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Purpose: Maximal speed is an important physical-fitness attribute for female Australian footballers. The effects of sprint training, maximal strength, and technical training have been reported in laboratory studies. However, no study has determined the combined effect and relative contribution of these training modalities on maximal speed adaptation in situ. Therefore, the aim of this study was to determine the training factors affecting maximal speed adaptation during a preseason in subelite female Australian Rules footballers. Methods: Maximal speed during field training, predicted 1-repetition maximum (1RM) for box squat and hip thrust, and sprint biomechanics were assessed during early and late preseason (∼9 wk apart) in 15 female subelite Australian Rules Football players (age 20 [3] y). On-field training volume and intensity (total distance, high-speed running, very-high-speed running, and maximal speed) were determined using a Global Positioning System. A multivariate regression model was used to determine the factors associated with changes in maximal speed across the preseason. Results: The preseason training program had a small effect on maximal speed and large to very large effects on strength and sprint biomechanics. The multivariate regression with the greatest fit (P <.001, R2 =.939) included change in estimated 1RM box squat (β = −0.63), total distance per week (β = −0.55), and change in hip projection (β = 0.16) as factors. Multivariate regression of biomechanical factors (P =.044, R2 =.717) and maximal strength factors (P =.003, R2 =.676) were also significant. Conclusion: The development of maximal speed across a preseason is dependent on (1) total distance per week, (2) maximal strength adaptation, and (3) sprint technique adaptation in female subelite Australian rules football players. [ABSTRACT FROM AUTHOR]

Background: Complete androgen insensitivity syndrome (CAIS) is a rare disorder of sex development characterized by 46,XY karyotype and testes, yet presenting with a complete female phenotype, which is related to mutations in the androgen receptor (AR) gene. Case presentation: We herein present the case of a 14-year-old adolescent with primary amenorrhea and suspected delayed puberty whose diagnostic journey led to the identification of CAIS through the demonstration of a novel AR variant (c.159_207del). Case-based review: Our report encompasses the complexity of CAIS management, focusing on the risk of malignancy, surveillance options, hormone replacement therapy, timing of an eventual gonadectomy, and the psychosocial impact of such a diagnosis. An algorithm has been formulated for the management of CAIS starting in adolescence, highlighting the conservative approach for those patients unwilling to undergo gonadectomy. Conclusions: Primary amenorrhea and delay in puberty development may provide clues, ultimately leading to a diagnosis of CAIS. This review emphasizes the cruciality of a multidisciplinary approach in managing patients with CAIS, needing for an individualized care to optimize the overall outcome. [ABSTRACT FROM AUTHOR]

Coastal ecosystems are increasingly experiencing anthropogenic pressures such as climate warming, CO2 increase, metal and organic pollution, overfishing, and resource extraction. Some resulting stressors are more direct like pollution and fisheries, and others more indirect like ocean acidification, yet they jointly affect marine biota, communities, and entire ecosystems. While single-stressor effects have been widely investigated, the interactive effects of multiple stressors on ecosystems are less researched. In this study, we review the literature on multiple stressors and their interactive effects in coastal environments across organisms. We classify the interactions into three categories: synergistic, additive, and antagonistic. We found phytoplankton and bivalves to be the most studied taxonomic groups. Climate warming is identified as the most dominant stressor which, in combination, with other stressors such as ocean acidification, eutrophication, and metal pollution exacerbate adverse effects on physiological traits such as growth rate, fitness, basal respiration, and size. Phytoplankton appears to be most sensitive to interactions between warming, metal and nutrient pollution. In warm and nutrient-enriched environments, the presence of metals considerably affects the uptake of nutrients, and increases respiration costs and toxin production in phytoplankton. For bivalves, warming and low pH are the most lethal stressors. The combined effect of heat stress and ocean acidification leads to decreased growth rate, shell size, and acid-base regulation capacity in bivalves. However, for a holistic understanding of how coastal food webs will evolve with ongoing changes, we suggest more research on ecosystem-level responses. This can be achieved by combining in-situ observations from controlled environments (e.g. mesocosm experiments) with modelling approaches. [ABSTRACT FROM AUTHOR]

Coding and computational thinking (CT) are important skills to include in early childhood education. Measuring these vital skills in preschool-age children can be challenging. We modified the TechCheck-PreK assessment, an unplugged measure of CT for 3-to-5-year-old children, to increase reliability and to add foundational coding concepts. We created the Coding Readiness Assessment (CRA) from a subset of nine TechCheck-PreK items and twelve new items that assess additional CT and coding readiness constructs. In an initial feasibility study of the CRA, teachers observed impulsive responses by children. We mitigated this by implementing a brief delay between the appearance of the question and the timeframe in which children could respond. In a subsequent randomized control trial, the CRA was administered 1637 times by Head Start educators. The assessment took an average of 9.8 min to administer. CRA scores were normally distributed and increased on average as a function of age. Girls scored slightly higher than boys, although the difference was not significant when age and race were taken into account. The CRA showed acceptable levels of reliability in terms of internal consistency (α = 0.78) and test–retest reliability (r = 0.65). Results from a 3PL indicate that the CRA has suitable levels of difficulty and skill level discrimination for 3-to-5-year-olds. The 3PL guessing parameter was 0.28, indicating that steps to reduce impulsive responses were successful. We conclude that the CRA has suitable properties for assessing preschool-age children's CT skills and coding readiness. [ABSTRACT FROM AUTHOR]

Pneumonia caused by Pneumocystis jirovecii infection (PCP) is a potentially life-threatening illness, particularly affecting the immunocompromised. The past two decades have shown an increase in PCP incidence; however, the underlying factors that promote disease severity and fatality have yet to be fully elucidated. Recent evidence suggests that the microbiota of the respiratory tract may play a role in stimulating or repressing pulmonary inflammation, as well as the progression of both bacterial and viral pneumonia. Here, we employed 16S rRNA metataxonomic sequencing to profile the respiratory microbiota of patients with mild-moderate and severe PCP. Our results show that the upper and lower airways of PCP patients have bacterial profiles which have been associated with a pro-inflammatory response. Furthermore, we find that severe PCP is associated with lower bacterial diversity and an increase in Prevotella and a decrease in Neisseria. Functionally, severe PCP was associated with a decrease in metabolic pathways of molecules with anti-inflammatory and antimicrobial properties. To our knowledge, this is the first study showing an association of PCP severity with shifts in the respiratory microbiome and may provide some insight into which patients are more susceptible to the more severe manifestations of the disease. [ABSTRACT FROM AUTHOR]

Purpose: The availability of care recommendations has improved survival and delayed the progression of clinical signs in Duchenne muscular dystrophy. The aim of the study was to perform a nationwide survey investigating the prevalence, age distribution, and functional status of Duchenne muscular dystrophyin Italy. Methods: The survey was performed by collecting data from all 31 reference centers for Duchenne muscular dystrophy in Italy using a structured form. We assessed age distribution, motor function, and the need for respiratory and nutritional support to evaluate their prevalence in different age and functional subgroups. Results: The estimated prevalence was 1.65/100,000 (3.4/100,000 males). There were 972 boys and adults with a confirmed diagnosis of Duchenne, of age ranging between 6 months and 48 years (mean = 16.5). Over 59% were below the age of 18 years and the remaining 41% were adults. Over 43% were ambulant and 57% non-ambulant; 14.7% were steroids naive (mean 20.6 years), 75% are currently on steroids (mean 14.6 years) with 604 on the daily regime, 126 intermittent. Nearly 73% did not require any ventilatory support, 16% had NIV ≤ 12 h, 9% > 12 h, and 1.4% had a tracheostomy. More than 82% did not require any nutritional support, 13% required food modification/semisolid and 4.4% had a G-tube. Conclusions: Our findings provide information to be used not only for epidemiological purposes but also for possible trial design to include older non-ambulant patients who until recently have been excluded and for whom clinical information is limited. What is Known • Duchenne muscular dystrophy is a progressive disorder associated with reduced survival. • As part of the disorder there is also a progressive loss of important milestones, including loss of ambulation, and increased need for respiratory and nutritional support. What is New • Our nationwide survey provides prevalence, age distribution, and functional status for Duchenne muscular dystrophyin Italy including both boys and adults. • Our findings can be used for epidemiological purposes and for possible trial design. [ABSTRACT FROM AUTHOR]

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Introduction: Piwi proteins and the associated Piwi-interacting RNAs (piRNAs) coordinate a surveillance system that protects the animal genome from DNA damage induced by transposable element (TE) mobilization. While the pathway has been described in detail in the fruit fly Drosophila melanogaster , much less is known in more basal insects. Rhodnius prolixus is an hemipteran insect and one of the major vectors of Chagas disease. Rhodnius acquired specific classes of horizontally transferred transposons (HTTs) by feeding on bats, opossums and squirrel monkeys, thus providing the opportunity to investigate the piRNA-base response against HTTs in this species. Methods: SmallRNA-Seq reads mapping to HTTs and resident transposable elements were quantified and checked for piRNA features like 1U a 10A biases, ping-pong and phasing signatures. Uniquely mapped piRNAs were used to identify piRNA clusters in Rhodnius ' genome. RNA-Seq data was used to quantify transposon and Rp-PIWI genes expression levels and were validated by qRT-PCR. Results: By analyzing the temporal dynamics of piRNA cluster expression and piRNA production during critical stages of Rhodnius development, we show that peak levels of ∼28 nt long piRNAs correlate with reduced HTT and resident TE expression primarily during embryogenesis. Strikingly, while resident TEs piRNAs seem to engage in a typical ping-pong amplification mechanism, sense and antisense HTT piRNAs instead overlap by ∼20 nt or do not display ping-pong signatures. Discussion: Our data shed light on the biogenesis and functions of the piRNAs in Rhodnius prolixus and reveal that piRNAs, but not the siRNA pathway, responded to HTTs that were recently transferred from vertebrate tetrapods to a hematophagous insect of medical relevance. [ABSTRACT FROM AUTHOR]

Technological innovation in transportation firms is currently supported by presence of directors with engineering / technology education background and younger generation as audience for this community service activity because they should give motivation and awareness that a technological mindset is needed to achieve success. They should equip themselves not only with formal education but also knowledge about technology to become top level carrier. This can be done through bootcamps, training and others. This service activity was carried out through a seminar at National Leader Forum event organized by KAPPIJA 21, various universities and the South Sumatra Provincial Government. As a result, students get enlightened to start looking for their character and passion when starting a career embedded with technology. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our study is to investigate the feasibility of retrograde cannulation using devices with inner branches (IB) for the endovascular treatment of thoracoabdominal aortic aneurysms (TAAAs). Materials and Methods: A retrospective analysis using IB configuration with retrograde cannulation was carried out on TAAAs patients undergoing endovascular treatment. Results: Seven patients underwent IB endovascular treatment with retrograde cannulation between September 2020 and November 2021. The mean age was 80.4 years and 4 patients were male. A total of 26 of 28 target vessels were cannulated by retrograde access with a technical success of 93% (2 of 26 target vessels). Two intra-procedural complications were observed (1 renal artery dissection and 1 collateral renal artery rupture). In total, 26 of 28 treated vessels were retrograde cannulated with a technical success of 93%. A total of 39 stent bridges were used (all Viabahn VBX devices). The mean duration of the procedure was 321±102 minutes, and the mean scan time was 134±62 minutes. Mortality at 30 days was observed in 1 case. During the follow-up, 1 stent bridge occlusion was observed without the need for reintervention. Conclusion: Retrograde cannulation can also be successfully performed in the case of inner branches. Clinical Impact: In inner branched cases, retrograde cannulation should be taken into consideration in particular cases or it could become the option of choice. Dedicated endovascular material available such as steerable catheters and latest generation covered stents is fundamental for the success of the treatment. [ABSTRACT FROM AUTHOR]

Historically, Friedreich's Ataxia (FRDA) has been linked to a relatively preserved cerebellar cortex. Recent advances in neuroimaging have revealed altered cerebello-cerebral functional connectivity (FC), but the extent of intra-cerebellar FC changes and their impact on cognition remains unclear. This study investigates intra-cerebellar FC alterations and their cognitive implications in FRDA. In this cross-sectional, single-center study, resting-state functional MRI data from 17 patients with FRDA (average age 27.7 ± 13.6 years; F/M = 6/11) and 20 healthy controls (HC) (average age 29.4 ± 9.7 years; F/M = 9/11), all of whom underwent neuropsychological testing, were analyzed. From functional connectivity matrices, graph measures were computed at both the network and node levels using two complementary parcellations. FRDA patients exhibited decreased global efficiency (p = 0.04), nodal degree (p = 0.001) and betweenness centrality (p = 0.04) in the vermal portion of lobule VIII, along with reduced global efficiency in cerebellar regions belonging to the Control-A network (p = 0.02), one of the three subdivisions of the Frontoparietal network. Verbal memory deficits correlated with global efficiency in both the vermal portion of lobule VIII (r = 0.53, p = 0.02) and the cerebellar regions of the Control-A network (r = 0.49, p = 0.05). Graph analysis revealed regional intra-cerebellar FC changes in FRDA, marked by reduced functional centrality in cerebellar regions of the vermis and responsible for executive functions. These changes correlated with cognitive alterations, highlighting the role of the cerebellar cortex in the cognitive impairment observed in FRDA. [ABSTRACT FROM AUTHOR]

Oral hygiene is an important self‐care skill that some children may lack, especially children with autism spectrum disorder (ASD). Although some studies have evaluated procedures for teaching toothbrushing, no previous studies have demonstrated procedures for teaching flossing, which is essential for oral hygiene. This study evaluated an intervention for teaching water flossing to two children with ASD and two children without an ASD diagnosis. The intervention package included backward chaining, video modeling, and reinforcement, with some components implemented by a caregiver and some components implemented by an experimenter via telehealth. Behavioral skills training was used to train caregivers prior to implementation of the study. Results indicated that the intervention package was effective in teaching all participants to independently floss their teeth with a water flosser. Effects maintained for all participants 1‐week after completion of teaching. Questionnaires given to caregivers, participants, and dental professionals indicated high social validity. [ABSTRACT FROM AUTHOR]

This paper identifies the architecture of the justiciability of the right to a healthy environment, analysing the contribution of national and international regimes in climate litigation. It argues that neither the former nor the latter alone can currently offer a fully implementable set of remedies to the catastrophic consequences of environmental degradation. In all the cases, collectiveness is a parameter that needs to be taken into consideration, and which is shaping the way most of successful environmental claims are framed. This calls for a reflection on what courts can contribute, and maybe also if they should contribute at all, in the absence of explicit political will in the form of a specific binding treaty. It is concluded that through the interaction between domestic and international courts we can envisage a full coverage of the rights involved. [ABSTRACT FROM AUTHOR]

Introduction/Purpose: Nusinersen, the first treatment approved for all spinal muscular atrophy (SMA) types, is administered intrathecally through lumbar puncture. We used ultrasound assistance or a landmark‐based technique to access the lumbar intrathecal space in adult SMA patients. This study aimed to evaluate the technical success and adverse events (AEs) in such patients using either technique over a long observation period. Methods: Fifty‐one adult patients received 507 consecutive interlaminar nusinersen administrations. Patients presented with both 'uncomplicated spines' or 'complicated spines'; two patients had previous back surgery. Technical success and AEs were recorded using either technique. A generalised linear mixed model was applied to evaluate predictors of technical success and complications. Results: An overall success rate of 99.6%, with only two procedures failing to reach the intrathecal space, and an overall optimal procedure rate of 90.3% have been reported. A total of 455 procedures (89.7%) were uneventfully performed. One (0.2%) case of severe AE (puncture of a bulky abdominal annexal cyst) was recorded. Twenty‐seven episodes (5.3%) of post‐dural puncture headache (PDPH) and 24 episodes (4.7%) of radicular or back pain, both successfully treated with medical therapy, have also been reported. Technical success was significantly associated with 'complicated spines' (P = 0.022) and the use of ultrasound assistance (P = 0.01), and the use of ultrasound was the only independent predictor of uncomplicated procedures (P = 0.007). Discussion: In adult patients with SMA both landmark‐based and ultrasound‐assisted techniques are safe and effective even in the long term. The use of assistance is associated with technical success and can predict uncomplicated procedures. Conclusion: Our results support the use of ultrasonography in order to improve the success and reduce the burden of nusinersen intrathecal administration. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Nusinersen intrathecal administration can be challenging in spinal muscular atrophy (SMA) adults. We aimed to determine if the ultrasound (US)‐assistance reduces the number of needle attempts and needle redirections needed for intrathecal drug administration and its impact on the procedure time, the incidence of adverse events (AEs), and patient satisfaction in these patients. Methods: Fifty‐eight patients aged 18 years and older scheduled for intrathecal nusinersen injection were enrolled and randomized (1:1 ratio) into Group 1 (nusinersen infusion with US‐assisted technique) or Group 2 (nusinersen infusion with landmark‐based technique). The number of attempts, number of redirections, periprocedural time, AEs and patient satisfaction were reported. Continuous variables were compared with the Student t‐test or Wilcoxon rank sum test. Categorical variables were evaluated with the Chi‐square test or Fisher's exact test in case of expected frequencies <5. The p‐values <.05 were considered statistically significant. Results: There were no statistical differences in the number of attempts, AEs, or patient satisfaction between the two groups. The number of needle redirections was significantly lower in the ultrasound group versus landmark‐based group (p <.05) in both the overall group of patients and in the subgroup with difficult spines. The periprocedural time was about 40 seconds longer in US‐group versus landmark‐based group (p <.05). Discussion: In SMA adults, US assistance reduces the number of needle redirections needed for intrathecal drug administration. These results suggest that the US assistance may be advantageous for nusinersen therapy to reduce the therapeutic burden of intrathecal infusion. [ABSTRACT FROM AUTHOR]

This study examines the impact of board characteristics on the environmental, social, and governance (ESG) performance of publicly listed companies in Indonesia. Focusing on firms listed in the KOMPAS100 index, the research explores how board composition, including the number of directors and commissioners, gender diversity, independence, the presence of foreign members, and the sustainability committee, influences ESG scores. Using data from Sustainalytics, financial reports, and sustainability reports, the analysis includes control variables such as public shares, return on assets, leverage, firm age, firm size, and state ownership. Significant correlations were discovered between the characteristics of the board, the sustainability committee, and the ratings related to environmental, social, and governance factors (ESG). Companies that have larger boards, a higher proportion of female and independent directors, and international members exhibit superior environmental, social, and governance (ESG) performance. Sustainability committees contribute to the improvement of ESG outcomes. The findings indicate that implementing well-organized governance systems and having diverse board compositions are essential for successfully managing sustainability. The study utilized regression models to examine the influence of board features on ESG performance. Data from the KOMPAS100 index, which includes prominent Indonesian companies, was used for analysis. This empirical investigation offers useful insights into the ways in which corporate governance frameworks can influence sustainable business practices in the Indonesian context. Policymakers are advised to establish policies that encourage the formation of board diversity and sustainability committees. Corporate executives are recommended to optimize the composition of their boards in order to align with sustainability objectives, consequently enhancing environmental, social, and governance (ESG) performance and attaining competitive advantages. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the need for tube feeding in a cohort of treated infants with type I SMA and to identify predictive factors. All patients were classified at baseline, when treatment started, and at follow-up according to their functional level and the need for tube feeding. Fisher's exact test was used to examine the associations between the outcome at the last follow-up and SMA type, SMN2 copy number, and baseline nutritional status. ANOVA was performed to compare CHOP INTEND scores and age at treatment initiation with outcomes. The cohort includes 75 type I SMA infants treated between 0.1 and 5 years of age. At the last follow-up, 34 had no need for tube feeding, 9 had tube feeding but were also able to be fed by mouth, and 32 had tube feeding and were unable to be fed by mouth. Thirty of the 41 infants with tube feeding at follow-up already had feeding difficulties when treatment was started. The need for tube feeding at follow-up was associated with the level of feeding involvement at baseline and with CHOP INTEND scores [p < 0.001] but not with SMN2 copy number, SMA type 1 subtypes or age at treatment. The results of this study suggest that the need for tube feeding is not frequent in treated infants with type I SMA and, when occurring, can be predicted by the level of feeding involvement and low CHOP INTEND scores at baseline. What is Known: • The advent of disease-modifying therapies is increasingly changing the approach to swallowing and nutritional management in type I SMA. • Clinical trials and real-world data using all three disease-modifying therapies report a rather wide variability of feeding outcome and need for tube feeding that is often related to different cohorts that makes comparison between studies very difficult. What is New: • The real-world findings of this study, including all the children treated since treatments became available, confirmed that the need for tube feeding is not an invariable finding. • The level of feeding involvement at baseline appears to be a reliable prognostic indicator of bulbar outcome. • The results highlight the need for interventional studies with structured Speech and Language Therapist protocols that will help to better understand the extent to which bulbar function can be maintained or regained even in children requiring tube feeding. [ABSTRACT FROM AUTHOR]

The assessment of stroke severity plays a crucial role in determining the appropriate medical interventions for stroke patients. It helps identify the necessary steps to be taken during these patients' monitoring, evaluation, and rehabilitation process. Neurologists solely depend on visualization to assess the extent of a stroke in patients during the examination session. In the process of observing through visualization, significant information is sometimes overlooked. Therefore, it is necessary to supplement visualization with the EEG signal analysis method to detect strokes. This approach presents difficulties because of the signal's non-stationary, non-linear, multi-band, multi-channel characteristics and the separate processing and feature extraction in each domain, leading to a high-dimensional space. This study addresses the challenges of signal processing and feature extraction by proposing a feature analysis methodology. The approach employs a multi-domain hybrid significant stroke feature set and the Hybrid Significant Stroke Feature (HSSF) method to determine stroke severity accurately. The HSSF method employs sampling of alpha low and alpha high sub-bands in the alpha band and beta low and beta high in the beta band. This approach utilizes ten characteristics in the time domain, frequency domain, signal decomposition domain, and three types of motion stimuli, specifically shoulder, elbow, and grab. The signal processing and feature analysis strategy comprises the steps of data collection, data preparation, feature extraction, and selection of salient characteristics for categorization. Dimensionality reduction involves prioritizing the selection of low-dimensional domains. Accuracy enhancement is attained by doing normalcy testing and significant feature testing to determine the most significant mean value. The experimental results demonstrate that the HSSF approach, which incorporates classification based on type, domain, feature, stimulus, and subband, achieves a 98% accuracy in identifying stroke severity through SVM classification of PSD, Hjorth Parameter Mobility, and Hjorth Parameter Complexity features with the high beta subband. This data validates that the HSSF technique proficiently detects the optimal parameters within a restricted dimensional space to assess stroke severity precisely. [ABSTRACT FROM AUTHOR]

The state of relaxation is an emotional condition that may be detected through various physical indicators in humans, such as sweat gland intensity, heart rate, breathing patterns, muscle tension and brain activity. Observation using physical patterns is challenging because each human has their own distinct pattern. In order to address this problem, neurologists are employing electroencephalography (EEG) to monitor the brain activity of patients. During this observation, neurologists depend on their own intuition to determine the relaxed state. However, the traditional observation method has drawbacks because each neurologist has their own subjective interpretation, which might lead to ambiguities. Thus, neurologists necessitate an automated recognition system capable of suggesting states of relaxation. To better assess the relaxed state, we divided the alpha band into two parts alpha sub-band: high and low alpha band. In order to obtain Spatio-Temporal features, both signals are transformed by wavelet. The ReliefF is used to select the features toward obtain optimal features. The maximum amplitude and standard deviation are two optimal features utilised as input to Mamdani-Intuitionistic Fuzzy Rules Set. The proposed approach is developed by integrating the fuzzy rules concept of Mamdani and Intuitionistic. In order to validate our model, we are collaborating with three neurologist experts and utilising majority decision to provide label annotation. According to this annotation, our model is performing well with an accuracy score of 92.45%. This investigation employs the DEAP public dataset. The level of accuracy seen in all examined subjects remained consistently high. [ABSTRACT FROM AUTHOR]

Introduction. Previous studies have shown that probiotics have positive effects on both motor and non-motor symptoms in Parkinson's disease (PD). Additionally, in preclinical settings, probiotics have demonstrated the ability to counteract neuronal loss and alpha-synuclein aggregation, important pathological hallmarks of PD. Notably, preliminary in vitro studies have revealed the immunomodulatory properties of probiotics. This study aims to evaluate the impact of probiotics on symptoms and peripheral cytokines levels in PD patients compared to placebo. Methods. Patients were enrolled and blindly randomized to receive either active probiotics (comprising Bifidobacterium animalis subsp. lactis BS01 LMG P-21384, Bifidobacterium longum BL03 DSM 16603, Bifidobacterium adolescentis BA02 DSM 18351, Fructo-oligosaccharides and Maltodextrin-Group A) or placebo (Maltodextrin-Group B). Clinical evaluations and plasma levels cytokines (TNF-α, IFN-γ, IL-6, and TGF-β) were also assessed at enrollment and after 12 weeks. Anti-parkinsonian therapy remained stable throughout the study. Results. Forty PD patients were recruited. After 12 weeks, Group A showed significant improvement in motor symptoms (UPDRS III: 13.89 ± 4.08 vs. 12.74 ± 4.57, p = 0.028) and non-motor symptoms (NMSS: 34.32 ± 21.41 vs. 30.11 ± 19.89, p = 0.041), with notable improvement in the gastrointestinal sub-item (3.79 ± 4.14 vs. 1.89 ± 2.54, p = 0.021). A reduction of IFN-γ levels was observed in both groups, but group A also showed a significant decrease in IL-6 and a slight increase in the anti-inflammatory cytokine TGF-β. Conclusions. Our data suggest that probiotics may modulate peripheral cytokines levels and improve clinical symptoms in PD patients. Probiotics may, therefore, represent a valuable adjunctive therapy to conventional anti-parkinsonian drugs. [ABSTRACT FROM AUTHOR]

Precise spatiotemporal regulation of gene expression is of paramount importance for eukaryotic development. The maternal-to-zygotic transition (MZT) during early embryogenesis in Drosophila involves the gradual replacement of maternally contributed mRNAs and proteins by zygotic gene products. The zygotic genome is transcriptionally activated during the first 3 hours of development, in a process known as "zygotic genome activation" (ZGA), by the orchestrated activities of a few pioneer factors. Their decisive role during ZGA has been characterized in detail, whereas the contribution of chromatin factors to this process has been historically overlooked. In this review, we aim to summarize the current knowledge of how chromatin regulation impacts the first stages of Drosophila embryonic development. In particular, we will address the following questions: how chromatin factors affect ZGA and transcriptional silencing, and how genome architecture promotes the integration of these processes early during development. Remarkably, certain chromatin marks can be intergenerationally inherited, and their presence in the early embryo becomes critical for the regulation of gene expression at later stages. Finally, we speculate on the possible roles of these chromatin marks as carriers of epialleles during transgenerational epigenetic inheritance (TEI). This review discusses the contribution of chromatin factors and genome architecture to zygotic genome activation in Drosophila embryos, and how chromatin marks might be carriers of epialleles during transgenerational epigenetic inheritance. [ABSTRACT FROM AUTHOR]

The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell‐based immune therapies including chimeric antigen receptor T lymphocyte (CAR‐T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune‐related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune‐related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI‐related myocarditis with cardiogenic shock to more common complications including less severe ICI‐related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non‐inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR‐T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is generally treated with vancomycin, metronidazole or fidaxomicin, although fecal microbiota transplantation (FMT) represents a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults. In pediatric cystic fibrosis (CF) patients, CDIs are generally asymptomatic and respond to treatment. Here, we present the case of an 8-year-old female, initially diagnosed as "CFTR-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis" (CMRS/CFSPID), who then progressed to CF at 12 months. In the absence of CF-related symptoms, she presented multiple and disabling episodes of bloody diarrhoea with positive tests for C. difficile antigen and A/B toxin. After conventional treatments failed and several CDI relapses, FMT was proposed. Donor screening and GM donor–receiver matching identified her mother as a donor. Metataxonomy and targeted metabolomics provided, through a pre- and post-FMT time course, gut microbiota (GM) profiling to assess GM engraftment. At first, the GM map revealed severe dysbiosis, with a prevalence of Bacteroidetes and Proteobacteria (i.e., Klebsiella spp., Escherichia coli), a reduction in Firmicutes, a GM nearly entirely composed of Enterococcaceae (i.e., Enterococcus) and an almost complete depletion of Verrucomicrobia and Actinobacteria, mostly represented by Veillonella dispar. Post FMT, an increment in Bifidobacterium spp. and Collinsella spp. with a decrease in V. dispar restored intestinal eubiosis. Consistently, four weeks after FMT treatment, the child's gut symptoms cleared, without CDI recurrence. [ABSTRACT FROM AUTHOR]

Oil palm (Elaeis guineensis) is a major contributor to global vegetable oil production; however, ensuring its sustainability remains a critical challenge, particularly concerning soil health. In this study, we investigated the impact of long-term organic matter application as part of good soil management (GSM) practices on oil palm plantations and compared it with poor soil management practices to determine the presence of plant growth-promoting bacteria (PGPB) in soil communities. The ten-years regular application of organic matter to the soil in the GSM plots led to notable improvements in soil chemical properties, including total organic carbon, total nitrogen, available phosphorus, available potassium, and cation exchange capacity. Metagenomic analysis revealed a significantly higher abundance of beneficial microbial species exclusively found in GSM plots, supporting oil palm growth. Furthermore, a novel finding emerged from this study, as it successfully predicted the metabolic function of PGPB in soil communities using PICRUST2 provided by the soil microbiome. PICRUST2 analysis indicated that the long-term application of organic matter in GSM plots increased functional enzymes related to PGP activities, such as nitrogen fixation, phosphate solubilization, potassium solubilization, and phytohormone synthesis. This study underscores the significance of implementing GSM practices in oil palm plantations by incorporating eco-friendly materials, such as organic matter, to enhance soil health and fertility and ensure oil palm sustainability. [ABSTRACT FROM AUTHOR]

Previous research has supported selecting development‐matched targets rather than age‐matched targets to teach play skills to children with autism spectrum disorder. However, few studies have been conducted, and replications and extensions of this research are needed. The current study replicated Pane et al. (2022) by comparing the acquisition of development‐matched and age‐matched play targets when teaching play skills to four children with autism. No contrived prompts or consequences were used to teach play skills in either condition. Extensions included identifying targets via a newer version of the Developmental Play Assessment, targeting different play categories, assessing additional imitation skills, and conducting a caregiver assessment to identify socially valid toys, play actions, and vocalizations based on each participant's common experiences and preferences as well as their caregiver's values and preferences. As in Pane et al., participants demonstrated a higher level of scripted play actions in the development‐matched condition. [ABSTRACT FROM AUTHOR]

Background: To counteract soil degradation, it is important to convert conventional agricultural practices to environmentally sustainable management practices. To this end, the application of biostimulants could be considered a good strategy. Compost, produced by the composting of biodegradable organic compounds, is a source of natural biostimulants, such as humic acids, which are naturally occurring organic compounds that arise from the decomposition and transformation of organic residues, and compost tea, a compost-derived liquid formulated produced by compost water-phase extraction. This study aimed to determine the molecular responses of the roots of tomato plants (cv. Crovarese) grown under hydroponic conditions and subjected to biostimulation with humic substances (HSs) and filtered sterile compost tea (SCT). Results: The 13C CPMAS NMR of humic acids (HA) and SCT revealed strong O-alkyl-C signals, indicating a high content of polysaccharides.Thermochemolysis identified over 100 molecules, predominantly from lignin, fatty acids, and biopolymers. RNA-Seq analysis of tomato roots treated with HA or SCT revealed differentially expressed genes (DEGs) with distinct patterns of transcriptional reprogramming. Notably, HA treatment affected carbohydrate metabolism and secondary metabolism, particularly phenylpropanoids and flavonoids, while SCT had a broader impact on hormone and redox metabolism. Both biostimulants induced significant gene expression changes within 24 h, including a reduction in cell wall degradation activity and an increase in the expression of hemicellulose synthesis genes, suggesting that the treatments prompted proactive cell wall development. Conclusions: The results demonstrate that HS and SCT can mitigate stress by activating specific molecular mechanisms and modifying root metabolic pathways, particularly those involved in cell wall synthesis. However, gene regulation in response to these treatments is complex and influenced by various factors. These findings highlight the biostimulatory effects of HS and SCT, suggesting their potential application in crop biofertilization and the development of innovative breeding strategies to maximize the benefits of humic substances for crops. Further research is needed to fully elucidate these mechanisms across various contexts and plant species. [ABSTRACT FROM AUTHOR]

The objective of this study is to determine the relationship between short-term temperature variability on neighboring days and mortality. The change in maximum temperature in Northern Virginia, Richmond, Roanoke, and Norfolk, Virginia, on neighboring days was calculated from airport observations and associated with total mortality over a multi-county area surrounding each weather station. The association between day-to-day temperature change and mortality, lagged over a 28-day period, was analyzed using distributed lag non-linear models that controlled for air quality, temporal trends, and other factors. Days following large temperature declines were associated with an increased risk of mortality in three of the four locations, and temperature increases were linked to higher mortality risk in two cities. For example, the relative risk of mortality for a 12°C daily temperature decline (1st percentile) was 1.74 [0.92, 3.27] in Roanoke and 1.16 [0.70, 1.92] in Richmond. The net effect of short-term temperature increases was smaller, with the largest relative risk of 1.03 [0.58, 1.83] for a 12°C increase (99th percentile) in maximum temperature in Norfolk. In Richmond and Roanoke, there was an observed lagged effect of increased mortality (maximum relative risks varying from 1.08 to 1.10) that extended from 5 to 25 days associated with large temperature declines of 15°C or more. In contrast, there was a strong and immediate (lag 0–3 day) increase in the risk of mortality (1.10 to 1.15) in northern Virginia and Norfolk when the temperature increase exceeded 10°C (short-term warming). In general, consecutive day warming had a more immediate mortality impact than short-term cooling, when the peak mortality is lagged by one week or more. However, cooling of at least 10°C after a hot (summer) day reduced mortality relative to comparable cooling following a cold (winter) day, which is associated with high mortality. This differential mortality response as a function of temperature suggests that there is some relationship between average temperature, temperature variability, and season. The findings of this study may be useful to public health officials in developing mitigation strategies to reduce the adverse health risks associated with short-term temperature variability. [ABSTRACT FROM AUTHOR]

Aim: The availability of disease-modifying therapies and newborn screening programs for spinal muscular atrophy (SMA) has generated an urgent need for reliable prognostic biomarkers to classify patients according to disease severity. We aim to identify cerebrospinal fluid (CSF) prognostic protein biomarkers in CSF samples of SMA patients collected at baseline (T0), and to describe proteomic profile changes and biological pathways influenced by nusinersen before the sixth nusinersen infusion (T302). Methods: In this multicenter retrospective longitudinal study, we employed an untargeted liquid chromatography mass spectrometry (LC-MS)-based proteomic approach on CSF samples collected from 61 SMA patients treated with nusinersen (SMA1 n=19, SMA2 n=19, SMA3 n=23) at T0 at T302. The Random Forest (RF) machine learning algorithm and pathway enrichment analysis were applied for analysis. Results: The RF algorithm, applied to the protein expression profile of naïve patients, revealed several proteins that could classify the different types of SMA according to their differential abundance at T0. Analysis of changes in proteomic profiles identified a total of 147 differentially expressed proteins after nusinersen treatment in SMA1, 135 in SMA2, and 289 in SMA3. Overall, nusinersen-induced changes on proteomic profile were consistent with i) common effects observed in allSMA types (i.e. regulation of axonogenesis), and ii) disease severity-specific changes, namely regulation of glucose metabolism in SMA1, of coagulation processes in SMA2, and of complement cascade in SMA3. Conclusions: This untargeted LC-MS proteomic profiling in the CSF of SMA patients revealed differences in protein expression in naïve patients and showed nusinersen-related modulation in several biological processes after 10 months of treatment. Further confirmatory studies are needed to validate these results in larger number of patients and over abroader timeframe. [ABSTRACT FROM AUTHOR]

Soil microorganisms play a crucial role in maintaining soil fertility sensu lato. Sustainable soil management aims to make the soil environment more hospitable increasing microorganism diversity and complexity by means of the minimal disturbance of soil and inputs of organic material. This results in the effective functioning of agricultural systems, better crop productivity, and a reduction in environmental impacts. A study was carried out to evaluate the effects of the long-term application (more than 15 years) of sustainable practices versus conventional ones on soil microbial biomass activity and its functional diversity within different Mediterranean commercial fruit orchards located in Southern Italy. A preliminary survey—performed using the electromagnetic induction technique (EMI)—guided the collection of representative soil samples by reducing the spatial heterogeneity of soil microorganisms. Soil management practices, based on no tillage and the recycling of organic materials of different origins and quality produced within the orchard, increased soil organic carbon, telluric microorganisms activity and their functional diversity compared to 'non-conservative' management methods such as continuous tillage. In addition, the rational use of the orchard-inside organic matter (natural/seeded grass cover and pruning material) allowed it to virtuously transform from useless waste into precious resources, eliminating the logistical and economic constraints for their disposal. The simultaneous use of different types of soil management strategies aimed at soil conservation reinforced the positive effects on the microbiological indicators of soil quality rather than the application of a single strategy. This study provides the opportunity to represent what could be the possible evolution of tilled orchards towards more balanced soil conditions when subjected to conservative practices, offering a reference model for fruit growers and technicians who want to improve the stability and the resiliency of their agrosystems. [ABSTRACT FROM AUTHOR]

Background and Objective: Untreated spinal muscular atrophy (SMA) is the leading genetic cause of death in children younger than 2 years of age. Early detection through newborn screening allows for presymptomatic diagnosis and treatment of SMA. With effective treatments available and reimbursed by the National Health Service, many regions in Italy are implementing newborn screening for SMA. We evaluated the cost effectiveness of universal newborn screening for SMA in Italy. Methods: A decision-analytic model assessed the cost effectiveness of newborn screening from the National Health Service perspective in 400,000 newborns. Newborn screening enabling early identification and presymptomatic treatment of SMA was compared with no newborn screening, symptomatic diagnosis, and treatment. Transition probabilities between health states were estimated from clinical trial data. Higher-functioning health states were associated with increased survival, higher utility values, and lower costs. Long-term survival and utilities were extrapolated from scientific literature. Health care costs were collected from official Italian sources. A lifetime time horizon was applied, and costs and outcomes were discounted at an annual rate of 3%. Deterministic and probabilistic sensitivity analyses were conducted. Results: Newborn screening followed by presymptomatic treatment yielded 324 incremental life-years, 390 incremental quality-adjusted life-years, and reduced costs by €1,513,375 over a lifetime time horizon compared with no newborn screening. Thus, newborn screening was less costly and more effective than no newborn screening. Newborn screening has a 100% probability of being cost effective, assuming a willingness-to-pay threshold of > €40,000. Conclusions: Newborn screening followed by presymptomatic SMA treatment is cost effective from the Italian National Health Service perspective. [ABSTRACT FROM AUTHOR]

In multiple myeloma (MM) bone marrow infiltration by monoclonal plasma cells can occur in both focal and diffuse manner, making staging and prognosis rather difficult. The aim of our study was to test whether texture analysis of 18 F-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) images can predict survival in MM patients. Forty-six patients underwent 18 F-FDG-PET/CT before treatment. We used an automated contouring program for segmenting the hottest focal lesion (FL) and a lumbar vertebra for assessing diffuse bone marrow involvement (DI). Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and texture features such as Coefficient of variation (CoV), were obtained from 46 FL and 46 DI. After a mean follow-up of 51 months, 24 patients died of myeloma and were compared to the 22 survivors. At univariate analysis, FL SUVmax (p = 0.0453), FL SUVmean (p = 0.0463), FL CoV (p = 0.0211) and DI SUVmax (p = 0.0538) predicted overall survival (OS). At multivariate analysis only FL CoV and DI SUVmax were retained in the model (p = 0.0154). By Kaplan-Meier method and log-rank testing, patients with FL CoV below the cut-off had significantly better OS than those with FL CoV above the cut-off (p = 0.0003), as well as patients with DI SUVmax below the threshold versus those with DI SUVmax above the threshold (p = 0.0006). Combining FL CoV and DI SUVmax by using their respective cut-off values, a statistically significant difference was found between the resulting four survival curves (p = 0.0001). Indeed, patients with both FL CoV and DI SUVmax below their respective cut-off values showed the best prognosis. Conventional and texture parameters derived from 18F-FDG PET/CT analysis can predict survival in MM patients by assessing the heterogeneity and aggressiveness of both focal and diffuse infiltration. [ABSTRACT FROM AUTHOR]

Introduction: Eculizumab, a complement active antibody, and efgartigimod, an Fc fragment that blocks neonatal Fc receptor, are both approved to treat generalized myasthenia gravis (gMG) patients. The objective of this study is to describe the clinical response to both treatments in a real-life setting. Methods: We collected baseline and follow-up clinical data using the Myasthenia Gravis-Activities of Daily Living (MG-ADL), and Quantitative Myasthenia Gravis (QMG). We included 63 patients, 32 treated with eculizumab and 31 with efgartigimod. Of the efgartigimod-treated patients, 22 were anti-acetylcholine receptor antibody-positive (AChR-Ab +) and 9 were AChR-Ab- (3 MuSK-Ab + and 6 seronegative). Results: Both treatments showed similar efficacy relative to the MG-ADL scale reduction (p = 0.237). Efgartigimod had a similar effect on both AChR-Ab + and AChR-Ab- (p = 0.280). Eculizumab was superior to efgartigimod relative to the QMG score reduction for the entire dataset (p = 0.003) and was more likely to achieve a clinical response at the QMG compared to efgartigimod (OR 1.373; p = 0.016). Steroid-sparing effect was higher for eculizumab than efgartigimod (– 16.7 vs – 5.2 mg of the baseline daily dose at follow-up; p = 0.001). Mean speed of prednisone reduction was – 13.1 mg of the daily dose for each month of follow-up for eculizumab-treated patients and – 3.2 for efgartigimod (p = 0.001). We found three serious events, all not related to treatment in the investigator's opinion. One eculizumab-treated patient experienced a severe pneumonia and died despite treatment. Conclusions: Our study provides evidence that eculizumab and efgartigimod can be used in clinical practice to reduce disability in gMG patients. Eculizumab-treated patients had a higher QMG response and steroid sparing effect. Efgartigimod may offer a more flexible schedule due to its cyclical use, no need for vaccination, and efficacy in AChR-Ab- patients. [ABSTRACT FROM AUTHOR]

The Sorrento Peninsula is characterized by a significant occurrence of examples of vernacular architecture, which exhibit distinctive morphological and constructive features. These have been the subject of numerous studies. However, some buildings have undergone a process of transformation over time, the details of which have yet to be investigated. Architectures that initially held a rural character were enlarged and ennobled, thereby becoming what could be termed as "villas of delights". However, these clearly manifest their origin based on the permanence of some vernacular features. This paper focuses on the analysis of a case study, Villa Murat, which is exemplary in illustrating this process. This thorough interdisciplinary research combines historical investigation, based mainly on archival documents, with a direct examination of the Villa. This has enabled the retracing of the building's evolution and of the events that occurred in it. An integrated survey, which employed photogrammetry and laser scanning, enabled the assessment of the current state of conservation. The ultimate objective of this research is to propose conservative interventions which, in conjunction with the suggested new intended use, could ensure the preservation of the Villa. [ABSTRACT FROM AUTHOR]

We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40–65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches. [ABSTRACT FROM AUTHOR]

This research investigates the significance of adopting a halal lifestyle in Cikole Village, situated within the disaster-prone region of West Bandung Regency. This research method is a qualitative approach with descriptive analysis method. Data collection was executed through focused group discussions, elucidating the perspectives and experiences of the local community. The findings of this study underscore the multifaceted nature of the halal lifestyle, revealing it as not merely a dietary restriction but a comprehensive knowledge system encompassing various aspects of daily life. In Cikole Village, the halal lifestyle has evolved beyond religious adherence to encompass broader ethical, environmental, and sustainable practices, thus laying the foundation for effective disaster management. By infusing the principles of halal living into their daily routines, the community has cultivated attitudes and behaviors conducive to disaster mitigation. In conclusion, this research underscores the pivotal role of a halal lifestyle as a proactive and holistic approach in disaster resilience, as it not only reflects religious observance but also shapes a value system that drives sustainable and resilient communities. [ABSTRACT FROM AUTHOR]

Introduction: Vulvovaginal candidiasis (VVC) significantly impacts women's quality of life and often shows a high recurrence rate despite conventional antifungal therapies. This study evaluates the efficacy of Limosilactobacillus fermentum (LF5), a probiotic, as an alternative treatment option to conventional miconazole therapy in managing VVC. Methods: The randomized, single-blind clinical trial involved 100 premenopausal women diagnosed with VVC. Participants were assigned to either a vaginal capsule containing LF5 probiotic strain or miconazole. Treatments were administered once daily for three consecutive days. Microbiological eradication of Candida spp. and recurrence rates were assessed at 30 days post-treatment. The trial was registered with the Italian Ministry of Health. Results: Both treatments achieved a high rate of microbiological eradication of Candida spp. within the three-day treatment period (96% for LF5 and 94% for miconazole). Recurrence rates within 2 weeks post-treatment were low and similar between the groups (10% for LF5 and 17% for miconazole). LF5 was found to have a significantly lower incidence of local adverse reactions compared to miconazole (4 vs. 12%). Discussion: LF5 presents a viable alternative to miconazole for the treatment of VVC, offering comparable efficacy with fewer side effects. The results suggest that probiotic treatments can potentially enhance patient compliance and quality of life by reducing adverse reactions and recurrence rates. Further research is needed to confirm these findings in larger and more diverse populations. [ABSTRACT FROM AUTHOR]

This paper describes a new species of Halamphora – Halamphora lombokensis sp. nov. and records for the first time Halamphora banzuensis for the coasts of Indonesia. The study utilized light and scanning electron microscopy to meticulously examine the morphology. These species were found at Kuta Beach on the island of Lombok in Indonesia in highly saline sandy environments. The newly identified species, H. lombokensis sp. nov., is characterized by its semi-lanceolate to narrowly semi-elliptic shape with a straight ventral and convex dorsal margin. The study contributes to our understanding of marine diatom flora in Indonesia's coastal regions. [ABSTRACT FROM AUTHOR]