrolled in the study was 68 years, and 23.9% (2099/8787) were female. At the baseline, the proportions of patients with New York Heart Association (NYHA) Class III symptoms were 30.9 (1288/4173), 42.8 (1974/4614), and 48.2% (1015/2108), in non‐S/V, S/V, and rS/V groups, respectively. After 12 months of treatment, the proportion of patients with NYHA Class III at baseline who improved to Class II was 32.0% (290/907) in the non‐S/V group vs. 46.3% (648/1399) in S/V group and 48.7% (349/717) in rS/V group. The overall mortality rate was 5.0 per 100 patient‐years. Rates of HF hospitalizations were high (20.9, 20.3, and 21.2 per 100 patient‐years in the non‐S/V, S/V, and rS/V groups, respectively). Emergency room visits without hospitalization occurred in 3.9, 3.2, and 3.9% of patients in the non‐S/V, S/V, and rS/V groups, respectively. Conclusions This large HFrEF European registry provides a contemporary outcome profile of outpatients with HFrEF treated with or without sacubitril/valsartan. In a real‐world setting, sacubitril/valsartan was associated with an improvement of symptoms in patients with HFrEF compared with the conventional HFrEF treatment.

BackgroundMachine learning (ML) is an inquiry domain that aims to establish methodologies that leverage information to enhance performance of various applications. In the healthcare domain, the ML concept has gained prominence over the years. As a result, the adoption of ML algorithms has become expansive. The aim of this scoping review is to evaluate the application of ML in pancreatic surgery.MethodsWe integrated the preferred reporting items for systematic reviews and meta-analyses for scoping reviews. Articles that contained relevant data specializing in ML in pancreas surgery were included.ResultsA search of the following four databases PubMed, Cochrane, EMBASE, and IEEE and files adopted from Google and Google Scholar was 21. The main features of included studies revolved around the year of publication, the country, and the type of article. Additionally, all the included articles were published within January 2019 to May 2022.ConclusionThe integration of ML in pancreas surgery has gained much attention in previous years. The outcomes derived from this study indicate an extensive literature gap on the topic despite efforts by various researchers. Hence, future studies exploring how pancreas surgeons can apply different learning algorithms to perform essential practices may ultimately improve patient outcomes.

Background: Synthetic glucocorticoids like dexamethasone can cause severe neuropsychiatric effects. They preferentially bind to the glucoc orticoid receptor (GR) over the mineralocorticoid receptor (MR). High dosages result i n strong GR activation but likely also result in lower MR activation based on GR-media ted negative feedback on cortisol levels. Therefore, reduced MR activity may contribu te to dexamethasone-induced neuropsychiatric symptoms. Objective: In this single case study, we evaluate whether dexamethasone leads to reduced MR activation in the human brain. Brain tissue of an 8-year-old brain tumor patient was used, who suffered chronically from dexa methasone-induced neuropsychiatric symptoms and deceased only hours after a high dose of dexamethasone. Main outcome measures: The efficacy of dexamethasone to induce MR activity was determined in HEK293T cells using a reporter construct. Subcell ular localization of GR and MR was assessed in paraffin-embedded hippocampal tissue from the patient and two controls. In hippocampal tissue from the patient and eight controls, mRNA of MR/GR target genes was measured. Results: In vitro, dexamethasone stimulated MR with low efficacy and low potency. Immunofluorescence showed the presence of both GR and MR in the hippocampal cell nuclei after dexamethasone exposure. The putative MR targe t gene JDP2 was consistently expressed at relatively low levels in the dexamethasone-treated brain samples. Gene expression showed substantial variation in MR/GR target gene expression in two different hippocampus tissue blocks from the same patient . Conclusions: Dexamethasone may induce MR nuclear translocation in the human brain. Conclusions on in vivo effects on gene expression in the brain await the availability of more tissue of dexamethasone-treated patients.

Abstract Understanding the stability and aggregation of nanoparticles in aqueous milieu is critical for assessing their behavior in the natural and engineered environmental systems and establishing their threat to human and ecosystems health. In this study, the colloidal stability and aggregation kinetics of nanocrystal quantum dots (QDs) —CdSe/ZnS QDs—were thoroughly explored under a wide range of aqueous environmental conditions. The z-average hydrodynamic diameters (z-avg. HDs) and zeta potential (ξ potential) of CdSe/ZnS QDs were measured in monovalent electrolyte (NaCl) and divalent electrolyte (CaCl2) solutions in both the absence and presence of natural organic matter (NOM)—Suwannee River natural organic matter, SRNOM to assess the dynamic growth of these nanoaggregate-QD-complexes, and the evaluation of their colloidal stability. Results show that CaCl2 was more effective to destabilize the QDs compared to NaCl at similar concentrations. An increase in NaCl concentration from 0.01 to 3.5 M increased the z-avg. HD of QD aggregates from 61.4 nm to 107.2 nm. The aggregation rates of QDs increased from 0.007 to 0.042 nm·s−1 with an increase in ionic strength from 0.5 to 3.5 M NaCl solutions, respectively. In the presence of Na+ cations, the aggregation of QDs was limited as steric forces generated by the original surface coating of QDs prevailed. In the presence of CaCl2, the aggregation of QDs was observed at a low concentration of CaCl2 (0.0001 M) with a z-avg. HD of 74.2 nm that significantly increased when the CaCl2 was higher than 0.002 M. Larger sizes of QD aggregates were observed at each level of CaCl2 concentration in suspensions of 0.002–0.1 M, as the z-avg. HDs of QDs increased from 125.1 to 560.4 nm, respectively. In the case of CaCl2, an increase in aggregation rates occurred from 0.035 to 0.865 nm·s−1 with an increase in ionic strength from 0.0001 M to 0.004 M, respectively. With Ca2+ cations, the aggregation of QDs was enhanced due to the bridging effects from the formation of complexes between Ca2+ cations in solution and the carboxyl group located on the surface coating of QDs. In the presence of SRNOM, the aggregation of QDs was enhanced in both monovalent and divalent electrolyte solutions. The degree of aggregation formation between QDs through cation-NOM bridges was superior for Ca2+ cations compared to Na+ cations. The presence of SRNOM resulted in a small increase in the size of the QD aggregates for each of NaCl concentrations tested (i.e., 0.01 to 3.5 M, except 0.1 M), and induced a monodispersed and narrower size distribution of QDs suspended in the monovalent electrolyte NaCl concentrations. In the presence of SRNOM, the aggregation rates of QDs increased from 0.01 to 0.024 nm 1 with the increase of NaCl concentrations from 0.01 to 2 M, respectively. The presence of SRNOM in QDs suspended in divalent electrolyte CaCl2 solutions enhanced the aggregation of QDs, resulting in the increase of z-avg. HDs of QDs by approximately 19.3%, 42.1%, 13.8%, 1.5%, and 24.8%, at CaCl2 concentrations of 0.002, 0.003, 0.005, 0.01, and 0.1 M, respectively. In the case of CaCl2, an increase in aggregation rates occurred from 0.035 to 0.865 nm·s−1 with an increase in ionic strength from 0.0001 to 0.004 M, respectively. Our findings demonstrated the colloidal stability of QDs and cations-NOM-QD nanoparticle complexes under a broad spectrum of conditions encountered in the natural and engineered environment, indicating and the potential risks from these nanoparticles in terms of human and ecosystem health.

Abstract Purpose Various parameters of mechanical dyssynchrony have been proposed to improve patient selection criteria for cardiac resynchronization therapy, but sensitivity and specificity are lacking. However, echocardiographic parameters are consistently investigated at rest, whereas heart failure (HF) symptoms predominately manifest during submaximal exertion. Although strain-based predictors of response are promising, feasibility and reproducibility during exercise has yet to be demonstrated. Methods Speckle-tracking echocardiography was performed in patients with HF at two separate visits. Echocardiography was performed at rest, during various exercise intensity levels, and during recovery from exercise. Systolic rebound stretch of the septum (SRSsept), systolic shortening, and septal discoordination index (SDI) were calculated. Results Echocardiography was feasible in about 70–80% of all examinations performed during exercise. Of these acquired views, 84% of the cine-loops were suitable for analysis of strain-based mechanical dyssynchrony. Test–retest variability and intra- and inter-operator reproducibility at 30% and 60% of the ventilatory threshold (VT) were about 2.5%. SDI improved in the majority of patients at 30% and 60% of the VT, with moderate to good agreement between both intensity levels. Conclusion Although various challenges remain, exercise echocardiography with strain analysis appears to be feasible in the majority of patients with dyssynchronous heart failure. Inter- and intra-observer agreement of SRSsept and SDI up to 60% of the VT were comparable to resting values. During exercise, the extent of SDI was variable, suggesting a heterogeneous response to exercise. Further research is warranted to establish its clinical significance.

Using a laser for cutting bones instead of the traditional saws improves a patient’s healing process. Additionally, the laser has the potential to reduce the collateral damage to the surrounding tissue if appropriately applied. This can be achieved by building additional sensing elements besides the laser itself into an endoscope. To this end, we use a microsecond pulsed Erbium-doped Yttrium Aluminium Garnet (Er:YAG) laser to cut bones. During ablation, each pulse emits an acoustic shock wave that is captured by an air-coupled transducer. In our research, we use the data from these acoustic waves to predict the depth of the cut during the ablation process. We use a Neural Network (NN) to estimate the depth, where we use one or multiple consecutive measurements of acoustic waves. The NN outperforms the base-line method that assumes a constant ablation rate with each pulse to predict the depth. The results are evaluated and compared against the ground-truth depth measurements from Optical Coherence Tomography (OCT) images that measure the depth in real-time during the ablation process.

Sugarcane (Saccharum spp.) is an important cash crop for production of sugar and bioethanol. Red stripe caused by Acidovorax avenae subsp. avenae (Aaa) is a disease that occurs in numerous sugarcane-growing regions worldwide. In this study, 17 strains of Aaa were isolated from 13 symptomatic leaf samples in China. Nine of these strains produced white-cream colonies on nutrient agar medium while the other eight produced yellow colonies. In pairwise sequence comparisons of the 16S-23S rRNA internally transcribed spacer (ITS), the 17 strains had 98.4-100% nucleotide identity among each other and 98.2-99.5% identity with the reference strain of Aaa (ATCC 19860). Three RFLP patterns based on this ITS sequence were also found among the strains of Aaa obtained in this study. Multilocus sequence typing (MLST) based on five housekeeping genes (ugpB, pilT, lepA, trpB, and gltA) revealed that the strains of Aaa from sugarcane in China and a strain of Aaa (30179) isolated from sorghum in Brazil formed a unique evolutionary subclade. Twenty-four additional strains of Aaa from sugarcane in Argentina and from other crops worldwide were distributed in two other and separate subclades, suggesting that strains of A. avenae from sugarcane are clonal populations with local specificities. Two strains of Aaa from China (CNGX08 forming white-cream colored colonies and CNGD05 forming yellow colonies) induced severe symptoms of red stripe in sugarcane varieties LC07-150 and ZZ8 but differed based on disease incidence in two separate inoculation experiments. Infected plants also exhibited increased salicylic acid (SA) content and transcript expression of gene PR-1, indicating that the SA-mediated signal pathway is involved in the response to infection by Aaa. Consequently, red stripe of sugarcane in China is caused by genetically different strains of Aaa and at least two morphological variants. The impact of these independent variations on epidemics of red stripe remains to be investigated.

Background: A preclinical model standardized at different remodeling stages after AV block induction in awake state is suitable for the evaluation of improved cardiac devices. We studied exercise-induced cardiorespiratory parameters at three different timepoints after inducing AV block in dogs. Methods: Mongrel dogs (n = 12) were placed on a treadmill with a 10% incline and performed a moderate exercise protocol (10-minute run at 6 km/h). Dogs ran at sinus rhythm (SR), at two days (AVB2d, initiation of remodeling), three weeks (CAVB3) and six weeks (CAVB6, completed remodeling) after AV block. Results: All dogs completed the exercise protocol at SR, CAVB3 and CAVB6, while 6/12 dogs at AVB2d failed to complete the exercise protocol. The atrial rate was higher at all AV block timepoints (126 ± 20 to 141 ± 19 bpm at rest and 221 ± 10 to 231 ± 13 bpm during exercise) compared to SR (100 ± 29 bpm at rest and 162 ± 28 bpm during exercise, p

BackgroundCardiovascular diseases (CVD) are the leading causes of death in the world, mainly occurring in low-and-middle income countries. The aim of this study was to estimate the prevalence of hypertension and other cardiovascular risk factors among university students at a National Polytechnic Institute in Côte d'Ivoire.MethodsA cross-sectional study was conducted among students of the National Polytechnic Institute of Côte d'Ivoire. Sample was selected using a non-probabilistic convenient sampling method. Anthropometric measurements, blood pressure and capillary blood glucose were measured. A logistic regression model allowed to determine factors associated with hypertension.ResultsA total of 2,030 students, 79.7% males and 20.3% females, with a median age of 20 years (IQR = [19-22]) participated in the study. On hypertension knowledge, 96.9% (n = 1,968) of students reported having heard of hypertension; salty foods were reported by more than a third as a cause of hypertension (n = 734; 37.3%), while 114 (5.8%) and 157 (8.0%) selected tobacco and alcohol as causes of hypertension, respectively. The overall prevalence of hypertension was 6.0%, higher in males (6.8%) compared to females (2.7%) (p < 0.001). As for CVD risk factors, 148 (7.3%) were overweight or obese; 44.0% of males and 36.6% of females reported alcohol consumption. In multivariate analysis, being a female (OR = 4.16; CI 95% = [1.96-9.09]; pConclusionCVD risk factors are prominent among young adults in Côte d'Ivoire. Appropriate behavioural health interventions promoting a healthy lifestyle for young adults should be urgently implemented for CVD burden reduction.

The characteristic endogenous circadian rhythm of plasma glucocorticoid concentrations is made up from an underlying ultradian pulsatile secretory pattern. Recent evidence has indicated that this ultradian cortisol pulsatility is crucial for normal emotional response in man. In this study, we investigate the anatomical transcriptional and cell type signature of brain regions sensitive to a loss of ultradian rhythmicity in the context of emotional processing. We combine human cell type and transcriptomic atlas data of high spatial resolution with functional magnetic resonance imaging (fMRI) data. We show that the loss of cortisol ultradian rhythm alters emotional processing response in cortical brain areas that are characterized by transcriptional and cellular profiles of GABAergic function. We find that two previously identified key components of rapid non-genomic GC signaling – the ANXA1 gene and retrograde endocannabinoid signaling – show most significant differential expression (q = 3.99e−10) and enrichment (fold enrichment = 5.56, q = 9.09e−4). Our results further indicate that specific cell types, including a specific NPY-expressing GABAergic neuronal cell type, and specific G protein signaling cascades underly the cerebral effects of a loss of ultradian cortisol rhythm. Our results provide a biological mechanistic underpinning of our fMRI findings, indicating specific cell types and cascades as a target for manipulation in future experimental studies.

IntroductionIn the 2022 multicountry mpox (formerly named monkeypox) outbreak, several countries offered primary preventive vaccination (PPV) to people at higher risk for infection. We study vaccine acceptance and its determinants, to target and tailor public health (communication-) strategies in the context of limited vaccine supply in the Netherlands.MethodsOnline survey in a convenience sample of gay, bisexual and other men who have sex with men, including transgender persons (22/07-05/09/2022, the Netherlands). We assessed determinants for being (un)willing to accept vaccination. We used multivariable multinominal regression and logistic regression analyses, calculating adjusted odds ratios (aOR) and 95 percent confidence-intervals. An open question asked for campaigning and procedural recommendations.ResultsOf respondents, 81.5% (n = 1,512/1,856) were willing to accept vaccination; this was 85.2% (799/938) in vaccination-eligible people and 77.7% (713/918) in those non-eligible. Determinants for non-acceptance included: urbanization (rural: aOR:2.2;1.2–3.7; low-urban: aOR:2.4;1.4–3.9; vs. high-urban), not knowing mpox-vaccinated persons (aOR:2.4;1.6–3.4), and lack of connection to gay/queer-community (aOR:2.0;1.5–2.7). Beliefs associated with acceptance were: perception of higher risk/severity of mpox, higher protection motivation, positive outcome expectations post vaccination, and perceived positive social norms regarding vaccination. Respondents recommended better accessible communication, delivered regularly and stigma-free, with facts on mpox, vaccination and procedures, and other preventive options. Also, they recommended, “vaccine provision also at non-clinic settings, discrete/anonymous options, self-registration” to be vaccinated and other inclusive vaccine-offers (e.g., also accessible to people not in existing patient-registries).ConclusionIn the public health response to the mpox outbreak, key is a broad and equitable access to information, and to low-threshold vaccination options for those at highest risk. Communication should be uniform and transparent and tailored to beliefs, and include other preventive options. Mpox vaccine willingness was high. Public health efforts may be strengthened in less urbanized areas and reach out to those who lack relevant (community) social network influences.

Leaf scald caused by Xanthomonas albilineans is one of the major bacterial diseases of sugarcane that threaten the sugar industry worldwide. Pathogenic divergence among strains of X. albilineans and interactions with the sugarcane host remain largely unexplored. In this study, 40 strains of X. albilineans from China were distributed into three distinct evolutionary groups based on multilocus sequence analysis and simple sequence repeats loci markers. In pathogenicity assays, the 40 strains of X. albilineans from China were divided into three pathogenicity groups (low, medium, and high). Twenty-four hours post inoculation (hpi) of leaf scald susceptible variety GT58, leaf populations of X. albilineans strain XaCN51 (high pathogenicity group) determined by qPCR were 3-fold higher than those of strain XaCN24 (low pathogenicity group). Inoculated sugarcane plants modulated the reactive oxygen species (ROS) homoeostasis by enhancing respiratory burst oxidase homolog (ScRBOH) expression and superoxide dismutase (SOD) activity and by decreasing catalase (CAT) activity, especially after infection by X. albilineans XaCN51. Furthermore, at 24 hpi, plants infected with XaCN51 maintained a lower content of endogenous salicylic acid (SA) and a lower expression level of SA-mediated genes (ScNPR3, ScTGA4, ScPR1, and ScPR5) as compared to plants infected with XaCN24. Altogether, these data revealed that the ROS production-scavenging system and activation of the SA pathway were involved in the sugarcane defense response to an attack by X. albilineans.

Hospitals are burdened with predicting, calculating, and managing various cost-affecting parameters regarding patients and their treatments. Accuracy in cost prediction is further affected when a patient suffers from other health issues that hinder the traditional prognosis. This can lead to an unavoidable deficit in the final revenue of medical centers. This study aims to determine whether machine learning (ML) algorithms can predict cost factors based on patients undergoing colon surgery. For the forecasting, multiple predictors will be taken into the model to provide a tool that can be helpful for hospitals to manage their costs, ultimately leading to operating more cost-efficiently. This proof of principle will lay the groundwork for an efficient ML-based prediction tool based on multicenter data from a range of international centers in the subsequent phases of the study. With a mean absolute percentage error result of 18%–25.6%, our model's prediction showed decent results in forecasting the costs regarding various diagnosed factors and surgical approaches. There is an urgent need for further studies on predicting cost factors, especially for cases with anastomotic leakage, to minimize unnecessary hospital costs.

The SRC Homology 3 (SH3) domains mediate protein–protein interactions (PPIs). Here, the authors assess the SH3-mediated PPIs in yeast, and show that the identity of the protein itself and the position of the SH3 both affect the interaction specificity and thus the PPI-dependent cellular functions.

Today’s mechanical tools for bone cutting (osteotomy) lead to mechanical trauma that prolong the healing process. Medical device manufacturers continuously strive to improve their tools to minimize such trauma. One example of such a new tool and procedure is minimally invasive surgery with laser as the cutting element. This setup allows for tissue ablation using laser light instead of mechanical tools, which reduces the post-surgery healing time. During surgery, a reliable feedback system is crucial to avoid collateral damage to the surrounding tissues. Therefore, we propose a tissue classification method that analyzes the acoustic waves produced during laser ablation and show its applicability in an ex-vivo experiment. The ablation process with a microsecond pulsed Erbium-doped Yttrium Aluminium Garnet (Er:YAG) laser produces acoustic waves that we captured with an air-coupled transducer. Consequently, we used these captured waves to classify five porcine tissue types: hard bone, soft bone, muscle, fat, and skin tissue. For automated tissue classification of the measured acoustic waves, we propose three Neural Network (NN) approaches: A Fully-connected Neural Network (FcNN), a one-dimensional Convolutional Neural Network (CNN), and a Recurrent Neural Network (RNN). The time- and the frequency-dependent parts of the measured waves’ pressure variation were used as separate inputs to train and validate the designed NNs. In a final step, we used Grad-CAM to find the frequencies’ activation map and conclude that the low frequencies are the most important ones for this classification task. In our experiments, we achieved an accuracy of 100% for the five tissue types for all the proposed NNs. We tested the different classifiers for their robustness and concluded that using frequency-dependent data together with a FcNN is the most robust approach.

The state-of-the art for solving the nonlinear material decomposition problem in spectral computed tomography is based on variational methods, but these are computationally slow and critically depend on the particular choice of the regularization functional. Convolutional neural networks have been proposed for addressing these issues. However, learning algorithms require large amounts of experimental data sets. We propose a deep learning strategy for solving the material decomposition problem based on a U-Net architecture and a Sim2Real transfer learning approach where the knowledge that we learn from synthetic data is transferred to a real-world scenario. In order for this approach to work, synthetic data must be realistic and representative of the experimental data. For this purpose, numerical phantoms are generated from human CT volumes of the KiTS19 Challenge dataset, segmented into specific materials (soft tissue and bone). These volumes are projected into sinogram space in order to simulate photon counting data, taking into account the energy response of the scanner. We compared projection- and image-based decomposition approaches where the network is trained to decompose the materials either in the projection or in the image domain. The proposed Sim2Real transfer strategies are compared to a regularized Gauss-Newton (RGN) method on synthetic data, experimental phantom data and human thorax data.

A convergent strategy is reported for the construction of nitrogen-containing heterocycles from common substrates: 1,4-diketones and primary amines. Indeed, by just varying the substrates, the substituents, or the heating mode, it is possible to selectively synthesize indole, indolone (1,5,6,7-tetrahydroindol-4-one), or cinnoline (5,6,7,8-tetrahydrocinnoline) derivatives in moderate to excellent yields.

Base editors allow for the precise modification of genes. Here the authors use Target-AID to systematically test 17,000 sites across the yeast genome.

The power of language to modify the reader's perception of interpreting biomedical results cannot be underestimated. Misreporting and misinterpretation are pressing problems in randomized controlled trials (RCT) output. This may be partially related to the statistical significance paradigm used in clinical trials centered around a P value below 0.05 cutoff. Strict use of this P value may lead to strategies of clinical researchers to describe their clinical results with P values approaching but not reaching the threshold to be "almost significant." The question is how phrases expressing nonsignificant results have been reported in RCTs over the past 30 years. To this end, we conducted a quantitative analysis of English full texts containing 567,758 RCTs recorded in PubMed between 1990 and 2020 (81.5% of all published RCTs in PubMed). We determined the exact presence of 505 predefined phrases denoting results that approach but do not cross the line of formal statistical significance (P < 0.05). We modeled temporal trends in phrase data with Bayesian linear regression. Evidence for temporal change was obtained through Bayes factor (BF) analysis. In a randomly sampled subset, the associated P values were manually extracted. We identified 61,741 phrases in 49,134 RCTs indicating almost significant results (8.65%; 95% confidence interval (CI): 8.58% to 8.73%). The overall prevalence of these phrases remained stable over time, with the most prevalent phrases being "marginally significant" (in 7,735 RCTs), "all but significant" (7,015), "a nonsignificant trend" (3,442), "failed to reach statistical significance" (2,578), and "a strong trend" (1,700). The strongest evidence for an increased temporal prevalence was found for "a numerical trend," "a positive trend," "an increasing trend," and "nominally significant." In contrast, the phrases "all but significant," "approaches statistical significance," "did not quite reach statistical significance," "difference was apparent," "failed to reach statistical significance," and "not quite significant" decreased over time. In a random sampled subset of 29,000 phrases, the manually identified and corresponding 11,926 P values, 68,1% ranged between 0.05 and 0.15 (CI: 67. to 69.0; median 0.06). Our results show that RCT reports regularly contain specific phrases describing marginally nonsignificant results to report P values close to but above the dominant 0.05 cutoff. The fact that the prevalence of the phrases remained stable over time indicates that this practice of broadly interpreting P values close to a predefined threshold remains prevalent. To enhance responsible and transparent interpretation of RCT results, researchers, clinicians, reviewers, and editors may reduce the focus on formal statistical significance thresholds and stimulate reporting of P values with corresponding effect sizes and CIs and focus on the clinical relevance of the statistical difference found in RCTs.

Continuum robots in robot-assisted minimally invasive surgeries provide adequate access to target anatomies that are not directly reachable through small incisions. Achieving precise and reliable shape estimation of such snake-like manipulators necessitates an accurate navigation system, that requires no line-of-sight and is immune to electromagnetic noise. Fiber Bragg grating (FBG) shape sensing, particularly eccentric FBG (eFBG), is a promising and cost-effective solution for this task. However, in eFBG sensors, the spectral intensity of the Bragg wavelengths that carries the strain information can be affected by undesired bending-induced phenomena, making standard characterization techniques less suitable for these sensors. We showed in our previous work that a deep learning model has the potential to extract the strain information from the eFBG sensor’s spectrum and accurately predict its shape. In this paper, we conducted a more thorough investigation to find a suitable architectural design of the deep learning model to further increase shape prediction accuracy. We used the Hyperband algorithm to search for optimal hyperparameters in two steps. First, we limited the search space to layer settings of the network, from which, the best-performing configuration was selected. Then, we modified the search space for tuning the training and loss calculation hyperparameters. We also analyzed various data transformations on the network’s input and output variables, as data rescaling can directly influence the model’s performance. Additionally, we performed discriminative training using the Siamese network architecture that employs two convolutional neural networks (CNN) with identical parameters to learn similarity metrics between the spectra of similar target values. The best-performing network architecture among all evaluated configurations can predict the shape of a 30 cm long sensor with a median tip error of 3.11 mm in a curvature range of 1.4 m ^−1 to 35.3 m ^−1 .

Objective To assess current management practice of heart failure with reduced ejection fraction (HFrEF) in multinational primary care (PC) and determine whether N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP)-guided referral of HFrEF patients from PC to a cardiologist could improve care, defined as adherence to European Society of Cardiology (ESC) guideline-recommended pharmacotherapy.Methods PRospective Evaluation of natriuretic peptide-based reFERral of patients with chronic HF in PC (PREFER) study enrolled HFrEF patients from PC considered clinically stable and those with NT-pro-BNP ≥600 pg/mL were referred to a cardiologist for optimisation of HF treatment. The primary outcome of adherence to ESC HF guidelines after referral to specialist was assessed at the second visit within 4 weeks of cardiologist’s referral and no later than 6 months after the baseline visit. Based on futility interim analysis, the study was terminated early.Results In total, 1415 HFrEF patients from 223 PCs from 18 countries in Europe were enrolled. Of these, 1324 (96.9%) were considered clinically stable and 920 (65.0%) had NT-pro-BNP ≥600 pg/mL (mean: 2631 pg/mL). In total, 861 (60.8%) patients fulfilled both criteria and were referred to a cardiologist. Before cardiologist consultation, 10.1% of patients were on ESC guideline-recommended HFrEF medications and 2.7% were on recommended dosages of HFrEF medication (defined as ≥50% of ESC guideline-recommended dose). Postreferral, prescribed HFrEF drugs remained largely unchanged except for an increase in diuretics (+4.6%) and mineralocorticoid receptor antagonists (+7.9%). No significant increase in patients’ adherence to guideline-defined drug combinations (11.2% post-referral vs 10.1% baseline) or drug combinations and dosages (3.3% postreferral vs 2.7% baseline) was observed after cardiologist consultation.Conclusions PREFER demonstrates substantial suboptimal treatment of HFrEF patients in the real world. Referral of patients with elevated NT-pro-BNP levels from PC to cardiologist did not result in meaningful treatment optimisation for treatments with known mortality and morbidity benefit.

Introduction Achieving optimal placement of the left ventricular (LV) lead in cardiac resynchronisation therapy (CRT) is a prerequisite in order to achieve maximum clinical benefit, and is likely to help avoid non-response. Pacing outside scar tissue and targeting late activated segments may improve outcome. The present study will be the first randomised controlled trial to compare the efficacy of real-time image-guided LV lead delivery to conventional CRT implantation. In addition, to estimate the cost-effectiveness of targeted lead implantation, an early decision analytic model was developed, and described here.Methods and analysis A multicentre, interventional, randomised, controlled trial will be conducted in a total of 130 patients with a class I or IIa indication for CRT implantation. Patients will be stratified to ischaemic heart failure aetiology and 1:1 randomised to either empirical lead placement or live image-guided lead placement. Ultimate lead location and echocardiographic assessment will be performed by core laboratories, blinded to treatment allocation and patient information. Late gadolinium enhancement cardiac magnetic resonance imaging (CMR) and CINE-CMR with feature-tracking postprocessing software will be used to semi-automatically determine myocardial scar and late mechanical activation. The subsequent treatment file with optimal LV-lead positions will be fused with the fluoroscopy, resulting in live target-visualisation during the procedure. The primary endpoint is the difference in percentage of successfully targeted LV-lead location. Secondary endpoints are relative percentage reduction in indexed LV end-systolic volume, a hierarchical clinical endpoint, and quality of life. The early analytic model was developed using a Markov-model, consisting of seven mutually exclusive health states.Ethics and dissemination The protocol was approved by the Medical Research Ethics Committee Utrecht (NL73416.041.20). All participants are required to provide written informed consent. Results will be submitted to peer-reviewed journals.Trial registration number NCT05053568; Trial NL8666.

Abstract Background Squamous cell carcinoma in the head and neck region is one of the most widespread cancers with high morbidity. Classic treatment comprises the complete removal of the lymphatics together with the cancerous tissue. Recent studies have shown that such interventions are only required in 30% of the patients. Sentinel lymph node biopsy is an alternative method to stage the malignancy in a less invasive manner and to avoid overtreatment. In this paper, we present a novel approach that enables a future augmented reality device which improves the biopsy procedure by visual means. Methods We propose a co-calibration scheme for axis-aligned miniature cameras with pinholes of a gamma ray collimating and sensing device and show results gained by experiments, based on a calibration target visible for both modalities. Results Visual inspection and quantitative evaluation of the augmentation of optical camera images with gamma information are congruent with known gamma source landmarks. Conclusions Combining a multi-pinhole collimator with axis-aligned miniature cameras to augment optical images using gamma detector data is promising. As such, our approach might be applicable for breast cancer and melanoma staging as well, which are also based on sentinel lymph node biopsy.

In this short essay, I will try to define contemporary populism in a “neutral” fashion; and to explore its virtues, as well as its (much better known) vices. To conclude, I shall attempt to draw up a balance sheet between its contrasting contributions to contemporary political life in Europe. To accomplish this, I will have to speak “generically” and, therefore, to ignore or set aside the traits populism has had and the outcomes it has produced in specific cases. I begin with the (hazardous) position that it can be good or bad for democracy… depending. And I will finally try to address the issue of the conditions under which it is more likely to harm or benefit the polity in which it has emerged.