Compensatory Modulation of Seed Storage Protein Synthesis and Alteration of Starch Accumulation by Selective Editing of 13 kDa Prolamin Genes by CRISPR-Cas9 in Rice.

Rice prolamins are categorized into three groups by molecular size (10, 13, or 16 kDa), while the 13 kDa prolamins are assigned to four subgroups (Pro13a-I, Pro13a-II, Pro13b-I, and Pro13b-II) based on cysteine residue content. Since lowering prolamin content in rice is essential to minimize indigestion and allergy risks, we generated four knockout lines using CRISPR-Cas9, which selectively reduced the expression of a specific subgroup of the 13 kDa prolamins. These four mutant rice lines also showed the compensatory expression of glutelins and non-targeted prolamins and were accompanied by low grain weight, altered starch content, and atypically-shaped starch granules and protein bodies. Transcriptome analysis identified 746 differentially expressed genes associated with 13 kDa prolamins during development. Correlation analysis revealed negative associations between genes in Pro13a-I and those in Pro13a-II and Pro13b-I/II subgroups. Furthermore, alterations in the transcription levels of 9 ER stress and 17 transcription factor genes were also observed in mutant rice lines with suppressed expression of 13 kDa prolamin. Our results provide profound insight into the functional role of 13 kDa rice prolamins in the regulatory mechanisms underlying rice seed development, suggesting their promising potential application to improve nutritional and immunological value.

The 2023 Annual Report of DataDerm™: The Database of The American Academy of Dermatology (AAD).

The American Academy of Dermatology (AAD) launched DataDerm™ in 2016 as the clinical data registry platform of AAD. DataDerm has evolved to be the largest database in the world containing information about dermatology patients, capturing information about their course of disease, associated therapeutic interventions, and health outcomes. As of December 31, 2022, DataDerm contained data from 14.2 million unique patients and 53.5 million unique patient visits, with 415 practices representing 1,663 clinicians actively participating in DataDerm in 2022. This article is the fourth in a series of Annual Reports about the status of DataDerm. This year's 2023 annual report presents the progress DataDerm has made in conjunction with OM1, the data analytics partner of DataDerm, with a special highlight on the longitudinal care of common dermatologic conditions in the registry and a detailed focus on skin cancer. Furthermore, we review the current status of DataDerm as a robust representation of real world specialty data, reflecting the day-to-day dermatologic care of patients over time.

A Rare Case of Panton-Valentine Leukocidin-Related Cervical Empyema.

Staphylococcus aureus is found in the normal skin and mucosa of approximately 30% of healthy populations and is the most common pathogen in human disease associated with bacteria. They are divided into methicillin-sensitive S . aureus (MSSA) and methicillin-resistant S. aureus (MRSA). The S. aureus strains carrying the Panton-Valentine leukocidin genes (SA-PVL) were initially believed to belong to the MRSA group; however, recent reports showed they also belonged to the MSSA group (MSSA-PVL). SA-PVL is common in skin and soft-tissue infections but rare in musculoskeletal infections, especially in spondylodiscitis. We are reporting a case suffering from cervical spondylodiscitis and epidural abscess associated with MSSA carrying the Panton-Valentine leukocidin genes.

Graphene and metal-organic framework hybrids for high-performance sensors for lung cancer biomarker detection supported by machine learning augmentation.

Conventional diagnostic methods for lung cancer, based on breath analysis using gas chromatography and mass spectrometry, have limitations for fast screening due to their limited availability, operational complexity, and high cost. As potential replacement, among several low-cost and portable methods, chemoresistive sensors for the detection of volatile organic compounds (VOCs) that represent biomarkers of lung cancer were explored as promising solutions, which unfortunately still face challenges. To address the key problems of these sensors, such as low sensitivity, high response time, and poor selectivity, this study presents the design of new chemoresistive sensors based on hybridised porous zeolitic imidazolate (ZIF-8) based metal-organic frameworks (MOFs) and laser-scribed graphene (LSG) structures, inspired by the architecture of the human lung. The sensing performance of the fabricated ZIF-8@LSG hybrid sensors was characterised using four dominant VOC biomarkers, including acetone, ethanol, methanol, and formaldehyde, which are identified as metabolomic signatures in lung cancer patients' exhaled breath. The results using simulated breath samples showed that the sensors exhibited excellent performance for a set of these biomarkers, including fast response (2-3 seconds), a wide detection range (0.8 ppm to 50 ppm), a low detection limit (0.8 ppm), and high selectivity, all obtained at room temperature. Intelligent machine learning (ML) recognition using the multilayer perceptron (MLP)-based classification algorithm was further employed to enhance the capability of these sensors, achieving an exceptional accuracy (approximately 96.5%) for the four targeted VOCs over the tested range (0.8-10 ppm). The developed hybridised nanomaterials, combined with the ML methodology, showcase robust identification of lung cancer biomarkers in simulated breath samples containing multiple biomarkers and a promising solution for their further improvements toward practical applications.

Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies.

BACKGROUND: Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period. MAIN FINDINGS: We conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0-89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13-45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5-28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count < 4000/mL). SHORT CONCLUSION: CP therapy can be considered a potentially effective and relatively safe therapeutic option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors).

Nanocarrier systems loaded with IR780, iron oxide nanoparticles and chlorambucil for cancer theragnostics.

Theragnostics has become a popular term nowadays, since it enables both diagnosis and therapy at the same time while only using one carrier platform. Therefore, formulating a nanocarrier system that could serve as theragnostic agent by using simple techniques would be an advantage during production. In this project, we aimed to develop a nanocarrier that can be loaded with the chemotherapeutic medication chlorambucil and magnetic resonance imaging agents (e.g., iron oxide nanoparticles and near-infrared fluorophore IR780) for theragnostics. Poly(lactic-co-glycolic acid) was combined with the aforementioned ingredients to generate poly(vinyl alcohol)-based nanoparticles (NPs) using the single emulsion technique. Then the NPs were coated with F127 and F127-folate by simple incubation for five days. The nanoparticles have the hydrodynamic size of approx. 250 nm with negative charge. Similar to chlorambucil and IR780, iron oxide loadings were observed for all three kinds of NPs. The release of chlorambucil was quicker at pH 5.4 than at pH 7.4 at 37 °C. The F127@NPs and F127-folate@NPs demonstrated much greater cell uptake and toxicity up to 72 h after incubation. Our in vitro results of F127@NPs and F127-folate@NPs have demonstrated the ability of these systems to serve as medication and imaging agent carriers for cancer treatment and diagnostics, respectively.

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

A genome-wide association study of contralateral breast cancer in the Women's Environmental Cancer and Radiation Epidemiology Study.

BACKGROUND: Contralateral breast cancer (CBC) is the most common second primary cancer diagnosed in breast cancer survivors, yet the understanding of the genetic susceptibility of CBC, particularly with respect to common variants, remains incomplete. This study aimed to investigate the genetic basis of CBC to better understand this malignancy. FINDINGS: We performed a genome-wide association analysis in the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study of women with first breast cancer diagnosed at age < 55 years including 1161 with CBC who served as cases and 1668 with unilateral breast cancer (UBC) who served as controls. We observed two loci (rs59657211, 9q32, SLC31A2/FAM225A and rs3815096, 6p22.1, TRIM31) with suggestive genome-wide significant associations (P < 1 × 10-6). We also found an increased risk of CBC associated with a breast cancer-specific polygenic risk score (PRS) comprised of 239 known breast cancer susceptibility single nucleotide polymorphisms (SNPs) (rate ratio per 1-SD change: 1.25; 95% confidence interval 1.14-1.36, P < 0.0001). The protective effect of chemotherapy on CBC risk was statistically significant only among patients with an elevated PRS (Pheterogeneity = 0.04). The AUC that included the PRS and known breast cancer risk factors was significantly elevated. CONCLUSIONS: The present GWAS identified two previously unreported loci with suggestive genome-wide significance. We also confirm that an elevated risk of CBC is associated with a comprehensive breast cancer susceptibility PRS that is independent of known breast cancer risk factors. These findings advance our understanding of genetic risk factors involved in CBC etiology.

A clinical marker-based modeling framework to preoperatively predict lymph node and vascular space involvement in endometrial cancer patients.

INTRODUCTION: Endometrial cancer (EC) has high mortality at advanced stages. Poor prognostic factors include grade 3 tumors, deep myometrial invasion, lymph node metastasis (LNM), and lymphovascular space invasion (LVSI). Preoperative knowledge of patients at higher risk of lymph node involvement, when such involvement is not suspected, would benefit surgery planning and patient prognosis. This study implements an ensemble machine learning approach that evaluates Cancer Antigen 125 (CA125) along with histologic type, preoperative grade, and age to predict LVSI, LNM and stage in EC patients. METHODS: A retrospective chart review spanning January 2000 to January 2015 at a regional hospital was performed. Women 18 years or older with a diagnosis of EC and preoperative or within one-week CA125 measurement were included (n = 842). An ensemble machine learning approach was implemented based on a stacked generalization technique to evaluate CA125 in combination with histologic type, preoperative grade, and age as predictors, and LVSI, LNM and disease stage as outcomes. RESULTS: The ensemble approach predicted LNM and LVSI in EC patients with AUROCTEST of 0.857 and 0.750, respectively, and predicted disease stage with AUROCTEST of 0.665. The approach achieved AUROCTEST for LVSI and LNM of 0.750 and 0.643 for grade 1 patients, and of 0.689 and 0.952 for grade 2 patients, respectively. CONCLUSION: An ensemble machine learning approach offers the potential to preoperatively predict LVSI, LNM and stage in EC patients with adequate accuracy based on CA125, histologic type, preoperative grade, and age.

Stomach-partitioning versus conventional gastrojejunostomy for unresectable gastric cancer with gastric outlet obstruction: A propensity score matched cohort study.

BACKGROUND: Stomach partitioning gastrojejunostomy (SPGJ) was introduced to deal with delayed gastric emptying (DGE). This study aimed to compare the short- and long-term outcomes of SPGJ versus conventional gastrojejunostomy (CGJ). METHOD: This cohort study analyzed 108 patients who underwent gastrojejunostomy for unresectable gastric cancer: 70 patients underwent SPGJ, and 38 patients underwent CGJ between 2018 and 2022. Propensity score-matched (PSM) analysis was used to balance the baseline characteristics. RESULTS: After PSM, there were 26 patients in each group. SPGJ group had significantly lower incidence of DGE (3.8% vs. 34.6%), vomiting (3.8% vs. 42.3%), and prokinetics requirement (11.5% vs. 46.2%). SPGJ group had significantly shorter time to solid diet tolerance (4.1 days vs. 5.7 days) and postoperative hospital stay (7.7 days vs. 9.3 days). There was no significant difference in relapse reinterventions, gastric outlet obstruction (GOO) recurrence, conversion surgery, and survival outcomes. CONCLUSIONS: SGPJ was associated with lower rate of DGE, prokinetics requirement, and shorter time of solid diet tolerance compared to CGJ in the treatment of unresectable gastric cancer patients with GOO.

Treatment Patterns of Long-Acting Somatostatin Analogs for Neuroendocrine Tumors.

Background: Long-acting somatostatin analog therapy (LA-SSA) is recommended as first-line therapy for treatment of unresectable or metastatic neuroendocrine tumors (NETs). Understanding treatment sequencing and dosing patterns of LA-SSA is essential for clinical decision-making to provide value-based management of NETs. Objective: To describe treatment patterns of LA-SSA among patients with NETs and subgroups with carcinoid syndrome (CS) in the United States. Methods: This retrospective study utilized claims data from MarketScan® databases to identify patients with NETs and newly treated with LA-SSA between January 1, 2015, and October 31, 2020. Patients were stratified by index LA-SSA (lanreotide and octreotide long-acting release [LAR]). Reported 28-day doses were based on claim fields for days' supply/drug quantity or units of service. Dose escalation was defined as increases in quantity or frequency. Continuous variables, categorical variables, and Kaplan-Meier estimated treatment durations were compared using t-tests, chi-square/Fisher's tests, and log-rank tests, respectively. Results: The study included 241 lanreotide and 521 octreotide LAR patients. Compared with octreotide LAR patients, treatment duration was longer for lanreotide patients (median, 41.3 vs 26.8 months; log-rank p=.004). Fewer lanreotide patients received rescue treatment with short-acting octreotide (7.9% vs 14.4%; p=.011), and a first (6.2% vs 27.3%) and second dose escalation (0.8% vs 5.2%; both p<.05). Among patients with doses reported, fewer lanreotide patients received above-label doses (2.5% [5/202] vs 14.4% [60/416]; p<.001). Among patients who ended treatment during follow-up, fewer lanreotide patients transitioned to another LA-SSA (18.9% [17/90] vs 33.6% [92/274]; p=.008). Similar treatment patterns were observed in CS subgroups. Results for switched treatment patterns were limited due to insufficient sample sizes. Discussion: Real-world treatment patterns of LA-SSA were assessed using more recent administrative claims data. Compared with octreotide LAR patients, lanreotide patients were more likely to remain longer on initial treatment and starting dose without dose escalations and less likely to use rescue treatment and transition to another LA-SSA after discontinuation of the index treatment. Conclusions: Findings from this claims study suggest a potential clinical benefit of lanreotide in NET management.

Adaptive-Partitioning Multilayer Dynamics Simulations: 2. Implementations of the Permuted and Interpolated Adaptive-Partitioning Gradients.

Recently, an adaptive-partitioning multilayer Q1/Q2/MM method was proposed, where Q1 and Q2 denote, respectively, two distinct quantum-mechanical levels of theory and MM, the molecular-mechanical force fields. Such a multilayer model resembles the ONIOM (our own N-layered integrated molecular orbital and molecular mechanics) model by Morokuma and co-workers, but it is distinguished by on-the-fly reclassifying atoms to be Q1, Q2, or MM in dynamics simulations. To smoothly blend the levels of descriptions of the atoms, buffer zones are introduced between adjacent layers, and the energy is smoothly interpolated. In particular, the Q1/Q2 interaction energy was expressed in two different formalisms: permuted and interpolated adaptive-partitioning (PAP and IAP), respectively. While the PAP energy is based on a weighted many-body expansion, the IAP energy is derived via alchemical quantum calculations with interpolated Fock and overlap matrices. In this article, we examine in-depth the irregularities in the IAP energy near the boundary between the buffer and Q2 zones, which were found prominent in some calculations. These irregularities are due to basis-set linear dependencies, which can be effectively suppressed using a cutoff for the weighted atomic orbital coefficients. Furthermore, we derived and implemented the gradients for both PAP and IAP. Test calculations on a series of water cluster models show perfectly smooth gradients in PAP, while a minor discontinuity occurs in IAP gradients at the buffer/Q2 boundary. The energy and gradient discontinuities in IAP become smaller when moving the buffer/Q2 boundary further away from the Q1 center and when increasing the size of the basis sets used. Overall, those discontinuities are controllable, and possible ways to further diminish them are discussed.

Identification of barriers at the primary care provider level to improve inflammatory breast cancer diagnosis and management.

The purpose of this study, based in the United States, was to evaluate knowledge gaps and barriers related to diagnosis and care of inflammatory breast cancer (IBC), a rare but lethal breast cancer subtype, amongst Primary Care Providers (PCP) as they are often the first point of contact when patients notice initial symptoms. PCP participants in the Duke University Health System, federally qualified health center, corporate employee health and community practices, nearby academic medical center, Duke physician assistant and advanced practice nurse leadership program alumni were first selected in a convenience sample and for semi-structured interviews (n = 11). Based on these data, an online survey tool was developed and disseminated (n = 78) to assess salient measures of IBC diagnosis, health disparity factors, referral and care coordination practices, COVID-19 impact, and continuing medical education (CME). PCP reported access to care and knowledge gaps in symptom recognition (mean = 3.3, range 1-7) as major barriers. Only 31 % reported ever suspecting IBC in a patient. PCP (n = 49) responded being challenged with referral delays in diagnostic imaging. Additionally, since the COVID-19 pandemic started, 63 % reported breast cancer referral delays, and 33 % reported diagnosing less breast cancer. PCP stated interest in CME in their practice for improved diagnosis and patient care, which included online (53 %), lunch time or other in-service training (33 %), patient and provider-facing websites (32 %). Challenges communicating rare cancer information, gaps in confidence in diagnosing IBC, and timely follow-up with patients and specialists underscores the need for developing PCP educational modules to improve guideline-concordant care.

Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization.

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening.

Intussusception following diaphragmatic rupture surgery: A rare case.

INTRODUCTION AND IMPORTANCE: Intussusception in adults is a rare manifestation after traumatic abdominal surgery, because after abdominal surgery patients often have functional bowel paralysis rather than increased intestinal motility. CASE PRESENTATION: 39-year-old male patient with acute intussusception appeared after surgery for diaphragmatic rupture and is undergoing postoperative treatment on day 7. The patient has clinical manifestations of small bowel obstruction. Computed tomography image shows evidence of jejuno-jejunal intussusception. Exploratory laparotomy and resection of the necrotic bowel were performed. CLINICAL DISCUSSION: Rare cases such as intussusception should be observed postoperatively and in similar manifestations with careful examination of the characteristic CT findings, because of early detection and surgical intervention with manual reduction can prevent the need for small bowel resection and possible unwanted complications. CONCLUSION: Postoperative intussusception occurs primarily in the small intestine and should be indicated for emergency surgery in all cases, and this should be kept in mind by the surgeon and the resuscitator. The early diagnosis and intervention of patients increase the survival rate and the surgical efficiency.

Machine Learning Methods for Endocrine Disrupting Potential Identification Based on Single-Cell Data.

Humans are continuously exposed to a variety of toxicants and chemicals which is exacerbated during and after environmental catastrophes such as floods, earthquakes, and hurricanes. The hazardous chemical mixtures generated during these events threaten the health and safety of humans and other living organisms. This necessitates the development of rapid decision-making tools to facilitate mitigating the adverse effects of exposure on the key modulators of the endocrine system, such as the estrogen receptor alpha (ERα), for example. The mechanistic stages of the estrogenic transcriptional activity can be measured with high content/high throughput microscopy-based biosensor assays at the single-cell level, which generates millions of object-based minable data points. By combining computational modeling and experimental analysis, we built a highly accurate data-driven classification framework to assess the endocrine disrupting potential of environmental compounds. The effects of these compounds on the ERα pathway are predicted as being receptor agonists or antagonists using the principal component analysis (PCA) projections of high throughput, high content image analysis descriptors. The framework also combines rigorous preprocessing steps and nonlinear machine learning algorithms, such as the Support Vector Machines and Random Forest classifiers, to develop highly accurate mathematical representations of the separation between ERα agonists and antagonists. The results show that Support Vector Machines classify the unseen chemicals correctly with more than 96% accuracy using the proposed framework, where the preprocessing and the PCA steps play a key role in suppressing experimental noise and unraveling hidden patterns in the dataset.

Prevalence and associated factors of antibiotic exposure during pregnancy in a large French population-based study during the 2010-19 period.

BACKGROUND: Although bacterial infections are frequent during pregnancy, the prescription of antibiotics to pregnant women represents a challenge for physicians, driven by the benefit-risk balance. OBJECTIVES: To assess the extent of prenatal antibiotic exposure and its associated factors. METHODS: This study included pregnancies in the National Mother-Child EPI-MERES Register 2010-19 (built from the French Healthcare Data System) regardless of outcome. Antibiotic exposure was defined as having at least one antibiotic prescription filled during pregnancy. The prevalence of pregnancies exposed to antibiotics was estimated. Univariable Poisson regression with generalized estimating equations was used to compare the number of antibiotic prescriptions filled during pregnancy and the period after pregnancy with the period 1 year before pregnancy. Multivariable Poisson regression was used to investigate factors associated with antibiotic exposure during pregnancy. RESULTS: Among 9 769 764 pregnancies, 3 501 294 (35.8%) were exposed to antibiotics and amoxicillin was the most common. Compared with a similar period 1 year before pregnancy, the number of filled antibiotic prescriptions was lower during pregnancy [incidence rate ratio (IRR) 0.903 (95% CI 0.902-0.905)] and during the period 1 year after pregnancy [IRR 0.880 (95% CI 0.879-0.881)]. Region of residence, deprivation index, smoking-related conditions and chronic diseases (especially chronic respiratory diseases) were associated with antibiotic exposure during pregnancy. CONCLUSIONS: Antibiotic prescriptions are filled less frequently during pregnancy than during the preceding year. This may be due to a more relevant benefit-risk assessment. Pregnant women living with social deprivation, those with smoking-related conditions and those with chronic diseases are more likely to fill antibiotic prescriptions.

Mapping the clinical care pathways for advanced stage non-small cell lung cancer patients in Victoria: A retrospective cohort study of supportive and palliative care.

The lung cancer Optimal Care Pathway recommends supportive care and palliative care integration throughout its various steps, with early referral to appropriate services improving the quality of life in advanced stage non-small cell lung cancer patients. Using Victorian Lung Cancer Registry data and linked administrative datasets, this retrospective cohort study mapped clinical care pathways of 525 Stage III-IV non-small cell lung cancer patients in Victoria to 11 recommendations in the Optimal Care Pathway, identifying unwarranted variations in clinical care. Supportive care and palliative care delivery were further examined to understand the involvement and timing of specialist care teams. Our findings showed that palliative care utilization is highest at the time of treatment, despite recommendations that it should be provided early after diagnosis to improve patient outcomes and satisfaction. Early supportive care screening was observed in half the cohort and almost three-quarters of the patients had been presented at a multidisciplinary meeting. Multidisciplinary meeting presentations and supportive care provide an opportunity to improve communication about palliative care needs and integration into routine clinical practice, such as at the time of treatment planning.

Regional Lymph Node Metastasis Distribution in Resectable Middle-Third Gastric Cancer: A Cross-Sectional Study.

Introduction Lymph node (LN) metastasis happens even in early gastric cancer (GC) even in LN stations that are not adjacent to the primary tumor. Total or subtotal gastrectomy (TG or sTG) can be performed in the middle third of the GC if the negative proximal margin is maintained. These procedures differed in the extent of LN dissection; therefore, oncology considerations must be taken into consideration when selecting the appropriate procedure. Methods This was a cross-sectional study involving 98 patients suffering from middle-third GC. The metastatic lymph nodes (mLN) ratio was calculated in each case by the ratio between the number of mLN and the number of total LNs retrieved. We compare the difference in the total LN retrieved, number of mLN, and rate of positive LN (N+) between the two groups TG and sTG. Results The majority of patients had advanced GC (82.7% pT2-4). About 65.3% of patients had metastasis LN. The events of LN metastasis and skipped LN metastasis happened even in tumors contained in the submucosal layer. The metastasis rates in each LN station were also increasing in correlation with the depth of tumor invasion. For LN station No. 2, 4sa, 10, 11d (which are not mandatory) in sTG, the rate of mLN was 0% for the pT1-3 tumor, regardless of tumor longitudinal location. The rate of mLN for each station was higher in adjacent stations of the tumor (No. 1-3-5-7 in lesser curvature, No. 4sb-4d-6 in greater curvature, No.1-3-4sb in the anterior wall, No. 3-7-12a in the posterior wall). The total LN retrieved, number of mLN, and rate of positive LN were statistically higher in the TG group compared to the sTG group. However, the mean mLN ratios between the two groups were comparable (p = 0.116). Conclusion In accordance with the macroscopic and microscopic characteristics, we observed a stratified distribution of mLN in the middle third of the GC. With these early results, sTG combined with standard lymphadenectomy was an acceptable treatment for T1-T3 middle-third GC in terms of mLN distribution. Total No. 4sb LN dissection might also be reserved in gastrectomy for T1-T3 GC.

Pollution characteristics, associated risks, and possible sources of heavy metals in road dust collected from different areas of a metropolis in Vietnam.

Road dust samples were collected from different areas in Ho Chi Minh City (HCMC)-the largest city in Vietnam to explore pollution characteristics, ecological and human health risks, and sources of heavy metals (HMs). Results revealed the level of HMs found in the samples from residential and industrial zones of HCMC in the order of Mn > Zn > Cu > Cr > Pb > Ni > Co > As > Cd, Zn > Mn > Cu > Cr > Pb > Ni > Co > As > Cd. Due to the high enrichment of Cu, Zn in residential areas and Cu, Pb, Zn in industrial areas, the HM contamination in these areas remained moderate to severe. The findings also revealed a rising trend in the level of HMs in road dust from the east to the west of HCMC, and a heavy metal contamination hotspot in the west. In addition, industrial areas were more contaminated with HMs, posing greater associated risks than residential areas. Children living in urban areas of HCMC were found to be exposed to unacceptable health risks. Meanwhile, adults living in industrial areas face intolerable cancer risk. Among the nine HMs, Cd, Pb, and Cu posed the greatest ecological risk, while Cr and As were the main culprits behind health risks. HMs in road dust might derive from non-exhaust vehicular emissions, crustal materials, and industrial activities. The results suggested that industrial areas to the west of HCMC should focus more on reducing and controlling severe pollution of HMs.