bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in the DNA methylome of T cells in adults with asthma of varying severity
Authors: Liao Yixuan , Cavalcante Raymond G. , Waller Jonathan B. , Deng Furong , Scruggs Anne M. , Huang Yvonne J. , Atasoy Ulus , Chen Yahong , Huang Steven K.
Published: October 2024

Background

DNA methylation plays a critical role in asthma development, but differences in DNA methylation among adults with varying asthma severity are less well-defined.

Objective

To examine how DNA methylomic patterns differ among adults with asthma based on asthma severity and airway inflammation.

Methods

Peripheral blood T cells from 35 adults with asthma in Beijing, China, were serially collected over time (130 samples total) and analyzed for global DNA methylation using the Illumina MethylationEPIC Array. Differential methylation was compared among subjects with varying airway inflammation and severity, as measured by fraction of exhaled nitric oxide, forced expiratory volume in one second (FEV1), and Asthma Control Test (ACT) scores.

Results

Significant differences in DNA methylation were noted among subjects with different degrees of airway inflammation and asthma severity. These differences in DNA methylation were annotated to genes that were enriched in pathways related to asthma or T cell function and included gene ontology categories related to MHC class II assembly, T cell activation, interleukin (IL)-1, and IL-12. Genes related to P450 drug metabolism, glutathione metabolism, and developmental pathways were also differentially methylated in comparisons between subjects with high vs low FEV1 and ACT. Notable genes that were differentially methylated based on asthma severity included RUNX3, several members of the HLA family, AGT, PTPRC, PTPRJ, and several genes downstream of the JAK2 and TNF signaling pathway.

Conclusion

These findings demonstrate how adults with asthma of varying severity possess differences in peripheral blood T cell DNA methylation that contribute to differences in clinical indices of asthma.
Unusual presentation of PYGM gene mutation as late-onset McArdle disease with camptocormia: a case report
Authors: Stalter Johannes , Gies Ursula , Mathys Christian , Witt Karsten
Published: October 2024

Background

Glycogen storage disease type 5 (McArdle disease) leads to a deficiency in the activity of myophosphorylase resulting in an impaired glucose utilization. The disease can be caused by a variety of mutations in the PYGM gene, and its typical clinical manifestation is muscles weakness within the first three decades of life.

Case presentation

In this case report we present the diagnostic work-up of a physically active 78-year-old Caucasian patient suffering from a 2-year history of progressive camptocormia including clinical, radiologic, histological, and genetic tests. There was no history of neuro-muscular diseases in the family. Serum CK levels were moderately increased while other blood/urine parameters were normal. Magnetic resonance imaging showed fatty remodeling of the muscles of the back. Histochemical examination of a muscle biopsy revealed the absence of myophosphorylase activity, while gene analysis identified a known early-onset McArdle mutation in the PYGM gene.

Conclusion

This case highlights that the clinical spectrum of PYGM gene mutation typically manifest during adolescence, but it is also a differential diagnosis in late onset muscle disorders and emphases the investigation of the role of ACE inhibitors in this disease.
Mesenchymal stromal cell therapy (REGENACIP®), a promising treatment option in chronic limb threatening ischemia – a narrative review
Authors: Desai Sanjay , Sharma Digvijay , Srinivas Rajesh , Balaji Venugopal , Thakore Vijay , Bedi Varinder Singh , Jindal Ravul , Sugumaran Amarnath , Mohanasundaram Senthilnathan , Gogtay Jaideep , Gupta Pawan Kumar , Bhuiyan Aniruddha , Atturu Gnaneswar
Published: October 2024

Chronic Limb Threatening Ischemia (CLTI) is a challenging clinical problem associated with high morbidity and mortality. Endovascular interventions have been the cornerstone of treatment whenever possible. It is estimated that CLTI represents < 10% of all Peripheral Artery Disease patients, yet 50% of the patients end up either with a major amputation of the lower limbs or die of cardiovascular causes within one year period, especially in those with unsuccessful revascularization or “no-option” CLTI. Cell-based therapeutics, especially bone marrow-derived mesenchymal stromal cells have emerged as a potential, promising, and novel alternate therapeutic modality in the management of CLTI, bolstered with positive results in numerous research, including randomized and nonrandomized trials. REGENACIP® is one such BM-MSC therapy approved by Central Drugs Standard Control Organization in India for the management of “no-option” Atherosclerotic Peripheral Arterial disease / Buerger’s disease patients with established critical limb ischemia in Rutherford Grade III-5 or III-6, not eligible for or have failed traditional revascularization treatment, with rest pain and / or ulcers in the affected limb. The current review aims to deliberate upon the various aspects of CLTI and clinical benefits of REGENACIP® therein.
A protocol for identifying the needs related to drug use, health and social (re)integration of people living in prison within five European countries
Authors: Plettinckx Els , Berndt Nadine , Seixas Rita , De Smet Stefaan , Antoine Jérôme , Bruggeman Helena , Harth Nina , Papadopoulou Athanasia , Bafi Ioulia , Fotiou Anastasios , Pridotkienė Evelina , Kalinauskaitė Rima , Rašimaitė Brigita , Tsiakkirou Myria , Balcaen Margot , Fernandez Kim , Gremeaux Lies , Dirkx Nicky , De Ridder Karin , Yiasemi Ioanna , Mavrou Josefina
Published: October 2024

Background

Compared to the general population, people living in prison are at an increased risk to experience negative (mental) health outcomes. Moreover, delinquency and drug use have many risk factors in common. A need exists for increasing the knowledge about health needs, drug use patterns and the coverage of drug-related interventions in prison within Europe. The current protocol describes the design of a study about wellbeing, drug use and related care in prison.

Methods/design

A multicentre mixed method design is implemented in five European countries (Belgium, Cyprus, Greece, Lithuania and Luxembourg). Qualitative and quantitative data collection tools are combined in order to generate complementary and comprehensive results. First, a cross-sectional survey among people living in prison is conducted. This survey is based on a model questionnaire, the European Questionnaire on Drug use among people living in Prison, developed by the European Monitoring Centre for Drug and Drugs Addiction. Second, people living in prison and people who have been recently released from prison are involved in qualitative semi-structured face-to-face interviews. The main topics of interest are the use of drugs and other health related topics such as loneliness, anxiety, depression, infectious diseases, suicide and treatment. Third, data regarding health and social reintegration measures in prison is collected through a quantitative survey addressed to the prison authorities.

Discussion

This study protocol presentes a European study which aims to assess drug use among people living in prison and recently released people who use drugs as well as the existing care services in prisons. Hereby, factors related to the prison environment and their needs, both inside and outside prison are taken into account. Importantly, this study protocol describes a methodology which is developed to be executed in different prison settings within different countries simultaneously. Accordingly, for each country the protocol is adjustable to specific national legal requirements, regional differences and distinct local regulations of prison administrations. However, extensive modularity inevitably comes with significant limitations of comparability and generalizability of the results.
Elevated plasma and CSF neurofilament light chain concentrations are stabilized in response to mutant huntingtin lowering in the brains of Huntington’s disease mice
Authors: Caron Nicholas S. , Byrne Lauren M. , Lemarié Fanny L. , Bone Jeffrey N. , Aly Amirah E.-E. , Ko Seunghyun , Anderson Christine , Casal Lorenzo L. , Hill Austin M. , Hawellek David J. , McColgan Peter , Wild Edward J. , Leavitt Blair R. , Hayden Michael R.
Published: October 2024

Background

Therapeutic approaches aimed at lowering toxic mutant huntingtin (mHTT) levels in the brain can reverse disease phenotypes in animal models of Huntington's disease (HD) and are currently being evaluated in clinical trials. Sensitive and dynamic response biomarkers are needed to assess the efficacy of such candidate therapies. Neurofilament light chain (NfL) is a biomarker of neurodegeneration that increases in cerebrospinal fluid (CSF) and blood with progression of HD. However, it remains unknown whether NfL in biofluids could serve as a response biomarker for assessing the efficacy of disease-modifying therapies for HD.

Methods

Longitudinal plasma and cross-sectional CSF samples were collected from the YAC128 transgenic mouse model of HD and wild-type (WT) littermate control mice throughout the natural history of disease. Additionally, biofluids were collected from YAC128 mice following intracerebroventricular administration of an antisense oligonucleotide (ASO) targeting the mutant HTT transgene (HTT ASO), at ages both before and after the onset of disease phenotypes. NfL concentrations in plasma and CSF were quantified using ultrasensitive single-molecule array technology.

Results

Plasma and CSF NfL concentrations were significantly elevated in YAC128 compared to WT littermate control mice from 9 months of age. Treatment of YAC128 mice with either 15 or 50 µg HTT ASO resulted in a dose-dependent, allele-selective reduction of mHTT throughout the brain at a 3-month interval, which was sustained with high-dose HTT ASO treatment for up to 6 months. Lowering of brain mHTT prior to the onset of regional brain atrophy and HD-like motor deficits in this model had minimal effect on plasma NfL at either dose, but led to a dose-dependent reduction of CSF NfL. In contrast, initiating mHTT lowering in the brain after the onset of neuropathological and behavioural phenotypes in YAC128 mice resulted in a dose-dependent stabilization of NfL increases in both plasma and CSF.

Conclusions

Our data provide evidence that the response of NfL in biofluids is influenced by the magnitude of mHTT lowering in the brain and the timing of intervention, suggesting that NfL may serve as a promising exploratory response biomarker for HD.
A process evaluation of a home garden intervention
Authors: Ritter Thea , Mockshell Jonathan , Garrett James , Ogutu Sylvester , Asante-Addo Collins
Published: October 2024

Background

Most reviews of nutrition-sensitive programs assess the evidence base for nutrition outcomes without considering how programs were delivered. Process evaluations can fill this void by exploring how or why impacts were or were not achieved. This mid-term process evaluation examines a home garden intervention implemented in a large-scale, livelihoods improvement program in Odisha, India. The objectives are to understand whether the intervention was operating as planned (fidelity), investigate potential pathways to achieve greater impact, and provide insights to help design future home garden programs.

Methodology

Data collection and analysis for this theory-driven process evaluation are based on a program impact pathway that shows the flow of inputs, processes, outputs, outcomes, and impacts. Quantitative and qualitative data from focus group discussions, semi-structured interviews, and a Process Net-Mapping exercise with beneficiaries, frontline workers, and program management staff.

Results

Despite a mismatch between the design and implementation (low fidelity), the process evaluation identified positive outputs, outcomes, and impacts on home garden production, consumption, income, health and nutritional outcomes, and women’s empowerment. Flexibility led to greater positive outcomes on nutrition, the adoption of sustainable agricultural practices and easy-to-understand nutrition models, and the likelihood of the intervention being sustained after the program ends.

Conclusions

To help food systems in rural settings reduce food insecurity by utilizing more sustainable agricultural practices, we recommend that home garden interventions include instruction on easy-to-understand nutrition models and on how to make natural fertilizer. Finding local solutions like home gardens to help address critical supply issues and food insecurity is paramount.
Dietary supplementation with pterostilbene activates the PI3K-AKT-mTOR signalling pathway to alleviate progressive oxidative stress and promote placental nutrient transport
Authors: Cao Mingming , Bai Liyun , Wei Haoyun , Guo Yantong , Sun Guodong , Sun Haoyang , Shi Baoming
Published: October 2024

Background

Progressive oxidative stress easily occurs as a result of a gradual increase in the intensity of maternal metabolism due to rapid foetal development and increased intensity of lactation. However, studies on the effects of processive oxidative stress on nutrient transport in the placenta have received little attention. The present study was conducted on sows at 85 days of gestation to study the effects of pterostilbene (PTE) on maternal oxidative stress status and placental nutrient transport.

Results

PTE increased the antioxidant capacity and immunoglobulin content in mothers’ blood and milk, reduced the level of inflammatory factors, and improved the nutrient content of milk. PTE also reduced sow backfat loss and the number of weak sons, and increased piglet weaning weight and total weaning litter weight. We subsequently found that PTE enhanced placental glucose and fatty acid transport and further affected glycolipid metabolism by increasing the expression of LAL, PYGM, and Gbe-1, which activated the PI3K phosphorylation pathway. Moreover, PTE addition altered the relative abundance of the Firmicutes, Proteobacteria, Parabacillus, and Bacteroidetes-like RF16 groups in sow faeces. PTE increased the levels of acetate, propionate, butyrate and isovalerate in the faeces.

Conclusions

These findings reveal that the addition of PTE during pregnancy and lactation mitigates the effects of processive oxidative stress on offspring development by altering maternal microbial and placental nutrient transport capacity.

Graphical Abstract
Flexible sensing probe for the simultaneous monitoring of neurotransmitters imbalance
Authors: Cha Hye Bin , Zhang Yao , Yu Hyun-Yong , Lee Yi Jae
Published: October 2024

Simultaneous detection of multiple neurotransmitters and their related activities is crucial for enhancing our understanding of complex neurological mechanisms and disorders. In this study, we developed a flexible, high-sensitivity multi-electrodes array probe capable of concurrent detection of four neurotransmitters: dopamine, serotonin, acetylcholine and glutamate. The probe was fabricated on a polyimide substrate with 16 circular gold-film electrodes. These electrodes were modified with PEDOT/GluOx and PEDOT/ChOx for enzymatic detection of glutamate and acetylcholine, and with rGO/PEDOT/Nafion for the detection of dopamine and serotonin. Our electrochemical sensor achieved sensitivities of 184.21 and 219.29 μA/μM cm2 for glutamate and acetylcholine, respectively, with limits of detection (LOD) of 0.0242 and 0.0351 μM within a concentration range of 0.1–100 μM. For dopamine and serotonin, the sensor showed sensitivities of 195.9 and 181.2 μA/μM cm2, respectively, with LOD of 0.4743 and 0.3568 μM. This research advances the field of neurochemical sensing and provides valuable insights into the balance of neurotransmitters associated with neurological disorders. These insights improve diagnostic and therapeutic strategies.
Combining virtual reality with asymmetric collaborative learning: a case study in chemistry education
Authors: De Lorenzis Federico , Visconti Alessandro , Restivo Simone , Mazzini Francesca , Esposito Serena , Garofalo Silvia Fraterrigo , Marmo Luca , Fino Debora , Lamberti Fabrizio
Published: October 2024

The use of Virtual Reality (VR) in education is getting more and more common, especially when hands-on learning experiences have to be delivered. With VR it becomes possible, e.g., to simulate dangerous or costly procedures that could hardly be implemented in real settings. However, engaging large classes in immersive laboratory activities may be difficult, since VR kits are still rather expensive for quantity purchases and may require powerful PCs as well as proper spaces to work. A possible way to deal with these issues could be to combine VR with so-called asymmetric Collaborative Learning (CL). CL is a particularly interesting pedagogical approach, as it make learners work in team to achieve a common educational goal, promoting critical thinking and active learning. In asymmetric CL, in particular, learners use different technologies to interact. When combined with VR, asymmetric CL could be used, e.g., to let some learners get immersed in a virtual environment, while some others actively participate in the experience using a desktop interface. This configuration could allow, in principle, to involve more learners in the same amount of time and with the same number of VR kits, while also letting them benefit of the advantages of CL. Based on these considerations, this paper investigates the impact of CL on VR-based education by leveraging an immersive virtual environment designed to support a laboratory experience in a Chemistry course. A user study was conducted by involving 46 university students enrolled in the course. Objective and subjective metrics were used to compare two education methods, i.e. one in which the students experienced the VR environment in isolation, another one in which pairs of students collaborated with an asymmetric approach. Students’ knowledge acquisition was assessed by means of theoretical quizzes, whereas practical performance was automatically measured during the VR experience. The experimental results showed that trading off VR-based, individual learning for CL may have positive effects on the acquisition of theoretical knowledge, but may be detrimental to the achievement of practical abilities if sufficient exposure to technology cannot be guaranteed.
ICESat-2 single photon laser point cloud denoising algorithm based on improved DBSCAN clustering
Authors: Wang Dong , Yu Jiachen , Liu Fengying , Li Qinghua
Published: October 2024

The Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) has great potential for development due to its advantages of the use of multiple beams, low energy consumption, high repetition frequency, and high measurement sensitivity. However, the weak photon signal emitted by the photon counting lidar is susceptible to the background noise caused by the sun and the atmosphere, which can seriously affect the processing and application of laser data. This paper proposes an improved DBSCAN clustering algorithm for denoising single photon laser point clouds in mountainous areas. Firstly, a grouping method based on elevation and distance statistics is proposed to reduce the influence of terrain undulations on denoising accuracy. Finally, an automatic radius search method is put forward to determine clustering radius of each group, automatically find the optimal radius, and improve the existing DBSCAN clustering method. The method proposed in this paper is compared with the classical DBSCAN algorithm. The results show that the proposed algorithm significantly improves denoising accuracy in mountainous areas and effectively filters out most background noise.

Graphical Abstract
Spotting missing or wanted people: racial biases in prospective person memory
Authors: Papesh Megan H. , Cash Daniella K. , Guevara Pinto Juan D. , Lomba Sofia V.
Published: October 2024

Searching for missing or wanted people is a crucial task in our society. Previous work on prospective person memory (PPM) has demonstrated that performance on this type of search task is worse relative to standard prospective memory tasks. Importantly, this process may be further affected by the race of the missing person, yet this has never been tested in laboratory settings. To test the effects of race on PPM, a convenience sample consisting primarily of self-identified Caucasian participants was asked to search for either a Caucasian or an Indian target person while judging the orientation of different Caucasian and Indian faces. Although the tasks were otherwise identical, 89% of Caucasian PPM targets were found while only 53% of Indian targets were found. Furthermore, relative to a control group with no PPM requirements, participants were slower and more error-prone when judging Indian faces relative to White faces, particularly if they were searching for an Indian face. We interpret these results as revealing other-race effects in prospective person memory, highlighting race as a critical factor for finding missing people. Importantly, this also emphasizes the need for real-world search efforts to factor in difficulty differences when people monitor for missing/wanted people from their own or different racial backgrounds. For example, media coverage of missing persons cases could perhaps be distributed more equitably by considering whether the missing person is from a racial minority in that region.
Quantitative brain T1 maps derived from T1-weighted MRI acquisitions: a proof-of-concept study
Authors: Lavielle Audrey , Pinaud Noël , Zhang Bei , Crémillieux Yannick
Published: October 2024

Background

Longitudinal T1 relaxation time is a key imaging biomarker. In addition, T1 values are modulated by the administration of T1 contrast agents used in patients with tumors and metastases. However, in clinical practice, dedicated T1 mapping sequences are often not included in brain MRI protocols. The aim of this study is to address the absence of dedicated T1 mapping sequences in imaging protocol by deriving T1 maps from standard T1-weighted sequences.

Methods

A phantom, composed of 144 solutions of paramagnetic agents at different concentrations, was imaged with a three-dimensional (3D) T1-weighed turbo spin-echo (TSE) sequence designed for brain imaging. The relationship between the T1 values and the signal intensities was established using this phantom acquisition. T1 mapping derived from 3D T1-weighted TSE acquisitions in four healthy volunteers and one patient with brain metastases were established and compared to reference T1 mapping technique. The concentration of Gd-based contrast agents in brain metastases were assessed from the derived T1 maps.

Results

Based on the phantom acquisition, the relationship between T1 values and signal intensity (SI) was found equal to T1 = 0.35 × SI−1.11 (R2 = 0.97). TSE-derived T1 values measured in white matter and gray matter in healthy volunteers were equal to 0.997 ± 0.096 s and 1.358 ± 0.056 s (mean ± standard deviation), respectively. Mean Gd3+ concentration value in brain metastases was 94.7 ± 30.0 μM.

Conclusion

The in vivo results support the relevance of the phantom-based approach: brain T1 maps can be derived from T1-weighted acquisitions.

Relevance statement

High-resolution brain T1 maps can be generated, and contrast agent concentration can be quantified and imaged in brain metastases using routine 3D T1-weighted TSE acquisitions.

Key Points

Quantitative T1 mapping adds significant value to MRI diagnostics.

T1 measurement sequences are rarely included in routine protocols.

T1 mapping and concentration of contrast agents can be derived from routine standard scans.

The diagnostic value of MRI can be improved without additional scan time.

Graphical Abstract
A prospective observational study on the anatomical variations of recurrent laryngeal nerve and its application in the prevention of injury during thyroid surgery in a tertiary care centre
Authors: Kale Vitthal Dada , Prajosh Aishwarya , Chavan Shrinivas S. , Patra Ananya
Published: October 2024

Background

Thyroid gland is the largest and most vascular structure among the endocrine glands. The recurrent laryngeal nerve and the superior laryngeal nerve are closely related to the thyroid gland; these nerves control voice and are vital in breathing. Anatomical preservation of the recurrent laryngeal nerve (RLN) is the gold standard in thyroid surgery. Visual identification of RLN has decreased the rates of permanent RLN palsy during thyroid and parathyroid operations. Prior knowledge about the branching patterns will help in predicting and preventing injury to the nerve during thyroid surgery.

Aim and objectives

The aim of the study is to observe the terminal branching pattern of recurrent laryngeal nerve before its entry into the larynx.

Methods

An observational study with 50 participants who fulfilled the inclusion and exclusion criteria were enrolled in the study. After a complete evaluation and pre-anaesthetic checkup, the patients were operated and intraoperative findings of RLN branching were recorded and compared for the study.

Results

In our study, out of the 50 patients who underwent thyroid surgery during the course of the study, right-sided RLN branching was demonstrated in 25 patients (21 right hemithyroidectomy and 4 total thyroidectomy). Ten patients had RLN bifurcation, 7 had trifurcation, 5 had numerous branches, and 3 with no branching pattern were noted. Similarly, out of 29 patients (25 left hemithyroidectomy and 4 total thyroidectomy) in whom left-sided RLN branching was studied, bifurcation was seen in 10 patients, trifurcation in 12 patients, and multiple branching was observed in 7.

Conclusion

The anatomical variations seen in RLN may increase the risk of vocal cord palsy due to its injury. Anatomical variations are categorized according to the original direction of the RLN and the number of terminal branches in the larynx. This classification aids in the identification and preservation of its branches, hence facilitating a safer thyroidectomy.
Use of 3D cross-gradient joint inversion of marine controlled-source electromagnetic and seismic refraction data for overburden geohazard mapping
Authors: Karpiah Arvin B. , Meju Max A. , Mackie Randall L. , Aziz Adam A. , Musa Mustaza
Published: October 2024

Offshore energy-transition activities typically require the construction of new subsurface facilities where overburden heterogeneity and deformation patterns may not be fully understood. Anisotropic marine controlled-source electromagnetic (CSEM) and seismic refraction imaging can be adapted to geohazard assessments of the overburden to mitigate safety and cost risks in such areas. This is investigated using an area in deepwater northwest Borneo as the case study. For this proof-of-concept study, a well-established multiphysics joint inversion code is extended to handle marine seismic refraction data from conventional towed streamers. Realistic field-scale synthetic models with anomalous resistivities and velocities in the shallow section (approximately 400 m below mudline) are built and their CSEM and seismic refraction responses are first inverted separately and then jointly in three dimensions using the cross-gradient method. The joint inversion recovers the anomalous bodies better than the separate inversions. The velocity model from the joint inversion indicates improvement from the separate inversion but requires a good starting model. As a further test of the methodology, first-break traveltimes are picked from legacy 3D seismic data and inverted with the available sparse CSEM data. For model verification, resistivity and velocity profiles from separate and joint inversion models are extracted at a well location in the survey area and compared with actual well logs. The joint inversion models match the well logs better than the separate inversion models. Moreover, known geohazards (complex fault sets and lateral inflows) from independent geomatics study are imaged in the joint inversion models. In addition, the resistivity anisotropy ratio tracks anomalous zones that correspond to areas of recent complex faulting and potential lateral inflows in the overburden mass transport systems. Thus, the joint inversion of CSEM and seismic refraction data has the potential to improve the mapping of overburden hazards offshore, with the associated resistivity anisotropy serving as a proxy for active ground deformation.
Quantifying the experiences of Black and Dual Heritage young people in a forensic child and adolescent mental health service
Authors: Sandiford Michelle A. , Moran David , Smith Jared G. , Hales Heidi
Published: October 2024

Background

Young people from racialised backgrounds are overrepresented in justice services. This study explored differences in community support offered to young people from racialised groups referred to a forensic child and adolescent mental health service.

Method

We compared support offered to 427 young people, according to five ethnic groups.

Results

Over 20% of young people referred were Black (compared with 14% of the local population) and 15.8% were Dual White and Black Heritage (compared with 4% of the local population). Odds ratios showed that Black and Dual Heritage groups were more frequently involved with youth offending services (Black: 2.59, Dual Heritage: 2.88), gangs services (Black: 4.31, Dual Heritage: 7.13) and have a national referral mechanism (Black: 3.61, Dual Heritage: 4.01) than their White peers, but were less often in mainstream education compared with their Asian peers (Black: 0.26, Dual Heritage: 0.29). Black (odds ratio 0.35) and Dual Heritage (odds ratio 0.40) young people were less frequently diagnosed with a neurodevelopmental disorder than their White peers.

Conclusions

Those from Black and Dual Heritage backgrounds were disproportionately disadvantaged.
Intraoperative Fluid Balance and Perioperative Complications in Ovarian Cancer Surgery
Authors: Egger Eva K. , Ullmann Janina , Hilbert Tobias , Ralser Damian J. , Padron Laura Tascon , Marinova Milka , Stope Matthias , Mustea Alexander
Published: October 2024

Background

Fluid overload and hypovolemia promote postoperative complications in patients undergoing cytoreductive surgery for ovarian cancer. In the present study, postoperative complications and anastomotic leakage were investigated before and after implementation of pulse pressure variation-guided fluid management (PPVGFM) during ovarian cancer surgery.

Patients and Methods

A total of n = 243 patients with ovarian cancer undergoing cytoreductive surgery at the University Hospital Bonn were retrospectively evaluated. Cohort A (CA; n = 185 patients) was treated before and cohort B (CB; n = 58 patients) after implementation of PPVGFM. Both cohorts were compared regarding postoperative complications.

Results

Ultrasevere complications (G4/G5) were exclusively present in CA (p = 0.0025). No difference between cohorts was observed regarding severe complications (G3–G5) (p = 0.062). Median positive fluid excess was lower in CB (p = 0.001). This was independent of tumor load [peritoneal cancer index] (p = 0.001) and FIGO stage (p = 0.001). Time to first postoperative defecation was shorter in CB (CB: d2 median versus CA: d3 median; p = 0.001). CB had a shorter length of hospital stay (p = 0.003), less requirement of intensive medical care (p = 0.001) and postoperative ventilation (p = 0.001). CB received higher doses of noradrenalin (p = 0.001). In the combined study cohort, there were more severe complications (G3–G5) in the case of a PFE ≥ 3000 ml (p = 0.034) and significantly more anastomotic leakage in the case of a PFE ≥ 4000 ml (p = 0.006).

Conclusions

Intraoperative fluid reduction in ovarian cancer surgery according to a PPVGFM is safe and significantly reduces ultrasevere postoperative complications. PFEs of ≥ 3000 ml and ≥ 4000 ml were identified as cutoffs for significantly more severe complications and anastomotic leakage, respectively.
Site-blocking antisense oligonucleotides as a mechanism to fine-tune MeCP2 expression
Authors: Vanderplow Amanda M. , Dodis Grace E. , Rhee Yewon , Cikowski Jakub J. , Gonzalez Sonia , Smith Mackenzie L. , Gogliotti Rocco G.
Published: October 2024

Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function mutations in themethyl-CpG-binding protein 2(MECP2) gene. Despite its severe phenotypes, studies in mouse models suggest that restoring MeCP2 levels can reverse RTT symptomology. Nevertheless, traditional gene therapy approaches are hindered by MeCP2's narrow therapeutic window, complicating the safe delivery of viral constructs without overshooting the threshold for toxicity. The 3′ untranslated region (3′ UTR) plays a key role in gene regulation, where factors like miRNAs bind to pre-mRNA and fine-tune expression. Given that each miRNA's contribution is modest, blocking miRNA binding may represent a potential therapeutic strategy for diseases with high dosage sensitivity, like RTT. Here, we present a series of site-blocking antisense oligonucleotides (sbASOs) designed to outcompete repressive miRNA binding at theMECP23′ UTR. This strategy aims to increase MeCP2 levels in patients with missense or late-truncating mutations, where the hypomorphic nature of the protein can be offset by enhanced abundance. Our results demonstrate that sbASOs can elevate MeCP2 levels in a dose-dependent manner in SH-SY5Y and patient fibroblast cell lines, plateauing at levels projected to be safe. Confirming in vivo functionality, sbASO administration in wild-type mice led to significant Mecp2 upregulation and the emergence of phenotypes associated with Mecp2 overexpression. In a T158M neural stem cell model of RTT, sbASO treatment significantly increased MeCP2 expression and levels of the downstream effector protein brain-derived neurotrophic factor (BDNF). These findings highlight the potential of sbASO-based therapies for MeCP2-related disorders and advocate for their continued development.
Narativ secanja i ratni film u filozofiji filma Zil Deleza
Authors: Νίκολιτς Σάντρα
Published: October 2024

Σε αυτή τη μελέτη, η αφήγηση της μνήμης στη σύγχρονη πολεμική ταινία αναλύεται μέσα από το θεωρητικό μοντέλο του Gilles Deleuze, δηλ. μέσα από τις κατηγορίες του χρόνου-εικόνας και κίνησης-εικόνας. Από τη μια η κίνηση-εικόνα, που χαρακτηρίζει τον κλασικό κινηματογράφο, είναι η βασική εικόνα που γεννά ένα αισθητηριοκινητικό σύνολο, ενώ από την άλλη η εικόνα του χρόνου και ο σύγχρονος κινηματογράφος χτίζονται πάνω στη βαση του αισθητηριοκινητικού τύπου και η δράση-εικόνα που οδηγεί σε ασυνέχεια και μη γραμμικότητα στην αφήγηση. Μια τέτοια αποσπασματική δομή είναι μια πολύ περίπλοκη μορφή και ένα σύστημα σχέσεων που αναπτύσσουν τις συγκεκριμένες έννοιές τους μέσα σε μια ταινία και στο επίπεδο κάθε σκηνής.Σε μια πολεμική ταινία, η αφήγηση χειραγωγεί τη μνήμη των χαρακτήρων, όπου η μνήμη παρουσιάζεται μέσω της τεχνικής του flashback. Και ενώ ο ρόλος της αναδρομής σε μια κινηματογραφική ταινία είναι να εξηγήσει στον θεατή γιατί ένα συγκεκριμένο γεγονός έλαβε χώρα με τον τρόπο που συνέβη, σε μια ταινία χρονικής εικόνας ο ρόλος της αναδρομής είναι να δημιουργήσει μεγαλύτερη σύγχυση.
Ανίχνευση του ιού των ανθρώπινων θηλωμάτων (HPV) στο γεννητικό σύστημα γυναικών στον ελληνικό πληθυσμό
Authors: Καφάση Αθανασία
Published: October 2024

Στην προσπάθεια εξάλειψης του καρκίνου του τραχήλου της μήτρας, βασική συνεισφορά έχει ο συνδυασμός της εκτεταμένης και έγκαιρης εμβολιαστικής κάλυψης του νεαρού γυναικείου πληθυσμού έναντι του ιού των ανθρώπινων θηλωμάτων (HPV) με την ταυτόχρονη χρήση ευαίσθητων μοριακών τεχνικών (HPV DNA test-HPV mRNA test) για την πρώιμη διάγνωση των λοιμώξεων υψηλού κινδύνου. Ωστόσο, αυξημένα ποσοστά παγκοσμίως προκαρκινικών αλλοιώσεων σχετιζόμενων με τύπους HPV που δεν καλύπτουν τα διαθέσιμα εμβόλια, δημιουργούν την ανάγκη περαιτέρω μελέτης του επιπολασμού των υποτύπων HPV στον ελληνικό γυναικείο πληθυσμό και της συμμετοχής αυτών στην πρόκληση χαμηλόβαθμων ή υψηλόβαθμων προκαρκινικών αλλοιώσεων. Σε πληθυσμό 253 γυναικών ηλικίας 18-65 που διαμένουν στην Ελλάδα πραγματοποιήθηκε προληπτικός κυτταρολογικός έλεγχος για τον καρκίνο του τραχήλου της μήτρας με τη μέθοδο του co-testing (test ΠΑΠ και HPV DNA test 41 τύπων). Οι γυναίκες με θετικό HPV High Risk DNA test, ανεξαρτήτως αποτελέσματος του test ΠΑΠ και οι γυναίκες με test ΠΑΠ ≥ ASC-US, ανεξαρτήτως του αποτελέσματος του HPV DNA test, οδηγήθηκαν σε κολποσκόπηση ή και βιοψία. Στα δείγματα των γυναικών που είχαν θετικό HPV DNA test για έναν ή περισσότερους από τους High Risk τύπους 16, 18, 31, 33, 45, πραγματοποιήθηκε και HPV mRNA test. Στο σύνολο του δείγματος παρατηρήθηκε υψηλός επιπολασμός High Risk υποτύπων HPV (25,7% - 65 γυναίκες). Αναδείχθηκε η υψηλή ευαισθησία του HPV DNA test μέσω του οποίου εντοπίστηκαν 25 γυναίκες με αλλοίωση CIN I έναντι 15 γυναικών που ανέδειξε το test ΠΑΠ, ενώ και οι δύο μεθοδολογίες αναγνώρισαν και παρέπεμψαν για ιστολογικό έλεγχο 2 γυναίκες με βλάβη CIN II. Ο κυρίαρχος τύπος σε αλλοιώσεις CIN I-CIN II με ποσοστό 36% ήταν ο HPV 16. Δεύτερος σε επιπολασμό σε γυναίκες με βιοψία CIN I ήταν ο HPV 51 με ποσοστό 24%, ο οποίος κατείχε την πρώτη θέση μεταξύ όλων των High Risk HPV που ανευρέθηκαν στον μοριακό έλεγχο με ποσοστό 25% και δεν καλύπτεται από τα διαθέσιμα εμβόλια. Από τη σύγκριση των αποτελεσμάτων του co-testing σε σχέση με τα αποτελέσματα υποθετικών εναλλακτικών σεναρίων πρωταρχικού προσυμπτωματικού ελέγχου, φαίνεται ότι το co-testing υπερτερεί εάν θέσουμε ως τελικό στόχο την ανίχνευση των CIN I. Η χρήση του mRNA test κατάφερε να εντοπίσει τα 2 περιστατικά με αλλοίωση CIN II και 13 από τα 25 περιστατικά με αλλοίωση CIN I. Συμπερασματικά μπορούμε να επιβεβαιώσουμε ότι είναι απαραίτητη περαιτέρω έρευνα μέσω ευρύτερων επιδημιολογικών μελετών και επαγρύπνηση εκ μέρους των γυναικολόγων έως ότου διευκρινιστεί πλήρως η δυναμική του HPV 51 για πρόκληση υψηλόβαθμων αλλοιώσεων ή καρκίνου στον τράχηλο της μήτρας. H ευρεία εμβολιαστική κάλυψη με το 9δύναμο εμβόλιο πριν την έναρξη της σεξουαλικής ζωής με την παράλληλη χρήση μοριακών μεθοδολογιών προσυμπτωματικού ελέγχου και την εξατομικευμένη προσέγγιση και καθοδήγηση κάθε γυναίκας, θα οδηγήσουν στο μέλλον στην οριστική εξάλειψη του καρκίνου του τραχήλου της μήτρας στη χώρα μας.
Evaluating a targeted selective speech, language, and communication intervention at scale – Protocol for the Happy Talk cluster randomised controlled trial.
Authors: Frizelle Pauline , O'Shea Aoife , Murphy Aileen , Dahly Darren , McKean Cristina
Published: October 2024

Background In areas of social disadvantage up to 40–50% of children enter preschool with speech and language skills significantly poorer than would be expected for their age. The Happy Talk trial tests if a community embedded, targeted selective speech and language programme that simultaneously engages with parents and early childhood educators, (1) improves language outcomes in children aged between 2 years 10 months and 6 years and (2) is cost effective for the health care system. Method The Happy Talk trial is a large scale cluster randomised trial of a 12-week manualised intervention delivered in pre/school settings serving socially disadvantaged communities, in Ireland. Seventy-two clusters will receive the intervention (12 participants per cluster). Parents and pre/school staff engage in group training and coaching in the form of 12 1-hour sessions for parents and four staff workshops, over the course of the pre/school year. Training/coaching includes core interaction skills (modelling, expanding, balancing questions and comments), early literacy and phonological awareness. Blinded assessments pre- and immediately post-intervention and at 6 months follow up, will measure the primary outcomes of children’s receptive and expressive language and functional impact, and secondary outcomes of quality of life. Parental responsiveness and educator-child interactions will also be evaluated. Discussion This robust study evaluates a public health approach to the delivery of speech language and communication intervention in the ‘real world’ in the community, which focuses on prevention and equity of access. Pilot work indicates that the programme is feasible, acceptable to parents and staff, cost effective, and suitable for implementation at scale. The trial includes a process evaluation, a well-developed economic evaluation and the outcomes are directly relevant to children, families and educators. This work has the potential to improve the long-term outcomes and life chances of people living in social disadvantage. Trial registration clinicaltrials.gov NCT06460090 Trial Management There is a formal governance structure to oversee the conduct and running of the trial, consisting of a trial management group and a steering committee. More details on the composition, roles and responsibilities of each committee can be found in the supplemental material.
Updates to the list of Estonian lichenized, lichenicolous and allied fungi
Authors: Suija Ave , Degtjarenko Polina , Jüriado Inga , Martin Ljudmilla , Oja Ede , Randlane Tiina
Published: October 2024

Herewith, we continue to upgrade the Estonian checklist of lichenized, lichenicolous and allied fungi, and report thirteen fungal species and one variety as new for Estonia, of them nine are lichenized and five are lichenicolous. Two species – Acarospora oligospora and Lathagrium auriforme – considered to be extinct in Estonia were rediscovered. One species, Usnea articulata, is excluded from the checklist of Estonian lichens.
Clinically oriented look into diagnostics and therapy of primary sclerosing cholangitis. Review of literature
Authors: Ślósarz Tymoteusz , Kaczorowski Rafał , Forenc Tomasz , Pelczarska Aleksandra , Krupa Paulina Maria , Witkowski Maciej , Mejza Patryk , Kaczorowska Anna
Published: October 2024

Introduction: Primary sclerosing cholangitis (PSC) is a complex liver disorder marked by multifocal bile duct strictures and dilatations, leading to cholestasis and liver fibrosis. Although the exact cause is unknown, autoimmune mechanisms are strongly suspected.
Aim of the Study: This paper reviews current knowledge on PSC, covering its etiology, prevalence, treatment options, and practical management strategies.
Current State of Knowledge: PSC management focuses on symptom relief and liver transplantation, with limited success in pharmacological treatments. New therapies, including immune modulators and anti-fibrotic agents, show promise but require further research. Liver transplantation remains the most effective treatment, though recurrence risks necessitate ongoing monitoring.
Materials and Methods: This article reviews the current understanding of PSC, including its pathophysiology, diagnostic approaches, clinical features, and management strategies. A comprehensive literature search was conducted using PubMed and Google Scholar, with articles selected based on relevant keywords and evaluated for inclusion in this review.
Conclusions: Effective management of PSC necessitates a multidisciplinary approach involving hepatologists, gastroenterologists, radiologists, and transplant surgeons. Ongoing efforts to better understand PSC’s pathogenesis, refine diagnostic methods, and develop more effective therapies are crucial for improving patient outcomes.
Code and Data Repository for An Iterated Dual Substitution Approach for Binary Integer Programming Problems under the Min–Max Regret Criterion
Authors: Wu Wei , Iori Manuel , Martello Silvano , Yagiura Mutsunori
Published: October 2024

The software and data in this repository are a snapshot of the software and data that were used in the research reported in the paper An iterated dual substitution approach for min-max binary integer programming by W. Wu, M. Iori, S. Martello, and M. Yagiura.
Code and Data Repository for Integrated Backup Rolling Stock Allocation and Timetable Rescheduling with Uncertain Time-Variant Passenger Demand Under Disruptive Events
Authors: Yin Jiateng , Yang Lixing , D’Ariano Andrea , Tang Tao , Gao Ziyou
Published: October 2024

This repository includes the computational results, source codes and source data (with no conflict of interest) for the experiments presented in the paper.
Code and Data Repository for An Algorithm for Maximizing a Convex Function Based on its Minimum
Authors: Ben-Tal Aharon , Roos Ernst
Published: October 2024

The goal of this software is to maximize convex functions over a convex feasible set.
Code and Data Repository for An Efficient Optimization Model and Tabu Search-Based Global Optimization Approach for the Continuous p-Dispersion Problem
Authors: Lai Xiangjing , Lin Zhenheng , Hao Jin-Kao , Wu Qinghua
Published: October 2024

The software and data in this repository are a snapshot of the software and data that were used in the research reported in the paper An efficient optimization model and tabu search-based global optimization approach for continuous p-dispersion problem by L.J. Lai, Z.H. Lin, J.K. Hao, and Q.H. Wu.
Code and Data Repository for Domain-Independent Dynamic Programming and Constraint Programming Approaches for Assembly Line Balancing Problems with Setups
Authors: Zhang Jiachen , Beck J. Christopher
Published: October 2024

The goal of this repository is to demonstrate the effect of DIDP and CP for SUALBP.
Mercadores e contrabandistas:
Authors: Kühn Fábio
Published: October 2024

O artigo procura analisar alguns casos de comerciantes envolvidos com o contrabando de escravizados no rio da Prata, extraídos de processos de apreensão efetuados pelas autoridades da Real Fazenda de Buenos Aires, no período posterior ao final da Guerra dos Sete Anos. A análise realizada possibilitou compreender quem eram os agentes mercantis envolvidos no comércio ilegal de escravizados, atividade realizada por diversos tipos de pessoas, desde o nível operacional, como os marinheiros e intérpretes, até os homens de negócio da Colônia do Sacramento que vendiam os cativos aos mercadores que os contrabandeavam para Buenos Aires. O comércio clandestino era realizado em pequenas embarcações, altamente adaptadas ao tipo de transação que realizavam, transportando algumas dezenas de escravizados, na maioria das vezes com sucesso, o que permitiu uma constante introdução de cativos na América espanhola.
Entrevista com Jorge Pedreira
Authors: Guimarães Carlos Gabriel , Moreira Vargas Jonas
Published: October 2024

Em dezembro de 2023, realizamos nosso primeiro contato com o Professor Jorge Miguel Viana Pedreira, que aceitou com satisfação o convite para conceder a presente entrevista. Desde então, trocamos algumas mensagens com o entrevistado e as perguntas e respostas foram realizadas por e-mail, entre abril e maio de 2024. Decidimos focar a entrevista no tema relacionado ao próprio Dossiê - "Capitalistas, comerciantes e homens de negócios: trajetórias de atuação e redes mercantis no mundo Atlântico (séc. XIX)" -, no qual o Professor Jorge Pedreira é um grande especialista, possuindo uma produção historiográfica internacionalmente reconhecida. Docente na Universidade Nova de Lisboa desde 1982, o entrevistado também foi professor visitante da Brown University e da Universidade de São Paulo (2004) e visiting scholar da John Carter Brown Library (2018). É autor de diversos livros, artigos e trabalhos acadêmicos, com destaque para Estrutura Industrial e Mercado Colonial. Portugal e Brasil 1780-1830 (Oeiras: Difel, 1994), Os Homens de Negócio da Praça de Lisboa, de Pombal ao Vintismo (1755-1822). Diferenciação, reprodução e identificação de um grupo social (Tese de Doutoramento em História, Universidade Nova de Lisboa, 1995) e D. João VI. Lisboa: Temas e Debates (2009), em parceria com Fernando Dores Costa. Ao longo das próximas páginas, os leitores e as leitoras poderão saber um pouco mais da trajetória acadêmica e das opiniões do entrevistado sobre alguns debates historiográficos e abordagens históricas mais recentes e algumas metodologias caras à História Social das Elites.