Spontaneous omental infarction as a rare differential for right iliac fossa pain: A case report and review of the literature.

Omental infarction is a rare cause of acute abdominal pain, often benign and self-limiting. The significance of infarction lies in the fact that it can mimic other abdominal pathologies including appendicitis, cholecystitis, pancreatitis, or reflux disease. Diagnostic laparoscopy provides the definitive diagnosis of omental infarction, but it is invasive and limited due to resources. Computed tomography of the abdomen and pelvis has been considered the gold standard to diagnosing omental infarction when a non-invasive diagnostic approach is required. Additionally, ultrasound can also be used alternatively for children. Currently, there is no consensus in the diagnosis and management of patients with imaging-proven omental infarction. Spontaneous infarcted omentum must be considered by surgeons and radiologists as a rare cause of acute abdominal pain as patients can experience good outcomes with either conservative or operative approach. However, conservative management must only be considered in stable patients where alternative pathology is unlikely.

Applications of natural language processing tools in the surgical journey.

Background: Natural language processing tools are becoming increasingly adopted in multiple industries worldwide. They have shown promising results however their use in the field of surgery is under-recognised. Many trials have assessed these benefits in small settings with promising results before large scale adoption can be considered in surgery. This study aims to review the current research and insights into the potential for implementation of natural language processing tools into surgery. Methods: A narrative review was conducted following a computer-assisted literature search on Medline, EMBASE and Google Scholar databases. Papers related to natural language processing tools and consideration into their use for surgery were considered. Results: Current applications of natural language processing tools within surgery are limited. From the literature, there is evidence of potential improvement in surgical capability and service delivery, such as through the use of these technologies to streamline processes including surgical triaging, data collection and auditing, surgical communication and documentation. Additionally, there is potential to extend these capabilities to surgical academia to improve processes in surgical research and allow innovation in the development of educational resources. Despite these outcomes, the evidence to support these findings are challenged by small sample sizes with limited applicability to broader settings. Conclusion: With the increasing adoption of natural language processing technology, such as in popular forms like ChatGPT, there has been increasing research in the use of these tools within surgery to improve surgical workflow and efficiency. This review highlights multifaceted applications of natural language processing within surgery, albeit with clear limitations due to the infancy of the infrastructure available to leverage these technologies. There remains room for more rigorous research into broader capability of natural language processing technology within the field of surgery and the need for cross-sectoral collaboration to understand the ways in which these algorithms can best be integrated.

The Role of Medicinal Cannabis as an Emerging Therapy for Opioid Use Disorder.

This narrative review explores current insights into the potential use of medicinal cannabis-related products as an emerging therapy for opioid use disorder in the landscape of increasing knowledge about medicinal cannabis-based products, commercialisation and global legalisation. Preclinical studies have provided preliminary insight into the putative neurobiological mechanisms that underpin the potential for medicinal cannabis to be considered a therapeutic in opioid use disorder and addiction. With the progressive legalisation of cannabis in many jurisdictions worldwide, contemporary research has highlighted further evidence that medicinal cannabis may have efficacy in reducing cravings and withdrawal effects, and therefore may be considered as an adjunct or standalone to current medications for opioid use disorder. Despite this potential, the landscape of research in this space draws from a large number of observational studies, with a paucity of rigorous randomised controlled trials to ascertain a true understanding of effect size and safety profile. With current challenges in implementation that arise from political and legal qualms about adopting medicinal cannabis on the background of associated social stigma, significant hurdles remain to be addressed by government, policy-makers, healthcare providers and researchers before medical cannabis can be introduced globally for the treatment of opioid use disorder.

The aim of this review was to synthesise current evidence to understand how medicinal cannabis products may be able to tackle the signs, symptoms and outcomes related to opioid dependence. At the present time, opioid dependence is associated with a significant burden of disease and death in the community. Current treatment for opioid dependence includes supplying controlled-release opioids in a regulated (and often observed) manner in the community. However, despite the implementation of this strategy, the outcomes related to opioid use and dependence remain relatively unchanged, indicating that the current gold standard treatment is not as effective as it should be. Following the legalisation and commercialisation of medicinal cannabis, there has been increased research into the ways these products can be leveraged for different conditions and indications, including in opioid dependence. Given this context, in this narrative we explore this preliminary evidence and evaluate the steps required in further research and policy changes before more widespread implementation of medical cannabis can be considered.

Let-7i enhances anti-tumour immunity and suppresses ovarian tumour growth.

Cancer immunotherapy has seen significant success in the last decade for cancer management by enhancing endogenous cancer immunity. However, immunotherapies developed thus far have seen limited success in the majority of high-grade serous carcinoma (HGSC) ovarian cancer patients. This is largely due to the highly immunosuppressive tumour microenvironment of HGSC and late-stage identification. Thus, novel treatment interventions are needed to overcome this immunosuppression and complement existing immunotherapies. Here, we have identified through analysis of > 600 human HGSC tumours a critical role for Let-7i in modulating the tumoural immune network. Tumoural expression of Let-7i had high positive correlation with anti-cancer immune signatures in HGSC patients. Confirming this role, enforced Let-7i expression in murine HGSC tumours resulted in a significant decrease in tumour burden with a significant increase in tumour T cell numbers in tumours. In concert with the improved tumoural immunity, Let-7i treatment also significantly increased CD86 expression in antigen presenting cells (APCs) in the draining lymph nodes, indicating enhanced APC activity. Collectively, our findings highlight an important role of Let-7i in anti-tumour immunity and its potential use for inducing an anti-tumour effect in HGSC.

The impact of stapled compared to handsewn repair on anastomotic outcomes in trauma patients: a systematic review and meta-analysis.

BACKGROUND: Approach to enteric anastomotic technique has been a subject of debate, with no clear consensus as to whether handsewn or stapled techniques are superior in trauma settings, which are influenced by unique perturbances to important processes such as immune function, coagulation, wound healing and response to infection. This systematic review and meta-analysis compares the risk of anastomotic complications in trauma patients with gastrointestinal injury requiring restoration of continuity with handsewn versus staples approaches. METHODS: A comprehensive computer assisted search of electronic databases Medline, Embase and Cochrane Central was performed. Comparative studies evaluating stapled versus handsewn gastrointestinal anastomoses in trauma patients were included in this review. All anastomoses involving small intestine to small intestine, small to large intestine, and large intestine to large intestine were eligible. Anastomosis to the rectum was excluded. Outcomes evaluated were (1) anastomotic leak (AL) (2) a composite anastomotic complication (CAC) end point consisting of AL, enterocutaneous fistula (ECF) and deep abdominal abscess. RESULTS: Eight studies involving 931 patients were included and of these patients, data from 790 patients were available for analysis. There was no significant difference identified for anastomotic leak between the two groups (OR = 0.77; 95% CI 0.24-2.45; P = 0.66). There was no significant improvement in composite anastomotic complication; defined as a composite of anastomotic leak, deep intra-abdominal abscess and intra-abdominal fistula, in the stapled anastomosis group (OR = 1.05; 95% CI 0.53-2.09; P = 0.90). Overall, there was limited evidence to suggest superiority with handsewn or stapled anastomosis for improving AL or CAC, however this was based on studies of moderate to high risk of bias with poor control for confounders. DISCUSSION: This meta-analysis demonstrates no superiority improvement in anastomotic outcomes with handsewn or stapled repair. These findings may represent no effect in anastomotic outcome by technique for all situations. However, considering the paucity of information on potential confounders, perhaps there is a difference in outcome with overall technique or for specific subgroups that have not been described due to limited sample size and data on confounders. Currently, there is insufficient evidence to recommend an anastomotic technique in trauma.

A web-based tool for real-time adequacy assessment of kidney biopsies.

The escalating incidence of kidney biopsies providing insufficient tissue for diagnosis poses a dual challenge, straining the healthcare system and jeopardizing patients who may require rebiopsy or face the prospect of an inaccurate diagnosis due to an unsampled disease. Here, we introduce a web-based tool that can provide real-time, quantitative assessment of kidney biopsy adequacy directly from photographs taken with a smartphone camera. The software tool was developed using a deep learning-driven automated segmentation technique, trained on a dataset comprising nephropathologist-confirmed annotations of the kidney cortex on digital biopsy images. Our framework demonstrated favorable performance in segmenting the cortex via 5-fold cross-validation (Dice coefficient: 0.788±0.130) (n=100). Offering a bedside tool for kidney biopsy adequacy assessment has the potential to provide real-time guidance to the physicians performing medical kidney biopsies, reducing the necessity for re-biopsies. Our tool can be accessed through our web-based platform: http://www.biopsyadequacy.org.

The Impact of Glucagon-like Peptide 1 Receptor Agonists on Obstructive Sleep Apnoea: A Scoping Review.

BACKGROUND: Obstructive sleep apnoea (OSA) and associated hypopnoea syndromes are chronic conditions of sleep-disordered breathing with significant sequelae if poorly managed, including hypertension, cardiovascular disease, metabolic syndrome and increased mortality. Glucagon-like peptide 1 receptor agonists (GLP-1RA) have recently garnered significant interest as a potential therapeutic, attributed to their durable effects in weight loss and glycaemic control in metabolic syndromes, such as obesity and type 2 diabetes mellitus. This has led to significant investment into companies that produce these medications and divestment from traditional gold standard methods of OSA management such as continuous positive airway pressure machines. Despite these sentiments, the impacts of these medications on OSA outcomes are poorly characterised, with no high-quality evidence at this stage to support this hypothesis. This scoping review therefore aims to address the research question of whether GLP-1RAs lead to a direct improvement in OSA and associated hypopnoea syndromes. METHODS: A scoping review was performed following a computer-assisted search of Medline, Embase and Cochrane Central databases. Papers that evaluated the use of GLP-1RA medications related to sleep-disordered breathing, OSA or other sleep-related apnoeic or hypopnoeic syndromes were included. RESULTS: Literature search and evaluation identified 9 articles that were eligible for inclusion. Of these, 1 was a study protocol, 1 was a case report, 1 was an abstract of a randomised controlled trial (RCT), 1 was a non-randomised clinical trial and the remaining 5 were randomised clinical trials of variable rigour. All studies evaluated the outcomes of GLP-1RAs in patients with diagnosed OSA or symptoms suggestive of this condition. CONCLUSION: This scoping review identified early evidence to suggest that GLP-1RAs may improve OSA as defined by reduction in apnoea-hypopnoea index (AHI). This evidence is however conflicting due to contradicting results demonstrated from other studies. Overall, these medications were tolerated well, with minor gastrointestinal side-effects reported in some cases. Of all included studies, the quality of evidence was low, with short lengths of follow-up to identify durable effects of these medications on OSA outcomes and identify adverse events. More rigorous, RCTs with sufficient length of follow-up are required before consideration of formalising these medications into OSA treatment guidelines, frameworks and policies are warranted.

Intravenous methadone in the management of acute postoperative pain in a chronic cancer pain patient: A case report and review of the literature.

Key Clinical Message: The current landscape of literature highlights that there is insufficient well-powered and robust evidence to support the integration of intravenous methadone into current guidelines and frameworks in supporting the pain management of cancer patient with complex pain syndromes. However, there is preliminary evidence, both from the literature as well as this case study that highlights intravenous methadone may be efficaciously and safety used for the management of postoperative pain in cancer patients with chronic pain undergoing operative management. Further research is required to fully elucidate key considerations of integrating this medication into clinical practice including consideration into dosing, opioid conversion, tolerance, and safety. Abstract: Methadone is a broad-spectrum analgesic with long duration of effect. Its multimodal mechanism of action, such as through effects on mu-opioid receptor and presynaptic N-methyl-D-aspartate receptors, has led to its current use in the management of opioid dependence in the community and in palliative care. These properties however make methadone appealing in the management of postoperative pain, particularly for patients with complex analgesic requirements. We report on an interesting case whereby intravenous methadone was effectively used for postoperative analgesia in a 56-year-old female with complex chronic pain secondary to a mucinous pelvic neoplasm of unclear primary who underwent palliative resection. Further, we review the literature surrounding usage of methadone in this setting to understand current challenges and barriers to implementation of methadone as an analgesia option for chronic pain patients following surgery. To do this, a case report and literature review was conducted in accordance to the CARE case report guidelines. The patient provided written consent for the de-identification and use of their medical information and data for the generation and publication of this case report. Our case report and literature review demonstrate there remains significant heterogeneity, unfamiliarity, and scarce use of intravenous methadone in the perioperative and postoperative space in the management of patients with complex pain regimens such as chronic cancer pain patients. Despite this, our case report and literature review highlight as a broad analgesic, intravenous methadone warrants consideration following more rigorous research and development of safe use guidelines into its use for this purpose.

Principles of Effective Simulation-Based Teaching Sessions in Medical Education: A Narrative Review.

A challenge for medical educators is to provide learning opportunities that allow students to develop technical and non-technical skills as set by the clearly defined learning objectives within their relevant institutions. This is particularly relevant in clinical education, which encompasses a vast majority of medical education. Specifically, clinical education is highly variable, with numerous distractions, interruptions and variability in learning experience and quality of clinical educators which often result in underprepared medical students by the time they transition into clinical practice. Simulation-based teaching (SBT) has been a key pedagogical approach that has been implemented into curriculum design to assist with addressing some of these educational challenges. However, their implementation is highly variable, and research into evidence-based best practice considerations in SBT design and implementation is fundamental to their success in medical student development. A narrative review was performed following a computer-assisted search on electronic databases Medline, Embase and Google Scholar. Relevant papers that explored the role of SBT in medical education were considered for this review. SBT is an important pedagogical approach to support the education of medical students. Their use has the benefit of providing a standardised and safe environment that mimics 'real life' as a means of allowing students to hone key skills with respect to clearly defined learning outcomes. The role of debriefing and feedback is crucial to the development of efficacious SBT programs, and therefore the upskilling and training of educators is a key aspect of evidence-based SBT design. Despite this, medical educators must be cognisant of the limitations of SBT. These include the cost and resources required to develop and implement SBT sessions, the effort and conceptualisation required to standardise and ensure these programs reflect real-life situations as well as the degree of training for facilitators to ensure they can best deliver and achieve learning outcomes and provide effective debriefing and feedback for students. Understanding the educational frameworks and the evidence-based best practice principles for SBT design and implementation is highly necessary for medical educators given the resource demands of SBT programs.

Atom-Based Machine Learning Model for Quantitative Property-Structure Relationship of Electronic Properties of Fusenes and Substituted Fusenes.

This study presents the development of machine-learning-based quantitative structure-property relationship (QSPR) models for predicting electron affinity, ionization potential, and band gap of fusenes from different chemical classes. Three variants of the atom-based Weisfeiler-Lehman (WL) graph kernel method and the machine learning model Gaussian process regressor (GPR) were used. The data pool comprises polycyclic aromatic hydrocarbons (PAHs), thienoacenes, cyano-substituted PAHs, and nitro-substituted PAHs computed with density functional theory (DFT) at the B3LYP-D3/6-31+G(d) level of theory. The results demonstrate that the GPR/WL kernel methods can accurately predict the electronic properties of PAHs and their derivatives with root-mean-square deviations of 0.15 eV. Additionally, we also demonstrate the effectiveness of the active learning protocol for the GPR/WL kernel methods pipeline, particularly for data sets with greater diversity. The interpretation of the model for contributions of individual atoms to the predicted electronic properties provides reasons for the success of our previous degree of π-orbital overlap model.

Accuracy of Subthalamic Nucleus Electrode Implantation in Deep Brain Stimulation Surgery for Parkinson's Disease Treatment and Affecting Factors: Outcomes at Two Centers in Vietnam.

BACKGROUND: Deep brain stimulation (DBS) surgery for Parkinson's Disease (PD) has become more and more popular in Vietnam. However, the accuracy of implantation and affecting factors are under investigation. The objective of this study is to evaluate the accuracy of the subthalamic nucleus (STN)-DBS electrode implantation technique for treatment PD at Nguyen Tri Phuong Hospital and University Medical Center. To investigate factors related to accuracy. METHODS: We carried out a retrospective analysis of 58 patients with advanced PD who underwent STN-DBS surgery at Nguyen Tri Phuong Hospital and University Medical Center in Ho Chi Minh City, Viet Nam between June 2014 and July 2021 (115 leads total). All patients underwent the procedure with standard frame-based techniques under local anesthesia with microelectrode recording and macrostimuation test. RESULTS: Twenty-six female (44.8%) and thirty-two male (55.2%) patients with a mean age of 60.4 ± 8.3 years old (40-76 years) were included. Of total of 115 electrodes implanted, the mean target error (ΔT), radial error (ΔR), angle error (Δθ) were 1.94 ± 0.73 mm; 1.16 ± 0.69 mm; 2.22 ± 4.24 degrees, respectively. Vector error on each coordinate axis ΔX, ΔY, ΔZ were -0.35 ± 1.02 mm, +0.99 ± 0.82 mm, +0.73 ± 0.99 mm, respectively. There was a statistically significant correlation between subdural air volume, cortical shift, intracranial electrode bending, and accuracy. CONCLUSIONS: The current STN-DBS electrode implantation technique applied in our centers was quite accurate with acceptable error. More clinical trials are necessary to directly compare affecting factors to the accuracy of electrode implantation.

Immune mediated colitis: a surgical perspective.

BACKGROUND: This study aims to review and summarize the current up to date literature that explore the current treatment approaches to immune mediated colitis and the role of surgical specialties in the landscape of management. METHODS: A narrative review of papers was performed following a literature search through Medline, EMBASE and Cochrane Central databases pertaining to immune mediated colitis as an adverse event of cancer immunotherapy. RESULTS: Current guidelines for the diagnosis and treatment of immune mediated colitis mirror the approach to the workup of inflammatory bowel disease and guided by treating oncology and gastroenterology specialties. Immune mediated colitis however relies on surgical specific skills as a consequence of obtaining a diagnosis as well as in the management of complications that may arise. CONCLUSION: Immune mediate colitis management has largely been under the purview of medical specialties. This review explores the current landscape of managing immune mediated colitis from a surgical perspective and highlights key areas in which surgeons can engage in the multidisciplinary care of this condition. To facilitate prompt diagnosis and management of immune-mediated colitis, there is an increasing necessity for surgeons to become familiar with the latest multidisciplinary approaches and recommendations.

Machine Learning-Based Quantitative Structure-Property Relationships for the Electronic Properties of Cyano Polycyclic Aromatic Hydrocarbons.

In this study, quantitative structure-property relationships (QSPR) based on a machine learning (ML) methodology and the truncated degree of π-orbital overlap (DPO) to predict the electronic properties, namely, the bandgaps, electron affinities, and ionization potentials of the cyano polycyclic aromatic hydrocarbon (CN-PAH) chemical class were developed. The level of theory B3LYP/6-31+G(d) of density functional theory (DFT) was used to calculate a total of 926 data points for the development of the QSPR model. To include the substituents effects, a new descriptor was added to the DPO model. Consequently, the new ML-DPO model yields excellent linear correlations to predict the desired electronic properties with high accuracy to within 0.2 eV for all multi-CN-substituted PAHs and 0.1 eV for the mono-CN-substituted PAH subclass.

The Therapeutic Potential of Cannabidiol in Revolutionising Opioid Use Disorder Management.

Opioid use disorder (OUD) is a significant cause of morbidity and mortality worldwide and is linked to a complex interplay of biopsychosocial factors as well as the increasing overprescription and availability of opioid medications. Current OUD management relies on the controlled provision of opioid medications, such as methadone or buprenorphine, known as opioid replacement therapy. There is variable evidence regarding the long-term efficacy of these medications in improving the management of OUD, thereby necessitating an exploration into innovative approaches to complement, or even take the place of, existing treatment paradigms. Cannabidiol (CBD), a non-psychoactive compound derived from the cannabis plant, has garnered attention for its diverse pharmacological properties, including anti-inflammatory, analgesic, and anxiolytic effects. Preliminary studies suggest that CBD may target opioid withdrawal pathways that make CBD a potential therapeutic option for OUD. This narrative review synthesises current literature surrounding OUD and offers a nuanced review of the current and future role of CBD in managing this condition. In doing so, we highlight the potential avenues to explore with respect to CBD research for the guidance and development of further research opportunities, framework and policy development, and clinical considerations before medicinal CBD can be integrated into evidence-based clinical guidelines.

Dose-related shifts in proteome and function of extracellular vesicles secreted by fetal neural stem cells following chronic alcohol exposure.

Accumulating evidence indicates that extracellular vesicles (EVs) mediate endocrine functions and also pathogenic effects of neurodevelopmental perturbagens like ethanol. We performed mass-spectrometry on EVs secreted by fetal murine cerebral cortical neural stem cells (NSCs), cultured ex-vivo as sex-specific neurosphere cultures, to identify overrepresented proteins and signaling pathways in EVs relative to parental NSCs in controls, and following exposure of parental NSCs to a dose range of ethanol. EV proteomes differ substantially from parental NSCs, and though EVs sequester proteins across sub-cellular compartments, they are enriched for distinct morphogenetic signals including the planar cell polarity pathway. Ethanol exposure favored selective protein sequestration in EVs and depletion in parental NSCs, and also resulted in dose-independent overrepresentation of cell-cycle and DNA replication pathways in EVs as well as dose-dependent overrepresentation of rRNA processing and mTor stress pathways. Transfer of untreated EVs to naïve cells resulted in decreased oxidative metabolism and S-phase, while EVs derived from ethanol-treated NSCs exhibited diminished effect. Collectively, these data show that NSCs secrete EVs with a distinct proteome that may have a general growth-inhibitory effect on recipient cells. Moreover, while ethanol results in selective transfer of proteins from NSCs to EVs, the efficacy of these exposure-derived EVs is diminished.

Influenza virus infection history shapes antibody responses to influenza vaccination.

Studies of successive vaccination suggest that immunological memory against past influenza viruses may limit responses to vaccines containing current strains. The impact of memory induced by prior infection is rarely considered and is difficult to ascertain, because infections are often subclinical. This study investigated influenza vaccination among adults from the Ha Nam cohort (Vietnam), who were purposefully selected to include 72 with and 28 without documented influenza A(H3N2) infection during the preceding 9 years (Australian New Zealand Clinical Trials Registry 12621000110886). The primary outcome was the effect of prior influenza A(H3N2) infection on hemagglutinin-inhibiting antibody responses induced by a locally available influenza vaccine administered in November 2016. Baseline and postvaccination sera were titrated against 40 influenza A(H3N2) strains spanning 1968-2018. At each time point (baseline, day 14 and day 280), geometric mean antibody titers against 2008-2018 strains were higher among participants with recent infection (34 (29-40), 187 (154-227) and 86 (72-103)) than among participants without recent infection (19 (17-22), 91 (64-130) and 38 (30-49)). On days 14 and 280, mean titer rises against 2014-2018 strains were 6.1-fold (5.0- to 7.4-fold) and 2.6-fold (2.2- to 3.1-fold) for participants with recent infection versus 4.8-fold (3.5- to 6.7-fold) and 1.9-fold (1.5- to 2.3-fold) for those without. One of 72 vaccinees with recent infection versus 4 of 28 without developed symptomatic A(H3N2) infection in the season after vaccination (P = 0.021). The range of A(H3N2) viruses recognized by vaccine-induced antibodies was associated with the prior infection strain. These results suggest that recall of immunological memory induced by prior infection enhances antibody responses to inactivated influenza vaccine and is important to attain protective antibody titers.

Liquid biopsy uncovers distinct patterns of DNA methylation and copy number changes in NSCLC patients with different EGFR-TKI resistant mutations.

Targeted therapy with tyrosine kinase inhibitors (TKI) provides survival benefits to a majority of patients with non-small cell lung cancer (NSCLC). However, resistance to TKI almost always develops after treatment. Although genetic and epigenetic alterations have each been shown to drive resistance to TKI in cell line models, clinical evidence for their contribution in the acquisition of resistance remains limited. Here, we employed liquid biopsy for simultaneous analysis of genetic and epigenetic changes in 122 Vietnamese NSCLC patients undergoing TKI therapy and displaying acquired resistance. We detected multiple profiles of resistance mutations in 51 patients (41.8%). Of those, genetic alterations in EGFR, particularly EGFR amplification (n = 6), showed pronounced genome instability and genome-wide hypomethylation. Interestingly, the level of hypomethylation was associated with the duration of response to TKI treatment. We also detected hypermethylation in regulatory regions of Homeobox genes which are known to be involved in tumor differentiation. In contrast, such changes were not observed in cases with MET (n = 4) and HER2 (n = 4) amplification. Thus, our study showed that liquid biopsy could provide important insights into the heterogeneity of TKI resistance mechanisms in NSCLC patients, providing essential information for prediction of resistance and selection of subsequent treatment.

Discovery of new genetic determinants of morphological plasticity in rice roots and shoots under phosphate starvation using GWAS.

Phosphorus is an essential nutrient for plants that is often in short supply. In rice (Oryza sativa L.), inorganic phosphate (Pi) deficiency leads to various physiological disorders that consequently affect plant productivity. In this study, a large-scale phenotyping experiment using 160 Vietnamese rice landraces was performed under greenhouse conditions, by employing an alpha lattice design with three replicates, to identify quantitative trait loci (QTLs) associated with plant growth inhibition caused by Pi deficiency. Rice plantlets were grown for six weeks in the PVC sand column (16 cm diameter × 80 cm height) supplied with Pi-deficient medium (10 µM P) or full-Pi Yoshida medium (320 µM P). The effects of Pi deficiency on the number of crown roots, root length, shoot length, root weight, shoot weight and total weight were studied. From 36 significant markers identified using a genome-wide association study, 21 QTLs associated with plant growth inhibition under Pi starvation were defined. In total, 158 candidate genes co-located with the defined QTLs were identified. Interestingly, one QTL (qRST9.14) was associated with all three weight-traits. The co-located gene GLYCEROPHOSPHODIESTER PHOSPHODIESTERASE 13 was found to be potentially involved in Pi transport. Understanding the molecular mechanisms of Pi-starvation responses, and identifying the potential QTLs responsible for low-Pi stress tolerance, will provide valuable information for developing new varieties tolerant of low-Pi conditions.

A genome-wide association study reveals the quantitative trait locus and candidate genes that regulate phosphate efficiency in a Vietnamese rice collection.

The crucial role of phosphate (Pi) for plant alongside the expected depletion of non-renewable phosphate rock have created an urgent need for phosphate-efficient rice varieties. In this study, 157 greenhouse-grown Vietnamese rice landraces were treated under Pi-deficient conditions to discover the genotypic variation among biochemical traits, including relative efficiency of phosphorus use (REP), relative root to shoot weight ratio (RRSR), relative physiological phosphate use efficiency (RPPUE), and relative phosphate uptake efficiency (RPUpE). Plants were grown in Yoshida nutrient media with either a full (320 µM) or a low Pi supply (10 µM) over six weeks. This genome-wide association study led to the discovery of 31 significant single nucleotide polymorphisms, 18 quantitative trait loci (QTLs), and 85 candidate genes. A common QTL named qRPUUE9.16 was found among the three investigated traits. Some interesting candidate genes, such as PLASMA MEMBRANE PROTEIN1 (OsPM1), CALMODULIN-RELATED CALCIUM SENSOR PROTEIN 15 (OsCML15), phosphatases 2C (PP2C), STRESS-ACTIVATED PROTEIN KINASE (OsSAPK2), and GLYCEROPHOSPHORYL DIESTER PHOSPHODIESTERASES (GDPD13), were found strongly correlated to the Pi starvation. RNA sequencing transcriptomes revealed that 45 out of 85 candidate genes were significantly regulated under Pi starvation. Furthermore, nearly two-thirds of genotypes did not possess the OsPsTOL1 gene; however, no significant difference was observed in response to Pi deficiency between genotypes with or without this gene, suggesting that other QTLs in rice may resist Pi starvation. These results provide new information on the genetics of nutrient use efficiency in rice and may potentially assist with developing more phosphate-efficient rice plants.

Healing of Periapical Lesions after Endodontic Treatment with the GentleWave Procedure: A Prospective Multicenter Clinical Study.

INTRODUCTION: This report includes outcomes for a group of patients with significant periapical lesions who were treated and evaluated in two single-arm, multicenter, prospective, nonsignificant risk clinical studies. METHODS: Forty-five teeth were from 45 patients who met the inclusion criteria and consented for the clinical studies and were diagnosed with periapical lesions with periapical index score ≥3. Patients were treated with a standardized treatment protocol including instrumentation to an apical diameter of #20 without orifice enlargement, the GentleWave Procedure, and warm vertical obturation. Clinical signs and radiographic assessments were evaluated at 12 months to assess healing. Success was classified as healing or healed and accounted for the cumulative success rate of healing. Statistical analyses were performed by using Fisher exact test, Pearson correlation, and multivariate logistic regression analyses. RESULTS: At 12 months, 44 of 45 teeth (97.8%) were evaluated. The cumulative success rate for the GentleWave Procedure was 97.7%. Forty-three of 44 teeth were completely functional; all teeth had complete resolution for measured indices of mobility, soft tissue lesions, sinus tract, and furcation involvement. No patients experienced moderate or severe pain at 2, 7, and 14 days after procedure. Although only 1 patient was unsuccessful and the presence of clinical symptoms and type of periradicular diagnosis at 12 months were correlated with an unsuccessful outcome, the analyses were limited by the sample size. CONCLUSIONS: In this case series analysis, treatment of sizable periapical lesions with the GentleWave Procedure resulted in a success rate of 97.7% at 12-month re-evaluation.