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Abstract Triple‐negative breast cancer (TNBC) often develops resistance to single‐agent treatment, which can be circumvented using targeted combinatorial approaches. Here, we demonstrate that the simultaneous inhibition of LOXL2 and BRD4 synergistically limits TNBC proliferation in vitro and in vivo. Mechanistically, LOXL2 interacts in the nucleus with the short isoform of BRD4 (BRD4S), MED1, and the cell cycle transcriptional regulator B‐MyB. These interactions sustain the formation of BRD4 and MED1 nuclear transcriptional foci and control cell cycle progression at the gene expression level. The pharmacological co‐inhibition of LOXL2 and BRD4 reduces BRD4 nuclear foci, BRD4‐MED1 colocalization, and the transcription of cell cycle genes, thus suppressing TNBC cell proliferation. Targeting the interaction between BRD4S and LOXL2 could be a starting point for the development of new anticancer strategies for the treatment of TNBC.

Abstract While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be achieved. Here, we investigate the metabolic enzymes and processes that are essential for the resolution of DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Further analysis identified that Peroxiredoxin 1, PRDX1, contributes to the DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it reduces DNA damage‐induced nuclear reactive oxygen species. Moreover, PRDX1 loss lowers aspartate availability, which is required for the DNA damage‐induced upregulation of de novo nucleotide synthesis. In the absence of PRDX1, cells accumulate replication stress and DNA damage, leading to proliferation defects that are exacerbated in the presence of etoposide, thus revealing a role for PRDX1 as a DNA damage surveillance factor.

Abstract Hate speech has become a social problem that needs to be addressed urgently. In many cases, these discourses and ideologies arrive through the media and the internet, and they are transferred to educational contexts. Debates of this type should be addressed at school and should be channelled into a democratic debate, and into the definition of shared objectives through the development of counterspeeches and alternative narratives based on Human Rights. In this research, we investigate the capacity of future teachers (n = 114) to identify online hate speech and how they develop counterspeeches. The results show that the majority are able to identify hate speech. However, future teachers present more difficulties developing counterspeeches or complex alternative narratives, which can be transferred to educational practices. We conclude that teacher training needs to be redesigned if we want them to be able to face these problems in their future educational practice.

Our aim was to compare hand radiation exposure using leaded vs. regular latex surgical gloves in endourological procedures. We conducted a single-center prospective comparative study between January 2017 and December 2020. Surgeon 1 wore leaded surgical gloves, while Surgeon 2 voluntarily wore regular latex surgical gloves. A ring badge and chest dosimeters were used to estimate hand and whole-body scattered radiation dose in all endourological stone procedures (ureteroscopy (URS), retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL)). We found that Surgeon 1 and 2 performed a mean of 158 (SD 15.2) and 158 (SD 15.1) procedures/year, respectively, for a total of 1,092 between 2017 and 2020 between the two surgeons (696 URS/RIRS and 396 PCNL). The overall mean hand annual radiation exposure dose for Surgeon 1 and 2 was 2.87 mSv (SD 1.3) and 14.89 mSv (SD 7.87), respectively (p = 0.027), which corresponds to a mean of 0.02 (SD 0.02) and 0.1 mSv (SD 0.1) per procedure (p < 0.001). The estimated annual scattered radiation was 0.0012 and 0.0016, respectively (p = 0.63). We concluded that the use of leaded gloves in endourological stone procedures showed a significant reduction of radiation dose per year and per procedure compared to regular latex gloves; no increase in whole-body scattered radiation was detected with their use. We believe that the use of leaded gloves may be recommended, especially in urologists who dedicate most of their practice to endoscopic stone surgery. Further studies are needed to define whether these gloves could increase patient radiation exposure. [ABSTRACT FROM AUTHOR]

Background: Prone positioning of patients with COVID-19 undergoing invasive mechanical ventilation (IMV) is widely used, but evidence of efficacy remains sparse. The COVID-19 Critical Care Consortium has generated one of the largest global datasets on the management and outcomes of critically ill COVID-19 patients. This prospective cohort study investigated the association between prone positioning and mortality and in particular focussed on timing of treatment. Methods: We investigated the incidence, demographic profile, management and outcomes of proned patients undergoing IMV for COVID-19 in the study. We compared outcomes between patients prone positioned within 48 h of IMV to those (i) never proned, and (ii) proned only after 48 h. Results: 3131 patients had data on prone positioning, 1482 (47%) were never proned, 1034 (33%) were proned within 48 h and 615 (20%) were proned only after 48 h of commencement of IMV. 28-day (hazard ratio 0.82, 95% confidence interval [CI] 0.68, 0.98, p = 0.03) and 90-day (hazard ratio 0.81, 95% CI 0.68, 0.96, p = 0.02) mortality risks were lower in those patients proned within 48 h of IMV compared to those never proned. However, there was no evidence for a statistically significant association between prone positioning after 48 h with 28-day (hazard ratio 0.93, 95% CI 0.75, 1.14, p = 0.47) or 90-day mortality (hazard ratio 0.95, 95% CI 0.78, 1.16, p = 0.59). Conclusions: Prone positioning is associated with improved outcomes in patients with COVID-19, but timing matters. We found no association between later proning and patient outcome. [ABSTRACT FROM AUTHOR]

Background: Neutrophil granulocytes are important parts of the defence against bacterial infections. Their action is a two-edged sword, the mediators killing the intruding bacteria are at the same time causing tissue damage. Neutrophil activation is part of the dysregulated immune response to infection defining sepsis and neutrophil elastase is one of the powerful proteases causing both effects and damage. Inhibition of neutrophil elastase has been tried in sepsis and ARDS, so far with inconclusive results. Methods: We used positron emission tomography (PET) combined with computed tomography (CT) and the selective and specific neutrophil elastase inhibitor PET-tracer [11C]GW457427 ([11C]NES), in an intensive care unit porcine Escherichia coli sepsis model with the primary aim to visualise the biodistribution of neutrophil elastase in the initial acute phase of the septic reaction. Repeated PET–CT investigations were performed before and after induction of sepsis. Results: At baseline [11C]NES uptake was found in the bone marrow, spleen and liver. The uptake in the bone marrow was markedly increased two hours into the sepsis, whereas in spleen and liver the uptake was not as markedly changed compared to baseline. At 4 h after the sepsis induction [11C]NES in the bone marrow decreased while the uptake increased in the spleen, liver and lungs. Conclusion: The neutrophil elastase PET-tracer [11C]NES is a novel and unique instrument to study the acute innate neutrophil immune response in sepsis and associated vital organ failure. We here present images and quantitative data of the neutrophil elastase distribution the first hours of acute experimental sepsis. Surprisingly, a pronounced increase of neutrophil elastase was found in the bone marrow 2 h into the sepsis reaction followed at 4 h by increase in the liver, spleen and lungs and a concomitant reduction of the tracer uptake in bone marrow. [ABSTRACT FROM AUTHOR]

We consider a pair (A , B) where A is an algebra over a base field F , and B = { e i } i ∈ I a basis of A satisfying the following property: for any i , j ∈ I we have e i e j ∈ F e k for some k ∈ I . We show that A decomposes as A = s ⊕ d where s is a semisimple ideal of A , (a direct sum of simple ideals), and d is the direct sum of non-simple indecomposable ideals of A . Moreover, this decomposition is unique. We show that the ideals s and d are characterized by a new linear property. An interpretation of this result in terms of graph theory is also provided. [ABSTRACT FROM AUTHOR]

The effects on the measurement of water sorption and apparent diffusivity when using different flow rate values and different experimental setups, i.e., closed pan, open pan and hanging setup, have been studied in a series of Dynamic Vapor Sorption (DVS) experiments on a spruce sample. The results confirm a concave exponential growth dependency between apparent diffusivity and flow rate and an effect from the setup used, with the hanging setup being optimal for conducting such experiments due to the exposure of both areas of the disk to the airflow. [ABSTRACT FROM AUTHOR]

When producing load-bearing timber products with one-component polyurethane adhesives and certain wood species, e.g., beech or larch, primers can be used to obtain stronger and more durable bonds. The active chemicals of three existing primer systems, hydroxymethylated resorcinol formaldehyde (HMR), polysorbate 20 (PS20), and poly(ethylene glycol) (PEG), were used to impregnate beech wood. Young’s modulus (E) in the radial direction was determined in tensile mode. A modified E can influence the deformation and stress distribution at the wood-glue interface. Compared to the untreated wood, the average E was reduced by 7% for the water-treated reference and the HMR treatment. With the PS20 treatment, the average E was reduced by 16%, compared to the untreated wood, and by 45% with the PEG treatment. [ABSTRACT FROM AUTHOR]

We study, for a continuous linear operator T acting on an F-space X, when the direct sum operator T ⊕ T is recurrent on the direct sum space X ⊕ X . In particular: we establish the analogous notion for recurrence to that of (topological) weak-mixing for transitivity/hypercyclicity, namely quasi-rigidity; and we construct a recurrent but not quasi-rigid operator on each separable infinite-dimensional Banach space, solving the T ⊕ T -recurrence problem in the negative way. [ABSTRACT FROM AUTHOR]

Soluble ST2 (sST2) is released in response to vascular congestion, inflammation, and pro-fibrotic stimuli. In heart failure (HF), elevated levels of sST2 are associated with a higher risk of adverse clinical outcomes. Emerging evidence suggests that carbohydrate antigen 125 (CA125) may act as a ligand that modulates the inflammatory response. We hypothesized that CA125 might be modulating sST2 activity. In a cohort of 160 patients with acute (AHF) and renal dysfunction, we investigated whether the prognostic value of sST2 varies according to CA125 levels. The endpoints were: (a) total cardiovascular and renal hospitalizations and (b) all-cause mortality during follow-up. Cox regression analyses assessed the association between admission sST2 and endpoints across CA125 (≤ 35 vs. > 35 U/ml). This sub-study of the IMPROVE-HF trial shows that sST2 predicted the composite of cardiovascular or renal rehospitalizations when CA125 was elevated (> 35 U/ml) but not when CA125 ≤ 35 U/ml. These results highlight a potential biological interaction between sST2 and CA125, suggesting that CA125 status may refine the prognostic utility of sST2 in AHF. Clinically, these insights could guide personalized risk stratification and management strategies in this high-risk population. [ABSTRACT FROM AUTHOR]

Given the heterogeneity of acute myeloid leukemia patients, it is necessary to identify patients considered fit for intensive therapy but who will perform poorly, and in whom alternative approaches deserve investigation. We analyzed 1034 fit adults ≤70 years intensively treated between 2012 and 2022 in the CETLAM group. Young adults (≤ 60 years) presented higher remission rates and improved survival than older adults above that age (CR 79% vs. 73%; p = 0.03 and 4-yr OS 53% vs. 33%; p < 0.001). Remission and survival outcomes varied among different genetic subsets. An especially adverse genetic group included complex, monosomal karyotype, TP53 alterations (deleted/mutated), and MECOMr. Transplant feasibility in this very adverse risk group was low, and OS and EFS at 4 years were 14% and 12%, in contrast to 70% and 57% in the favorable group and 38% and 32% in all other patients. We integrated clinical and genetic data into the Intensive Chemotherapy Score for AML (ICSA) with 6-risk categories with significantly different remission rates and OS, validated in another cohort of 581 AML patients from a previous CETLAM protocol. In summary, we identified groups of fit patients that benefit differently from an intensive approach which may be helpful in future treatment decisions. [ABSTRACT FROM AUTHOR]

Purpose: To determine the occurrence of gastrointestinal (GI) symptoms in different settings among cyclists participating in a non-professional cycling event. The nutritional intake during the event and the association between GI symptoms and both nutritional and non-nutritional factors were also analyzed. Methods: A descriptive correlational study was performed among participants in the 2023 'Mallorca 312-Milestone Series' cycling event. A pre-race questionnaire was completed by 247 participants (37 women) while a post-race questionnaire was completed by 138 participants (24 women). Results: The prevalence of GI symptoms in training sessions and in previous cycling events were 22–26%. GI complaints during the race were reported by 38.4% of participants. GI symptoms during training (p = 0.003), in previous cycling events (p = 0.012) and in the Mallorca 312 event (during: p = 0.010; after p = 0.014) were associated with rest GI symptoms. Furthermore, GI symptoms during the Mallorca 312 event were associated with an immediately previous more nervous feeling (p = 0.016). Participants with shorter previous experience in similar events reported a more nervous feeling (p = 0.023). On average, participants in the Mallorca 312 achieved the recommended carbohydrate intake (59.2 g/h; recommended 30–60 g/h) and the fluid intake (500 ml; recommended 400–800 ml/h) rates. No association was found between GI symptoms and nutritional parameters or food intake. Conclusion: GI symptoms at rest could be considered the main factor associated with GI symptoms in cyclists. GI symptoms during the event were also associated with a more nervous feeling, which could be explained, at least in part, by shorter previous experience. [ABSTRACT FROM AUTHOR]

Practices for controlling intracranial pressure (ICP) in traumatic brain injury (TBI) patients admitted to the intensive care unit (ICU) vary considerably between centres. To help understand the rational basis for such variance in care, this study aims to identify the patient-level predictors of changes in ICP management. We extracted all heterogeneous data (2008 pre-ICU and ICU variables) collected from a prospective cohort (n = 844, 51 ICUs) of ICP-monitored TBI patients in the Collaborative European NeuroTrauma Effectiveness Research in TBI study. We developed the TILTomorrow modelling strategy, which leverages recurrent neural networks to map a token-embedded time series representation of all variables (including missing values) to an ordinal, dynamic prediction of the following day's five-category therapy intensity level (TIL(Basic)) score. With 20 repeats of fivefold cross-validation, we trained TILTomorrow on different variable sets and applied the TimeSHAP (temporal extension of SHapley Additive exPlanations) algorithm to estimate variable contributions towards predictions of next-day changes in TIL(Basic). Based on Somers' Dxy, the full range of variables explained 68% (95% CI 65–72%) of the ordinal variation in next-day changes in TIL(Basic) on day one and up to 51% (95% CI 45–56%) thereafter, when changes in TIL(Basic) became less frequent. Up to 81% (95% CI 78–85%) of this explanation could be derived from non-treatment variables (i.e., markers of pathophysiology and injury severity), but the prior trajectory of ICU management significantly improved prediction of future de-escalations in ICP-targeted treatment. Whilst there was no significant difference in the predictive discriminability (i.e., area under receiver operating characteristic curve) between next-day escalations (0.80 [95% CI 0.77–0.84]) and de-escalations (0.79 [95% CI 0.76–0.82]) in TIL(Basic) after day two, we found specific predictor effects to be more robust with de-escalations. The most important predictors of day-to-day changes in ICP management included preceding treatments, age, space-occupying lesions, ICP, metabolic derangements, and neurological function. Serial protein biomarkers were also important and may serve a useful role in the clinical armamentarium for assessing therapeutic needs. Approximately half of the ordinal variation in day-to-day changes in TIL(Basic) after day two remained unexplained, underscoring the significant contribution of unmeasured factors or clinicians' personal preferences in ICP treatment. At the same time, specific dynamic markers of pathophysiology associated strongly with changes in treatment intensity and, upon mechanistic investigation, may improve the timing and personalised targeting of future care. [ABSTRACT FROM AUTHOR]

This study presents characterisation of diatom's PtLPCAT1 (acyl-CoA: lysophosphatidylcholine acyltransferase) activity in phospholipid remodelling. In this research microsomal fractions of yeast Δale1 mutant overexpressing PtLPCAT1 were used as a source of the tested enzyme. In the assays evaluating remodelling of different phospholipids by PtLPCAT1 not modified microsomal fractions of the tested yeast were used. The enzyme most intensively remodelled fatty acid composition of microsomal phosphatidylcholine (PC), however, it was also able to remodel phosphatidylethanolamine (PE) and phosphatidic acid (PA). To study the ability of the tested enzyme to remodel PC molecules containing fatty acids from the VLC-PUFA biosynthetic pathway the tested microsomes were enriched biochemically with: sn-1-18:1-sn-2-18:3(n-3)-PC, sn-1-18:1-sn-2-18:3(n-6)-PC, sn-1-18:1-sn-2-18:4(n-3)-PC, sn-1-18:1-sn-2-20:4(n-3)-PC and sn-1-18:1-sn-2-20:5(n-3)-PC. Further on it was shown that PtLPCAT1 was able to remodel PC of such modified microsomes with higher intensity than PC of unmodified microsomes. The remodelling efficiency of PtLPCAT1 was affected also by fatty acid donors; the process was most efficient when acyl-CoAs with unsaturated fatty acids were in the assays. In comparative studies the properties of Arabidopsis AtLPCAT1 and yeast ALE1 were tested. Effect of the temperature and pH values on the remodelling activity of PtLPCAT1 was also examined. [ABSTRACT FROM AUTHOR]

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neuro-developmental disorder that often persists into adulthood. Moreover, it is frequently accompanied by bipolar disorder (BD) as well as borderline personality disorder (BPD). It is unclear whether these disorders share underlying pathomechanisms, given that all three are characterized by alterations in affective states, either long or short-term. BD is characterized by infrequent but intense mood shifts, while ADHD and BPD involve more dynamic emotional fluctuations. It is yet to be determined whether these disorders represent distinct phenomena or different points on a spectrum of affective dysregulation. Methods: This study seeks to distinguish the emotional dysregulation of BPD, ADHD, and BD by using digital phenotyping, a measurement burst electronic-diary method with different sampling rates, and accelerometry to measure participants' activity. Our study will include 480 participants aged 14 to 50 (120 each from BPD, ADHD, BD, and healthy control groups) from five European sites. Participants' smartphones will provide continuous data on their digital phenotypes, i.e., by indicators of physical activity and communication, for one year, along with daily evening ratings of mood and sleep. Moreover, five intensive measurement periods of five days each, called measurement bursts, will occur throughout the year, with electronic diaries asking participants to report on mood, self-esteem, impulsivity, life events, social interactions, and dysfunctional behaviors ten times a day. Moreover, participants will wear activity sensors during the five measurement bursts. Statistical analysis aims to identify whether affective dysregulation aspects share or differ across disorders. Specifically, data analysis aims to investigate the differences in parameters of affect fluctuation such as attractor strength and variability between disorders and to test the association of genetic risk factors for psychiatric disorders and resilience factors with critical parameters of affect modulation. Discussion: The results of this study offer the potential to link patients' external exposures with their affective state, reduce misdiagnosis, and determine the best timing for therapeutic interventions. Potential limitations of the study include insufficient recruitment of patients and drop-outs due to various protocol violations. Trial registration: Study code: DRKS00028917, registered 27.07.2022, https://drks.de/search/de/trial/DRKS00028917. [ABSTRACT FROM AUTHOR]

Introduction: Autophagy, a catabolic process enabling cellular organelles and proteins' reuse for energy, has been observed in varicocele models, but the effect of surgical treatment on this process remains unknown. This study aims to assess autophagy in varicocele models undergoing surgical correction. Materials and Methods: Twenty-one adolescent male rats were induced with varicocele and divided into three groups: sham, varicocele, and varicocele with varicocelectomy. After 21 days, testicles were examined histologically for spermatogenesis (Jonhsen's score) and immunohistochemically for autophagy markers (LC3A, Beclin-1, Ambra-1, ULK-1, p62). Positive germ cells were quantitatively evaluated, and data were statistically analyzed (p < 0.05). Results: Histological examination revealed significantly reduced Jonhsen's scores in varicocele compared to sham and varicocelectomy groups (p < 0.05). Expression of autophagy markers (LC3A, Beclin-1, Ambra-1, ULK-1, p62) was significantly higher in varicocele than sham and varicocelectomy groups (p < 0.05), and in varicocelectomy than sham (p < 0.05). Conclusions: Varicocele activates autophagy markers, with p62 potentially modulating autophagy despite being considered an inhibitor. While varicocelectomy improves histology, it doesn't fully inhibit autophagy, suggesting ongoing germ cell dysfunction despite treatment. This underscores varicocele's detrimental effects on germ cell functionality. [ABSTRACT FROM AUTHOR]

The extraordinary preservation of Cueva de Los Murciélagos (Albuñol, Spain) provides a unique opportunity to identify the materials and the techniques involved in archery during the Early Neolithic period. Arrows with preserved feathers, tied fibres, adhesive substance, and two probable bowstrings have been studied trough an unprecedented multi-proxy investigation, including microscopy and biomolecular methods, to unravel archery techniques. The study has identified the oldest known sinew bowstrings, the first evidence for the use of olive tree (Olea europaea) and reed (Phragmites sp.) to produce arrow shafts in prehistoric European archery, and the identification of birch bark tar as a coating on the shafts. The results of this study provide insights into ancient craft, technological solutions, and adaptations to local resources in the production of these reed-shafted hardwood tipped arrows and bowstrings. Their deposition in a burial cave sheds new light on the role of these artefacts in a Neolithic farming community. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by a progressive β-cell destruction. There are no clinically established methods for quantifying endocrine cells of the pancreas and current knowledge is almost exclusively based on autopsy material and functional measurements. Based on the expression of the γ-aminobutyric acid A receptors (GABAARs) in pancreatic islets and the fact that GABAAR agonists are being explored as treatment for T1D, we hypothesized that the positron emission tomography (PET) tracer [11C]flumazenil ([11C]FMZ) could serve as a marker of the endocrine mass of the pancreas. The in vivo uptake of [11C]FMZ in pig pancreas was evaluated by PET/CT, either tracer alone or after blockade of GABAAR by unlabeled flumazenil. The pancreatic binding of [11C]FMZ was investigated in vitro with frozen sections of pig pancreas as well as human organ donors, in addition to isolated mouse and human islets and exocrine preparations. The expression of GABAAR subunits in pig, human and mouse pancreas was explored by immunohistochemistry. Results: Strong specific in vivo uptake of [11C]FMZ was observed in the pig brain as expected, but in the pancreas the signal was moderate and only partially reduced by blockade. In vitro experiments revealed a positive but weak and variable binding of [11C]FMZ in islets compared to exocrine tissue in the mouse, pig and human pancreas. In pig and mouse pancreatic islets we identified the GABAAR subunits β2 and γ2 but not α2. In the human pancreas from non-diabetic donors, we have identified the α2, β2 (although weak) and γ2 subunits, whereas from a T2D donor the α2 subunit was missing. Conclusions: Our findings suggest that [11C]FMZ bind to GABAARs in the islets, but not with a sufficient contrast or magnitude to be implemented as an in vivo PET marker for the endocrine mass of the pancreas. However, GABAARs with different subunits are widely expressed in the endocrine cells within the pancreas in pig, human and mouse. Hence, the GABAAR could still be a potential imaging target for the endocrine cells of the pancreas but would require tracers with higher affinity and selectivity for individual GABAAR subunits. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes most of the cases of bronchiolitis and thousands of deaths annually, particularly in infants less than 6 months old. In Catalonia (Spain), infants born between April 2023 and March 2024 aged 0–6 months during their first RSV season have been candidates to receive nirsevimab, the novel monoclonal antibody against RSV, since October 2023. We aimed to analyse the dynamics of all-causes bronchiolitis diagnoses and RSV community infections in the current season and compare them to pre-nirsevimab epidemics. We collected epidemiological data from the Information System for Surveillance of Infections in Catalonia (SIVIC) on daily all-causes bronchiolitis clinical diagnoses and RSV-confirmed cases provided by rapid antigen tests in primary care practices. We calculated the rate ratio (RR) for the incidence of all-causes bronchiolitis for children aged 0-11 m-old with respect to 12-35 m-old between September 2014 and January 2024. We analysed the RR of the incidence of RSV-confirmed infection for 0-11 m-old and 12-35 m-old with respect to the > 35 m-old, from January 2021 to January 2024. We then computed the relative difference of the RR, designated as percentage of reduction of risk, between season 2023/2024 and former epidemics. With a global coverage recorded rate for nirsevimab of 82.2% in January 2024, the age-specific 0-11 m-old RR (95% CI) of RSV infection incidence for > 35 m-old was 1.7 (1.5–2.0) in season 2023/2024. The RR (95% CI) had been 7.4 (5.6–9.9), 8.8 (6.9–11.3), and 7.1 (5.7–8.9) in 2020/2021, 2021/2022, and 2022/2023, respectively. Regarding the incidence of all-causes bronchiolitis for the 0-11 m-old group compared to the 12-35 m-old, the pre-pandemic (2014/2015–2019/2020) and 2022/2023 RR (95% CI) were 9.4 (9.2–9.6) and 6.0 (5.7–6.2), respectively, significantly higher than the RR of 3.6 (3.4–3.8) for the most recent season, 2023/2024. Conclusion: Concurring with the introduction of nirsevimab, the risk of RSV infection for infants aged 0-11 m-old compared to > 35 m-old has been reduced by 75.6% (73.4–77.5) in last season, and the risk for all-causes bronchiolitis for 12-35 m-old by 61.9% (60.9–62.9) from the pre-pandemic period and by 39.8% (39.3–40.2) from the 2022/2023 epidemic, despite high RSV community transmission, especially in older infants What is Known: • RSV is responsible for approximately 70% of bronchiolitis cases and causes severe disease, particularly in infants < 6 months of age. • Nirsevimab effectiveness against RSV-associated disease, particularly hospitalisations, was expected to be around 80%; other Spanish regions, such as Galicia and Valencia, and European countries including Luxembourg and Germany, have already reported good results in implementing nirsevimab to prevent RSV-associated hospitalisations and PICU stays. What is New: • We provide insight into the community incidence of RSV and all-causes bronchiolitis for season 2023/2024, when nirsevimab has been introduced to the Catalan population, using. primary healthcare data, which enabled us to assess the burden of RSV infections and bronchiolitis in the commonly seasonally saturated primary healthcare practices. • Our study reveals that the risk of all-causes bronchiolitis for infants aged 0-11 m-old compared to older infants was reduced by 40% compared to the previous season and 62% compared to pre-pandemic standards, and for RSV infection it was reduced by 76%. [ABSTRACT FROM AUTHOR]

Background: Our Hospital in Northern Italy assists 3817 people living with HIV (PLWH) and has faced the impact of COVID-19. Little is known about the impact of HIV infection on the risk of post-COVID-19 conditions (PCCs) onset. We aim to assess the incidence of PCC in PLWH and the factors associated with its occurrence. Methods: We performed a retrospective, observational study including all PLWH > 18 years registered in the Brescia Health Protection Agency database, assessing SARS-CoV-2 burden, vaccination status, socio-demographic, and viro-immunological parameters from February 2020 until May 2022. Persistence of self-reported symptoms (clustered into gastrointestinal, respiratory, osteo-muscular, and neuro-behavioral symptoms) was evaluated after 3 months by a telephone-administered questionnaire. We estimated the associations between all variables and outcomes through univariate and multivariable logistic models. Results: In the study period, 653 PLWH were diagnosed with SARS-CoV-2 infection (17.1%). We observed 19 (2.9%) reinfections, 71 (10.9%) hospitalizations, and 3 (0.5%) deaths. We interviewed 510/653 PLWH (78%), and 178 (PCCs prevalence 34.9%; CI 95% 30.7–39.2) reported persistent symptoms. Asthenia/fatigue was the most reported symptom (60/178), followed by muscular pain (54/178). In the multivariate regression model, there was a lower risk of PCCs in males respect to females (adjusted OR = 0.64; CI 95% 0.99–3.66), while hospitalization during acute infection was associated with an increased the risk of PCCs (adjusted OR = 1.9; CI 95% 0.99–3.66). Notably, no viro-immunological variable modified the PCCs risk onset. Conclusions: Our study highlights a substantial prevalence of PCCs among PLWH, three months post-SARS-CoV-2 infection, independent of viro-immunological features or vaccination status. [ABSTRACT FROM AUTHOR]

Abstract Inhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non‐invasive tests. Here, we propose monoamine‐derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine‐derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF‐D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L‐histidine analog, or a low L‐histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.

In the present paper, we introduce a high-resolution spatiotemporal point cloud time series, acquired using a LiDAR sensor mounted 30 metres above ground on a flux observation tower monitoring a boreal forest. The dataset comprises a 18-month long (April 2020 - September 2021) time series with an average interval of 3.5 days between observations. The data acquisition, transfer, and storage systems established at Hyytiälä (Finland) are named the LiDAR Phenology station (LiPhe). The dataset consists of 103 time points of LiDAR point clouds covering a total of 458 individual trees, comprising three distinct Boreal species. Additional reference information includes the respective location, the species, and the initial height (at the first time point) of each individual tree. The processing scripts are included to outline the workflow used to generate the individual tree point clouds (LiPheKit). The presented dataset offers a comprehensive insight into inter- and intra-species variations of the individual trees regarding their growth strategies, phenological dynamics, and other functioning processes over two growth seasons. [ABSTRACT FROM AUTHOR]

As society experiences accelerated ageing, understanding the complex biological processes of human ageing, which are affected by a large number of variables and factors, becomes increasingly crucial. Artificial intelligence (AI) presents a promising avenue for ageing research, offering the ability to detect patterns, make accurate predictions, and extract valuable insights from large volumes of complex, heterogeneous data. As ageing research increasingly leverages AI techniques, we present a timely systematic literature review to explore the current state-of-the-art in this field following a rigorous and transparent review methodology. As a result, a total of 77 articles have been identified, summarised, and categorised based on their characteristics. AI techniques, such as machine learning and deep learning, have been extensively used to analyse diverse datasets, comprising imaging, genetic, behavioural, and contextual data. Findings showcase the potential of AI in predicting age-related outcomes, developing ageing biomarkers, and determining factors associated with healthy ageing. However, challenges related to data quality, interpretability of AI models, and privacy and ethical considerations have also been identified. Despite the advancements, novel approaches suggest that there is still room for improvement to provide personalised AI-driven healthcare services and promote active ageing initiatives with the ultimate goal of enhancing the quality of life and well-being of older adults. Overview of the literature review. [ABSTRACT FROM AUTHOR]

Adapting our behavior to environmental demands relies on our capacity to perceive and manage potential conflicts within our surroundings. While evidence implicates the involvement of the lateral prefrontal cortex and theta oscillations in detecting conflict stimuli, their causal role in conflict expectation remains elusive. Consequently, the exact computations and neural mechanisms underlying these cognitive processes still need to be determined. We employed an integrative approach involving cognitive computational modeling, fMRI, TMS, and EEG to establish a causal link between oscillatory brain function, its neurocomputational role, and the resulting conflict processing and adaptation behavior. Our results reveal a computational process underlying conflict expectation, which correlates with BOLD-fMRI and theta activity in the superior frontal gyrus (SFG). Modulation of theta activity via rhythmic TMS applied over the SFG induces endogenous theta activity, which in turn enhances computations associated with conflict expectation. These findings provide evidence for the causal involvement of SFG theta activity in learning and allocating cognitive resources to address forthcoming conflict stimuli.Martínez-Molina et al. utilized fMRI, EEG-TMS, and cognitive modeling to reveal the mechanisms behind expectation and adaptation to upcoming conflicting events, demonstrating the causal role of theta oscillations in the lateral prefrontal cortex. [ABSTRACT FROM AUTHOR]

The selective photoreduction of CO2 in aqueous media based on earth-abundant elements only, is today a challenging topic. Here we present the anchoring of discrete molecular catalysts on organic polymeric semiconductors via covalent bonding, generating molecular hybrid materials with well-defined active sites for CO2 photoreduction, exclusively to CO in purely aqueous media. The molecular catalysts are based on aryl substituted Co phthalocyanines that can be coordinated by dangling pyridyl attached to a polymeric covalent triazine framework that acts as a light absorber. This generates a molecular hybrid material that efficiently and selectively achieves the photoreduction of CO2 to CO in KHCO3 aqueous buffer, giving high yields in the range of 22 mmol g−1 (458 μmol g−1 h−1) and turnover numbers above 550 in 48 h, with no deactivation and no detectable H2. The electron transfer mechanism for the activation of the catalyst is proposed based on the combined results from time-resolved fluorescence spectroscopy, in situ spectroscopies and quantum chemical calculations. The selective CO2 photoreduction in water mediated by earth-abundant photocatalysts remains highly challenging. Here the authors present the coordinative anchorage of molecular catalysts on a pyridine-armed covalent triazine framework for CO2 photoreduction to CO in fully aqueous solutions. [ABSTRACT FROM AUTHOR]

Nuclear metabolism and DNA damage response are intertwined processes, but the precise molecular links remain elusive. Here, we explore this crosstalk using triple-negative breast cancer (TNBC) as a model, a subtype often prone to DNA damage accumulation. We show that the de novo purine synthesis enzyme IMPDH2 is enriched on chromatin in TNBC compared to other subtypes. IMPDH2 chromatin localization is DNA damage dependent, and IMPDH2 repression leads to DNA damage accumulation. On chromatin, IMPDH2 interacts with and modulates PARP1 activity by controlling the nuclear availability of NAD+ to fine-tune the DNA damage response. However, when IMPDH2 is restricted to the nucleus, it depletes nuclear NAD+, leading to PARP1 cleavage and cell death. Our study identifies a non-canonical nuclear role for IMPDH2, acting as a convergence point of nuclear metabolism and DNA damage response. Metabolism plays an important role in response to DNA damage, however the underlying mechanisms are less clear. Here, the authors identify a non-canonical role of IMPDH2 wherein it is recruited to the chromatin following DNA damage and mediates PARP1-dependent DNA damage repair via the regulation of nuclear NAD+ levels. [ABSTRACT FROM AUTHOR]

Subcellular compartmentalization of metabolic enzymes establishes a unique metabolic environment that elicits specific cellular functions. Indeed, the nuclear translocation of certain metabolic enzymes is required for epigenetic regulation and gene expression control. Here, we show that the nuclear localization of the mitochondrial enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) ensures mitosis progression. Nuclear MTHFD2 interacts with proteins involved in mitosis regulation and centromere stability, including the methyltransferases KMT5A and DNMT3B. Loss of MTHFD2 induces severe methylation defects and impedes correct mitosis completion. MTHFD2 deficient cells display chromosome congression and segregation defects and accumulate chromosomal aberrations. Blocking the catalytic nuclear function of MTHFD2 recapitulates the phenotype observed in MTHFD2 deficient cells, whereas restricting MTHFD2 to the nucleus is sufficient to ensure correct mitotic progression. Our discovery uncovers a nuclear role for MTHFD2, supporting the notion that translocation of metabolic enzymes to the nucleus is required to meet precise chromatin needs. The nuclear localization of metabolic enzymes is fascinating and in most cases remains a mystery. Here, Pardo Lorente and colleagues show that nuclear MTHFD2 is required for successful mitosis by controlling centromeric histone methylation. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to determine the effectiveness of natural (NatZeo) and acid-treated (AcidZeo) zeolites in increasing the nitrogen (N) recovery of sugarcane grown under conditions highly conducive for N losses. Methods: This glasshouse trial replicated the pedoclimatic conditions typical of the Australian sugarcane industry in the Wet Tropics to evaluate the capacity and economic feasibility of using NatZeo and AcidZeo to reduce leaching and increase plant and soil N recovery in a highly permeable sandy-loam soil. Nitrogen fertiliser was applied at two rates (84 and 120 kg N ha−1) as 15N-enriched urea. Results: Compared with the unamended treatments, AcidZeo led to significantly higher average fertiliser N recoveries in both the soil (+24%) and plant (+54%), which resulted in significantly lower overall N losses (−22%). However, the significantly higher capacity of AcidZeo in retaining ions limited the availability of potassium and sulphur to the plants and led to a 4% yield reduction. The use of NatZeo led to lower abatements of N losses (−6%) but increased N recoveries in the plant (+22%). NatZeo did not result in as much cation immobilisation, which, combined with the increased plant/soil N recovery, resulted in the highest yield of the trial (+8% compared with the unamended treatments). The economic analysis indicated that only NatZeo could potentially increase farmer's income when applied in 20 cm wide strips around the fertiliser band. Conclusions: This study highlights that zeolites have potential to improve the environmental sustainability and profitability of sugarcane cropping systems. [ABSTRACT FROM AUTHOR]

Background: Despite higher breast cancer screening rates, black women still are more likely to have late-stage disease diagnosed. This disparity is influenced in part by structural and interpersonal racism. This prospective study sought to determine how interpersonal factors, including perceived discrimination, influence screening and stage of disease at diagnosis. Methods: A prospective cohort study analyzed adult women with stages I to IV breast cancer from the Miami Breast Cancer Disparities Study. Perceived discrimination and mistrust of providers were assessed using previously validated questionnaires. Multivariable logistic regression was used to evaluate the odds of screening mammography utilization and late-stage breast cancer at diagnosis. Results: The study enrolled 342 patients (54.4 % Hispanic, 15.8 % white, and 17.3 % black). Multivariate regression, after control for both individual- and neighborhood-level factors, showed that a higher level of perceived discrimination was associated with greater odds of late-stage disease (adjusted odds ratio [aOR], 1.06; range, 1.01–1.12); p = 0.022) and lower odds of screening mammography (aOR, 0.96; range, 0.92–0.99; p = 0.046). A higher level of perceived discrimination also was negatively correlated with multiple measures of provider trust. Discussion: This study identified that high perceived level of discrimination is associated with decreased odds of ever having a screening mammogram and increased odds of late-stage disease. Efforts are needed to reach women who experience perceived discrimination and to improve the patient–provider trust relationship because these may be modifiable risk factors for barriers to screening and late-stage disease presentation, which ultimately have an impact on breast cancer survival. [ABSTRACT FROM AUTHOR]

The conservation of threatened plant species needs precise monitoring studies to assess population trends and improve management strategies. Here, we investigated the viability of employing high-accuracy RTK-GPS technology for demographic evaluation of Euphorbia fontqueriana, a critically endangered species of the western Mediterranean Basin. Our study aimed to evaluate the utility of RTK-GPS technology, compare its applicability with traditional methods, and determine its impact on decision-making in conservation. We used permanent plots and comprehensive field surveys to monitor population dynamics, and transitions between plant stages and vital rates were recorded and analysed. Results revealed a positive population trend for E. fontqueriana, contrasting with previous studies. Vegetative stage was the most representative of the population, and high survival rates were observed for vegetative and reproductive individuals. Elasticity analysis showed higher value for vegetative stage. The study underscores the importance of employing high-accuracy plant monitoring methods for effective conservation assessments and emphasizes the potential of RTK-GPS technology in enhancing conservation efforts for threatened plant species. [ABSTRACT FROM AUTHOR]

Purpose: Disease heterogeneity in coronavirus disease 2019 (COVID-19) may render the current one-size-fits-all treatment approach suboptimal. We aimed to identify and immunologically characterize clinical phenotypes among critically ill COVID-19 patients, and to assess heterogeneity of corticosteroid treatment effect. Methods: We applied consensus k-means clustering on 21 clinical parameters obtained within 24 h after admission to the intensive care unit (ICU) from 13,279 COVID-19 patients admitted to 82 Dutch ICUs from February 2020 to February 2022. Derived phenotypes were reproduced in 6225 COVID-19 ICU patients from Spain (February 2020 to December 2021). Longitudinal immunological characterization was performed in three COVID-19 ICU cohorts from the Netherlands and Germany, and associations between corticosteroid treatment and survival were assessed across phenotypes. Results: We derived three phenotypes: COVIDICU1 (43% of patients) consisted of younger patients with the lowest Acute Physiology And Chronic Health Evaluation (APACHE) scores, highest body mass index (BMI), lowest PaO2/FiO2 ratio, and a 90-day in-hospital mortality rate of 18%. COVIDICU2 patients (37%) had the lowest BMI, were older and had higher APACHE scores and mortality rate (24%) than COVIDICU1. Patients with COVIDICU3 (20%) were the eldest with the most comorbidities, the highest APACHE scores, acute kidney injury and metabolic dysregulations, and the highest mortality rate (47%). These patients also displayed the most pronounced inflammatory response. Corticosteroid therapy started at day 5 [2–9] after ICU admission and administered for 5 [3–7] days was associated with an increased risk for 90-day mortality in patients with the COVIDICU1 and COVIDICU2 phenotypes (hazard ratio [HR] 1.59 [1.09–2.31], p = 0.015 and HR 1.79 [1.42–2.26], p < 0.001, respectively), but not in patients with the COVIDICU3 phenotype (HR 1.08 [0.76–1.54], p = 0.654). Conclusion: Our multinational study identified three distinct clinical COVID-19 phenotypes, each exhibiting marked differences in demographic, clinical, and immunological features, and in the response to late and short-term corticosteroid treatment. [ABSTRACT FROM AUTHOR]

There are more ways to synthesize a 100-amino acid (aa) protein (20100) than there are atoms in the universe. Only a very small fraction of such a vast sequence space can ever be experimentally or computationally surveyed. Deep neural networks are increasingly being used to navigate high-dimensional sequence spaces1. However, these models are extremely complicated. Here, by experimentally sampling from sequence spaces larger than 1010, we show that the genetic architecture of at least some proteins is remarkably simple, allowing accurate genetic prediction in high-dimensional sequence spaces with fully interpretable energy models. These models capture the nonlinear relationships between free energies and phenotypes but otherwise consist of additive free energy changes with a small contribution from pairwise energetic couplings. These energetic couplings are sparse and associated with structural contacts and backbone proximity. Our results indicate that protein genetics is actually both rather simple and intelligible.By experimentally sampling from sequence spaces larger than 1010 and using thermodynamic models, the genetic structure of at least some proteins can be well described, indicating that protein genetics is simpler than anticipated. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present study is to assess the role of indocyanine green (ICG) to evaluate distal ureteral vascularity during robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion and its impact on the incidence of benign ureteroenteric strictures (UES). Methods: The study included patients who underwent RARC for bladder cancer between 2018 and 2023. All patients included underwent intracorporeal urinary diversion with ileal conduit or neobladder. Bricker technique was performed in all ureteroenteric anastomosis. ICG was employed during the study period to evaluate ureteral vascularity. We divided patients into 2 groups depending on the utilization of ICG during surgery and compared demographic, clinicopathological and perioperative outcomes, including benign UES rates. Results: We identified 221 patients that underwent RARC with intracorporeal urinary diversion. Ileal conduit was performed in 173 (78.3%) patients and neobladder in 48 (21.7%) cases. A total of 142 (64.3%) and 79 (35.7%) patients were in the non-ICG and ICG group, respectively. With a median follow-up of the entire cohort of 21.1 months, there were no differences in the rate of benign UES after RARC between the non-ICG and the ICG group (p = 0.901). In the non-ICG group, 26 (18.3%) patients developed benign UES and in the ICG group 15 (19.0%) patients. Most of the strictures appeared in the left ureter in both groups (80.8% non-ICG vs. 66.7% ICG, p = 0.599). Median time to stricture diagnosis was 4 months (IQR 3-7.25) for the non-ICG and 3 months (IQR 2–5) for the ICG group (p = 0.091). The ICG group had a slightly greater length of ureter resected compared with the non-ICG group (1.5 vs. 1.3 cm, p = 0.007). Conclusion: In our experience, choosing to use ICG intraoperatively to evaluate distal ureteral vascularity may not reduce the rate of benign UES after robot-assisted radical cystectomy with intracorporeal urinary diversion and Bricker ureteroileal anastomosis. [ABSTRACT FROM AUTHOR]

The valorization of biogas as a renewable energy source faces a major obstacle regarding its purification. Siloxane is one of the impurities that cause problems such as damages to equipment of combustion engines, turbines, and boilers used for biogas conversion to heat and electricity. In this review, adsorption for siloxane removal is widely discussed, with two specific approaches: adsorbents sensitivity to water and regeneration, two essential points for industrial application. Thus, determining factors in adsorbents capacity, reusability, and water tolerance including textural properties, surface functional groups, and hydrophobicity are deeply analyzed. Studies oriented to the optimization of traditional adsorbents such as activated carbon, silica gel, and aluminosilicates as well as newly emerging adsorbents such as metal organic frameworks, graphene oxides, and waste-derived materials are studied in detail in terms of reusability and water tolerance. Although activated carbon is commercially used, its low selectivity, pore blockage due to siloxane polymerization, and unsuccessful regeneration make it disadvantageous. Silica gel, however, shows better reusability as a result of less adsorbent-adsorbate dissociation energy. In addition, aluminosilicates, despite its low adsorption capacity, proved to be more practical for real biogas due to their high hydrophobicity. Graphene oxide cost and energy efficiency in their synthesis make them more industrially appealing candidates despite their low adsorption capacity. Finally, metal organic frameworks demonstrated high selectivity, high adsorption capacity, and more efficient regeneration and therefore have more advantages and less drawbacks, although the number of published studies is still limited. [ABSTRACT FROM AUTHOR]

The spatial mismatch between jobs and housing in cities creates long daily travels that exacerbate climate change, air pollution, and traffic congestion. Yet, not enough research on occupational differences has been done. This study first applies the Hidden Markov Mixture Model (H3M) to model travel patterns for different occupation groups in Hong Kong. Then, the Variational Bayesian Hierarchical EM algorithm is used to identify common lifestyle clusters. Next, a binary logistic regression is developed to examine whether the lifestyle clusters can be explained by jobs-housing balance. This study is among the first to consider travel patterns as a Markov process and apply H3M to examine jobs-housing balance by fine-grain occupation group. The method is transferable and universally applicable; and the results provide occupation-specific insights on jobs-housing balance in an Asian context. The research findings suggest that different occupation groups have different travel patterns in Hong Kong. Two lifestyle clusters, "balanced and compact activity space" and "work-oriented and extensive travels", are unveiled. Notably, the latter is associated a lower level of jobs-housing balance. Some occupations in the quaternary industry ("information and communications", "profession, science and technology", "real estate", and "finance and insurance") are having more serious jobs-housing imbalance. The paper concludes with a discussion on improving the occupation-specific jobs-housing balance in accordance with Hong Kong's future development goals. [ABSTRACT FROM AUTHOR]

Objective: Many stroke survivors still present with upper-limb paresis six months post-stroke, impacting their autonomy and quality of life (QoL). We designed an enriched Music-supported Therapy (eMST) program to reduce disability in this population. We evaluated the eMST's effectiveness in improving functional abilities and QoL in chronic stroke individuals compared to the conventional motor program Graded Repetitive Arm Supplementary Program (GRASP). Methods: We conducted a pragmatic two-arm parallel-group randomized controlled trial with a 3-month follow-up and masked assessment. The eMST involved playing instruments during individual self-administered and group music therapy sessions. The GRASP consisted of self-administered motor exercises using daily objects. Both interventions were completed at home with telemonitoring and involved four one-hour weekly sessions for 10 weeks. The primary outcome was upper-limb motor function measured with the Action Research Arm Test. Secondary outcomes included motor impairment, daily life motor performance, cognitive functions, emotional well-being, QoL, self-regulation, and self-efficacy. Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted including participants who discontinued the intervention and those who completed it entirely, respectively. Results: Fifty-eight chronic stroke patients were randomized to the eMST-group (n = 26; age: 64.2 ± 12.5; 6 [23.1%] females; 2.8 ± 2.9 years post-stroke), and the control group (n = 32; age: 62.2 ± 12; 8 [25%] females; 1.8 ± 6.2 years post-stroke). The eMST-group had more participants achieving a clinically relevant improvement in motor impairment post-intervention than the control group for the ITT (55% vs 21.6%; OR = 4.5 (95% CI 1.4–14); p =.019) and PP analyses (60% vs 20%; OR = 6 (95% CI 1.5–24.7); p =.024), sustained at follow-up. The eMST-group reported greater improvements in emotion (difference = 11.1 (95% CI 0.8–21.5; p = 0.36) and participation (difference = 10.3 (95% CI 0.6–25.9); p = 0.41) subscales of QoL, and higher enjoyment during the sessions (difference = 1 (95% CI 0.3–1.5); p = 0.12). No changes were found in other outcomes. Conclusion: eMST demonstrated superiority over conventional motor rehabilitation program in enhancing upper-limb functions and QoL in chronic stroke individuals. Trial Registration: ClinicalTrials.gov (ID: NCT04507542). [ABSTRACT FROM AUTHOR]

Inflammation is relevant in the pathogenesis and progression of heart failure (HF). Previous studies have shown that elevated high-sensitivity C-reactive protein (hsCRP) are associated with greater severity and may be associated with adverse outcomes. In this study, we sought to evaluate the prognostic role of hsCRP in a non-selected cohort of patients with acute HF. We prospectively included a multicenter cohort of 3,395 patients following an admission for acute HF. HsCRP levels were evaluated during the first 24 h following admission. Study endpoints were the risks of all-cause mortality, CV-mortality, and total HF readmissions. The mean age was 74.2 ± 11.2 years and 1,826 (53.8%) showed a left ventricular ejection fraction (LVEF) ≥ 50%. Median hsCRP was 12.9 mg/L (5.4–30 mg/L). Over a median follow-up of 1.8 (0.6–4.1) years, 1,574 (46.4%) patients died, and 1,341 (39.5%) patients were readmitted for worsening HF. After multivariable adjustment, hsCRP values were significantly and positively associated with a higher risk of all-cause and CV mortality (p = 0.003 and p = 0.001, respectively), as well as a higher risk of recurrent HF admissions (p < 0.001). These results remained consistent across important subgroups, such as LVEF, sex, age, or renal function. In patients with acute HF, hsCRP levels were independently associated with an increased risk of long-term death and total HF readmissions. [ABSTRACT FROM AUTHOR]

Background: Alveolar macrophages activation to the pro-inflammatory phenotype M1 is pivotal in the pathophysiology of Ventilator-Induced Lung Injury (VILI). Increased lung strain is a known determinant of VILI, but a direct correspondence between regional lung strain and macrophagic activation remains unestablished. [68Ga]Ga-DOTA-TATE is a Positron Emission Tomography (PET) radiopharmaceutical with a high affinity for somatostatin receptor subtype 2 (SSTR2), which is overexpressed by pro-inflammatory-activated macrophages. Aim of the study was to determine, in a porcine model of VILI, whether mechanical strain correlates topographically with distribution of activated macrophages detected by [68Ga]Ga-DOTA-TATE uptake. Methods: Seven anesthetized pigs underwent VILI, while three served as control. Lung CT scans were acquired at incremental tidal volumes, simultaneously recording lung mechanics. [68Ga]Ga-DOTA-TATE was administered, followed by dynamic PET scans. Custom MatLab scripts generated voxel-by-voxel gas volume and strain maps from CT slices at para-diaphragmatic (Para-D) and mid-thoracic (Mid-T) levels. Analysis of regional Voxel-associated Normal Strain (VoStrain) and [68Ga]Ga-DOTA-TATE uptake was performed and a measure of the statistical correlation between these two variables was quantified using the linear mutual information (LMI) method. Results: Compared to controls, the VILI group exhibited statistically significant higher VoStrain and Standardized Uptake Value Ratios (SUVR) both at Para-D and Mid-T levels. Both VoStrain and SUVR increased along the gravitational axis with an increment described by statistically different regression lines between VILI and healthy controls and reaching the peak in the dependent regions of the lung (for strain in VILI vs. control was at Para-D: 760 ± 210 vs. 449 ± 106; at Mid-T level 497 ± 373 vs. 193 ± 160; for SUVR, in VILI vs. control was at Para-D: 2.2 ± 1.3 vs. 1.3 ± 0.1; at Mid-T level 1.3 ± 1.0 vs. 0.6 ± 0.03). LMI in both Para-D and Mid-T was statistically significantly higher in VILI than in controls. Conclusions: In this porcine model of VILI, we found a topographical correlation between lung strain and [68Ga]Ga-DOTA-TATE uptake at voxel level, suggesting that mechanical alteration and specific activation of inflammatory cells are strongly linked in VILI. This study represents the first voxel-by-voxel examination of this relationship in a multi-modal imaging analysis. [ABSTRACT FROM AUTHOR]

Apalutamide is a selective androgen receptor signalling inhibitor that is used in the treatment of prostate cancer. Skin rash is one of the most common adverse events with apalutamide. Although the majority of rash events are grade 1 and 2, the appearance of skin rash during treatment can lead to dose reduction, a pause in treatment or even treatment discontinuation, especially if patients present late when the rash has become severe. This in turn can result in a significant delay or even a permanent discontinuation in the patient's treatment of prostate cancer. As apalutamide is a generally well tolerated and an effective treatment for many men with advanced prostate cancer, it is extremely important to make attempts to prevent skin problems or to manage them at the earliest stage possible. We therefore have developed practical guidance for the management of apalutamide-related rash, including an infographic with recommendations for rash management by grade. Central to this approach is patient education and awareness. Encouraging patients to proactively care for their skin from the start of treatment and informing them of the risk of rash with apalutamide therapy are essential. If the patient observes any skin changes, they should be advised to report it straight away to their cancer care team. Adopting this simple, proactive approach of patient education and increased vigilance from the care team is expected to lead to early identification of rash and subsequent intervention to allow for quicker resolution and enable patients to continue their cancer treatment with a drug that can delay disease progression and increase survival in patients with prostate cancer. [ABSTRACT FROM AUTHOR]

Increasing seawater influence in coastal areas is an ongoing environmental issue. Gardening is a widespread activity mainly in touristic areas such as the Mediterranean coasts. However, the use of exotic species well adapted to salinity encompasses the risk of invasive species introduction. This study aimed to evaluate salinity tolerance of native geophytes, Pancratium maritimum L. and Eryngium maritimum L., to assess their use as ornamental species in salt affected coastal areas. Experiments were conducted using cultivated plants for flowering response and physiological and enzymatic antioxidant response. Six treatments were applied for two months, exposing plants to seawater (SW) dilutions (Tap-Water, 6.25%SW, 12.5%SW, 25%SW, 50%SW and 100%SW). Taxa decreased inflorescence production being this effect more architectonical in E. maritimum and affecting all inflorescence integrity in P. maritimum. Flowering time was strongly delayed and reduced in P. maritimum, while E. maritimum showed smaller effects among treatments. Physiological and biochemical response showed at moderate salinity levels (1/4SW) variation concomitant with late stress response and senescence in P. maritimum, with decreased water use efficiency, NPQ values, and enzymatic activity, and increased malondialdehyde (MDA) levels. In contrast, E. maritimum showed early stress response with steady gas exchange response, increasing NPQ values and catalase (CAT) and superoxide dimutase (SOD) activity, and decreasing MDA levels with salinity. Glutathione enzymes showed limited participation in both species. The results of this study suggest that neither species can be classified as halophytes, but they exhibit tolerance to low and moderate salinity levels, making them suitable for ornamental use. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the potential of inflammatory parameters (IP), symptoms, and patient-related outcome measurements as biomarkers of severity and their ability to predict tuberculosis (TB) evolution. Methods: People with TB were included prospectively in the Stage-TB study conducted at five clinical sites in Barcelona (Spain) between April 2018 and December 2021. Data on demographics, epidemiology, clinical features, microbiology, and Sanit George Respiratory Questionnaire (SGRQ) and Kessler-10 as Health-Related Quality of Life (HRQoL) were collected at three time points during treatment. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), neutrophil/lymphocyte, and monocyte/lymphocyte ratios (NLR and MLR), complement factors C3, C4, and cH50, clinical and microbiological data, and HRQoL questionnaires were assessed at baseline, 2 months, and 6 months. Their ability to predict sputum culture conversion (SCC) and symptom presence after 2 months of treatment was also analysed. Results: The study included 81 adults and 13 children with TB. The CRP, ESR, NLR, and MLR values, as well as the presence of symptoms, decreased significantly over time in both groups. Higher IP levels at baseline were associated with greater bacillary load and persistent symptoms. Clinical severity at baseline predicted a delayed SCC. Kessler-10 improved during follow-up, but self-reported lung impairment (SGRQ) persisted in all individuals after 6 months. Conclusions: IP levels may indicate disease severity, and sustained high levels are linked to lower treatment efficacy. Baseline clinical severity is the best predictor of SCC. Implementing health strategies to evaluate lung function and mental health throughout the disease process may be crucial for individuals with TB. [ABSTRACT FROM AUTHOR]

Phase retrieval methods used in computer generated holograms such as Gerchberg-Saxton and gradient descent give results which are prone to noise and other defects. This work builds up on the idea of time-averaging multiple hologram frames, first introduced in methods like One-Step Phase-Retrieval and Adaptive One-Step Phase-Retrieval. The proposed technique called Multi-Frame Holograms Batched Optimization uses the L-BFGS optimization algorithm to simultaneously generate a batch of binary phase holograms which result in an average reconstructed image of improved fidelity and fast algorithmic convergence, both in the Fraunhoffer and the Fresnel regimes. The results are compared to One-Step Phase-Retrieval and Adaptive One-Step Phase-Retrieval in simulation and experimentally, proving the superiority of the proposed approach. This technique can be easily extended to other spatial modulation methods. [ABSTRACT FROM AUTHOR]

To explore preoperative and operative risk factors for red blood cell (RBC) transfusion requirements during liver transplantation (LT) and up to 24 h afterwards. We evaluated the associations between risk factors and units of RBC transfused in 176 LT patients using a log-binomial regression model. Relative risk was adjusted for age, sex, and the model for end-stage liver disease score (MELD) (adjustment 1) and baseline hemoglobin concentration (adjustment 2). Forty-six patients (26.14%) did not receive transfusion. Grafts from cardiac-death donors were used in 32.61% and 31.54% of non-transfused and transfused patients, respectively. The transfused group required more reoperation for bleeding (P = 0.035), longer mechanical ventilation after LT (P < 0.001), and longer ICU length of stay (P < 0.001). MELD and hemoglobin concentrations determined RBC requirements. For each unit of increase in the MELD score, 2% more RBC units were transfused, and non-transfusion was 0.83-fold less likely. For each 10-g/L higher hemoglobin concentration at baseline, 16% less RBC transfused, and non-transfusion was 1.95-fold more likely. Ascites was associated with 26% more RBC transfusions. With an increase of 2 mm from the baseline in the A10Fibtem measurement of maximum clot firmness, non-transfusion was 1.14-fold more likely. A 10-min longer cold ischemia time was associated with 1% more RBC units transfused, and the presence of post-reperfusion syndrome with 45% more RBC units. We conclude that preoperative correction of anemia should be included in LT. An intervention to prevent severe hypotension and fibrinolysis during graft reperfusion should be explored. Trial register: European Clinical Trials Database (EudraCT 2018–002,510-13) and ClinicalTrials.gov (NCT01539057). [ABSTRACT FROM AUTHOR]

piRNAs are crucial for transposon silencing, germ cell maturation, and fertility in male mice. Here, we report on the genetic landscape of piRNA dysfunction in humans and present 39 infertile men carrying biallelic variants in 14 different piRNA pathway genes, including PIWIL1, GTSF1, GPAT2, MAEL, TDRD1, and DDX4. In some affected men, the testicular phenotypes differ from those of the respective knockout mice and range from complete germ cell loss to the production of a few morphologically abnormal sperm. A reduced number of pachytene piRNAs was detected in the testicular tissue of variant carriers, demonstrating impaired piRNA biogenesis. Furthermore, LINE1 expression in spermatogonia links impaired piRNA biogenesis to transposon de-silencing and serves to classify variants as functionally relevant. These results establish the disrupted piRNA pathway as a major cause of human spermatogenic failure and provide insights into transposon silencing in human male germ cells. piRNAs are small RNA molecules found primarily in the testes of mice and men. Stallmeyer et al. demonstrate that variants in specific genes can disrupt the formation of piRNAs, impairing spermatogenesis and causing human male infertility. [ABSTRACT FROM AUTHOR]