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Abstract Measuring vertical velocity in the atmosphere has long been a challenge due to its small magnitude. Taking advantage of the modulation of free tropospheric relative humidity by vertical motions, we derive analytical relationships that allow us to retrieve vertical motions in clear air from geostationary measurements of brightness temperature in the infrared absorption band of water vapor. The new observations have a resolution of 1 hr and 2 km in time and space, respectively. They capture the variability of mesoscale and large‐scale vertical velocity measured during field campaigns. In the mid‐troposphere, clear‐sky vertical motions are mostly subsiding but highly heterogeneous in space and time. Around organized deep convective systems, strong subsidence (>500 hPa·day−1) is observed within a distance of a few hundred kilometers. In contrast, transient upward motions of up to 100 hPa·day−1 can occur at the mesoscale. Vertical motions in the clear‐sky atmosphere appear to be primarily associated with buoyancy and gravity waves at the mesoscale, and with radiative cooling and equatorial waves at larger spatial scales. This new retrieval reveals a rich range of dynamical features that were previously invisible, thus shedding new light on tropical meteorology.

Key Clinical Message Inferior vena cava atresia is a rare condition with highly variable anatomy due to the complexity of caval embryology. When endovascular venovenous reconstruction is considered for severe persistent sequelae, multimodality imaging with CT and invasive venography is used to determine the appropriateness of intervention and for procedural planning.

Abstract In the tropics, more precisely in equatorial dense rainforest, xylogenesis is driven by a little distinct climatological seasonality, and many tropical trees do not show clear growth rings. This makes retrospective analyses and modeling of future tree performance difficult. This research investigates the presence, the distinctness, and the periodicity of growth ring for dominant tree species in two semi‐deciduous rainforests, which contrast in terms of precipitation dynamics. Eighteen tree species common to both forests were investigated. We used the cambial marking technique and then verified the presence and periodicity of growth‐ring boundaries in the wood produced between pinning and collection by microscopic and macroscopic observation. The study showed that all eighteen species can form visible growth rings in both sites. However, the periodicity of ring formation varied significantly within and between species, and within sites. Trees from the site with clearly defined dry season had a higher likelihood to form periodical growth rings compared to those from the site where rainfall seasonality is less pronounced. The distinctness of the formed rings however did not show a site dependency. Periodical growth‐ring formation was more likely in fast‐growing trees. Furthermore, improvements can be made by a detailed study of the cambial activity through microcores taken at high temporal resolution, to get insight on the phenology of the lateral meristem.

Abstract Introduction The gut microbiota (GM) can influence the pathogenesis of immune‐mediated adverse events (irAEs). Proton pump inhibitors (PPIs) can affect the integrity of GM, but their role in promoting irAEs is still poorly understood. Methods In this retrospective single‐center cohort study, the primary endpoint was the evaluation of the incidence of gastrointestinal (GI) irAEs in cancer patients on PPIs (exposed) versus cancer patients who were not on PPIs (unexposed). Results Three hundred and sixty three patients' records (248 M/115F, median age 69) were reviewed. Twenty‐three exposed patients (92%) developed GI irAEs while only two unexposed patients (8%) developed GI irAEs (hazard ratio [HR] 13.22, 95% confidence interval [CI] 3.11–56.10, p

Key Clinical Message Tumor‐induced osteomalacia is a paraneoplastic syndrome characterized by renal phosphate wasting and deranged bone turnover. Clinicians should consider tumor‐induced osteomalacia in unexplained hypophosphatemia and investigate for underlying tumors. Abstract Tumor‐induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, which leads to deranged bone turnover. TIO is usually associated with benign mesenchymal tumors, although it has also been reported in malignant tumors. We present the case of a 56‐year‐old individual who experienced a protracted 6‐year clinical course characterized by hypophosphatemia, weakness, and kyphosis, alongside the presence of a foot tumor. Subsequently, this lesion displayed malignant behavior and was ultimately diagnosed as a high‐grade sarcoma. To date, this case is among the 10 reported cases in the literature of a mesenchymal tumor associated with TIO undergoing malignant transformation. This report underscores the importance of a comprehensive evaluation of patients with unexplained hypophosphatemia and highlights the need for diligent follow‐up to detect possible malignant transformation of the underlying tumor. Clinicians should consider TIO in the differential diagnosis of hypophosphatemia and promptly investigate for the presence of an underlying tumor, as early detection may improve the patient's prognosis.

Abstract Heart failure is a leading cause of morbidity and mortality, with relevant social and economic burden on global healthcare system. Although the development of novel diagnostic tools and the advance in therapies have deeply influenced the diagnosis and treatment of this disease, improving both prognosis and life expectancy of patients, hospitalization is still high, and mortality remains considerable. MicroRNAs are small endogenous RNA molecules that post‐transcriptionally regulate gene expression in both physiological and pathological processes. In recent years, microRNA have arisen as attractive therapeutic targets in the treatment of a wide spectrum of pathologies, including heart failure. In cardiac pathology, deregulation of microRNAs expression and function is associated to adverse outcome and heart failure progression. Circulating levels of specific microRNAs have emerged as useful biomarkers for the diagnosis of heart failure or as prognostic indicators. In the present review, we summarize the state of current research on the role of miRNAs as biomarkers for diagnosis and prognosis in patients with heart failure and their use as potential therapeutic targets for this condition.

Key Clinical Message The detection of a novel HMBS gene mutation (c.457C > T) in a Mexican woman with acute intermittent porphyria underscores the importance of expanding genetic analyses in diverse populations to improve diagnosis, management, and knowledge of the disease's clinical implications. Abstract Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a deficiency in the enzymatic activity of porphobilinogen deaminase (HMBS), resulting in the accumulation of toxic heme metabolites. In this report, we present the case of a Mexican woman with AIP who experienced recurrent episodes of severe abdominal pain, weakness, vomiting, and insomnia. Despite the challenges in diagnosis and treatment, genetic analysis revealed a novel HMBS mutation, c.457C > T (p.Q153X), located in exon 9. This mutation induces a premature translational stop codon and had not been previously reported in medical literature among individuals with AIP. Remarkably, the patient exhibited a positive response to RNA interference therapy. We hypothesize that this novel HMBS mutation may potentially account for the more severe clinical presentation observed in this case. However, further research is necessary to establish a definitive link between this specific mutation and disease severity. The prevalence and genetic variants of AIP in Mexico remain largely unknown, underscoring the importance of conducting additional research and expanding genetic analyses to gain a better understanding of the clinical implications associated with these mutations.

Abstract Ocean mesoscale eddies enhance meridional buoyancy transport, notably in the Antarctic Circumpolar Current where they contribute to setting the deep stratification of the neighboring ocean basins. The much‐needed parameterization of this buoyancy transport in global climate models requires a theory for the overall flux, but also for its vertical structure inside the fluid column. Based on the quasi‐geostrophic dynamics of an idealized patch of ocean hosting an arbitrary vertically sheared zonal flow, we provide a quantitative prediction for the vertical structure of the buoyancy flux without adjustable parameters. The prediction agrees quantitatively with meridional flux profiles obtained through numerical simulations of an idealized patch of ocean with realistic parameter values. This work empowers modelers with an explicit and physically based expression for the vertical profile of buoyancy transport by ocean baroclinic turbulence, as opposed to the common practice of using arbitrary prescriptions for the depth‐dependence of the transport coefficients.

Abstract Meteorological data are useful in many fields related to climate change studies and their use often requires them to be continuous. To date, marginal distribution sampling (MDS), which consists of filling a missing value with an average of the data that are found in similar meteorological conditions over a flexible time window, is widely adopted in the FLUXNET community. In this work, we evaluate the performance of MDS at diurnal and monthly scales for the incoming shortwave radiation (Swin), relative humidity (RH), vapour pressure deficit (VPD), air and soil temperatures (Tair, Tsoil) acquired across seven sites in West Africa. The criteria tested are the MDS's ability to (i) fill gaps while reducing the error rate, (ii) represent proper variability within data and finally (iii) ensure homogeneity between its output and original data. We found during the daytime that MDS is adequate for filling gaps in Swin when both reducing error rate and a good representation of variability are targeted. If the goal is to have a small error rate, then this approach is recommended for all investigated variables except VPD. During nighttime, MDS is satisfactory to minimize the error when filling gaps in Tair, Tsoil and RH while to represent their variabilities it becomes more sensitive to the rate of missing data. At a monthly scale, the gap‐filled data are consistent with the original ones for all variables attributable to data size and a wider sliding window that allows more data under similar conditions to be considered.

Abstract Over the last 3 years new definitions of sarcopenia by the Sarcopenia Definition and Outcome Consortium (2020, SDOC), European Working Group on Sarcopenia in Older People (2019, EWGSOP2) and Asian Working Group on Sarcopenia (2019, AWGS2) have been proposed. The objective of this scoping review was to explore predictive validity of these current sarcopenia definitions for clinical outcomes. We followed the PRISMA checklist for scoping reviews. Based on a systematic search performed by two independent reviewers of databases (Pubmed and Embase) articles comparing predictive validity of two or more sarcopenia definitions on prospective clinical outcomes published since January 2019 (the year these definitions were introduced) were included. Data were extracted and results collated by clinical outcomes and by sarcopenia definitions, respectively. Of 4493 articles screened, 11 studies (mean age of participants 77.6 (SD 5.7) years and 50.0% female) comprising 82 validity tests were included. Overall, validity tests on the following categories of clinical outcomes were performed: fracture (n = 40, assessed in one study), mortality (n = 18), function (n = 11), institutionalization (n = 7), falls (n = 4), and hospitalization (n = 2). Thereby, EWGSOP2 was investigated in 15 validity tests (18.3%) on all categories of clinical outcomes, whereas SDOC was investigated in four validity tests (4.9%) in one study on fractures in men only, and none of the validity tests investigated predictive validity by the AWGS2. However, we were not able to pool the data using a meta‐analytic approach due to important methodological heterogeneity between the studies. We identified various definitions of clinical outcomes that were used to test predictive validity of sarcopenia definitions suggesting that an agreement on an operational definition of a clinical outcome is key to advance in the field of sarcopenia. Moreover, data on predictive validity using the sarcopenia definitions by the SDOC and AWGS2 are still scarce and lacking, respectively. In a next step, prospective studies including both women and men are needed to compare predictive validity of current sarcopenia definitions on defined key clinical outcomes.

Abstract The fan mussel Pinna nobilis is currently on the brink of extinction due to a multifactorial disease mainly caused to the highly pathogenic parasite Haplosporidium pinnae, meaning that the selection pressure outweighs the adaptive potential of the species. Hopefully, rare individuals have been observed somehow resistant to the parasite, stretching the need to identify the traits underlying this better fitness. Among the candidate to explore at first intention are fast‐evolving immune genes, of which toll‐like receptor (TLR). In this study, we examined the genetic diversity at 14 TLR loci across P. nobilis, Pinna rudis and P. nobilis × P. rudis hybrid genomes, collected at four physically distant regions, that were found to be either resistant or sensitive to the parasite H. pinnae. We report a high genetic diversity, mainly observed at cell surface TLRs compared with that of endosomal TLRs. However, the endosomal TLR‐7 exhibited unexpected level of diversity and haplotype phylogeny. The lack of population structure, associated with a high genetic diversity and elevated dN/dS ratio, was interpreted as balancing selection, though both directional and purifying selection were detected. Interestingly, roughly 40% of the P. nobilis identified as resistant to H. pinnae were introgressed with P. rudis TLR. Specifically, they all carried a TLR‐7 of P. rudis origin, whereas sensitive P. nobilis were not introgressed, at least at TLR loci. Small contributions of TLR‐6 and TLR‐4 single‐nucleotide polymorphisms to the clustering of resistant and susceptible individuals could be detected, but their specific role in resistance remains highly speculative. This study provides new information on the diversity of TLR genes within the P. nobilis species after MME and additional insights into adaptation to H. pinnae that should contribute to the conservation of this Mediterranean endemic species.

Abstract Aims The assessment of frailty in older adults with heart failure (HF) is still debated. Here, we compare the predictive role and the diagnostic accuracy of physical vs. multidimensional frailty assessment on mortality, disability, and hospitalization in older adults with and without HF. Methods and results A total of 1077 elderly (≥65 years) outpatients were evaluated with the physical (phy‐Fi) and multidimensional (m‐Fi) frailty scores and according to the presence or the absence of HF. Mortality, disability, and hospitalizations were assessed at baseline and after a 24 month follow‐up. Cox regression analysis demonstrated that, compared with phy‐Fi score, m‐Fi score was more predictive of mortality [hazard ratio (HR) = 1.05 vs. 0.66], disability (HR = 1.02 vs. 0.89), and hospitalization (HR = 1.03 vs. 0.96) in the absence and even more in the presence of HF (HR = 1.11 vs. 0.63, 1.06 vs. 0.98, and 1.14 vs. 1.03, respectively). The area under the curve indicated a better diagnostic accuracy with m‐Fi score than with phy‐Fi score for mortality, disability, and hospitalizations, both in absence (0.782 vs. 0.649, 0.763 vs. 0.695, and 0.732 vs. 0.666, respectively) and in presence of HF (0.824 vs. 0.625, 0.886 vs. 0.793, and 0.812 vs. 0.688, respectively). Conclusions The m‐Fi score is able to predict mortality, disability, and hospitalizations better than the phy‐Fi score, not only in absence but also in presence of HF. Our data also demonstrate that the m‐Fi score has better diagnostic accuracy than the phy‐Fi score. Thus, the use of the m‐FI score should be considered for the assessment of frailty in older HF adults.

Abstract The meridional temperature profile of the upper layers of planetary atmospheres is set through a balance between differential radiative heating by a nearby star, or by intrinsic heat fluxes emanating from the deep interior, and the redistribution of that heat across latitudes by turbulent flows. These flows spontaneously arise through baroclinic instability of the meridional temperature gradients maintained by the forcing. When planetary curvature is neglected, this turbulence takes the form of coherent vortices that mix the meridional temperature profiles. However, the curvature of the planet favors the emergence of Rossby waves and zonal jets that restrict the meridional wandering of the fluid columns, thereby reducing the mixing efficiency across latitudes. A similar situation arises in the ocean, where the baroclinic instability of zonal currents leads to enhanced meridional heat transport by a turbulent flow consisting of vortices and zonal jets. A recent scaling theory for the turbulent heat transport by vortices is extended to include the impact of planetary curvature, in the framework of the two‐layer quasi‐geostrophic beta‐plane model. This leads to a quantitative parameterization providing the meridional temperature profile in terms of the externally imposed heat flux in an idealized model of planetary atmospheres and oceans. In addition, it provides a quantitative prediction for the emergent criticality, that is, the degree of instability in a canonical model of planetary atmosphere or ocean.

We have previously shown that secreted BAG3 is a potential target for the treatment of pancreatic ductal adenocarcinoma and that pancreatic tumor growth and metastatic dissemination can be reduced by treatment with an anti‐BAG3 murine antibody. Here, we used complementarity‐determining region (CDR) grafting to generate a humanized version of the anti‐BAG3 antibody that may be further developed for possible clinical use. We show that the humanized anti‐BAG3 antibody, named BAG3‐H2L4, abrogates BAG3 binding to macrophages and subsequent release of IL‐6. Furthermore, it specifically localizes into tumor tissues and significantly inhibits the growth of Mia PaCa‐2 pancreatic cancer cell xenografts. We propose BAG3‐H2L4 antibody as a potential clinical candidate for BAG3‐targeted therapy in pancreatic cancer.

Abstract Background Pancreatic cancer (PC) patients have multiple risk factors for sarcopenia and loss of skeletal muscle mass (LSMM), which may cause greater treatment toxicities, reduced response to cancer therapy, prolonged hospitalization, impaired quality of life, and worse prognosis. Methods This is a retrospective study on advanced PC patients treated at the Department of Oncology of Udine, Italy, from January 2012 to November 2017. Among 162 patients who received chemotherapy, 94 consecutive patients with an available computed tomography (CT) scan were retrospectively analyzed. The primary objective of our study was to explore if an early LSMM ≥ 10% (measured at first radiological evaluation and compared with baseline) and/or baseline sarcopenia may impact prognosis. Baseline sarcopenia was defined according to Prado's criteria. Skeletal muscle area was measured as cross‐sectional areas (cm2) using CT scan data through the Picture archiving and communication system (PACS) image system. Results In the whole cohort, 48% of patients were ≤70 years old, and 50% had metastatic disease. At baseline, 73% of patients had sarcopenia, and 16% presented a visceral fat area ≥ 44 cm2/m2. Overall, 21% experienced an early LSMM ≥ 10%. Approximately 33% of sarcopenic patients at baseline and ~35% of patients with early LSMM ≥ 10% had a body mass index > 25 kg/m2. Of note, 71% of patients were evaluated by a nutritionist, and 56% received a dietary supplementation (oral and/or parenteral). After a median follow‐up of 30.44 months, median overall survival (OS) was 11.28 months, whereas median progression‐free survival (PFS) was 5.72 months. By multivariate analysis, early LSMM ≥ 10% was significantly associated with worse OS [hazard ratio (HR): 2.16; 95% confidence interval (CI) 1.23–3.78; P = 0.007] and PFS (HR: 2.31; 95% CI 1.30–4.09; P = 0.004). Moreover, an exploratory analysis showed that inflammatory indexes, such as neutrophil–lymphocyte ratio variation, impact early LSMM ≥ 10% (odds ratio 1.31, 95% CI 1.06–1.61, P = 0.010). Conclusions Early LSMM ≥ 10% has a negative prognostic role in advanced PC patients. Further prospective investigations are needed to confirm these preliminary data.