ALLIANCE A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.

Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N+) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (+/- 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 296 evaluable patients (148 per arm) will provide statistical power of 90.5% to detect an 17% increase in cCR rate, at a one-sided alpha=0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse effects. Biospecimens including archival tumor tissue, plasma and buffy coat in EDTA tubes, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and has a current accrual of 312. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion: Building off of data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed the current trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial Registration: Clinicaltrials.gov ID: NCT05610163 ; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Assessing periparturient ewe characteristics and nemabiome composition to guide targeted selective treatment for sustainable gastrointestinal nematodes control in sheep.

Gastrointestinal nematodes (GINs) are a significant threat to the sustainability of global sheep production. Periparturient ewes play a key role in GIN epidemiology, with increased GIN faecal egg counts (FECs) in these ewes resulting in heavy pasture contamination that facilitates parasitic gastroenteritis in immunologically naïve lambs later during the grazing period. Traditionally, blanket anthelmintic treatment would suppress GIN egg outputs in these ewes and subsequent pasture contamination. However, farmers are now advised to implement targeted selective treatment (TST) to reduce anthelmintic use and subsequent anthelmintic resistance development, yet, there is currently limited evidence to determine optimal TST strategies in ewes. In this study, the characteristics of 226 ewes on seven Welsh farms were assessed postlambing to identify factors associated with their individual strongyle FECs using negative binomial mixed model analysis. Nemabiome analysis was conducted on 34 ewes across two study farms using the Oxford Nanopore MinIon platform with an aim of identifying factors associated with variations in ewe nemabiome composition within flocks. The best-fitted model of ewe FEC incorporated ewe body condition score, dag score, breed, and an interaction effect between ewe age and litter size as fixed factors. The addition of a mean FEC value for ewes of a specific litter size on each farm further improved model fit and reduced between-farm variance in the model. Nemabiome analysis revealed significant variation in within flock nemabiome diversity on individual farms, with significantly reduced nemabiome diversity recorded in ewes exhibiting dags and in twin-bearing ewes on respective farms, whilst T. circumcincta was present as a significantly higher proportion of the nemabiome in Suffolk ewes and twin bearing ewes (P < 0.05) in respective flocks. Our data demonstrate that commonly recorded ewe characteristics can be exploited to predict individual periparturient ewe FEC and subsequently may be used as a guide for TST strategies on sheep farms once specific TST thresholds are identified to deliver the optimal balance between minimal pasture contamination and maximal GIN refugia. This study is the first to utilise Oxford Nanopore MinIon sequencing to evaluate the nemabiome of sheep, and to molecularly assess the nemabiome of individual ruminants within a flock/herd, with results indicating that significant within flock variations in nemabiome composition which may have implications for TST and flock management strategies.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

Renal Neuroendocrine Tumor: A Case Report with Evaluation of Grading Criteria and Relationship with Carbonic Anhydrase 9 Immunoreactivity.

Neuroendocrine tumors (NETs) are only exceptionally primary to the kidney. At present, scant information is known regarding the behavior and prognosis of renal NETs, especially according to the assessment of grading parameters used for NETs originating from other more commonplace sites such as the pancreas and lungs. There are only rare reports of grade assessment in renal NETs, with most of these reports relying upon now antiquated World Health Organization gastroenteropancreatic and lung/thymus criteria. As an additional prognostic factor, positive CA9 staining in NETs may correlate with elevated grade, stage and risk of metastasis while serving as a potential target of chemotherapy and immunotherapy and indicator of Von Hippel-Lindau Syndrome. Rarer still are descriptions of renal NETs presenting with renal cell carcinoma in the ipsilateral or contralateral kidney. Thus, we present a patient with a primary renal NET of the right kidney with regional lymphovascular invasion and distant metastasis with an emphasis on grading criteria concordant with the World Health Organization 2022 gastroenteropancreatic and lung/thymus systems. In addition, we discuss unusual staining for CA9 in the patient's tumor and a concomitant left kidney clear cell renal cell carcinoma that may act as a clinicopathologic mimic of Von Hippel-Lindau Syndrome.

John R. Ward, MD: Pioneer-Clinical Trials in Rheumatology.

John Robert Ward was one of the early academic rheumatologists in the United States. He was the founding father of rheumatology in the Intermountain West, the first Chief of the Division of Rheumatology in the Department of Internal Medicine at the University of Utah. Dr Ward became a national leader in the understanding and treatment of rheumatic disease. His foundational work established gold-standard techniques for the successful investigation of anti-rheumatic drugs. His leadership and scientific contributions clearly qualify him as a "giant in rheumatology."

Vascularized Sural Nerve Graft, Fascial Free Flap, and Regenerative Peripheral Nerve Interface in the Setting of Recurrent Thigh Liposarcoma: A Case Report.

Background: There is no clear consensus in the literature regarding clinical indications for vascularized nerve grafts. Most studies indicate that vascularized nerve grafting, rather than non-vascularized nerve grafting, is indicated for nerve gaps of greater than 7 cm. Vascularized nerve grafts are superior to non-vascularized nerve grafts because they possess an independent blood supply. However, not all nerve injuries can be repaired via vascularized nerve grafts. Methods: A 32-year-old female received a fascial free flap and vascularized sural nerve graft after having multiple reresections of a recurrent thigh liposarcoma. Results: A 25-cm segment of the sural nerve was isolated alongside the lesser saphenous vein and intervening fascia. The free fascial flap was subsequently reversed and placed into the thigh. Vascular anastomoses were created, and the sural nerve was anastomosed to the peroneal nerve. A small portion of muscle from the thigh was wrapped around tibial nerve fascicles of the sciatic nerve to create a regenerative nerve interface. Conclusions: Benefits of vascularized sural nerve graft compared with other vascularized nerve grafts include negligible sensory loss at the donor site and a nerve graft that can be designed on itself due to its vast length. Additionally, vascularized sural nerve grafts provided a better rate of axonal regeneration, rate of electromyographic return, and motor and sensory outcome compared with non-vascularized sural nerve grafts.

Community knowledge, attitude, practices and beliefs associated with persistence of malaria transmission in North-western and Southern regions of Tanzania.

BACKGROUND: Despite significant decline in the past two decades, malaria is still a major public health concern in Tanzania; with over 93% of the population still at risk. Community knowledge, attitudes and practices (KAP), and beliefs are key in enhancing uptake and utilization of malaria control interventions, but there is a lack of information on their contribution to effective control of the disease. This study was undertaken to determine KAP and beliefs of community members and service providers on malaria, and how they might be associated with increased risk and persistence of the disease burden in North-western and Southern regions of Tanzania. METHODS: This was an exploratory study that used qualitative methods including 16 in-depth interviews (IDI) and 32 focus group discussions (FGDs) to collect data from health service providers and community members, respectively. The study was conducted from September to October 2017 and covered 16 villages within eight districts from four regions of mainland Tanzania (Geita, Kigoma, Mtwara and Ruvuma) with persistently high malaria transmission for more than two decades. RESULTS: Most of the participants had good knowledge of malaria and how it is transmitted but some FGD participants did not know the actual cause of malaria, and thought that it is caused by bathing and drinking un-boiled water, or consuming contaminated food that has malaria parasites without warming it. Reported barriers to malaria prevention and control (by FGD and IDI participants) included shortage of qualified health workers, inefficient health financing, low care-seeking behaviour, consulting traditional healers, use of local herbs to treat malaria, poverty, increased breeding sites by socio-economic activities and misconceptions related to the use of bed nets and indoor residual spraying (IRS). Among the misconceptions, some participants believed that bed nets provided for free by the government came with bedbugs while others reported that free bed nets caused impotence among men. CONCLUSION: Despite good knowledge of malaria, several risk factors, such as socio-economic and behavioural issues, and misconceptions related to the use of bed nets and IRS were reported. Other key factors included unavailability or limited access to health services, poor health financing and economic activities that potentially contributed to persistence of malaria burden in these regions. Relevant policies and targeted malaria interventions, focusing on understanding socio-cultural factors, should be implemented to reduce and finally eliminate the disease in the study regions and others with persistent transmission.

CHEK2 C1100del mutation associated with papillary renal cell carcinoma type II.

CHEK2 mutations have been noted in bone, brain, breast, colon, lung, thyroid, and prostate cancer. Although now reported in both clear cell and non-clear cell renal cancer, we have not found CHEK2 2 mutations reported in the papillary type II subtype (PRCC). Here, we report a 63-year-old female with a PRCC type II with a concomitant CHEK2 C1100del mutation, who is currently in complete remission three years post tumor resection.

Functional immune boosters; the herb or its dead microbiome? Antigenic TLR4 agonist MAMPs found in 65 medicinal roots and algae's.

Background: Humans have been consuming medicinal plants (as herbs/ spices) to combat illness for centuries while ascribing beneficial effects predominantly to the plant/phytochemical constituents, without recognizing the power of obligatory resident microorganism' communities (MOCs) (live/dead bacteria, fungus, yeast, molds etc.) which remain after industrial microbial reduction methods. Very little is known about the taxonomic identity of residual antigenic microbial associated molecular patterns (MAMPs) debris in our botanical over the counter (OTC) products, which if present would be recognized as foreign (non-self) antigenic matter by host pattern recognition receptors (PRRs) provoking a host immune response; this the basis of vaccine adjuvants. As of today, only few research groups have removed the herbal MAMP biomass from herbs, all suggesting that immune activation may not be from the plant but rather its microbial biomass; a hypothesis we corroborate. Purpose: The purpose of this work was to conduct a high through put screening (HTPS) of over 2500 natural plants, OTC botanical supplements and phytochemicals to elucidate those with pro-inflammatory; toll like receptor 4 (TLR4) activating properties in macrophages. Study Design: The HTPS was conducted on RAW 264.7 cells vs. lipopolysaccharide (LPS) E. coli 0111:B4, testing iNOS / nitric oxide production (NO2-) as a perimeter endpoint. The data show not a single drug/chemical/ phytochemical and approximately 98 % of botanicals to be immune idle (not effective) with only 65 pro-inflammatory (hits) in a potency range of LPS. Method validation studies eliminated the possibility of false artifact or contamination, and results were cross verified through multiple vendors/ manufacturers/lot numbers by botanical species. Lead botanicals were evaluated for plant concentration of LPS, 1,3:1,6-ß-glucan, 1,3:1,4-ß-D-glucan and α-glucans; where the former paralleled strength in vitro. LPS was then removed from plants using high-capacity endotoxin poly lysine columns, where bioactivity of LPS null "plant" extracts were lost. The stability of E.Coli 0111:B4 in an acid stomach mimetic model was confirmed. Last, we conducted a reverse culture on aerobic plate counts (APCs) from select hits, with subsequent isolation of gram-negative bacteria (MacConkey agar). Cultures were 1) heat destroyed (retested/ confirming bioactivity) and 2) subject to taxonomical identification by genetic sequencing 18S, ITS1, 5.8 s, ITS2 28S, and 16S. Conclusion: The data show significant gram negative MAMP biomass dominance in A) roots (e.g. echinacea, yucca, burdock, stinging nettle, sarsaparilla, hydrangea, poke, madder, calamus, rhaponticum, pleurisy, aconite etc.) and B) oceanic plants / algae's (e.g. bladderwrack, chlorella, spirulina, kelp, and "OTC Seamoss-blends" (irish moss, bladderwrack, burdock root etc), as well as other random herbs (eg. corn silk, cleavers, watercress, cardamom seed, tribulus, duckweed, puffball, hordeum and pollen). The results show a dominance of gram negative microbes (e.g. Klebsilla aerogenes, Pantoae agglomerans, Cronobacter sakazakii), fungus (Glomeracaea, Ascomycota, Irpex lacteus, Aureobasidium pullulans, Fibroporia albicans, Chlorociboria clavula, Aspergillus_sp JUC-2), with black walnut hull, echinacea and burdock root also containing gram positive microbial strains (Fontibacillus, Paenibacillus, Enterococcus gallinarum, Bromate-reducing bacterium B6 and various strains of Clostridium). Conclusion: This work brings attention to the existence of a functional immune bioactive herbal microbiome, independent from the plant. There is need to further this avenue of research, which should be carried out with consideration as to both positive or negative consequences arising from daily consumption of botanicals highly laden with bioactive MAMPS.

Implementation of the HOME core outcome set for clinical trials of atopic eczema-barriers and opportunities: the HOME IX meeting report.

The Harmonising Outcome Measures for Eczema (HOME) initiative established a core outcome set (COS) for atopic eczema (AE) clinical trials in 2019. This set encompasses four core outcome domains and corresponding measurement instruments: clinical signs (EASI), patient-reported symptoms (POEM and NRS 11 point for worst itch over the last 24 h), quality of life (DLQI/CDLQI/IDQoLI), and long-term control (Recap or ADCT). Following its roadmap, the HOME initiative is now focused on supporting implementation of the COS. To identify barriers and facilitators to implementation of the COS, and to guide the effort to promote COS uptake, a virtual consensus meeting was held over 2 days (September 25-26, 2021) attended by 55 participants (26 healthcare professionals, 16 methodologists, 5 patients, 4 industry representatives, and 4 students). Implementation themes were identified by a pre-meeting survey distributed to HOME members, presentations, and whole-group discussion. Participants were divided into five multi-professional small groups which ranked their top 3 most important themes, followed by whole-group discussion and anonymous consensus voting (consensus criteria: < 30% disagreement). Three most important implementation themes were identified and agreed upon: (1) awareness and stakeholder engagement, (2) universal applicability of the COS, and (3) ensuring minimum administrative burden. Working groups to address these issues are now a priority for the HOME initiative. The results from this meeting will inform the development of a HOME Implementation Roadmap in an effort to support other COS groups planning for effective implementation of their core sets.

An Improved System to Measure Leaf Gas Exchange on Adaxial and Abaxial Surfaces.

Measurement of leaf carbon gain and water loss (gas exchange) in planta is a standard procedure in plant science research for attempting to understand physiological traits related to water use and photosynthesis. Leaves carry out gas exchange through the upper (adaxial) and lower (abaxial) surfaces at different magnitudes, depending on the stomatal density, stomatal aperture, cuticular permeability, etc., of each surface, which we account for in gas exchange parameters such as stomatal conductance. Most commercial devices measure leaf gas exchange by combining the adaxial and abaxial fluxes and calculating bulk gas exchange parameters, missing details of the plant's physiological response on each side. Additionally, the widely used equations to estimate gas exchange parameters neglect the contribution of small fluxes such as cuticular conductance, adding extra uncertainties to measurements performed in water-stress or low-light conditions. Accounting for the gas exchange fluxes from each side of the leaf allows us to better describe plants' physiological traits under different environmental conditions and account for genetic variability. Here, apparatus and materials are presented for adapting two LI-6800 Portable Photosynthesis Systems to work as one gas exchange system to measure adaxial and abaxial gas exchange simultaneously. The modification includes a template script with the equations to account for small fluxes. Instructions are provided for incorporating the add-on script into the device's computational sequence, display, variables, and spreadsheet results. We explain the method to obtain an equation to estimate boundary layer conductance to water for the new setup and how to embed this equation in the devices' calculations using the provided add-on script. The apparatus, methods, and protocols presented here provide a simple adaptation combining two LI-6800s to obtain an improved system to measure leaf gas exchange on adaxial and abaxial surfaces. Graphical overview Figure 1.Diagram of the connection of two LI-6800s.Figure adapted from Márquez et al. (2021).

Pathologic, immunologic, and clinical analysis of the microsatellite instability phenotype in endometrial carcinoma.

The objective of this study was to determine if quantifying the microsatellite instability (MSI) phenotype could serve as a biomarker for clinical and immunologic features of deficient mismatch repair (dMMR) endometrial cancer (EC). Patients with EC undergoing hysterectomy whose tumors demonstrated dMMR were included. Immunohistochemistry (IHC) of mismatch repair proteins and polymerase chain reaction analysis of NR27, BAT25, BAT26, NR24, and NR21 microsatellite loci were performed on each case. The MSI phenotype was quantified by subtracting the number of nucleotides of each microsatellite in tumor tissue from the corresponding microsatellite in paired normal tissue and summing the absolute differences. This was termed marker sum (MS) and is a novel quantification. Tumor-infiltrating lymphocytes (TILs) were identified by IHC for CD3, CD4, and CD8 and quantified with digital image analysis. Tumor infiltration of lymphocytes and clinical characteristics were stratified by MS. Four hundred fifty-nine consecutive patients with dMMR EC were analyzed. MS ranged from 1 to 32. Post hoc, 2 cohorts were defined using receiver operating characteristic curves (MS less than 13 and MS greater than 12). With the exception of tumor grade, all clinical and pathologic features, all tumor characteristics, and the numbers of TILs were similar between cohorts. The MSI phenotype is highly variable in dMMR EC, and no correlation between the immune profile and the severity of the MSI phenotype was observed.

Mouse organoids as an in vitro tool to study the in vivo intestinal response to cytotoxicants.

Cross-species comparison of drug responses at the organoid level could help to determine the human relevance of findings from animal studies. To this end, we first need to evaluate the in vitro to in vivo translatability of preclinical organoids. Here, we used 5-fluorouracil (5-FU) as an exemplar drug to test whether the in vivo gut response to this cytotoxicant was preserved in murine intestinal organoids. Mice treated with 5-FU at 20 or 50 mg/kg IV (low and high dose, respectively) displayed diarrhea at clinically relevant exposures. 5-FU also induced intestinal lesions, increased epithelial apoptosis, and decreased proliferation in a dose-dependent manner. To enable comparison between the in vitro and in vivo response, top nominal in vitro drug concentrations that caused significant cytotoxicity were chosen (dose range 1-1000 µM). The inferred intracellular concentration in organoids at 1000 µM was within the tissue exposure range related to intestinal toxicity in vivo. 5-FU at ≥ 100 µM decreased ATP levels and increased Caspase-3 activity in intestinal organoids. In keeping with the in vivo findings, 5-FU increased the percentage of Caspase-3-positive cells and reduced Ki67 staining. At the transcriptome level, there was an overlap in the activity of pathways related to 5-FU's mode of action, lipid and cholesterol metabolism and integrin signaling across in vivo gut and organoids. The predicted activity state of upstream regulators was generally well preserved between setups. Collectively, our results suggest that despite their inherent limitations, organoids represent an adequate tool to explore the intestinal response to cytotoxicants.

Froth Flotation of Chalcopyrite/Pyrite Ore: A Critical Review.

In the present work an intense bibliographic search is developed, with updated information on the microscopic fundamentals that govern the behavior of flotation operations of chalcopyrite, the main copper mineral in nature. In particular, the effect caused by the presence of pyrite, a non-valuable mineral, but challenging for the operation due to its ability to capture a portion of collector and float, decreasing the quality of the concentrate, is addressed. This manuscript discusses the main chemical and physical mechanisms involved in the phenomena of reagent adsorption on the mineral surface, the impact of pH and type of alkalizing agent, and the effect of pyrite depressants, some already used in the industry and others under investigation. Modern collector reagents are also described, for which, although not yet implemented on an industrial scale, promising results have been obtained in the laboratory, including better copper recovery and selectivity, and even some green reagents present biodegradable properties that generate a better environmental perspective for mineral processing.

A report of Bilharziella polonica cercariae in Knowsley Safari, Prescot, United Kingdom, with notes on other trematodes implicated in human cercarial dermatitis.

As part of surveillance of snail-borne trematodiasis in Knowsley Safari (KS), Prescot, United Kingdom, a collection was made in July 2021 of various planorbid (n = 173) and lymnaeid (n = 218) snails. These were taken from 15 purposely selected freshwater habitats. In the laboratory emergent trematode cercariae, often from single snails, were identified by morphology with a sub-set, of those most accessible, later characterized by cytochrome oxidase subunit 1 (cox1) DNA barcoding. Two schistosomatid cercariae were of special note in the context of human cercarial dermatitis (HCD), Bilharziella polonica emergent from Planorbarius corneus and Trichobilharzia spp. emergent from Ampullacaena balthica. The former schistosomatid was last reported in the United Kingdom over 50 years ago. From cox1 analyses, the latter likely consisted of two taxa, Trichobilharzia anseri, a first report in the United Kingdom, and a hitherto unnamed genetic lineage having some affiliation with Trichobilharzia longicauda. The chronobiology of emergent cercariae from P. corneus was assessed, with the vertical swimming rate of B. polonica measured. We provide a brief risk appraisal of HCD for public activities typically undertaken within KS educational and recreational programmes.

Selective angioembolization as a management strategy for angiomyolipoma causing urinary tract obstruction.

Angiomyolipoma (AML) is a benign renal tumor usually found incidentally. Rarely, AML can present with renal colic due to urinary tract obstruction. Prior cases of obstructing AML have been presented and managed successfully with surgical removal. Selective angioembolization has emerged as an alternative management strategy for AML, but no documented cases have been presented for this strategy in the setting of obstruction. Here, we present a case of obstructing AML treated with selective angioembolization with subsequent resolution of obstruction.

Materials on Plant Leaf Surfaces Are Deliquescent in a Variety of Environments.

Materials on plant leaf surfaces that attract water impact penetration of foliar-applied agrochemicals, foliar water uptake, gas exchange, and stomatal density. Few studies are available on the nature of these substances, and we quantify the hygroscopicity of these materials. Water vapor sorption experiments on twelve leaf washes of sample leaves were conducted and analyzed with inductively coupled plasma-optical emission spectroscopy (ICP-OES) and X-ray diffraction. All leaf surface materials studied were hygroscopic. Oils were found on the surface of the Eucalyptus studied. For mangroves that excrete salt to the leaf surfaces, significant sorption occurred at high humidity of a total of 316 mg (~0.3 ml) over 6-10 leaves and fitted a Guggenheim, Anderson, and de Böer sorption isotherm. Materials on the plant leaf surface can deliquesce and form an aqueous solution in a variety of environments where plants grow, including glasshouses and by the ocean, which is an important factor when considering plant-atmosphere relations.

Artificial intelligence and machine learning algorithms for early detection of skin cancer in community and primary care settings: a systematic review.

Skin cancers occur commonly worldwide. The prognosis and disease burden are highly dependent on the cancer type and disease stage at diagnosis. We systematically reviewed studies on artificial intelligence and machine learning (AI/ML) algorithms that aim to facilitate the early diagnosis of skin cancers, focusing on their application in primary and community care settings. We searched MEDLINE, Embase, Scopus, and Web of Science (from Jan 1, 2000, to Aug 9, 2021) for all studies providing evidence on applying AI/ML algorithms to the early diagnosis of skin cancer, including all study designs and languages. The primary outcome was diagnostic accuracy of the algorithms for skin cancers. The secondary outcomes included an overview of AI/ML methods, evaluation approaches, cost-effectiveness, and acceptability to patients and clinicians. We identified 14 224 studies. Only two studies used data from clinical settings with a low prevalence of skin cancers. We reported data from all 272 studies that could be relevant in primary care. The primary outcomes showed reasonable mean diagnostic accuracy for melanoma (89·5% [range 59·7-100%]), squamous cell carcinoma (85·3% [71·0-97·8%]), and basal cell carcinoma (87·6% [70·0-99·7%]). The secondary outcomes showed a heterogeneity of AI/ML methods and study designs, with high amounts of incomplete reporting (eg, patient demographics and methods of data collection). Few studies used data on populations with a low prevalence of skin cancers to train and test their algorithms; therefore, the widespread adoption into community and primary care practice cannot currently be recommended until efficacy in these populations is shown. We did not identify any health economic, patient, or clinician acceptability data for any of the included studies. We propose a methodological checklist for use in the development of new AI/ML algorithms to detect skin cancer, to facilitate their design, evaluation, and implementation.