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Objectives: Tactile acuity is a somatosensory measure of the extent to which humans can discern tactile stimuli. It is influenced by how peripheral signals are processed centrally. In the oral cavity, Occlusal Tactile Acuity (OTA) is the ability to perceive minimal thicknesses between antagonist teeth. The aim of the current study was to assess the association between psychological traits and OTA of otherwise healthy individuals. Methods: Sixty‐three volunteers (32 males; mean age ± SD: 24.6 ± 2.7 years) participated in this study. Somatosensory amplification, anxiety, depression, physical symptoms and pain catastrophizing were scored using questionnaires, and subgroups of severity were created per variable based on cut‐offs. OTA was measured using 9 aluminium foils with thickness (ranging from 8 to 72 μm) and one sham test (without foil). Each thickness was tested 10 times in random order, the participants were instructed to report whether they felt the foil between their molars and the mean percentage of correct answers was computed. A linear mixed model was used with OTA as a dependent variable and psychological domain as an independent variable. Results: Significantly different OTA was observed among the anxiety subgroups (p =.003), supporting a decreased perception of thicknesses 24 and 32 μm (p =.018 and p <.001, respectively) in participants with moderate/severe anxiety compared to those with no/mild anxiety. Significantly different OTA was also observed among the pain catastrophizing subgroups (p =.008), showing decreased perception of thicknesses 32 and 40 μm (p <.001 and p =.007, respectively) in severe catastrophizing levels, compared to no/mild catastrophizing levels. No significant differences were observed for the other variables. Conclusions: Healthy adults with increased anxiety or pain catastrophizing levels show decreased interdental acuity as compared to participants with minor or no psychological impairment. [ABSTRACT FROM AUTHOR]

The article discusses the challenges and gaps in knowledge regarding the use of medicines during pregnancy. It highlights the need for a clinical pharmacology extrapolation framework based on model-informed drug development to support pregnancy drug development strategies. The article also addresses the regulatory landscape, emphasizing the importance of including pregnant and breastfeeding women in clinical trials to generate data supporting safe medication use during pregnancy. Additionally, it discusses the impact of pregnancy-related physiological changes on drug exposure and the importance of adapting pediatric extrapolation frameworks to pregnancy to optimize treatment strategies. [Extracted from the article]

Objectives: In addition to studying facial anatomy, stereophotogrammetry is an efficient diagnostic tool for assessing facial expressions through 3D video recordings. Current technology produces high‐quality recordings but also generates extremely excessive data. Here, we compare various recording speeds for three standardized movements using the 3dMDface camera system, to assess its accuracy and reliability. Materials and Methods: A linear and two circular movements were performed using a 3D‐printed cube mounted on a robotic arm. All movements were recorded initially at 60 fps (frames/second) and then at 30 and 15 fps. Recording accuracy was tested with best‐fit superimpositions of consecutive frames of the 3D cube and calculation of the Mean Absolute Distance (MAD). The reliability of the recordings were tested with evaluation of the inter‐ and intra‐examiner error. Results: The accuracy of movement recordings was excellent at all speeds (60, 30 and 15 fps), with variability in MAD values consistently being less than 1 mm. The reliability of the camera recordings was excellent at all recording speeds. Conclusions: This study demonstrated that 3D recordings of facial expressions can be performed at 30 or even at 15 fps without significant loss of information. This considerably reduces the amount of produced data facilitating further processing and analyses. [ABSTRACT FROM AUTHOR]

Objectives: This study investigates the psychological impact of COVID‐19 on burning mouth syndrome (BMS) patients. It focuses on comparing post‐traumatic stress symptoms (PTSS), post‐traumatic growth (PTG), and resilience between BMS patients and Controls. Methods: A total of 100 BMS patients and 100 Controls from five Italian centers participated in this observational cross‐sectional study. They completed several assessments, including the General Health Questionnaire, Depression Anxiety and Stress Scale, Insomnia Severity Index, National Stressful Events Survey Short Scale, Impact of Event Scale‐Revised, Post Traumatic Growth Inventory Short Form, and Connor‐Davidson Resilience Scale. Results: BMS patients had significantly higher stress, anxiety, and depression (DASS‐21 score) and post‐traumatic stress symptoms (IES‐R‐6 score), particularly in terms of intrusive thoughts. They showed lower post‐traumatic growth (PTGI‐SF score) compared to Controls. The resilience scale (CDRS‐10) was a key predictor of PTG in both groups, explaining a significant variance in PTGI‐SF scores. Conclusions: BMS patients experienced heightened post‐traumatic stress, stress, anxiety, and depression during the COVID‐19 pandemic, with reduced post‐traumatic growth. This highlights the need to prioritize their psychological well‐being, focusing on stress management and fostering post‐traumatic growth in challenging times. [ABSTRACT FROM AUTHOR]

Objective: Rare and complex epilepsies encompass a diverse range of disorders characterized by seizures. We aimed to establish a consensus on key issues related to these conditions through collaboration among experienced neurologists, neuropediatricians, and patient advocacy representatives. Methods: Employing a modified Delphi method, a scientific board comprising 20 physicians and 4 patient advocacy representatives synthesized existing literature with their expertise to formulate statements on contentious topics. A final 32‐member expert panel, representing diverse regions of Italy, validated these statements through a two‐round voting process, with consensus defined as an average score ≥7. Results: Sixteen statements reached a consensus, emphasizing the necessity for epidemiological studies to ascertain the true prevalence of rare epilepsies. Etiology emerged as a crucial factor influencing therapeutic strategies and outcome prediction, with particular concern regarding prolonged and tonic–clonic seizures. The importance of early implementation of specific drugs and non‐pharmacological interventions in the treatment algorithm for developmental and epileptic encephalopathies (DEEs) was underscored. Multidisciplinary care involving experts with diverse skills was deemed essential, emphasizing non‐seizure outcomes in adolescence and adulthood. Significance: This national consensus underscores the imperative for personalized, comprehensive, and multidisciplinary management of rare epilepsies/DEEs. It advocates for increased research, particularly in epidemiology and therapeutic approaches, to inform clinical decision‐making and healthcare policies, ultimately enhancing patients' outcomes. Plain Language Summary: The modified Delphi method is broadly used to evaluate debated topics. In this work, we sought the consensus on integrated and social care in epilepsy management. Both representatives of high‐level epilepsy centers and patients' caregivers were directly involved. [ABSTRACT FROM AUTHOR]

Objective: Here we investigate infectious diseases that potentially contribute to osteological lesions in individuals from the early medieval necropolis of La Olmeda (6th‐11th c. CE) in North Iberia. Materials and methods: We studied a minimum number of 268 individuals (33 adult females; 38 adult males, 77 unknown/indeterminate sex; and 120 non‐adults), including articulated and commingled remains. Individuals with differential diagnoses suggesting chronic systemic infectious diseases were sampled and bioinformatically screened for ancient pathogen DNA. Results: Five non‐adults (and no adults) presented skeletal evidence of chronic systemic infectious disease (1.87% of the population; 4.67% of non‐adults). The preferred diagnoses for these individuals included tuberculosis, brucellosis, and malaria. Ancient DNA fragments assigned to the malaria‐causing pathogen, Plasmodium spp., were identified in three of the five individuals. Observed pathology includes lesions generally consistent with malaria; however, additional lesions in two of the individuals may represent hitherto unknown variation in the skeletal manifestation of this disease or co‐infection with tuberculosis or brucellosis. Additionally, spondylolysis was observed in one individual with skeletal lesions suggestive of infectious disease. Conclusions: This study sheds light on the pathological landscape in Iberia during a time of great social, demographic, and environmental change. Genetic evidence challenges the hypothesis that malaria was absent from early medieval Iberia and demonstrates the value of combining osteological and archaeogenetic methods. Additionally, all of the preferred infectious diagnoses for the individuals included in this study (malaria, tuberculosis, and brucellosis) could have contributed to the febrile cases described in historical sources from this time. [ABSTRACT FROM AUTHOR]

Background: Treatment options for people with haemophilia are evolving at a rapid pace and a range of prophylactic treatment options using various technologies are currently available, each with their own distinct safety and efficacy profile. Treatment goals: The access to replacement therapy and prophylaxis has driven a dramatic reduction in mortality and resultant increase in life expectancy. Beyond this, the abolition of bleeds and preservation of joint health represent the expected, but rarely attained, goals of haemophilia treatment and care. These outcomes also do not address the complexity of health‐related quality of life impacted by haemophilia and its treatment. Conclusion: Capitalizing on the major potential of therapeutic innovations, 'Normalization' of haemostasis, as a concept, should include the aspiration of enabling individuals to live as normal a life as possible, free from haemophilia‐imposed limitations. To achieve this—being supported by the data reviewed in this manuscript—the concept of haemostatic and life Normalization needs to be explored and debated within the wider multidisciplinary teams and haemophilia community. [ABSTRACT FROM AUTHOR]

Open‐vent volcanoes continuously emit magmatic products and frequently feature multiple adjacent craters. Temporal shifts of thermal emissions between craters are especially detectable by InfraRed satellites. Here, SENTINEL‐2 and LANDSAT‐8/9 Short Wave InfraRed (SWIR) high‐spatial resolution satellite data, are combined to investigate 10 years (2013–2023) of thermal activity at Stromboli volcano (Italy). The correlation between Volcanic Radiative Power (VRP, in Watts) and Volcanic Radiative Energy (VRE, in Joules), retrieved by moderate MODIS and VIIRS Middle InfraRed (MIR) data, with the Thermal Index SWIR (TISWIR) data, allows us to quantify long‐term series of heat fluxes (VRPSWIR) and energy (VRESWIR). Combining moderate and higher spatial resolution data and fitting cumulative trends of TISWIR with VREMIR allows to measure thermal activity sourced by single craters during Strombolian activity. Long‐term results highlight that thermal emissions are clustered in the northern and southern parts of the crater terrace, with total energy emitted (∼12 × 1014 J) equally distributed. The thermal increase since April 2017 marked a reactivation of shallow magma transportation and an intensification of the activity after the 2014 eruption. Distinct thermal behaviors are shown by the NE, C, and SW craters, related to mechanisms of explosions. We found that short‐term thermal variations match well those resolved by ground‐based signals, and the NE crater as the most sensitive to the transition to higher‐intensity activity. Our multispatial/multisensory investigation allows, for the first time, the long‐term quantification of heat flux from Stromboli's craters, with an improved understanding of open‐vent dynamics and a new approach to monitor multiple active craters. Plain Language Summary: Stromboli is a volcano in southern Italy, historically well‐known, considered unique and fascinating for its persistent emission of magma and gas through multiple adjacent craters lasting for millennia. This study focuses on tracking the thermal activity of Stromboli using modern satellite data over 2013–2023, with unprecedented levels of detail able to distinguish the heat released by single craters. The analysis revealed that most thermal emissions at Stromboli were concentrated in two primary sectors of the summit terrace. Notably, a significant increase in thermal activity was observed since April 2017, indicating a resurgence in volcanic activity after a period of relatively calm following the previous eruption. Distinct thermal behaviors of the three historically active craters of Stromboli have been recognized and reconciled with different styles of volcanic explosions. Furthermore, the study identified patterns of heat release within Stromboli's main craters which agreed with the fluctuations in gas emissions and explosive activity characterizing the volcano. Overall, this comprehensive analysis provides valuable insights to scientists and volcano‐involved communities into the long‐term quantification of heat flux from multiple craters at Stromboli, contributing to a better understanding of open‐vent eruptive dynamics and enhancing continuous monitoring of Stromboli and similar volcanoes. Key Points: Ten years (2013–2023) quantification of heat flux VRPSWIR from active craters at Stromboli using Sentinel‐2 and Landsat‐8/‐9 SWIR imagesTwo main thermal clusters emitting ∼12 × 1014 J. Thermal increase since April 2017 marks a reactivation of intense Strombolian activityNE, C, and SW craters show distinct thermal behavior, with the NE as the most energetic. VRPSWIR tracks transition to more explosive phases [ABSTRACT FROM AUTHOR]

Summary: Cow milk protein allergy (CMPA) is one of the most common food allergies in the pediatric age worldwide. Prevalence, persistence, and severity of this condition are on the rise, with a negative impact on the health‐related quality of life of the patients and families and on the costs related to its management. Another relevant issue is that CMPA in early life may be the first stage of the "allergic march," leading to the occurrence of other atopic manifestations later in life, especially asthma, atopic eczema, urticaria, and rhinoconjunctivitis. Thus, "disease modification" options that are able to modulate the disease course of pediatric patients affected by CMPA would be very welcomed by affected families and healthcare systems. In this review, we report the most relevant progress on this topic. [ABSTRACT FROM AUTHOR]

Background: Consumption of ultra‐processed foods [UPFs] may be associated with negative health outcomes. Limited data exist regarding the potential role of UPFs in the occurrence of allergic diseases. The underlying mechanisms underpinning any such associations are also poorly elucidated. Methods: We performed a systematic review and narrative evidence synthesis of the available literature to assess associations between UPF consumption and pediatric allergy outcomes (n = 26 papers), including data on the association seen with the gut microbiome (n = 16 papers) or immune system (n = 3 papers) structure and function following PRISMA guidelines. Results: Dietary exposure to fructose, carbonated soft drinks, and sugar intake was associated with an increased risk of asthma, allergic rhinitis, and food allergies in children. Commercial baby food intake was associated with childhood food allergy. Childhood intake of fructose, fruit juices, sugar‐sweetened beverages, high carbohydrate UPFs, monosodium glutamate, UPFs, and advanced glycated end‐products (AGEs) was associated with the occurrence of allergic diseases. Exposure to UPFs and common ingredients in UPFs seem to be associated with increased occurrence of allergic diseases such as asthma, wheezing, food allergies, atopic dermatitis, and allergic rhinitis, in many, but not all studies. Conclusion: More preclinical and clinical studies are required to better define the link between UPF consumption and the risk of allergies and asthma. These observational studies ideally require supporting data with clearly defined UPF consumption, validated dietary measures, and mechanistic assessments to definitively link UPFs with the risk of allergies and asthma. [ABSTRACT FROM AUTHOR]

Chromosomal abnormalities are associated with a broad spectrum of clinical manifestations, one of the more commonly observed of which is epilepsy. The frequency, severity, and type of epileptic seizures vary according to the macro‐ and microrearrangements present. Even within a single chromosomal anomaly, we most often deal with a phenotypic spectrum. The aim of the study was to look for chromosomal rearrangements with a characteristic electroencephalographic pattern. Only a few disorders have peculiar electroclinical abnormalities: 1p36, 4p16, 6q terminal or trisomy 12p, Angelman syndrome, inv dup 15, 15q13.3 deletions, ring 20, Down syndrome, or Xp11.22–11.23 duplication. We also reviewed studies on epileptic seizures and typical electroencephalographic patterns described in certain chromosomal rearrangements, focusing on the quest for potential electroclinical biomarkers. The comprehensive review concludes with clinical presentations of the most common micro and macro chromosomal rearrangements, such as 17q21.31 microdeletion, 6q terminal deletion, 15q inv dup syndrome, 2q24.4 deletion, Xp11.22–11.23 duplication, 15q13.3 microdeletion, 1p36 terminal deletion, 5q14.3 microdeletion, and Xq28 duplication. The papers reviewed did not identify any specific interictal electroencephalographic patterns that were unique and significant biomarkers for a given chromosomal microrearrangement. The types of seizures described varied, with both generalized and focal seizures of various morphologies being reported. Patients with chromosomal anomalies may also meet the criteria for specific epileptic syndromes such as Infantile Epilepsy Spasms Syndrome (IESS, West syndrome): 16p13.11, 15q13.3 and 17q21.31 microdeletions, 5q inv dup. syndrome; Dravet syndrome (2q24.4 deletion), Lennox–Gastaut syndrome (15q11 duplication. 1q13.3, 5q inv dup.); or Self‐Limited Epilepsy with Autonomic Features (SeLEAS, Panayiotopoulos syndrome: terminal deletion of 6q.n), Self‐Limited Epilepsy with Centrotemporal Spikes (SeLECT): fragile X syndrome. It is essential to better characterize groups of patients to more accurately define patterns of epilepsy and EEG abnormalities. This could lead to new treatment strategies. Future research is required to better understand epileptic syndromes and chromosomal rearrangements. Plain Language Summary: This paper presents EEG recording abnormalities in patients with various gene abnormalities that can cause epilepsy. The authors summarize these EEG variations based on a literature review to see if they occur frequently enough in other chromosomal abnormalities (in addition to those already known) to be a clue for further diagnosis. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted in Italy that evaluated the use of recombinant factor IX-albumin fusion protein (rIX-FP) as a treatment for adult patients with hemophilia B. The study found that rIX-FP prophylaxis was effective in reducing bleeding episodes and required fewer infusions compared to previous treatments. The most common dosing regimen was every 14-15 days, with one patient using a 21-day regimen. The study concluded that rIX-FP is a flexible and effective treatment option for adult patients with hemophilia B, but further research is needed to assess long-term outcomes. It is important to consider physical activity levels and lifestyle when personalizing prophylaxis regimens. [Extracted from the article]

Background: Several studies have evaluated the role of QRS duration (QRSd) or QRS narrowing as a predictor of response to cardiac resynchronization therapy (CRT) to reduce nonresponders. Aim: Our study aimed to determine the correlation between the relative change in QRS index (QI) compared to clinical outcome and prognosis in patients who underwent CRT implantation. Methods: A three‐centers study involving 398 patients with a CRT device was conducted. Clinical, echocardiographic and pharmacological variables, QRSd before and after CRT implantation and QI were measured. Results: In a 6‐month follow‐up, a significant improvement in left ventricular ejection fraction (LVEF), left ventricular end‐diastolic and systolic volumes (LVEDV and LVESV) were observed. QI was related to reverse remodeling (multiple r‐squared: 0.48, adjusted r‐squared: 0.43, p =.001), and the cut‐off value that best predicted LV reverse remodeling after 6 months of CRT was 12.25% (AUC 0.7, p =.001). At 24 months, a statistically significant difference was found between patients with a QI ≤ 12.25% and those with a QI > 12.25% regarding NYHA class worsening (p =.04). The mean of the QI of patients who died from cardiovascular causes was lower than patients who died of other causes (p =.0179). A correlation between pre‐CRT QRSd/LVEDV and QI was observed (r = + 0.20; p =.0003). A higher QRSd/LVEDV ratio was associated with an improved LVEF, LVEDV, and LVESV (p <.0001) at follow‐up. Conclusions: QI narrowing after CRT was related to greater echocardiographic reverse remodeling and a lower rate of adverse events (death or cardiovascular hospitalizations). The QI can improve the prediction of adverse events in a population with CRT regardless of comorbidities according to the Charlson Comorbidity Index. QI could be used to predict CRT response. [ABSTRACT FROM AUTHOR]

Backgrounds: Rectal robotic surgery gained momentum in the last decade, but it is still associated with not‐negligible costs. In order to reduce costs, recently different robotic systems have received approval for clinical use. This study aims to present the first case series of rectal resection with the novel cost‐effective platform Robotic Assisted Surgery (RAS) Hugo™. Tips for effective set up of the system and detailed configuration of tilt and docking angles are also provided. Methods: Three cases of rectal resection with Hugo RAS™ system are reported. After the first two cases of resection with partial mesorectal excision in which surgeries were performed with the setup proposed by the vendor company, in the third case we tested a novel setup that allowed a full robotic low rectal resection performing vascular ligations, TME and colonic splenic flexure mobilization without the need of any de‐docking. Results: Our first three robotic rectal resections with the Hugo RAS™ system were completed without complications with a median docking time of 12 min (range 8–15) and a median console time of 345 minutes (range 271–475). In the first two cases, hybrid robotic and laparoscopic surgeries were performed to obtain an adequate haemostasis and traction during the pelvic phase. In the third case, a full robotic TME was successfully accomplished. Conclusion: Our experience demonstrates that a full robotic low rectal resection with TME with Hugo™ RAS system is feasible, safe and associated with satisfactory postoperative outcomes. [ABSTRACT FROM AUTHOR]

The integration of photovoltaic technologies within agricultural settings, also known as agrivoltaics, is attracting increasing attention as a sustainable approach to ensure both clean energy and food supply. The success of this strategy relies on the development of innovative materials that can selectively convert specific wavelengths into energy while being transparent to photosynthetically relevant light. To this aim, here we report our endeavors in the synthesis of a new class of D‐π‐A‐π‐D quinoxaline fluorophores and their use in the preparation of wavelength‐selective luminescent solar concentrators. The dyes were expeditiously prepared following a direct arylation protocol and extensively characterized by spectroscopic analyses and computational studies. They present high light harvesting ability in the green region of the visible spectrum and good emission properties, which were fully retained in the solid state when embedded into a poly methyl methacrylate (PMMA) matrix. These materials were employed to construct LSC devices of promising efficiency, fostering further developments for the use of wavelength‐selective LSC in agrivoltaic systems. [ABSTRACT FROM AUTHOR]

Vitamin B6 is a critical molecule for metabolism, development, and stress sensitivity in plants. It is a cofactor for numerous biochemical reactions, can serve as an antioxidant, and has the potential to increase tolerance against both biotic and abiotic stressors. Due to the importance of vitamin B6, its biosynthesis is likely tightly regulated. Plants can synthesize vitamin B6de novo via the concerted activity of Pyridoxine Biosynthesis Protein 1 (PDX1) and PDX2. Previously, PDX proteins have been identified as targets for ubiquitination, indicating they could be marked for degradation by two highly conserved pathways: the Ubiquitin Proteasome Pathway (UPP) and the autophagy pathway. Initial experiments show that PDXs are in fact degraded, but surprisingly, in a ubiquitin‐independent manner. Inhibitor studies pointed toward cathepsin B, a conserved lysosomal cysteine protease, which is implicated in both programed cell death and autophagy in humans and plants. In plants, cathepsin Bs are poorly described, and no confirmed substrates have been identified. Here, we present PDX proteins from Arabidopsis thaliana as interactors and substrates of a plant Cathepsin B. These findings not only describe a novel cathepsin B substrate in plants, but also provide new insights into how plants regulate de novo biosynthesis of vitamin B6. [ABSTRACT FROM AUTHOR]

Physiologically based pharmacokinetic (PBPK) modelling in pregnancy is a relatively new approach that is increasingly being used to assess drug systemic exposure in pregnant women to potentially inform dosing adjustments. Physiological changes throughout pregnancy are incorporated into mathematical models to simulate drug disposition in the maternal and fetal compartments as well as the transfer of drugs across the placenta. This mini‐review gathers currently available pregnancy PBPK models for drugs commonly used during pregnancy. In addition, information about the main PBPK modelling platforms used, metabolism pathways, drug transporters, data availability and drug labels were collected. The aim of this mini‐review is to provide a concise overview, demonstrate trends in the field, highlight understudied areas and identify current gaps of PBPK modelling in pregnancy. Possible future applications of this PBPK approach are discussed from a clinical, regulatory and industry perspective. [ABSTRACT FROM AUTHOR]

This study aimed to review the lesser‐known intraoral manifestations of immunoglobulin G4‐related disease (IgG4‐RD). In this paper we report an unprecedented case of oral IgG4‐RD mimicking angiolymphoid hyperplasia with eosinophilia (ALHE), and another case presenting as plasma cell gingivitis. We then performed a scoping review of published cases of IgG4‐RD involving the oral cavity. The following data were collected for each case: age, sex, intraoral site(s) involved, clinical appearance, imaging features, serum IgG4 values, histopathology, treatment, and follow‐up duration. Fifty‐one cases of oral IgG4‐RD were published in literature. The hard palate and jaw bones were the two main locations reported, while the histological identification of a IgG4/IgG plasma cells ratio ≥40% was fundamental for diagnosis. Conversely, the pathological features of storiform fibrosis and obliterative phlebitis were not common. Future reports regarding oral IgG4‐RD should report clear adherence to the recognized international diagnostic criteria of the disease. [ABSTRACT FROM AUTHOR]

Summary: Programmed cell death (PCD) is fundamentally important for plant development, abiotic stress responses and immunity, but our understanding of its regulation remains fragmented. Building a stronger research community is required to accelerate progress in this area through knowledge exchange and constructive debate. In this Viewpoint, we aim to initiate a collective effort to integrate data across a diverse set of experimental models to facilitate characterisation of the fundamental mechanisms underlying plant PCD and ultimately aid the development of a new plant cell death classification system in the future. We also put forward our vision for the next decade of plant PCD research stemming from discussions held during the 31st New Phytologist workshop, 'The Life and Death Decisions of Plant Cells' that took place at University College Dublin in Ireland (14–15 June 2023). We convey the key areas of significant progress and possible future research directions identified, including resolving the spatiotemporal control of cell death, isolation of its molecular and genetic regulators, and harnessing technical advances for studying PCD events in plants. Further, we review the breadth of potential impacts of plant PCD research and highlight the promising new applications of findings from this dynamically evolving field. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a primary tumor in the central nervous system with poor prognosis. It exhibits elevated glucose uptake and lactate production. This metabolic state of aerobic glycolysis is known as the Warburg effect. N6‐isopentenyladenosine (iPA), a natural cytokine modified with an isopentenyl moiety derived from the mevalonate pathway, has well‐established anti‐tumor activity. It inhibits cell proliferation in glioma cells, inducing cell death by apoptosis and/or necroptosis. In the present study, we found that iPA inhibits aerobic glycolysis in unmodified U87MG cells and in the same cell line engineered to over‐express wild‐type epidermal growth factor receptor (EGFR) or EGFR variant III (vIII), as well as in a primary GBM4 patient‐derived cell line. The detection of glycolysis showed that iPA treatment suppressed ATP and lactate production. We also evaluated the response of iPA treatment in normal human astrocyte primary cells, healthy counterpart cells of the brain. Aerobic glycolysis in treated normal human astrocyte cells did not show significant changes compared to GBM cells. To determine the mechanism of iPA action on aerobic glycolysis, we investigated the expression of certain enzymes involved in this metabolic pathway. We observed that iPA reduced the expression of pyruvate kinase M2 (PKM2), which plays a key role in the regulation of aerobic glycolysis, promoting tumor cell proliferation. The reduction of PKM2 expression is a result of the inhibition of the inhibitor of nuclear factor kappa‐B kinase subunit, beta/nuclear factor‐kappa B pathway upon iPA treatment. In conclusion, these experimental results show that iPA may inhibit aerobic glycolysis of GBM in stabilized cell lines and primary GBM cells by targeting the expression and activity of PKM2. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate pattern of use and clinical outcomes in pediatric/adolescent patients enrolled in the IDEAL study. Methods: This post‐hoc analysis of IDEAL retrospective‐prospective observational study focused on patients <18 years, 100% on prophylaxis during the entire observation period. Results: Thirteen subjects (median age 10.0 years; 61.5% ≤ 11 years) were analyzed. The infusion frequency changed from 2/week in 84.6% (N = 11) of patients with previous rFIX, to less than 1/weekly in 76.9% (N = 9) with rIX‐FP and the annualized number of infusions reduced of 57% (p =.002), from a mean ± SD of 95.1 ± 22.77 to 40.4 ± 6.79, respectively. Annualized mean consumption decreased of about 56% (p =.001), from 3748.4 ± 1155.40 IU/kg with previous rFIX, to 1656.8 ± 456.63 IU/kg of rIX‐FP. Mean FIX trough level changed from 3.0% ± 1.98% to 10.92% ± 3.6%. Low mean Annualized Bleeding Rate was maintained across all prophylaxis regimens (0.8 ± 1.69 vs. 0.3 ± 0.89) and zero bleeding patients moved from 69.2% (N = 9) with previous rFIX to 84.6% (N = 11) with rIX‐FP (p =.63). Two adverse events, none related to rIX‐FP, occurred in two patients. No inhibitors development was reported. Conclusions: The results in this pediatric/adolescent subgroup support rIX‐FP prophylaxis may reduce infusion frequency, while providing high FIX trough levels, stable annualized bleeding rate and a good safety profile. [ABSTRACT FROM AUTHOR]

Background: Programmed death ligand‐1 (PD‐L1) expression is a well‐known predictive biomarker of response to immune checkpoint blockade in non‐small cell lung cancer (NSCLC). However, there is limited evidence of the relationship between PD‐L1 expression, clinicopathological features, and their association with major driver mutations in NSCLC patients in Latin America. Methods: This retrospective study included patients from Argentina with advanced NSCLC, and centralized evaluation of PD‐L1 expression concurrently with genomic alterations in the driver genes EGFR, ALK, ROS1, BRAF, and/or KRAS G12C in FFPE tissue samples. Results: A total of 10 441 patients with advanced NSCLC were analyzed. Adenocarcinoma was the most frequent histological subtype (71.1%). PD‐L1 expression was categorized as PD‐L1 negative (45.1%), PD‐L1 positive low‐expression 1%–49% (32.3%), and PD‐L1 positive high‐expression ≥50% (22.6%). Notably, current smokers and males were more likely to have tumors with PD‐L1 tumor proportion score (TPS) ≥50% and ≥ 80% expression, respectively (p < 0.001 and p = 0.013). Tumors with non‐adenocarcinoma histology had a significantly higher median PD‐L1 expression (p < 0.001). Additionally, PD‐L1 in distant nodes was more likely ≥50% (OR 1.60 [95% CI: 1.14–2.25, p < 0.01]). In the multivariate analysis, EGFR‐positive tumors were more commonly associated with PD‐L1 low expression (OR 0.62 [95% CI: 0.51–0.75], p < 0.01), while ALK‐positive tumors had a significant risk of being PD‐L1 positive (OR 1.81 [95% CI: 1.30–2.52], p < 0.01). Conclusions: PD‐L1 expression was associated with well‐defined clinicopathological and genomic features. These findings provide a comprehensive view of the expression of PD‐L1 in patients with advanced NSCLC in a large Latin American cohort. [ABSTRACT FROM AUTHOR]

In the search for novel, effective inhibitors of High‐Mobility Group Box1 (HMGB1)—a protein involved in various inflammatory and autoimmune diseases as well as in cancer—we herein discovered a set of anti‐HMGB1 G‐quadruplex(G4)‐forming aptamers by using an in vitro selection procedure applied to a doped library of guanine‐rich oligonucleotides. The selected DNA sequences were then studied in a pseudo‐physiological buffer mimicking the extracellular medium, where HMGB1 exerts its pathological activity, using spectroscopic, electrophoretic, and chromatographic techniques. All the oligonucleotides proved to fold into monomeric G4s and in some cases also dimeric species, stable at physiological temperature. Remarkably, the protein preferentially recognized the sequences forming dimeric parallel G4 structures, as evidenced by a properly designed chemiluminescent binding assay which also highlighted a good selectivity of these aptamers for HMGB1. Moreover, all aptamers showed anti‐HMGB1 activity, inhibiting protein‐induced cell migration. The acquired data allowed identifying L12 as the best anti‐HMGB1 aptamer, featured by high thermal and enzymatic stability, no toxicity at least up to 5 μM concentration on healthy cells, along with potent anti‐HMGB1 activity (IC50 ca. 28 nM) and good binding affinity for the protein, thus indicating it as a very promising lead candidate for in vivo studies. [ABSTRACT FROM AUTHOR]

Aim: The aim of this review was to summarise the most recent evidence about the use of omics‐based techniques as an instrument for a more rapid and accurate characterisation of respiratory tract infections, neurological infections and sepsis in paediatrics. Methods: We performed a narrative review using PubMed and a set of inclusion criteria: English language articles, clinical trials, meta‐analysis and reviews including only paediatric population inherited to this topic in the last 15 years. Results: The examined studies suggest that host gene expression signatures are an effective method to characterise the different types of infections, to distinguish infection from colonisation and, in some cases, to assess the severity of the disease in children. Conclusions: 'Omics‐based techniques' may help to define the aetiology of infections in paediatrics, representing a useful tool to choose the most appropriate therapies and limit antibiotic resistance. [ABSTRACT FROM AUTHOR]

Myoclonus classically presents as a brief (10–50 ms duration), non‐rhythmic jerk movement. The etiology could vary considerably ranging from self‐limited to chronic or even progressive disorders, the latter falling into encephalopathic pictures that need a prompt diagnosis. Beyond the etiological classification, others evaluate myoclonus' body distribution (i.e., clinical classification) or the location of the generator (i.e., neurophysiological classification); particularly, knowing the anatomical source of myoclonus gives inputs on the observable clinical patterns, such as EMG bursts duration or EEG correlate, and guides the therapeutic choices. Among all the chronic disorders, myoclonus often presents itself as a manifestation of epilepsy. In this context, myoclonus has many facets. Myoclonus occurs as one, or the only, seizure manifestation while it can also present as a peculiar type of movement disorder; moreover, its electroclinical features within specific genetically determined epileptic syndromes have seldom been investigated. In this review, following a meeting of recognized experts, we provide an up‐to‐date overview of the neurophysiology and nosology surrounding myoclonus. Through the dedicated exploration of epileptic syndromes, coupled with pragmatic guidance, we aim to furnish clinicians and researchers alike with practical advice for heightened diagnostic management and refined treatment strategies. Plain Language Summary: In this work, we described myoclonus, a movement characterized by brief, shock‐like jerks. Myoclonus could be present in different diseases and its correct diagnosis helps treatment. [ABSTRACT FROM AUTHOR]

Objectives: To assess the diagnostic delay, the number and type of referrals and the clinical and psychological profile in a wide sample of patients with Burning Mouth Syndrome (BMS). Materials and Methods: Data on the disease onset, oral symptoms, type and number of practitioners consulted, misdiagnoses, and the presence of medically unexplained extraoral physical symptoms were recorded in 500 BMS patients. Potential predictors of diagnostic delay were also evaluated. Results: The mean diagnostic delay was 29.71 ± 47.19 months. An average of 2.61 ± 1.65 practitioners were consulted by each patient, the most frequent being the general physicians (287; 57.4%), maxillofacial surgeons (111; 22.2%), and otolaryngologists (104; 20.8%). The mean number of misdiagnoses was 3.54 ± 1.85. Nonspecific stomatitis, candidiasis, and gastroesophageal reflux were the most common misdiagnoses. Higher age, low education, the presence of dysgeusia, and a previous history of psychiatric illness were predictors of a longer diagnostic delay (p‐value: 0.028, 0.050, 0.007, 0.034, respectively). Conclusions: The lack of knowledge among specialists, the high rate of misdiagnosis, and the diagnostic delay of BMS highlight the need to introduce educational interventions in all medical specialties in order to promote an early and appropriate diagnosis, thereby improving the prognosis and quality of life of the patients. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure‐induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM. Methods: We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM− (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental/psychiatric disorder). Results: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM− subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM− an established association. Burden analysis did not identify any single burdened gene or gene set. Significance: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene–disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM− and IFIH1, are also reported. Although we provide robust evidence for gene variants associated with EEM+, the core genetic etiology of EEM− remains to be elucidated. [ABSTRACT FROM AUTHOR]

Background and Aims: Drug‐induced liver injury (DILI) is one of the most frequent reasons for failure of drugs in clinical trials or market withdrawal. Early assessment of DILI risk remains a major challenge during drug development. Here, we present a mechanism‐based weight‐of‐evidence approach able to identify certain candidate compounds with DILI liabilities due to mitochondrial toxicity. Methods: A total of 1587 FDA‐approved drugs and 378 kinase inhibitors were screened for cellular stress response activation associated with DILI using an imaging‐based HepG2 BAC‐GFP reporter platform including the integrated stress response (CHOP), DNA damage response (P21) and oxidative stress response (SRXN1). Results: In total 389, 219 and 104 drugs were able to induce CHOP‐GFP, P21‐GFP and SRXN1‐GFP expression at 50 μM respectively. Concentration response analysis identified 154 FDA‐approved drugs as critical CHOP‐GFP inducers. Based on predicted and observed (pre‐)clinical DILI liabilities of these drugs, nine antimycotic drugs (e.g. butoconazole, miconazole, tioconazole) and 13 central nervous system (CNS) agents (e.g. duloxetine, fluoxetine) were selected for transcriptomic evaluation using whole‐genome RNA‐sequencing of primary human hepatocytes. Gene network analysis uncovered mitochondrial processes, NRF2 signalling and xenobiotic metabolism as most affected by the antimycotic drugs and CNS agents. Both the selected antimycotics and CNS agents caused impairment of mitochondrial oxygen consumption in both HepG2 and primary human hepatocytes. Conclusions: Together, the results suggest that early pre‐clinical screening for CHOP expression could indicate liability of mitochondrial toxicity in the context of DILI, and, therefore, could serve as an important warning signal to consider during decision‐making in drug development. [ABSTRACT FROM AUTHOR]

Epstein–Barr Virus (EBV) is a ubiquitous herpes type virus that is associated with post‐transplant lymphoproliferative disorder (PTLD). Usual management includes reduction or cessation of immunosuppression and in some cases chemotherapy including rituximab. However, limited therapies are available if PTLD is refractory to rituximab. Several clinical trials have investigated the use of EBV‐directed T cells in rituximab‐refractory patients; however, data regarding response is scarce and inconclusive. Herein, we describe a patient with EBV‐PTLD refractory to rituximab after orthotopic heart transplantation (OHT) requiring EBV‐directed T‐cell therapy. This article aims to highlight the unique and aggressive clinical presentation and progression of PTLD with utilization of EBV‐directed T‐cell therapy for management and associated pitfalls. [ABSTRACT FROM AUTHOR]

Introduction: Considering the advances in haemophilia management and treatment observed in the last decades, a new set of value‐based outcome indicators is needed to assess the quality of care and the impact of these medical innovations. Aim: The Value‐Based Healthcare in Haemophilia project aimed to define a set of clinical outcome indicators (COIs) and patient‐reported outcome indicators (PROIs) to assess quality of care in haemophilia in high‐income countries with a value‐based approach to inform and guide the decision‐making process. Methods: A Value‐based healthcare approach based on the available literature, current guidelines and the involvement of a multidisciplinary group of experts was applied to generate a set of indicators to assess the quality of care of haemophilia. Results: A final list of three COIs and five PROIs was created and validated. The identified COIs focus on two domains: musculoskeletal health and function, and safety. The identified PROIs cover five domains: bleeding frequency, pain, mobility and physical activities, Health‐Related Quality of Life and satisfaction. Finally, two composite outcomes, one based on COIs, and one based on PROIs, were proposed as synthetic outcome indicators of quality of care. Conclusion: The presented standard set of health outcome indicators provides the basis for harmonised longitudinal and cross‐sectional monitoring and comparison. The implementation of this value‐based approach would enable a more robust assessment of quality of care in haemophilia, within a framework of continuous treatment improvements with potential added value for patients. Moreover, proposed COIs and PROIs should be reviewed and updated routinely. [ABSTRACT FROM AUTHOR]

Backgroud: A huge amount of data about psychosocial issues of people with haemophilia (PwH) are available; however, these materials are fragmentary and largely outdated, failing to reflect the impact of current treatment strategies. Aim: Describing the influence of illness on psychosocial aspects of adult PwH (≥18 years) and caregivers of children with haemophilia (CPwH) without inhibitors, in Italy. Methods: Surveys (for adult PwH, CPwH and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. Results: A total of 120 PwH without inhibitors and 79 CPwH completed the survey. Adult patients reported a significant impairment in many psychosocial aspects, including working activities, relations with family members and social relations. Caregivers generally reported better scores in all aspects of the survey. Mobility, Pain and Mental health domains of EQ‐5D were the most frequently impaired in both patients and caregivers, reducing the perceived quality of life. Genetic counselling was an important issue, 53% of CPwH declaring unawareness of their carrier status, as well as the psychological support offered by the reference center, 67.0% of respondents reporting that no psychological support was provided at the time of diagnosis communication. Conclusion: This study provides information about PwH's and CPwH's point of view in the current scenario of continuous innovations in haemophilia treatment and management furthermore, updated insights on psychosocial problems faced by patients and caregivers are reported. [ABSTRACT FROM AUTHOR]

Background: The Hugo RAS™ system (Medtronic, Minneapolis, MN, USA), approved for gynaecological and urological procedures, has been recently certified for the use in few general surgeries. Only bariatric and colorectal procedures have been described so far. Methods: Here, we report the first worldwide experience with three cases of full‐robotic cholecystectomies with the Hugo RAS™ system. Results: A description of the operative room setup, of the docking angles and details of the procedures is reported. Docking time was 12, 10, and 6 min, respectively. The total operative time was 105 min in the first case, 100 min in the second and 88 in the third case. Intra‐ and post‐operative courses were uneventful. Conclusions: With this pre‐defined set up, the innovative conformation of Hugo RAS™ system can safely allow performing full robotic cholecystectomy avoiding the need for additional ports. [ABSTRACT FROM AUTHOR]

Several advanced imaging techniques are now available for endoscopists managing inflammatory bowel disease (IBD) patients. These tools, including dye‐based and virtual chromoendoscopy, probe‐based confocal laser endomicroscopy and endocytoscopy, are increasingly innovative applications in clinical practice. They allow for a more in‐depth and refined evaluation of the mucosal and vascular bowel surface, getting closer to histology. They have demonstrated a remarkable ability in assessing intestinal inflammation, histologic remission, and predicting relapse and favorable long‐term outcomes. In addition, the future application of molecular endoscopy to predict biological drug responses has yielded preliminary but encouraging results. Furthermore, these techniques are crucial in detecting and characterizing IBD‐related dysplasia, assisting endoscopic mucosal resection and submucosal dissection towards a surgery‐sparing approach. Artificial intelligence (AI) holds great potential in this promising landscape, as it can provide an objective and reproducible assessment of inflammation and dysplasia. Moreover, it can improve the prediction of outcomes and aid in subsequent therapeutic decision‐making. This review aims to summarize the promising role of state‐of‐the‐art advanced endoscopic techniques and related AI‐enabled models for managing IBD, paving the way for precision medicine. [ABSTRACT FROM AUTHOR]

Photo‐induced charge transfer (CT) states are pivotal in many technological and biological processes. A deeper knowledge of such states is mandatory for modeling the charge migration dynamics. Real‐time time‐dependent density functional theory (RT‐TD‐DFT) electronic dynamics simulations are employed to explicitly observe the electronic density time‐evolution upon photo‐excitation. Asymmetrically substituted indenotetracene molecules, given their potential application as n‐type semiconductors in organic photovoltaic materials, are here investigated. Effects of substituents with different electron‐donating characters are analyzed in terms of the overall electronic energy spacing and resulting ultrafast CT dynamics through linear response (LR‐)TD‐DFT and RT‐TD‐DFT based approaches. The combination of the computational techniques here employed provided direct access to the electronic density reorganization in time and to its spatial and rational representation in terms of molecular orbital occupation time evolution. Such results can be exploited to design peculiar directional charge dynamics, crucial when photoactive materials are used for light‐harvesting applications. [ABSTRACT FROM AUTHOR]

Background and Purpose: Physiotherapy is gaining a central role in oncology. However, the training and competencies needed by physiotherapists in oncology rehabilitation are still unclear. This study aims to articulate the training trajectory of physiotherapists in oncology rehabilitation from entry‐level education to advanced education degrees. Methods: Qualitative focus group study following a 'Reflexive Thematic Analysis' for data analysis. Participants were Italian physiotherapists with expertise in Oncology Rehabilitation (either clinically or academically) and Physiotherapy Bachelor of Science (BSc) course leaders, selected through purposive sampling. Results: Two focus groups were conducted with 14 participants. Six themes were developed: 1. 'Entry‐Level Education in Oncology Rehabilitation: Let's Have a Taste', as the BSc introduces oncology rehabilitation. 2. 'Basic Knowledge: Building up the Library' as students acquire basic knowledge on oncology rehabilitation during their BSc; 3. 'Learning by Experience: The Relevance of the Placement' to answer the question "Is this the right road for me?"; 4. 'Clinical Reasoning and Competencies in Oncology Rehabilitation Embedded in Uncertainty' because oncology physiotherapists need to deal with the uncertainty of their patients' status; 5. 'Advanced Education Degree Skills: from Appetiser to the Main Course', as advanced education degree courses allow for becoming an expert in the field; 6. 'A Call to Action for Physiotherapists: Prevention—Diagnosis—Survivorship & End of Life', to realise their critical role in all the phases of the oncology path. Conclusions: The BSc in Physiotherapy provides a foundation for future physiotherapists to understand oncology rehabilitation, but advanced education is necessary for expertise. The findings of this study have important implications for creating a shared physiotherapy curriculum in oncology rehabilitation. Implication for Physiotherapy Practice: This study has significant implications for improving physiotherapy curricula in oncology rehabilitation, positively impacting the skills and competencies of practitioners in this paramount field. [ABSTRACT FROM AUTHOR]

Anion exchange membranes have aroused much interest for use in electrolyzers and alkaline fuel cells. In this work, two double‐charged anion exchange membranes based on poly(2,5‐benzimidazole) and poly(vinylbenzyl chloride) prepared by the casting method are reported. The effect of two different quaternizing agents based on 1,4‐diazabicyclo[2.2.2]octane (DABCO) was evaluated. These membranes were characterized by means of Fourier transform infrared spectroscopy, SEM, TGA, water contact angle, swelling ratio, KOH and water uptake, ionic exchange capacity and ionic conductivity. The results showed that the length of the alkyl chain has a strong effect on the membrane properties. A good performance in a zero‐gap water alkaline electrolyzer was obtained for the membrane based on the butyl derivate of DABCO (BDABCO). © 2023 Society of Industrial Chemistry. [ABSTRACT FROM AUTHOR]

Venetoclax, a potent BCL‐2 inhibitor, is currently under development for treatment of t(11;14) Multiple myeloma (MM). The objective of this research was to investigate the exposure–response relationships of venetoclax for a phase 1/2 study evaluating venetoclax monotherapy or in combination with dexamethasone in relapsed or refractory MM. A total of 117 patients receiving venetoclax at 300, 600, 800, 900, or 1200 mg were included in the analysis. The impact of venetoclax exposures on efficacy (objective response rate [ORR], progression‐free survival [PFS] and overall survival [OS]) as well as safety (treatment‐emergent adverse effects (grade ≥3) of neutropenia, infection, and any grade of serious treatment‐emergent adverse effects) was evaluated. In the t(11;14)‐positive subpopulation, venetoclax exposure relationships to PFS and OS indicated a trend of longer PFS and OS with higher exposures. Moreover, logistic regression analyses for clinical response (ORR and ≥VGPR rate) demonstrated a statistically significant (p < 0.05) relationship with exposure. Evaluation of the exposure‐safety relationships demonstrated a lack of a relationship between venetoclax exposures (AUCavg) and grade ≥3 infections, grade ≥3 neutropenia, grade ≥3 treatment‐emergent adverse events or any grade serious treatment‐emergent adverse events. These findings support further study of venetoclax at 800 mg QD dose in combination with dexamethasone in the t(11;14)‐positive patient population where increased efficacy was observed without an increase in safety events.Clinical Trial: NCT01794520 registered 20 February 2013. [ABSTRACT FROM AUTHOR]

ClC‐6 and ClC‐7 are closely related, intracellular Cl−/H+ antiporters belonging to the CLC family of channels and transporters. They localize to acidic late endosomes and lysosomes and probably function in ionic homeostasis of these contiguous compartments. ClC‐7 transport function requires association with the accessory protein Ostm1, whereas ClC‐6 transport does not. To elucidate their roles in endo‐lysosomes, we measured Cl−‐ and pH‐dependences of over‐expressed wild‐type ClC‐6 and ClC‐7, as well as disease‐associated mutants, using high‐resolution recording protocols. Lowering extracellular Cl− (corresponding to luminal Cl− in endo‐lysosomes) reduced ClC‐6 currents, whereas it increased transport activity of ClC‐7/Ostm1. Low extracellular Cl− activated ClC‐7/Ostm 1 under acidic extracellular conditions, as well as under conditions of low intracellular chloride. Activation is conserved in ClC‐7Y713C, a variant displaying disrupted PI(3,5)P2 inhibition. Detailed biophysical analysis of disease‐associated ClC‐6 and ClC‐7 gain‐of‐function (GoF) variants, ClC‐6Y553C and ClC‐7Y713C, and the ClC‐7Y577C and ClC‐6Y781C correlates, identified additional functional nuances distinguishing ClC‐6 and ClC‐7. ClC‐7Y577C recapitulated GoF produced by ClC‐6Y553C. ClC‐6Y781C displayed transport activation qualitatively similar to ClC‐7Y713C, although current density did not differ from that of wild‐type ClC‐6. Finally, rClC‐7R760Q, homologous to hClC‐7R762Q, an osteopetrosis variant with fast gating kinetics, appeared indifferent to extracellular Cl−, identifying altered Cl− sensitivity as a plausible mechanism underlying disease. Collectively, the present studies underscore the distinct roles of ClC‐6 and ClC‐7 within the context of their respective localization to late endosomes and lysosomes. In particular, we suggest the atypical inhibition of ClC‐7 by luminal Cl− serves to limit excessive intraluminal Cl− accumulation. Key points: ClC‐6 and ClC‐7 are late endosomal and lysosomal 2 Cl−/1 H+ exchangers, respectively. When targeted to the plasma membrane, both activate slowly at positive voltages.ClC‐6 activity is decreased in low extracellular (i.e. luminal) chloride, whereas ClC‐7 is activated by low luminal chloride, even at acidic pH.The functional gain‐of‐function phenotypes of the ClC‐6 and ClC‐7 disease mutations ClC‐6Y553C and ClC‐7Y715C are maintained when introduced in their respective homologues, ClC‐7Y577C and ClC‐6Y781C, with all mutations retaining chloride dependence of the respective wild type (WT).An osteopetrosis mutation of ClC‐7 displaying fast gating kinetics (R762Q) was less sensitive to extracellular chloride compared to WT.The opposing substrate dependences of ClC‐6 and ClC‐7 Cl− / H+ exchangers point to non‐overlapping physiological functions, leading us to propose that inhibition of ClC‐7 by luminal chloride and protons serves to prevent osmotic stress imposed by hyper‐accumulation of chloride. [ABSTRACT FROM AUTHOR]

A 6‐year‐old, female, neutered labrador retriever was presented for investigation of cervical pain. At initial presentation, pain was localised to the cervical region. No neurological deficits were observed. Computed tomography scan and magnetic resonance imaging revealed an extra‐axial cyst‐like lesion at the level of the foramen magnum, with extension into the caudal fossa. Conservative management, which included activity restriction and a 4‐week course of corticosteroids failed to resolve the clinical signs, and the cyst was eventually surgically excised. Histological examination of the sample submitted confirmed a synovial cyst. The dog recovered uneventfully after surgery and remained pain free until the last follow‐up (9 months). Thus, surgical excision of an extradural intraspinal synovial cyst in a dog provided resolution of the clinical signs. [ABSTRACT FROM AUTHOR]

Flower nectar, a sugar‐rich solution containing amino acids as major secondary solutes, is the primary energy source for bees. Proline is one of the most abundant protein nectar amino acids, showing several effects on bee physiology. Mason bees are outstanding pollinators, often preferred to Apis mellifera for pollination of fruit trees. Among them, Osmia cornuta (Latreille) is one of the most successfully managed species on a commercial scale. In this work, the effects of 10 mM proline‐enriched diet administration on O. cornuta feed consumption, survival, behaviour and haemolymph amino acid composition were investigated. Feed intake was higher for the proline diet, while survival rate was not affected. Behaviour was affected only in the senescence of the mason bees with a reduction in locomotor activity induced by proline intake. Proline diet also affected the haemolymph amino acid composition, decreasing concentration of tyrosine, methionine, leucine and phenylalanine after 10 days of feeding. These results were discussed in relation to the potential involvement of proline in oxidative stress in insects and proline's ability to be converted to other amino acids. Further investigations are necessary to better understand the molecular mechanisms of proline effects on locomotion and oxidative stress. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to explore knowledge, practice, and attitude on oral cancer (OC) among a cohort of Italian dental hygienists, in consideration of their role in the field of early diagnosis. Materials and Methods: A cross‐sectional study of 150 Italian dental hygienists was performed to assess the participant's knowledge, practice, and attitude on OC. Data were collected using a structured self‐administered questionnaire (through Google Forms). The questionnaire included four sections: sociodemographic information, disease knowledge, answers related to attitudes toward OC, and a questionnaire assessing the practice of dental hygienists on oral screening. Results: Responses were received from 137 participants (83 women and 54 men). Overall, there is a good knowledge of the real risk factors among the participants (98.5%, 98.5%, and 94.2% regard smoking, alcohol, and HPV, respectively). The analysis related to the knowledge of non‐risk factors, oral potentially malignant disorders, and clinical features of OC showed more heterogeneous results. Only 60% considered university education to be adequate. The totality of dental hygienists considered continuing education necessary, but despite this, only half took updating courses. Finally, 90% performed intraoral screening visits, and 95% and 69% investigated smoking and alcohol consumption, respectively. Conclusions: Our data showed the need to implement OC training courses by re‐evaluating pre‐ and post‐graduate training programs. [ABSTRACT FROM AUTHOR]

Aim: The distribution of mesoplankton communities has been poorly studied at global scale, especially from in situ instruments. This study aims to (1) describe the global distribution of mesoplankton communities in relation to their environment and (2) assess the ability of various environmental‐based ocean regionalizations to explain the distribution of these communities. Location: Global ocean, 0–500 m depth. Time Period: 2008–2019. Major Taxa Studied: Twenty‐eight groups of large mesoplanktonic and macroplanktonic organisms, covering Metazoa, Rhizaria and Cyanobacteria. Methods: From a global data set of 2500 vertical profiles making use of the Underwater Vision Profiler 5 (UVP5), an in situ imaging instrument, we studied the global distribution of large (>600 μm) mesoplanktonic organisms. Among the 6.8 million imaged objects, 330,000 were large zooplanktonic organisms and phytoplankton colonies, the rest consisting of marine snow particles. Multivariate ordination (PCA) and clustering were used to describe patterns in community composition, while comparison with existing regionalizations was performed with regression methods (RDA). Results: Within the observed size range, epipelagic plankton communities were Trichodesmium‐enriched in the intertropical Atlantic, Copepoda‐enriched at high latitudes and in upwelling areas, and Rhizaria‐enriched in oligotrophic areas. In the mesopelagic layer, Copepoda‐enriched communities were also found at high latitudes and in the Atlantic Ocean, while Rhizaria‐enriched communities prevailed in the Peruvian upwelling system and a few mixed communities were found elsewhere. The comparison between the distribution of these communities and a set of existing regionalizations of the ocean suggested that the structure of plankton communities described above is mostly driven by basin‐level environmental conditions. Main Conclusions: In both layers, three types of plankton communities emerged and seemed to be mostly driven by regional environmental conditions. This work sheds light on the role not only of metazoans, but also of unexpected large protists and cyanobacteria in structuring large mesoplankton communities. [ABSTRACT FROM AUTHOR]

During the last decade, perovskite solar technologies underwent an impressive development, with power conversion efficiencies reaching 25.5% for single‐junction devices and 29.8% for Silicon‐Perovskite tandem configurations. Even though research mainly focused on improving the efficiency of perovskite photovoltaics (PV), stability and scalability remain fundamental aspects of a mature photovoltaics technology. For n‐i‐p structure perovskite solar cells, using poly‐triaryl(amine) (PTAA) as hole transport layer (HTL) allowed to achieve marked improvements in device stability compared with other common hole conductors. For p‐i‐n structure, poly‐triaryl(amine) is also routinely used as dopant‐free hole transport layer, but problems in perovskite film growth, and its limited resistance to stress and imperfect batch‐to‐batch reproducibility, hamper its use for device upscaling. Following previous computational investigations, in this work, we report the synthesis of two small‐molecule organic hole transport layers (BPT‐1,2), aiming to solve the above‐mentioned issues and allow upscale to the module level. By using BPT‐1 and methylammonium‐free perovskite, max. Power conversion efficiencies of 17.26% and 15.42% on a small area (0.09 cm2) and mini‐module size (2.25 cm2), respectively, were obtained, with a better reproducibility than with poly‐triaryl(amine). Moreover, BPT‐1 was demonstrated to yield more stable devices compared with poly‐triaryl(amine) under ISOS‐D1, T1, and L1 accelerated life‐test protocols, reaching maximum T90 values >1000 h on all tests. [ABSTRACT FROM AUTHOR]

Implementing the circular economy (CE) through the design of a restorative industrial system is a major challenge. This study investigates the capabilities that underpin the circular competitive advantages of firms in the textile and clothing industry in Italy, which is one of the country's most polluting sectors. We have developed a framework of dynamic capabilities needed for circular transition, using the theoretical lenses of a natural‐resource‐based view. Using a multiple‐case study, the strategies of pollution prevention, product stewardship, and sustainable development and the associated capabilities of sensing, seizing, and reconfiguring are investigated. Internal practices, the role of the downstream actors in the supply chain, co‐creation dynamics with external actors, and the social potential of the CE emerge as key factors. Managers may also benefit from our recommendations aimed at increasing the environmental performance of their firms and scaling up their born‐circular businesses. [ABSTRACT FROM AUTHOR]

Background: The Step‐Down Approach for Cow's Milk Allergy (SDACMA) trial evaluated the tolerability and the rate of immune tolerance acquisition in CMA children starting dietary treatment with amino acid‐based formula (AAF) and then switching to EHCF containing the probiotic Lacticaseibacillus rhamnosus GG (EHCF + LGG). Methods: Randomized controlled trial involving IgE‐mediated CMA children receiving AAF from at least 4 weeks. EHCF + LGG tolerance was evaluated by the results of double‐blind placebo‐controlled food challenge (DBPCFC). Subjects tolerating EHCF + LGG were randomly allocated to remain on AAF, or to switch to EHCF + LGG. Immune tolerance acquisition to cow's milk proteins was evaluated with DBPCFC after 12 months of treatment. Allergy screening tests and body growth were also monitored. Results: Sixty IgE‐mediated CMA children were enrolled. The proportion of children treated with AAF who resulted tolerant to the first exposure of EHCF + LGG was 0.98 (exact 95% CI 0.91–0.99). The rate of the immune tolerance acquisition to cow milk proteins after 12 months treatment was higher in the EHCF + LGG (0.48, 95% exact CI 0.29–0.67, n/N = 14/29) than in the AAF group (0.03, 95% exact CI 0.001–0.17, n/N = 1/30). There was an absolute benefit increase (ABI) of tolerance rate equal to 0.45 (95% CI 0.23–0.63, Newcombe method 10) for EHCF + LGG versus AAF, corresponding to a NNT of 2 (2–4, Bender's method). A normal body growth pattern was observed in the two study groups. Conclusion: In IgE‐mediated CMA children the step‐down from AAF to EHCF + LGG is well tolerated and could facilitate the immune tolerance acquisition. [ABSTRACT FROM AUTHOR]

Four pinaceae pine resins analyzed in this study: black pine, shore pine, Baltic amber, and rosin demonstrate excellent dielectric properties, outstanding film forming, and ease of processability from ethyl alcohol solutions. Their trap‐free nature allows fabrication of virtually hysteresis‐free organic field effect transistors operating in a low voltage window with excellent stability under bias stress. Such green constituents represent an excellent choice of materials for applications targeting biocompatibility and biodegradability of electronics and sensors, within the overall effort of sustainable electronics development and environmental friendliness. [ABSTRACT FROM AUTHOR]