bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Microwave Exposure at Different Doses in the Pre/Postnatal Period Affect Growing Rat Bone Development?
Authors: Karadayi A , Sarsmaz H , Çiğel A , Engiz B , Ünal N , ÜRKMEZ S , Gürgen S
Published: March 2024

Effects of pre/postnatal 2.45 GHz continuous wave (CW), Wireless-Fidelity (Wi-Fi) Microwave (MW) irradiation on bone have yet to be well defined. The present study used biochemical and histological methods to investigate effects on bone formation and resorption in the serum and the tibia bone tissues of growing rats exposed to MW irradiation during the pre/postnatal period. Six groups were created: one control group and five experimental groups subjected to low-level different electromagnetic fields (EMF) of growing male rats born from pregnant rats. During the experiment, the bodies of all five groups were exposed to 2.45 GHz CW-MW for one hour/day. EMF exposure started after fertilization in the experimental group. When the growing male rats were 45 days old in the postnatal period, the control and five experimental groups’ growing male and maternal rats were sacrificed, and their tibia tissues were removed. Maternal rats were not included in the study. No differences were observed between the control and five experimental groups in Receptor Activator Nuclear factor-kB (RANK) biochemical results. In contrast, there was a statistically significant increase in soluble Receptor Activator of Nuclear factor-kB Ligand (sRANKL) and Osteoprotegerin (OPG) for 10 V/m and 15 V/m EMF values. Histologically, changes in the same groups supported biochemical results. These results indicate that pre/postnatal exposure to 2.45 GHz EMF at 10 and 15 V/m potentially affects bone development.
Biological method of apple tree protection against green (Aphis pomi Deg.) and grey (Dysaphis devecta) apple aphids in the conditions of Western ForestSteppe of Ukraine
Authors: Hunchak M. , Zaitsev Yu. , Shapran S.
Published: March 2024

It was established that the investigated systems of biological protection of apple tree in the conditions of Western Forest Steppe of Ukraine showed high efficiency against green and grey apple aphids. The highest efficiency was obtained when using protection system No. 3 (Biospectr BT; Metarizin BT + Boverin BT; Bitoxybacillin BT + Biospectr BT): the efficiency against green apple aphid was 76.4–85.3%, and against gray apple aphid — 65.2–79.0%. The biological system of apple tree protection No. 1 (Aktophyt BT; Biospectr BT; Bitoxybacillin BT) showed effectiveness against green apple aphid 61.2–69.1%, and against gray apple aphid — 58.7–63.4%. When using the biological protection system No. 2 (Bitoxybacillin BT; Actofit BT + Bitoxybacillin BT; Boverin BT), the effectiveness against green apple aphid was 61.5–74.3%, and against gray apple aphid — 52.5–73.3%. The yield of apple fruits when using the biological protection system No. 1 was 13.6 t/ha, including 6.1 t/ha of the 1st grade, 5.9 t/ha of the 2nd grade and 1.9 t/ha of non-standard fruits. The yield when using the biological protection system No. 2 was 13.9 t/ha, of which 6.8 t/ha of the 1st grade, 5.3 t/ha of the 2nd grade and 1.8 t/ha of non-standard fruits. The yield when applying the biological protection system No. 3 was at the level of 14.0 t/ha, including 7.1 t/ha of the 1st grade, 5.4 t/ha of the 2nd grade and 1.5 t/ha of non-standard fruits. When using biological system No. 1 profitability was 389.8% and the income from its use was UAH 8,754.0/ha. From the application of system No. 2, they received a notional net income in the amount of UAH 10,686.0/ha and a profitability of 322.5%. By using system No. 3, conditional net income was obtained in the amount of UAH 11,692.0/ha, and the profitability of protective measures when using it was 353.4%.
Modal Sosial Kelompok Langgak Craft Desa Koto Tandun Kecamatan Tandun Kabupaten Rokan Hulu
Authors: Masdelina Masdelina , Asriwandari Hesti , Nurhamlin Nurhamlin
Published: March 2024

The wealth of local potential existing in a community can inspire creativity which can create some opportunities for the community through establishing home-based businesses or what is now known as Home Industry. IKM Langgak Craft group is able to construct a palm oil stick waste processing plant considered as having contributing ability in the long term. The objective of current research is to analyze the elements of social capital contributing and the weaknesses of each social capital element in the IKM Langgak Craft group in Koto Tandun Village, Tandun  Sub District, Rokan Hulu Regency. This research used Putnam’s theory stating that social capital includes (1) trust, (2) norm/ethics, and (3) network. This research used qualitative methodology with purposive sampling technique; the author also lived in the location of research for 2 (two) months. The result of research analyzing the Bonding of IKM Langgak Craft group shows that the group has high solidarity. Strong solidarity social care), mutual help, and support for each other create emotional relation in the IKM Langgak Craft group as shown with sympathy and empathy appearing in the group. Bridging Social Capital can be seen from the net wok relation between IKM Langgak Craft group and other groups or IKMs; through this network, the IKM Langgak Craft group will exchange ideas and information on how to produce business innovation and other varying common knowledge.  The Linking Social Capital of IKM Langgak Craft group has fairly broad network that has been created since 2019-2022 with both governmental institutions and private companies around it.
Effect of Heating/Cooling Rate on the Local Electronic Structure of Amorphous Calcium Carbonate
Authors: Lim Weon Cheol , Song Jonghan
Published: March 2024

Here, in the impact of heating/cooling rate was investigated on the formation of amorphous calcium carbonate (calcite) during sol-gel synthesis by probing local electronic structure. The amorphous calcium carbonate was synthesized by annealing precursor at 400oC at different heating/cooling rates i.e., 1.5 and 3oC /min. X-ray diffraction studies revealed amorphous nature at both heating/cooling rates. Fourier transformed infrared spectroscopic measurements characteristics bands in the spectra of both materials. Near edge X-ray absorption fine structure measurements at Ca L-edge, C K-edge and O K-edge were utilized to reveal the associated changes in the local electronic structure during synthesis. Local electronic structure investigation using near edge X-ray absorption fine structure measurements shows onset of moisture absorption on the surface particles when kept in the open environment.
Cellular abundance-based prognostic model associated with deregulated gene expression of leukemic stem cells in acute myeloid leukemia
Authors: Han Dong-Jin , Kim Sunmin , Lee Seo-Young , Kang Su Jung , Moon Youngbeen , Kim Hoon Seok , Kim Myungshin , Kim Tae-Min
Published: March 2024

Background: Previous studies have reported that genes highly expressed in leukemic stem cells (LSC) may dictate the survival probability of patients and expression-based cellular deconvolution may be informative in forecasting prognosis. However, whether the prognosis of acute myeloid leukemia (AML) can be predicted using gene expression and deconvoluted cellular abundances is debatable.

Methods: Nine different cell-type abundances of a training set composed of the AML samples of 422 patients, were used to build a model for predicting prognosis by least absolute shrinkage and selection operator Cox regression. This model was validated in two different validation sets, TCGA-LAML and Beat AML (n = 179 and 451, respectively).

Results: We introduce a new prognosis predicting model for AML called the LSC activity (LSCA) score, which incorporates the abundance of 5 cell types, granulocyte-monocyte progenitors, common myeloid progenitors, CD45RA + cells, megakaryocyte-erythrocyte progenitors, and multipotent progenitors. Overall survival probabilities between the high and low LSCA score groups were significantly different in TCGA-LAML and Beat AML cohorts (log-rank p-value = 3.3×10−4 and 4.3×10−3, respectively). Also, multivariate Cox regression analysis on these two validation sets shows that LSCA score is independent prognostic factor when considering age, sex, and cytogenetic risk (hazard ratio, HR = 2.17; 95% CI 1.40–3.34; p < 0.001 and HR = 1.20; 95% CI 1.02–1.43; p < 0.03, respectively). The performance of the LSCA score was comparable to other prognostic models, LSC17, APS, and CTC scores, as indicated by the area under the curve. Gene set variation analysis with six LSC-related functional gene sets indicated that high and low LSCA scores are associated with upregulated and downregulated genes in LSCs.

Conclusion: We have developed a new prognosis prediction scoring system for AML patients, the LSCA score, which uses deconvoluted cell-type abundance only.
Impact of head-down-tilt body position on abdomen resistance for urinary bladder monitory applications
Authors: Freeborn Todd J. , Critcher Shelby , Hooper Gwendolyn L.
Published: March 2024

Tissue electrical impedance (or bioimpedance) is a quantity related to the passive, frequency-dependent electrical properties of a biological tissue and is a promising modality for continuous monitoring of relative bladder volume and bladder activity. In this study, the impact of body position [specifically 6° head-down tilt (HDT)] intended to induce fluid redistribution and, therefore, result in a change in the electrical resistance of the abdomen is evaluated. The abdomen resistance (10 kHz–100 kHz) of nine healthy young adults was measured before and after 240 min in a 6° HDT position. Over this period, the resistance increase was not statistically significant even though the average bladder volume increased by 506 mL. It was expected that the abdomen resistance would decrease with an increase in bladder volume over this period. The masking of the expected resistance decrease is attributed to the shift in the fluid from the legs/abdomen to the neck/chest caused by the HDT body position over this period. Overall, this suggests that methods to differentiate bladder volume changes from other types of fluid shifts in the body are needed for resistance-based monitoring under free-living conditions.
Prediction of immunotherapy response in idiopathic membranous nephropathy using deep learning-pathological and clinical factors
Authors: Wei Xuejiao , Long Mengtuan , Fan Zhongyu , Hou Yue , Zhu Xiaoyu , Qu Zhihui , Du Yujun
Published: March 2024

Background

Owing to individual heterogeneity, patients with idiopathic membranous nephropathy (IMN) exhibit varying sensitivities to immunotherapy. This study aimed to establish and validate a model incorporating pathological and clinical features using deep learning training to evaluate the response of patients with IMN to immunosuppressive therapy.

Methods

The 291 patients were randomly categorized into training (n = 219) and validation (n = 72) cohorts. Patch-level convolutional neural network training in a weakly supervised manner was utilized to analyze whole-slide histopathological features. We developed a machine-learning model to assess the predictive value of pathological signatures compared to clinical factors. The performance levels of the models were evaluated using the area under the receiver operating characteristic curve (AUC) on the training and validation tests, and the prediction accuracies of the models for immunotherapy response were compared.

Results

Multivariate analysis indicated that diabetes and smoking were independent risk factors affecting the response to immunotherapy in IMN patients. The model integrating pathologic features had a favorable predictive value for determining the response to immunotherapy in IMN patients, with AUCs of 0.85 and 0.77 when employed in the training and test cohorts, respectively. However, when incorporating clinical features into the model, the predictive efficacy diminishes, as evidenced by lower AUC values of 0.75 and 0.62 on the training and testing cohorts, respectively.

Conclusions

The model incorporating pathological signatures demonstrated a superior predictive ability for determining the response to immunosuppressive therapy in IMN patients compared to the integration of clinical factors.
Effectiveness and safety of glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes: evidence from a retrospective real-world study
Authors: Jiang Yan , Bai Han-Sheng , Liu Guo-Xin , Wang Shi-Yi , Yin Li , Hou Zhao-Ting , Zhao Chen-Yang , Fan Guang-Jun
Published: March 2024

Introduction

Global phase III clinical trials have shown superior hypoglycemic efficacy to insulin and other oral hypoglycemic agents. However, there is a scarcity of real-world data comparing different glucagon-like peptide 1 receptor agonist (GLP-1RA) directly. This study aimed to assess the safety and effectiveness of various GLP-1RA in treating type 2 diabetes mellitus (T2DM) in a real-world clinical setting and identify predictive factors for favorable treatment outcomes.

Methods

This was a retrospective, single-center, real-world study. The changes in HbA1c, fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the percentage of participants who achieved HbA1c of <7%, 7%-8%, and ≥ 8% after GLP-1RA treatment was analyzed. The clinical factors that affect the effectiveness of GLP-1RA were analyzed.

Results

At baseline, the 249 participants had a mean baseline HbA1c of 8.7 ± 1.1%. After at least three months of follow-up, the change in HbA1c was -0.89 ± 1.3% from baseline. Dulaglutide exerted a more significant hypoglycemic effect than immediate-release exenatide. The percentage of participants who achieved HbA1c<7% was substantial, from 6.0% at baseline to 28.9%. Average body weight decreased by 2.02 ± 3.8 kg compared to baseline. After GLP-1RA treatment, the reduction in SBP was 2.4 ± 7.1 mmHg from baseline. A shorter duration of diabetes and a higher baseline HbA1c level were more likely to achieve a good response in blood glucose reduction.

Conclusions

This study provided real-world evidence showing that GLP-1RA significantly improved HbA1c, body weight, and SBP. The results can inform the decision-making about GLP-1RA treatment in daily clinical practice.
Structure-guided engineering and molecular simulations to design a potent monoclonal antibody to target aP2 antigen for adaptive immune response instigation against type 2 diabetes
Authors: Khan Abbas , Zahid Muhammad Ammar , Mohammad Anwar , Agouni Abdelali
Published: March 2024

Introduction

Diabetes mellitus (DM) is recognized as one of the oldest chronic diseases and has become a significant public health issue, necessitating innovative therapeutic strategies to enhance patient outcomes. Traditional treatments have provided limited success, highlighting the need for novel approaches in managing this complex disease.

Methods

In our study, we employed graph signature-based methodologies in conjunction with molecular simulation and free energy calculations. The objective was to engineer the CA33 monoclonal antibody for effective targeting of the aP2 antigen, aiming to elicit a potent immune response. This approach involved screening a mutational landscape comprising 57 mutants to identify modifications that yield significant enhancements in binding efficacy and stability.

Results

Analysis of the mutational landscape revealed that only five substitutions resulted in noteworthy improvements. Among these, mutations T94M, A96E, A96Q, and T94W were identified through molecular docking experiments to exhibit higher docking scores compared to the wild-type. Further validation was provided by calculating the dissociation constant (KD), which showed a similar trend in favor of these mutations. Molecular simulation analyses highlighted T94M as the most stable complex, with reduced internal fluctuations upon binding. Principal components analysis (PCA) indicated that both the wild-type and T94M mutant displayed similar patterns of constrained and restricted motion across principal components. The free energy landscape analysis underscored a single metastable state for all complexes, indicating limited structural variability and potential for high therapeutic efficacy against aP2. Total binding free energy (TBE) calculations further supported the superior performance of the T94M mutation, with TBE values demonstrating the enhanced binding affinity of selected mutants over the wild-type.

Discussion

Our findings suggest that the T94M substitution, along with other identified mutations, significantly enhances the therapeutic potential of the CA33 antibody against DM by improving its binding affinity and stability. These results not only contribute to a deeper understanding of antibody-antigen interactions in the context of DM but also provide a valuable framework for the rational design of antibodies aimed at targeting this disease more effectively.
An updated management approach of Pompe disease patients with high-sustained anti-rhGAA IgG antibody titers: experience with bortezomib-based immunomodulation
Authors: Desai Ankit K. , Shrivastava Garima , Grant Christina L. , Wang Raymond Y. , Burt Trevor D. , Kishnani Priya S.
Published: March 2024

Introduction

High sustained anti-rhGAA antibody titers (HSAT; ≥12,800) are directly linked to reduced efficacy of enzyme replacement therapy (ERT) and subsequent clinical deterioration in infantile-onset Pompe disease (IOPD). We have previously demonstrated the safety and effectiveness of a bortezomib-based immune-tolerance induction (ITI) regimen (bortezomib, rituximab, methotrexate, and IVIG) in eliminating HSAT.

Methods

Here, we describe two IOPD cases (patients 6 and 8) who developed HSAT at 8 and 10 weeks on ERT despite transient low-dose methotrexate ITI administration in the ERT-naïve setting and were treated with a bortezomib-based ITI regimen, and we compare their courses to a series of six historical patients (patients 1-5, and 7) with a similar presentation who exemplify our evolving approach to treatment.

Results

In total, patients 6 and 8 received 16 and 8 doses of bortezomib (4 doses=1 cycle) respectively reducing titers from 25,600 to seronegative, but differences in the course of their therapy were instructive regarding the optimal approach to initial treatment of HSAT; specifically, patient 6 was treated initially with only a single course of bortezomib rescue therapy, while patient 8 received two back-to-back courses. Patient 8 received IVIG therapy throughout the immunosuppression whereas patient 6 received IVIG therapy and was switched to subcutaneous IgG replacement. Patient 6 had a transient reduction in anti-rhGAA antibodies, after receiving a single initial cycle of bortezomib, but had a recurrence of high anti-rhGAA antibody titer after 160 weeks that required 3 additional cycles of bortezomib to ultimately achieve tolerance. In contrast, patient 8 achieved tolerance after being given two consecutive cycles of bortezomib during their initial treatment and had B cell recovery by week 54. Since the reduction in anti-rhGAA antibodies, both patients are doing well clinically, and have decreasing ALT, AST, and CK. No major infections leading to interruption of treatment were observed in either patient. The bortezomib-based ITI was safe and well-tolerated, and patients continue to receive ERT at 40 mg/kg/week.

Discussion

These case studies and our previous experience suggest that to achieve an effective reduction of anti-rhGAA antibodies in the setting of HSAT, bortezomib should be initiated at the earliest sign of high anti-rhGAA antibodies with a minimum of two consecutive cycles as shown in the case of patient 8. It is important to note that, despite initiation of ERT at age 2.3 weeks, patient 8 quickly developed HSAT. We recommend close monitoring of anti-rhGAA antibodies and early intervention with ITI as soon as significantly elevated anti-rhGAA antibody titers are noted.
A mini-review: phosphodiesterases in charge to balance intracellular cAMP during T-cell activation
Authors: Bielenberg Marie , Kurelic Roberta , Frantz Stefan , Nikolaev Viacheslav O.
Published: March 2024

T-cell activation is a pivotal process of the adaptive immune response with 3′,5′-cyclic adenosine monophosphate (cAMP) as a key regulator of T-cell activation and function. It governs crucial control over T-cell differentiation and production of pro-inflammatory cytokines, such as IFN-γ. Intriguingly, levels of intracellular cAMP differ between regulatory (Treg) and conventional T-cells (Tcon). During cell-cell contact, cAMP is transferred via gap junctions between these T-cell subsets to mediate the immunosuppressive function of Treg. Moreover, the activation of T-cells via CD3 and CD28 co-stimulation leads to a transient upregulation of cAMP. Elevated intracellular cAMP levels are balanced precisely by phosphodiesterases (PDEs), a family of enzymes that hydrolyze cyclic nucleotides. Various PDEs play distinct roles in regulating cAMP and cyclic guanosine monophosphate (cGMP) in T-cells. Research on PDEs has gained growing interest due to their therapeutic potential to manipulate T-cell responses. So far, PDE4 is the best-described PDE in T-cells and the first PDE that is currently targeted in clinical practice to treat autoimmune diseases. But also, other PDE families harbor additional therapeutic potential. PDE2A is a dual-substrate phosphodiesterase which is selectively upregulated in Tcon upon activation. In this Mini-Review, we will highlight the impact of cAMP regulation on T-cell activation and function and summarize recent findings on different PDEs regulating intracellular cAMP levels in T-cells.
Mortality of continuous infusion versus intermittent bolus of meropenem: a systematic review and meta-analysis of randomized controlled trials
Authors: Ai Ming-Ying , Chang Wei-Lun , Liu Chia-Ying
Published: March 2024

Background

Meropenem belongs to the carbapenem class, which is categorized as beta-lactam antibiotics. These antibiotics are administered in intermittent bolus doses at specific time intervals. However, the continuous infusion approach ensures sustained drug exposure, maintaining the drug concentration above the minimum inhibitory concentration (MIC) throughout the entire treatment period. This study aimed to find out the association between continuous infusions of meropenem and mortality rates.

Materials and methods

We conducted a search of the PubMed/Medline, EMBASE, Cochrane Central, and ClinicalTrials.gov databases up to 14 August 2023. The six randomized controlled trials (RCTs) were identified and included in our analysis. The random-effects model was implemented using Comprehensive Meta-Analysis software to examine the outcomes.

Results

Our study included a total of 1,529 adult patients from six randomized controlled trials. The primary outcome indicated that continuous infusion of meropenem did not lead to reduction in the mortality rate (odds ratio = 0.844, 95% CI: 0.671–1.061, P =0.147). Secondary outcomes revealed no significant differences in ICU length of stay (LOS), ICU mortality, clinical cure, or adverse events between continuous infusion and traditional intermittent bolus strategies of meropenem. Notably, we observed significant improvements in bacterial eradication (odds ratio 19 = 2.207, 95% CI: 1.467–3.320, P < 0.001) with continuous infusion of meropenem. Our study also suggested that performing continuous infusion may lead to better bacterial eradication effects in resistant pathogens (coefficient: 2.5175, P = 0.0138*).

Conclusion

Continuous infusion of meropenem did not result in the reduction of mortality rates but showed potential in improving bacterial eradication. Furthermore, this strategy may be particularly beneficial for achieving better bacterial eradication, especially in cases involving resistant pathogens.
Hyalangiumruber sp. nov, characterization of a novel myxobacterium strain s54d21 and their secondary metabolites
Authors: Zang Yi , Zhang Xianjiao , Wang Zhe , Tong Qingyi , Zhou Yang , Yao Qing , Zhu Honghui
Published: March 2024

Myxobacteria are special bacteria with wide adaptability, which are rich sources of structurally diverse natural products with intriguing biological properties. Here, a gram-negative myxobacterium strain s54d21T was isolated from the sediment of a wetland park in China using the Escherichia coli baiting method. Based on 16S rRNA gene sequence and genomic data, the strain was demonstrated to be a novel species of a rare genus Hyalangium, designated Hyalangium ruber sp. nov (type strain s54d21T = GDMCC 1.1945T = JCM 39263T). The subsequent chemical investigation of the strain s54d21T led to the isolation of three rare 3,5,6-trisubstituted 2(1H)-pyrazinones, namely, hyalanones A–C (1–3), together with a known macrolactin A (4). Those new structures and their absolute configurations were unambiguously assigned by extensive analyses of spectroscopic data and density functional theory (DFT) calculations. In biological assays, compound 4 exhibited moderate cytotoxic activities against human cell lines RKO, A549, and NCM460 with IC50 values ranging from 27.21 to 32.14 μM.
Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort
Authors: Shebl Nourhan , El-Jaafary Shaimaa , Saeed Ayman A. , Elkafrawy Passent , El-Sayed Amr , Shamma Samir , Elnemr Rasha , Mekky Jaidaa , Mohamed Lobna A. , Kittaneh Omar , El-Fawal Hassan , Rizig Mie , Salama Mohamed
Published: March 2024

Introduction: Parkinson’s disease (PD) is the most common motor neurodegenerative disease worldwide. Given the complexity of PD etiology and the different metabolic derangements correlated to the disease, metabolomics profiling of patients is a helpful tool to identify patho-mechanistic pathways for the disease development. Dopamine metabolism has been the target of several previous studies, of which some have reported lower phenylalanine and tyrosine levels in PD patients compared to controls.

Methods: In this study, we have collected plasma from 27 PD patients, 18 reference controls, and 8 high-risk controls to perform a metabolomic study using liquid chromatography-electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS).

Results: Our findings revealed higher intensities of trans-cinnamate, a phenylalanine metabolite, in patients compared to reference controls. Thus, we hypothesize that phenylalanine metabolism has been shifted to produce trans-cinnamate via L-phenylalanine ammonia lyase (PAL), instead of producing tyrosine, a dopamine precursor, via phenylalanine hydroxylase (PAH).

Discussion: Given that these metabolites are precursors to several other metabolic pathways, the intensities of many metabolites such as dopamine, norepinephrine, and 3-hydroxyanthranilic acid, which connects phenylalanine metabolism to that of tryptophan, have been altered. Consequently, and in respect to Metabolic Control Analysis (MCA) theory, the levels of tryptophan metabolites have also been altered. Some of these metabolites are tryptamine, melatonin, and nicotinamide. Thus, we assume that these alterations could contribute to the dopaminergic, adrenergic, and serotonergic neurodegeneration that happen in the disease.
Age-related differences in affective behaviors in mice: possible role of prefrontal cortical-hippocampal functional connectivity and metabolomic profiles
Authors: Febo Marcelo , Mahar Rohit , Rodriguez Nicholas A. , Buraima Joy , Pompilus Marjory , Pinto Aeja M. , Grudny Matteo M. , Bruijnzeel Adriaan W. , Merritt Matthew E.
Published: March 2024

Introduction

The differential expression of emotional reactivity from early to late adulthood may involve maturation of prefrontal cortical responses to negative valence stimuli. In mice, age-related changes in affective behaviors have been reported, but the functional neural circuitry warrants further investigation.

Methods

We assessed age variations in affective behaviors and functional connectivity in male and female C57BL6/J mice. Mice aged 10, 30 and 60 weeks (wo) were tested over 8 weeks for open field activity, sucrose preference, social interactions, fear conditioning, and functional neuroimaging. Prefrontal cortical and hippocampal tissues were excised for metabolomics.

Results

Our results indicate that young and old mice differ significantly in affective behavioral, functional connectome and prefrontal cortical-hippocampal metabolome. Young mice show a greater responsivity to novel environmental and social stimuli compared to older mice. Conversely, late middle-aged mice (60wo group) display variable patterns of fear conditioning and during re-testing in a modified context. Functional connectivity between a temporal cortical/auditory cortex network and subregions of the anterior cingulate cortex and ventral hippocampus, and a greater network modularity and assortative mixing of nodes was stronger in young versus older adult mice. Metabolome analyses identified differences in several essential amino acids between 10wo mice and the other age groups.

Discussion

The results support differential expression of ‘emotionality’ across distinct stages of the mouse lifespan involving greater prefrontal-hippocampal connectivity and neurochemistry.
The effects of Tai Chi exercise on sleep quality among the elderly: a study based on polysomnographic monitoring
Authors: Wang Chao , Jiang Tao , Li Hansen , Cao Guikang , Zhang Guodong
Published: March 2024

Background

Sleep disorders contribute to an increased risk of depression, cardiovascular issues, and various other diseases among older individuals. Consequently, enhancing the sleep quality of this demographic population has become a pressing concern. The objective of this study was to investigate the influence of an 8-week Tai Chi exercise intervention in the sleep quality of older adults.

Methods

Sixty individuals aged 60 years and above, recruited from the community around Southwest University in Beibei District, Chongqing City, were randomly assigned to either a control group (30 participants) or an intervention group (30 participants). The control group adhered to their normal daily routines during the 8-week experimental period, while the intervention group engaged in a 60-min Tai Chi practice three times a week for 8 weeks. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale (ESS). Additionally, the Polysomnographic Sleep Quality Monitoring System (PSG) was employed to monitor the sleep process before and after the Tai Chi intervention.

Results

After the experiment, significant differences were observed in PSQI and IEI scores between the intervention and control groups (p < 0.05). In the experimental group, the pre-post comparisons revealed a significant increase in time spent in bed (p < 0.05), total sleep time (p < 0.05), and non-REM sleep stage 2 (p < 0.05).

Conclusion

The findings indicate that Tai Chi exercise may improve subjective reported sleep quality. In addition, Tai Chi exercise may alleviate general drowsiness, extend sleep duration, and optimize the sleep process and structure. Consequently, Tai Chi exercise may be a suitable exercise to improve sleep quality in older individuals.
Using the gross motor function measure evolution ratio to compare different dosage of hyperbaric treatment with conventional therapies in children with cerebral palsy – could it end the controversy?
Authors: Marois Pierre , Letellier Guy , Marois Mikaël , Ballaz Laurent
Published: March 2024

The Gross Motor Function Measure is used in most studies measuring gross motor function in children with cerebral palsy. In many studies, including those evaluating the effect of hyperbaric treatment, the Gross Motor Function Measure variations were potentially misinterpreted because of the lack of control groups. The Gross Motor Function Measure Evolution Ratio (GMFMER) uses historical data from the Gross Motor Function Classification System curves and allows to re-analyze previous published studies which used the Gross Motor Function Measure by considering the natural expected evolution of the Gross Motor Function Measure. As the GMFMER is defined by the ratio between the recorded Gross Motor Function Measure score increase and the expected increase attributed to natural evolution during the duration of the study (natural evolution yields a GMFMER of 1), it becomes easy to assess and compare the efficacy of different treatments.

Objective

The objective of this study is to revisit studies done with different dosage of hyperbaric treatment and to compare the GMFMER measured in these studies with those assessing the effects of various recommended treatments in children with cerebral palsy.

Methods

PubMed Searches were conducted to included studies that used the Gross Motor Function Measure to evaluate the effect of physical therapy, selective dorsal rhizotomy, botulinum toxin injection, hippotherapy, stem cell, or hyperbaric treatment. The GMFMER were computed for each group of the included studies.

Results

Forty-four studies were included, counting 4 studies evaluating the effects of various dosage of hyperbaric treatment in children with cerebral palsy. Since some studies had several arms, the GMFMER has been computed for 69 groups. The average GMFMER for the groups receiving less than 2 h/week of physical therapy was 2.5 ± 1.8 whereas in context of very intensive physical therapy it increased to 10.3 ± 6.1. The GMFMER of stem cell, selective dorsal rhizotomy, hippotherapy, and botulinum toxin treatment was, 6.0 ± 5.9, 6.5 ± 2.0, 13.3 ± 0.6, and 5.0 ± 2.9, respectively. The GMFMER of the groups of children receiving hyperbaric treatment were 28.1 ± 13.0 for hyperbaric oxygen therapy and 29.8 ± 6.8 for hyperbaric air.

Conclusion

The analysis of the included studies with the GMFMER showed that hyperbaric treatment can result in progress of gross motor function more than other recognized treatments in children with cerebral palsy.
Association of vitamins B1 and B2 intake with early-onset sarcopenia in the general adult population of the US: a cross-sectional study of NHANES data from 2011 to 2018
Authors: Yang Sha , Dong Zhenyu , Zhao Jiaqi , Yuan Lijia , Xiao Yao , Luo Xing , Zhao Zhuyang , Kang Xia , Tang Kanglai , Chen Ming , Feng Liu
Published: March 2024

Background

Early-onset sarcopenia refers to the progressive loss of muscle mass and function that occurs at an early age. This condition perpetuates the vicious cycle of muscle loss and is associated with adverse outcomes. It is important to identify the contributing factors for early intervention and prevention. While diet is known to impact muscle mass, the association of B vitamins with early-onset sarcopenia remains unexplored.

Objectives

To investigate the association of B vitamins intake with early-onset sarcopenia risk in a cross-sectional study.

Methods

We conducted data analysis on a total of 8,711 participants aged between 20 and 59 years who took part in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Early-onset sarcopenia was defined as a SMI measured by DXA that was one standard deviation below the sex-specific mean of the reference population. B vitamins intake (B1, B2, B3, B6, B9, and B12) was assessed by 24-h dietary recall. We used weighted multiple logistic regression and RCS models to estimate the OR and 95% CI of sarcopenia by B vitamins intake, adjusting for demographic, physical, lifestyle, comorbidities, and nutritional covariates.

Results

Higher intake of vitamin B1 was associated with a 22% lower sarcopenia risk (OR = 0.78, CI = 0.63–0.97, p = 0.022), and higher intake of vitamin B2 with a 16% lower risk (OR = 0.84, CI = 0.74–0.97, p = 0.012) in both genders. Gender-specific analyses showed a 28% reduction in sarcopenia risk among males with each additional mg of vitamin B1 intake (OR = 0.72, CI = 0.52–0.97, p = 0.038), and a 26% decrease among females with each additional mg of vitamin B2 intake (OR = 0.74, CI = 0.57–0.96, p = 0.021). No significant differences were found between vitamin B2 and males, or between vitamin B1 and females. The RCS model suggested a nonlinear relationship between vitamin B2 intake and sarcopenia risk (POverall = 0.001, PNonlinear = 0.033), with a plateau effect above 3 mg/d.

Conclusion

Higher intake of vitamin B1 and B2 may lower the risk of early-onset sarcopenia, with gender differences. This suggests the potential of nutritional intervention by increasing these vitamins intake through diet and supplements. Further research is warranted to elucidate the mechanisms and design targeted interventions.
How BRCA and homologous recombination deficiency change therapeutic strategies in ovarian cancer: a review of literature
Authors: Arcieri Martina , Tius Veronica , Andreetta Claudia , Restaino Stefano , Biasioli Anna , Poletto Elena , Damante Giuseppe , Ercoli Alfredo , Driul Lorenza , Fagotti Anna , Lorusso Domenica , Scambia Giovanni , Vizzielli Giuseppe
Published: March 2024

About 50% of High Grade Serous Ovarian Cancer exhibit a high degree of genomic instability due to mutation of genes involved in Homologous Recombination (HRD) and such defect accounts for synthetic lethality mechanism of PARP inhibitors (PARP-i). Several clinical trials have shown how BRCA and HRD mutational status profoundly affect first line chemotherapy as well as response to maintenance therapy with PARP-i, hence Progression Free Survival and Overall Survival. Consequently, there is urgent need for the development of increasingly reliable HRD tests, overcoming present limitations, as they play a key role in the diagnostic and therapeutic process as well as have a prognostic and predictive value. In this review we offer an overview of the state of the art regarding the actual knowledge about BRCA and HRD mutational status, the rationale of PARPi use and HRD testing (current and in development assays) and their implications in clinical practice and in the treatment decision process, in order to optimize and choose the best tailored therapy in patients with ovarian cancer.
Clinical aspects of reimbursement policies for orphan drugs in Central and Eastern European countries
Authors: Jakubowski Szczepan , Kawalec Pawel , Holko Przemyslaw , Kowalska-Bobko Iwona , Kamusheva Maria , Petrova Guenka , Draganić Pero , Fuksa Leos , Männik Agnes , Ispán Fanni , Briedis Vitalis , Bianchi Ioana , Paveliu Marian Sorin , Tesar Tomas
Published: March 2024

Objectives: The aim of this study was to characterize the reimbursement policy for orphan drugs (ODs) in Central and Eastern European (CEE) countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedure, selected economic indicators, and the drug type according to indications.

Materials and methods: A list of authorized medicines with orphan designation and information about active substance, Anatomical Therapeutic Chemical (ATC) classification, and therapeutic area was extracted from the web-based register of the European Medicines Agency (EMA). A country-based questionnaire survey was performed between September 2021 and January 2022 in a group of selected experts from nine CEE countries (an invitation was sent to 11 countries). A descriptive and statistical analysis was conducted to determine statistical significance, correlations, between the drug or country characteristic and the positive recommendation or reimbursement of ODs.

Results: The proportion of reimbursed orphan drugs differed between countries, ranging from 17.7% in Estonia to 49.6% in Hungary (p < 0.001). The odds that ODs were reimbursed were reduced in countries with a “strong” level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), the presence of other additional specific clinical aspects (e.g., genomic data) considered in the reimbursement decision (p < 0.001) and mandatory (without exception) safety assessments (p=0.004). The probability that ODs were reimbursed was increased in countries with a “moderate” level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), when reimbursement decisions are dependent on the EMA registration status and orphan drug designation (p < 0.001), the presence of the “positive HTA recommendation guarantees reimbursement” policy (p < 0.001), higher GDP per inhabitant (p=0.003), and higher healthcare expenditure (p < 0.001).

Conclusion: We found that there are differences among CEE countries in the reimbursement of orphan drugs, and we identified aspects that may influence these differences. Safety, efficacy, and specific clinical aspect issues significantly influenced reimbursement decisions. Antineoplastic and immunomodulating agents drugs were the largest group of ODs and increased the chance of getting a positive recommendation. The higher GDP per inhabitant and healthcare expenditures per inhabitant were positively linked to the chance that an OD receives reimbursement.
Transcriptomic and physiological analyses reveal different grape varieties response to high temperature stress
Authors: Dou Feifei , Phillip Fesobi Olumide , Liu Gang , Zhu Jingjing , Zhang Lipeng , Wang Yongkang , Liu Huaifeng
Published: March 2024

High temperatures affect grape yield and quality. Grapes can develop thermotolerance under extreme temperature stress. However, little is known about the changes in transcription that occur because of high-temperature stress. The heat resistance indices and transcriptome data of five grape cultivars, ‘Xinyu’ (XY), ‘Miguang’ (MG), ‘Summer Black’ (XH), ‘Beihong’ (BH), and ‘Flame seedless’ (FL), were compared in this study to evaluate the similarities and differences between the regulatory genes and to understand the mechanisms of heat stress resistance differences. High temperatures caused varying degrees of damage in five grape cultivars, with substantial changes observed in gene expression patterns and enriched pathway responses between natural environmental conditions (35 °C ± 2 °C) and extreme high temperature stress (40 °C ± 2 °C). Genes belonging to the HSPs, HSFs, WRKYs, MYBs, and NACs transcription factor families, and those involved in auxin (IAA) signaling, abscisic acid (ABA) signaling, starch and sucrose pathways, and protein processing in the endoplasmic reticulum pathway, were found to be differentially regulated and may play important roles in the response of grape plants to high-temperature stress. In conclusion, the comparison of transcriptional changes among the five grape cultivars revealed a significant variability in the activation of key pathways that influence grape response to high temperatures. This enhances our understanding of the molecular mechanisms underlying grape response to high-temperature stress.
A chromosome-level genome assembly of Solanum chilense, a tomato wild relative associated with resistance to salinity and drought
Authors: Molitor Corentin , Kurowski Tomasz J. , Fidalgo de Almeida Pedro M. , Kevei Zoltan , Spindlow Daniel J. , Chacko Kaitholil Steffimol R. , Iheanyichi Justice U. , Prasanna H. C. , Thompson Andrew J. , Mohareb Fady R.
Published: March 2024

Introduction

Solanum chilense is a wild relative of tomato reported to exhibit resistance to biotic and abiotic stresses. There is potential to improve tomato cultivars via breeding with wild relatives, a process greatly accelerated by suitable genomic and genetic resources.

Methods

In this study we generated a high-quality, chromosome-level, de novo assembly for the S. chilense accession LA1972 using a hybrid assembly strategy with ~180 Gbp of Illumina short reads and ~50 Gbp long PacBio reads. Further scaffolding was performed using Bionano optical maps and 10x Chromium reads.

Results

The resulting sequences were arranged into 12 pseudomolecules using Hi-C sequencing. This resulted in a 901 Mbp assembly, with a completeness of 95%, as determined by Benchmarking with Universal Single-Copy Orthologs (BUSCO). Sequencing of RNA from multiple tissues resulting in ~219 Gbp of reads was used to annotate the genome assembly with an RNA-Seq guided gene prediction, and for a de novo transcriptome assembly. This chromosome-level, high-quality reference genome for S. chilense accession LA1972 will support future breeding efforts for more sustainable tomato production.

Discussion

Gene sequences related to drought and salt resistance were compared between S. chilense and S. lycopersicum to identify amino acid variations with high potential for functional impact. These variants were subsequently analysed in 84 resequenced tomato lines across 12 different related species to explore the variant distributions. We identified a set of 7 putative impactful amino acid variants some of which may also impact on fruit development for example the ethylene-responsive transcription factor WIN1 and ethylene-insensitive protein 2. These variants could be tested for their ability to confer functional phenotypes to cultivars that have lost these variants.
Cross-level transformation of creativity from entrepreneurs to organizations
Authors: Yang Xiu , Zhang Meng , Meng Zixuan , Shen Yingxian , Du Xiaomin
Published: March 2024

With the intensification of competition in the business environment, organizational creativity is increasingly becoming crucial for organizations to build competitive advantages and promote organizational development. For innovative enterprises, their entrepreneurs largely determine the development orientation of the enterprise. They are one of the most critical factors determining the level of corporate innovation, but there need to be more effective creativity transformation path to pursue innovation development. The findings in this study show that entrepreneurial individual creativity has a significant positive effect on organizational creativity, platform leadership mediates the path of creativity transformation across hierarchical levels, and organizational culture has positive moderating effect between platform leadership and organizational creativity. The study results explain the transformation mechanism of creativity from the entrepreneur's perspective, expand the potential transformation path of organizational creativity, and are instructive for enhancing organizational creativity.
The effectiveness of web-based training for parents on post-traumatic stress disorder in children
Authors: Omidvar Eshkalak Zakieh , Parvizy Soroor , Seyedfatemi Naima , Haghani Hamid , Nazari Hadis
Published: March 2024

Introduction

Post-traumatic stress disorder (PTSD) after an injury such as accidents is common in children and can affect their overall physical and mental functioning and quality of life. Early intervention can have significant health benefits for children. This study aimed to investigate the effectiveness of web-based training for parents on post-traumatic stress disorder in children.

Method

This was a quasi-experimental study with intervention and control group. 110 parents of children aged 10–18 years with PTSD after a traumatic event were selected through available sampling and assigned to intervention and control groups. Data was collected by a researcher-made demographic questionnaire and the Child Revised Impact of Events Scale (CRIES-8). Parents in the intervention group received a 4-week training course through a researcher-designed website, but the control group received routine care by the clinical team, which the main focus of care and training was on the physical aspects of the disease, and no intervention was done for PTSD. Two weeks after the intervention, the level of child stress was measured and compared in both groups. Data were analyzed using SPSS V.22.

Results

The difference between the mean score of total traumatic stress and its subscales before intervention was not statistically significant (p = 0.23). But after intervention, the mean score of total traumatic stress and its subscales decreased in the intervention group and increased in the control group and this difference was statistically significant (p < 0.001).

Conclusion

E-learning parent training has the potential to support children with PTSD. This available and cost-effective procedure can be recommended to help children with PTSD and possibly increase recovery in these patients.