bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Efficacy of Deep Transcranial Magnetic Stimulation for Management of Emotional Dysregulation in Children and Adolescents with Externalizing Behavior Disorders: Protocol of a Transdiagnostic Sham Controlled fMRI Study
Authors: Shukla Devangi , Sharma Pooja , Roy Chandramouli , Goyal Nishant 
Published: March 2024

Background: High-frequency deep transcranial magnetic stimulation (dTMS) on the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) has been known to be effective in modulating emotional experience but not studied in children and adolescents with externalizing behavior disorders (EBDs). We present a novel protocol for a study that aims to assess the safety and efficacy of adjuvant dTMS in managing emotional dysregulation in EBDs in children and adolescents. Methods: The trial is prospectively registered in the Clinical Trial Registry of India (CTRI) at www.ctri.nic.in with registration number: CTRI/2023/03/050701. In total, 40 subjects with age less than 18 years with EBDs would be randomized into two groups (active and sham dTMS); receiving 15 sessions of high-frequency dTMS, each, over 3 weeks. The subjects and rater would remain blind to treatment allocation. Assessments would be done at baseline and immediately after completion of the treatment using the Child Behavior Checklist (CBCL), Difficulty in Emotional Regulation Scale (DERS), Modified Overt Aggression Scale (MOAS), Affective Reactivity Index (ARI), Barratt’s Impulsivity Scale (BIS), Drug Abuse Screening Test (DAST), Children Global Assessment Scale (CGAS), and Clinical Global Impression (CGI). A checklist for side effects will be administered following each session in both groups. Result: Data shall be analyzed utilizing the statistical software Statistical Package for Social Sciences for outcome variables as defined for the purpose of the study. Safety of dTMS in young subjects as assessed by TMSens_Q and reduction in scores of DERS would be primary outcome variables. Functional Magnetic Resonance Imaging (fMRI) task-based assessment of the difference in activation of mPFC and ACC at baseline and after application of dTMS and reduction in scores of BIS, ARI, MOAS, CGI, and CGAS would be measured as secondary outcome variables. Conclusion: The study’s results are going to provide insight into potential role of dTMS in addressing emotional dysregulation in EBDs in children and adolescents adding one more tool to the armamentarium.
Impact of SARS-COV-2 Infection on Maternal, Obstetric and Neonatal Outcomes in a Cohort of Vaccinated Women: A Pilot Study
Authors: Cruz-Calvente María , Rueda-Medina Blanca , Gil-Gutiérrez Rocío , Medina-Martínez Irene , Gómez-Urquiza José L. , Correa-Rodríguez María 
Published: March 2024

We aimed to investigate the impact of COVID-19 infection on maternal characteristics and obstetric and neonatal outcomes in a cohort of women in labor previously vaccinated who tested positive for SARS-CoV-2 infection, compared to aged-matched healthy controls. A retrospective case-control study was conducted among 66 women in labor. Clinical data were obtained from medical records. The attendance rates at childbirth and parenting classes, as well as the implementation of a birth plan, were significantly lower in the COVID-19 infection group (6.1% vs. 48.5%, <0.001; 6.1% vs. 33.3%, p = .005, respectively). Women with COVID-19 had a higher prevalence of prolonged postpartum hospital stay (33.3% vs. 9.1%, p = .016), and significantly higher prevalence of spontaneous preterm birth (27.3% vs. 1.09%, p = .006). Breastfeeding within the first 24 hr was also lower in women with COVID-19 (72.7% vs. 97.0%, p = .006). Maternal characteristics and neonatal outcomes are influenced by COVID-19 infection in vaccinated women. Complications include spontaneous preterm birth, prolonged postpartum hospital stay, and lack of breastfeeding within the first 24 hr. Childbirth education, parenting classes and implementing a birth plan may be associated with a decreased risk of COVID-19 infection.
Edoxaban for the treatment of hypercoagulability and cerebral thromboembolism associated with cancer: A randomized clinical trial of biomarker targets
Authors: Chung Jong-Won , Hwang Jaechun , Kim Hyung Jun , Seo Woo-Keun , Ahn Myung-Ju , Saver Jeffrey L , Bang Oh Young 
Published: March 2024

Background: This study aimed compare efficacy of edoxaban and enoxaparin upon biomarkers of hypercoagulability in patients with cancer-related embolic stroke of undetermined source (ESUS). Methods: In this open-label, randomized, pilot trial, patients with cancer-related ESUS within 30 days of diagnosis were randomly assigned (1:1) to receive edoxaban (60 mg once daily) or enoxaparin (1 mg/kg twice daily) for 90 days. The primary endpoint was interval change of serum D-dimer level between days 0 and 7. The secondary endpoints were microembolic signals detected by transcranial Doppler at 7 and 90 days, the modified Rankin scale score, and stroke recurrence during 90 days. Safety outcomes included major bleeding and all-cause death at 90 days. Results: Of 303 patients with ischemic stroke and cancer, 40 fully met enrollment criteria and were randomized. Baseline D-dimer levels were numerically higher in the edoxaban group (22.9 ± 15.9 μg/mL vs 16.9 ± 16.9 μg/mL). D-dimer level change (%) between days 0 and 7 was similar in the two groups (53.2 ± 25.7 vs 52.2 ± 52.0; P = 0.11). Microembolic signals were detected in 41.1% and 43.8% at baseline, 41.2% and 42.9% at day 7, and 25.0% and 28.6% at day 90 in the edoxaban and enoxaparin groups, respectively. Non-significantly higher major bleeding (35.0% vs 10.0%, P = 0.06) and 90-day mortality (40.0% vs 25.0%, P = 0.31) were noted in the edoxaban group. Conclusion: Edoxaban and enoxaparin were comparable with respect to the biomarkers of hypercoagulability and cerebral thromboembolism. Larger trials are warranted to compare effects of edoxaban and enoxaparin upon recurrent stroke and major bleeding in patients with cancer-related ESUS. Trial registration: clinicaltrials.gov Identifier: NCT03570281 ( https://clinicaltrials.gov/ct2/show/NCT03570281 )
Association of LDL-cholesterol <1.8 mmol/L and statin use with the recurrence of intracerebral hemorrhage
Authors: Lee Tsz-Ching , Leung William CY , Ho Chun , Chiu Megan WL , Leung Ian YH , Wong Yuen-Kwun , Roxanna Liu KC , Sum Christopher HF , Lui David TW , Cheung Raymond TF , Leung Gilberto KK , Chan Koon-Ho , Teo Kay-Cheong , Lau Kui-Kai 
Published: March 2024

Background: Recent intensive low-density lipoprotein cholesterol (LDL-C) lowering trials, including FOURIER, ODYSSEY OUTCOMES, and Treat Stroke to Target (TST) trials, have mostly refuted the concern surrounding statin use, LDL-C lowering, and intracerebral hemorrhage (ICH) risk. However, the results from these trials may not be fully applied to ICH survivors, as the populations studied were mainly patients without prior ICH, in whom the inherent ICH risk is more than 10 times lower than that of ICH survivors. Although available literature on statin use after ICH has demonstrated no excess risk of recurrent ICH, other potential factors that may modify ICH risk, especially hypertension control and ICH etiology, have not generally been considered. Notably, data on LDL-C levels following ICH are lacking. Aims: We aim to investigate the association between LDL-C levels and statin use with ICH risk among ICH survivors, and to determine whether the risk differed with patients’ characteristics, especially ICH etiology. Methods: Follow-up data of consecutive spontaneous ICH survivors enrolled in the University of Hong Kong prospective stroke registry from 2011 to 2019 were retrospectively analyzed. ICH etiology was classified as cerebral amyloid angiopathy (CAA) using the modified Boston criteria or hypertensive arteriopathy, while the mean follow-up LDL-C value was categorized as <1.8 or ⩾1.8 mmol/L. The primary endpoint was recurrent ICH. The association of LDL-C level and statin use with recurrent ICH was determined using multivariable Cox regression. Pre-specified subgroup analyses were performed, including based on ICH etiology and statin prescription. Follow-up blood pressure was included in all the regression models. Results: In 502 ICH survivors (mean age = 64.2 ± 13.5 years, mean follow-up LDL-C = 2.2 ± 0.6 mmol/L, 28% with LDL-C <1.8 mmol/L), 44 had ICH recurrence during a mean follow-up of 5.9 ± 2.8 years. Statin use after ICH was not associated with recurrent ICH (adjusted hazard ratio (AHR) = 1.07, 95% confidence interval (CI) = 0.57–2.00). The risk of ICH recurrence was increased for follow-up LDL-C <1.8 mmol/L (AHR = 1.99, 95% CI = 1.06–3.73). This association was predominantly observed in ICH attributable to CAA (AHR = 2.52, 95% CI = 1.06–5.99) and non-statin users (AHR = 2.91, 95% CI = 1.08–7.86). Conclusion: The association between post-ICH LDL-C <1.8 mmol/L and recurrent ICH was predominantly observed in CAA patients and those with intrinsically low LDL-C (non-statin users). While statins can be safely prescribed in ICH survivors, LDL-C targets should be individualized and caution must be exercised in CAA patients.
Immobilisation of chromium in magnesium carbonate minerals
Authors: Lacinska Alicja M. , Bateman Keith , Chenery Simon , Kemp Simon J , Liddy Thomas , Rushton Jeremy C , Saha Dipankar , Schroeder Sven L.M. 
Published: March 2024

AbstractHexavalent chromium (Cr6+) is a toxic carcinogenic pollutant that might be released by the mining and processing of ultramafic rocks and nickel laterites and which requires permanent removal from the contaminated biosphere. Ultramafic material can also serve as a feedstock for the sequestration of CO2 resulting from the growth of new minerals, raising the intriguing proposition of integrated sequestration of both pollutants, CO2 and chromium, into magnesium carbonates. Such a synergistic process downstream of ore recovery and mineral processing could be an elegant proposition for more sustainable utilisation and management of the Earth's resources. We have therefore carried out an experimental and microanalytical study to investigate potentially suitable carbonate minerals. Uptake of chromium in carbonate phases was determined, followed by identification of the crystalline phases and characterisation of the local structural environment around the incorporated chromium centres. The results suggest that neither nesquehonite nor hydromagnesite have the structural capacity to incorporate Cr6+ or Cr3+ significantly at room temperature. We therefore propose that further research into this technology should focus on laboratory assessments of other phases, such as layered double hyroxides, that have a natural structural capacity to uptake both chromium and CO2.
Differential effects of itacitinib, fedratinib, and ruxolitinib in mouse models of hemophagocytic lymphohistiocytosis
Authors: Keenan Camille , Albeituni Sabrin , Oak Ninad , Stroh Alexa , Tillman Heather S. , Wang Yingzhe , Freeman Burgess B. , Alemán-Arteaga Silvia , Meyer Lauren K. , Woods Rolanda , Verbist Katherine C. , Zhou Yinmei , Cheng Cheng , Nichols Kim E. 
Published: March 2024

Abstract
Hemophagocytic lymphohistiocytosis (HLH) comprises a severe hyperinflammatory phenotype driven by the overproduction of cytokines, many of which signal via the JAK/STAT pathway. Indeed, the JAK1/2 inhibitor ruxolitinib has demonstrated efficacy in preclinical studies and early-phase clinical trials in HLH. Nevertheless, concerns remain for ruxolitinib-induced cytopenias, which are postulated to result from the blockade of JAK2-dependent hematopoietic growth factors. To explore the therapeutic effects of selective JAK inhibition in mouse models of HLH, we carried out studies incorporating the JAK1 inhibitor itacitinib, JAK2 inhibitor fedratinib, and JAK1/2 inhibitor ruxolitinib. All 3 drugs were well-tolerated and at the doses tested, they suppressed interferon-gamma (IFN-γ)–induced STAT1 phosphorylation in vitro and in vivo. Itacitinib, but not fedratinib, significantly improved survival and clinical scores in CpG–induced secondary HLH. Conversely, in primary HLH, in which perforin-deficient (Prf1−/−) mice are infected with lymphocytic choriomeningitis virus (LCMV), itacitinib, and fedratinib performed suboptimally. Ruxolitinib demonstrated excellent clinical efficacy in both HLH models. RNA-sequencing of splenocytes from LCMV-infected Prf1−/− mice revealed that itacitinib targeted inflammatory and metabolic pathway genes in CD8 T cells, whereas fedratinib targeted genes regulating cell proliferation and metabolism. In monocytes, neither drug conferred major transcriptional impacts. Consistent with its superior clinical effects, ruxolitinib exerted the greatest transcriptional changes in CD8 T cells and monocytes, targeting more genes across several biologic pathways, most notably JAK-dependent proinflammatory signaling. We conclude that JAK1 inhibition is sufficient to curtail CpG-induced disease, but combined inhibition of JAK1 and JAK2 is needed to best control LCMV-induced immunopathology.
Pooled analysis of pralatrexate single-agent studies in patients with relapsed/refractory peripheral T-cell lymphoma
Authors: O’Connor Owen A. , Ko Bor-Sheng , Wang Ming-Chung , Maruyama Dai , Song Yuqin , Yeoh Ee-Min , Manamley Nick , Tobinai Kensei 
Published: March 2024

Abstract
Patients with relapsed or refractory (R/R) mature natural killer cell and T-cell lymphoma have limited treatment options. To evaluate pralatrexate’s performance and factors influencing its safety and efficacy in R/R peripheral T-cell lymphoma (PTCL), we performed a pooled analysis of data from 4 similarly designed, regulatory-mandated prospective clinical trials. Of 221 patients (median age, 59 years; 67.0% male) in the study population, 48.9% had PTCL not otherwise specified (PTCL-NOS), 21.3% angioimmunoblastic T-cell lymphoma, and 11.8% ALK-negative anaplastic large cell lymphoma (ALCL). Patients received pralatrexate for a median of 2.56 months (range, 0.03-24.18) and had a 40.7% objective response rate with a median duration of response of 9.1 months, progression-free survival 4.6 months, and overall survival 16.3 months. The most common treatment-related all-grade adverse events were stomatitis, thrombocytopenia, white blood cell count decrease, pyrexia, and vomiting. Subgroup exploratory analyses suggest improved efficacy with 1 prior line of chemotherapy vs 2 or ≥4 prior lines; PTCL-NOS or ALCL vs transformed mycosis fungoides; chemotherapy and transplant before pralatrexate vs chemotherapy alone or chemotherapy with other nontransplant treatments. In conclusion, these pooled analysis results further support using pralatrexate in patients with R/R PTCL. Prospective studies are needed to confirm the findings of subgroups analyses.
The impact of vitamin D on type 2 diabetes management: boosting PTP1B gene expression and physical activity benefits in rats
Authors: Khaledi Kimya , Hoseini Rastegar , Gharzi Ahmad 
Published: March 2024

Abstract
Background
The protein tyrosine phosphatase 1B (PTP1B) plays a crucial role in the development of insulin resistance. Aerobic training (AT) and vitamin D (Vit D) supplementation have been shown to individually improve glucose tolerance and diabetes-related factors. However, the impact of their combined effect on PTP1B gene expression and serum irisin in the visceral adipose tissue remains unknown. This study aims to investigate whether 8 weeks of combined AT with Vit D supplementation can improve the expression of PTP1B in adipose tissue and serum irisin in obese rats with type 2 diabetes (T2D).

Methods
Fifty male Wistar rats were divided into two groups: diabetic (n = 40) and non-diabetic (ND; n = 10). The diabetic rats were further divided into four groups: aerobic training with vitamin D supplementation (D + AT + Vit D; n = 10), aerobic training only (D + AT; n = 10), vitamin D supplementation only (D + Vit D; n = 10), and control (D + C; n = 10). The D + Vit D and D + AT + Vit D groups received 5000 IU of vitamin D via injection once a week, while the D + AT and D + C groups received sesame oil. Diabetes was induced in all groups except the nondiabetic group by intraperitoneal (IP) injection of streptozotocin. At the end of the intervention, blood and adipose tissue samples were collected, and RNA was extracted from adipose tissue for real-time PCR analysis of PPTP1B gene expression.

Results
There was an increase in serum Vit D and irisin levels and a decrease in HOMA-IR and PTP1B gene expression in the diabetic rat model treated with D + AT and injected with 50,000 IU/kg/week of Vit D. Comparatively, when treated with D + AT + Vit D, the downregulation of PTP1B was significantly higher (p = 0.049; p = 0.004), and there was a significant increase in irisin (p = 0.010; p = 0.001).

Conclusion
The present study shows that the combined AT and Vit D supplementation positively impacts the expression of PTP1B in adipose tissue and serum irisin in rats with T2D. These findings suggest that combining AT with Vit D supplementation can provide a new and effective strategy to improve glucose tolerance and diabetes-related factors in individuals with T2D by regulating the expression of PTP1B in adipose tissue and promoting the synthesis of beneficial irisin protein.
A chromosome level genome assembly of Pseudoroegneria Libanotica reveals a key Kcs gene involves in the cuticular wax elongation for drought resistance
Authors: Zhai Xingguang , Wu Dandan , Chen Chen , Yang Xunzhe , Cheng Shaobo , Sha Lina , Deng Shuhan , Cheng Yiran , Fan Xing , Kang Houyang , Wang Yi , Liu Dengcai , Zhou Yonghong , Zhang Haiqin 
Published: March 2024

Abstract
Background
The genus Pseudoroegneria (Nevski) Löve (Triticeae, Poaceae), whose genome symbol was designed as “St”, accounts for more than 60% of perennial Triticeae species. The diploid species Psudoroegneria libanotica (2n = 14) contains the most ancient St genome, exhibited strong drought resistance, and was morphologically covered by cuticular wax on the aerial part. Therefore, the St-genome sequencing data could provide fundamental information for studies of genome evolution and reveal its mechanisms of cuticular wax and drought resistance.

Results
In this study, we reported the chromosome-level genome assembly for the St genome of Pse. libanotica, with a total size of 2.99 Gb. 46,369 protein-coding genes annotated and 71.62% was repeat sequences. Comparative analyses revealed that the genus Pseudoroegneria diverged during the middle and late Miocene. During this period, unique genes, gene family expansion, and contraction in Pse. libanotica were enriched in biotic and abiotic stresses, such as fatty acid biosynthesis which may greatly contribute to its drought adaption. Furthermore, we investigated genes associated with the cuticular wax formation and water deficit and found a new Kcs gene evm.TU.CTG175.54. It plays a critical role in the very long chain fatty acid (VLCFA) elongation from C18 to C26 in Pse. libanotica. The function needs more evidence to be verified.

Conclusions
We sequenced and assembled the St genome in Triticeae and discovered a new KCS gene that plays a role in wax extension to cope with drought. Our study lays a foundation for the genome diversification of Triticeae species and deciphers cuticular wax formation genes involved in drought resistance.
Effect of hydrogen sulfide (H2S) on the growth and development of tobacco seedlings in absence of stress
Authors: Dai Jingcheng , Wen Dingxin , Li Hao , Yang Jingpeng , Rao Xiongfei , Yang Yong , Yang Jiangke , Yang Chunlei , Yu Jun 
Published: March 2024

Abstract
Background
Hydrogen sulfide (H2S) is a novel signaling molecule involved in the growth and development of plants and their response to stress. However, the involvement of H2S in promoting the growth and development of tobacco plants is still unclear.

Results
In this study, we explored the effect of pre-soaking or irrigating the roots of tobacco plants with 0.0, 2.0, 4.0, 6.0, and 8.0 mM of sodium hydrosulfide (NaHS) on endogenous H2S production, antioxidant enzymatic and cysteine desulfhydrase activities, seed germination, agronomic traits, photosynthetic pigments contents, and root vigor. The results revealed that exogenous NaHS treatment could significantly promote endogenous H2S production by inducing gene expression of D/L-CD and the activities of D/L-CD enzymes. Additionally, a significant increase in the agronomic traits and the contents of photosynthetic pigments, and no significant difference in carotenoid content among tobacco plants treated with 0.0 to 8.0 mM of NaHS was observed. Additionally, a significant increase in the germination speed, dry weight, and vigor of tobacco seeds, whereas no significant effect on the percentage of seed germination was observed on NaHS treatment. Furthermore, NaHS treatment could significantly increase the activity of superoxide dismutase (SOD) and peroxidase (POD) enzymes, which reduces damage due to oxidative stress by maintaining reactive oxygen species homeostasis.

Conclusions
These results would aid in enhancing our understanding of the involvement of H2S, a novel signaling molecule to promote the growth and development of tobacco plants.
Differential responses of two fenugreek (Trigonella foenum-graecum L.) landraces pretreated with melatonin to prolonged drought stress and subsequent recovery
Authors: Maleki Masoud , Shojaeiyan Abdolali , Mokhtassi-Bidgoli Ali 
Published: March 2024

Abstract
Background
Drought impairs growth, disturbs photosynthesis, and induces senescence in plants, which results in crop productivity reduction and ultimately jeopardizes human food security. The objective of this study was to determine major parameters associated with drought tolerance and recovery ability of fenugreek (Trigonella foenum-graecum L.), by examining differential biochemical and phenological responses and underlying enzyme activities as well as melatonin roles during drought stress and re-watering for two contrasting landraces. Moreover, the relative expression of three key genes involved in the biosynthesis pathway of diosgenin, including SQS, CAS, and BG, was investigated.

Results
Depending on the conditions, drought stress enhanced the activity of antioxidant enzymes and the osmoregulating compounds, non-enzymatic antioxidants, hydrogen peroxide content, and lipid peroxidation levels in most cases. Severe drought stress accelerated flowering time in Shushtar landrace (SHR) but had no significant effects on Varamin (VR). Pretreatment with melatonin delayed flowering time in SHR and caused high drought resistance in this landrace. Furthermore, melatonin significantly enhanced drought adaptability in VR by improving plant recovery ability.

Discussion
Based on our results plants’ responses to drought stress and melatonin pretreatment were completely landrace-specific. Drought stress caused an increase in the relative expression of CAS gene and ultimately the accumulation of steroidal saponins in SHR. Melatonin compensated for the decrease in biomass production due to drought stress and finally increased steroidal saponins performance in SHR. Our study showed that melatonin can improve drought stress and recovery in fenugreek, but different factors such as genotype, melatonin concentration, and plant age should be considered.