bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term safety of oral edaravone in Japanese patients with amyotrophic lateral sclerosis: Sub‐analysis of a global, open‐label, phase 3 study
Authors: Sun Xuezhu , Hirai Manabu , Tezuka Tomoaki , Hirota Shinya , Yuki Satoshi 
Published: December 2023

AbstractIntroduction/AimsPatients with amyotrophic lateral sclerosis (ALS) experience a slower rate of physical function decline when treated with intravenous edaravone. The oral suspension formulation of edaravone (105 mg) has a similar pharmacokinetic profile to intravenous edaravone (60 mg/60 min). The long‐term safety of oral edaravone in Japanese patients with ALS has not been reported. Therefore, a sub‐analysis of Japanese patients in a global phase 3 study (NCT04165824) was conducted to evaluate the safety and tolerability of oral edaravone in Japanese patients with ALS.MethodsThis study was a global, open‐label, phase 3 study to evaluate the long‐term safety and tolerability of oral edaravone in patients with ALS. Patients with ALS received oral edaravone (105 mg/day) for 48 weeks. Adverse events in Japanese patients were assessed at week 48.ResultsAmong the 185 patients enrolled globally, 65 patients were enrolled in Japan (mean age, 59.3 years; mean disease duration, 1.5 years). Most patients experienced treatment‐emergent adverse events (TEAEs) (84.6%), and the most common TEAEs by week 48 were constipation (15.4%), insomnia (12.3%), and back pain (10.8%). Two serious TEAEs were reported: atrial fibrillation and pleural effusion (both n = 1). Three adverse drug reactions (ADRs) were reported: diarrhea, abnormal hepatic function, and fatigue (all n = 1). There were no serious ADRs or TEAEs/ADRs that led to study drug discontinuation.DiscussionOral edaravone had a similar safety profile to intravenous edaravone in Japanese patients, and good tolerability over 48 weeks. No new safety concerns were observed in this population.
Local distribution of manganese to leaf sheath is mediated by OsNramp5 in rice
Authors: Huang Sheng , Konishi Noriyuki , Yamaji Naoki , Ma Jian Feng 
Published: December 2023

Summary
To play essential roles of manganese (Mn) in plant growth and development, it needs to be transported to different organs and tissues after uptake. However, the molecular mechanisms underlying Mn distribution between different tissues are poorly understood.
We functionally characterized a member of rice natural resistance‐associated macrophage protein (NRAMP) family, OsNramp5 in terms of its tissue specificity of gene expression, cell‐specificity of protein localization, phenotypic analysis of leaf growth and response to Mn fluctuations.
OsNramp5 is highly expressed in the leaf sheath. Immunostaining revealed that OsNramp5 is polarly localized at the proximal side of xylem parenchyma cells of the leaf sheath. Both the gene expression and protein abundance of OsNramp5 are unaffected by different Mn concentrations. Knockout of OsNramp5 decreased the distribution of Mn to the leaf sheath, but increased the distribution to the leaf blade at both low and high Mn supplies, resulting in reduced growth of leaf sheath. Furthermore, expression of OsNramp5 under the control of root‐specific promoter in osnramp5 mutant complemented Mn uptake, but could not complement Mn distribution to the leaf sheath.
These results indicate that OsNramp5 expressed in the leaf sheath plays an important role in unloading Mn from the xylem for the local distribution in rice.
Segregation of neuronal and vascular retinal damage in patients with hypertension and diabetes
Authors: Chua Jacqueline , Wong Damon , Yow Ai Ping , Tan Bingyao , Liu Xinyu , Ismail Munirah Binte , Chin Calvin Woon Loong , Lamoureux Ecosse , Husain Rahat , Schmetterer Leopold 
Published: December 2023

AbstractThis study aimed to examine the impact of diabetes and hypertension on retinal nerve fiber layer (RNFL) thickness components. Optical coherence tomography (OCT) measurements do not consider blood vessel contribution, which this study addressed. We hypothesized that diabetes and/or hypertension would lead to thinner RNFL versus controls due to the vascular component. OCT angiography was used to measure the RNFL in 121 controls, 50 diabetes patients, 371 hypertension patients, and 177 diabetes patients with hypertension. A novel technique separated the RNFL thickness into original (vascular component) and corrected (no vascular component) measurements. Diabetes‐only (98 ± 1.7 µm; p = 0.002) and diabetes with hypertension (99 ± 0.8 µm; p = 0.001) patients had thinner original RNFL versus controls (102 ± 0.8 µm). No difference was seen between hypertension‐only patients (101 ± 0.5 µm; p = 0.083) and controls. After removing the blood vessel component, diabetes/hypertension groups had thinner corrected RNFL versus controls (p = 0.024). Discrepancies in diabetes/hypertension patients were due to thicker retinal blood vessels within the RNFL thickness (p = 0.002). Our findings suggest that diabetes and/or hypertension independently contribute to neurodegenerative thinning of the RNFL, even in the absence of retinopathy. The differentiation of neuronal and vascular components in RNFL thickness measurements provided by the novel technique highlights the importance of considering vascular changes in individuals with these conditions.
Zeolites synthesized from agro‐industrial residues applied in agriculture: A review and future prospects
Authors: de Carvalho Izidoro Juliana , Fungaro Denise Alves , Cataldo Eleonora 
Published: December 2023

AbstractZeolites have been widely applied as catalysts, wastewater treatment agents, gas adsorbents and fertilizers, among others. However, the use of natural zeolites or those synthesized from oversaturated commercial solutions are more explored commercially than the zeolites synthesized from residues. Therefore, the aim of this review is to highlight the importance of zeolites synthesized from agro‐industrial residues and their use in agriculture. This review has been divided into three different sections, that is, zeolites, agriculture applications, synthesis of zeolites from residues and their application in plant growth. In the first section, the definition, types and the critical properties of zeolites are explained. The second section gives a brief review of the application of zeolites in agriculture. Finally, the synthesis of zeolites from residues, such as coal ash, rice husk ash and sugarcane ash, with special attention to renewable sources is presented. The optimization of the synthesis of zeolites from residues with the incorporation of specific nutrients necessary for the cultivation of soybeans, corn and sugarcane (considered the most significant crops in Brazilian agriculture in terms of the planted area) can significantly contribute to the concept of circular economy at the industries and the fulfilment of sustainable development objectives, especially, the number 12 (SDO—12—Responsible consumption and production).
A vesicular Warburg effect: Aerobic glycolysis occurs on axonal vesicles for local NAD+ recycling and transport
Authors: Mc Cluskey Maximilian , Dubouchaud Hervé , Nicot Anne‐Sophie , Saudou Frédéric 
Published: December 2023

AbstractIn neurons, fast axonal transport (FAT) of vesicles occurs over long distances and requires constant and local energy supply for molecular motors in the form of adenosine triphosphate (ATP). FAT is independent of mitochondrial metabolism. Indeed, the glycolytic machinery is present on vesicles and locally produces ATP, as well as nicotinamide adenine dinucleotide bonded with hydrogen (NADH) and pyruvate, using glucose as a substrate. It remains unclear whether pyruvate is transferred to mitochondria from the vesicles as well as how NADH is recycled into NAD+ on vesicles for continuous glycolysis activity. The optimization of a glycolytic activity test for subcellular compartments allowed the evaluation of the kinetics of vesicular glycolysis in the brain. This revealed that glycolysis is more efficient on vesicles than in the cytosol. We also found that lactate dehydrogenase (LDH) enzymatic activity is required for effective vesicular ATP production. Indeed, inhibition of LDH or the forced degradation of pyruvate inhibited ATP production from axonal vesicles. We found LDHA rather than the B isoform to be enriched on axonal vesicles suggesting a preferential transformation of pyruvate to lactate and a concomitant recycling of NADH into NAD+ on vesicles. Finally, we found that LDHA inhibition dramatically reduces the FAT of both dense‐core vesicles and synaptic vesicle precursors in a reconstituted cortico‐striatal circuit on‐a‐chip. Together, this shows that aerobic glycolysis is required to supply energy for vesicular transport in neurons, similar to the Warburg effect.
Deubiquitinase USP1 regulates sarbecovirus ORF6 protein function
Authors: Gao Wenying , Wang Liuli , Cui Wenzhe , Wang Hongfei , Huang Guofeng , Li Zhaolong , Li Guangquan , Zhang Wenyan 
Published: December 2023

ABSTRACT

SARS-CoV-2 belongs to the subgenus
Sarbecovirus
, which universally encodes the accessory protein ORF6. SARS-CoV-2 ORF6 is an antagonist of the interferon (IFN)-mediated antiviral response and plays an important role in viral infections. However, the mechanism by which the host counteracts the function of ORF6 to restrict viral replication remains unclear. In this study, we found that most ORF6 proteins encoded by sarbecoviruses could be ubiquitinated and subsequently degraded via the proteasome pathway. Through extensive screening, we identified that the deubiquitinase USP1, which effectively and broadly deubiquitinates sarbecovirus ORF6 proteins, stabilizes ORF6 proteins, resulting in enhanced viral replication. Therefore, ubiquitination and deubiquitination of ORF6 are important for antagonizing IFN-mediated antiviral signaling and influencing the virulence of SARS-CoV-2. These findings highlight an essential molecular mechanism and may provide a novel target for therapeutic interventions against viral infections.

IMPORTANCE
The ORF6 proteins encoded by sarbecoviruses are essential for effective viral replication and infection and are important targets for developing effective intervention strategies. In this study, we confirmed that sarbecovirus ORF6 proteins are important antagonists of the host immune response and identified the regulatory mechanisms of ubiquitination and deubiquitination of most sarbecovirus ORF6 proteins. Moreover, we revealed that DUB USP1 prevents the proteasomal degradation of all ORF6 proteins, thereby promoting the virulence of SARS-CoV-2. Thus, impeding ORF6 function is helpful for attenuating the virulence of sarbecoviruses. Therefore, our findings provide a deeper understanding of the molecular mechanisms underlying sarbecovirus infections and offer potential new therapeutic targets for the prevention and treatment of these infections.
Fecal and skin microbiota of two rescued Mediterranean monk seal pups during rehabilitation
Authors: Dosi Aggeliki , Meziti Alexandra , Tounta Eleni , Koemtzopoulos Kimon , Komnenou Anastasia , Dendrinos Panagiotis , Kormas Konstantinos 
Published: December 2023

ABSTRACT

The role of animal host-associated microbiomes is becoming more apparent and defined for wild animals, especially for the species under conservation strategies. This study investigated the succession of fecal and skin bacterial microbiota of two rescued female Mediterranean monk seal (
Monachus monachus
) pups for most of their rehabilitation period. Bacterial species richness and diversity were assessed by high-throughput sequencing of nine freshly collected fecal samples and four skin swabs per individual. Both the fecal and skin microbiota highly overlapped in their containing operational taxonomic units (OTUs) and abundance patterns. The fecal microbiota was separated in two distinct periods and was dominated by OTUs related to the
Shigella
,
Streptococcus
,
Enterococcus
,
Lactobacillus,
and
Escherichia
genera in the first period, while in the second period, the dominating genera were the
Clostridium, Blautia, Fusobacterium, Edwardsiella,
and
Bacteroides
. The skin microbiota was highly similar between the two individuals in each sampling and was dominated by
Psychrobacter-, Elizabethkingia-,
and
Bergeyella
-related OTUs. The provided antibiotic treatment, along with the provided probiotics and nutritional supplements, resulted in a major turnover of the bacterial microbiota with the potentially detrimental OTUs being eliminated toward the end of the rehabilitation period, prior to the release of the pups in the wild.

IMPORTANCE

This study showed that during the rehabilitation of two rescued Mediterranean monk seal pups (
Monachus monachus
), the skin and fecal bacterial communities showed similar succession patterns between the two individuals. This finding means that co-housed pups share their microbiomes, and this needs to be considered in cases of infection outbreaks and their treatment. The housing conditions, along with the feeding scheme and care protocols, including the admission of antibiotics as prophylaxis, probiotics, and essential food supplements, resulted in bacterial communities with no apparent pathogenic bacteria. This is the first contribution to the microbiome of the protected seal species of
M. monachus
and contributes to the animal’s conservation practices through its microbiome.
Early Cambrian Cambroclavus is a scleritomous eumetazoan unrelated to bryozoan or dasyclad algae
Authors: Xiang Kai , Yin Zongjun , Liu Wei , Zhao Fangchen , Zhu Maoyan 
Published: December 2023

Abstract
The origin of Bryozoa has long been an intriguing mystery, largely due to the dearth of unambiguous bryozoan fossils within Cambrian strata. The earliest bryozoan thus far identified, Protomelission, an early Cambrian microfossil from Australia and China, was recently contested and proposed to be dasyclad algae. Our reanalysis of micro-computed tomography data from Protomelission specimens, however, unveils previously unrevealed structures, indicating Protomelission to be neither bryozoan nor alga, but a scleritome of Cambroclavus, an early Cambrian microfossil typically found as disarticulated sclerites. The long-sought scleritomes suggest that enigmatic cambroclaves likely represent an extinct group of epitheliozoan-grade eumetazoan, with spiny sclerites covering their epidermis for defense. The prevalence of bizarre animals like cambroclaves, lacking modern analogues, implies a greater disparity of animal body plans during the Cambrian explosion than previously recognized. Our findings underscore the absence of definitive early Cambrian bryozoan fossils, further highlighting the dilemma of the origin of Bryozoa.
Genetic Diversity of the Amur Tiger (Panthera tigris altaica): Are There Differences between the 20th and the Early 21st Centuries?
Authors: Sorokin P. A. , Yudin V. G. , Naidenko S. V. , Hernandez-Blanco J. A. , Chistopolova M. D. , Rozhnov V. V. 
Published: December 2023

Abstract
Polymorphism of nine microsatellite loci in the Sikhote-Alin tiger population was analyzed in the modern and recent historical periods, using blood, excrement, and museum bone samples. Tests for excess heterozygosity to determine whether the population went through a period of low abundance and a low value of the Garza–Williamson coefficient indicated that such events were highly probable to occur in both recent and earlier history. The mean effective population size Ne of a current sample was 34.4 (95% confidence interval 17–106.8). This fact is of great interest in the contest of conservation and restoration of endangered large cat species.
Elbow septic arthritis in an infant: an unusual presentation of invasive pneumococcal disease
Authors: Santos Paula , Gouveia Catarina , Ovídio Joana , Ribeiro Catarina 
Published: December 2023

Acute septic arthritis is a rare, potentially severe infection that requires immediate treatment to avoid long-term morbidity. Most common aetiological agents are commonly used for empirical treatment, but the choice of antibiotics may be influenced by other factors, such as the patient’s age and the epidemiological context.We report an infant with elbow arthritis, whose treatment was changed afterStreptococcus pneumoniaeserotype 9N was isolated in the blood and synovial fluid. The child underwent arthrocentesis and received intravenous ampicillin followed by oral amoxicillin, with a favourable response and no sequelae at 1-year follow-up.We report an uncommon manifestation of invasive pneumococcal disease in a young immunised healthy infant caused by a non-vaccine serotype. The presence ofS. pneumoniaeshould be considered in joint infections, especially in infants and those with a history of respiratory symptoms.
Advancing Suicide Intervention Strategies for Teens (ASSIST): study protocol for a multisite randomised controlled trial
Authors: Adrian Molly , McCauley Elizabeth , Gallop Robert , Stevens Jack , Jobes David A , Crumlish Jennifer , Stanley Barbara , Brown Gregory K , Green Kelly L , Hughes Jennifer L , Bridge Jeffrey A 
Published: December 2023

IntroductionBrief interventions that reduce suicide risk following youth’s experience with acute care due to suicidality are needed.Methods and analysisThe study will use a three-arm randomised controlled trial designed to test the effectiveness of the Safety Planning Intervention with structured follow-up (SPI+) and the Collaborative Assessment and Management of Suicidality (CAMS) compared with enhanced usual care. The primary outcomes measure will be suicidal events, defined as death by suicide, attempted suicide, preparatory acts toward imminent suicidal behaviour or suicidal ideation resulting in a change in emergency evaluation or inpatient admission. Secondary measures will be the number of suicide attempts and severity of suicidal ideation. The experimental interventions, SPI+ and CAMS, consist of up to eight sessions over approximately 8 weeks that are designed to manage (SPI+) or treat (CAMS) patient-identified ‘drivers’ of suicidal thoughts and behaviours. Mechanisms and moderators of change will be evaluated to understand treatment impacts.Ethics and disseminationThis study has been approved by the Seattle Children’s Institutional Review Board and is monitored by external agencies including the University of Washington Institute for Translational Health Sciences, and a National Institute of Mental Health (NIMH)-appointed Data Safety and Monitoring Board. Trial results will help establish evidence towards safe and effective treatment strategies for youth transitioning from acute to outpatient care due to a suicidal crisis. The data will be shared with the NIMH Data Archives and disseminated through publications and conferences.Trial registration numberNCT05078970.
Lisdexamphetamine versus methylphenidate for paediatric patients with attention-deficit hyperactivity disorder and type 1 diabetes (LAMAinDiab): protocol for a multicentre, randomised cross-over clinical trial in an outpatient telemedicine-supported setting
Authors: Michalak Arkadiusz , Chrzanowski Jędrzej , Kuśmierczyk-Kozieł Hanna , Klejman Ewa , Błaziak Katarzyna , Mianowska Beata , Szadkowska Agnieszka , Chobot Agata P , Jarosz-Chobot Przemysława , Myśliwiec Małgorzata , Makowska Iwona , Kalenik Anna , Zamarlik Monika , Wolańczyk Tomasz , Fendler Wojciech , Butwicka Agnieszka 
Published: December 2023

IntroductionAttention deficit hyperactivity disorder (ADHD) affects 5%–10% of paediatric population and is reportedly more common in children with type 1 diabetes (T1D), exacerbating its clinical course. Proper treatment of ADHD in such patients may thus provide neurological and metabolic benefits. To test this, we designed a non-commercial second phase clinical trial comparing the impact of different pharmacological interventions for ADHD in children with T1D.Methods and analysisThis is a multicentre, randomised, open-label, cross-over clinical trial in children and adolescents with ADHD and T1D. The trial will be conducted in four reference paediatric diabetes centres in Poland. Over 36 months, eligible patients with both T1D and ADHD (aged 8–16.5 years, T1D duration >1 year) will be offered participation. Patients’ guardians will undergo online once-weekly training sessions behaviour management for 10 weeks. Afterward, children will be randomised to methylphenidate (long-release capsule, doses 18-36-54 mg) versus lisdexamphetamine (LDX, 30-50-70 mg). Pharmacotherapy will continue for 6 months before switching to alternative medication. Throughout the trial, the participants will be evaluated every 3 months by their diabetologist and online psychological assessments. The primary endpoint (ADHD symptom severity, Conners 3.0 questionnaire) will be assessed by a blinded investigator. Secondary endpoints will include HbA1c, continuous glucose monitoring indices and quality-of-life (PedsQL).Ethics and disseminationThe trial is approved by Bioethical Committee at Medical University of Lodz and Polish regulatory agency (RNN/142/22/KE, UR/DBL/D/263/2022). The results will be communicated to the research and clinical community, and Polish agencies responsible for healthcare policy. Patient organisations focused on paediatric T1D will be notified by a consortium member. We hope to use the trial’s results to promote collaboration between mental health professionals and diabetes teams, evaluate the economic feasibility of using LDX in patients with both diseases and the long run improve ADHD treatment in children with T1D.Trial registration numbersEU Clinical Trials Register (EU-CTR, 2022-001906-24) andNCT05957055.
‘I wouldn’t trust it …’ Digital transformation of young people’s sexual health services: a systems-informed qualitative enquiry
Authors: Bennett Clare , Kelly Daniel , Dunn Catherine , Musa Massirfufulay Kpehe , Young Honor , Couzens Zoë , McSorley John , Jones Emma 
Published: December 2023

IntroductionDigital sexual health technologies for young people, such as websites, texting services and apps, could address some of the sexual health inequalities that many experience, since they have the potential to overcome concerns associated with traditional clinic based services such as embarrassment, privacy and accessibility. However, they are currently under-utilised internationally.MethodsUsing complexity theory and systems thinking as a theoretical framework, this qualitative descriptive study sought to explore the acceptability of digital sexual health technologies for 16–18 year olds. Data generation with 10 sexual health nurses with experience of digital service delivery took the form of minimally structured online one-to-one interviews lasting between 20 and 50 min. Focus groups of up to eight young people or individual interviews were used to explore 32 16–18 year olds’ perspectives. Interviews lasted between 18 and 48 min. Both datasets were analysed using Braun and Clarke’s reflexive thematic analysis.ResultsThree themes emerged from each dataset. Nurses’ themes were: (1) digital sexual health services can be more comfortable for young people, (2) digital sexual health services can be complimentary to clinic visits but do not replace them and (3) challenges exist in providing sexual health services to young people through digital technologies. The young people’s themes were: (1) sexual health is a ‘difficult issue’, (2) young people have specific expectations yet a desire for choice and (3) digital health interventions are not a panacea.ConclusionsWhile digital sexual health interventions hold great potential, they need to be integral to the wider systems in which both young people and sexual health promotion services operate, otherwise there is a risk that their impact will be compromised. Collaborative approaches that connect causal factors and policy objectives and involve full engagement with all stakeholders are more likely to be efficacious.