bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electric field stimulation boosts neuronal differentiation of neural stem cells for spinal cord injury treatment via PI3K/Akt/GSK-3β/β-catenin activation
Authors: Liu Qian , Telezhkin Vsevolod , Jiang Wenkai , Gu Yu , Wang Yan , Hong Wei , Tian Weiming , Yarova Polina , Zhang Gaofeng , Lee Simon Ming-yuen , Zhang Peng , Zhao Min , Allen Nicholas D. , Hirsch Emilio , Penninger Josef , Song Bing 
Published: January 2023

Abstract
Background
Neural stem cells (NSCs) are considered as candidates for cell replacement therapy in many neurological disorders. However, the propensity for their differentiation to proceed more glial rather than neuronal phenotypes in pathological conditions limits positive outcomes of reparative transplantation. Exogenous physical stimulation to favor the neuronal differentiation of NSCs without extra chemical side effect could alleviate the problem, providing a safe and highly efficient cell therapy to accelerate neurological recovery following neuronal injuries.

Results
With 7-day physiological electric field (EF) stimulation at 100 mV/mm, we recorded the boosted neuronal differentiation of NSCs, comparing to the non-EF treated cells with 2.3-fold higher MAP2 positive cell ratio, 1.6-fold longer neuronal process and 2.4-fold higher cells ratio with neuronal spontaneous action potential. While with the classical medium induction, the neuronal spontaneous potential may only achieve after 21-day induction. Deficiency of either PI3Kγ or β-catenin abolished the above improvement, demonstrating the requirement of the PI3K/Akt/GSK-3β/β-catenin cascade activation in the physiological EF stimulation boosted neuronal differentiation of NSCs. When transplanted into the spinal cord injury (SCI) modelled mice, these EF pre-stimulated NSCs were recorded to develop twofold higher proportion of neurons, comparing to the non-EF treated NSCs. Along with the boosted neuronal differentiation following transplantation, we also recorded the improved neurogenesis in the impacted spinal cord and the significantly benefitted hind limp motor function repair of the SCI mice.

Conclusions
In conclusion, we demonstrated physiological EF stimulation as an efficient method to boost the neuronal differentiation of NSCs via the PI3K/Akt/GSK-3β/β-catenin activation. Pre-treatment with the EF stimulation induction before NSCs transplantation would notably improve the therapeutic outcome for neurogenesis and neurofunction recovery of SCI.
The burden of disease of fatal and non-fatal burn injuries for the full spectrum of care in the Netherlands
Authors: Spronk Inge , van Baar Margriet E. , Verheij Robert A. , Panneman Martien J. , Dokter Jan , Polinder Suzanne , Haagsma Juanita A. 
Published: January 2023

Abstract
Background
A comprehensive overview of the burden of disease of burns for the full spectrum of care is not available. Therefore, we estimated the burden of disease of burns for the full spectrum in the Netherlands in 2018, and explored whether the burden of disease changed over the past 5 years (2014-2018).

Methods
Data were collected at four levels: general practice, emergency department, hospital, and mortality data. For each level, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life-years (DALY) were estimated using a tailored methodology.

Results
Burns resulted in a total of 9278 DALYs in the Netherlands in 2018, comprising of 7385 YLDs (80%) and 1892 YLLs (20%). Burn patients who visited the general practice contributed most DALYs (64%), followed by deceased burn patients (20%), burn patients admitted to hospital (14%) and those treated at the emergency department (2%). The burden of disease was comparable in both sexes (4734 DALYs (51%) for females; 4544 DALYs (49%) for males), though the distribution of DALYs by level of care varied; females contributed more DALYs at the general practice level, and males at all other levels of care. Among children boys 0-4 years had the highest burden of disease (784 DALYs (9%)), and among adults, females 18-34 years old (1319 DALYs (14.2%)) had the highest burden of disease. Between 2014 and 2018 there was a marginal increase of 0.8% in the number of DALYs.

Conclusions
Burns cause a substantial burden of disease, with burns requiring care at the general practice level contributing most DALYs. Information on burden of burns by the full level of care as well as by subgroup is important for the development of tailored burn prevention strategies, and the updated figures are recommended to be used for priority setting and resource allocation.
p85S6K sustains synaptic GluA1 to ameliorate cognitive deficits in Alzheimer’s disease
Authors: Li Jia-Bing , Hu Xiao-Yu , Chen Mu-Wen , Xiong Cai-Hong , Zhao Na , Ge Yan-Hui , Wang Hao , Gao Xiao-Ling , Xu Nan-Jie , Zhao Lan-Xue , Yu Zhi-Hua , Chen Hong-Zhuan , Qiu Yu 
Published: January 2023

Abstract
Background
Ribosomal protein S6 kinase 1 (S6K1) is a serine–threonine kinase that has two main isoforms: p70S6K (70-kDa isoform) and p85S6K (85-kDa isoform). p70S6K, with its upstream mammalian target of rapamycin (mTOR), has been shown to be involved in learning and memory and participate in the pathophysiology of Alzheimer’s disease (AD). However, the function of p85S6K has long been neglected due to its high similarity to p70S6k. The role of p85S6K in learning and memory is still largely unknown.

Methods
We fractionated the postsynaptic densities to illustrate the differential distribution of p85S6K and p70S6K. Coimmunoprecipitation was performed to unveil interactions between p85S6K and the GluA1 subunit of AMPA receptor. The roles of p85S6K in synaptic targeting of GluA1 and learning and memory were evaluated by specific knockdown or overexpression of p85S6K followed by a broad range of methodologies including immunofluorescence, Western blot, in situ proximity ligation assay, morphological staining and behavioral examination. Further, the expression level of p85S6K was measured in brains from AD patients and AD model mice.

Results
p85S6K, but not p70S6K, was enriched in the postsynaptic densities. Moreover, knockdown of p85S6K resulted in defective spatial and recognition memory. In addition, p85S6K could interact with the GluA1 subunit of AMPA receptor through synapse-associated protein 97 and A-kinase anchoring protein 79/150. Mechanistic studies demonstrated that p85S6K could directly phosphorylate GluA1 at Ser845 and increase the amount of GluA1 in synapses, thus sustaining synaptic function and spine densities. Moreover, p85S6K was found to be specifically decreased in the synaptosomal compartment in the brains of AD patients and AD mice. Overexpression of p85S6K ameliorated the synaptic deficits and cognitive impairment in transgenic AD model mice.

Conclusions
These results strongly imply a significant role for p85S6K in maintaining synaptic and cognitive function by interacting with GluA1. The findings provide an insight into the rational targeting of p85S6K as a therapeutic potential for AD.
Challenges to joint planning, monitoring, and evaluation for nutrition-sensitive agriculture in Ethiopia: an exploratory qualitative study
Authors: Bezabih Afework Mulugeta , Kahsay Znabu Hadush , Kahsay Amaha , Bekele Abate , Seid Omer , Asfaw Selemawit , Gebrearegay Freweeini , Tadesse Kidane , Bazzano Alessandra N. , Jogo Wellington , Covic Namukolo , Busse Heidi 
Published: January 2023

Abstract
Background
Nutrition-sensitive agriculture is an effective multi-sectoral approach to address the underlying causes of malnutrition. However, successful implementation requires the involvement of different sectors to jointly plan, monitor, and evaluate key activities, which is often challenged by contextual barriers. Previous studies in Ethiopia have not adequately explored these contextual barriers. Hence, the current study aimed to qualitatively explore the challenges to joint planning, monitoring, and evaluation for nutrition-sensitive agriculture among sectors in Ethiopia.

Methods
A qualitative exploratory study was conducted in Tigray and Southern Nations, Nationalities, and Peoples (SNNP) of Ethiopia regional states in 2017. Ninety-four key informants were purposively selected from government agencies primarily in health and agriculture, from local (kebele) to national levels, and ranging from academic organizations, research institutions, and implementing partners. Researchers developed a semi-structured guide and conducted key informant interviews which were audiotaped, transcribed verbatim in local language, and translated to English. All transcriptions were imported into ATLAS.ti Version 7.5 software for coding and analysis. The data analysis followed an inductive approach. Transcriptions were coded line by line; then similar codes were grouped into categories. Subsequently, non-repetitive themes were identified from the categories using thematic analysis methodology.

Results
The following themes were identified as challenges that hinder joint planning, monitoring, and evaluation to link nutrition to agriculture: (1) limited capacity, (2) workload in home sector (agriculture or nutrition), (3) lack of attention to nutrition interventions, (4) inadequate supportive supervision, (5) problematic reporting system, and (6) weak technical coordinating committees.

Conclusions and recommendations
Gaps in human and technical resources, limited attention from different sectors, and absence of routine monitoring data hindered joint planning, monitoring, and evaluation activities for nutrition-sensitive agriculture in Ethiopia. Short-term and long-term training for experts and intensification of supportive supervision may address gaps in capacity. Future studies should address whether routine monitoring and surveillance in nutrition-sensitive multi-sectoral activities provides long-term improvement in outcomes.
Differential effects of mutations of POPDC proteins on heteromeric interaction and membrane trafficking
Authors: Swan Alexander H. , Schindler Roland F. R. , Savarese Marco , Mayer Isabelle , Rinné Susanne , Bleser Felix , Schänzer Anne , Hahn Andreas , Sabatelli Mario , Perna Francesco , Chapman Kathryn , Pfuhl Mark , Spivey Alan C. , Decher Niels , Udd Bjarne , Tasca Giorgio , Brand Thomas 
Published: January 2023

AbstractThe Popeye domain containing (POPDC) genes encode sarcolemma-localized cAMP effector proteins. Mutations in blood vessel epicardial substance (BVES) also known as POPDC1 and POPDC2 have been associated with limb-girdle muscular dystrophy and cardiac arrhythmia. Muscle biopsies of affected patients display impaired membrane trafficking of both POPDC isoforms. Biopsy material of patients carrying mutations in BVES were immunostained with POPDC antibodies. The interaction of POPDC proteins was investigated by co-precipitation, proximity ligation, bioluminescence resonance energy transfer and bimolecular fluorescence complementation. Site-directed mutagenesis was utilised to map the domains involved in protein–protein interaction. Patients carrying a novel homozygous variant, BVES (c.547G > T, p.V183F) displayed only a skeletal muscle pathology and a mild impairment of membrane trafficking of both POPDC isoforms. In contrast, variants such as BVES p.Q153X or POPDC2 p.W188X were associated with a greater impairment of membrane trafficking. Co-transfection analysis in HEK293 cells revealed that POPDC proteins interact with each other through a helix-helix interface located at the C-terminus of the Popeye domain. Site-directed mutagenesis of an array of ultra-conserved hydrophobic residues demonstrated that some of them are required for membrane trafficking of the POPDC1–POPDC2 complex. Mutations in POPDC proteins that cause an impairment in membrane localization affect POPDC complex formation while mutations which leave protein–protein interaction intact likely affect some other essential function of POPDC proteins.
Population pharmacokinetics and limited sampling strategy for therapeutic drug monitoring of mycophenolate mofetil in Japanese patients with lupus nephritis
Authors: Mizaki Tomoko , Nobata Hironobu , Banno Shogo , Yamaguchi Makoto , Kinashi Hiroshi , Iwagaitsu Shiho , Ishimoto Takuji , Kuru Yukiko , Ohnishi Masafumi , Sako Ken-ichi , Ito Yasuhiko 
Published: January 2023

Abstract
Background
Mycophenolate mofetil (MMF), a prodrug of the immunosuppressive agent mycophenolic acid (MPA), is difficult to administer because of the pharmacokinetic complexity of MPA. Although dosage adjustment according to the 12-h area under the concentration–time curve (AUC0-12) is thought to be desirable, multiple blood samplings for AUC calculation may pose a clinical challenge. A limited sampling strategy (LSS) would provide a solution; however, little is known about MPA pharmacokinetics in lupus nephritis patients, especially in those with Asian backgrounds, or few, if any, LSSs are reported for them.

Methods
Thirty-four adult Japanese patients receiving MMF for lupus nephritis were examined retrospectively. MPA pharmacokinetics were investigated, and a PPK model was developed using Phoenix® NLME™ software. Single and double blood sampling strategies from Bayesian estimation using the PPK model and from multiple linear regression were compared. Tolerability was also evaluated.

Results
In the pharmacokinetic analysis, renal function and serum albumin had significant effects on dose-normalized AUC0-12; and serum albumin, concomitant proton pump inhibitor (PPI) and iron/magnesium oxide did on dose-normalized maximum concentration. As a PPK model, a two-compartment model was developed with a transit absorption model and first-order elimination, in which creatinine clearance and serum albumin were covariates for MPA clearance. The double sampling strategy at 1 and 4 h by multiple linear regression showed the best agreement with the observed AUC0-12 (r2 = 0.885). Of the single sampling strategies, the one at 6 h by Bayesian estimation performed best (r2 = 0.769). The tolerability evaluation showed that correlations were suggested for gastrointestinal involvement.

Conclusions
The present study developed the first PPK model of MPA for Japanese lupus nephritis patients. As for LSSs, a double sampling strategy at 1 and 4 h by multiple linear regression would work best; when only a single blood sampling is allowed, a strategy at 6 h by Bayesian estimation using the PPK model developed in this study would be best. The LSSs good enough for clinical use may facilitate safer, more effective, and individualized therapy.
Transient loss of consciousness immediately after total pancreatectomy for pancreatic metastases from renal cell carcinoma: a case report
Authors: Masuda Yasutaka , Kiritani Sho , Arita Junichi , Ichida Akihiko , Kawaguchi Yoshikuni , Akamatsu Nobuhisa , Kaneko Junichi , Hasegawa Kiyoshi 
Published: January 2023

Abstract
Background
Total pancreatectomy (TP) is often selected for treatment of various pancreatic diseases. However, the resultant lack of autoregulation of glycometabolism necessitates careful postoperative management.

Case presentation
A 77-year-old man who had undergone right nephrectomy for renal cell carcinoma 11 years previously presented with multiple histologically diagnosed pancreatic metastases. The patient had no notable comorbidities, including diabetes. Because no extrapancreatic organ metastasis was identified, he underwent TP as a curative treatment. He awoke from anesthesia and was extubated without any problems in the operating room. However, 15 min after entering the intensive care unit, he suddenly lost consciousness and became apneic, resulting in reintubation. Blood gas analysis revealed an increased glucose concentration (302 mg/dL) and mixed acid–base disorder (pH of 7.21) due to insulin insufficiency and fentanyl administration. After induction of continuous intravenous insulin infusion and termination of fentanyl, the glucose concentration and pH gradually improved. He regained clear consciousness and spontaneous ventilation and was extubated the next day with no difficulties or complications.

Conclusion
This case highlights the importance of active monitoring of the glycemic state and pH after TP because of the possibility of deterioration due to TP itself as well as the lingering effects of anesthesia.
Exercise Mode in Heart Failure: A Systematic Review and Meta-Analysis
Authors: Edwards Jamie , Shanmugam Nesan , Ray Robin , Jouhra Fadi , Mancio Jennifer , Wiles Jonathan , Marciniak Anna , Sharma Rajan , O’Driscoll Jamie 
Published: January 2023

Abstract
Background
Optimising exercise prescription in heart failure (HF) with a preserved (HFpEF) or reduced (HFrEF) ejection fraction is clinically important. As such, the aim of this meta-analysis was to compare traditional moderate intensity training (MIT) against combined aerobic and resistance training (CT) and high-intensity interval training (HIIT) for improving aerobic capacity (VO2), as well as other clinically relevant parameters.

Methods
A comprehensive systematic search was performed to identify randomised controlled trials published between 1990 and May 2021. Research trials reporting the effects of MIT against CT or HIIT on peak VO2 in HFpEF or HFrEF were considered. Left-ventricular ejection fraction (LVEF) and various markers of diastolic function were also analysed.

Results
Seventeen studies were included in the final analysis, 4 of which compared MIT against CT and 13 compared MIT against HIIT. There were no significant differences between MIT and CT for peak VO2 (weighted mean difference [WMD]: 0.521 ml min−1 kg−1, [95% CI] =  − 0.7 to 1.8, Pfixed = 0.412) or LVEF (WMD: − 1.129%, [95% CI] =  − 3.8 to 1.5, Pfixed = 0.408). However, HIIT was significantly more effective than MIT at improving peak VO2 (WMD: 1.62 ml min−1 kg−1, [95% CI] = 0.6–2.6, Prandom = 0.002) and LVEF (WMD: 3.24%, [95% CI] = 1.7–4.8, Prandom < 0.001) in HF patients. When dichotomized by HF phenotype, HIIT remained significantly more effective than MIT in all analyses except for peak VO2 in HFpEF.

Conclusions
HIIT is significantly more effective than MIT for improving peak VO2 and LVEF in HF patients. With the exception of peak VO2 in HFpEF, these findings remain consistent in both phenotypes. Separately, there is no difference in peak VO2 and LVEF change following MIT or CT, suggesting that the addition of resistance exercise does not inhibit aerobic adaptations in HF.

Graphical Abstract
Effect of Moringa oleifera leaves powder in diets of lactating buffaloes
Authors: El-Badawi Alaa-Eldin Y. , Hassan Ayman A. , Khalel Mohamed S. , Yacout Mohamed H. M. , El Naggar Soad 
Published: January 2023

Abstract
Background
Egyptian water buffalo as a dairy animal is adapted to the environmental conditions in Egypt and most of it is with small farmers, therefore, it was necessary to pay attention to improve its nutrition, increase its milk production, and improve its components by adding some feedstuffs of high nutritional value as Moringa oleifera which is a rapidly growing plant that is planted in tropical and subtropical area, in addition its leaves have high nutritive value, and it contains anti-oxidative and bioactive compounds, low anti-nutrient content and high amount of magnesium, which has positive effects on milk yield.

Results
The results revealed that, daily milk or 4% FCM yields was significantly (P < 0.05) highest for diet supplemented by 50 g Moringa olifera leaves powder (MOLP, R2) compared with the other groups. By increasing MOLP supplementation level there was a significant (P < 0.05) decrease in daily milk yield than control. Milk contents of protein, fat and total solids were significantly (P < 0.05) increased, but lactose or solid not fat contents were significantly (P < 0.05) decreased than control with increasing MOLP level. The highest values of dietary nutrients digestibility and nutritive values (TDN and DCP%) were recorded with R2 and the lowest were recorded for R4. Blood serum total protein, albumin and globulin contents were significantly (P < 0.05) higher with feeding MOLP supplemented diets than control particularly for R2 and R3. While, there were significant (P < 0.05) decrease in urea, glucose and cholesterol but creatinine, AST and ALT were gradually increased with increasing MOLP level. Rations supplemented with MOLP was associated with obvious increase (P < 0.05) of antioxidant enzymes (GR, GPx, Cat and SOD) and decrease free radicals and the effect was more pronounced with increasing the supplementation level.

Conclusions
These results indicated that 50 g Moringa olifera leaves powder supplementation to the diets of milking buffaloes improved milk yield, milk composition, nutrients digestibility, nutritive value and total antioxidant capacity.
Re-evaluating benzodiazepines for anxiety disorders – déjà-vu all over again?
Authors: Anderson Ian M. 
Published: January 2023

SUMMARYBenzodiazepines have attracted controversy from shortly after their introduction. They have been subject to periodic calls for their use to be re-evaluated on the basis that their risks have been overstated and their benefits underappreciated. Claims made in recent editorials from the International Task Force on Benzodiazepines in support of their wider use are critiqued in this issue. I examine here whether there is a case to change the conclusions of previous reconsiderations of the question.
Hypoparathyroidism, Sensorineural Deafness, and Renal Disease Syndrome Presenting With Febrile Seizures and Hypocalcemia
Authors: Gandolfi Anne , Ratnasamy Kevin , Minutti Carla 
Published: January 2023

Abstract
HDR syndrome is a rare genetic disorder caused by mutations in the GATA3 gene and characterized by hypoparathyroidism, sensorineural deafness, and renal disease. Here, we report case of a 9-month-old male with history of hydronephrosis and sensorineural deafness who presented with febrile seizures. He was found to have hypocalcemia and inappropriately normal parathyroid hormone. His neurologic and infectious workup were negative. Genetic testing revealed a nonsense mutation in the GATA3 gene, consistent with HDR syndrome. Hypocalcemia was responsive to calcium carbonate and calcitriol treatment. This case highlights hypocalcemia caused by hypoparathyroidism as a potential etiology of seizures. When hypoparathyroidism is detected with either hearing loss or renal disease, HDR syndrome should be considered, and other features of the syndrome should be investigated.