bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening and oenological property analysis of ethanol-tolerant non-Saccharomyces yeasts isolated from Rosa roxburghii Tratt
Authors: Li Yinfeng , Ding Peipei , Tang Xiaoyu , Zhu Wenli , Huang Mingzheng , Kang Mei , Liu Xiaozhu
Published: June 2023

Ethanol tolerance is crucial for the oenological yeasts. Rosa roxburghii Tratt, a Rosaceae plant native to China, is rich in nutritional and medicinal ingredients. In this study, ethanol-tolerant non-Saccharomyces yeasts were screened, and their oenological properties were further evaluated. Three ethanol-tolerant yeast strains (designated as C6, F112, and F15), which could tolerate 12% (v/v) ethanol treatment, were isolated from R. roxburghii, and identified as Candida tropicalis, Pichia guilliermondii, and Wickerhamomyces anomalus, respectively. The winemaking condition tolerances of these ethanol-tolerant yeast strains were similar to those of Saccharomyces cerevisiae X16. However, their growth, sugar metabolic performance and sulphureted hydrogen activities, were different. The β-glucosidase production ability of strain W. anomalus F15 was lower than that of S. cerevisiae X16, and strains of C. tropicalis C6 and P. guilliermondii F112 were similar to S. cerevisiae X16. Electronic sensory properties of the R. roxburghii wines fermented using ethanol-tolerant yeasts together with S. cerevisiae showed no significant differences. However, the mixed inoculation of the ethanol-tolerant yeast strains with S. cerevisiae could regulate the volatile aroma characteristics of the fermented R. roxburghii wine, enriching and enhancing the aroma flavor. Therefore, the selected ethanol-tolerant yeasts have the potential for application in the production of unique R. roxburghii wine.
Structural identification of pyridinopyrone compounds with anti-neuroinflammatory activity from streptomyces sulphureus DSM 40104
Authors: Hu Juan , Wang Zi-Xuan , Li Pei-Meng , Qian Pei-Yuan , Liu Ling-Li
Published: June 2023

This study investigated the chemical composition and biosynthesis pathway of compounds produced by Streptomyces sulphureus DSM 40104. With the guild of molecular networking analysis, we isolated and identified six uncommon structural characteristics of compounds, including four newly discovered pyridinopyrones. Based on genomic analysis, we proposed a possible hybrid NRPS-PKS biosynthesis pathway for pyridinopyrones. Notably, this pathway starts with the use of nicotinic acid as the starting unit, which is a unique feature. Compounds 1–3 exhibited moderate anti-neuroinflammatory activity against LPS-induced BV-2 cell inflammation. Our study demonstrates the diversity of polyene pyrone compounds regarding their chemical structure and bioactivity while providing new insights into their biosynthesis pathway. These findings may lead to the development of new treatments for inflammation-related diseases.
PI3K/Akt/Nrf2 mediated cellular signaling and virus-host interactions: latest updates on the potential therapeutic management of SARS-CoV-2 infection
Authors: Lekshmi V. S. , Asha Kumari , Sanicas Melvin , Asi Abhila , Arya U. M. , Kumar Binod
Published: June 2023

The emergence and re-emergence of viral diseases, which cause significant global mortality and morbidity, are the major concerns of this decade. Of these, current research is focused majorly on the etiological agent of the COVID-19 pandemic, SARS-CoV-2. Understanding the host response and metabolic changes during viral infection may provide better therapeutic targets for the proper management of pathophysiological conditions associated with SARS-CoV-2 infection. We have achieved control over most emerging viral diseases; however, a lack of understanding of the underlying molecular events prevents us from exploring novel therapeutic targets, leaving us forced to witness re-emerging viral infections. SARS-CoV-2 infection is usually accompanied by oxidative stress, which leads to an overactive immune response, the release of inflammatory cytokines, increasing lipid production, and also alterations in the endothelial and mitochondrial functions. PI3K/Akt signaling pathway confers protection against oxidative injury by various cell survival mechanisms including Nrf2-ARE mediated antioxidant transcriptional response. SARS-CoV-2 is also reported to hijack this pathway for its survival within host and few studies have suggested the role of antioxidants in modulating the Nrf2 pathway to manage disease severity. This review highlights the interrelated pathophysiological conditions associated with SARS-CoV-2 infection and the host survival mechanisms mediated by PI3K/Akt/Nrf2 signaling pathways that can help ameliorate the severity of the disease and provide effective antiviral targets against SARS-CoV-2.
Apolipoprotein E ε4 accelerates the longitudinal cerebral atrophy in open access series of imaging studies-3 elders without dementia at enrollment
Authors: Huang Yuda , Shan Yongzhi , Qin Wen , Zhao Guoguang
Published: May 2023

Introduction

Early studies have reported that APOE is strongly associated with brain atrophy and cognitive decline among healthy elders and Alzheimer’s disease (AD). However, previous research has not directly outlined the modulation of APOE on the trajectory of cerebral atrophy with aging during the conversion from cognitive normal (CN) to dementia (CN2D).

Methods

This study tried to elucidate this issue from a voxel-wise whole-brain perspective based on 416 qualified participants from a longitudinal OASIS-3 neuroimaging cohort. A voxel-wise linear mixed-effects model was applied for detecting cerebrum regions whose nonlinear atrophic trajectories were driven by AD conversion and to elucidate the effect of APOE variants on the cerebral atrophic trajectories during the process.

Results

We found that CN2D participants had faster quadratically accelerated atrophy in bilateral hippocampi than persistent CN. Moreover, APOE ε4 carriers had faster-accelerated atrophy in the left hippocampus than ε4 noncarriers in both CN2D and persistent CN, and CN2D ε4 carriers an noncarriers presented a faster atrophic speed than CN ε4 carriers. These findings could be replicated in a sub-sample with a tough match in demographic information.

Discussion

Our findings filled the gap that APOE ε4 accelerates hippocampal atrophy and the conversion from normal cognition to dementia.
Behavioral pattern separation and cognitive flexibility are enhanced in a mouse model of increased lateral entorhinal cortex-dentate gyrus circuit activity
Authors: Yun Sanghee , Soler Ivan , Tran Fionya H. , Haas Harley A. , Shi Raymon , Bancroft Grace L. , Suarez Maiko , de Santis Christopher R. , Reynolds Ryan P. , Eisch Amelia J.
Published: June 2023

Behavioral pattern separation and cognitive flexibility are essential cognitive abilities that are disrupted in many brain disorders. A better understanding of the neural circuitry involved in these abilities will open paths to treatment. In humans and mice, discrimination and adaptation rely on the integrity of the hippocampal dentate gyrus (DG) which receives glutamatergic input from the entorhinal cortex (EC), including the lateral EC (LEC). An inducible increase of EC-DG circuit activity improves simple hippocampal-dependent associative learning and increases DG neurogenesis. Here, we asked if the activity of LEC fan cells that directly project to the DG (LEC → DG neurons) regulates the relatively more complex hippocampal-dependent abilities of behavioral pattern separation or cognitive flexibility. C57BL/6J male mice received bilateral LEC infusions of a virus expressing shRNA TRIP8b, an auxiliary protein of an HCN channel or a control virus (SCR shRNA). Prior work shows that 4 weeks post-surgery, TRIP8b mice have more DG neurogenesis and greater activity of LEC → DG neurons compared to SCR shRNA mice. Here, 4 weeks post-surgery, the mice underwent testing for behavioral pattern separation and reversal learning (touchscreen-based location discrimination reversal [LDR]) and innate fear of open spaces (elevated plus maze [EPM]) followed by quantification of new DG neurons (doublecortin-immunoreactive cells [DCX+] cells). There was no effect of treatment (SCR shRNA vs. TRIP8b) on performance during general touchscreen training, LDR training, or the 1st days of LDR testing. However, in the last days of LDR testing, the TRIP8b shRNA mice had improved pattern separation (reached the first reversal more quickly and had more accurate discrimination) compared to the SCR shRNA mice, specifically when the load on pattern separation was high (lit squares close together or “small separation”). The TRIP8b shRNA mice were also more cognitively flexible (achieved more reversals) compared to the SCR shRNA mice in the last days of LDR testing. Supporting a specific influence on cognitive behavior, the SCR shRNA and TRIP8b shRNA mice did not differ in total distance traveled or in time spent in the closed arms of the EPM. Supporting an inducible increase in LEC-DG activity, DG neurogenesis was increased. These data indicate that the TRIP8b shRNA mice had better pattern separation and reversal learning and more neurogenesis compared to the SCR shRNA mice. This study advances fundamental and translational neuroscience knowledge relevant to two cognitive functions critical for adaptation and survival—behavioral pattern separation and cognitive flexibility—and suggests that the activity of LEC → DG neurons merits exploration as a therapeutic target to normalize dysfunctional DG behavioral output.
Impaired spatial working memory and reduced hippocampal neuronal density in a rat model of neurocysticercosis
Authors: Baquedano Laura E. , Bernal Edson G. , Carrion Daniel J. , Delgado Ana D. , Gavidia Cesar M. , Kirwan Daniela E. , Gilman Robert H. , Verastegui Manuela R.
Published: June 2023

Neurocysticercosis (NCC) is the most common parasitic disease affecting the nervous system and is a leading cause of acquired epilepsy worldwide, as well as cognitive impairment, especially affecting memory. The aim of this study was to evaluate the effect of NCC on spatial working memory and its correlation with hippocampal neuronal density, in a rat model of NCC. This experimental study was conducted on female (n = 60) and male (n = 73) Holtzman rats. NCC was induced by intracranial inoculation of T. solium oncospheres in 14 day-old-rats. Spatial working memory was assessed using the T-maze test at 3, 6, 9, and 12 months post-inoculation, and sensorimotor evaluation was performed at 12 months post-inoculation. Hippocampal neuronal density was evaluated by immunostaining of NeuN-positive cells of the CA1 region. Of the rats inoculated with T. solium oncospheres, 87.2% (82/94) developed NCC. The study showed a significant decline in spatial working memory over a 1-year follow-up period in rats experimentally infected with NCC. Males showed an early decline that started at 3 months, while females demonstrated it at 9 months. Additionally, a decrease in neuronal density was observed in the hippocampus of NCC-infected rats, with a more significant reduction in rats with cysts in the hippocampus than in rats with cysts in other brain areas and control rats. This rat model of NCC provides valuable support for the relationship between neurocysticercosis and spatial working memory deficits. Further investigations are required to determine the mechanisms involved in cognitive impairment and establish the basis for future treatments.
Cisplatin ototoxicity mechanism and antagonistic intervention strategy: a scope review
Authors: Li Yingru , Zhang Tianyang , Song Qiang , Gao Dekun , Li Yue , Jie Huiqun , Huang Ping , Zheng Guiliang , Yang Jun , He Jingchun
Published: June 2023

Cisplatin is a first-line chemotherapeutic agent in the treatment of malignant tumors with remarkable clinical effects and low cost. However, the ototoxicity and neurotoxicity of cisplatin greatly limit its clinical application. This article reviews the possible pathways and molecular mechanisms of cisplatin trafficking from peripheral blood into the inner ear, the toxic response of cisplatin to inner ear cells, as well as the cascade reactions leading to cell death. Moreover, this article highlights the latest research progress in cisplatin resistance mechanism and cisplatin ototoxicity. Two effective protective mechanisms, anti-apoptosis and mitophagy activation, and their interaction in the inner ear are discussed. Additionally, the current clinical preventive measures and novel therapeutic agents for cisplatin ototoxicity are described. Finally, this article also forecasts the prospect of possible drug targets for mitigating cisplatin-induced ototoxicity. These include the use of antioxidants, inhibitors of transporter proteins, inhibitors of cellular pathways, combination drug delivery methods, and other mechanisms that have shown promise in preclinical studies. Further research is needed to evaluate the efficacy and safety of these approaches.
Effects of additive sensory noise on cognition
Authors: Sherman Sage O. , Greenstein Maya , Basner Mathias , Clark Torin K. , Anderson Allison P.
Published: June 2023

Background

Adding noise to a system to improve a weak signal’s throughput is known as stochastic resonance (SR). SR has been shown to improve sensory perception. Some limited research shows noise can also improve higher order processing, such as working memory, but it is unknown whether SR can broadly improve cognition.

Objective

We investigated cognitive performance while applying auditory white noise (AWN) and/or noisy galvanic vestibular stimulation (nGVS).

Methods

We measured cognitive performance (n = 13 subjects) while completing seven tasks in the cognition test battery (CTB). Cognition was assessed with and without the influence of AWN, nGVS, and both simultaneously. Performance in speed, accuracy, and efficiency was observed. A subjective questionnaire regarding preference for working in noisy environments was collected.

Results

We did not find broad cognitive performance improvement under the influence of noise (p > 0.1). However, a significant interaction was found between subject and noise condition for accuracy (p = 0.023), indicating that some subjects exhibited cognitive changes with the addition of noise. Across all metrics, noisy environment preference may trend to be a potential indicator of whether subjects will exhibit SR cognitive benefits with a significant predictor in efficiency (p = 0.048).

Conclusion

This study investigated using additive sensory noise to induce SR in overall cognition. Our results suggest that using noise to improve cognition is not applicable for a broad population; however, the effect of noise differs across individuals. Further, subjective questionnaires may be a means to identify which individuals are sensitive to SR cognitive benefits, but further investigation is needed.
Understanding speech and language in tuberous sclerosis complex
Authors: Gipson Tanjala T. , Oller D. Kimbrough , Messinger Daniel S. , Perry Lynn K.
Published: June 2023

Tuberous Sclerosis Complex (TSC), is a neurocutaneous disorder, associated with a high prevalence of autism spectrum disorder (ASD; ∼50% of individuals). As TSC is a leading cause of syndromic ASD, understanding language development in this population would not only be important for individuals with TSC but may also have implications for those with other causes of syndromic and idiopathic ASD. In this mini review, we consider what is known about language development in this population and how speech and language in TSC are related to ASD. Although up to 70% of individuals with TSC report language difficulties, much of the limited research to date on language in TSC has been based on summary scores from standardized assessments. Missing is a detailed understanding of the mechanisms driving speech and language in TSC and how they relate to ASD. Here, we review recent work suggesting that canonical babbling and volubility—two precursors of language development that predict the emergence of speech and are delayed in infants with idiopathic ASD—are also delayed in infants with TSC. We then look to the broader literature on language development to identify other early precursors of language development that tend to be delayed in children with autism as a guide for future research on speech and language in TSC. We argue that vocal turn-taking, shared attention, and fast mapping are three such skills that can provide important information about how speech and language develop in TSC and where potential delays come from. The overall goal of this line of research is to not only illuminate the trajectory of language in TSC with and without ASD, but to ultimately find strategies for earlier recognition and treatment of the pervasive language difficulties in this population.
Grip force makes wrist joint position sense worse
Authors: Li Lin , Li Shuwang
Published: May 2023

Background

The purpose of this study was to investigate how grip force affects wrist joint position sense.

Methods

Twenty-two healthy participants (11 men and 11 women) underwent an ipsilateral wrist joint reposition test at 2 distinct grip forces [0 and 15% of maximal voluntary isometric contraction (MVIC)] and 6 different wrist positions (pronation 24°, supination 24°, radial deviation 16°, ulnar deviation 16°, extension 32°, and flexion 32°).

Results

The findings demonstrated significantly elevated absolute error values at 15% MVIC (3.8 ± 0.3°) than at 0% MVIC grip force [3.1 ± 0.2°, t(20) = 2.303, P = 0.032].

Conclusion

These findings demonstrated that there was significantly worse proprioceptive accuracy at 15% MVIC than at 0% MVIC grip force. These results may contribute to a better comprehension of the mechanisms underlying wrist joint injuries, the development of preventative measures to lower the risk of injuries, and the best possible design of engineering or rehabilitation devices.
Neuroprotective Effects of Fingolimod Supplement on the Retina and Optic Nerve in the Mouse Model of Experimental Autoimmune Encephalomyelitis
Authors: Yang Tao , Zha Zheng , Yang Xiao , Kang YueZhi , Wang Xin , Tong Yanping , Zhao XueSong , Wang Lei , Fan YongPing
Published: June 2023

Graphical Abstract

Our results show that fingolimod is a potential therapeutic approach to prevent EAE-induced visual impairment. Moreover, we show that the observed neuro-ophthalmological protective effects of fingolimod were dependent on hampering hyper-gliosis in the retina and optic nerve.
Tonic activation of GABAB receptors via GAT-3 mediated GABA release reduces network activity in the developing somatosensory cortex in GAD67-GFP mice
Authors: Ueberbach Timo , Simacek Clara A. , Tegeder Irmgard , Kirischuk Sergei , Mittmann Thomas
Published: June 2023

The efficiency of neocortical information processing critically depends on the balance between the glutamatergic (excitatory, E) and GABAergic (inhibitory, I) synaptic transmission. A transient imbalance of the E/I-ratio during early development might lead to neuropsychiatric disorders later in life. The transgenic glutamic acid decarboxylase 67-green fluorescent protein (GAD67-GFP) mouse line (KI) was developed to selectively visualize GABAergic interneurons in the CNS. However, haplodeficiency of the GAD67 enzyme, the main GABA synthetizing enzyme in the brain, temporarily leads to a low GABA level in the developing brain of these animals. However, KI mice did not demonstrate any epileptic activity and only few and mild behavioral deficits. In the present study we investigated how the developing somatosensory cortex of KI-mice compensates the reduced GABA level to prevent brain hyperexcitability. Whole-cell patch clamp recordings from layer 2/3 pyramidal neurons at P14 and at P21 revealed a reduced frequency of miniature inhibitory postsynaptic currents (mIPSCs) in KI mice without any change in amplitude or kinetics. Interestingly, mEPSC frequencies were also decreased, while the E/I-ratio was nevertheless shifted toward excitation. Surprisingly, multi-electrode-recordings (MEA) from acute slices revealed a decreased spontaneous neuronal network activity in KI mice compared to wild-type (WT) littermates, pointing to a compensatory mechanism that prevents hyperexcitability. Blockade of GABAB receptors (GABABRs) with CGP55845 strongly increased the frequency of mEPSCs in KI, but failed to affect mIPSCs in any genotype or age. It also induced a membrane depolarization in P14 KI, but not in P21 KI or WT mice. MEA recordings in presence of CGP55845 revealed comparable levels of network activity in both genotypes, indicating that tonically activated GABABRs balance neuronal activity in P14 KI cortex despite the reduced GABA levels. Blockade of GABA transporter 3 (GAT-3) reproduced the CGP55845 effects suggesting that tonic activation of GABABRs is mediated by ambient GABA released via GAT-3 operating in reverse mode. We conclude that GAT-3-mediated GABA release leads to tonic activation of both pre- and postsynaptic GABABRs and restricts neuronal excitability in the developing cortex to compensate for reduced neuronal GABA synthesis. Since GAT-3 is predominantly located in astrocytes, GAD67 haplodeficiency may potentially stimulate astrocytic GABA synthesis through GAD67-independent pathways.
B-Vitamins and Choline in Human Milk Are Not Impacted by a Preconception Lipid-Based Nutrient Supplement, but Differ Among Three Low-to-Middle Income Settings—Findings From the Women First Trial
Authors: Young Bridget E. , Westcott Jamie , Kemp Jennifer , Allen Lindsay , Hampel Daniela , Garcés Ana L. , Figueroa Lester , Goudar Shivaprasad S. , Dhaded Sangappa M. , Somannavar Manjunath , Saleem Sarah , Ali Sumera Aziz , Hambidge K. Michael , Krebs Nancy F. ,   The Women First Working Group
Published: May 2023

Introduction: Optimal human milk (HM) B-vitamin concentrations remain undefined, especially in areas where undernutrition is prevalent. The impact of supplementation pre-conception through pregnancy on HM B-vitamin composition remains unknown.

Methods: Human milk (HM) was collected at 2-weeks postpartum from 200 women in Guatemala, India, and Pakistan (the Women First Trial). The women were randomized to start a lipid-based nutrient supplement before conception, at end of the first trimester, or not at all; intervention continued until delivery. HM concentrations of eight B-vitamins and choline were assessed via ultra-performance liquid chromatography-tandem mass spectrometry. Maternal diet was assessed in early pregnancy, and infant growth followed through 6 months post-delivery.

Results: Despite supplement exposure averaging 15.7 (pre-conception arm) and 6.0 months (prenatal arm), HM B-vitamins did not differ between arms, but site differences were evident. Guatemala had higher HM concentrations of vitamin B3 than Pakistan and India. Pakistan had higher HM concentrations of thiamin and vitamin B6 than India and Guatemala. Cohort average HM vitamin B2 (162 ± 79 μg/L) and B6 (31.8 ± 24.6 μg/L) fell below values defined as deficient in 81.5 and 85.5% of samples, potentially reflecting sampling procedures and timing. Maternal dietary intakes of only vitamin B6 and choline were associated with the corresponding concentrations in HM (p < 0.005). No HM B-vitamin concentrations were associated with infant growth.

Conclusion: Prenatal supplementation for at least 6 months had no impact on HM B-vitamin concentrations at 2-weeks postpartum. Results suggest that the adequacy of HM composition was generally maintained, with potential exceptions of vitamin B2 and B6.
Interventional radiological therapies in colorectal hepatic metastases
Authors: Vulasala Sai Swarupa R. , Sutphin Patrick D. , Kethu Samira , Onteddu Nirmal K. , Kalva Sanjeeva P.
Published: May 2023

Colorectal malignancy is the third most common cancer and one of the prevalent causes of death globally. Around 20-25% of patients present with metastases at the time of diagnosis, and 50-60% of patients develop metastases in due course of the disease. Liver, followed by lung and lymph nodes, are the most common sites of colorectal cancer metastases. In such patients, the 5-year survival rate is approximately 19.2%. Although surgical resection is the primary mode of managing colorectal cancer metastases, only 10-25% of patients are competent for curative therapy. Hepatic insufficiency may be the aftermath of extensive surgical hepatectomy. Hence formal assessment of future liver remnant volume (FLR) is imperative prior to surgery to prevent hepatic failure. The evolution of minimally invasive interventional radiological techniques has enhanced the treatment algorithm of patients with colorectal cancer metastases. Studies have demonstrated that these techniques may address the limitations of curative resection, such as insufficient FLR, bi-lobar disease, and patients at higher risk for surgery. This review focuses on curative and palliative role through procedures including portal vein embolization, radioembolization, and ablation. Alongside, we deliberate various studies on conventional chemoembolization and chemoembolization with irinotecan-loaded drug-eluting beads. The radioembolization with Yttrium-90 microspheres has evolved as salvage therapy in surgically unresectable and chemo-resistant metastases.
Long-term sleep apnea CPAP via tracheostomy in children with tracheomalacia: 20-year experience
Authors: Sriboonyong Tidarat , Preutthipan Aroonwan , Nugboon Malinee
Published: May 2023

Introduction

Children with severe tracheobronchomalacia may need placements of tracheostomies and long-term mechanical ventilation. Due to financial constraints, continuous positive airway pressure (CPAP) machines commonly used to treat obstructive sleep apnea in adults have been utilized to deliver positive distending pressure to such children at our institution for more than 20 years with favorable outcomes. We, therefore, reported our experience with 15 children using this machine.

Methods

This is a retrospective study during 2001–2021.

Results

Fifteen children, 9 boys, aged ranged 3 months–5.6 years, were discharged home with CPAP via tracheostomies. All had co-morbidities including gastroesophageal reflux (n = 9, 60%), neuromuscular disorders (n = 6, 40%), genetic abnormalities (n = 6, 40%), cardiac diseases (n = 4, 27%) and chronic lungs (n = 3, 20%). Eight (53%) children were aged less than 1 year old. The smallest child was aged 3 months old, weighing 4.9 kg. All caregivers were relatives and non-medical health professionals. The 1-month and 1-year readmission rates were 13% and 66% respectively. No factor-associated unfavorable outcomes were statistically identified. No complications related to CPAP malfunction were found. Five (33%) were weaned off CPAP, and 3 died (2 from sepsis and 1 from a sudden unknown cause).

Conclusion

We first reported the use of sleep apnea CPAP via tracheostomy in children with severe tracheomalacia. In limited-resource countries, this simple device may be another option for long-term invasive ventilatory support. The CPAP use in children with tracheobronchomalacia requires adequately trained caregivers.
Predicted health care profile after transition to adult care in Turner syndrome children—experience of single center
Authors: Witkowska-Krawczak Ewa , Erazmus Michał , Majcher Anna , Pyrżak Beata , Kucharska Anna Małgorzata
Published: May 2023

Introduction

Turner Syndrome (TS) is caused by the complete or partial loss of one of the X chromosomes in all or some female cell lines. The variable genotypes are responsible for a large phenotypic diversity, nevertheless most studies emphasize a weak correlation between genotype and phenotype. The study aimed to assess the occurrence of defects and diseases depending on the karyotype in patients with TS and correlation with the predicted health care profile after the transition to adulthood.

Materials and methods

45 patients of the Department of Endocrinology and Pediatrics of the Medical University of Warsaw in 1990–2002 were analyzed. Girls were divided into 2 subgroups: “A”, which included 16 patients with the karyotype 45,X, and “B”, which included 29 girls with mosaic karyotypes. Based on the literature data, characteristic phenotypic features and the typical defects or diseases accompanying TS were selected, and the frequency of their occurrence was compared in both subgroups. Accordingly to this data, the predicted medical care profile was determined.

Results

In our study, patients with complete monosomy of the X chromosome had more characteristic phenotypic features. They needed sex hormone replacement therapy more often and started to menstruate spontaneously much less frequently (only 18.18% in monosomy vs. 73.91% in mosaic patients, p = 0.006). In patients with monosomy, congenital defects of the circulatory system were found more often (46.67% vs. 30.77%). The diagnosis in patients with mosaic karyotype was more often delayed, therefore the optimal time of growth hormone therapy was shorter. In our study, the X isochromosome determined the higher prevalence of autoimmune thyroiditis (83.33% vs. 12.5%, p = 0.049). We didn't find a correlation between the type of karyotype and health care profile after the transition, most of the patients needed more than 2 specialists. Most often, they required: gynecologists, cardiologists, and orthopedics.

Conclusions

After the transition from pediatric to adulthood, patients with TS need multidisciplinary care, but not all need the same kind of assistance. The phenotype and comorbidities determine the profile of patients' health care, however it wasn't directly related to the type of karyotype in our study.
Vitamin D status and tic disorder: a systematic review and meta-analysis of observational studies
Authors: Xiaoxia Lin , Jilong Jiang , Xianrui Chen , Yanhui Chen
Published: June 2023

Objective

Tic disorders (TD) are a common neurodevelopmental disorder, it can be divided into transient tic disorder (TTD), chronic motor or vocal tic disorder (CTD), and Tourette syndrome (TS). Our research is to evaluate the clinical relationship between tic disorders and vitamin D level in children.

Methods

Online databases, including CNKI, Wanfang, VIP, Cochrane Library, PubMed and Embase digital knowledge service platform, were checked up to June 2022 for relevant observational studies published in Chinese and English. A random-effects model was incorporated to summarize the study results. The RevMan5.3 software was used for meta-analysis.

Results

Out of 132 retrieved articles, 13 observational studies were eligible for inclusion in the systematic review and meta-analysis, comparing serum Vitamin D levels between children with TD and HC (healthy controls), including different subtypes of TD (TTD, CTD and TS). The results showed that the serum vitamin D levels in the TD group were lower than those in the HC group (MD = −6.64, 95% CI: −9.36 to −3.93, P < 0.001, Heterogeneity test: P < 0.001, I2 = 94%). There were no statistically significant differences in serum vitamin D levels between the TTD group and the CTD group (MD = 3.84, 95% CI: −0.59 to 8.26, P = 0.09, Heterogeneity test: P < 0.001, I2 = 90%), or between the CTD group and the TS group (MD = 1.06, 95% CI: −0.04 to 2.16, P = 0.0, Heterogeneity test: P = 0.54, I2 = 0%). However, there was a statistically significant difference in serum vitamin D levels between the TTD group and the TS group (MD = 5.24, 95% CI: 0.68–9.80, P = 0.02, Heterogeneity test: P < 0.001, I2 = 92%). The study also found a statistically significant difference in the ratio of male children between the TD group and the HC group (OR = 1.48, 95% CI: 1.07–2.03, P = 0.02, Heterogeneity test: P < 0.001, I2 = 74%), but no statistically significant difference in the age of children between the TD group and the HC group (OR = 0.46, 95% CI: −0.33 to 1.24, P = 0.25, Heterogeneity test: P < 0.001, I2 = 96%).

Conclusions

Our meta-analysis showed that the vitamin D level of children with TD was lower than that of healthy children. However, there was no difference between the subgroup. Due to the limitations of included studies in research design and diagnostic criteria, large samples, multi-center and high-quality studies are still needed for further analysis and confirmation.
Cytomegalovirus in children undergoing haematopoietic stem cell transplantation: a diagnostic and therapeutic approach to antiviral resistance
Authors: Hume Jocelyn , Sweeney Emma L. , Lowry Kym , Fraser Chris , Clark Julia E. , Whiley David M. , Irwin Adam D.
Published: June 2023

Cytomegalovirus (CMV) is a ubiquitous virus which causes a mild illness in healthy individuals. In immunocompromised individuals, such as children receiving haematopoietic stem cell transplantation, CMV can reactivate, causing serious disease and increasing the risk of death. CMV can be effectively treated with antiviral drugs, but antiviral resistance is an increasingly common complication. Available therapies are associated with adverse effects such as bone marrow suppression and renal impairment, making the choice of appropriate treatment challenging. New agents are emerging and require evaluation in children to establish their role. This review will discuss established and emerging diagnostic tools and treatment options for CMV, including antiviral resistant CMV, in children undergoing haematopoietic stem cell transplant.
The role of anion gap normalization time in the management of pediatric diabetic ketoacidosis
Authors: Lazar Isaac , Wizeman-Orlov Dorit , Hazan Guy , Orbach Asaf , Haim Alon , Cavari Yuval , Feinstein Yael , Neeman Eitan , Hershkovitz Eli , Faingelernt Yaniv
Published: June 2023

Introduction

Our aims were to determine whether anion gap normalization time (AGNT) correlates with risk factors related to the severity of diabetic ketoacidosis (DKA) in children, and to characterize AGNT as a criterion for DKA resolution in children admitted with moderate or severe disease.

Methods

A ten-year retrospective cohort study of children admitted to the intensive care unit with DKA. We used a survival analysis approach to determine changes in serum glucose, bicarbonate, pH, and anion gap following admission. Using multivariate analysis, we examined associations between patients' demographic and laboratory characteristics with delayed normalization of the anion gap.

Results

A total of 95 patients were analyzed. The median AGNT was 8 h. Delayed AGNT (>8 h) correlated with pH < 7.1 and serum glucose >500 mg/dL. In multivariate analysis, glucose >500 mg/dL was associated with an increased risk for delayed AGNT, by 3.41 fold. Each 25 mg/dL elevation in glucose was associated with a 10% increment in risk for delayed AGNT. Median AGNT preceded median PICU discharge by 15 h (8 vs. 23 h).

Discussion

AGNT represents a return to normal glucose-based physiology and an improvement in dehydration. The correlation observed between delayed AGNT and markers of DKA severity supports the usefulness of AGNT for assessing DKA recovery.
Protective effects of paeoniflorin on cardiovascular diseases: A pharmacological and mechanistic overview
Authors: Li Xiaoya , Sun Changxin , Zhang Jingyi , Hu Lanqing , Yu Zongliang , Zhang Xiaonan , Wang Zeping , Chen Jiye , Wu Min , Liu Longtao
Published: June 2023

Background and ethnopharmacological relevance:The morbidity and mortality of cardiovascular diseases (CVDs) are among the highest of all diseases, necessitating the search for effective drugs and the improvement of prognosis for CVD patients. Paeoniflorin (5beta-[(Benzoyloxy)methyl] tetrahydro-5-hydroxy-2-methyl-2,5-methano-1H-3,4-dioxacyclobuta [cd] pentalen-1alpha (2H)-yl-beta-D-glucopyranoside, C23H28O11) is mostly derived from the plants of the family Paeoniaceae (a single genus family) and is known to possess multiple pharmacological properties in the treatment of CVDs, making it a promising agent for the protection of the cardiovascular system.

Aim of the study:This review evaluates the pharmacological effects and potential mechanisms of paeoniflorin in the treatment of CVDs, with the aim of advancing its further development and application.

Methods:Various relevant literatures were searched in PubMed, ScienceDirect, Google Scholar and Web of Science. All eligible studies were analyzed and summarized in this review.

Results:Paeoniflorin is a natural drug with great potential for development, which can protect the cardiovascular system by regulating glucose and lipid metabolism, exerting anti-inflammatory, anti-oxidative stress, and anti-arteriosclerotic activities, improving cardiac function, and inhibiting cardiac remodeling. However, paeoniflorin was found to have low bioavailability, and its toxicology and safety must be further studied and analyzed, and clinical studies related to it must be carried out.

Conclusion:Before paeoniflorin can be used as an effective therapeutic drug for CVDs, further in-depth experimental research, clinical trials, and structural modifications or development of new preparations are required.
Development of a UPLC–MS/MS method for simultaneous therapeutic drug monitoring of anti-hepatocellular carcinoma drugs and analgesics in human plasma
Authors: Lu Shijia , Zhao Mingming , Zhao Limei , Li Guofei
Published: May 2023

In hepatocellular carcinoma treatment, sorafenib, oxaliplatin, 5-fluorouracil, capecitabine, lenvatinib, and donafenib are first-line drugs; regorafenib, apatinib, and cabozantinib are second-line drugs; and oxycodone, morphine, and fentanyl are commonly used analgesics. However, the high degree of inter- and intra-individual variability in the efficacy and toxicity of these drugs remains an urgent issue. Therapeutic drug monitoring (TDM) is the most reliable technical means for evaluating drug safety and efficacy. Therefore, we developed an ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for simultaneous TDM of three chemotherapy drugs (5-fluorouracil, oxaliplatin, and capecitabin), six targeted drugs (sorafenib, donafenib, apatinib, cabozantinib, regorafenib, and lenvatinib), and three analgesics (morphine, fentanyl, and oxycodone). We extracted 12 analytes and isotope internal standards (ISs) from plasma samples by magnetic solid phase extraction (mSPE) and separated them using a ZORBAX Eclipse Plus C18 column with water containing 0.1% formic acid and methanol containing 0.1% formic acid as the mobile phase. The analytical performance of our method in terms of sensitivity, linearity, specificity, carryover, precision, limit of quantification, matrix effect, accuracy, dilution integrity, extraction recovery, stability, and crosstalk of all the analytes under different conditions met all the criteria stipulated by the guidelines of the Chinese Pharmacopoeia and U.S. Food and Drug Administration. The response function was estimated at 10.0–10 000.0 ng/mL for sorafenib, donafenib, apatinib, cabozantinib, regorafenib, and lenvatinib, and 20.0–20 000.0 ng/mL for 5-fluorouracil, oxaliplatin, capecitabin, morphine, fentanyl, and oxycodone, with a correlation of > 0.9956 for all compounds. The precision and accuracy of all analytes were < 7.21% and 5.62%, respectively. Our study provides empirical support for a simple, reliable, specific, and suitable technique for clinical TDM and pharmacokinetics.
Natural flavones from edible and medicinal plants exhibit enormous potential to treat ulcerative colitis
Authors: Lu Qiang , Xie Yuhong , Luo Jingbin , Gong Qihai , Li Cailan
Published: June 2023

Ulcerative colitis (UC) is a chronic aspecific gut inflammatory disorder that primarily involves the recta and colons. It mostly presents as a long course of repeated attacks. This disease, characterized by intermittent diarrhoea, fecal blood, stomachache, and tenesmus, severely decreases the living quality of sick persons. UC is difficult to heal, has a high recurrence rate, and is tightly related to the incidence of colon cancer. Although there are a number of drugs available for the suppression of colitis, the conventional therapy possesses certain limitations and severe adverse reactions. Thus, it is extremely required for safe and effective medicines for colitis, and naturally derived flavones exhibited huge prospects. This study focused on the advancement of naturally derived flavones from edible and pharmaceutical plants for treating colitis. The underlying mechanisms of natural-derived flavones in treating UC were closely linked to the regulation of enteric barrier function, immune-inflammatory responses, oxidative stress, gut microflora, and SCFAs production. The prominent effects and safety of natural-derived flavones make them promising candidate drugs for colitis treatment.
Acute osimertinib exposure induces electrocardiac changes by synchronously inhibiting the currents of cardiac ion channels
Authors: Li Peiwen , Tian Xiaohui , Wang Gongxin , Jiang Enshe , Li Yanming , Hao Guoliang
Published: June 2023

Introduction: As the third generation of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib has demonstrated more significant cardiotoxicity than previous generations of EGFR-TKIs. Investigating the mechanism of osimertinib cardiotoxicity can provide a reference for a comprehensive understanding of osimertinib-induced cardiotoxicity and the safety of the usage of this drug in clinical practice.

Methods: Multichannel electrical mapping with synchronous ECG recording was used to investigate the effects of varying osimertinib concentrations on electrophysiological indicators in isolated Langendorff-perfused hearts of guinea pigs. Additionally, a whole-cell patch clamp was used to detect the impact of osimertinib on the currents of hERG channels transfected into HEK293 cells and the Nav1.5 channel transfected into Chinese hamster ovary cells and acute isolated ventricular myocytes from SD rats.

Results: Acute exposure to varying osimertinib concentrations produced prolongation in the PR interval, QT interval, and QRS complex in isolated hearts of guinea pigs. Meanwhile, this exposure could concentration-dependently increase the conduction time in the left atrium, left ventricle, and atrioventricular without affecting the left ventricle conduction velocity. Osimertinib inhibited the hERG channel in a concentration-dependent manner, with an IC50 of 2.21 ± 1.29 μM. Osimertinib also inhibited the Nav1.5 channel in a concentration-dependent manner, with IC50 values in the absence of inactivation, 20% inactivation, and 50% inactivation of 15.58 ± 0.83 μM, 3.24 ± 0.09 μM, and 2.03 ± 0.57 μM, respectively. Osimertinib slightly inhibited the currents of L-type Ca2+ channels in a concentration-dependent manner in acutely isolated rat ventricular myocytes.

Discussion: Osimertinib could prolong the QT interval; PR interval; QRS complex; left atrium, left ventricle, and atrioventricular conduction time in isolated guinea pig hearts. Furthermore, osimertinib could block the hERG, Nav1.5, and L-type Ca2+ channels in concentration-dependent manners. Therefore, these findings might be the leading cause of the cardiotoxicity effects, such as QT prolongation and decreased left ventricular ejection fraction.
Research trends and hotspots of post-stroke cognitive impairment: a bibliometric analysis
Authors: Chi Xiansu , Fan Xueming , Fu Guojing , Liu Yue , Zhang Yunling , Shen Wei
Published: June 2023

Background: Post-stroke cognitive impairment (PSCI) is a major complication of stroke that affects more than one-third of stroke survivors, threatening their quality of life and increasing the risk of disability and death. Although various studies have described the etiology, epidemiology, and risk factors of PSCI, there are a limited number of comprehensive and accurate reports on research trends and hotspots in this field. Therefore, this review aimed to evaluate research trends, hotspots, and frontiers in PSCI using bibliometric analysis.

Methods: We screened the literature spanning 20 years in the Web of Science Core Collection: Science Citation Index Expanded (SCI-Expanded) database from 1 January 2003 to 31 December 2022. We included all eligible literature reports based on our comprehensive search strategy, inclusion criteria, and exclusion criteria. The analysis of annual publications, countries/regions, institutions, journals, co-cited references, and keywords was conducted using CiteSpace and VOSviewer, and the hotspots and major findings of PSCI were summarized.

Results: A total of 1,024 publications were included in this review. We found that the number of publications on PSCI increased annually. These publications were published in 75 countries or regions by over 400 institutions. Although Chinese institutions had the highest number of publications, their international influence was limited. The United States showed a strong influence in the field. The journal “Stroke” published the most publications (57) with a high impact factor and was considered the most co-cited journal. The most frequently cited references focused on the prevalence, incidence, neuropsychological assessment scales, criteria, and guidelines of PSCI. The strongest citation burst keywords for PSCI were “neurotrophic factor” and “synaptic plasticity”, which were regarded as research focuses and research hotspots, respectively.

Conclusion: This review provided a comprehensive summary of the literature of PSCI, identified the authoritative and frequently cited literature and journals, clarified the trends in PSCI research, and highlighted the hotspots in this field. Currently, studies on the mechanisms and treatment of PSCI are limited, and we hope that this review has effectively highlighted the research trajectory of PSCI and will lay the foundation for more innovative research in the future.
Traditional Chinese medicine use is associated with lower risk of pneumonia in patients with systemic lupus erythematosus: a population-based retrospective cohort study
Authors: Wang Weijie , Wang Yu-Hsun , Yang Kepeng , Ye Xiangsheng , Wang Xinchang , Wei James Cheng-Chung
Published: June 2023

Objectives: To investigate the association between traditional Chinese medicine (TCM) therapy and the risk of pneumonia in patients with systemic lupus erythematosus (SLE).

Methods: This population-based control study analyzed the data retrieved from the National Health Insurance Research database in Taiwan. From a cohort of 2 million records of the 2000–2018 period, 9,714 newly diagnosed patients with SLE were initially included. 532 patients with pneumonia and 532 patients without pneumonia were matched 1:1 based on age, sex, and year of SLE diagnosis using propensity score matching. The use of TCM therapy was considered from the SLE diagnosis date to the index date and the cumulative days of TCM therapy were used to calculate the dose effect. Conditional logistic regression was used to investigate the risk of pneumonia infection. Furthermore, to explore the severity of pneumonia in SLE, sensitivity analyses were performed after stratification using the parameters of emergency room visit, admission time, and antibiotic use.

Results: TCM therapy for >60 days could significantly reduce the risk of pneumonia in patients with SLE (95% CI = 0.46–0.91; p = 0.012). Stratified analysis showed that TCM use also reduced the risk of pneumonia in younger and female patients with SLE by 34% and 35%, respectively. TCM for >60 days significantly reduced the risk of pneumonia in the follow-up periods of >2, >3, >7, and >8 years. In addition, the exposure of TCM for >60 days reduced the risk of pneumonia in patients with SLE who were treated with antibiotics for moderate or severe pneumonia. Finally, the study found that using formulae to tonify the kidney for more than 90 days and formulae to activate blood circulation for less than 30 days could significantly reduce the risk of pneumonia infection in patients with SLE.

Conclusion: TCM use is associated with a lower risk of pneumonia among patients with SLE.