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ABSTRACT: Increasing consumer concerns underscore the importance of verifying the practices and origins of food, especially certified premium products. The aim of this study was to evaluate the ability of Fourier-transform mid-infrared (FT-MIR) spectroscopy to authenticate animal welfare parameters, farming practices, and dairy systems. Data on farm characteristics were obtained from the Parmigiano Reggiano Consortium in northern Italy. Animal welfare data were collected by trained veterinarians using the assessment protocol developed by the Italian National Reference Center for Animal Welfare (CReNBA), and bulk milk test-day data were obtained from the laboratory of the Breeders Association of the Emilia Romagna Region. A merged final dataset of 12,083 bulk FT-MIR spectra records from 949 farms was created. Using a nonhierarchical clustering approach, the farms were classified into 5 dairy systems: 2 traditional systems comprising farms located in either the Apennines or the Po Plain; 2 modern systems, one that used TMR and one did not; and one traditional dairy system comprising farms rearing local breeds. To evaluate the ability of bulk milk to capture differences in farming systems, we conducted an ANOVA on milk composition. The linear models included the following effects: season, dairy system, farm, and the interaction between dairy system and season. The effect of the dairy system was significant for all milk composition traits. A 10-iteration linear discriminant analysis was used to evaluate the discriminative ability of the spectra in classifying farming practices and dairy systems. The average results of the area under the receiver operating characteristic curve revealed good authentication performance for genetic type (0.98), housing system (0.91), and feeding system (0.89), and medium-low authentication performance for geographical area (0.70); poor results were obtained for the percentage of concentrate in the diet and animal welfare parameters (0.57–0.64). With regard to dairy systems, the best result was obtained when dairy systems were grouped into 2 simplified categories, traditional versus modern (0.89), instead of the 5 categories (0.87). The results of this study show that FT-MIR is a useful tool for authenticating farming practices and dairy systems, but not animal welfare as defined by CReNBA evaluation criteria. Our results show that infrared spectroscopy has the potential to authenticate dairy products and quality label certifications.

Abstract Background Histotripsy is a novel, non-invasive, non-ionizing, and non-thermal ablation technique that disrupts tumors using acoustic cavitation. We report the first use of Histotripsy as bridging therapy prior to liver transplant for hepatocellular carcinoma (HCC) treated with histotripsy. Case presentation A 59-year-old woman presented with Metabolic-Associated Steatotic Liver Disease (MASLD) cirrhosis (labMELD = 14), hepatic encephalopathy, and a single 2 cm OPTN V lesion in the left lateral segment consistent with HCC. The patient underwent histotripsy treatment of the lesion as bridging therapy before receiving liver transplantation. Histopathology analysis of the explanted liver showed total necrosis of the treated area, with no residual viable tissue tumor. Conclusion This case demonstrates the potential utility of histotripsy as an effective bridging therapy for patients with combined cirrhosis and hepatocellular carcinoma (HCC) awaiting liver transplantation, with complete tumor necrosis on explant pathology demonstrating its therapeutic efficacy.

Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

This study aimed to study the relationship between milk quality for cheese manufacturing and farm’s environmental impacts in grass-based mountain systems. Beforehand, the multi-criteria evaluation methodology proposed by Botreau et al. and Rey-Cadilhac et al. was adapted to a routine use. Milk quality scores were constructed by weighing traits possibly predicted by spectroscopic analyses currently available in milk labs into 4 dimensions: health, nutritional, technological and sensory. Environmental impact scores were constructed by combining 6 indicators of the CAP'2ER® software in 5 dimensions: greenhouse gas emissions, eutrophication, air acidification, consumption of space and non-renewable energies and ecosystem biodiversity. The study sample included 15 dairy farms located in the French Massif Central mountains. An analysis of variance was carried out to study the effect of system’s types on milk quality and environmental impact scores. A principal component analysis was used to study the relationship between milk quality and environmental impact dimensions scores. No correlation has been established between overall milk quality and overall environmental impact scores. High scores for the nutritional and biodiversity dimensions and low scores for the resource consumption dimension, were associated with farming practices such as a high proportion of grasslands in the usable agricultural area, low stocking rate and low productivity per cow. This demonstrates the importance of defining specific priority objectives, on a farm-by-farm basis, in order to drive changes in agricultural practices. The multi-criteria evaluation model tested here appeared sensitive, but it needs to be tested on a larger scale and in different contexts.

The Arctic is as a key place to perform environmental measurements given its combination of reduced human activity and increased sensitivity to climate change. The Svalbard archipelago constitutes an invaluable measurement location, due to its ease of access and the presence of the Ny-Ålesund research center. Sensors are usually not designed to sustain prolonged periods of time in demanding environments like the Arctic; therefore, chances of failures, drift, and errors are higher than elsewhere. Maintenance and calibration of these sensors must be rigorous and frequent, to avoid poor-quality data, or even their loss. Within the frame of EURAMET EMRP project “MeteoMet 2”, calibration of the temperature sensors hosted by the Climate Change Tower (CCT), a unique research facility designed to monitor lower-atmosphere profiles of several meteorological quantities, has been performed. The calibration campaign pointed out sensor errors up to 1 °C and corrected the measurements, straightening the skewed temperature profiles. Absolute calibration uncertainties have been evaluated at ∼0.2 °C, less than half of those stated by the manufacturer, while an evaluation of relative uncertainties yielded values of just few 0.01 °C. This experience stimulated the creation of an in-situ calibration facility, to the benefit of the whole scientific community based in Ny-Ålesund.

Transitional care management (TCM) visits have been shown to reduce 30-day readmissions, but it is unclear whether the decrease arises from the TCM visit itself or from clinic-level changes to meet the requirements of the TCM visits. We conducted a cross-sectional analysis using data from Northwell Health to examine the association between the type of post-discharge follow-up visits (TCM visits versus non-TCM visits based on billing) and 30-day readmission. Furthermore, we assessed whether being seen by a provider who frequently utilizes TCM visits or the TCM visit itself was associated with 30-day readmission. We included adult patients hospitalized to Medicine service and subsequent follow-up visits within two weeks of discharge between February 24, 2018, and February 24, 2020. We examined 1) post-discharge follow-up visit type (TCM visit versus non-TCM visit) and 2) provider characteristics (frequent TCM visit utilization or not). The primary outcome was unplanned hospital readmission within 30 days following hospital discharge. After propensity matching, TCM follow-up visits were associated with decreased 30-day readmissions (hazard ratio = 0.74 [0.63-0.88]) compared to non-TCM visits. Among patients with non-TCM follow-up visits, those seen by a provider who frequently used TCM visits had decreased odds (OR = 0.84 [0.71-0.99]) of 30-day readmission compared to those seen by providers who did not use TCM visits regularly. Among patients who followed up with providers who frequently use TCM visits, TCM visits were associated with decreased 30-day readmission compared to patients with non-TCM visits (OR = 0.78 [0.62-0.98]). The study has limitations, including the health system database not capturing all out-of-network follow-up visits. The reduction in 30-day readmission associated with TCM visits likely arises from both the visit itself and being seen by a provider who frequently uses TCM visits.

ABSTRACT Background The identification of actionable molecular targets of pancreatic cancer (PAC) is key to improving patient outcomes. We hypothesized O6‐methylguanine‐DNA methyltransferase (MGMT) silencing may occur in a subset of PAC tumors, with unexplored clinical and molecular correlates. Experimental Design We leveraged sequencing data from The Cancer Genome Atlas (TCGA), the Clinical Proteomic Tumor Analysis Consortium 3 (CPTAC‐3), and the (Australian Pancreatic Cancer Genome Initiative) PACA‐AU cohorts to characterize MGMT‐silenced PAC. Genomic, transcriptomic, methylation, and clinical data were investigated, and findings were validated in silico using methylation, transcriptomic and drug sensitivity data from Cancer Cell Line Encyclopedia (CCLE) project, and in a real‐world cohort of PAC patients profiled for MGMT status at Istituto Nazionale Tumori of Milan (INT). Results On the basis of Human Methylation 450k data, MGMT silencing was identified in ~6% of PAC cases and was enriched in tumors with non‐ductal histology, with a trend toward longer overall survival. MGMT‐silenced tumors were associated with a lower frequency of KRAS mutations and showed features of immune exclusion. In the INT cohort, MGMT‐silencing was confirmed in ~7% of cases and prevalent in KRAS wild type tumors, with a favorable prognostic impact. In silico analysis suggested a higher sensitivity to alkylating and DNA damaging agents in MGMT‐silenced PAC cell lines. Conclusions MGMT silencing occurs in a small subgroup of PACs and is enriched in KRAS wild type cases, with a favorable prognostic impact. Our findings provide the rationale to explore combinations of alkylating with DNA damaging agents in MGMT‐silenced PAC.

Agriculture is facing complex and unprecedented challenges, such as climate change and global population growth, associated with the increase of food demand. Durum wheat (DW) is a strategic crop for food security in the Mediterranean region. In this work, the effect of two biostimulant compounds on drought response of two DW genotypes with different drought tolerance degree was evaluated: the tolerant genotype Svems16 and the sensitive cv. Iride. Genotyping-By-Sequencing analysis allowed to identify variants in response to water-related genes, such as those encoding dehydrins, with Svems16 exhibiting a missense variant divergent from the sequence found in Iride. Drought significantly hindered growth of cv. Iride by increasing oxidative stress and diminishing stomata density. This difficulty was mitigated by the application of biostimulants, which induced root morphological changes, and increased stomata density. On the other hand, the growth of Svems16 seedlings was not significantly affected by drought, confirming its significant degree of tolerance toward that stress compared with Iride. As a result, both biostimulants showed limited efficacy when applied to Svems16 stressed plants. In conclusion, the application of biostimulants emerges as a valuable agronomic strategy for mitigating drought stress in sensitive DW cultivars.

Aim To determine the prevalence and characteristics of pulmonary embolism (PE) in patients presenting with haemoptysis. Additionally, we assessed the efficiency and failure rates of different clinical diagnostic algorithms for PE in this patient population. Methods We enrolled consecutive adult patients who presented to nine Italian emergency departments with haemoptysis as the primary complaint. PE diagnosis was ruled out in patients with a low pre-test probability in combination with a negative age-adjusted D-dimer (referred to as the “age-adjusted” D-dimer strategy), a negative computed tomography pulmonary angiography or when a clear alternative source of bleeding was identified, along with negative findings for venous thromboembolism during a 30-day follow-up. Results A total of 546 patients were included in the study. The prevalence of PE, including the 30-day follow-up, was 4.2% (95% CI 2.7–6.3%). The majority of these cases (78%) exhibited distal (segmental or subsegmental) emboli and there were no PE-related fatalities. The “age-adjusted” D-dimer strategy initially excluded PE in 24% of patients (95% CI 21–28%), with a failure rate of 0.8% (95% CI 0.0–4.1%). Retrospectively applied, the “clinical probability-adjusted” D-dimer strategies, specifically the YEARS and Pulmonary Embolism Graduated d-Dimer (PEGeD) algorithms, excluded PE in a significantly higher proportion (30% and 32%, respectively) compared with the “age-adjusted” D-dimer strategy (p

The residency program in Emergency Medicine should include formal training in Non-Technical Skills (NTS). We evaluated the effectiveness of a program based on High-Fidelity Simulation (HFS) to improve the leadership and communication skills of residents in Emergency Medicine. In this prospective observational study, we performed 6 simulation sessions, each with 3 scenarios about the management of the critically ill. In the second to the fifth session, participants received specific training about: the ABCDE (Airway, Breathing, Circulation, Disability, Exposure) approach, leadership, communication, and situation awareness, one topic per session. Technical Skills (TS) were measured as the percentage of critical actions correctly performed by participants during the primary examination. NTS were rated by the Leadership Behavior Description Questionnaire (LBDQ), Communication Competence Questionnaire (CCP), and Clinical Teamwork Scale (CTS). The trend over the following sessions was evaluated. We examined 90 scenarios, 15 scenarios per session (three scenarios repeated 5 times). The LBDQ score reached in the fifth and sixth sessions (fifth: 25 [20-30]; sixth: 25 [22-29]), was significantly higher than that obtained in the first, second, and third ones (first: 23 [18-24]; second: 22 [16-26]; third: 20 [14-26], all p

This paper presents the mission analysis of 3Cat-8, a 6-Unit CubeSat mission being developed by the UPC NanoSat Lab for ionospheric research. The primary objective of the mission is to monitor the ionospheric scintillation of the aurora, and to perform several technological demonstrations. The satellite incorporates several novel systems, including a deployable Fresnel Zone Plate Antenna (FZPA), an integrated PocketQube deployer, a dual-receiver GNSS board for radio occultation and reflectometry experiments, and a polarimetric multi-spectral imager for auroral emission observations. The mission design, the suite of payloads, and the concept of operations are described in detail. This paper discusses the current development status of 3Cat-8, with several subsystems already developed and others in the final design phase. It is expected that the data gathered by 3Cat-8 will contribute to a better understanding of ionospheric effects on radio wave propagation and demonstrate the feasibility of compact remote sensors in a CubeSat platform.

Abstract In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated neuroendocrine tumors (WDNETs). However, prospective evidence of metformin safety and activity is lacking. Here, we conducted the first-in-human phase Ib MetNET2 trial to investigate the safety and antitumor activity of metformin in combination with the somatostatin analog lanreotide autogel (ATG) in both diabetic and non-diabetic patients with advanced WDNETs of the gastrointestinal (GI) or thoracic tract. Enrolled patients received lanreotide ATG 120 mg plus oral metformin, up to a maximum dosage of 2550 mg/day. We enrolled 20 patients, of whom 18 (90%) and 2 (10%) had WDNETs of the GI and thoracic tract, respectively. Fourteen patients (70%) were non-diabetic. With a 5% incidence of SAEs, the study met its primary objective of demonstrating treatment safety. With a median follow-up of 39 months (95% CI 28-NE), median PFS was 24 months (95% CI 16-NE), with 12-month and 24-month PFS probability of 75% (95% CI 58–97) and 49% (95% CI 31–77), respectively. We found no statistically significant PFS differences between diabetic and non-diabetic patients. Among exploratory analyses, the presence of tumor genomic alterations in DNA damage pathways was associated with trend towards worse PFS, whereas a precocious reduction of HOMA-IR index and plasma cholesterol concentration showed a trend towards an association with better PFS. In conclusion, metformin plus lanreotide ATG is a safe and well tolerated combination treatment that is associated with promising antitumor activity in both non-diabetic and diabetic patients with WDNETs, and that warrants further investigation in larger clinical trials.

This work aimed to investigate the effect of energy nature (lipids vs. carbohydrates) on enteric methane emission (eCH4) and performance in dairy cows fed grass silage-based diets. Eight multiparous Holstein cows were used in a 4 × 4 Latin square design, with 4 experimental periods of 28 days each. Cows were fed with 4 iso-energetic diets based on grass silage and supplemented with different levels of rapeseed oil (RO) (0, 1.5, 3.0, 4.5% of dietary dry matter (DM), Control, RO-low, RO-medium, RO-high diets, respectively) in substitution of starch from concentrate. Dairy performance, total-tract digestibility, and rumen parameters were measured when animals were in individual respiration chambers for quantifying eCH4. Intake of DM decreased with RO-high compared to other diets. Methane emissions were lowered similarly with all diets containing RO compared to Control (on average, -19% in g/d, −13% in g/kg DMI, −21% in g/kg milk). Ruminal propionate proportion was higher, whereas that of butyrate was lower with RO-high compared to the other diets. Milk yield was higher with RO-low and RO-medium, and was lower for RO-high compared to Control. Milk C16:0 concentration was lower, and C18:1c9, C18:1t11, and other rumen biohydrogenation intermediate concentrations were higher with diets containing RO compared to Control. The shift from the C18:1t11 to C18:1t10 biohydrogenation pathway is in agreement with the milk fat depression observed with RO-medium and RO-high. The inclusion of RO at 1.5% was the best compromise between eCH4, feed efficiency, and milk nutritional quality in cows fed grass silage-based diets.

The dataset available here comes from an experimental dairy cattle farm located in a mountain region in Central France, where the feeding systems are mostly pasture grazing combined with a period of indoor overwintering during the colder months. The dataset comprises individual productive and functional traits covering over 36 different variables in 185 primiparous Montbéliarde and Holstein cows, followed by data on productive longevity and reason for culling. The data was collected over a 20-year period during which animal husbandry and data collection protocols remained consistent. Potential re-users of the data are private-sector professionals, farmer associations, and researchers interested in developing statistical and mechanistic models and simulations of individual dairy cows under low-input grassland-based systems.