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Improving the understanding of the causes and effects of anthropogenic hybridization is fundamental to ensure species conservation, particularly in the case of hybridization between wild species and their domestic relatives. Knowledge is missing for many species also because of a lack of appropriate tools for hybrid identification. Here, coupling genotype and phenotype analysis, we carried out an extensive investigation of ongoing hybridization in Alpine ibex Capra ibex, a mountain ungulate of conservation concern from a genetic perspective. By genotyping 63 diagnostic and 465 neutral SNPs, 20 suspected hybrids and 126 Alpine ibex without suspicious phenotype, representing 8 populations across a major part of the species distribution, we found evidence for ongoing hybridization between Alpine ibex and domestic goat. We identified different levels of hybridization including backcrosses into both Alpine ibex and domestic goat. Our results suggest a lack of reproductive barriers between the two species and good survival and reproductive success of the hybrids. Hybridization was locally intense, like a hybrid swarm, but not spread across the rest of the species distribution. Most of the hybrids were discovered in two locations in the north‐west of Italy, while random sampling of individuals from different areas did not provide evidence of recent hybridization. Our method, based on amplicon sequencing of 63 diagnostic SNPs specifically developed for this purpose, allowed us to identify hybrids and backcrosses up to the fourth to fifth generations and was suitable for genetic samples of different quality, although with varying levels of certainty regarding the exact number of generations passed since hybridization. Based on the paired analysis of genotype and phenotype, we provide guidelines for the first identification of hybrids in the field and suggest a procedure for the reliable identification of hybrids. [ABSTRACT FROM AUTHOR]

Exposure to nanoparticles (NPs) in pregnancy is increasingly linked to adverse effects on embryo‐fetal development and health later in life. However, the developmental toxicity mechanisms of NPs are largely unknown, in particular potential effects on the placental secretome, which orchestrates many developmental processes pivotal for pregnancy success. This study demonstrates extensive material‐ and pregnancy stage‐specific deregulation of placental signaling from a single exposure of human placental explants to physiologically relevant concentrations of engineered (silica (SiO2) and titanium dioxide (TiO2) NPs) and environmental NPs (diesel exhaust particles, DEPs). This includes a multitude of secreted inflammatory, vascular, and endocrine placental factors as well as extracellular vesicle (EV)‐associated proteins. Moreover, conditioned media (CM) from NP‐exposed explants induce pronounced anti‐angiogenic and anti‐vasculogenic effects, while early neurodevelopmental processes are only marginally affected. These findings underscore the potential of metal oxide NPs and DEPs for widespread interference with the placental secretome and identify vascular morphogenesis as a sensitive outcome for the indirect developmental toxicity of different NPs. Overall, this work has profound implications for the future safety assessment of NPs for industrial, commercial, or medical applications in pregnancy, which should consider placenta‐mediated toxicity by holistic secretomics approaches to ensure the development of safe nanotechnologies. [ABSTRACT FROM AUTHOR]

Aim: The aim was to develop a standardized curved root canal model in bovine dentine and to assess whether that natural substrate would behave differently from the resin in standard plastic training blocks when prepared chemo‐mechanically. The impact of substrate microhardness on simulated canal transportation was considered. Methodology: High‐precision computer numerical control (CNC) milling was used to recreate a simulated root canal from a resin training block (Endo Training Bloc J‐Shape, size 15) in longitudinally sectioned, dis‐ and re‐assembled bovine incisor roots. Optical overlays obtained from 10 resin blocks were used to identify an average canal and program the CNC milling apparatus accordingly. Resin and dentine microhardness were measured. Simulated root canals in resin training blocks and their bovine counterparts were then instrumented at 37°C using Reciproc R25 instruments (VDW) with water or 17% EDTA (n = 10). Open‐access image processing software was used to superimpose and analyse pre‐ and postoperative images obtained with a digital microscope. Centering ratios were averaged to indicate canal transportation. The effects of substrate and irrigant on canal transportation were assessed by two‐way anova. Results: Superimposed images showed that resin blocks under investigation varied considerably in terms of simulated canal length and curvature, whilst the milled canals were highly similar. The microhardness of dentine was more than three times higher than that of the resin. Conversely, canal transportation was considerably greater in dentine compared to resin, and in dentine had a tendency to be increased by EDTA. There was a strong effect of substrate on canal transportation (p <.001), no overall effect of irrigant, and a marginally significant interaction between irrigant and substrate (p =.077). Conclusions: CNC milling allows to create standardized simulated curved root canals in bovine dentine. These models may be useful to test and compare materials and concepts of chemo‐mechanical root canal instrumentation. Microhardness is a bulk feature that does not predict the response to chemo‐mechanical instrumentation of a composite material such as dentine. [ABSTRACT FROM AUTHOR]

Summary: Cyclic thrombocytopenia (CTP) is characterized by periodic platelet oscillation with substantial amplitude. Most CTP cases have a thrombocytopenic background and are often misdiagnosed as immune thrombocytopenia with erratically effective treatment choices. CTP also occurs during hydroxyurea treatment in patients with myeloproliferative diseases. While the aetiology of CTP remains uncertain, here we evaluate historical, theoretical and clinical findings to provide a framework for understanding CTP pathophysiology. CTP retains the intrinsic oscillatory factors defined by the homeostatic regulation of platelet count, presenting as reciprocal platelet/thrombopoietin oscillations and stable oscillation periodicity. Moreover, CTP patients possess pathogenic factors destabilizing the platelet homeostatic system thereby creating opportunities for external perturbations to initiate and sustain the exaggerated platelet oscillations. Beyond humoral and cell‐mediated autoimmunity, we propose recently uncovered germline and somatic genetic variants, such as those of MPL, STAT3 or DNMT3A, as pathogenic factors in thrombocytopenia‐related CTP. Likewise, the JAK2 V617F or BCR::ABL1 translocation that drives underlying myeloproliferative diseases may also play a pathogenic role in hydroxyurea‐induced CTP, where hydroxyurea treatment can serve as both a trigger and a pathogenic factor of platelet oscillation. Elucidating the pathogenic landscape of CTP provides an opportunity for targeted therapeutic approaches in the future. [ABSTRACT FROM AUTHOR]

Determination of alkali elements is important to Earth scientists, yet suitable and reliable microanalytical reference materials are lacking. This paper proposes a new albite reference material and evaluates the potential for future K‐feldspar reference materials. The proposed Piz Beverin albite reference material from Switzerland yields a homogeneous composition at the centimetre‐ to micrometre‐scale for Si, Al and Na with < 2000 μg g‐1 total trace elements (mostly heterogeneously distributed Ca, K and Sr). EPMA and LA‐ICP‐MS measurements confirm a composition of 99.5(2)% albite component, which is supported further by bulk XRF measurements. A round robin evaluation involving nine independent EPMA laboratories confirms its composition and homogeneity for Si, Al and Na. In addition, a set of five distinct clear K‐feldspar samples was evaluated as possible reference materials. The first two crystals of adular and orthoclase yield unacceptable inhomogeneities with > 2% relative local variations of Na, K and Ba contents. The three other investigated sets of K‐feldspar crystals are yellow sanidine crystals from Itrongay (Madagascar). Despite distinct compositions, EPMA confirms they are each homogeneous at the centimetre to micrometre scale for Si, Al and K and have no apparent inclusions; further investigation to find larger amounts of these materials is therefore justified. [ABSTRACT FROM AUTHOR]

Wastewater‐based epidemiology (WBE) has been proven to be a useful tool in monitoring public health‐related issues such as drug use, and disease. By sampling wastewater and applying WBE methods, wastewater‐detectable pathogens such as viruses can be cheaply and effectively monitored, tracking people who might be missed or under‐represented in traditional disease surveillance. There is a gap in current knowledge in combining hydraulic modeling with WBE. Recent literature has also identified a gap in combining machine learning with WBE for the detection of viral outbreaks. In this study, we loosely coupled a physically‐based hydraulic model of pathogen introduction and transport with a machine learning model to track and trace the source of a pathogen within a sewer network and to evaluate its usefulness under various conditions. The methodology developed was applied to a hypothetical sewer network for the rapid detection of disease hotspots of the disease caused by the SARS‐CoV‐2 virus. Results showed that the machine learning model's ability to recognize hotspots is promising, but requires a high time‐resolution of monitoring data and is highly sensitive to the sewer system's physical layout and properties such as flow velocity, the pathogen sampling procedure, and the model's boundary conditions. The methodology proposed and developed in this paper opens new possibilities for WBE, suggesting a rapid back‐tracing of human‐excreted biomarkers based on only sampling at the outlet or other key points, but would require high‐frequency, contaminant‐specific sensor systems that are not available currently. Plain Language Summary: Viral outbreaks such as COVID‐19 are commonly monitored using traditional surveillance methods (e.g., nose swabs). However, individuals may not follow such testing schemes for different reasons, such as if they do not have symptoms. When people are infected by COVID‐19, they excrete SARS‐CoV‐2, the virus that causes the disease. Hence, analyzing sewage using wastewater‐based epidemiology (WBE) methods could help monitor the virus outbreak. Recent literature has identified a gap in combining machine learning and hydraulic models with WBE to detect viral outbreaks. In this study, we combine a hydraulic model that simulates virus transport with a machine learning model that tracks hotspot areas within a sewer network. The methodology developed in this paper was applied to a hypothetical sewer network to detect COVID‐19 disease hotspots rapidly. Results showed that the machine learning model has the potential to recognize hotspots but requires high time‐resolution data and is dependent on the sewer system's characteristics, such as flow velocity and virus sampling procedure. The developed methodology opens new possibilities for WBE to potentially trace human‐excreted viral genetic material based on only sampling at particular points. However, it would require high‐frequency sampling sensor systems that are not available currently. Key Points: Using a numerical model of wastewater network and machine learning has the potential for the early detection of viral outbreaksThe ability to recognize disease hotspots depends on sampling frequency and methodThe use of sewer models can improve the usefulness of wastewater‐based epidemiology data [ABSTRACT FROM AUTHOR]

Biochemical reactions occurring in highly crowded cellular environments require different means of control to ensure productivity and specificity. Compartmentalization of reagents by liquid‐liquid phase separation is one of these means. However, extremely high local protein concentrations of up to 400 mg/ml can result in pathological aggregation into fibrillar amyloid structures, a phenomenon that has been linked to various neurodegenerative diseases. Despite its relevance, the process of liquid‐to‐solid transition inside condensates is still not well understood at the molecular level. We thus herein use small peptide derivatives that can undergo both liquid‐liquid and subsequent liquid‐to‐solid phase transition as model systems to study both processes. Using solid‐state nuclear magnetic resonance (NMR) and transmission electron microscopy (TEM), we compare the structure of condensed states of leucine, tryptophan and phenylalanine containing derivatives, distinguishing between liquid‐like condensates, amorphous aggregates and fibrils, respectively. A structural model for the fibrils formed by the phenylalanine derivative was obtained by an NMR‐based structure calculation. The fibrils are stabilised by hydrogen bonds and side‐chain π‐π interactions, which are likely much less pronounced or absent in the liquid and amorphous state. Such noncovalent interactions are equally important for the liquid‐to‐solid transition of proteins, particularly those related to neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Postoperative anastomotic leaks are the most feared complications after gastric surgery. For diagnostics clinicians mostly rely on clinical symptoms such as fever and tachycardia, often developing as a result of an already fully developed, i.e., symptomatic, surgical leak. A gastric fluid responsive, dual modality, electronic‐free, leak sensor system integrable into surgical adhesive suture support materials is introduced. Leak sensors contain high atomic number carbonates embedded in a polyacrylamide matrix, that upon exposure to gastric fluid convert into gaseous carbon dioxide (CO2). CO2 bubbles remain entrapped in the hydrogel matrix, leading to a distinctly increased echogenic contrast detectable by a low‐cost and portable ultrasound transducer, while the dissolution of the carbonate species and the resulting diffusion of the cation produces a markedly reduced contrast in computed tomography imaging. The sensing elements can be patterned into a variety of characteristic shapes and can be combined with nonreactive tantalum oxide reference elements, allowing the design of shape‐morphing sensing elements visible to the naked eye as well as artificial intelligence‐assisted automated detection. In summary, shape‐morphing dual modality sensors for the early and robust detection of postoperative complications at deep tissue sites, opening new routes for postoperative patient surveillance using existing hospital infrastructure is reported. [ABSTRACT FROM AUTHOR]

Acute bouts of physical exercise have the potential to benefit children's cognition. Inconsistent evidence calls for systematic investigations of dose–response relations between quantitative (intensity and duration) and qualitative (modality) exercise characteristics. Thus, in this study the optimal duration of an acute cognitively challenging physical exercise to benefit children's cognition was investigated, also exploring the moderating role of individual characteristics. In a within‐subject experimental design, 104 children (Mage = 11.5, SD = 0.8, 51% female) participated weekly in one of four exergaming conditions of different durations (5, 10, 15, 20 min) followed by an Attention Network task (ANT‐R). Exergame sessions were designed to keep physical intensity constant (65% HRmax) and to have a high cognitive challenge level (adapted to the individual ongoing performance). Repeated measures ANOVAs revealed a significant effect of exercise duration on reaction times (RTs; p = 0.009, ƞ2p = 0.11), but not on response accuracy. Post hoc analyses showed faster information processing speed after 15 min of exercise compared to 10 min (p = 0.019, ƞ2p = 0.09). Executive control, alerting and orienting performances and interactions were unaffected by exercise duration (ps > 0.05). Among individual characteristics, habitual physical activity moderated duration effects on RTs. For more active children, exercise duration influenced the interaction between executive control and orienting (p = 0.034; ƞ2p = 0.17) with best performances after the 15 min duration. Results suggest that an acute 15 min cognitively high‐challenging bout of physical exercise enhances allocable resources, which in turn facilitate information processing, and—for more active children only—also executive processes. Results are interpreted according to the arousal theory and cognitive stimulation hypothesis. [ABSTRACT FROM AUTHOR]

Summary: Patients with refractory immune thrombocytopenia (rITP) have increased morbidity and mortality. Currently, there is limited understanding of the cause of refractoriness and no markers to help direct novel treatment options. Understanding the reason(s) for refractoriness is crucial to determining novel treatment options. The pathogenesis underlying rITP has generally been thought to be an underlying genetic predisposition with an environmental trigger. Familial ITP remains rare, and there are few twin studies, suggesting that a simple genetic cause is unlikely. However, genetic mutations provide the background for several autoimmune diseases. In this review, we explore the evidence of either an inherited genetic cause of rITP or an acquired mutation, in particular one resulting in clonal expansion of cytotoxic T cells. [ABSTRACT FROM AUTHOR]

We describe the development of an efficient method for the olefination of hydrazones and oximes. The key design approach that enables this transformation is tuning of the energy/polarity of C=N π‐bonds by employing heteroatom functionalities (NR2, OR). The resulting hydrazones or oximes facilitate olefination with ruthenium alkylidenes. Through this approach, we show that air‐stable, commercially available ruthenium alkylidenes provide access to functionalized alkenes (20 examples) in ring‐closing reactions with yields up to 88 %. [ABSTRACT FROM AUTHOR]

Green alder shrubs Alnus viridis increasingly overgrow European mountain pastures but hinder natural forest succession. This nitrogen‐fixing, autochthonous invasive species has numerous negative effects including the loss of biodiversity and landscape aesthetic, eutrophication of soils and downstream waters, and greenhouse gas emission. Over centuries, A. viridis encroachment was impeded by grazing livestock, particularly goats. However, in modern agriculture, livestock numbers decreased on remote mountain pastures and goat farming became unprofitable.A grazing experiment tested if hardy breeds of the more economically attractive livestock species, cattle and sheep can replace goats as A. viridis antagonists. On a subalpine pasture heavily encroached by A. viridis, space use and debarking (bark foraging) by Dexter cattle, Engadine sheep and Pfauen goats were analysed using GPS tracking and vegetation mapping.Dexter cattle used space least evenly (Camargo evenness: cattle = 0.39; sheep = 0.52; and goats = 0.47) and preferred flat slopes and open pastures. They spent least time foraging in A. viridis stands (relative presence while foraging: cattle = 0.55; sheep = 0.76; and goats = 0.80). Dexter cattle did not debark any A. viridis, but damaged shrubs by trampling.Engadine sheep visited A. viridis stands nearly as often as goats, but preferred flat slopes, short vegetation and shrub edges more clearly than goats. This sheep breed debarked significantly more A. viridis branches (average 244 branches per paddock; 7.4% of all A. viridis branches) than goats (45; 0.8%). Goats preferred mountain‐ash shrubs Sorbus aucuparia covering only 2% of the shrub layer.Synthesis and applications. Green alder shrubs, controlled by goats traditionally, overgrow valuable mountain pasture ecosystems today. Cattle, kept instead of goats, may slow down but not hinder shrub encroachment, because they avoid shrub stands and do not debark green alder. However, this study is the first to show that Engadine sheep are even better suited for green alder clearance than goats. Moreover, if management goals include forest re‐establishment, Engadine sheep outperform goats, because they debark green alder (which hinders forest regeneration), but do not destroy elderberry—a valuable forest pioneer. Hardy breeds are an important tool to maintain biodiverse, open pastures, restore natural mountain forests and mitigate the negative environmental effects of shrub encroachment. [ABSTRACT FROM AUTHOR]

The authors of this narrative review aimed to address various experimental methods and make recommendations for how research should move forward in the context of studying biomarkers in clinical Endodontic research. The approach adopted is exemplified using two prominent clinical problems, namely (a) the 'reversible' versus 'irreversible' pulpitis conundrum and (b) persistent idiopathic dentoalveolar pain (PIDAP). Pulpitis under deep caries or dentinal cracks is understood from a histological perspective, but clinical assessment tools to indicate irreversibly inflamed aspects of the dental pulp are elusive. PIDAP, on the other hand, is a diagnosis of exclusion; its pathophysiology is complex and not understood sufficiently to avoid unnecessary dental treatments. This review addresses how diagnostic biomarkers could further our understanding of those and other clinical problems, and how issues can be tackled from a methodological point of view. Hence, different methodological approaches to identify suitable diagnostic biomarker(s) or use known biomarkers are presented. The importance of asking a relevant research question, collecting the most suitable fluid and using the ideal collection vehicle for the research question under investigation is discussed based on the defined clinical problems. [ABSTRACT FROM AUTHOR]

Background: Pityriasis lichenoides (PL) is a papulosquamous disease that affects both adults and children. Previous studies have shown a subset of this entity to have clonal T-cell populations via PCR-based assays. In this study, we sought to implement next-generation sequencing (NGS) as a more sensitive and specific test to examine for T-cell clonality within the pediatric population. Methods: We identified 18 biopsy specimens from 12 pediatric patients with clinical and histopathologic findings compatible with PL. Patient demographics, clinical features, management, and histopathologic findings were reviewed. All specimens were analyzed for clonality with NGS of T-cell receptor beta (TRB) and gamma (TRG) genes. Results: Of the 12 patients, 9 (75%) had complete resolution of lesions at the time of data collection (mean follow-up 31 months). The remaining three patients significantly improved with methotrexate (with or without acitretin). Interestingly, 7 of 12 patients (58%) and 9 of 17 biopsy specimens (53%) showed evidence of T-cell clonality. Two patients showed matching TRB clones from different anatomic sites. Conclusions: T-cell clonality is a common finding in PL, probably representing a "reactive clonality" rather than a true lymphoproliferative disorder. Clonality alone cannot be used as a means to distinguish PL from lymphomatoid papulosis or cutaneous lymphoma. [ABSTRACT FROM AUTHOR]

Aim: To assess whether persistent idiopathic dentoalveolar pain (PIDAP), a diagnosis of exclusion, exhibits common features that can facilitate its diagnosis. PIDAP is defined by the International Classification of Orofacial Pain (ICOP 6.3.) as 'Persistent unilateral intraoral dentoalveolar pain, rarely occurring in multiple sites, with variable features but recurring daily for more than 2 h per day for more than 3 months, in the absence of any preceding causative event'. Methodology: In this observational study, participants fulfilling the new ICOP diagnostic criteria of PIDAP were included, covering 16 years of consecutive data. A systematic, retrospective assessment of patients utilizing the new PIDAP criteria on complaints of chronic tooth pain in a referral‐based endodontic practice was undertaken. Non‐idiopathic cases were excluded on the basis of clinical and radiologic findings. A modified neuropathic pain questionnaire was used to describe the painful sensations. Furthermore, allodynia in the periodontal space and sensory changes in the oral mucosa were assessed using a periodontal probe. Results: Amongst the 160 patients assessed, 78 (63 women) fulfilled the strict PIDAP criteria. Pain history of PIDAP included no nocturnal awakening (85%) and a 'pulling/dragging' pain quality (59%). In 69% of the patients with PIDAP, pain was associated with a root filled tooth at the same site. In 14% of the cases, no endodontic treatment was performed in the affected quadrant. Mechanical allodynia in the gingival sulcus was observed in 91% of patients with painful teeth or implants. Conclusions: In this observational study, PIDAP mainly affected females and was associated with undisturbed sleep and periodontal allodynia. [ABSTRACT FROM AUTHOR]

Paramagnetic metal ions can be inserted into ATP‐fueled motor proteins by exchanging the diamagnetic Mg2+ cofactor with Mn2+ or Co2+. Then, paramagnetic relaxation enhancement (PRE) or pseudo‐contact shifts (PCSs) can be measured to report on the localization of the metal ion within the protein. We determine the metal position in the oligomeric bacterial DnaB helicase from Helicobacter pylori complexed with the transition‐state ATP‐analogue ADP:AlF4− and single‐stranded DNA using solid‐state NMR and a structure‐calculation protocol employing CYANA. We discuss and compare the use of Mn2+ and Co2+ in localizing the ATP cofactor in large oligomeric protein assemblies. 31P PCSs induced in the Co2+‐containing sample are then used to localize the DNA phosphate groups on the Co2+ PCS tensor surface enabling structural insights into DNA binding to the DnaB helicase. [ABSTRACT FROM AUTHOR]

Increasing demand for digital evidence in criminal investigations is driving decentralization of forensic capabilities closer to the crime scene. Law enforcement agencies are struggling to keep pace with technological developments, cybercrime growth, and scientific advances. In federated environments, digital forensic knowledge and practices vary widely across regions. To reduce delays, wasted resources, missed opportunities, mistakes, and misinterpretations, there is a pressing need to balance the democratization of digital forensic capabilities with knowledge management and sharing between decentralized regions. There are multiple forms of knowledge to be managed, including procedural, technical, investigative, scientific, behavioral, crime analysis, and forensic intelligence. In addition, there are multiple knowledge producers and consumers, including police investigators, digital forensic practitioners, criminal intelligence analysts, attorneys, and judges. Knowledge management becomes even more challenging when multiple interdependent regions are involved, speaking different languages. Taking all of these factors into consideration, this work presents an inter‐regional knowledge management solution for improving the quality, consistency, reliability, efficiency, cost‐effectiveness, and return on investment of digital forensic capabilities. The basis of this work is a community‐driven initiative of Swiss regional police authorities. Interviews were conducted with 15 digital forensic units to determine their current knowledge management practices and needs. The results were then generalized into a prioritized set of requirements for inter‐regional digital forensic knowledge management that may be applicable in other countries. These requirements were used to evaluate knowledge management platforms, and one was selected. Implementation, operations, and maintenance challenges of an inter‐regional digital forensic knowledge management platform are discussed. [ABSTRACT FROM AUTHOR]

Aim: To validate a new method for the evaluation of pulp tissue debridement in the root canals of extracted teeth using an impregnation protocol involving potassium triiodide, a radiocontrast solution known as Lugol's, combined with micro‐computed tomographic (micro‐CT) imaging. Methodology: The impact of NaOCl on the radiopacity of Lugol's solution was assessed using a two‐fold dilution series of Lugol in distilled water and 5.25% NaOCl, which were then pipetted into transparent dishes and radiographed. To verify the influence of Lugol on the proteolytic effect of NaOCl, a dissolution test was performed using fresh bovine meat. Ten slices did not undergo any tissue processing, whilst twenty slices were fixed in formaldehyde for 24 h. After that, 10 of them were immersed in Lugol for another 24 h. Then, all specimens were placed in NaOCl and the time required for a complete tissue dissolution was recorded. For the last experiments (histological validation and micro‐CT assessment), 8 extracted mandibular premolars with formerly vital pulps were immersed in buffered formalin, scanned in a micro‐CT device, accessed, immersed in Lugol for 7 days and scanned again. Then, the root canals of 5 teeth were prepared and scanned, and the volume of remaining pulp tissue identified and quantified, whilst 3 teeth were histologically processed. The same specimens were subjected to histological assessment, and the images of the histologic sections were registered with the corresponding micro‐CT images to verify whether the pulp tissue in the histological sections matched its counterpart in the Lugol‐impregnated tissues identified in the micro‐CT slices. Results: There was no discernible effect on radiopacity when NaOCl was mixed with Lugol's solution. Tissue processing did not affect the time required for the complete dissolution of fresh bovine meat. Histological evaluation revealed a correlation between micro‐CT and histological images confirming the identification of Lugol‐impregnated pulp tissue in micro‐CT images. Conclusions: The radiocontrast Lugol's solution was unaffected by NaOCl and did not interfere with its soft tissue dissolution capability. The impregnation protocol using Lugol's solution allowed the visualization of pulp tissue on the micro‐CT images and the identification of pulp remnants after chemical–mechanical canal procedures. [ABSTRACT FROM AUTHOR]

Aim: To assess and correlate three distinct states of severely painful endodontically derived inflammation with their depiction on periapical radiographs using periapical index (PAI) scores. Methodology: During a period of 15 months, 368 consecutively enrolled patients with suspected endodontic emergency conditions were examined at the University of Zurich, Center of Dental Medicine. Cases with a severely painful (numeric rating scale, NRS‐11 > 6) endodontically involved tooth and a clear pulpal and apical diagnosis (n = 162) were selected (one tooth per patient). Teeth were divided into three groups according to the clinically diagnosed main location of the inflammatory process: level 1: pulp (positive response to cold test), level 2: periodontium (no response to cold without swelling) and level 3: periapical tissues (no response to cold with swelling). Periapical radiographs were obtained using a digital unit and analysed by two calibrated observers. For level 2, which had the highest PAI variance (n = 76), the PAI scores were further scrutinized regarding their dependence on tooth location and the duration of pain. Data were analysed using chi‐squared and non‐parametric tests, alpha = 0.05. Results: Overall, the PAI scores correlated well with the clinically diagnosed main location of periapical inflammation (Spearman's rho = 0.5131, P < 0.001), with level 1 having the lowest scores by far (P < 0.001) and level 2 having significantly lower scores compared to level 3 (P < 0.05). However, a PAI score of 5 was found in merely 3 teeth within the entire cohort, and 49% of the teeth in the level 2 group had no radiolucency (PAI < 3). Within level 2, the PAI scores were not dependent on tooth location but were substantially (P < 0.001) higher for teeth which had hurt for more than one week, and for root filled teeth. Conclusions: For the analysed, severely painful endodontically involved teeth, the clinically diagnosed main location of inflammation was reflected by the periapical index. PAI scores were not significantly influenced by anatomical noise, yet in some cases under‐estimated the clinical situation. [ABSTRACT FROM AUTHOR]

Black pepper in Sarawak, Malaysia, is mainly cultivated using the conventional method involving heavy usage of chemical compound fertilizers. Organic soil amendments can reduce the required amounts of chemical fertilizers. So, the objectives of this study were to compare selected properties of soils as well as the physiological performances of mature vines following the application of fermented juices, biochar, and compost. There were five treatments; each replicated five times in a randomized complete block design. Treatments were as follows: (i) FNPK–NPK 15 : 15 : 15 compound fertilizer; (ii) FPJ (fermented plant juice); (iii) FPJBC (FPJ, biochar, and compost); (iv) FFJ (fermented fruit juice); and (v) FFJBC (FFJ, biochar, and compost). The results revealed that combined fermented juices, biochar, and compost positively improved soil bulk density, soil porosity, TOC, C/N ratio, available P, exchangeable K, and exchangeable Ca. The fermented juices incorporated with biochar and compost had favourable effects on the leaf chlorophyll concentration, Normalized Difference Vegetation Index (NDVI), and gas exchange rates such as photosynthesis, stomatal conductance, and transpiration. Pepper leaf chlorophyll, NDVI, and photosynthesis rate were negatively correlated with soil total N. These results suggested that introducing organic soil amendments such as fermented juices, biochar, and compost improved soil physiochemical properties and black pepper physiological traits. [ABSTRACT FROM AUTHOR]

Aim: To study the impact of dentine cutting efficiency of rotary instruments on the lateral force they create when instrumenting simulated root canals in bovine dentine. Methodology: Lateral cutting efficiency of austenitic files (ProTaper Universal) was compared to that of counterparts of a reported identical geometrical design with a martensite phase component (ProTaper Gold) in bovine dentine disks (n = 6). Instrument shapes were studied using digital microscopy. The intracanal lateral force exerted by the two systems in simulated premolars (n = 9) made from bovine incisor roots containing a standardized narrow root canal of 16 mm length was monitored using a testing apparatus equipped with a torque‐controlled endodontic motor/handpiece. Data were compared using parametric statistics, alpha error = 0.05. Results: The geometrical design of the two systems under investigation was found to be identical. The martensitic nickel‐titanium rotary files had a significantly (t‐test, P < 0.05) higher lateral cutting efficiency than austenitic counterparts. This difference, however, did not impact the lateral force that was created when instrumenting simulated premolar root canals. Furthermore, lateral force peaks were generated with the progressively tapered instruments under investigation towards the full working length. Even though a glide path was prepared, the first instrument in the full‐length sequence (S1) created the highest lateral force (anova/Tukey's HSD, P < 0.05). Conclusions: The current experimental set‐up allows the study of the lateral force generated during root canal instrumentation. This force was not influenced by the dentine cutting efficiency of the instruments under investigation, but rather by their geometrical design. [ABSTRACT FROM AUTHOR]

Electroluminescent QD‐LEDs with heavy metal free InP and ZnTeSe quantum dots are one of the most promising future display technologies. Here we report improved efficiency of 19.6%, 17.6%, and 11.5% for red, green, and blue QD‐LEDs, respectively. The blue QD‐LEDs exhibit true blue emission with peak wavelength of 453 nm. [ABSTRACT FROM AUTHOR]

Aims: Colorectal carcinomas (CRC) with mismatch repair (MMR) deficiency have increased tumour mutation burden and respond to immune check‐point inhibitor therapy. The Cancer Genome Atlas identified hypermutated CRCs with somatic mutations in DNA polymerase ε (POLE) with mutation burdens exceeding that of MMR‐deficient CRCs. Methods and results: To identify the morphological, immunophenotypical and molecular features of POLE‐mutated CRCs, 63 consecutive MMR‐intact CRCs were evaluated by Sanger sequencing for POLE exonuclease domain mutations in exons 9, 11, 13 and 14 and confirmed by next‐generation sequencing. Tumour immune microenvironment and IMMUNOSCORE®1 were assessed in POLE‐mutated CRCs using immunohistochemistry to detect CD3+/CD8+ tumour‐infiltrating lymphocytes and compared to 59 non‐POLE mutated MMR‐intact CRC, 10 non‐POLE mutated MMR‐deficient CRCs and 223 normal colonic mucosa. Conclusions: A total of 4.8% CRC (four MMR‐intact primary and one MMR‐intact metastasis) harboured POLE mutations in amino acid 286 in exon 9 (p.P286R) or exon 13 (p.V411L). POLE‐mutated CRCs arose in the transverse colon and rectum, were male‐predominant, younger and showed increased tumour‐infiltrating lymphocytes and immune cells at the tumour–stromal interface. The patient with metastatic POLE‐mutated CRC was placed on PD‐1 inhibitor treatment with marked and sustained response. These data indicate that POLE‐mutated CRCs have hypermutated phenotypes despite MMR‐intact status, with mutation burdens higher than that in microsatellite‐unstable CRCs. Given the recent approval for treatment of microsatellite‐unstable cancer with immune check‐point inhibitors, assessment of POLE status may help to guide therapeutic decisions for hypermutated tumours with intact MMR that would otherwise be missed by routine testing. [ABSTRACT FROM AUTHOR]

Carbonyl‐olefin metathesis and carbonyl‐alkyne metathesis represent established reactivity modes between carbonyls, alkenes, and alkynes under Lewis and Brønsted acid catalysis. Recently, an interrupted carbonyl‐olefin metathesis reaction has been reported that results in tetrahydrofluorenes via a distinct fragmentation of the reactive intermediate. We herein report the development of an analogous transformation interrupting the carbonyl‐alkyne metathesis reaction path resulting in dihydrofluorene products relying on Lewis acidic superelectrophiles as active catalytic species. [ABSTRACT FROM AUTHOR]

Background: Liquid biopsy using cell‐free DNA (cfDNA) presents new opportunities for solid tumor genotyping. While studies have demonstrated the utility of cfDNA from plasma, cfDNA from other body fluids remains underexplored. Methods: We evaluated the molecular features and clinicopathologic correlates of cfDNA from serous body cavity fluids by performing hybrid capture‐based next‐generation sequencing (NGS) on cfDNA isolated from residual effusion supernatants. Twenty‐one serous effusions from pleural (n = 15), peritoneal (n = 5), and pericardial (n = 1) cavity were analyzed. Results: The supernatants provided a median cfDNA concentration of 10.3 ng/µL. Notably, all effusions were sequenced successfully to a median depth >1000×, revealing a broad range of genetic alterations including single nucleotide variants, small insertions and deletions, amplifications, and fusions. Specifically, pathogenic alterations were identified in all malignant fluids (13/13), all fluids suspicious for malignancy (2/2), and 1 benign fluid (1/6) from a patient with metastatic cancer. To validate our findings, we examined matching results from 11 patients who underwent additional testing using formalin‐fixed, paraffin‐embedded (FFPE) specimens. In 8 patients, the paired results between FFPE and supernatant testing were concordant, whereas in the remaining 3 patients, supernatant analysis identified additional variants likely associated with resistance to targeted therapies. Additional comparison between FFPE and supernatant testing showed no difference in DNA concentration (P =.5), depth of coverage (P =.6), or allele frequency of pathogenic mutations (P =.7). Conclusion: cfDNA isolated from serous body cavity fluids represents a promising source of genomic input for targeted NGS. We performed targeted next‐generation sequencing on cell‐free DNA isolated from serous body cavity fluids. By applying cell‐free DNA testing to residual effusion supernatants, our custom liquid biopsy allows for robust detection of clinically actionable genetic alterations from routinely discarded material and may serve as a potential alternative to formalin‐fixed, paraffin‐embedded specimens in select patients. [ABSTRACT FROM AUTHOR]

Aim: To assess whether Dual Rinse HEDP, an etidronate that can be combined with NaOCl to create an endodontic irrigating solution containing both hypochlorite and a chelator in the form of 1‐hydroxyethane 1,1‐diphosphonic acid (HEDP), alters the clinical efficacy of NaOCl or adds any untoward clinical effects. Methodology: In this randomized controlled double‐blind single‐centre trial, a pure NaOCl solution was compared to a HEDP‐containing counterpart regarding antimicrobial efficacy, postoperative pain, and the host response by means of changes in MMP‐9 levels in periapical fluid. Sixty patients presenting with asymptomatic apical periodontitis (one tooth each) were randomly divided into two groups (N = 30) based on irrigation regime. Pre‐ and post‐treatment microbial aerobic and anaerobic cultures and MMP‐9/total protein (TP) periapical fluid samples were collected. Postoperative pain levels were assessed 24 h after treatment. Categorical data were compared between groups using the Fisher's exact test, continuous data using the Wilcoxon signed‐rank test, α = 0.05. Results: Irrigation with pure NaOCl rendered 40% canals free of culturable microorganisms, compared to 50% with the NaOCl/HEDP mixture (P = 0.60). As assessed by matrix‐assisted laser desorption/ionization‐time‐of‐flight analysis (MALDI‐TOF), no apparent selection of aerobic or anaerobic taxa occurred in either group. One patient in the NaOCl group experienced moderate pain, whilst two patients in the NaOCl/HEDP group experienced mild postoperative pain. MMP‐9/TP levels in periapical fluid declined significantly (P < 0.001) after 1 week with no medication in the root canal, without significant difference between treatment groups (P > 0.05). Conclusions: This trial found no influence of HEDP on clinical NaOCl effects. [ABSTRACT FROM AUTHOR]

Aim: To test whether the incorporation of a chelation powder, etidronate, marketed for root canal irrigation (Dual Rinse HEDP) into a sodium hypochlorite (NaOCl) solution induced additional cytotoxic and genotoxic effects not observed with NaOCl alone. Methodology: Fresh and 24‐h‐old mixtures of 0.9 g of etidronate in 10 mL of 2.5% NaOCl were assessed for their basic chemical features including pH and the ability to chelate Ca2+ from hydroxylapatite. Pure NaOCl and phosphate‐buffered saline (PBS) with/without etidronate served as control solutions. Cytotoxic and genotoxic effects of diluted solutions (1:10, 1:100, and 1:1000) were assessed on Chinese hamster lung fibroblast (V79) using the MTT, clonogenic and micronucleus assays, respectively. One‐way ANOVA and Tukey's HSD test were applied with an alpha‐type error of 5% (P < 0.05). Results: In mixtures of NaOCl and etidronate, the free available chlorine was lost completely after 24 h, and the pH dropped by more than 3 units. However, the ability of the etidronate to chelate Ca2+ was maintained. The fresh mixtures of NaOCl and etidronate were not more toxic than NaOCl alone (P > 0.05), whilst the 24‐h‐old mixtures were less toxic (P < 0.05) and statistically similar to pure etidronate. Etidronate per se showed little cytotoxicity and no genotoxicity at the tested dilutions. Conclusions: The ability of the used etidronate, Dual Rinse HEDP, to chelate calcium is not affected by NaOCl. Cytotoxicity and genotoxicity of mixed solutions is dictated by the presence of free available chlorine therein. [ABSTRACT FROM AUTHOR]

This position statement on the management of deep caries and the exposed pulp represents the consensus of an expert committee, convened by the European Society of Endodontology (ESE). Preserving the pulp in a healthy state with sustained vitality, preventing apical periodontitis and developing minimally invasive biologically based therapies are key themes within contemporary clinical endodontics. The aim of this statement was to summarize current best evidence on the diagnosis and classification of deep caries and caries‐induced pulpal disease, as well as indicating appropriate clinical management strategies for avoiding and treating pulp exposure in permanent teeth with deep or extremely deep caries. In presenting these findings, areas of controversy, low‐quality evidence and uncertainties are highlighted, prior to recommendations for each area of interest. A recently published review article provides more detailed information and was the basis for this position statement (Bjørndal et al. 2019, International Endodontic Journal, doi:10.1111/iej.13128). The intention of this position statement is to provide the practitioner with relevant clinical guidance in this rapidly developing area. An update will be provided within 5 years as further evidence emerges. [ABSTRACT FROM AUTHOR]

In this paper we report on our progress on developing heavy metal free (or Cd‐free) QD‐LEDs for all three colors. With improvement in synthesis we have developed high quantum yield heavy metal free QDs (>95% for Red and Green; >80% for Blue) with peak wavelengths suitable for BT.2020. Building upon these high performance QDs and through novel device structure design and optimization we have demonstrated high efficiency heavy metal free QD‐LEDs with EQE=16.9%, 13%, 9% for Red, Green, Blue, respectively. [ABSTRACT FROM AUTHOR]

In this paper, we report on our progress on developing heavy metal free (or Cd‐free) QD‐LEDs for all three colors. With improvement in synthesis, we have developed high quantum yield heavy metal free quantum dots (more than 95% for red and green and more than 80% for blue), with peak wavelengths suitable for BT.2020. Building upon these high‐performance quantum dots and through novel device structure design and optimization we have demonstrated high efficiency heavy metal free QD‐LEDs with EQE = 16.9%, 13%, 9% for red, green, and blue, respectively. Specifically, we report a systematic study on the impact of shell thickness to the device efficiency performance. [ABSTRACT FROM AUTHOR]

Introduction: Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN‐RS‐T) is a rare disease in the 2016 revised World Health Organization (WHO) classification. Diagnostic criteria include the following: persistent thrombocytosis (>450 × 109/L) with clustering of atypical megakaryocytes, refractory anemia, dyserythropoiesis with ring sideroblasts, and the presence of the spliceosome factor 3b subunit (SF3B1) mutation. It is unclear if anemia should be a required criterion for this diagnosis as cases which show all other features of MDS/MPN‐RS‐T but without anemia exist. Methods: We searched for borderline cases of MDS/MPN‐RS‐T in which refractory anemia was absent at diagnosis in two major academic institutes. Results: Three cases without anemia were identified. These cases all showed other classic morphologic and clinical features of MDS/MPN‐RS‐T, including thrombocytosis, atypical megakaryocytes with clustering, and characteristic SF3B1 and JAK2 V617F mutations. Conclusion: Given these findings, the requirement of refractory anemia as a diagnostic criterion for MDS/MPN‐RS‐T should be re‐evaluated. Removal of refractory anemia as a diagnostic criterion would incorporate current borderline cases and extend the spectrum of this disorder. [ABSTRACT FROM AUTHOR]

Introduction: Platelet function disorders (PFD) are an important group of bleeding disorders that require validated and practical laboratory strategies for diagnosis. Methods: This review summarizes the authors' experiences, current literature, and an international survey to evaluate the practices of diagnostic laboratories that offer tests for PFD. Results: Blood counts, blood film review, and aggregation tests are the most commonly performed investigations for PFD and help determine whether there is thrombocytopenia and/or defective platelet function due to a variety of causes. The performance characteristics of tests for PFD, and the level of evidence that these tests detect bleeding problems, are important issues to determine where tests are useful for diagnostic or correlative purposes, or research only uses. Platelet aggregation assays, and quantitative analysis of platelet dense granule numbers, are tests with good performance characteristics that detect abnormalities associated with increased bleeding in a significant proportion of individuals referred for PFD investigations. Lumiaggregometry estimates of platelet adenosine triphosphate release show greater variability which limits the diagnostic usefulness. Diagnostic laboratories report that fiscal and other constraints, including a lack of high‐quality evidence, limit their ability to offer an expanded test menu for PFD. Conclusion: PFD are clinically important bleeding disorders that remain challenging for diagnostic laboratories to investigate. While some PFD tests are well validated for diagnostic purposes, gaps in scientific evidence and resource limitations influence diagnostic laboratory decisions on which PFD tests to offer. [ABSTRACT FROM AUTHOR]

Aim: To compare solutions of di‐ and tetrasodium ethylenediaminetetraacetic acid (EDTA) and 1‐hydroxyethane‐1,1‐diphosphonic acid (HEDP) regarding their ability to solubilize calcium from dentine and remove smear layer. Methodology: Solutions with a molarity corresponding to that of 17% Na2EDTA (pH adjusted to 8.5) were prepared by dissolving Na2 and Na4 salts of HEDP (etidronate), or Na4EDTA in deionized water. Standardized root dentine discs covered by a smear layer were prepared from human third molars. These discs (n = 10 per group) were immersed in test solutions or phosphate‐buffered saline for 1 min. The dissolved Ca2+ was determined by atomic absorption spectroscopy, apparently opened dentinal tubules by laser scanning microscopy and automated image analysis. Ca2+ values were compared between groups by parametric, tubular areas by nonparametric methods, α = 0.05. Results: Solutions prepared from the tetrasodium salts were alkaline (pH 11.3–11.4), whilst counterparts made from the disodium salts were acidic. The EDTA solutions dissolved more calcium than the HEDP counterparts (P < 0.05); solutions prepared with the disodium salts dissolved more calcium than those made from the tetrasodium salts (P < 0.05). There was a high correlation between dissolved calcium and the apparently opened tubular areas (Spearman's ρ = 0.81). Differences between groups regarding opened tubules were similar to those observed regarding the Ca2+ values, with a slightly reduced discerning power due to high variance. Conclusion: Calcium chelation and thus smear layer removal by EDTA and HEDP are influenced by pH. [ABSTRACT FROM AUTHOR]

The authors discuss the need for a review of diagnostic terminology and nomenclature utilized in the Endodontics field. They comment on problems with terms that the American Association of Endodontics created in the past including the avoidance of the term acute. They mention how chronic and atypical dental pain were not considered in the classification of periapical or pulpal conditions and instead were listed separately. They also discuss the evolution of diagnostic tools since the 1970s.

Abstract Although experiments are the gold standard for establishing causality, several threats can undermine the internal validity of experimental findings. In this article, we first discuss these threats, which include the lack of consequential decisions and outcomes, deception, demand effects and unfair comparisons, as well as issues concerning statistical validity (e.g., minimum sample size per cell, estimating variance correctly). We expose each problem, show potential solutions, and bring to the fore issues of relevance of the findings (i.e., external and ecological validity). Thereafter, we take stock of the state-of-the-science regarding validity threats using a representative sample of 468 recent experiments from 258 articles published in top-tier journals. We compare research practices in three fields of study—management, social psychology, and economics, which regularly use experimental research—to operations management, which has more recently begun to use the experimental paradigm. Our results underscore the importance for journals and authors to follow what we identify to be best-practice methodological suggestions (i.e., the "ten commandments" of experimental research). We show that—on average—markers of methodological rigor and generalizability positively and significantly predict the citations received by published articles. Finally, given that experiments are infeasible in some settings, we conclude with a brief review of often overlooked quasi-experimental designs, which are useful for generating strong counterfactuals and hence allow making causal claims in the field. [ABSTRACT FROM AUTHOR]

Objective: First rib resection is a well-recognized treatment option for thoracic outlet syndrome (TOS). In case of a vascular insufficiency that can be provoked and/or progressive neurologic symptoms without response to conservative treatment, surgical decompression of the space between the clavicle and the first rib is indicated. The aim of this paper is to present our experience with a new minimally invasive robotic approach using the da Vinci Surgical System®.Methods: Between January 2015 and October 2017, eight consecutive first rib resections in seven patients were performed at our institution. Four patients presented with neurologic (one bilateral), and three patients with vascular (venous) impairment. In all cases, a transthoracic robotic-assisted approach was used. The first rib was removed using a 3-port robotic approach with an additional 2-cm axillary incision in the first six patients. The latest resection was performed through only three thoracic ports.Results: Median operative time was 108 min, and the median hospital stay was 2 days. Postoperative courses were uneventful in all patients. Clinical follow-up examinations showed relief of symptoms in all nonspecific TOS patients, and duplex ultrasonography confirmed complete vein patency in the remaining patients 3 months after surgery.Conclusions: While there are limitations in conventional transaxillary, subclavicular and supraclavicular approaches in the first rib resection, the robotic method is not only less invasive but also allows better exposure and visualization of the first rib. Furthermore, the technique takes advantage of the benefits of the da Vinci Surgical System® in terms of 3D visualization and improved instrument maneuverability. Our early experience clearly demonstrates these advantages, which are also supported by the very good outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Natural products have historically been a major source of antibiotics and therefore novel scaffolds are constantly of interest. The lipoxazolidinone family of marine natural products, with an unusual 4‐oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow‐up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogues to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4‐oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To assess the stability of NaOCl solutions when combined with a novel product for clinical use, Dual Rinse HEDP, which contains etidronate (1‐hydroxyethane 1,1‐diphosphonate). Methodology: Mixtures of NaOCl solutions with Dual Rinse HEDP were prepared so that they initially contained 5.0%, 2.5% or 1.0% NaOCl and always 9.0% of dissolved Dual Rinse HEDP powder per total weight. NaOCl solutions alone were used as controls. The stability of these solutions over 8 h was assessed in transparent borosilicate glass bottles at ambient temperature (23 °C). Subsequently, the effects of heating (60 °C) or storing the solutions at 5 °C were studied in polypropylene syringes. NaOCl concentrations were measured by iodometric titration, that is free available chlorine contents. Experiments were performed in triplicate. Results: In the glass bottles at 23 °C, the 5.0% NaOCl/9.0% Dual Rinse HEDP solution lost 20% of the available chlorine after 1 h, whilst the corresponding 2.5% NaOCl and 1.0% NaOCl solutions retained this relative amount of available chlorine for 2 and 4 h, respectively. Results obtained in the glass bottles were similar to those achieved in the syringes. Heating of the NaOCl/Dual Rinse HEDP mixtures had a detrimental effect on available chlorine, with a complete loss after 1 h. In contrast, storing the NaOCl/Dual Rinse HEDP mixtures in a refrigerator at 5 °C kept the available chlorine high for 7 h, with the expected loss after a further hour of storage at 23 °C. Conclusions: Initial NaOCl concentration and temperature both affected short‐term storage stability of combined solutions containing Dual Rinse HEDP. [ABSTRACT FROM AUTHOR]

Aim To present a novel miniaturized and minimally invasive treatment approach for root canal localization in mandibular incisors with pulp canal calcification and apical periodontitis. Summary A 51-year-old male patient presented with pain from his mandibular incisors. The patient had a history of severe dental trauma over 30 years ago. Both mandibular central incisors (teeth 31, 41) were tender to percussion and had a yellowish discoloration. They did not respond to thermal and electrical sensitivity tests. Two periapical radiographs from different projections revealed severe pulp canal calcifications and signs of periapical periodontitis. To facilitate the 'Microguided Endodontics' technique, a CBCT and an intra-oral surface scan were aligned using special software. This allowed the virtual planning of optimal access cavities up to the apical third of the root. In this technique, a 3D-printed template guides a customized drill to the orifice of the root canal. After negotiation of the root canals, conventional root canal treatment was performed. This case report demonstrates that minimally invasive and apically extended access cavities are feasible in mandibular incisors with this technique. Key learning points The 'Microguided Endodontics' technique is a safe and minimally invasive method for root canal location and prevention of technical failures in anterior teeth with pulp canal calcification. [ABSTRACT FROM AUTHOR]

This paper reviews the role of Natural Farming as an ecological farming method to produce organically grown food of safe and high quality and at the same time improve soil quality and soil health. Currently, there is a dearth of information on the effects of Natural Farming approach on black pepper farms particularly in Sarawak, Malaysia. Previous studies on other crops had indicated positive outcome using the Natural Farming method. Thus, this paper discusses the essential role of effective microorganisms in Natural Farming and their potential in pepper cultivation. Through the action of effective microorganisms, this approach should be able to transform a degraded soil ecosystem into one that is fertile and has high nutrients availability. The mixed culture of effective microorganisms applied must be mutually compatible and coexist with one another to ensure its favorable establishment and interaction in the soil. Therefore, it is anticipated that introducing Natural Farming in black pepper cultivation can enhance the predominance of effective microorganisms in the soil, which in turn could lead to promising growth and yield of the crop. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the fracture behavior and marginal gap region of CAD/CAM fabricated lithium disilicate (L) and zirconium dioxide (Z) crowns using palatal venting (PV), pre‐cementation with custom analogs (CA), or conventional cementation technique (SP) with adhesive cement (A) or resin‐modified glass ionomer cement (B). Material and methods: Twelve groups (n = 6) were set according to material (L, Z), cement (A, B), and technique (PV, CA, SP). Specimens were thermo‐mechanical aged (TML), loaded until fracture (LF) and fracture patterns recorded. Marginal gap width and quality were assessed and compared to replicas obtained before and after TML. Results: Crown material significantly influenced LF with a mean of 1037.6 ± 282.4 N in L and 5356.3 ± 1207.0 N in Z groups (p < .001). Neither cement material nor cementation method affected the outcome. Fractures occurred along the mesial‐distal central fissure in both materials. Gap width before TML was 22.04 ± 13.42 μm for L and 19.98 ± 12.72 μm for Z specimens, with overall no influence of crown material, cement type, or method. Marginal cleanliness just below the polished implant shoulder reached 66.7%–88.9% with A, and 91.7%–100% with B, and tended to increase in all groups during TML indicating a decrease in excess cement. Implant‐crown junctions were cleaner with B compared to A (p ≤ .001) and along Z crown surfaces compared to L (p ≤ .007). Conclusions: Crown venting of lithium disilicate and zirconium dioxide crowns did not affect the fracture load and patterns. Complete cement removal was rare, and the observed particle ablation requires further clinical attention, particularly with submucosal margins. [ABSTRACT FROM AUTHOR]