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Abstract Spontaneous preterm birth (sPTB) poses significant challenges, affecting neonatal health and neurodevelopmental outcomes worldwide. The specific effects of placental trophoblasts on the pathological development of sPTB subtypes—preterm premature rupture of fetal membranes (pPROM) and spontaneous preterm labor (sPTL)—are not fully understood, making it crucial to uncover these impacts for the development of effective therapeutic strategies. Using single-nucleus RNA sequencing, we investigated transcriptomic and cellular differences at the maternal–fetal interface in pPROM and sPTL placentas. Our findings revealed distinct trophoblast compositions with pPROM characterized predominantly by extravillous trophoblasts (EVTs), while sPTL showed an abundance of syncytiotrophoblasts (STBs). Through cell differentiation and cell-to-cell communication analyses, other distinguishing factors were also found. In pPROM, heightened inflammation, oxidative stress, and vascular dysregulation with key pathways including tumor necrosis factor signaling, matrix metalloproteinase activation, and integrin-mediated cell adhesion, highlighted an invasive EVT profile potentially driven by hypoxic conditions and immune cell recruitment. In contrast, sPTL was marked by increased smooth muscle contraction, vascular remodeling, and altered signaling dynamics involving fibroblasts, including TGF-β and WNT pathways. Our study highlights the critical need to distinguish sPTB subtypes to improve diagnostic precision and therapeutic targeting. The molecular insights gained provide a foundation for future investigations aimed at functional validation of key pathways and exploration of trophoblasts on the development of sPTB. Ultimately, these findings pave the way for more personalized and effective interventions to mitigate adverse outcomes associated with preterm birth.

IntroductionWith ageing there are changes in the ability to orient attention, which affect more endogenous than exogenous orienting. However, orienting attention by the gaze direction of others shares characteristics of both exogenous and endogenous attention and it is unclear how it is affected by ageing. Being able to orient attention by the gaze direction of others is important to establish successful social interactions (i.e., joint attention), and when gaze direction predicts where in the environment salient events occur, it helps to successfully navigate the environment.MethodsHere we investigated whether older individuals learn implicit regularities between the direction of eye gaze and a spatial location where salient events occur. We also assessed the association between orienting attention by the gaze of others and loneliness. Seventy older individuals completed the three-items UCLA loneliness scale and the gaze cueing task, in which gaze cues were non-predictive of target location (block 1), but unbeknownst to participants became predictive of the spatial location where the target appeared (block 2) and then, returned to being non-predictive (block 3).ResultsFindings clearly show that older individuals are less able to orient attention by non-predictive gaze cues, but they successfully learn from environmental regularities implemented with direction of eye gaze. This learning biases attention as it enhances the gaze cueing effect even when the regularities are not present. Importantly, gaze cueing was not affected by self-reported loneliness.DiscussionThese findings point to a training strategy to improve joint attention in older individuals.

Robust Satellite Technique (RST) was applied to detect small-scale landslides along electrical lines in Sicily, Italy. To this end, electrical poles were selected as targets within the study area. The methodology, implemented in Google Earth Engine (GEE) environment, exploits the Copernicus Sentinel-2 platform to identify anomalous land cover variation, in terms of Normalized Difference Vegetation Index (NDVI), possibly related to small displacements affecting electric poles. Since the applied methodology is based on land cover change, dense vegetation plays an important role in detecting small-scale landslides. Therefore, we targeted months with the highest vegetation density, such as February, March, and April from 2016–2023. The results obtained reveal that out of the five targeted electrical poles, four of them exhibited anomalies > 2-sigma indicating significant changes in land cover possibly related to local ground movement as confirmed by aerial photos collected in the period 2015–2023. Our findings reveal anomalies of −2.17 and −2.36 on 7/17/2017 and 9/05/2017 for pole 1. For pole 2, the results show an anomaly of −2.02 on 8/11/2018. The results also indicate anomalies of −4.40 and −2.99 on 7/09/2021 and 9/27/2022 for pole 3. For pole 4, the findings show an anomaly of −3.10 on 1/18/2019.

IntroductionTime is a crucial abstract construct, allowing us to perceive the duration of events. Working memory (WM) plays an important role in manipulating and storing the different features of environmental stimuli, including temporal features. Different brain structures, including the dorsolateral prefrontal cortex, are involved in time processing.MethodsHere we investigated the functional aspects of time processing by using functional near-infrared spectroscopy (fNIRS) to assess changes in DLPFC activity. A modified version of the “Times Squares Sequences” (TSS) task was used, in which participants are required to match sequences of squares that have fixed or variable durations.ResultsFindings showed that the DLPFC activates when information necessary for later comparison needs to be maintained online, as is common in visuo-spatial WM tasks. Importantly, the DLPFC deactivates when a temporal anomaly is detected.DiscussionThis deactivation occurs because the temporal anomaly does not require ongoing maintenance for later comparison, thus demanding fewer cognitive resources from the DLPFC. This seemingly counterintuitive effect can be attributed to the temporal aspects being irrelevant to the primary task goals. This finding highlights the crucial role of implicit temporal interference and establishes a strong connection between timing and executive cognitive processes.

Abstract Visual hallucinations in Lewy body disease (LBD) can be differentiated based on phenomenology into minor phenomena (MVH) and complex hallucinations (CVH). MVH include a variety of phenomena, such as illusions, presence and passage hallucinations occurring at early stages of LBD. The neural mechanisms of visual hallucinations are largely unknown. The hodotopic model posits that the hallucination state is due to abnormal activity in specialized visual areas, that occurs in the context of wider network connectivity alterations and that phenomenology of VH, including content and temporal characteristics, may help identify brain regions underpinning these phenomena. Here we investigated both the topological and hodological neural basis of visual hallucinations integrating grey and white matter imaging analyses. We studied LBD patients with VH and age matched healthy controls (HC). VH were assessed using a North-East-Visual-Hallucinations-Interview that captures phenomenological detail. Then we applied voxel-based morphometry and tract based spatial statistics approaches to identify grey and white matter changes. First, we compared LBD patients and HC. We found a reduced grey matter volume and a widespread damage of white tracts in LBD compared to HC. Then we tested the association between CVH and MVH and grey and white matter indices. We found that CVH duration was associated with decreased grey matter volume in the fusiform gyrus suggesting that LBD neurodegeneration-related abnormal activity in this area is responsible for CVH. An unexpected finding was that MVH severity was associated with a greater integrity of white matter tracts, specifically those connecting dorsal, ventral attention networks and visual areas. Our results suggest that networks underlying MVH need to be partly intact and functional for MVH experiences to occur, while CVH occur when cortical areas are damaged. The findings support the hodotopic view and the hypothesis that MVH and CVH relate to different neural mechanisms, with wider implications for the treatment of these symptoms in a clinical context.

Among the pathophysiological correlates of schizophrenia, recent research suggests a potential role for the Hedgehog (Hh) signalling pathway, which has been traditionally studied in embryonic development and oncology. Its dysregulation may impact brain homeostasis, neuroplasticity, and potential involvement in neural processes. This systematic review provides an overview of the involvement of Hh signalling in the pathophysiology of schizophrenia and antipsychotic responses. We searched the PubMed and Scopus databases to identify peer-reviewed scientific studies focusing on Hh and schizophrenia, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, finally including eight studies, including three articles focused on patients with schizophrenia, two animal models of schizophrenia, two animal embryo studies, and one cellular differentiation study. The Hh pathway is crucial in the development of midbrain dopaminergic neurons, neuroplasticity mechanisms, regulating astrocyte phenotype and function, brain-derived neurotrophic factor expression, brain glutamatergic neural transmission, and responses to antipsychotics. Overall, results indicate an involvement of Hh in the pathophysiology of schizophrenia and antipsychotic responses, although an exiguity of studies characterises the literature. The heterogeneity between animal and human studies is another main limitation. Further research can lead to better comprehension and the development of novel personalised drug treatments and therapeutic interventions.

Background: Post-transplant cyclophosphamide (PTCY) is widely used as graft versus host disease (GvHD) prophylaxis in allogeneic hematopoietic stem cell transplant (HSCT) recipients, with reported clinical benefits in patients who underwent transplant from a matched unrelated donor (MUD). However, real-life data on clinical efficacy and safety of PTCY in haploidentical and MUD transplantations are still poor. Methods: In our real-life retrospective observational study, we included a total of 40 consecutive adult patients who underwent haploidentical or MUD HSCT for various hematological malignancies and who received PTCY (n = 24) or ATG (n = 16) as GvHD prophylaxis at Hematology Units from hospitals of Salerno and Avellino, Italy, and clinical outcomes were compared. Results: We showed protective effects of PTCY against disease relapse with the relapse rate after transplantation of 16% versus 50% in the ATG arm (p = 0.02). All-cause mortality was lower (36% vs. 75%; p = 0.02) and the 2-year overall survival was slightly superior in patients administered PTCY (61% vs. 42%; p = 0.26). Conclusions: We support the use of PTCY, even in a real-life setting; however, the optimization of this protocol should be further investigated to better balance relapse prevention and GvHD prophylaxis.

Abstract Background Viral reactivations are frequent in hematologial patients due to their cancer‐related and drug‐induced immunosuppressive status. Daratumumab, an anti‐CD38 monoclonal antibody, is used for multiple myeloma (MM) treatment, and causes immunosuppression by targeting CD38‐expressing normal lymphocytes. In this single‐center two‐arm real‐life experience, we evaluated incidence of cytomegalovirus (CMV) reactivation in MM patients treated with daratumumab‐based regimens as first‐ or second‐line therapy. Methods A total of 101 consecutive MM patients were included in this study and were divided into two cohorts: daratumumab and nondaratumumab‐based (control) regimens. Patients treated with >2 lines of therapies were excluded to reduce the confounding factor of multi‐treated cases. Primary endpoint was the CMV reactivation rate. Results CMV reactivation rate was significantly higher in the daratumumab cohort compared to control group (33% vs. 4%; p 1000 UI/mL in 12% of cases; p

Abstract Timing alterations occur in Alzheimer’s disease (AD), even in early stages (mild cognitive impairment, MCI). Moreover, a stage named subjective cognitive decline (SCD), in which individuals perceive a change in cognitive performance not revealed by neuropsychological tests, has been identified as a preclinical phase of AD. However, no study to date has investigated different dimensions of time processing along the continuum from physiological to pathological aging, and whether timing alterations occur in SCD. Here a sample of participants with SCD, MCI, AD and healthy controls (HC) performed tasks assessing prospective duration estimation, production, reproduction, implicit temporal learning in conditions dependent from external cues (externally-cued learning, ECL) or independent from external cues (internally-based learning, IBL), retrospective duration estimation, the subjective experience of time and the temporal collocation of events. AD patients performed worse than HC and SCD in prospective timing, and in collocating events in time. The subjective experience of time did not differ between groups. Concerning temporal learning, AD performed worse in ECL than in IBL, whereas SCD performed worse in IBL than in ECL. SCD, MCI and AD patients all showed errors greater than HC in retrospective duration estimation. Results point to implicit temporal learning in externally-cued conditions and retrospective time estimation as possible early markers of cognitive decline.

Abstract Biological age captures physiological deterioration better than chronological age and is amenable to interventions. Blood-based biomarkers have been identified as suitable candidates for biological age estimation. This study aims to improve biological age estimation using machine learning models and a feature-set of 60 circulating biomarkers available from the UK Biobank (n = 306,116). We implement an Elastic-Net derived Cox model with 25 selected biomarkers to predict mortality risk (C-Index = 0.778; 95% CI [0.767–0.788]), which outperforms the well-known blood-biomarker based PhenoAge model (C-Index = 0.750; 95% CI [0.739–0.761]), providing a C-Index lift of 0.028 representing an 11% relative increase in predictive value. Importantly, we then show that using common clinical assay panels, with few biomarkers, alongside imputation and the model derived on the full set of biomarkers, does not substantially degrade predictive accuracy from the theoretical maximum achievable for the available biomarkers. Biological age is estimated as the equivalent age within the same-sex population which corresponds to an individual’s mortality risk. Values ranged between 20-years younger and 20-years older than individuals’ chronological age, exposing the magnitude of ageing signals contained in blood markers. Thus, we demonstrate a practical and cost-efficient method of estimating an improved measure of Biological Age, available to the general population.

Abstract Background The impact of family and personal cancer history and emotional factors, such as depression and anxiety, on disease representation has received limited attention in studies investigating the development of cancer‐related worry and risk perception within the context of genetic counseling. The current study endeavors to fill this gap by exploring the extent to which depression and anxiety influence cancer worry and risk perception, and the role of health care‐related fear as potential mediator in this relationship. Methods A sample of 178 women who underwent their first genetic counseling for breast/ovarian cancer, 52% of whom had previous cancer diagnoses, completed questionnaires assessing sociodemographic and clinical information, emotional distress in terms of anxiety and depression, cancer‐related worry, risk perception, and health care‐related fears. Results Results of mediation analyses showed that cancer‐related worry and risk perception increased with rising levels of depression and anxiety, with health care‐related fears acting as a mediator in the relationship of depression and anxiety with cancer worry and risk perception. Covariate analysis revealed that previous cancer diagnosis increases cancer‐related worry but not risk perception, while the number of family members affected by cancer increases both outcomes. Conclusion These findings emphasize the need for a holistic approach in genetic counseling and have implications for the clinical practice.

Il contributo prende in esame i membra disiecta dell’Archivio Comunale di Gemona del Friuli (UD). Si è scelto, per onorare il tema del convegno, di analizzare tre frammenti pergamenacei (1654.26; 1654.32; 1654.33) di ambito religioso. Si tratta di tre testi utilizzati per la Messa, che uniscono parti cantate a testi agiografici, come la Vita di Santa Cecilia, e Biblici (es. Vangelo di Luca). Di ogni frammento si fornisce una descrizione e l’edizione del testo. Lo studio dei tre codici inediti permette di continuare la discussione sul Medioevo friulano, molto spesso lacunoso, e di ricostruire la vita religiosa e culturale nella comunità di Gemona del Friuli.

Background Professional soccer athletes are exposed to repetitive head impacts and are at risk of developing chronic traumatic encephalopathy. Objective To evaluate regional brain glucose metabolism (rBGM) and gray matter (GM) volume in retired soccer players (RSPs). Methods Male RSPs and age and sex-matched controls prospectively enrolled between 2017 and 2019 underwent neurological and neuropsychological evaluations, brain MRI and [18F]FDG-PET in a 3.0-Tesla PET/MRI scanner. Visual analysis was performed by a blinded neuroradiologist and a blinded nuclear physician. Regional brain glucose metabolism and GM volume were assessed using SPM8 software. Groups were compared using appropriate statistical tests available at SPM8 and R. Results Nineteen RSPs (median [IQR]: 62 [50–64.5] years old) and 20 controls (60 [48–73] years old) were included. Retired soccer players performed worse on mini-mental state examination, digit span, clock drawing, phonemic and semantic verbal fluency tests, and had reduced rBGM in the left temporal pole (pFDR = 0.008) and the anterior left middle temporal gyrus (pFDR = 0.043). Semantic verbal fluency correlated with rBGM in the right hippocampus, left temporal pole, and posterior left middle temporal gyrus (p ≤ 0.042). Gray matter volume reduction was observed in similar anatomic regions but was less extensive and did not survive correction for multiple comparisons (pFDR ≥ 0.085). Individual [18F]FDG-PET visual analysis revealed seven RSPs with overt hypometabolism in the medial and lateral temporal lobes, frontal lobes, and temporoparietal regions. Retired soccer players had a higher prevalence of septum pellucidum abnormalities on MRI. Conclusion Retired soccer players had reduced rBGM and GM volume in the temporal lobes and septum pellucidum abnormalities, findings possibly related to repetitive head impacts.

BACKGROUND: Stillbirth at term has great emotional impact on both parents and professionals. In developed countries, efforts to identify risk factors are mandatory to plan area-specific prevention strategies. OBJECTIVE: The aim of the study was to identify independent risk factors that contribute to stillbirth at 37 weeks’ gestation or later. STUDY DESIGN: This was an area-based, prospective cohort study on pregnancy at term with enrolled from 2014 to 2021 in Emilia-Romagna, a north Italian region. Data were retrieved from both birth certificates and the Stillbirth Surveillance system database. To identify independent risk factors, a multivariate analysis using logistic regression was performed. A descriptive analysis of the causes of stillbirth is also reported. RESULTS: In the observation period, 246,437 babies born at term (including 260 stillbirths, giving a rate of 1.06/1000) were considered. The risk factors independently associated with stillbirth were small for gestational age babies (odds ratio, 2.58; 95% confidence interval, 1.88–3.53), pregnancy achieved though fertility treatments (odds ratio, 2.01; 95% confidence interval, 1.15–3.51), and delayed access to pregnancy services (odds ratio, 1.56; 95% confidence interval, 1.10–2.22). In multipara, the presence of a previous stillbirth (odds ratio, 3.91; 95% confidence interval, 1.98–7.72) was also associated with an increased risk for recurrence. Early- rather than late-term was an additional risk factor. The most frequent causes of death were placental and cord disorders (61/260 and 56/260, respectively). However, 28.1% of cases remain unexplained. CONCLUSION: The risks for stillbirth at term are known early in pregnancy or could be identified through tailored antenatal management, allowing effective preventive strategies to reduce preventable cases.

Growing old involves changes in physical, psychological, and cognitive functions. Promoting physical and mental health has become one of the priorities for an aging population. Studies have demonstrated the benefits of engaging in regular physical activity. Here, we aimed to understand the relationships between physical activity and working memory complaints in attention, memory storage, and executive functions. We hypothesized that physical activity was negatively associated with complaints in working memory domains after controlling for socio-demographics and distress factors, such as anxiety, stress, and depression. Two hundred and twenty-three individuals aged between 65 and 100 years (74.84; SD = 7.74; 133 males) without self-reported neurological and/or psychiatric disorders completed a questionnaire on socio-demographic, with questions on physical activity and the Italian version of the working memory questionnaire (WMQ) and the DASS-21 measuring anxiety, stress, and depression. Results from three linear regression models showed that low physical activity was associated with complaints in attention (R2 = 0.35) and executive functions (R2 = 0.37) but not in memory storage (R2 = 0.28). Notably, age, gender, and total emotional distress (DASS score) were significant in all regression models. Our results suggested regular physical activity, even just walking, is crucial for maintaining efficient cognitive function. Theoretical and practical implications for engaging in physical activity programs and social aggregation during exercise are considered. Limitations are also presented.

We propose the concept of law enforcement officers as supercitizens in the body politic of the United States. We explore the ways in which citizenship in the United States is, [...]

The Developmental Topographical Disorientation (DTD) is a pathological condition that impairs an individual’s ability to orient in space, even in the most familiar environments. It is a lifelong selective condition in individuals without brain damage or without impaired general cognitive functions. Here, we aimed at characterizing 54 individuals with DTD identified in a previous study, aged between 18 and 35 years and assessed through a 4-year-long online survey. To this purpose, we compared them with 54 matched healthy participants. We described the demographics, sense of direction, town knowledge, navigational strategies, left-right confusion as well as agnosic disorders (for landmarks, faces and objects). This novel study attempts to characterize the phenotype of DTD, providing an important contribution to the worldwide definition of a condition that was first described only 13 years ago, but which, considering the growing number of cases complaining of the disorder, deserves continuous and increasing attention.

Abstract Alzheimer’s disease (AD) diagnosis often requires invasive examinations (e.g., liquor analyses), expensive tools (e.g., brain imaging) and highly specialized personnel. The diagnosis commonly is established when the disorder has already caused severe brain damage, and the clinical signs begin to be apparent. Instead, accessible and low-cost approaches for early identification of subjects at high risk for developing AD years before they show overt symptoms are fundamental to provide a critical time window for more effective clinical management, treatment, and care planning. This article proposes an ensemble-based machine learning algorithm for predicting AD development within 9 years from first overt signs and using just five clinical features that are easily detectable with neuropsychological tests. The validation of the system involved both healthy individuals and mild cognitive impairment (MCI) patients drawn from the ADNI open dataset, at variance with previous studies that considered only MCI. The system shows higher levels of balanced accuracy, negative predictive value, and specificity than other similar solutions. These results represent a further important step to build a preventive fast-screening machine-learning-based tool to be used as a part of routine healthcare screenings.

IntroductionSeveral studies have shown that the working memory is sensitive to temporal variations. We used a new visuospatial working memory task, the “Time Squares Sequences,” to investigate whether implicit variations in stimuli presentation time affect task performance.MethodsA total of 50 healthy participants saw two sequences (S1 and S2) of seven white squares presented in a matrix of gray squares and assessed whether S2 matched S1. There were four conditions depending on the spatial position and the presentation time (i.e., timing) of the white squares in S1 and S2: two with the same (S1 fixed/S2 fixed and S1 variable/S2 variable) and two with different (S1 fixed/S2 variable and S1 variable/S2 fixed) presentation times.ResultsFindings showed impaired performance when S1 had a fixed presentation time and S2 had a variable presentation time.ConclusionThese findings are attributed to increased cognitive load due to S2 timing difference, pointing to a monitoring process, sensitive to temporal variations.

Treatment of relapsed/refractory or elderly unfit acute myeloid leukemia (AML) is still challenging, and hypomethylating agents in combination with venetoclax, an oral selective BCL2 inhibitor, might be successfully used as salvage therapy. However, clinical trials evaluating the efficacy and safety of this combination in the setting of multiresistant AML treatment also as a bridge to transplant are still ongoing. Here, we reported a 50-year-old male diagnosed with AML with normal cytogenetics and wild type for fms-like tyrosine kinase 3, nucleophosmin 1, and KIT, and treated with decitabine and venetoclax as the fifth line of therapy and after a relapse post-allogeneic transplant. The patient achieved a complete remission and successfully underwent a haploidentical transplant with an overall survival of 48.6 months.