bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antisense oligonucleotide-based targeting of Tau-tubulin kinase 1 prevents hippocampal accumulation of phosphorylated tau in PS19 tauopathy mice
Authors: Yukawa Kayo , Yamamoto-Mcguire Satomi , Cafaro Louis , Hong Christine , Kamme Fredrik , Ikezu Tsuneya , Ikezu Seiko 
Published: October 2023

AbstractTau tubulin kinase-1 (TTBK1), a neuron-specific tau kinase, is highly expressed in the entorhinal cortex and hippocampal regions, where early tau pathology evolves in Alzheimer’s disease (AD). The protein expression level of TTBK1 is elevated in the cortex brain tissues with AD patients compared to the control subjects. We therefore hypothesized that antisense oligonucleotide (ASO) based targeting Ttbk1 could prevent the accumulation of phosphorylated tau, thereby delaying the development of tau pathology in AD. Here we show that in vivo administration of ASO targeting mouse Ttbk1 (ASO-Ttbk1) specifically suppressed the expression of Ttbk1 without affecting Ttbk2 expression in the temporal cortex of PS19 tau transgenic mice. Central administration of ASO-Ttbk1 in PS19 mice significantly reduced the expression level of representative phosphor-tau epitopes relevant to AD at 8 weeks post-dose, including pT231, pT181, and pS396 in the sarkosyl soluble and insoluble fractions isolated from hippocampal tissues as determined by ELISA and pS422 in soluble fractions as determined by western blotting. Immunofluorescence demonstrated that ASO-Ttbk1 significantly reduced pS422 phosphorylated tau intensity in mossy fibers region of the dentate gyrus in PS19 mice. RNA-sequence analysis of the temporal cortex tissue revealed significant enrichment of interferon-gamma and complement pathways and increased expression of antigen presenting molecules (Cd86, Cd74, and H2-Aa) in PS19 mice treated with ASO-Ttbk1, suggesting its potential effect on microglial phenotype although neurotoxic effect was absent. These data suggest that TTBK1 is an attractive therapeutic target to suppress TTBK1 without compromising TTBK2 expression and pathological tau phosphorylation in the early stages of AD.
Concordance between head and neck MRI and histopathology in detecting laryngeal subsite invasion among patients with laryngeal cancer
Authors: Mohamad Issa , Hejleh Taher Abu , Qandeel Monther , Al-Hussaini Maysa , Koro Sami , Taqash Ayat , Almousa Abdelatif , Abuhijla Fawzi , Abuhijlih Ramiz , Ajlouni Fatenah , Al-Ibraheem Akram , Laban Dima Abu , Hussein Tariq , Mayta Ebrahim , Al-Gargaz Wisam , Hosni Ali 
Published: October 2023

Abstract
Background
Accuracy of head and neck MRI (HN-MRI) in predicting tumor invasion of laryngeal site/subsites in patients with laryngeal cancer prior to laryngectomy is poorly evaluated in the literature. Therefore, we aim to evaluate the diagnostic value of HN-MRI in accurate pre-operative estimation of tumor invasion to laryngeal subsites in patients with laryngeal cancer.

Methods
Patients with laryngeal cancer who underwent HN-MRI for cancer staging and underwent total laryngectomy between 2008 and 2021 were included. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of HN-MRI in predicting tumor invasion of laryngeal subsites were calculated based on concordance between the HN-MRI and histopathological results.

Results
One hundred and thirty-seven patients underwent total laryngectomy [primary: 82/137(60%), salvage 55/137(40%)]. The utilization of HN-MRI resulted in the downstaging of 16/137 (11.6%) patients and the upstaging of 8/137 (5.8%) patients. For the whole cohort, there was a significant discordance between HN-MRI and histopathology for T-category; out of 116 cT4a disease, 102(87.9%) were confirmed to have pT4a disease, and out of 17 cT3 disease, 9(52.9%) were confirmed to have pT3 disease, p < 0.001. The MRI overall diagnostic accuracy of predicting tumor invasion was 91%, 92%, 82%, 87%, 72%, 76%, 65% and 68% for base of tongue, arytenoid, vocal cord, posterior commissure, pre-epiglottic space, cricoid cartilage, inner thyroid cortex, and subglottis, respectively.

Conclusions
In patients with laryngeal cancer undergoing total laryngectomy, HN-MRI demonstrates promising accuracy in predicting tumor invasion of specific laryngeal subsites (e.g., base of tongue). Our findings showed the potential of HN-MRI as a valuable tool for pre-operative planning and treatment decision-making in this patient population.
Effects of combined application of benzoic acid and 1-monolaurin on growth performance, nutrient digestibility, gut microbiome and inflammatory factor levels in weaned piglets
Authors: Wei Kai , Yang Xia , Zhao Huasheng , Chen Huanchun , Bei Weicheng 
Published: October 2023

Abstract
Background
Our previous study observed that benzoic acid and 1-monolaurin have a synergistic bactericidal effect. Moreover, their improvement effect of benzoic acid and 1-monolaurin on the growth performance and diarrhea of weaned piglets was better than the two feedings alone. However, it is not clear how the combination of benzoic acid and 1-monolaurin affects the growth performance of weaned piglets. Therefore, 100 weaned piglets (mean weight 7.03 ± 1.04 kg, mean weaning age 26 d) were randomly divided into two groups: (1) basal diet control (CON); (2) basal diet supplemented with 0.6% benzoic acid and 0.1% 1-monolaurin (CA). The experiment lasted 28 days after weaning. The effects of benzoic acid and 1-monolaurin supplementation on growth performance, apparent nutrient digestibility, intestinal flora composition and function, and inflammatory factor levels of weaned piglets were investigated.

Results
The feed conversion efficiency of piglets in the CA group between 15 and 28 d and 1 and 28 d after weaning was significantly higher than that in the CON group (P < 0.05). Additionally, the diarrhea proportion and frequency of piglets in the CA group 1–14 days post-weaning were significantly decreased (P < 0.05). The apparent digestibility of dry matter, organic matter and crude protein of piglets in the CA group was significantly higher than the CON group on days 14 and 28 (P < 0.05). The microbial composition in the cecal digesta of piglets was detected. The results indicated that the CA group piglets were significantly supplemented with g_YRC22 at day 14 and g_Treponema, g_Pseudomonas, and g_Lachnobacterium at day 28 (P < 0.05; log LDA > 2). No significant difference was observed between the CON and CA groups in the content of short-chain fatty acids. In addition, serum IL−1β level significantly decreased at day 28 in the CA group compared with the CON group, while serum endotoxin content was significantly reduced at day 14.

Conclusion
Therefore, dietary supplementation of 0.6% benzoic acid and 0.1% 1-monolaurin enhanced growth performance and nutrient digestibility, affected gut microflora composition, and decreased systemic inflammatory response and intestinal permeability of weaned piglets. These outcomes provide a theoretical basis for applying of benzoic acid and 1-monolaurin over weaned piglets.
Cognitive performance outcomes: considerations for drug development
Authors: Zupan Zorana 
Published: October 2023

AbstractEnsuring that cognitive assessments are fit for purpose is critical in the evaluation of the clinical benefit of new therapeutic interventions. Although guidelines for Clinical Outcome Assessments (COA) are available, performance outcome (PerfO) assessments, and in particular those assessing cognition (Cog-PerfOs) are more complex and have additional requirements that need to be considered. I outline three areas where further discussion around validation methods for Cog-PerfOs and best practices is warranted: (1) content validity (2) ecological validity, and (3) construct validity in multinational contexts. I conclude with a discussion of several potential avenues for the improvement of validation of Cog-PerfOs used to evaluate the efficacy of medical products that target cognitive symptomatology. These include the involvement of cognitive psychologists in establishing content validity of Cog-PerfOs, evaluating the congruence of laypeople’s and expert understanding of cognitive concepts, supplementing qualitative with quantitative evidence when establishing content validity, demonstrating ecological validity, and ensuring normative data are available in multinational contexts.
AI temporal planning for energy smart buildings
Authors: Georgievski Ilche , Shahid Muhammad Zamik , Aiello Marco 
Published: October 2023

AbstractBuildings are responsible for about one-third of industrialised countries’ overall energy consumption and greenhouse gas emissions. As if this was not enough, recently, energy prices significantly increased and affected all economic areas. Making buildings more efficient and effective is the step needed toward cost reductions. Key enablers of cost-effectiveness are leveraging batteries, awareness of and adaptability to energy prices, and integrating powerful reasoning techniques to optimally and flexibly operate buildings. Researchers have tackled many of these aspects using a variety of approaches. Whereas a less investigated one is that of AI planning to coordinate actions and save energy in buildings. However, generating plans based on signals of energy prices and leveraging batteries is still an open research problem. To address this high-potential aspect, we engineer an AI planning system for improving the energy-cost effectiveness in buildings by coordinating the building’s operation based on day-ahead prices and the use of a battery, all without sacrificing the comfort of building occupants. We propose to exploit temporal planning due to its powerful modelling and reasoning features, especially in explicitly addressing time. We evaluate the effectiveness of the system in several scenarios with varying building environmental conditions. We compare the energy cost from using our planning system to a baseline cost, where we record a reduction of 43rage in favour of our system.
Quantum–classical co-simulation for smart grids: a proof-of-concept study on feasibility and obstacles
Authors: Vereno Dominik , Khodaei Amin , Neureiter Christian , Lehnhoff Sebastian 
Published: October 2023

AbstractWith the rising complexity of our electricity infrastructure, smart grid simulations increasingly rely on co-simulation, which involves jointly executing independent subsystem simulations. However, in large-scale simulation scenarios, such as those involving costly power-flow analysis, co-simulation may experience computational-performance issues. Quantum computing offers a potential solution through quantum–classical co-simulation, in which one or more simulators of an otherwise classical co-simulation are executed on quantum hardware. However, there is no practical realization of this concept that establishes its feasibility. To address this gap, we integrate a quantum power flow simulator with a smart grid co-simulation and conduct an exploratory simulation study using a fictitious case-study scenario. The experiments demonstrate the feasibility of quantum–classical co-simulation; at the same time, they highlight four obstacles to the concept’s realization in practice: (1) To use quantum computing for co-simulation, session-based scheduling is required. (2) Distributed simulation limits possible applications and requires proximity of computing resources. (3) For the efficient extraction of classical information from the quantum states, we need carefully designed operators. (4) Current hardware limitations—such as noise susceptibility and the lack of quantum random access memory—limit practical near-term uses of quantum power flow; therefore, attention should be turned to alternative applications that are more promising in the near term. These findings pave the way for future research on quantum–classical co-simulation and its potential applications in smart grids.
INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas
Authors: Grassl Niklas , Sahm Katharina , Süße Heike , Poschke Isabel , Bunse Lukas , Bunse Theresa , Boschert Tamara , Mildenberger Iris , Rupp Anne-Kathleen , Ewinger Max Philipp , Lanz Lisa-Marie , Denk Monika , Tabatabai Ghazaleh , Ronellenfitsch Michael W. , Herrlinger Ulrich , Glas Martin , Krex Dietmar , Vajkoczy Peter , Wick Antje , Harting Inga , Sahm Felix , von Deimling Andreas , Bendszus Martin , Wick Wolfgang , Platten Michael 
Published: October 2023

Abstract
Introduction
Diffuse midline gliomas (DMG) are universally lethal central nervous system tumors that carry almost unanimously the clonal driver mutation histone-3 K27M (H3K27M). The single amino acid substitution of lysine to methionine harbors a neoantigen that is presented in tumor tissue. The long peptide vaccine H3K27M-vac targeting this major histocompatibility complex class II (MHC class II)-restricted neoantigen induces mutation-specific immune responses that suppress the growth of H3K27M+ flank tumors in an MHC-humanized rodent model.

Methods
INTERCEPT H3 is a non-controlled open label, single arm, multicenter national phase 1 trial to assess safety, tolerability and immunogenicity of H3K27M-vac in combination with standard radiotherapy and the immune checkpoint inhibitor atezolizumab (ATE). 15 adult patients with newly diagnosed K27M-mutant histone-3.1 (H3.1K27M) or histone-3.3 (H3.3K27M) DMG will be enrolled in this trial. The 27mer peptide vaccine H3K27M-vac will be administered concomitantly to standard radiotherapy (RT) followed by combinatorial treatment with the programmed death‐ligand 1 (PD-L1) targeting antibody ATE. The first three vaccines will be administered bi-weekly (q2w) followed by a dose at the beginning of recovery after RT and six-weekly administrations of doses 5 to 11 thereafter. In a safety lead-in, the first three patients (pts. 1–3) will be enrolled sequentially.

Perspective
H3K27M-vac is a neoepitope targeting long peptide vaccine derived from the clonal driver mutation H3K27M in DMG. The INTERCEPT H3 trial aims at demonstrating (1) safety and (2) immunogenicity of repeated fixed dose vaccinations of H3K27M-vac administered with RT and ATE in adult patients with newly diagnosed H3K27M-mutant DMG.

Trial registration
NCT04808245.
Early onset Caroli’s disease with associated renal cystic disease presented with recurrent fever and epigastric pain: a case report
Authors: Mishra Abhishek , Mallick Achinta Kumar , Singh A. K. , Mishra Anushree 
Published: October 2023

Abstract
Background
Caroli’s disease is characterized by non-obstructive dilatation of intrahepatic biliary radicals with formation of calculi followed by recurrent episodes of cholangitis. It is a rare congenital malformation and often remains silent, diagnosed accidentally. But if kept unattended, and without any early intervention, it may lead to fatal residual complications. Hence, its early recognition is of utmost importance to prevent recurrent cholangitis, hepatic abscess, liver cirrhosis and cholangiocarcinoma. Hence, we feel that this case must be reported so as to increase awareness among physicians regarding this entity.

Case presentation
We hereby report a case of 10-year-old boy who reported with complaints of recurrent episodes of fever, breathing difficulty and multiple episodes of epigastric abdominal pain with apparently healthy siblings. His routine investigation, laboratory parameters were within normal limits. Ultrasonography abdomen showed liver with normal echo-texture with varying sized multiple thin walled cysts involving both the lobes, right more than left with saccular dilatation of 2nd and 3rd order intra-hepatic biliary radicals without calcification without any colour flow on Doppler evaluation. The common hepatic and common bile ducts were normal in calibre and lumen. Magnetic resonance imaging abdomen had similar findings and upper GI endoscopy was also normal. He was finally diagnosed to be a case of Caroli’s disease and was managed with broad spectrum antibiotics, ursodeoxycholic acid, multivitamins, and calcium supplements. He made an uneventful recovery thereafter. Parents were counselled about the risk of cholangitis and cholangiocarcinoma and was referred to tertiary care centre for genetic counselling and for future need of liver transplantation.

Conclusion
Age presentation of Caroli’s disease varies. Majority present during adolescence and early adulthood. This often poses a diagnostic challenge owing its rare entity and silent presentation. A strong index of suspicion and prompt diagnosis is warranted to prevent its fatal residual complications.
Characteristics of low back pain and its associated factors among healthcare providers at a tertiary hospital in Sylhet city: a cross-sectional study
Authors: Islam Mohammad Jahirul , Ahmed Sohel , Islam Khandaker Md Kamrul , Al Mamun Muhammad Abdullah , Roy Shankar Kumar , Chakraborty Shishir Ranjan 
Published: October 2023

Abstract
Background
Healthcare providers serve as the backbone of the healthcare system, yet they frequently have low back pain (LBP) due to ergonomic factors. Therefore, the objective of this research was to identify the characteristics of LBP and its associated factors among healthcare providers in Bangladesh.

Methodology
In this cross-sectional study, 310 medical providers, both male and female, participated. An interviewer-administered questionnaire was used to evaluate data regarding different measures of LBP. The chi-square test and descriptive statistics were used to evaluate the data. To identify the predicted risk factor for LBP, binary logistic regression was performed.

Result
A total of 51.9% of healthcare providers reported having LBP at least once a day in the past 12 months, 25.8% had chronic LBP, 18.1% had to take time off work due to LBP, and 57.89% had received combination medication and physiotherapy in the previous 12 months. The advanced age (41–59 years) adjusted odds ratio (AOR) = 1.83, 95% confidence interval (CI) = 1.04–3.22; p = 0.034), lifting objects (AOR = 2.00, 95% CI = 1.06–3.78; p = 0.032), awkward position (AOR = 6.54, 95% CI = 3.04–14.10; p = 0.001), physical exercise (AOR = 3.81, 95% CI = 2.23–6.52; p = 0.001), and comorbidities (AOR = 1.79, 95% CI = 1.00–3.20) were predictors for developing LBP at least once in the past 12 months.

Conclusion
According to this study, more than half of healthcare professionals reported having LBP at least once in the previous 12 months. Good working posture, ergonomic knowledge, and safe lifting techniques are essential to getting rid of this problem. In addition, good medical attention and regular exercise are required.
Brain-derived neurotrophic factor is associated with cardiometabolic risk factors in HIV patients on combination antiretroviral therapy in Ghana
Authors: Yeboah Kwame , Otu Francys Frimpong , Agyekum Jennifer Adjepong , Dzudzor Bartholomew 
Published: October 2023

Abstract
Background
Brain-derived neurotrophic factor (BDNF) has been implicated in the development of cardiometabolic risk factors in some populations. However, few studies have investigated the role of BDNF and cardiometabolic risk factors in HIV patients despite the plethora of evidence linking HIV infection with the dysregulation of circulating BDNF levels. We investigated the association between serum BDNF and cardiometabolic risk factors in HIV patients in a primary hospital in Ghana. We recruited 450 participants, comprising 150 combination antiretroviral (cART)-treated HIV patients, 150 cART-naïve HIV patients, and 150 non-HIV controls. Data on sociodemographic parameters and medical history were collected using a structured questionnaire. Fasting venous blood samples were collected to measure plasma glucose levels, lipid profiles, and BDNF. Metabolic syndrome (MetS) was defined using the joint interim statement criteria.

Results
Compared to untreated HIV patients and uninfected controls, the proportion of participants having MetS was high in cART-exposed HIV patients (26.8% vs 21.1% vs 52.1%, respectively, p < 0.001). Generally, BDNF levels were higher in uninfected controls compared with untreated and cART-exposed HIV patients [7.1 (3.4–13.3) vs 4.9 (2.7–9.6) vs 5.6 (2.9–8.9) ng/ml, p = 0.025]. In participants without MetS, square root-transformed serum BDNF was lowest in cART-exposed HIV patients, followed by untreated HIV patients, with uninfected controls having the highest (1.8 ± 0.8 vs 2.4 ± 1.2 vs 2.9 ± 1.2 ng/ml, p < 0.001). MetS was associated with serum BDNF levels in only the cART-exposed HIV patients [OR (95% CI) = 2.98 (1.64–5.41), p < 0.001]. In cART-exposed HIV patients, an increase in BDNF was associated with increased likelihood of having impaired fasting glucose [2.49 (1.51–4.11), p < 0.001], high systolic blood pressure [1.64 (1.1–2.46), p = 0.016], and hypertriglyceridemia [2.73 (1.65–4.52), p < 0.001], as well as decreased likelihood of having low HDL cholesterol levels [0.32 (0.19–0.56), p < 0.001].

Conclusion
In our study population, MetS was higher in cART-exposed HIV patients. HIV patients have low levels of serum BDNF, especially those without MetS. BDNF was associated with MetS and its components in HIV patients on cART management.
A Moonless Night
Authors: Suess Solveig Qu 
Published: October 2023

Abstract
Curated Spaces features the work of artist and filmmaker Solveig Qu Suess. This essay provides narrative and visual context for her film Little Grass. The film explores the history of geopolitical division between China and the West through the lens of her mother’s career as an optical engineer, expelled from the Chinese state in 1987 for marrying a Western colleague. “A Moonless Night” offers a reflection on memory, belonging, Cold War politics, and state power.
Demystification and feasibility of CRISPR technology and gene editing in African laboratories
Authors: Jemaà Mohamed 
Published: October 2023

ABSTRACT
Clustered regularly interspaced short palindromic repeats, or CRISPR, is a powerful molecular biology tool that is enabling high-quality genetic research and engineering. However, for practical reasons, but more specifically because of the lack of training and the rapid development of gene-editing technology, the technique is still not well established in African laboratories. For this reason, a consortium formed by the Institut Pasteur of Tunis and Learn and Win decided to organise an international conference and workshop on CRISPR technology in particular and gene editing in general, focusing on the low-budget model more appropriate to the African context. From 12 to 17 June 2023, more than 200 interdisciplinary researchers and students from the life sciences and more than 20 international speakers and trainers gathered at the Institut Pasteur in Tunis, Tunisia, for the First African Conference and Workshop on CRISPR to discuss the latest gene editing technologies and discoveries. This Meeting Review describes the scientific event and highlights the main outcomes of both the conferences and the practical sessions. The symposium was a real success and thrives to educate, train and network international and young scientists in the field of gene editing and gene engineering.