bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-time polymerase chain reaction methods for strain specific identification and enumeration of strain Lacticaseibacillus paracasei 8700:2
Authors: Shehata Hanan R. , Hassane Basma , Newmaster Steven G. 
Published: January 2023

IntroductionReliable and accurate methods for probiotic identification and enumeration, at the strain level plays a major role in confirming product efficacy since probiotic health benefits are strain-specific and dose-dependent. In this study, real-time PCR methods were developed for strain specific identification and enumeration of L. paracasei 8700:2, a probiotic strain that plays a role in fighting the common cold.MethodsThe assay was designed to target a unique region in L. paracasei 8700:2 genome sequence to achieve strain level specificity. The identification assay was evaluated for specificity and sensitivity. The enumeration viability real-time PCR (v-qPCR) method was first optimized for the viability treatment, then the method was evaluated for efficiency, limit of quantification, precision, and its performance was compared to plate count (PC) and viability droplet digital PCR (v-ddPCR) methods.ResultsThe identification method proved to be strain specific and highly sensitive with a limit of detection of 0.5 pg of DNA. The optimal viability dye (PMAxx) concentration was 50 μM. The method was efficient (&gt; 90% with R2 values &gt; 0.99), with a linear dynamic range between 6*102 and 6*105 copies. The method was highly precise with a relative standard deviation below 5%. The Pearson correlation coefficient (r) was 0.707 for PC and v-qPCR methods, and 0.922 for v-qPCR and v-ddPCR. Bland-Altman method comparison showed that v-qPCR always gave higher values compared to PC method (relative difference ranging from 119% to 184%) and showed no consistent trend (relative difference ranging from −20% to 22%) when comparing v-qPCR and v-ddPCR methods.DiscussionThe difference between PC and v-PCR methods can potentially be attributed to the proportion of cells that exist in a viable but non culturable (VBNC) state, which can be count by v-PCR but not with PC. The developed v-qPCR method was confirmed to be strain specific, sensitive, efficient, with low variance, able to count VBNC cells, and has shorter time to results compared to plate count methods. Thus, the identification and enumeration methods developed for L. paracasei 8700:2 will be of great importance to achieve high quality and efficacious probiotic products.
Enzymatic and proteomic exploration into the inhibitory activities of lemongrass and lemon essential oils against Botrytis cinerea (causative pathogen of gray mold)
Authors: Kgang Itumeleng E. , Klein Ashwil , Mohamed Gadija G. , Mathabe Patricia M. K. , Belay Zinash A. , Caleb Oluwafemi James 
Published: January 2023

IntroductionEssential oils (EOs) have been demonstrated as efficacious against B. cinerea. However, the underpinning enzymatic and proteomic mechanism for these inhibitory effects is not entirely clear.MethodsThus, this study examined the effects of lemon (Le) and lemongrass (Lg) EOs (individually and in combination) against B. cinerea based on enzymatic and proteomic analyses. Proteomics data are available via ProteomeXchange with identifier PXD038894.Results and discussionBoth EOs (individually and in combination) displayed abilities to induce scavenging as observed with the reduction of H2O2. Measured malondialdehyde (MDA) and superoxide dismutase (SOD) activity were increased in all EOs treated B. cinerea mycelia compared to the control. Ascorbate peroxidase (APX) activity was highest in Lg treated B. cinerea (206% increase), followed by combined (Le + Lg) treatment with 73% compared to the untreated control. Based on GC-MS analysis, the number of volatile compounds identified in lemon and lemongrass EOs were 7 and 10, respectively. Major chemical constituent of lemon EO was d-limonene (71%), while lemongrass EO was a-citral (50.1%). Based on the interrogated LC-MS data, 42 distinct proteins were identified, and 13 of these proteins were unique with 1, 8, and 4 found in Le-, Lg-, and (Le + Lg) EOs treated B. cinerea, respectively, and none in control. Overall, 72% of identified proteins were localized within cellular anatomical entity, and 28% in protein-complexes. Proteins involved in translation initiation, antioxidant activity, protein macromolecule adaptor activity and microtubule motor activity were only identified in the Lg and (Le + Lg) EOs treated B. cinerea mycelia, which was consistent with their APX activities.
Unveiling age-independent spectral markers of propofol-induced loss of consciousness by decomposing the electroencephalographic spectrum into its periodic and aperiodic components
Authors: Leroy Sophie , Major Sebastian , Bublitz Viktor , Dreier Jens P. , Koch Susanne 
Published: January 2023

BackgroundInduction of general anesthesia with propofol induces radical changes in cortical network organization, leading to unconsciousness. While perioperative frontal electroencephalography (EEG) has been widely implemented in the past decades, validated and age-independent EEG markers for the timepoint of loss of consciousness (LOC) are lacking. Especially the appearance of spatially coherent frontal alpha oscillations (8–12 Hz) marks the transition to unconsciousness.Here we explored whether decomposing the EEG spectrum into its periodic and aperiodic components unveiled markers of LOC and investigated their age-dependency. We further characterized the LOC-associated alpha oscillations by parametrizing the adjusted power over the aperiodic component, the center frequency, and the bandwidth of the peak in the alpha range.MethodsIn this prospective observational trial, EEG were recorded in a young (18–30 years) and an elderly age-cohort (≥ 70 years) over the transition to propofol-induced unconsciousness. An event marker was set in the EEG recordings at the timepoint of LOC, defined with the suppression of the lid closure reflex. Spectral analysis was conducted with the multitaper method. Aperiodic and periodic components were parametrized with the FOOOF toolbox. Aperiodic parametrization comprised the exponent and the offset. The periodic parametrization consisted in the characterization of the peak in the alpha range with its adjusted power, center frequency and bandwidth. Three time-segments were defined: preLOC (105 – 75 s before LOC), LOC (15 s before to 15 s after LOC), postLOC (190 – 220 s after LOC). Statistical significance was determined with a repeated-measures ANOVA.ResultsLoss of consciousness was associated with an increase in the aperiodic exponent (young: p = 0.004, elderly: p = 0.007) and offset (young: p = 0.020, elderly: p = 0.004) as well as an increase in the adjusted power (young: p &lt; 0.001, elderly p = 0.011) and center frequency (young: p = 0.008, elderly: p &lt; 0.001) of the periodic alpha peak. We saw age-related differences in the aperiodic exponent and offset after LOC as well as in the power and bandwidth of the periodic alpha peak during LOC.ConclusionDecomposing the EEG spectrum over induction of anesthesia into its periodic and aperiodic components unveiled novel age-independent EEG markers of propofol-induced LOC: the aperiodic exponent and offset as well as the center frequency and adjusted power of the power peak in the alpha range.
Motivational and myopic mechanisms underlying dopamine medication-induced impulsive-compulsive behaviors in Parkinson's disease
Authors: Dawson Andrew , Ortelli Paola , Carter Adrian , Ferrazzoli Davide , Dissanayaka Nadeeka N. , Evans Andrew , Chye Yann , Lorenzetti Valentina , Frazzitta Giuseppe , Yücel Murat 
Published: January 2023

IntroductionDopaminergic medications can trigger impulsive-compulsive behaviors (ICBs) in pre-disposed patients with Parkinson's disease (PD), but what this implies on a neurocognitive level is unclear. Previous findings highlighted potentially exacerbated incentive motivation (willingness to work for rewards) and choice impulsivity (preferring smaller, immediate rewards over larger, delayed rewards) in PD patients with ICBs (PD + ICBs).MethodsTo deeply understand this evidence, we studied 24 PD + ICBs and 28 PD patients without ICBs (PD-ICBs). First of all, patients underwent the assessment of impulsivity traits, mood, anxiety, and addiction condition. We further administered robust objective and subjective measures of specific aspects of motivation. Finally, we explored whether these processes might link to any heightened antisocial behavior (aggression and risky driving) in PD + ICBs.ResultsHigh levels of positive urgency trait characterized PD + ICBs. They choose to exert more effort for rewards under the conditions of low and medium reward probability and as reward magnitude increases. Findings on choice impulsivity show a great tendency to delay discounting in PD + ICBs, other than a high correlation between delay and probability discounting. In addition, we found what appears to be the first evidence of heightened reactive aggression in PD patients with ICBs. Exacerbated incentive motivation and delay discounting trended toward positively predicting reactive aggression in PD + ICBs.DiscussionOur promising results suggest that there might be immense value in future large-scale studies adopting a transdiagnostic neurocognitive endophenotype approach to understanding and predicting the addictive and aggressive behaviors that can arise from dopaminergic medication in PD.
One-stop stroke management platform reduces workflow times in patients receiving mechanical thrombectomy
Authors: Zhou Tengfei , Li Tianxiao , Zhu Liangfu , Li Zhaoshuo , Li Qiang , Wang Ziliang , Wu Liheng , He Yingkun , Li Yucheng , Zhou Zhilong , Guan Min , Ma Zhenkai , pei Xiaoxi , Meng Shuhui , Feng Yingpu , Zhang Guifang , Zhao Wenli , Liu Xiao , Wang Meiyun 
Published: January 2023

Background and purposeClinical outcome in patients who received thrombectomy treatment is time-dependent. The purpose of this study was to evaluate the efficacy of the one-stop stroke management (OSSM) platform in reducing in-hospital workflow times in patients receiving thrombectomy compared with the traditional model.MethodsThe data of patients who received thrombectomy treatment through the OSSM platform and traditional protocol transshipment pathway were retrospectively analyzed and compared. The treatment-related time interval and the clinical outcome of the two groups were also assessed and compared. The primary efficacy endpoint was the time from door to groin puncture (DPT).ResultsThere were 196 patients in the OSSM group and 210 patients in the control group, in which they were treated by the traditional approach. The mean DPT was significantly shorter in the OSSM group than in the control group (76 vs. 122 min; P &lt; 0.001). The percentages of good clinical outcomes at the 90-day time point of the two groups were comparable (P = 0.110). A total of 121 patients in the OSSM group and 124 patients in the control group arrived at the hospital within 360 min from symptom onset. The mean DPT and time from symptom onset to recanalization (ORT) were significantly shorter in the OSSM group than in the control group. Finally, a higher rate of good functional outcomes was achieved in the OSSM group than in the control group (53.71 vs. 40.32%; P = 0.036).ConclusionCompared to the traditional transfer model, the OSSM transfer model significantly reduced the in-hospital delay in patients with acute stroke receiving thrombectomy treatment. This novel model significantly improved the clinical outcomes of patients presenting within the first 6 h after symptom onset.
High-proportion breast milk feeding is associated with a reduction in the incidence of IVH in very preterm infants
Authors: Zheng Zhi , Shen Wei , Tang Li-Xia , Zhang Rong , Cheng Rui , Wang San-Nan , Chen Dong-Mei , Chen Chao , Lin Xin-Zhu 
Published: January 2023

ObjectiveTo investigate the protective effect of high-proportion breast milk feeding (&gt;50%) on intraventricular hemorrhage (IVH) in very preterm infants (VPIs).MethodsThis was a retrospective secondary analysis of a prospective multi-center study, which included 604 VPIs from six hospitals in eastern China between September 2019 and December 2020. The 604 VPIs were divided into two groups according to whether IVH occurred. High-proportion breast milk feeding was defined as breast milk accounting for 51–100% of the total feeding amount both within 7 days and throughout the hospitalization. The IVH grades and the rate of high-proportion breast milk feeding were analyzed. Furthermore, to explore the relationship between high-proportion breast milk feeding and IVH grading, the VPIs' general information, perinatal factors, growth, and nutritional status during hospitalization, and related complications were compared between the two groups.ResultsHigh-proportion breast milk feeding was reported in 63.41% of the VPIs. Furthermore, IVH grades I–II and III–IV were noted in 39.73% (240/604) and 1.66% (10/604) of the VPIs, respectively. Univariate analysis revealed that IVH occurrence in VPIs is influenced by perinatal factors, invasive respiratory therapy, high-proportion breast milk feeding, start feeding with breast milk, the cumulative amount of early parenteral nutrition, postnatal complications, physical growth, and other factors (P &lt; 0.05). After adjustments for gestational age, birth weight, and possible influencing factors through binary logistic regression analysis, the results revealed that high-proportion breast milk feeding and and start feeding with breast milk were associated with a lower total incidence of IVH. Further stratification showed that high-proportion breast milk feeding was associated with a lower incidence of grade I–II IVH. Similarly, after adjusting for the same factors, breast milk feeding &gt;50% in the 1st week was associated with a decreased incidence of total IVH and further stratification showed that it was associated with a lower incidence of grade I–II IVH.ConclusionHigh-proportion breast milk feeding and breast milk feeding more than 50% of total intake during the 1st week might be protective factors for IVH grade I–II in VPIs, which further verified the neuroprotective effect of breast milk. In clinical practice, the construction of breast milk banks should be strengthened, breast milk feeding should be encouraged in neonatal intensive care units, and efforts should be made to increase breast milk feeding rates to improve the outcomes of VPIs.
Knockdown of ATF3 suppresses the progression of ischemic stroke through inhibiting ferroptosis
Authors: Ye Jin , Zhang Fan , Li Bin , Liu Qing , Zeng Guoyong 
Published: January 2023

ObjectiveCurrent therapies towards ischemic stroke (IS) are still not satisfied, and alternative strategies targeting ferroptosis may be another choice. The purpose of this study is to screen potential ferroptosis-related genes involving in IS.MethodsA rat model of IS was established via middle cerebral artery occlusion. Differentially expressed genes (DEGs) were screened from the model rats through transcriptional sequencing. Among the isolated DEGs, the expression of several attractive DEGs relating with ischemic injury was confirmed by qRT-PCR. Then, ATF3 relating with both IS and ferroptosis was selected a candidate gene for functional assays. After knockdown of ATF3 in the model rats, the infarction, histopathology, apoptosis, and ferroptosis in brain tissues were evaluated.ResultsIS model was successfully established in rats, exhibiting the emergence of infarction area, histopathological injury, and enhanced cell apoptosis. Total 699 up-regulated DEGs and 461 down-regulated DEGs were screened from the model rats. qRT-PCR verified the up-regulation of Hspa1b, Tfpi2, Ptx3, and Atf3, and the down-regulation of Smyd1 and Tacr2 in the Model group compared with those in the Sham group. It is noteworthy that knockdown of ATF3 decreased the infarction area, relieved histopathological injury, weakened apoptosis, and inhibited ferroptosis in the model rats.ConclusionSeveral candidate genes in relation with IS were revealed. More importantly, knockdown of ATF3 may relieve IS through inhibiting ferroptosis.
Effects of magnesium supplementation on improving hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes: A pooled analysis of 24 randomized controlled trials
Authors: Xu Lianbin , Li Xiuli , Wang Xinhui , Xu Mingqing 
Published: January 2023

BackgroundPrevious studies have demonstrated that diabetes is often accompanied with lower magnesium status. However, practical details regarding the influences of magnesium intervention on hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes (T2D) need to be further investigated.MethodsWeb of Science, ScienceDirect, and PubMed were searched for relevant literatures published through April 30, 2022, and high-quality data were pooled to evaluate the effects of magnesium supplementation on glycemic, circulating lipids, and blood pressure control in T2D, and to explore the associated practical details.ResultsPooled analyses of 24 randomized controlled trials with 1,325 T2D individuals revealed that subjects who received magnesium supplementation had statistically significant reductions in fasting plasma glucose, glycated hemoglobin, systolic blood pressure and diastolic blood pressure, with WMD values of –0.20 mM (95% CI: –0.30, –0.09), –0.22% (95% CI: –0.41, –0.03), –7.69 mmHg (95% CI: –11.71, –3.66) and –2.71 mmHg (95% CI: –4.02, –1.40), respectively. Detailed subgroup analyses demonstrated that health status of participants including age, body mass index, country, duration of disease, baseline magnesium level and baseline glycemic control condition as well as magnesium formulation, dosage and duration of intervention influenced the effects of magnesium addition. Dose-effect analysis showed that 279 mg/d for 116 d, 429 mg/d for 88 d and 300 mg/d for 120 d are the average optimal dosages and durations for improving glycemic, circulating lipids, and blood pressure controls, respectively.ConclusionOur findings provide clinically relevant information on the adjuvant therapy of magnesium for improving hyperglycemia, hypercholesterolemia, and hypertension in T2D.
Assessing the pathogenicity of BRCA1/2 variants of unknown significance: Relevance and challenges for breast cancer precision medicine
Authors: De Paolis Elisa , Paris Ida , Tilocca Bruno , Roncada Paola , Foca Laura , Tiberi Giordana , D’Angelo Tatiana , Pavese Francesco , Muratore Margherita , Carbognin Luisa , Garganese Giorgia , Masetti Riccardo , Di Leone Alba , Fabi Alessandra , Scambia Giovanni , Urbani Andrea , Generali Daniele , Minucci Angelo , Santonocito Concetta 
Published: January 2023

IntroductionBreast cancer (BC) is the leading cause of cancer-related death in women worldwide. Pathogenic variants in BRCA1 and BRCA2 genes account for approximately 50% of all hereditary BC, with 60-80% of patients characterized by Triple Negative Breast Cancer (TNBC) at an early stage phenotype. The identification of a pathogenic BRCA1/2 variant has important and expanding roles in risk-reducing surgeries, treatment planning, and familial surveillance. Otherwise, finding unclassified Variants of Unknown Significance (VUS) limits the clinical utility of the molecular test, leading to an “imprecise medicine”.MethodsWe reported the explanatory example of the BRCA1 c.5057A&gt;C, p.(His1686Pro) VUS identified in a patient with TNBC. We integrated data from family history and clinic-pathological evaluations, genetic analyses, and bioinformatics in silico investigations to evaluate the VUS classification.ResultsOur evaluation posed evidences for the pathogenicity significance of the investigated VUS: 1) association of the BRCA1 variant to cancer-affected members of the family; 2) absence of another high-risk mutation; 3) multiple indirect evidences derived from gene and protein structural analysis.DiscussionIn line with the ongoing efforts to uncertain variants classification, we speculated about the relevance of an in-depth assessment of pathogenicity of BRCA1/2 VUS for a personalized management of patients with BC. We underlined that the efficient integration of clinical data with the widest number of supporting molecular evidences should be adopted for the proper management of patients, with the final aim of effectively guide the best prognostic and therapeutic paths.
Case report: Successful management of a refractory double-expressor diffuse large B-cell lymphoma patient under the guidance of in vitro high-throughput drug sensitivity test
Authors: Xing Lijie , Wang Hui , Liu Dan , He Qiang , Li Zengjun 
Published: January 2023

IntroductionDouble-expressor diffuse large B-cell lymphoma (DEL), harboring double expression of MYC and BCL2, has an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). We initiated a clinical trial to treat newly diagnosed DEL with R-CHOP plus Bruton’s tyrosine kinase (BTK) inhibitor (BTKi) zanubrutinib (ZR-CHOP) and achieved a high complete response (CR) rate while four patients progressed during therapy, one of them carrying ATM and CD58 mutations. We applied an in vitro high-throughput drug sensitivity test for the prediction of clinical responses to different drugs in this patient.Case presentationWe report a 30-year-old female patient diagnosed with stage III (DEL), with ATM and CD58 mutations. The patient achieved partial response (PR) after two cycles of ZR-CHOP and remained PR after four cycles of ZR-CHOP, while the disease progressed after six cycles of ZR-CHOP. High-throughput drug screening using a panel of 117 compounds identified a range of therapies with efficacy for this patient. The primary tumor cells showed moderate sensitivity to bortezomib, thalidomide, and gemcitabine as a single agent and bortezomib, thalidomide, and dexamethasone (VTD) as a combined regimen. The patient was treated with two cycles of VTD regimen (bortezomib 1.3 mg/m2, d1, 4, 8, 11; thalidomide 100 mg, d1-21; dexamethasone 20 mg, d1, 2, 4, 5, 8, 9) and achieved PR with only a small lesion left. Another two cycles of VTD plus gemcitabine were then administered, and the patient achieved CR. Stem cells were mobilized, and autologous hematopoietic stem cell transplantation was carried out afterward. The patient remained CR for more than 3 months after transplantation.ConclusionIn this article, we present a first-line chemoresistant DEL patient with ATM and CD58 mutations who was treated successfully with VTD plus gemcitabine under the guidance of in vitro high-throughput drug sensitivity test.