bluuebunny/crossref_metadata_2025 huggingface dataset:
The growing burden of generalized myasthenia gravis: a population-based retrospective cohort study in Taiwan
Authors: Herr Keira Joann , Shen Shih-Pei , Liu Yanfang , Yang Chih-Chao , Tang Chao-Hsiun
Published: June 2023

Background

The prevalence of myasthenia gravis is increasing in many countries, including Asia. As treatment options expand, population-based information about the disease burden can inform health technology assessments.

Methods

We conducted a population-based retrospective cohort study using the Taiwan National Healthcare Insurance Research database and Death Registry to describe the epidemiology, disease burden and treatment patterns of generalized myasthenia gravis (gMG) from 2009 to 2019. Episodes of hepatitis B virus (HBV) infection or reactivation were explored.

Results

The number of patients with gMG increased from 1,576 in 2009 to 2,638 in 2019 and the mean (standard deviation) age from 51.63 (17.32) to 55.38 (16.29) years. The female:male ratio was 1.3:1. Frequently reported co-morbidities were hypertension (32–34% of patients), diabetes mellitus (16–21%) and malignancies (12–17%). The prevalence of patients with gMG increased annually from 6.83/100,000 population in 2009 to 11.18/100,000 population in 2019 (p < 0.0001). There was no temporal trend in all-cause fatality rates (range 2.76–3.79/100 patients annually) or gMG incidence rates (2.4–3.17/100,000 population annually). First-line treatment was with pyridostigmine (82%), steroids (58%), and azathioprine (11%). There was minimal change in treatment patterns over time. Among 147 new HBV infections, 32 (22%) received ≥4 weeks of antiviral therapy suggesting chronic infection. The HBV reactivation rate was 7.2%.

Conclusion

The epidemiology of gMG in Taiwan is evolving rapidly, with higher prevalence rates and increasing involvement of older age-groups suggesting a growing burden of disease and associated healthcare costs. HBV infection or reactivation may pose a previously unrecognized recognized risk for patients with gMG receiving immunosuppressants.
Dose-dependent effects of GAT107, a novel allosteric agonist-positive allosteric modulator (ago-PAM) for the α7 nicotinic cholinergic receptor: a BOLD phMRI and connectivity study on awake rats
Authors: Brems Brittany M. , Sullivan Erin E. , Connolly Jenna G. , Zhang Jingchun , Chang Arnold , Ortiz Richard , Cantwell Lucas , Kulkarni Praveen , Thakur Ganesh A. , Ferris Craig F.
Published: June 2023

Background

Alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonists have been developed to treat schizophrenia but failed in clinical trials due to rapid desensitization. GAT107, a type 2 allosteric agonist-positive allosteric modulator (ago-PAM) to the α7 nAChR was designed to activate the α7 nAChR while reducing desensitization. We hypothesized GAT107 would alter the activity of thalamocortical neural circuitry associated with cognition, emotion, and sensory perception.

Methods

The present study used pharmacological magnetic resonance imaging (phMRI) to evaluate the dose-dependent effect of GAT107 on brain activity in awake male rats. Rats were given a vehicle or one of three different doses of GAT107 (1, 3, and 10 mg/kg) during a 35 min scanning session. Changes in BOLD signal and resting state functional connectivity were evaluated and analyzed using a rat 3D MRI atlas with 173 brain areas.

Results

GAT107 presented with an inverted-U dose response curve with the 3 mg/kg dose having the greatest effect on the positive BOLD volume of activation. The primary somatosensory cortex, prefrontal cortex, thalamus, and basal ganglia, particularly areas with efferent connections from the midbrain dopaminergic system were activated as compared to vehicle. The hippocampus, hypothalamus, amygdala, brainstem, and cerebellum showed little activation. Forty-five min post treatment with GAT107, data for resting state functional connectivity were acquired and showed a global decrease in connectivity as compared to vehicle.

Discussion

GAT107 activated specific brain regions involved in cognitive control, motivation, and sensory perception using a BOLD provocation imaging protocol. However, when analyzed for resting state functional connectivity there was an inexplicable, general decrease in connectivity across all brain areas.
Proanthocyanidins induce analgesic and anxiolytic effects in spared nerve injured mice by decreasing in vivo firing rate of pyramidal cells in the insular cortex
Authors: Wang Pan , Si Hua-Xing , Zhu Da-Yu , Xing Ke-Ke , Wang Jian , Cao Ting-Ting , Zhao Han , Liu Xiao-Die , Zhang Ming-Ming , Chen Tao
Published: June 2023

Neuropathic pain is one of the most common symptoms of clinical pain that often accompanied by severe emotional changes such as anxiety. However, the treatment for comorbidity of chronic pain and anxiety is limited. Proanthocyanidins (PACs), a group of polyphenols enriched in plants and foods, have been reported to cause pain-alleviating effects. However, whether and how PACs induce analgesic and anxiolytic effects in the central nervous system remain obscure. In the present study, we observed that microinjection of PACs into the insular cortex (IC) inhibited mechanical and spontaneous pain sensitivity and anxiety-like behaviors in mice with spared nerve injury. Meanwhile, PACs application exclusively reduced the FOS expression in the pyramidal cells but not interneurons in the IC. In vivo electrophysiological recording of the IC further showed that PACS application inhibited the firing rate of spikes of pyramidal cells of IC in neuropathic pain mice. In summary, PACs induce analgesic and anxiolytic effects by inhibiting the spiking of pyramidal cells of the IC in mice with neuropathic pain, which should provide new evidence of PACs as the potential clinical treatment of chronic pain and anxiety comorbidity.
PTPδ is a presynaptic organizer for the formation and maintenance of climbing fiber to Purkinje cell synapses in the developing cerebellum
Authors: Okuno Yuto , Sakoori Kazuto , Matsuyama Kyoko , Yamasaki Miwako , Watanabe Masahiko , Hashimoto Kouichi , Watanabe Takaki , Kano Masanobu
Published: June 2023

Functionally mature neural circuits are shaped during postnatal development by eliminating redundant synapses formed during the perinatal period. In the cerebellum of neonatal rodents, each Purkinje cell (PC) receives synaptic inputs from multiple (more than 4) climbing fibers (CFs). During the first 3 postnatal weeks, synaptic inputs from a single CF become markedly larger and those from the other CFs are eliminated in each PC, leading to mono-innervation of each PC by a strong CF in adulthood. While molecules involved in the strengthening and elimination of CF synapses during postnatal development are being elucidated, much less is known about the molecular mechanisms underlying CF synapse formation during the early postnatal period. Here, we show experimental evidence that suggests that a synapse organizer, PTPδ, is required for early postnatal CF synapse formation and the subsequent establishment of CF to PC synaptic wiring. We showed that PTPδ was localized at CF-PC synapses from postnatal day 0 (P0) irrespective of the expression of Aldolase C (Aldoc), a major marker of PC that distinguishes the cerebellar compartments. We found that the extension of a single strong CF along PC dendrites (CF translocation) was impaired in global PTPδ knockout (KO) mice from P12 to P29-31 predominantly in PCs that did not express Aldoc [Aldoc (–) PCs]. We also demonstrated via morphological and electrophysiological analyses that the number of CFs innervating individual PCs in PTPδ KO mice were fewer than in wild-type (WT) mice from P3 to P13 with a significant decrease in the strength of CF synaptic inputs in cerebellar anterior lobules where most PCs are Aldoc (–). Furthermore, CF-specific PTPδ-knockdown (KD) caused a reduction in the number of CFs innervating PCs with decreased CF synaptic inputs at P10-13 in anterior lobules. We found a mild impairment of motor performance in adult PTPδ KO mice. These results indicate that PTPδ acts as a presynaptic organizer for CF-PC formation and is required for normal CF-PC synaptic transmission, CF translocation, and presumably CF synapse maintenance predominantly in Aldoc (–) PCs. Furthermore, this study suggests that the impaired CF-PC synapse formation and development by the lack of PTPδ causes mild impairment of motor performance.
Physicochemical, technofunctional, in vitro antioxidant, and in situ muscle protein synthesis properties of a sprat (Sprattus sprattus) protein hydrolysate
Authors: Shekoohi Niloofar , Naik Azza Silotry , Amigo-Benavent Miryam , Harnedy-Rothwell Pádraigín A. , Carson Brian P. , FitzGerald Richard J.
Published: June 2023

Introduction

Sprat (Sprattus sprattus) is an underutilized fish species that may act as an economic and sustainable alternative source of protein due to its good amino acid (AA) profile along with its potential to act as a source of multiple bioactive peptide sequences.

Method and results

This study characterized the physicochemical, technofunctional, and in vitro antioxidant properties along with the AA profile and score of a sprat protein enzymatic hydrolysate (SPH). Furthermore, the impact of the SPH on the growth, proliferation, and muscle protein synthesis (MPS) in skeletal muscle (C2C12) myotubes was examined. The SPH displayed good solubility and emulsion stabilization properties containing all essential and non-essential AAs. Limited additional hydrolysis was observed following in vitro-simulated gastrointestinal digestion (SGID) of the SPH. The SGID-treated SPH (SPH-SGID) displayed in vitro oxygen radical antioxidant capacity (ORAC) activity (549.42 μmol TE/g sample) and the ability to reduce (68%) reactive oxygen species (ROS) production in C2C12 myotubes. Muscle growth and myotube thickness were analyzed using an xCELLigence™ platform in C2C12 myotubes treated with 1 mg protein equivalent.mL−1 of SPH-SGID for 4 h. Anabolic signaling (phosphorylation of mTOR, rpS6, and 4E-BP1) and MPS (measured by puromycin incorporation) were assessed using immunoblotting. SPH-SGID significantly increased myotube thickness (p < 0.0001) compared to the negative control (cells grown in AA and serum-free medium). MPS was also significantly higher after incubation with SPH-SGID compared with the negative control (p < 0.05).

Conclusions

These preliminary in situ results indicate that SPH may have the ability to promote muscle enhancement. In vivo human studies are required to verify these findings.
Perioperative nutritional risk and its influencing factors in patients with oral cancer: a longitudinal study
Authors: Wang Guifen , Ou Meijun , Chen Hong , Zhu Shujuan , Chen Yongyi , Xu Xianghua
Published: June 2023

Introduction

We aimed to investigate the nutritional risk status and dynamic changes in patients with perioperative oral cancer at different stages and analyze the factors influencing nutritional risk and the correlation among body mass index, nutrition-related symptoms, and nutritional risk.

Methods

In total, 198 patients with oral cancer who were hospitalized in the Head & Neck Surgery Departments of a tertiary cancer hospital in Hunan Province, China, from May 2020 to January 2021, were selected as participants. The Nutritional Risk Screening 2002 scale and Head and Neck Patient Symptom Checklist were used to assess patients on admission day, 7 days post-surgery, and 1 month post-discharge. Multivariate analysis of variance, paired t-test, and generalized estimating equation were used to analyze the trajectory and influencing factors of nutritional risk in patients with perioperative oral cancer. Spearman’s correlation analysis was used to explore the correlation among body mass index, symptoms, and nutritional risk.

Results

The nutritional risk scores of patients with oral cancer at the three time points were 2.30 ± 0.84, 3.21 ± 0.94, and 2.11 ± 0.84, respectively, and the differences were significant (p < 0.05). The incidences of nutritional risk were 30.3, 52.5, and 37.9%, respectively. The factors influencing nutritional risk included education level, smoking status, clinical stage, flap repair, and tracheotomy (β = −0.326, 0.386, 0.387, 0.336, and 0.240, respectively, p < 0.05). Nutritional risk was negatively correlated with body mass index (rs = −0.455, p < 0.01) and positively correlated with pain, loss of appetite, sore mouth, bothersome smells, swallowing difficulty, taste changes, depression, chewing difficulty, thick saliva, and anxiety (rs = 0.252, 0.179, 0.269, 0.155, 0.252, 0.212, 0.244, 0.384, 0.260, and 0.157, respectively, p < 0.05).

Conclusion

The incidence of nutritional risk in patients with perioperative oral cancer was high, and the trajectory of nutritional risk changed over time. Strengthening the nutritional monitoring and management of postoperative patients or those with low education level, advanced-stage cancer, flap repair, tracheotomy, and low body mass index; strengthening tobacco control management; and controlling nutrition-related discomfort symptoms in perioperative oral cancer patients are necessary.
Moving towards a unified classification of glioblastomas utilizing artificial intelligence and deep machine learning integration
Authors: Hill Ciaran Scott , Pandit Anand S.
Published: June 2023

Glioblastoma a deadly brain cancer that is nearly universally fatal. Accurate prognostication and the successful application of emerging precision medicine in glioblastoma relies upon the resolution and exactitude of classification. We discuss limitations of our current classification systems and their inability to capture the full heterogeneity of the disease. We review the various layers of data that are available to substratify glioblastoma and we discuss how artificial intelligence and machine learning tools provide the opportunity to organize and integrate this data in a nuanced way. In doing so there is the potential to generate clinically relevant disease sub-stratifications, which could help predict neuro-oncological patient outcomes with greater certainty. We discuss limitations of this approach and how these might be overcome. The development of a comprehensive unified classification of glioblastoma would be a major advance in the field. This will require the fusion of advances in understanding glioblastoma biology with technological innovation in data processing and organization.
Immune microenvironment analysis and novel biomarkers of early-stage lung adenocarcinoma evolution
Authors: Liu Jun , Ji Yaxin , Weng Xiaodan , Shao Wei , Zhao Jiaping , Chen Hanlin , Shen Lu , Wang Fufeng , Meng Qi , Wu Xue , Wang Xiaonan , Ou Qiuxiang , Ke Honggang
Published: June 2023

Background

Lung cancer is the deadliest and most diagnosed type of cancer worldwide. The 5-year survival rate of lung adenocarcinoma (LUAD) dropped significantly when tumor stages advanced. Patients who received surgically resecting at the pre-invasive stage had a 5-year survival rate of nearly 100%. However, the study on the differences in gene expression profiles and immune microenvironment among pre-invasive LUAD patients is still lacking.

Methods

In this study, the gene expression profiles of three pre-invasive LUAD stages were compared using the RNA-sequencing data of 10 adenocarcinoma in situ (AIS) samples, 12 minimally invasive adenocarcinoma (MIA) samples, and 10 invasive adenocarcinoma (IAC) samples.

Results

The high expression levels of PTGFRN (Hazard Ratio [HR] = 1.45; 95% Confidence Interval [CI]: 1.08-1.94; log-rank P = 0.013) and SPP1 (HR = 1.44; 95% CI: 1.07-1.93; log-rank P = 0.015) were identified to be associated with LUAD prognosis. Moreover, the early LUAD invasion was accompanied by the enhancement of antigen presentation ability, reflected by the increase of myeloid dendritic cells infiltration rate (Cuzick test P < 0.01) and the upregulation of seven important genes participating in the antigen presentation, including HLA-A (Cuzick test P = 0.03), MICA (Cuzick test P = 0.01), MICB (Cuzick test P = 0.01), HLA-DPA1 (Cuzick test P = 0.04), HLA-DQA2 (Cuzick test P < 0.01), HLA-DQB1 (Cuzick test P = 0.03), and HLA-DQB2 (Cuzick test P < 0.01). However, the tumor-killing ability of the immune system was inhibited during this process, as there were no rising cytotoxic T cell activity (Cuzick test P = 0.20) and no increasing expression in genes encoding cytotoxic proteins.

Conclusion

In all, our research elucidated the changes in the immune microenvironment during early-stage LUAD evolution and may provide a theoretical basis for developing novel early-stage lung cancer therapeutic targets.
Concordance between microsatellite instability and mismatch repair protein expression in colorectal cancer and their clinicopathological characteristics: a retrospective analysis of 502 cases
Authors: Ye Meihua , Ru Guoqing , Yuan Hang , Qian Lili , He Xianglei , Li Shuangshuang
Published: June 2023

Microsatellite instability (MSI) is one of the hallmarks of colorectal cancer (CRC). Mismatch repair (MMR) protein expression may reflect MSI status. To analyze the concordance between MSI and MMR expression in CRC and their clinicopathological characteristics, 502 CRC patients were retrospectively collected in this study. Polymerase chain reaction-capillary electrophoresis (PCR-CE) was used to measure MSI, and MMR expression was determined by immunohistochemistry (IHC). The causes of non-concordance were analyzed. Chi-square test was used to find the correlation between MSI and various clinicopathological parameters. PCR-CE results showed 64 (12.7%) patients had high microsatellite instability (MSI-H); low microsatellite instability (MSI-L) and microsatellite stable (MSS) cases were 19 (3.8%)and 419 (83.5%), respectively. With regard to IHC, 430 (85.7%) showed proficient mismatch repair (pMMR) and 72 (14.3%) showed deficient mismatch repair (dMMR). The coincidence rate of MSI and MMR expression in CRC was 98.4% (494/502), with good concordance (Kappa = 0.932). Using PCR-CE as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value of IHC were 100%, 98.2%, 88.9%, and 100%, respectively. MSI-H was more common in women, right colon, tumors ≥ 5 cm, ulcerative type, mucinous adenocarcinoma, poor differentiation, T stage I/II, and without lymph node or distant metastasis for CRC patients. In summary, MSI exhibited some typical clinicopathological characteristics. MSI and MMR expression in CRC had good concordance. However, it is still extremely necessary to perform PCR-CE. We recommend that testing packages of different sizes should be developed in clinical practice to create a testing echelon, to facilitate comprehensive selection according to experimental conditions, clinical diagnosis, and treatment needs.
Integrated gut microbiota and metabolome analysis reveals the mechanism of Xiaoai Jiedu recipe in ameliorating colorectal cancer
Authors: Qiu Wenli , Xie Hui , Chen Haibin , Zhou Hongli , Wang Zhongqiu , Zhou Hongguang
Published: June 2023

Introduction

Xiaoai Jiedu recipe (XJR), a classical prescription of traditional Chinese medicine (TCM), has been clinically proven to be effective in ameliorating colorectal cancer (CRC). However, its exact mechanism of action is still elusive, limiting its clinical application and promotion to a certain extent. This study aims to evaluate the effect of XJR on CRC and further illustrate mechanism underlying its action.

Methods

We investigated the anti-tumor efficacy of XJR in vitro and vivo experiments. An integrated 16S rRNA gene sequencing and UPLC-MS based metabolomics approach were performed to explore possible mechanism of XJR anti-CRC on the gut microbiota and serum metabolic profiles. The correlation between altered gut microbiota and disturbed serum metabolites was investigated using Pearson’s correlation analysis.

Results

XJR effectively displayed anti-CRC effect both in vitro and in vivo. The abundance of aggressive bacteria such as Bacteroidetes, Bacteroides, and Prevotellaceae decreased, while the levels of beneficial bacteria increased (Firmicutes, Roseburia, and Actinobacteria). Metabolomics analysis identified 12 potential metabolic pathways and 50 serum metabolites with different abundances possibly affected by XJR. Correlation analysis showed that the relative abundance of aggressive bacteria was positively correlated with the levels of Arachidonic acid, Adrenic acid, 15(S)−HpETE, DL−Arginine, and Lysopc 18:2, which was different from the beneficial bacteria.

Discussion

The regulation of gut microbiota and related metabolites may be potential breakthrough point to elucidate the mechanism of XJR in the treatment of the CRC. The strategy employed would provide theoretical basis for clinical application of TCM.
Mechanisms of immune modulation in the tumor microenvironment and implications for targeted therapy
Authors: Czajka-Francuz Paulina , Prendes Maria J. , Mankan Arun , Quintana Ángela , Pabla Sarabjot , Ramkissoon Shakti , Jensen Taylor J. , Peiró Sandra , Severson Eric A. , Achyut Bhagelu R. , Vidal Laura , Poelman Martine , Saini Kamal S.
Published: June 2023

The efficacy of cancer therapies is limited to a great extent by immunosuppressive mechanisms within the tumor microenvironment (TME). Numerous immune escape mechanisms have been identified. These include not only processes associated with tumor, immune or stromal cells, but also humoral, metabolic, genetic and epigenetic factors within the TME. The identification of immune escape mechanisms has enabled the development of small molecules, nanomedicines, immune checkpoint inhibitors, adoptive cell and epigenetic therapies that can reprogram the TME and shift the host immune response towards promoting an antitumor effect. These approaches have translated into series of breakthroughs in cancer therapies, some of which have already been implemented in clinical practice. In the present article the authors provide an overview of some of the most important mechanisms of immunosuppression within the TME and the implications for targeted therapies against different cancers.
How molecular advances may improve the diagnosis and management of PTCL patients
Authors: Drieux Fanny , Lemonnier François , Gaulard Philippe
Published: June 2023

Peripheral T-cell lymphomas (PTCL) comprised more than 30 rare heterogeneous entities, representing 10 to 15% of adult non-Hodgkin lymphomas. Although their diagnosis is still mainly based on clinical, pathological, and phenotypic features, molecular studies have allowed for a better understanding of the oncogenic mechanisms involved and the refinement of many PTCL entities in the recently updated classifications. The prognosis remains poor for most entities (5-year overall survival < 30%), with current conventional therapies based on anthracyclin-based polychemotherapy regimen, despite many years of clinical trials. The recent use of new targeted therapies appears to be promising for relapsed/refractory patients, such as demethylating agents in T-follicular helper (TFH) PTCL. However further studies are needed to evaluate the proper combination of these drugs in the setting of front-line therapy. In this review, we will summarize the oncogenic events for the main PTCL entities and report the molecular targets that have led to the development of new therapies. We will also discuss the development of innovative high throughput technologies that aid the routine workflow for the histopathological diagnosis and management of PTCL patients.
Treatment of bilateral congenital extensor tendon dislocation on multiple digits with only one sagittal band reconstruction: a case report
Authors: Lim Jun-Hyuk , Jung Sung-Taek , Cheon Jae Hyeok , Kim Sungmin
Published: June 2023

Bilateral congenital dislocation of the extensor tendon in the metacarpophalangeal joint is an exceedingly rare disease and often involves multiple fingers. Surgical treatment of multiple congenital extensor tendon dislocations in both hands has been reported; however, no report has clearly stated whether all fingers should be surgically treated in patients with multiple finger involvement. We report a case in which we successfully treated bilateral congenital extensor tendon dislocation on multiple digits with only one single-loop reconstruction of the sagittal band instead of operating on all involved fingers.
Ureteral dilation recovery after intravesical reimplantation in children with primary obstructive megaureter
Authors: He Yan , Wu Xuemin , Xu Yingrui , Liu Zhaoquan , Du Guoqiang , Wu Xiangyu , Liu Wei , Wu Rongde
Published: June 2023

Background

To observe the postoperative recovery following ureteral dilation in primary obstructive megaureter (POM) after ureteral implantation, and evaluate the risk factors affecting ureter diameter resolution.

Materials and Methods

A retrospective study was performed in patients with POM who underwent ureteral reimplantation using the Cohen procedure. Patient characteristics, perioperative parameters, and postoperative outcomes were also analysed. A widest ureteral diameter of <7 mm was defined as a normal shape and outcome. Survival time was defined as the time from surgery to ureteral dilation recovery or to the last follow-up.

Results

A total of 49 patients (54 ureters) were included in the analysis. The survival time ranged from 1 to 53 months. The shapes of a total of 47 (87.04%) megaureters recovered, and most (29/47) resolutions happened within 6 months after surgery. In the univariate analysis, bilateral ureterovesical reimplantation (p = 0.015), ureteral terminal tapering (p = 0.019), weight (p = 0.036), and age (p = 0.015) were associated with the recovery time of ureteral dilation. A delayed recovery of ureteral diameter was noted in bilateral reimplantation (HR = 0.336, p = 0.017) using multivariate Cox regression.

Conclusions

Ureteral dilation in POM mostly returned to normal within six postoperative months. Moreover, bilateral ureterovesical reimplantation is a risk factor for delayed postoperative recovery of ureter dilation in POM.
Can early-onset acquired demyelinating syndrome (ADS) hide pediatric Behcet's disease? A case report
Authors: Pozzato Mattia , Dilena Robertino , Rogani Greta , Beretta Gisella , Torreggiani Sofia , Lanni Stefano , Tozzo Alessandra , Andreetta Francesca , Cavalcante Paola , Triulzi Fabio , Martinelli Boneschi Filippo , Minoia Francesca , Filocamo Giovanni
Published: June 2023

Behcet's disease (BD) is a rare vasculitis characterized by multisystemic inflammation. Central nervous system (CNS) involvement is rare and heterogeneous, particularly in the pediatric population. A diagnosis of neuro-Behcet could be highly challenging, especially if neurological manifestations precede other systemic features; however, its timely definition is crucial to prevent long-term sequelae. In this study, we describe the case of a girl who, at 13 months of age, presented with a first episode of encephalopathy compatible with acute disseminated encephalomyelitis, followed, after 6 months, by a neurological relapse characterized by ophthalmoparesis and gait ataxia, in association with new inflammatory lesions in the brain and spinal cord, suggesting a neuromyelitis optica spectrum disorder. The neurological manifestations were successfully treated with high-dose steroids and intravenous immunoglobulins. In the following months, the patient developed a multisystemic involvement suggestive of Behcet's disease, characterized by polyarthritis and uveitis, associated with HLA-B51 positivity. The challenge presented by this unique case required a multidisciplinary approach involving pediatric neurologists, neuro-radiologists, and pediatric rheumatologists, with all of these specialists creating awareness about early-onset acquired demyelinating syndromes (ADSs). Given the rarity of this presentation, we performed a review of the literature focusing on neurological manifestations in BD and differential diagnosis of patients with early-onset ADS.
Impact of the 2017 AAP clinical guideline on the prevalence of high blood pressure among adolescents in Lagos, Nigeria
Authors: Atoh Ifeoma , Ezeogu Joseph , Ekure Ekanem , Omokhodion Samuel Ilenre , Njokanma Fidelis Olisamedua
Published: June 2023

Introduction

Adolescent high blood pressure (HBP) can lead to several end-organ complications if it continues into adulthood. The 2017 AAP Guideline has lower blood pressure cut-off points and consequently leads to the identification of more people with high blood pressure. This study evaluated the impact of the 2017 American Academy of Pediatrics (AAP) Clinical Guideline on the prevalence of high blood pressure among adolescents when compared to the 2004 Fourth Report.

Methodology

A descriptive cross-sectional study was conducted from August 2020 to December 2020. The selection of 1,490 students, 10–19 years old, was by a two-stage sampling technique. Socio-demographic information and relevant clinical data were obtained using a structured questionnaire. Blood pressure was measured according to standard protocol. Categorical and numerical variables were summarized using frequency, percentages, mean, and standard deviation. The McNemar-Bowker test of symmetry was used to compare the blood pressure values in the 2004 Fourth Report and the 2017 AAP Clinical Guideline. The Kappa statistic was used to test for the degree of agreement between the 2004 Fourth Report and the 2017 AAP Clinical Guideline.

Results

The prevalence rates of high blood pressure, elevated blood pressure, and hypertension among adolescents were 26.7%, 13.8%, and 12.9%, respectively, using the 2017 AAP Clinical Guideline, and 14.5%, 6.1%, and 8.4%, respectively, using the 2004 Fourth Report. The degree of agreement between the 2004 and 2017 guidelines with respect to the classification of blood pressure was 84.8%. The Kappa statistic was 0.71 (CI: 0.67–0.75). The impact of this was a 12.2%, 7.7%, and 4.5% increase in the prevalence of high blood pressure, elevated blood pressure, and hypertension, respectively, using the 2017 AAP Clinical Guideline.

Conclusion

The 2017 AAP Clinical Guideline detects a greater proportion of high blood pressure among adolescents. The adoption of this new guideline in clinical practice and its use in the routine screening of high blood pressure among adolescents is recommended.
Characteristics and risk factors for spontaneous and postoperative consecutive exotropia in children with esotropia
Authors: Wen Jing , Li Ruiying , Li Ruoshi , Li Xiaoqing , Zhu Dehai
Published: June 2023

Background

To investigate the risk factors for the development of consecutive exotropia (CXT) by comparing patients with spontaneous or postoperative CXT during follow-up with another group of patients who had no deviation or less than 10 prism dioptre (PD) esotropia.

Methods

In this retrospective cohort study, 6 patients with spontaneous CXT (group A), 13 patients with postoperative CXT (group B), and 39 patients with no exotropia (group C) were enrolled. Probable risk factors for CXT were evaluated among the groups. Kruskal-Wallis H test was used to determine if any significant differences were present among the groups. Fisher’s exact test or Mann-Whitney U test was used for univariate analyses to compare differences between case groups or between case and control groups. The Bonferroni method was used to conduct multiple comparisons.

Results

The follow-up period of spontaneous CXT patients was significantly longer than that of postoperative CXT and nonconsecutive exotropia patients (p = 0.035 and p < 0.001, respectively). The interval between alignment and CXT onset in spontaneous CXT patients was slightly longer than that in postoperative CXT patients, but not significantly difference (6.50 vs. 5.00 years, p = 0.072). Vertical deviation was associated with a high risk of postoperative CXT (p = 0.001). Most [38 (97.44%)] nonconsecutive exotropia patients had fusion; conversely, the absence of fusion function (p < 0.001) as well as stereoacuity (p = 0.029) were associated with a high risk of CXT.

Conclusion

Vertical deviation and poor binocular function are strongly associated with a high risk of CXT. Children with spontaneous CXT are highly recommended to be followed-up long-term, while they maintain long-term ocular alignment before developing consecutive exotropia from comitant esotropia (CE).
The activation of GABAergic neurons in the hypothalamic tuberomammillary nucleus attenuates sevoflurane and propofol-induced anesthesia in mice
Authors: Liu Jing , Liu Xiao , Zhou Wen-Yu , Gan Jun , Wang Jie , Zhang Qi , Li Jun-Liang , Shen Zhong-Shan , Zhang Yue-Ying , Tang Qiong-Yao , Zhang Zhe
Published: June 2023

Background: The histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) have been suggested to play a vital role in maintaining a rising state. But the neuronal types of the TMN are in debate and the role of GABAergic neurons remains unclear.

Methods: In the present study, we examined the role of TMN GABAergic neurons in general anesthesia using chemogenetics and optogenetics strategies to regulate the activity of TMN GABAergic neurons.

Results: The results indicated that either chemogenetic or optogenetic activation of TMN GABAergic neurons in mice decreased the effect of sevoflurane and propofol anesthesia. In contrast, inhibition of the TMN GABAergic neurons facilitates the sevoflurane anesthesia effect.

Conclusion: Our results suggest that the activity of TMN GABAergic neurons produces an anti-anesthesia effect in loss of consciousness and analgesia.
Update on poly(ADP-ribose) polymerase inhibitors resistance in ovarian cancer
Authors: Dong Ruihong , Ding Ting , Li Zhengyu
Published: June 2023

Ovarian cancer is one of the most common reproductive system tumors. The incidence of ovarian cancer in China is on the rise. Poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) is a DNA repair enzyme associated with DNA damage repair. PARPi takes PARP as a target to kill tumor cells, especially for tumors with homologous recombination (HR) dysfunction. Currently, PARPi has been widely used in clinical practice, mainly for the maintenance of advanced ovarian epithelial cancer. The intrinsic or acquired drug resistance of PARPi has gradually become an important clinical problem with the wide application of PARPi. This review summarizes the mechanisms of PARPi resistance and the current progress on PARPi-based combination strategies.
Superconducting undulator activities at the European X-ray Free-Electron Laser Facility
Authors: Casalbuoni Sara , Abeghyan Suren , Alanakyan Levon , Baader Johann , Barbanotti Serena , Decking Winfried , Felice Massimiliano Di , Eckoldt Hans-Jörg , Englisch Uwe , Geloni Gianluca , Grattoni Vanessa , Grau Andreas , Hauberg Axel , Helwich Christian , Hobl Achim , Jensch Kay , Karabekyan Suren , Civita Daniele La , Lederer Sven , Lechner Christoph , Lilje Lutz , Liu Shan , Marchetti Barbara , Potter Andrew , Schnautz Tobias , Schneidmiller Evgeny , Sinn Harald , Walter Wolfgang , Wichmann Riko , Wohlenberg Torsten , Yakopov Grigory , Yakopov Mikhail , Zagorodnov Igor , Zimmermann René , Ziolkowski Pawel
Published: June 2023

For more than 5 years, superconducting undulators (SCUs) have been successfully delivering X-rays in storage rings. The European X-Ray Free-Electron Laser Facility (XFEL) plans to demonstrate the operation of SCUs in X-ray free-electron lasers (FELs). For the same geometry, SCUs can reach a higher peak field on the axis with respect to all other available technologies, offering a larger photon energy tunability range. The application of short-period SCUs in a high electron beam energy FEL > 11 GeV will enable lasing at very hard X-rays > 40 keV. The large tunability range of SCUs will allow covering the complete photon energy range of the soft X-ray experiments at the European XFEL without changing electron beam energy, as currently needed with the installed permanent magnet undulators. For a possible continuous-wave (CW) upgrade under discussion at the European XFEL with a lower electron beam energy of approximately 7–8 GeV, SCUs can provide the same photon energy range as available at present with the permanent magnet undulators and electron energies. This paper will describe the potential of SCUs for X-ray FELs. In particular, it will focus on the different activities ongoing at the European XFEL and in collaboration with DESY to allow the implementation of SCUs in the European XFEL in the upcoming years.
Moore–Gibson–Thompson model with the influence of moisture diffusivity of semiconductor materials during photothermal excitation
Authors: El-Sapa Shreen , Becheikh Nidhal , Chtioui Houda , Lotfy Kh. , Seddeek M. A. , El-Bary Alaa A. , El-Dali A.
Published: June 2023

In the present work, the semiconductor material is used to study the moisture diffusivity when a modified Moore–Gibson–Thompson (MGT) model is taken into account. The influence of moisture concentration is included in the governing equations throughout the photothermal transfer process. Based on the dissimilar relaxation durations of the coupled optoelectronic and thermoelastic waves, the MGT model is used to investigate the issue at hand. The method of the Laplace transform is used to obtain analytical solutions for the physical quantities, constitutive relationships, elastic waves, carrier density, heat equation conduction, and moisture diffusivity for the thermo-elastic medium. To extract the primary physical quantities in the space–time domain, the boundary conditions, temperature, plasma, displacement, and mechanical stress are inverted numerically using the Laplace transform. The effect of the new parameter like the reference moisture parameter with various values is discussed graphically on the primary physical quantities. The comparison between silicon and germanium is taken into account to achieve numerical computations.
Effects of rest interval and training intensity on jumping performance: a systematic review and meta-analysis investigating post-activation performance enhancement
Authors: Chen Yiyan , Su Qing , Yang Juan , Li Gen , Zhang Shiyan , Lv Yuanyuan , Yu Laikang
Published: June 2023

Background: There is no clear agreement regarding the ideal rest interval and training intensity to optimize post-activation performance enhancement (PAPE) after barbell squat (BS). Therefore, the aim of this study was to investigate the effects of rest interval and training intensity on jumping performance due to PAPE.

Methods: Searches were performed in PubMed, Web of Science, and EBSCO databases. We included studies that satisfied the following criteria: (1) eligible studies should be randomized controlled trials; (2) eligible studies should investigate the acute effect of barbell squat-induced PAPE on jump performance; (3) eligible studies should use countermovement jump, squat jump, or vertical jump as the outcome measure.

Results: From 2518 search records initially identified, 19 studies were eligible for meta-analysis. Our meta-analysis results showed that BS had no significant effect on improving jumping performance due to PAPE (Cohen’s d = 0.09, p = 0.08). Subgroup analysis showed that rest interval between 0–1 min was detrimental to jumping performance (Cohen’s d = −0.33, p < 0.01), while rest intervals between 4–7 min (Cohen’s d = 0.31, p < 0.01) and 8-9 min (Cohen’s d = 0.26, p = 0.02) provided favorable jumping performance outcomes. In addition, low-intensity and moderate-intensity BS had no significant effect on jump performance, while high-intensity BS showed results consistent with rest interval.

Conclusion: Our study indicated that both low-intensity and moderate-intensity BS failed to induce PAPE, and it is recommended that future studies use high-intensity BS to induce PAPE. A rest interval of 4–9 min had a beneficial impact on jump height, and an interval range of 4–7 min seems to be the best rest interval between conditioning activity and jumping performance.
Impact of biofertilisers on iron homeostasis and grain quality in the rice variety Uma under Elevated CO2
Authors: Bhavya M. S. P. , Manju R. V. , Viji M. M. , Roy S. , Anith K. N. , Beena R.
Published: June 2023

The diminishing nutritional quality of rice with increasing concentrations of atmospheric CO2 is currently a major global concern. The present study was designed with the objective of assessing the impact of biofertilisers on grain quality and iron homeostasis in rice under elevated CO2. A completely randomised design with four treatments ([KAU, POP (control), POP+Azolla, POP+PGPR, and POP+AMF]), each replicated three times under ambient and elevated CO2 conditions, was followed. The analysed data revealed that yield, grain quality, and iron uptake and translocation were modified in an unfavourable manner under elevated CO2, which was reflected in the lower quality and iron content of the grains. The response of iron homeostasis in the experimental plants to the application of biofertilisers, especially plant-growth-promoting rhizobacteria (PGPR), under elevated CO2 strongly suggests the possibility of utilising them for designing iron management strategies for achieving higher quality in rice.
Dynamic monitoring of maize grain quality based on remote sensing data
Authors: Sun Weiwei , He Qijin , Liu Jiahong , Xiao Xiao , Wu Yaxin , Zhou Sijia , Ma Selimai , Wang Rongwan
Published: June 2023

Remote sensing data have been widely used to monitor crop development, grain yield, and quality, while precise monitoring of quality traits, especially grain starch and oil contents considering meteorological elements, still needs to be improved. In this study, the field experiment with different sowing time, i.e., 8 June, 18 June, 28 June, and 8 July, was conducted in 2018–2020. The scalable annual and inter-annual quality prediction model for summer maize in different growth periods was established using hierarchical linear modeling (HLM), which combined hyperspectral and meteorological data. Compared with the multiple linear regression (MLR) using vegetation indices (VIs), the prediction accuracy of HLM was obviously improved with the highest R2, root mean square error (RMSE), and mean absolute error (MAE) values of 0.90, 0.10, and 0.08, respectively (grain starch content (GSC)); 0.87, 0.10, and 0.08, respectively (grain protein content (GPC)); and 0.74, 0.13, and 0.10, respectively (grain oil content (GOC)). In addition, the combination of the tasseling, grain-filling, and maturity stages further improved the predictive power for GSC (R2 = 0.96). The combination of the grain-filling and maturity stages further improved the predictive power for GPC (R2 = 0.90). The prediction accuracy developed in the combination of the jointing and tasseling stages for GOC (R2 = 0.85). The results also showed that meteorological factors, especially precipitation, had a great influence on grain quality monitoring. Our study provided a new idea for crop quality monitoring by remote sensing.
Two plant-associated Bacillus velezensis strains selected after genome analysis, metabolite profiling, and with proved biocontrol potential, were enhancing harvest yield of coffee and black pepper in large field trials
Authors: Thanh Tam Le Thi , Jähne Jennifer , Luong Pham Thi , Phuong Thao Le Thi , Nhat Le Mai , Blumenscheit Christian , Schneider Andy , Blom Jochen , Kim Chung Le Thi , Anh Minh Pham Le , Thanh Ha Minh , Hoat Trinh Xuan , Hoat Pham Cong , Son Tran Cao , Weinmann Markus , Herfort Stefanie , Vater Joachim , Van Liem Nguyen , Schweder Thomas , Lasch Peter , Borriss Rainer
Published: June 2023

Elimination of chemically synthesized pesticides, such as fungicides and nematicides, in agricultural products is a key to successful practice of the Vietnamese agriculture. We describe here the route for developing successful biostimulants based on members of the Bacillus subtilis species complex. A number of endospore-forming Gram-positive bacterial strains with antagonistic action against plant pathogens were isolated from Vietnamese crop plants. Based on their draft genome sequence, thirty of them were assigned to the Bacillus subtilis species complex. Most of them were assigned to the species Bacillus velezensis. Whole genome sequencing of strains BT2.4 and BP1.2A corroborated their close relatedness to B. velezensis FZB42, the model strain for Gram-positive plant growth-promoting bacteria. Genome mining revealed that at least 15 natural product biosynthesis gene clusters (BGCs) are well conserved in all B. velezensis strains. In total, 36 different BGCs were identified in the genomes of the strains representing B. velezensis, B. subtilis, Bacillus tequilensis, and Bacillus. altitudinis. In vitro and in vivo assays demonstrated the potential of the B. velezensis strains to enhance plant growth and to suppress phytopathogenic fungi and nematodes. Due to their promising potential to stimulate plant growth and to support plant health, the B. velezensis strains TL7 and S1 were selected as starting material for the development of novel biostimulants, and biocontrol agents efficient in protecting the important Vietnamese crop plants black pepper and coffee against phytopathogens. The results of the large-scale field trials performed in the Central Highlands in Vietnam corroborated that TL7 and S1 are efficient in stimulating plant growth and protecting plant health in large-scale applications. It was shown that treatment with both bioformulations resulted in prevention of the pathogenic pressure exerted by nematodes, fungi, and oomycetes, and increased harvest yield in coffee, and pepper.
Who belongs to the swiss body politique—A diaspora perspective
Authors: King-Savic Sandra
Published: June 2023

In this paper, I try to better understand the intersection between “integration” in legal terms, and how long-term resident “non-citizens” and migrants from the former Socialist Federal Republic of Yugoslavia (SFRY) situate themselves in narratives of belonging vis a vis the normative power structure that constitutes the Swiss body politique. More specifically, how do labor and forced migrants from former Yugoslavia negotiate the shifting understanding of “integration” in Switzerland in legal and social terms? Former Yugoslavs constitute not only a comparatively large number of “non-citizens” in Switzerland, but individuals from-and-with-connections to this community also embody numerous labels and categories of migrant that statistical databases, the media, and legal practices attach to them since the 1970s. Key findings in this paper illustrate a two-tiered narrative: “non-citizens” seemed to have maintain(ed) their pursuit of not attracting attention to their persona—a strategy that allowed individuals to disappear within the larger society. Ensuing Europeanization processes, coupled with the Wars of Yugoslav Succession during the 1990s, however, brought to the fore “a politics of rupture” that called into question othering processes, and the seemingly tightening sociolegal basis of belonging to the Swiss body politique. Hitherto examined data suggests that interlocutors pursue a “positive essentialist frame” to counter exclusionary narratives “non-citizens” experience to postulate “rights claims”. Interviewees, in other words, activate diaspora connections and networks to support and aid each other when legal and socio-political questions arise, but also to actively influence the political and legal landscape in Switzerland.