Fishers' ecological knowledge points to fishing-induced changes in the Peruvian Amazon.

Scientists increasingly draw on fishers' ecological knowledge (FEK) to gain a better understanding of fish biology and ecology, and inform options for fisheries management. We report on a study of FEK among fishers along the Lower Ucayali River in Peru, a region of exceptional productivity and diversity, which is also a major supplier of fish to the largest city in the Peruvian Amazon. Given a lack of available scientific information on stock status, we sought to identify temporal changes in the composition and size of exploited species by interviewing fishers from 18 communities who vary in years of fishing experience since the mid-1950s. We develop four FEK-based indicators to assess changes in the fish assemblage and compare findings with landings data. We find an intensification of fishing gear deployed over time and spatiotemporal shifts in the fish assemblage and reported declines in species weight, which point to a fishing-down process with declines across multiple species. This finding is reflected in a shifting baseline among our participants, whereby younger generations of fishers have different expectations regarding the distribution and size of species. Our study points to the importance of spillover effects from the nearby Pacaya-Samira National Reserve and community initiatives to support the regional fishery. Reference to fishers' knowledge also suggests that species decline is likely underreported in aggregated landings data. Despite the dynamism and diversity of Amazonian floodplain fisheries, simple FEK-based indicators can provide useful information for understanding fishing-induced changes in the fish assemblage. Fishers hold valuable knowledge for fishery management and conservation initiatives in the region.

HER2/ ERBB2 Immunohistochemical Expression and Copy Number Status in Ovarian Mucinous Tumors.

Primary mucinous ovarian carcinoma (MOC) is a rare ovarian epithelial cancer, which is often refractory to chemotherapy. HER2-targeting therapy is being increasingly considered in gynecologic malignancies. Although there have been limited studies examining the HER2 status of such tumors, the criteria for HER2 expression scoring have not been standardized for MOC as it has for other sites. This study aimed to survey immunohistochemical HER2 expression patterns in MOC and its precursor, mucinous borderline tumor in correlation with fluorescence in situ hybridization (FISH). Immunohistochemistry (IHC) for HER2 was performed on 12 cases of MOC and 15 mucinous borderline tumors, including 7 with intraepithelial carcinoma. HER2 expression was quantified using the gastric/gastroesophageal carcinoma protocol. Cases were considered 3+ if the tumor cells displayed strong complete or basolateral/lateral membranous staining in ≥10% of tumor cells. Cases (2+) had weak to moderate staining in ≥10% of tumor cells. Cases (1+) had faint staining in ≥10% of tumor cells. Cases considered 0 had no staining or faint staining in <10% of tumor cells. HER2 expression was also quantified with the endometrial serous carcinoma protocol, which uses a 30% tumor cell positivity cutoff. FISH for HER2 was performed on all 3+ and 2+ and a subset of 1+ cases. Of the MOC cases, 25% were 3+ and 1 mucinous borderline tumor with intraepithelial carcinoma had 3+ staining. All 3+ IHC MOC cases had >30% basolateral membranous staining. HER2 amplification was confirmed by FISH on all 3+ IHC cases and in one 2+ IHC case of MOC. Up to 25% of mucinous ovarian tumors showed HER2 IHC overexpression with an excellent correlation between IHC and FISH using the HER2 scoring protocol for either gastric/gastroesophageal carcinoma or uterine serous carcinoma.

Targeting altered glycosylation in secreted tumor glycoproteins for broad cancer detection.

There is an urgent need to develop new tumor biomarkers for early cancer detection, but the variability of tumor-derived antigens has been a limitation. Here we demonstrate a novel anti-Tn antibody microarray platform to detect Tn+ glycoproteins, a near universal antigen in carcinoma-derived glycoproteins, for broad detection of cancer. The platform uses a specific recombinant IgG1 to the Tn antigen (CD175) as a capture reagent and a recombinant IgM to the Tn antigen as a detecting reagent. These reagents were validated by immunohistochemistry in recognizing the Tn antigen using hundreds of human tumor specimens. Using this approach, we could detect Tn+ glycoproteins at subnanogram levels using cell lines and culture media, serum, and stool samples from mice engineered to express the Tn antigen in intestinal epithelial cells. The development of a general cancer detection platform using recombinant antibodies for detection of altered tumor glycoproteins expressing a unique antigen could have a significant impact on cancer detection and monitoring.

Copolymerization of single-cell nucleic acids into balls of acrylamide gel.

We show the use of 5'-Acrydite oligonucleotides to copolymerize single-cell DNA or RNA into balls of acrylamide gel (BAGs). Combining this step with split-and-pool techniques for creating barcodes yields a method with advantages in cost and scalability, depth of coverage, ease of operation, minimal cross-contamination, and efficient use of samples. We perform DNA copy number profiling on mixtures of cell lines, nuclei from frozen prostate tumors, and biopsy washes. As applied to RNA, the method has high capture efficiency of transcripts and sufficient consistency to clearly distinguish the expression patterns of cell lines and individual nuclei from neurons dissected from the mouse brain. By using varietal tags (UMIs) to achieve sequence error correction, we show extremely low levels of cross-contamination by tracking source-specific SNVs. The method is readily modifiable, and we will discuss its adaptability and diverse applications.

Analysis of KRAS Mutations in Gastrointestinal Tract Adenocarcinomas Reveals Site-Specific Mutational Signatures.

Adenocarcinomas of the luminal gastrointestinal tract and pancreatobiliary system often show histologic and immunohistochemical overlap, making delineation of the primary site in a metastatic setting difficult. Previous studies have shown that site-specific missense mutations in the oncogene KRAS could be used in conjunction with immunohistochemistry to differentiate metastatic pancreatic adenocarcinoma from primary lung adenocarcinoma. In this study, we assessed the patterning of KRAS mutations across sites in the gastrointestinal and pancreatobiliary system. By integrating sequencing data from 44 separate studies, we assessed 2523 KRAS mutations in 7382 distinct cases of adenocarcinoma, including those from the esophagus, stomach, ampulla, biliary system, pancreas, and colon. We found that gastrointestinal adenocarcinomas demonstrate a marked regional variation in the frequency of KRAS mutations, with the most frequent KRAS mutation observed in pancreatic adenocarcinoma (up to 94.9%), whereas the frequency is much lower in adenocarcinomas from the esophagus and stomach (5.4% and 8.7%, respectively). Intriguingly, the pattern of missense mutations showed site specificity as well, with c.35G>T (p.G12V) and c.34G>C (p.G12R) mutations enriched in pancreatic primaries and codon 13 and non-codon 12/13 alterations enriched in gastric primaries (specificity of 98.9% and 93.2%, respectively, with a negative predictive value of 93.6% and 92.93% against pancreatic adenocarcinoma). Furthermore, we found that esophageal and gastric adenocarcinomas show an enrichment in transitional mutations, whereas other sites showed an equal distribution. Importantly, the examination of a validation cohort from our own institution revealed similar trends. These findings indicate that, in addition to providing therapeutic and diagnostic information, KRAS mutational analysis may also prove useful in delineating the site of origin in gastrointestinal adenocarcinomas that share morphologic and immunohistochemical overlap. Moreover, transitional mutations are more frequent in esophageal and gastric adenocarcinomas, reiterating the role of chronic inflammation in the pathogenesis of foregut adenocarcinomas.

Comparative genomics of primary prostate cancer and paired metastases: insights from 12 molecular case studies.

Primary prostate cancer (PCa) can show marked molecular heterogeneity. However, systematic analyses comparing primary PCa and matched metastases in individual patients are lacking. We aimed to address the molecular aspects of metastatic progression while accounting for the heterogeneity of primary PCa. In this pilot study, we collected 12 radical prostatectomy (RP) specimens from men who subsequently developed metastatic castration-resistant prostate cancer (mCRPC). We used histomorphology (Gleason grade, focus size, stage) and immunohistochemistry (IHC) (ERG and p53) to identify independent tumors and/or distinct subclones of primary PCa. We then compared molecular profiles of these primary PCa areas to matched metastatic samples using whole-exome sequencing (WES) and amplicon-based DNA and RNA sequencing. Based on combined pathology and molecular analysis, seven (58%) RP specimens harbored monoclonal and topographically continuous disease, albeit with some degree of intratumor heterogeneity; four (33%) specimens showed true multifocal disease; and one displayed monoclonal disease with discontinuous topography. Early (truncal) events in primary PCa included SPOP p.F133V (one patient), BRAF p.K601E (one patient), and TMPRSS2:ETS rearrangements (eight patients). Activating AR alterations were seen in nine (75%) mCRPC patients, but not in matched primary PCa. Hotspot TP53 mutations, found in metastases from three patients, were readily present in matched primary disease. Alterations in genes encoding epigenetic modifiers were observed in several patients (either shared between primary foci and metastases or in metastatic samples only). WES-based phylogenetic reconstruction and/or clonality scores were consistent with the index focus designated by pathology review in six out of nine (67%) cases. The three instances of discordance pertained to monoclonal, topographically continuous tumors, which would have been considered as unique disease in routine practice. Overall, our results emphasize pathologic and molecular heterogeneity of primary PCa, and suggest that comprehensive IHC-assisted pathology review and genomic analysis are highly concordant in nominating the 'index' primary PCa area. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Identifying deprived "slum" neighbourhoods in the Greater Accra Metropolitan Area of Ghana using census and remote sensing data.

Background: Identifying urban deprived areas, including slums, can facilitate more targeted planning and development policies in cities to reduce socio-economic and health inequities, but methods to identify them are often ad-hoc, resource intensive, and cannot keep pace with rapidly urbanizing communities. Objectives: We apply a spatial modelling approach to identify census enumeration areas (EAs) in the Greater Accra Metropolitan Area (GAMA) of Ghana with a high probability of being a deprived area using publicly available census and remote sensing data. Methods: We obtained United Nations (UN) supported field mapping data that identified deprived "slum" areas in Accra's urban core, data on housing and population conditions from the most recent census, and remotely sensed data on environmental conditions in the GAMA. We first fitted a Bayesian logistic regression model on the data in Accra's urban core (n=2,414 EAs) that estimated the relationship between housing, population, and environmental predictors and being a deprived area according to the UN's deprived area assessment. Using these relationships, we predicted the probability of being a deprived area for each of the 4,615 urban EAs in GAMA. Results: 899 (19%) of the 4,615 urban EAs in GAMA, with an estimated 745,714 residents (22% of its urban population), had a high predicted probability (≥80%) of being a deprived area. These deprived EAs were dispersed across GAMA and relatively heterogeneous in their housing and environmental conditions, but shared some common features including a higher population density, lower elevation and vegetation abundance, and less access to indoor piped water and sanitation. Conclusion: Our approach using ubiquitously available administrative and satellite data can be used to identify deprived neighbourhoods where interventions are warranted to improve living conditions, and track progress in achieving the Sustainable Development Goals aiming to reduce the population living in unsafe or vulnerable human settlements.

Temperate Coastal Microbial Communities Rapidly Respond to Low Concentrations of Partially Weathered Diesel.

Diesel is frequently encountered in coastal ecosystems due to land run-off from road surfaces. The current study investigates how partially weathered diesel at environmentally relevant concentrations, as may be seen during a run-off event, affect coastal microbial communities. A mesocosm experiment using seawater from the Bedford Basin, Nova Scotia, was followed for 72 h after the addition of partially weathered diesel. Sequencing data suggests partially weathered diesel acts quickly to alter the prokaryotic community, as both opportunistic (Vibrio and Lentibacter) and oil-degrading (Colwellia, Sulfitobacter, and Pseudoalteromonas) bacteria proliferated after 24 h in comparison to the control. In addition, total prokaryotes seemed to recover in abundance after 24 h, where eukaryotes only ceased to decrease slightly at 72 h, likely because of an inability to adapt to the oil-laden conditions, unlike the prokaryotes. Considering there were no highly volatile components (benzene, toluene, ethylbenzene, and xylene) present in the diesel when the communities were exposed, the results indicate that even a relatively small concentration of diesel run-off can cause a drastic change to the microbial community under low energy conditions. Higher energy conditions due to wave action may mitigate the response of the microbial communities by dilution and additional weathering of the diesel.

Socioeconomic and Demographic Associations with Wintertime Air Pollution Exposures at Household, Community, and District Scales in Rural Beijing, China.

The Chinese government implemented a national household energy transition program that replaced residential coal heating stoves with electricity-powered heat pumps for space heating in northern China. As part of a baseline assessment of the program, this study investigated variability in personal air pollution exposures within villages and between villages and evaluated exposure patterns by sociodemographic factors. We randomly recruited 446 participants in 50 villages in four districts in rural Beijing and measured 24 h personal exposures to fine particulate matter (PM2.5) and black carbon (BC). The geometric mean personal exposure to PM2.5 and BC was 72 and 2.5 µg/m3, respectively. The variability in PM2.5 and BC exposures was greater within villages than between villages. Study participants who used traditional stoves as their dominant source of space heating were exposed to the highest levels of PM2.5 and BC. Wealthier households tended to burn more coal for space heating, whereas less wealthy households used more biomass. PM2.5 and BC exposures were almost uniformly distributed by socioeconomic status. Future work that combines these results with PM2.5 chemical composition analysis will shed light on whether air pollution source contributors (e.g., industrial, traffic, and household solid fuel burning) follow similar distributions.

Spatial modelling and inequalities of environmental noise in Accra, Ghana.

Noise pollution is a growing environmental health concern in rapidly urbanizing sub-Saharan African (SSA) cities. However, limited city-wide data constitutes a major barrier to investigating health impacts as well as implementing environmental policy in this growing population. As such, in this first of its kind study in West Africa, we measured, modelled and predicted environmental noise across the Greater Accra Metropolitan Area (GAMA) in Ghana, and evaluated inequalities in exposures by socioeconomic factors. Specifically, we measured environmental noise at 146 locations with weekly (n = 136 locations) and yearlong monitoring (n = 10 locations). We combined these data with geospatial and meteorological predictor variables to develop high-resolution land use regression (LUR) models to predict annual average noise levels (LAeq24hr, Lden, Lday, Lnight). The final LUR models were selected with a forward stepwise procedure and performance was evaluated with cross-validation. We spatially joined model predictions with national census data to estimate population levels of, and potential socioeconomic inequalities in, noise levels at the census enumeration-area level. Variables representing road-traffic and vegetation explained the most variation in noise levels at each site. Predicted day-evening-night (Lden) noise levels were highest in the city-center (Accra Metropolis) (median: 64.0 dBA) and near major roads (median: 68.5 dBA). In the Accra Metropolis, almost the entire population lived in areas where predicted Lden and night-time noise (Lnight) surpassed World Health Organization guidelines for road-traffic noise (Lden <53; and Lnight <45). The poorest areas in Accra also had significantly higher median Lden and Lnight compared with the wealthiest ones, with a difference of ∼5 dBA. The models can support environmental epidemiological studies, burden of disease assessments, and policies and interventions that address underlying causes of noise exposure inequalities within Accra.

Field measurements of indoor and community air quality in rural Beijing before, during, and after the COVID-19 lockdown.

The coronavirus (COVID-19) lockdown in China is thought to have reduced air pollution emissions due to reduced human mobility and economic activities. Few studies have assessed the impacts of COVID-19 on community and indoor air quality in environments with diverse socioeconomic and household energy use patterns. The main goal of this study was to evaluate whether indoor and community air pollution differed before, during, and after the COVID-19 lockdown in homes with different energy use patterns. Using calibrated real-time PM2.5 sensors, we measured indoor and community air quality in 147 homes from 30 villages in Beijing over 4 months including periods before, during, and after the COVID-19 lockdown. Community pollution was higher during the lockdown (61 ± 47 µg/m3 ) compared with before (45 ± 35 µg/m3 , p < 0.001) and after (47 ± 37 µg/m3 , p < 0.001) the lockdown. However, we did not observe significantly increased indoor PM2.5 during the COVID-19 lockdown. Indoor-generated PM2.5 in homes using clean energy for heating without smokers was the lowest compared with those using solid fuel with/without smokers, implying air pollutant emissions are reduced in homes using clean energy. Indoor air quality may not have been impacted by the COVID-19 lockdown in rural settings in China and appeared to be more impacted by the household energy choice and indoor smoking than the COVID-19 lockdown. As clean energy transitions occurred in rural households in northern China, our work highlights the importance of understanding multiple possible indoor sources to interpret the impacts of interventions, intended or otherwise.

Realizing the values of natural capital for inclusive, sustainable development: Informing China's new ecological development strategy.

A major challenge in transforming development to inclusive, sustainable pathways is the pervasive and persistent trade-off between provisioning services (e.g., agricultural production) on the one hand and regulating services (e.g., water purification, flood control) and biodiversity conservation on the other. We report on an application of China's new Ecological Development Strategy, now being formally tested and refined for subsequent scaling nationwide, which aims to mitigate and even eliminate these trade-offs. Our focus is the Ecosystem Function Conservation Area of Hainan Island, a rural, tropical region where expansion of rubber plantations has driven extensive loss of natural forest and its vital benefits to people. We explored both the biophysical and the socioeconomic options for achieving simultaneous improvements in product provision, regulating services, biodiversity, and livelihoods. We quantified historic trade-offs between rubber production and vital regulating services, finding that, over the past 20 y (1998-2017), there was a 72.2% increase in rubber plantation area, leading to decreases in soil retention (17.8%), water purification [reduced retention of nitrogen (56.3%) and phosphorus (27.4%)], flood mitigation (21.9%), carbon sequestration (1.7%), and habitat for biodiversity (6.9%). Using scenario analyses, we identified a two-pronged strategy that would significantly reduce these trade-offs, enhancing regulating services and biodiversity, while simultaneously diversifying and increasing product provision and improving livelihoods. This general approach to analyzing product provision, regulating services, biodiversity, and livelihoods has applicability in rural landscapes across China, South and Southeast Asia, and beyond.

Genomic correlates of clinical outcome in advanced prostate cancer.

Heterogeneity in the genomic landscape of metastatic prostate cancer has become apparent through several comprehensive profiling efforts, but little is known about the impact of this heterogeneity on clinical outcome. Here, we report comprehensive genomic and transcriptomic analysis of 429 patients with metastatic castration-resistant prostate cancer (mCRPC) linked with longitudinal clinical outcomes, integrating findings from whole-exome, transcriptome, and histologic analysis. For 128 patients treated with a first-line next-generation androgen receptor signaling inhibitor (ARSI; abiraterone or enzalutamide), we examined the association of 18 recurrent DNA- and RNA-based genomic alterations, including androgen receptor (AR) variant expression, AR transcriptional output, and neuroendocrine expression signatures, with clinical outcomes. Of these, only RB1 alteration was significantly associated with poor survival, whereas alterations in RB1, AR, and TP53 were associated with shorter time on treatment with an ARSI. This large analysis integrating mCRPC genomics with histology and clinical outcomes identifies RB1 genomic alteration as a potent predictor of poor outcome, and is a community resource for further interrogation of clinical and molecular associations.

Detection of PKD1 and PKD2 Somatic Variants in Autosomal Dominant Polycystic Kidney Cyst Epithelial Cells by Whole-Genome Sequencing.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the development of multiple cysts in the kidneys. It is often caused by pathogenic mutations in PKD1 and PKD2 genes that encode polycystin proteins. Although the molecular mechanisms for cystogenesis are not established, concurrent inactivating germline and somatic mutations in PKD1 and PKD2 have been previously observed in renal tubular epithelium (RTE). METHODS: To further investigate the cellular recessive mechanism of cystogenesis in RTE, we conducted whole-genome DNA sequencing analysis to identify germline variants and somatic alterations in RTE of 90 unique kidney cysts obtained during nephrectomy from 24 unrelated participants. RESULTS: Kidney cysts were overall genomically stable, with low burdens of somatic short mutations or large-scale structural alterations. Pathogenic somatic "second hit" alterations disrupting PKD1 or PKD2 were identified in 93% of the cysts. Of these, 77% of cysts acquired short mutations in PKD1 or PKD2 ; specifically, 60% resulted in protein truncations (nonsense, frameshift, or splice site) and 17% caused non-truncating mutations (missense, in-frame insertions, or deletions). Another 18% of cysts acquired somatic chromosomal loss of heterozygosity (LOH) events encompassing PKD1 or PKD2 ranging from 2.6 to 81.3 Mb. 14% of these cysts harbored copy number neutral LOH events, while the other 3% had hemizygous chromosomal deletions. LOH events frequently occurred at chromosomal fragile sites, or in regions comprising chromosome microdeletion diseases/syndromes. Almost all somatic "second hit" alterations occurred at the same germline mutated PKD1/2 gene. CONCLUSIONS: These findings further support a cellular recessive mechanism for cystogenesis in ADPKD primarily caused by inactivating germline and somatic variants of PKD1 or PKD2 genes in kidney cyst epithelium.

Virtual reality is beneficial in decreasing pain in labouring women: A preliminary study.

BACKGROUND: Women use a range of non-pharmacological pain relief methods to reduce labour pain intensity and to help manage labour pain. AIMS: The purpose of this intervention study was to determine whether virtual reality would have an effect on labour pain intensity. Virtual reality has been shown to be effective in reducing pain in other acute pain settings. MATERIALS AND METHODS: This study was an intervention study in labour in a cross-over within-subjects design (Clinical Trials Registry Number: ACTRN12618001776291P). Fourteen participants reported their pain and had their heart rate and blood pressure measured during active labour while using and not using virtual reality. RESULTS: There were significantly lower reported pain scores (6.14 compared to 7.61, P < 0.001) and maternal heart rate (79.86 beats per minute compared to 85.57, P = 0.033) and mean arterial pressure (88.78 mmHg compared to 92.61 mmHg, P = 0.022) were lower when using virtual reality compared to when not using virtual reality during active labour. CONCLUSION: This study makes an important contribution to the field of virtual reality in labour and birth. It is consistent with other recent findings of reduced pain in labour and links decreased pain scales to heart rate and blood pressure, the physiological markers of pain.

Spatial heterogeneity in drinking water sources in the Greater Accra Metropolitan Area (GAMA), Ghana.

Universal access to safe drinking water is essential to population health and well-being, as recognized in the Sustainable Development Goals (SDG). To develop targeted policies which improve urban access to improved water and ensure equity, there is the need to understand the spatial heterogeneity in drinking water sources and the factors underlying these patterns. Using the Shannon Entropy Index and the Index of Concentration at the Extremes at the enumeration area level, we analyzed census data to examine the spatial heterogeneity in drinking water sources and neighborhood income in the Greater Accra Metropolitan Area (GAMA), the largest urban agglomeration in Ghana. GAMA has been a laboratory for studying urban growth, economic security, and other concomitant socio-environmental and demographic issues in the recent past. The current study adds to this literature by telling a different story about the spatial heterogeneity of GAMA's water landscape at the enumeration area level. The findings of the study reveal considerable geographical heterogeneity and inequality in drinking water sources not evidenced in previous studies. We conclude that heterogeneity is neither good nor bad in GAMA judging by the dominance of both piped water sources and sachet water (machine-sealed 500-ml plastic bag of drinking water). The lessons from this study can be used to inform the planning of appropriate localized solutions targeted at providing piped water sources in neighborhoods lacking these services and to monitor progress in achieving universal access to improved drinking water as recognized in the SDG 6 and improving population health and well-being.

Lactococcus lactis Subspecies cremoris Elicits Protection Against Metabolic Changes Induced by a Western-Style Diet.

BACKGROUND & AIMS: A Western-style diet, which is high in fat and sugar, can cause significant dyslipidemia and nonalcoholic fatty liver disease; the diet has an especially strong effect in women, regardless of total calorie intake. Dietary supplementation with beneficial microbes might reduce the detrimental effects of a Western-style diet. We assessed the effects of Lactococcus lactis subspecies (subsp) cremoris on weight gain, liver fat, serum cholesterol, and insulin resistance in female mice on a high-fat, high-carbohydrate diet. METHODS: Female C57BL/6 mice were fed either a high-fat, high-carbohydrate (Western-style) diet that contained 40% fat (mostly milk fat) and 43% carbohydrate (mostly sucrose) or a calorie-matched-per-gram control diet. The diets of mice were supplemented with 1 × 109 colony-forming units of L lactis subsp cremoris ATCC 19257 or Lactobacillus rhamnosus GG ATCC 53103 (control bacteria) 3 times per week for 16 weeks. Body weights were measured, and fecal, blood, and liver tissues were collected and analyzed. Livers were analyzed for fat accumulation and inflammation, and blood samples were analyzed for cholesterol and glucose levels. Mice were housed within Comprehensive Lab Animal Monitoring System cages, and respiratory exchange ratio and activity were measured. Hepatic lipid profiles of L lactis subsp cremoris-supplemented mice were characterized by lipidomics mass spectrometry analysis. RESULTS: Mice fed L lactis subsp cremoris while on the Western-style diet gained less weight, developed less hepatic steatosis and inflammation, and had a lower mean serum level of cholesterol and body mass index than mice fed the control bacteria. Mice fed the L lactis subsp cremoris had increased glucose tolerance while on the Western-style diet compared to mice fed control bacteria and had alterations in hepatic lipids, including oxylipins. CONCLUSIONS: Dietary supplementation with L lactis subsp cremoris in female mice on a high-fat, high-carbohydrate (Western-style) diet caused them to gain less weight, develop less liver fat and inflammation, reduce serum cholesterol levels, and increase glucose tolerance compared with mice on the same diet fed control bacteria. L lactis subsp cremoris is safe for oral ingestion and might be developed for persons with metabolic and liver disorders caused by a Western-style diet.

Galectin-9 Is a Novel Regulator of Epithelial Restitution.

Increasingly, the ß-galactoside binding lectins, termed galectins, are being recognized as critical regulators of cell function and organismal homeostasis. Within the context of the mucosal surface, galectins are established regulators of innate and adaptive immune responses, microbial populations, and several critical epithelial functions, including cell migration, proliferation, and response to injury. However, given their complex tissue distribution and expression patterns, their role within specific processes remains poorly understood. We took a genetic approach to understand the role of endogenous galectin-9 (Gal-9), a mucosal galectin that has been linked to inflammatory bowel disease, within the context of the murine intestine. Gal-9-deficient (Gal9-/-, also known as Lgals9-/-) animals show increased sensitivity to chemically induced colitis and impaired proliferation in the setting of acute injury. Moreover, Gal9-/--derived enteroids showed impaired growth ex vivo. Consistent with a model in which endogenous Gal-9 controls epithelial growth and repair, Gal9-/- animals showed increased sensitivity to intestinal challenge in multiple models of epithelial injury, including acute irradiation injury and ectopic wound biopsies. Finally, regenerating crypts from patient biopsies showed increased expression of Gal-9, indicating these processes may be conserved in humans. Taken together, these studies implicate Gal-9 in the regulation of cellular proliferation and epithelial restitution after intestinal epithelial injury.

A Deep Learning Approach to Diagnostic Classification of Prostate Cancer Using Pathology-Radiology Fusion.

BACKGROUND: A definitive diagnosis of prostate cancer requires a biopsy to obtain tissue for pathologic analysis, but this is an invasive procedure and is associated with complications. PURPOSE: To develop an artificial intelligence (AI)-based model (named AI-biopsy) for the early diagnosis of prostate cancer using magnetic resonance (MR) images labeled with histopathology information. STUDY TYPE: Retrospective. POPULATION: Magnetic resonance imaging (MRI) data sets from 400 patients with suspected prostate cancer and with histological data (228 acquired in-house and 172 from external publicly available databases). FIELD STRENGTH/SEQUENCE: 1.5 to 3.0 Tesla, T2-weighted image pulse sequences. ASSESSMENT: MR images reviewed and selected by two radiologists (with 6 and 17 years of experience). The patient images were labeled with prostate biopsy including Gleason Score (6 to 10) or Grade Group (1 to 5) and reviewed by one pathologist (with 15 years of experience). Deep learning models were developed to distinguish 1) benign from cancerous tumor and 2) high-risk tumor from low-risk tumor. STATISTICAL TESTS: To evaluate our models, we calculated negative predictive value, positive predictive value, specificity, sensitivity, and accuracy. We also calculated areas under the receiver operating characteristic (ROC) curves (AUCs) and Cohen's kappa. RESULTS: Our computational method (https://github.com/ih-lab/AI-biopsy) achieved AUCs of 0.89 (95% confidence interval [CI]: [0.86-0.92]) and 0.78 (95% CI: [0.74-0.82]) to classify cancer vs. benign and high- vs. low-risk of prostate disease, respectively. DATA CONCLUSION: AI-biopsy provided a data-driven and reproducible way to assess cancer risk from MR images and a personalized strategy to potentially reduce the number of unnecessary biopsies. AI-biopsy highlighted the regions of MR images that contained the predictive features the algorithm used for diagnosis using the class activation map method. It is a fully automatic method with a drag-and-drop web interface (https://ai-biopsy.eipm-research.org) that allows radiologists to review AI-assessed MR images in real time. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Participatory Modeling of Water Vulnerability in Remote Alaskan Households Using Causal Loop Diagrams.

Despite perceptions of high water availability, adequate access to sufficient water resources remains a major challenge in Alaska. This paper uses a participatory modeling approach to investigate household water vulnerability in remote Alaska and to examine factors that affect water availability and water access. Specifically, the work asks: how do water policy stakeholders conceptualize the key processes that affect household water vulnerability in the context of rural Alaska? Fourteen water policy stakeholders participated in the modeling process, which included defining the problem of household water vulnerability and constructing individual causal loop diagrams (CLDs) that represent their conceptualization of household water vulnerability. Individual CLDs were subsequently combined and five sub-models emerged: environmental, economic, infrastructure, social, and health. The environmental and economic sub-models of the CLD are explored in depth. In the environmental sub-model, climate change and environmental barriers due to geography influence household water vulnerability. In the economic sub-model, four processes and one feedback loop affect household water vulnerability, including operations and maintenance funding, the strength of the rural Alaskan economy, and the impact of regulations. To overcome household water vulnerability and make households more resilient, stakeholders highlighted policy solutions under five themes: economics, social, regulatory, technological, and environmental.