bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics, outcomes, and risk factors for in-hospital mortality of COVID-19 patients: A retrospective study in Thailand
Authors: Naorungroj Thummaporn , Viarasilpa Tanuwong , Tongyoo Surat , Detkaew Aeckapholpholladet , Pinpak Thanchanok , Wimolwattanaphan Rawish , Ratanarat Ranistha , Promsin Panuwat , Thamrongpiroj Preecha , Phumpichet Akekarin , Permpikul Chairat
Published: January 2023

Introduction

Data on the characteristics and outcomes of patients hospitalized for Coronavirus Disease 2019 (COVID-19) in Thailand are limited.

Objective

To determine characteristics and outcomes and identify risk factors for hospital mortality for hospitalized patients with COVID-19.

Methods

We retrospectively reviewed the medical records of patients who had COVID-19 infection and were admitted to the cohort ward or ICUs at Siriraj Hospital between January 2020 and December 2021.

Results

Of the 2,430 patients included in this study, 229 (9.4%) died; the mean age was 54 years, 40% were men, 81% had at least one comorbidity, and 13% required intensive care unit (ICU). Favipiravir (86%) was the main antiviral treatment. Corticosteroids and rescue anti-inflammatory therapy were used in 74 and 6%, respectively. Admission to the ICU was the only factor associated with reduced mortality [odds ratio (OR) 0.01, 95% confidence interval (CI) 0.01–0.05, P < 0.001], whereas older age (OR 14.3, 95%CI 5.76–35.54, P < 0.001), high flow nasal cannula (HFNC; OR 9.2, 95% CI 3.9–21.6, P < 0.001), mechanical ventilation (OR 269.39, 95%CI 3.6–2173.63, P < 0.001), septic shock (OR 7.79, 95%CI, 2.01–30.18, P = 0.003), and hydrocortisone treatment (OR 27.01, 95%CI 5.29–138.31, P < 0.001) were factors associated with in-hospital mortality.

Conclusion

The overall mortality of hospitalized patients with COVID-19 was 9%. The only factor associated with reduced mortality was admission to the ICU. Therefore, appropriate selection of patients for admission to the ICU, strategies to limit disease progression and prevent intubation, and early detection and prompt treatment of nosocomial infection can improve survival in these patients.
Clinical imaging of primary pulmonary nucleoprotein of the testis carcinoma
Authors: Huang Wenpeng , Zhang Yongbai , Yang Qi , Gao Ge , Qiu Yongkang , Li Liming , Kang Lei
Published: January 2023

Objective

Primary pulmonary nucleoprotein of the testis (NUT) carcinoma is very rare in the clinic. In this study, the clinicopathological manifestations and imaging features of the primary pulmonary NUT carcinoma were investigated to improve the diagnosis of this disease.

Methods

Six patients with pathologically diagnosed pulmonary NUT carcinoma were analyzed, including three males and three females, aged 19–64 (49.00 ± 16.40) years, with clinical manifestations of cough in two cases, hoarseness in one case, blood in sputum in one case, chest pain in one case, and physical examination findings in one case, with a disease duration of 5 days to 4 months. The clinical and imaging data including CT and PET/CT were retrospectively analyzed. Further literature reviews were analyzed in both pulmonary and extrapulmonary NUT carcinoma cases who performed18F-FDG PET/CT.

Results

Most of the patients with pulmonary NUT carcinomas presented as heterogeneous lobulated masses (83.33%), four cases (66.67%) were located in the upper lobe of the left lung, one case (16.67%) in the middle lobe of the right lung, and one case (16.67%) in the lower lobe of the right lung, with the maximum diameter ranging from 1.30 to 8.90 cm and the median of 3.55 cm, most of them were irregularly shaped, with more lobulated margins and more heterogeneous density (83.33%), and the enhancement was mild. PET/CT showed increased18F-FDG uptake in the lesion and metastatic areas. Both the pulmonary NUT patients in this study and literature reviews showed the SUVmaxof the tumor ranged from 5 to 40 with an average value of 12.8, whereas that of extrapulmonary lesions had a range of SUVmaxat 4.5–64.1 and a mean of 13.8.

Conclusion

In patients with central lung masses, rapid disease progression, and poor response to initial treatment, the possibility of NUT cancer should be considered and anti-NUT monoclonal antibody immunohistochemical staining, combined with genetic detection, if necessary, should be performed as soon as possible. CT and PET/CT imaging are essential for the staging, management, treatment response assessment, and monitoring of pulmonary NUT cancer.
In-depth characterization of phytase-producing plant growth promotion bacteria isolated in alpine grassland of Qinghai-Tibetan Plateau
Authors: Li Qi , Yang Xiaolei , Li Jianhong , Li Mingyuan , Li Changning , Yao Tuo
Published: January 2023

The use of plant growth promoting bacteria (PGPB) express phytase (myo-inositol hexakisphosphate phosphohydrolase) capable of hydrolyzing inositol phosphate in soil was a sustainable approach to supply available phosphorus (P) to plants. A total of 73 bacterial isolates with extracellular phytase activity were selected from seven dominant grass species rhizosphere in alpine grassland of Qinghai-Tibetan Plateau. Then, the plant growth promoting (PGP) traits of candidate bacteria were screened by qualitative and quantitative methods, including organic/inorganic Phosphorus solubilization (P. solubilization), plant hormones (PHs) production, nitrogen fixation, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity and antimicrobial activity. Further experiment were conducted to test their growth promoting effect on Lolium perenne L. under P-limitation. Our results indicated that these bacteria as members of phyla Proteobacteria (90.41%) and Actinobacteria (9.59%) were related to 16 different genera. The isolates of Pseudomonas species showed the highest isolates number (36) and average values of phytase activity (0.267 ± 0.012 U mL–1), and showed a multiple of PGP traits, which was a great candidate for PGPBs. In addition, six strains were positive in phytase gene (β-propeller phytase, bpp) amplification, which significantly increased the shoot length, shoot/root fresh weight, root average diameter and root system phytase activity of Lolium perenne L. under P-limitation, and the expression of phytase gene (bppP) in root system were verified by qPCR. Finally, the PHY101 gene encoding phytase from Pseudomonas mandelii GS10-1 was cloned, sequenced, and recombinantly expressed in Escherichia coli. Biochemical characterization demonstrated that the recombinant phytase PHY101 revealed the highest activity at pH 6 and 40°C temperature. In particular, more than 60% of activity was retained at a low temperature of 15°C. This study demonstrates the opportunity for commercialization of the phytase-producing PGPB to developing localized microbial inoculants and engineering rhizobacteria for sustainable use in alpine grasslands.
Intestinal epithelial cell-derived components regulate transcriptome of Lactobacillus rhamnosus GG
Authors: Schalich Kasey , Rajagopala Seesandra , Das Suman , O’Connell Ryan , Yan Fang
Published: January 2023

Introduction

Intestinal epithelial cells (IECs) provide the frontline responses to the gut microbiota for maintaining intestinal homeostasis. Our previous work revealed that IEC-derived components promote the beneficial effects of a commensal and probiotic bacterium, Lactobacillus rhamnosus GG (LGG). This study aimed to elucidate the regulatory effects of IEC-derived components on LGG at the molecular level.

Methods

Differential gene expression in LGG cultured with IEC-derived components at the timepoint between the exponential and stationary phase was studied by RNA sequencing and functional analysis.

Results

The transcriptomic profile of LGG cultured with IEC-derived components was significantly different from that of control LGG, with 231 genes were significantly upregulated and 235 genes significantly down regulated (FDR <0.05). The Clusters of Orthologous Groups (COGs) and Gene Ontology (GO) analysis demonstrated that the predominant genes enriched by IEC-derived components are involved in nutrient acquisition, including transporters for amino acids, metals, and sugars, biosynthesis of amino acids, and in the biosynthesis of cell membrane and cell wall, including biosynthesis of fatty acid and lipoteichoic acid. In addition, genes associated with cell division and translation are upregulated by IEC-derived components. The outcome of the increased transcription of these genes is supported by the result that IEC-derived components significantly promoted LGG growth. The main repressed genes are associated with the metabolism of amino acids, purines, carbohydrates, glycerophospholipid, and transcription, which may reflect regulation of metabolic mechanisms in response to the availability of nutrients in bacteria.

Discussion

These results provide mechanistic insight into the interactions between the gut microbiota and the host.
Biocontrol activity of Bacillus halotolerans strain Pl7 against Botryosphaeria dothidea causing apple postharvest decay and potential mechanisms
Authors: Yuan Hongbo , Yuan Mengjia , Shi Bingke , Wang Zhuoni , Huang Tianxiang , Zhu Jiahong , Hou Hui , Wang Li , Tu Hongtao
Published: January 2023

Apple ring rot, one of the most common apple postharvest diseases during storage, is caused by Botryosphaeria dothidea. Fungicide application is the most widely used method to control this disease, but the increasing environmental and food safety concerns greatly limit their use. The present study aimed to examine the biocontrol activity and underlying action mechanism of Bacillus halotolerans strain Pl7 against B. dothidea. The results revealed that B. halotolerans strain Pl7 exhibited strong inhibitory activity against B. dothidea by 69% in vitro. The culture filtrate of strain Pl7 possessed cellulase, β-1, 3-glucanase, protease activity and mediated the antifungal activity against B. dothidea. Further analysis demonstrated that culture filtrate of strain Pl7 could cause cell membrane permeabilization of B. dothidea. Apple fruit suffering from ring rot induced by a carbendazim (CBZ)-sensitive or -resistant B. dothidea isolate was much suppressed after being treated with strain Pl7, maintaining postharvest quality. The ability of strain Pl7 to swiftly colonize and thrive in apple fruit wounds was demonstrated by a re-isolation assay. Additional transcriptome studies of untreated and treated apple fruit with strain Pl7 revealed that strain Pl7 mostly changed the expression of genes functioning in plant secondary metabolite biosynthesis and plant-pathogen interaction. In light of these outcomes, the underlying antagonistic mechanism was investigated, and B. halotolerans strain Pl7 was identified as a promsing microbial biocontrol agent against apple postharvest decay.
Whole-genome sequencing, annotation, and biological characterization of a novel Siphoviridae phage against multi-drug resistant Propionibacterium acne
Authors: Liao Danxi , Zhang Jian , Liu Ruolan , Chen Kui , Liu Yuanyuan , Shao Yuming , Shi Xi , Zhang Yiming , Yang Zichen
Published: January 2023

Antibiotics-resistant Propionibacterium acne (P. acne) causes severe acne vulgaris, serious public health, and psychological threat. A new lytic bacteriophage (phage), φPaP11-13, infecting P. acne, was isolated from the sewage management center of Xinqiao Hospital. It can form transparent plaque with diameters of 1.0 ~ 5.0 mm on the double-layer agar plate, indicating a robust lytic ability against its host. Transmission electron microscopy (TEM) showed that φPaP11-13 belonged to the Siphoviridae family (head diameter 60 ± 4.5 nm, tail length 170 ± 6.4 nm, tail width 14 ± 2.4 nm). The one-step growth curve showed the incubation period was 5 h, and the burst size was 26 PFU (plaque-forming unit)/cell. Moreover, it exhibited tolerance over a broad range of pH and temperature ranges but was utterly inactivated by ultraviolet (UV) irradiation for 1 h. The whole-genome sequencing results revealed φPaP11-13 had a linear dsDNA with 29,648 bp length. The G/C content was 54.08%. Non-coding RNA genes and virulence factors were not found. Forty five open reading frames (ORFs) were identified after online annotation. This study reports a novel P. acne phage φPaP11-13, which has a robust lytic ability, no virulence factors, and good stability. The characterization and genomic analysis of φPaP11-13 will develop our understanding of phage biology and diversity and provide a potential arsenal for controlling antibiotics-resistant P. acne-induced severe acne vulgaris.
Pan-genome association study of Mycobacterium tuberculosis lineage-4 revealed specific genes related to the high and low prevalence of the disease in patients from the North-Eastern area of Medellín, Colombia
Authors: Hurtado-Páez Uriel , Álvarez Zuluaga Nataly , Arango Isaza Rafael Eduardo , Contreras-Moreira Bruno , Rouzaud François , Robledo Jaime
Published: January 2023

Mycobacterium tuberculosis (Mtb) lineage 4 is responsible for the highest burden of tuberculosis (TB) worldwide. This lineage has been the most prevalent lineage in Colombia, especially in the North-Eastern (NE) area of Medellin, where it has been shown to have a high prevalence of LAM9 SIT42 and Haarlem1 SIT62 sublineages. There is evidence that regardless of environmental factors and host genetics, differences among sublineages of Mtb strains play an important role in the course of infection and disease. Nevertheless, the genetic basis of the success of a sublineage in a specific geographic area remains uncertain. We used a pan-genome-wide association study (pan-GWAS) of 47 Mtb strains isolated from NE Medellin between 2005 and 2008 to identify the genes responsible for the phenotypic differences among high and low prevalence sublineages. Our results allowed the identification of 12 variants in 11 genes, of which 4 genes showed the strongest association to low prevalence (mmpL12, PPE29, Rv1419, and Rv1762c). The first three have been described as necessary for invasion and intracellular survival. Polymorphisms identified in low prevalence isolates may suggest related to a fitness cost of Mtb, which might reflect a decrease in their capacity to be transmitted or to cause an active infection. These results contribute to understanding the success of some sublineages of lineage-4 in a specific geographical area.
Identification of pathogens and detection of antibiotic susceptibility at single-cell resolution by Raman spectroscopy combined with machine learning
Authors: Lu Weilai , Li Haifei , Qiu Haoning , Wang Lu , Feng Jie , Fu Yu Vincent
Published: January 2023

Rapid, accurate, and label-free detection of pathogenic bacteria and antibiotic resistance at single-cell resolution is a technological challenge for clinical diagnosis. Overcoming the cumbersome culture process of pathogenic bacteria and time-consuming antibiotic susceptibility assays will significantly benefit early diagnosis and optimize the use of antibiotics in clinics. Raman spectroscopy can collect molecular fingerprints of pathogenic bacteria in a label-free and culture-independent manner, which is suitable for pathogen diagnosis at single-cell resolution. Here, we report a method based on Raman spectroscopy combined with machine learning to rapidly and accurately identify pathogenic bacteria and detect antibiotic resistance at single-cell resolution. Our results show that the average accuracy of identification of 12 species of common pathogenic bacteria by the machine learning method is 90.73 ± 9.72%. Antibiotic-sensitive and antibiotic-resistant strains of Acinetobacter baumannii isolated from hospital patients were distinguished with 99.92 ± 0.06% accuracy using the machine learning model. Meanwhile, we found that sensitive strains had a higher nucleic acid/protein ratio and antibiotic-resistant strains possessed abundant amide II structures in proteins. This study suggests that Raman spectroscopy is a promising method for rapidly identifying pathogens and detecting their antibiotic susceptibility.
Acclimation of Nodularia spumigena CCY9414 to inorganic phosphate limitation – Identification of the P-limitation stimulon via RNA-seq
Authors: Santoro Mariano , Hassenrück Christiane , Labrenz Matthias , Hagemann Martin
Published: January 2023

Nodularia spumigena is a toxic, filamentous cyanobacterium capable of fixing atmospheric N2, which is often dominating cyanobacterial bloom events in the Baltic Sea and other brackish water systems worldwide. Increasing phosphate limitation has been considered as one environmental factor promoting cyanobacterial mass developments. In the present study, we analyzed the response of N. spumigena strain CCY9414 toward strong phosphate limitation. Growth of the strain was diminished under P-deplete conditions; however, filaments contained more polyphosphate under P-deplete compared to P-replete conditions. Using RNA-seq, gene expression was compared in N. spumigena CCY9414 after 7 and 14 days in P-deplete and P-replete conditions, respectively. After 7 days, 112 genes were significantly up-regulated in P-deplete filaments, among them was a high proportion of genes encoding proteins related to P-homeostasis such as transport systems for different P species. Many of these genes became also up-regulated after 14 days compared to 7 days in filaments grown under P-replete conditions, which was consistent with the almost complete consumption of dissolved P in these cultures after 14 days. In addition to genes directly related to P starvation, genes encoding proteins for bioactive compound synthesis, gas vesicles formation, or sugar catabolism were stimulated under P-deplete conditions. Collectively, our data describe an experimentally validated P-stimulon in N. spumigena CCY9414 and provide the indication that severe P limitation could indeed support bloom formation by this filamentous strain.
Variable number tandem repeats of a 9-base insertion in the N-terminal domain of severe acute respiratory syndrome coronavirus 2 spike gene
Authors: Akaishi Tetsuya , Fujiwara Kei , Ishii Tadashi
Published: January 2023

Introduction

The world is still struggling against the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in 2022. The pandemic has been facilitated by the intermittent emergence of variant strains, which has been explained and classified mainly by the patterns of point mutations of the spike (S) gene. However, the profiles of insertions/deletions (indels) in SARS-CoV-2 genomes during the pandemic remain largely unevaluated yet.

Methods

In this study, we first screened for the genome regions of polymorphic indel sites by performing multiple sequence alignment; then, NCBI BLAST search and GISAID database search were performed to comprehensively investigate the indel profiles at the polymorphic indel hotspot and elucidate the emergence and spread of the indels in time and geographical distribution.

Results

A polymorphic indel hotspot was identified in the N-terminal domain of the S gene at approximately 22,200 nucleotide position, corresponding to 210–215 amino acid positions of SARS-CoV-2 S protein. This polymorphic hotspot was comprised of adjacent 3-base deletion (5′-ATT-3′; Spike_N211del) and 9-base insertion (5’-AGCCAGAAG-3′; Spike_ins214EPE). By performing NCBI BLAST search and GISAID database search, we identified several types of tandem repeats of the 9-base insertion, creating an 18-base insertion (Spike_ins214EPEEPE, Spike_ins214EPDEPE). The results of the searches suggested that the two-cycle tandem repeats of the 9-base insertion were created in November 2021 in Central Europe, whereas the emergence of the original one-cycle 9-base insertion (Spike_ins214EPE) would date back to the middle of 2020 and was away from the Central Europe. The identified 18-base insertions based on 2-cycle tandem repeat of the 9-base insertion were collected between November 2021 and April 2022, suggesting that these mutations could not survive and have been already eliminated.

Discussion

The GISAID database search implied that this polymorphic indel hotspot to be with one of the highest tolerability for incorporating indels in SARS-CoV-2 S gene. In summary, the present study identified a variable number of tandem repeat of 9-base insertion in the N-terminal domain of SARS-CoV-2 S gene, and the repeat could have occurred at different time from the insertion of the original 9-base insertion.
Expression of tardigrade disordered proteins impacts the tolerance to biofuels in a model cyanobacterium Synechocystis sp. PCC 6803
Authors: Zhang Heao , Liu Qingyang , Liang Qing , Wang Boxiang , Chen Zixi , Wang Jiangxin
Published: January 2023

Tardigrades, known colloquially as water bears or moss piglets, are diminutive animals capable of surviving many extreme environments, even been exposed to space in low Earth orbit. Recently termed tardigrade disordered proteins (TDPs) include three families as cytoplasmic-(CAHS), secreted-(SAHS), and mitochondrial-abundant heat soluble (MAHS) proteins. How these tiny animals survive these stresses has remained relatively mysterious. Cyanobacteria cast attention as a “microbial factory” to produce biofuels and high-value-added chemicals due to their ability to photosynthesis and CO2 sequestration. We explored a lot about biofuel stress and related mechanisms in Synechocystis sp. PCC 6803. The previous studies show that CAHS protein heterogenous expression in bacteria, yeast, and human cells increases desiccation tolerance in these hosts. In this study, the expression of three CAHS proteins in cyanobacterium was found to affect the tolerance to biofuels, while the tolerance to Cd2+ and Zn2+ were slightly affected in several mutants. A quantitative transcriptomics approach was applied to decipher response mechanisms at the transcriptional level further.
Effectiveness of a self-reporting yes/no survey for dementia screening—trial in Fukui, Japan
Authors: Hamano Tadanori , Nagata Miwako , Matsubara Rokuro , Ikebata Yukihiko , Ito Tatsuhiko , Ibe Akihiro , Fujita Youshi , Kusaka Yukinori , Tokunaga Takahiro , Enomoto Soichi , Endo Yoshinori , Ueno Asako , Shirafuji Norimichi , Ikawa Masamichi , Hayashi Kouji , Yamamura Osamu , Nakamoto Yasunari
Published: January 2023

Background: Early intervention for dementia patients is extremely important for the prevention of dementia. However, so far, it is not clear as to what kind of screening will be useful for the early detection of dementia.

Objective: We aimed to investigate the relationship between the results of a short self-reporting yes/no survey selected in Kihon Checklist, developed by the Japanese Ministry of Health, Labor and Welfare to identify older adults who are at risk of requiring support/care, and other original items developed by Dementia Prevention Team, Fukui, Japan, and Mini-Mental State Examination (MMSE) scores, and determine the diagnostic efficacy of the self-reporting yes/no survey.

Methods: Self-reporting yes/no surveys were conducted for 87,687 individuals aged ≥65 years, living in Fukui, Japan, and did not have Long-Term Care Insurance, Japan. According to the survey results, selected individuals were advised to visit a local hospital to be assessed with MMSE.

Results: Individuals who could not make a call by looking up phone numbers and manage their own deposits and savings at the bank or automatic teller machine (ATM) had an increased risk of low MMSE score (≤23; odds ratio: 2.74 [1.89–3.97]; 95% confidence interval: 2.12 [1.46–3.07]).

Conclusions: Self-reporting yes/no survey could effectively screen for dementia. Not being able to make a call by looking up phone numbers and not being able to manage their own deposits and savings at the bank or ATM are signs of dementia.
Health-related heterogeneity in brain aging and associations with longitudinal change in cognitive function
Authors: Wrigglesworth Jo , Ryan Joanne , Ward Phillip G. D. , Woods Robyn L. , Storey Elsdon , Egan Gary F. , Murray Anne , Espinoza Sara E. , Shah Raj C. , Trevaks Ruth E. , Ward Stephanie A. , Harding Ian H.
Published: January 2023

Introduction

Neuroimaging-based ‘brain age’ can identify individuals with ‘advanced’ or ‘resilient’ brain aging. Brain-predicted age difference (brain-PAD) is predictive of cognitive and physical health outcomes. However, it is unknown how individual health and lifestyle factors may modify the relationship between brain-PAD and future cognitive or functional performance. We aimed to identify health-related subgroups of older individuals with resilient or advanced brain-PAD, and determine if membership in these subgroups is differentially associated with changes in cognition and frailty over three to five years.

Methods

Brain-PAD was predicted from T1-weighted images acquired from 326 community-dwelling older adults (73.8 ± 3.6 years, 42.3% female), recruited from the larger ASPREE (ASPirin in Reducing Events in the Elderly) trial. Participants were grouped as having resilient (n=159) or advanced (n=167) brain-PAD, and latent class analysis (LCA) was performed using a set of cognitive, lifestyle, and health measures. We examined associations of class membership with longitudinal change in cognitive function and frailty deficit accumulation index (FI) using linear mixed models adjusted for age, sex and education.

Results

Subgroups of resilient and advanced brain aging were comparable in all characteristics before LCA. Two typically similar latent classes were identified for both subgroups of brain agers: class 1 were characterized by low prevalence of obesity and better physical health and class 2 by poor cardiometabolic, physical and cognitive health. Among resilient brain agers, class 1 was associated with a decrease in cognition, and class 2 with an increase over 5 years, though was a small effect that was equivalent to a 0.04 standard deviation difference per year. No significant class distinctions were evident with FI. For advanced brain agers, there was no evidence of an association between class membership and changes in cognition or FI.

Conclusion

These results demonstrate that the relationship between brain age and cognitive trajectories may be influenced by other health-related factors. In particular, people with age-resilient brains had different trajectories of cognitive change depending on their cognitive and physical health status at baseline. Future predictive models of aging outcomes will likely be aided by considering the mediating or synergistic influence of multiple lifestyle and health indices alongside brain age.
Comparative efficacy of transcranial magnetic stimulation on different targets in Parkinson’s disease: A Bayesian network meta-analysis
Authors: Dong Ke , Zhu Xiaoxia , Xiao Wenwu , Gan Chu , Luo Yulu , Jiang Manying , Liu Hanjun , Chen Xi
Published: January 2023

Background/Objective

The efficacy of transcranial magnetic stimulation (TMS) on Parkinson’s disease (PD) varies across the stimulation targets. This study aims to estimate the effect of different TMS targets on motor symptoms in PD.

Methods

A Bayesian hierarchical model was built to assess the effects across different TMS targets, and the rank probabilities and the surface under the cumulative ranking curve (SUCRA) values were calculated to determine the ranks of each target. The primary outcome was the Unified Parkinson’s Disease Rating Scale part-III. Inconsistency between direct and indirect comparisons was assessed using the node-splitting method.

Results

Thirty-six trials with 1,122 subjects were included for analysis. The pair-wise meta-analysis results showed that TMS could significantly improve motor symptoms in PD patients. Network meta-analysis results showed that the high-frequency stimulation over bilateral M1, bilateral DLPFC, and M1+DLPFC could significantly reduce the UPDRS-III scores compared with sham conditions. The high-frequency stimulation over both M1 and DLPFC had a more significant effect when compared with other parameters, and ranked first with the highest SCURA value. There was no significant inconsistency between direct and indirect comparisons.

Conclusion

Considering all settings reported in our research, high-frequency stimulation over bilateral M1 or bilateral DLPFC has a moderate beneficial effect on the improvement of motor symptoms in PD (high confidence rating). High-frequency stimulation over M1+DLPFC has a prominent beneficial effect and appears to be the most effective TMS parameter setting for ameliorating motor symptoms of PD patients (high confidence rating).
Cell numbers in the reflected blade of CA3 and their relation to other hippocampal principal cell populations across seven species
Authors: Maliković Jovana , Amrein Irmgard , Vinciguerra Lorenzo , Lalošević Dušan , Wolfer David P. , Slomianka Lutz
Published: January 2023

The hippocampus of many mammals contains a histoarchitectural region that is not present in laboratory mice and rats—the reflected blade of the CA3 pyramidal cell layer. Pyramidal cells of the reflected blade do not extend dendrites into the hippocampal molecular layer, and recent evidence indicates that they, like the proximal CA3 pyramids in laboratory rats and mice, partially integrate functionally with the dentate circuitry in pattern separation. Quantitative assessments of phylogenetic or disease-related changes in the hippocampal structure and function treat the reflected blade heterogeneously. Depending on the ease with which it can be differentiated, it is either assigned to the dentate hilus or to the remainder of CA3. Here, we investigate the impact that the differential assignment of reflected blade neurons may have on the outcomes of quantitative comparisons. We find it to be massive. If reflected blade neurons are treated as a separate entity or pooled with dentate hilar cells, the quantitative makeup of hippocampal cell populations can differentiate between species in a taxonomically sensible way. Assigning reflected blade neurons to CA3 greatly diminishes the differentiating power of all hippocampal principal cell populations, which may point towards a quantitative hippocampal archetype. A heterogeneous assignment results in a differentiation pattern with little taxonomic semblance. The outcomes point towards the reflected blade as either a major potential player in hippocampal functional and structural differentiation or a region that may have cloaked that hippocampi are more similarly organized across species than generally believed.
Neurotransmitter content heterogeneity within an interneuron class shapes inhibitory transmission at a central synapse
Authors: Dumontier Dimitri , Mailhes-Hamon Caroline , Supplisson Stéphane , Dieudonné Stéphane
Published: January 2023

Neurotransmitter content is deemed the most basic defining criterion for neuronal classes, contrasting with the intercellular heterogeneity of many other molecular and functional features. Here we show, in the adult mouse brain, that neurotransmitter content variegation within a neuronal class is a component of its functional heterogeneity. Golgi cells (GoCs), the well-defined class of cerebellar interneurons inhibiting granule cells (GrCs), contain cytosolic glycine, accumulated by the neuronal transporter GlyT2, and GABA in various proportions. By performing acute manipulations of cytosolic GABA and glycine supply, we find that competition of glycine with GABA reduces the charge of IPSC evoked in GrCs and, more specifically, the amplitude of a slow component of the IPSC decay. We then pair GrCs recordings with optogenetic stimulations of single GoCs, which preserve the intracellular transmitter mixed content. We show that the strength and decay kinetics of GrCs IPSCs, which are entirely mediated by GABAA receptors, are negatively correlated to the presynaptic expression of GlyT2 by GoCs. We isolate a slow spillover component of GrCs inhibition that is also affected by the expression of GlyT2, leading to a 56% decrease in relative charge. Our results support the hypothesis that presynaptic loading of glycine negatively impacts the GABAergic transmission in mixed interneurons, most likely through a competition for vesicular filling. We discuss how the heterogeneity of neurotransmitter supply within mixed interneurons like the GoC class may provide a presynaptic mechanism to tune the gain of microcircuits such as the granular layer, thereby expanding the realm of their possible dynamic behaviors.
Contrast-induced encephalopathy and permanent neurological deficit following cerebral angiography: A case report and review of the literature
Authors: Zhang Yujing , Zhang Jiancheng , Yuan Shiying , Shu Huaqing
Published: January 2023

Contrast-induced encephalopathy (CIE) is an uncommon complication associated with contrast exposure during angiographic procedures that is usually transient but occasionally leads to permanent complications or death. Due to the low incidence of CIE, there are still insufficient reports. This study was used to summarize the clinical features of CIE through a case report and systematic review. We summarized and reviewed 127 patients with CIE, and we found that the total incidence of CIE between men and women had no difference (49.61 and 50.39%, respectively), but the average age in female patients with CIE was older than that in male patients (62.19 and 58.77 years, respectively). Interestingly, the incidence of female patients with CIE in the poor prognosis group was significantly higher than that in the good prognosis group (62.50 and 36.51%, respectively), and the average age of these female patients in the poor prognosis group was younger than that in the good prognosis group (61.39 and 62.82 years, respectively). The contrast medium types were mainly nonionic (79.69 and 73.02%, respectively) and low-osmolar (54.69 and 71.43%, respectively) in both groups. Importantly, the total contrast media administrated in patients with poor prognoses was greater than that administrated in patients with good prognoses (198.07 and 188.60 ml, respectively). In addition, comorbidities in both groups included hypertension (55.91%), diabetes mellitus (20.47%), previous contrast history (15.75%), renal impairment (11.81%), and hyperlipidemia (3.15%). The percentage of patients with cerebral angiography was significantly higher in the poor prognosis group than that in the good prognosis group (37.50 and 9.52%, respectively), whereas the percentage of patients with coronary angiography in both groups had the opposite results (35.94 and 77.78%, respectively). In conclusion, CIE may not always have a benign outcome and can cause permanent deficits. Female gender, younger age, the higher dose of contrast medium, and the procedure of cerebral angiography may be related to the patient’s poor prognosis.
Schwann cells-derived exosomes promote functional recovery after spinal cord injury by promoting angiogenesis
Authors: Huang Jiang-Hu , Chen Yong-Neng , He Hang , Fu Chun-Hui , Xu Zhao-Yi , Lin Fei-Yue
Published: January 2023

Exosomes are small vesicles that contain diverse miRNA, mRNA, and proteins that are secreted by multiple cells, and play a vital function in cell–cell communication. Numerous exosomes produced by cells have been demonstrated to be protective against spinal cord injury (SCI). This study aims to investigate the neuroprotective effect of Schwann cells-derived exosomes (SCs-Exos) on spinal cord injury. We found that SCs-Exos can be taken directly by brain-derived endothelial cells.3 (bEnd.3 cells) and promoted to proliferate, migrate, and form bEnd.3 tube. Additionally, our results showed that the pro-angiogenesis molecules, Integrin-β1, were highly expressed in SCs-Exos. Moreover, we used special shRNA technology to investigate the role of Integrin-β1 in mediating the effect of SCs-Exos-induced angiogenesis on bEnd.3 cells. We observed that the pro-angiogenic effect of SCs-Exos on bEnd.3 cells was suppressed by inhibiting the expression of integrin-β1 in SCs-Exos. In the SCI model, we found that SCs-Exos attenuated tissue damage and improved functional recovery after SCI. Using immunofluorescence staining, we observed that SCs-Exos treatment promoted angiogenesis in SCI, and integrin-β1 was required to promote angiogenesis. In conclusion, our results indicate that SCs-Exos promote angiogenesis by delivering integrin-β1 and may serve as a promising novel therapeutic agent for enhancing neurological functional recovery after SCI.
Integrative treatment program for the treatment of children with autism spectrum disorder: A prospective observational case series
Authors: Lee Boram , Park Serin , Kwon Hyun Jeong , Hwang Gwi Seo , Kim Moonju
Published: January 2023

Background

In a situation where conventional treatments for autism spectrum disorder (ASD) are labor-intensive and there are concerns about the side effects of conventional medications, a 6-month integrative treatment program, including herbal medicine (HM), Floortime, and sensory enrichment therapy (SET) has been used on children with ASD in Korean medicine clinical settings.

Methods

We observed the treatment responses of 18 children with ASD (66.7% male, mean age 3.9 ± 0.9 years) to the integrative treatment program as part of a prospective, single-center, observational case series. Individualized HMs were administered according to the patient's symptoms, and parents were instructed to perform Floortime and SET with their children at home for 2 h and 20 min a day, 5 days a week, respectively. The Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC) were used to evaluate the core symptoms of ASD. A linear mixed model for repeated measures was used for analyzing the effect of the program over time, and logistic regression used to explore the predictors of treatment response.

Results

The CARS and ABC scores were significantly improved from 34.58 ± 6.27 and 69.28 ± 15.73 at baseline to 28.56 ± 6.05 and 39.67 ± 20.36 after 6 months (p < 0.0001, respectively). No serious adverse events (AEs) were reported, and compliance with HM, Floortime, and SET was high at >90%.

Conclusion

This 6-month integrative treatment program appears to be a potentially effective, safe, and feasible option for children with ASD. Low baseline CARS scores may be predictors of higher treatment response.
Long-term outcomes of adult cryptogenic febrile infection–related epilepsy syndrome (FIRES)
Authors: Shi Xiaojing , Wang Yuanyuan , Wang Xuan , Kang Xiaogang , Yang Fang , Yuan Fang , Jiang Wen
Published: January 2023

Background

Cryptogenic febrile infection-related epilepsy syndrome (FIRES) is a rare but catastrophic encephalopathic condition. We aimed to investigate the long-term outcome in adult cryptogenic FIRES.

Methods

This was a retrospective study based on the prospective database in the neuro-intensive care unit of a tertiary hospital in China. Consecutive adult patients with cryptogenic FIRES between July 2007 to December 2021 were included. Long-term outcomes included function independence, the development of drug-resistant epilepsy (DRE), remote recurrent status epilepticus (SE), anti-seizure medications (ASMs), and changes in the brain Magnetic Resonance Imaging (MRI).

Results

A total of 11 adult patients with cryptogenic FIRES were identified from 270 patients with SE. Four (36%) patients died in the hospital, with three of them withdrawing treatments, and one patient died 12 months after discharge. After the follow-up ranging from 12 to 112 months, 6 (55%) patients were still alive, and all of them achieved functional independence [modified Rankin Scale (mRS) 0-3]. 45% (5/11) patients developed DRE, 18% (2/11) had remote recurrent SE, and 55% (6/11) were on polytherapy with ASMs at the last follow-up. Most of the patients with initial normal or abnormal MRI had abnormalities in the hippocampus at follow-up, and most of the other MRI abnormalities found in the acute stage disappeared over time.

Conclusion

The outcome of adult cryptogenic FIRES is daunting. More than one-third of patients die in the hospital. Survivors of cryptogenic FIRES may regain functional independence, but they usually develop DRE and receive polytherapy of ASMs for a long time.
Global research hot spot and trends in tinnitus treatment between 2000 and 2021: A bibliometric and visualized study
Authors: Ye Tao , Chen Kefan , Li Dongyang , Yin Kailong , Li Yuan , Long Jin , Hui Lian
Published: January 2023

Background

In the 21st century, the prevalence of tinnitus is increasing, impacting approximately one in five people. It is a very complicated condition that significantly affects quality of life. Despite the availability of hundreds of tinnitus treatment options, none are very successful. In light of this, there has been a steady increase in studies on tinnitus treatments in the recent past. To comprehend them better, this study used bibliometric approaches to analyze and summarize 21st century scientific research accomplishments in tinnitus treatment.

Methods

The Web of Science Core Collection (WoSCC) was searched for papers that had been published and related to the treatment of tinnitus. VOSviewer, CiteSpace, R, and Tableau software programs were used to conduct bibliometric studies. To evaluate and visualize the results.

Results

2,933 publications on tinnitus treatment were found in 74 countries. Between 2000 and 2021, publications increased steadily. Otolaryngology-Head & Neck Surgery had the highest impact factor, whereas Otology & Neurotology had the most magazines and the highest h, g, and m index. Langguth B was the most prolific author in terms of productivity during the past 21 years. Numerous eminent authors and organizations from multiple nations collaborated. With 626 papers, the United States of America (USA) contributed the most to this field, making them the leading contributor. Neuroplasticity, sound therapy, and cognitive behavioral therapy (CBT) have attracted the attention of researchers, leading to the development of innovative diagnostic and treatment strategies for tinnitus.

Conclusion

This bibliometric study provides a comprehensive analysis of worldwide publications, cooperation, and research hotspots in tinnitus therapy, revealing the present status of research on this issue and guiding tinnitus treatment research in the coming years.
Does whole-body vibration training have a positive effect on balance and walking function in patients with stroke? A meta-analysis
Authors: Yin Yikun , Wang Jialin , Yu Zhengze , Zhou Lina , Liu Xiaoman , Cai Hejia , Sun Junzhi
Published: January 2023

Objective

After a stroke, patients usually suffer from dysfunction, such as decreased balance ability, and abnormal walking function. Whole-body vibration training can promote muscle contraction, stimulate the proprioceptive system, enhance the muscle strength of low limbs and improve motor control ability. The study aims to evaluate the effectiveness of whole-body vibration training on the balance and walking function of patients with stroke.

Methods

PubMed, CNKI, VIP, CBM, EBSCO, Embase and Web of Science were searched. According to the inclusion and exclusion criteria, randomized controlled trials on the effectiveness of whole-body vibration training on the balance and walking function of patients with stroke were collected. The search time ranged from the date of database construction to November 2022. The included trials were evaluated by the Cochrane risk-of-bias tool. The meta-analysis was performed using two software packages, consisting of RevMan 5.4 and Stata 12.2. If the results included in the literature were continuous variables, use the mean difference (MD) and 95% confidence interval (CI) for statistics.

Results

(1) A total of 22 randomized controlled trials (RCTs) with a total of 1089 patients were included. (2) The results of meta-analysis showed that: compared with the controls, step length (MD = 6.12, 95%CI [5.63, 6.62], p < 0.001), step speed (MD = 0.14, 95%CI [0.09, 0.20], p < 0.001), cadence (MD = 9.03, 95%CI [2.23, 15.83], p = 0.009), stride length (MD = 6.74, 95%CI [−3.47, 10.01], p < 0.001), Berg Balance Scale (BBS) (MD = 4.08, 95%CI [2.39, 5.76], p < 0.001), Timed Up-and-Go test (TUGT) (MD = −2.88, 95%CI [−4.94, 0.81], p = 0.006), 10-meter Walk Test (10MWT) (MD = −2.69, 95%CI [−3.35, −2.03], p < 0.001), functional ambulation category scale (FAC) (MD = 0.78, 95%CI [0.65, 0.91], p < 0.001), Fugl-Meyer motor assessment of lower extremity (FMA-LE) (MD = 4.10, 95%CI [2.01, 6.20], p = 0.0001). (3) The results of subgroup analysis showed that, compared with other vibration frequencies, at 20–30 Hz frequency, WBV training had an obvious improvement effect only in TUGT. (4) The safety analysis showed that WBV training may be safe.

Conclusion

Whole-body vibration training has a positive effect on the balance and walking function of patients with stroke. Thus, whole-body vibration training is a safe treatment method to improve the motor dysfunction of patients with stroke.

Systematic review registration

[http://www.crd.york.ac.uk/PROSPERO], identifier [CRD4202348263].
Microglial heterogeneity and complement component 3 elimination within emerging multisensory midbrain compartments during an early critical period
Authors: Carroll Julianne B. , Hamidi Shaida , Gabriele Mark L.
Published: January 2023

The lateral cortex of the inferior colliculus (LCIC) is a midbrain shell region that receives multimodal inputs that target discrete zones of its compartmental (modular-matrix) framework. This arrangement emerges perinatally in mice (postnatal day, P0-P12) as somatosensory and auditory inputs segregate into their respective modular and matrix terminal patterns. Microglial cells (MGCs) perform a variety of critical functions in the developing brain, among them identifying areas of active circuit assembly and selectively pruning exuberant or underutilized connections. Recent evidence in other brain structures suggest considerable MGC heterogeneity across the lifespan, particularly during established developmental critical periods. The present study examines the potential involvement of classical complement cascade signaling (C3-CR3/CD11b) in refining early multisensory networks, and identifies several microglial subsets exhibiting distinct molecular signatures within the nascent LCIC. Immunostaining was performed in GAD67-green fluorescent protein (GFP) and CX3CR1-GFP mice throughout and after the defined LCIC critical period. GAD labeling highlights the emerging LCIC modularity, while CX3CR1 labeling depicts MGCs expressing the fractalkine receptor. C3 expression is widespread throughout the LCIC neuropil early on, prior to its conspicuous absence from modular zones at P8, and more global disappearance following critical period closure. CD11b-expressing microglia while homogeneously distributed at birth, are biased to modular fields at P8 and then the surrounding matrix by P12. Temporal and spatial matching of the disappearance of C3 by LCIC compartment (i.e., modules then matrix) with CD11b-positive MGC occupancy implicates complement signaling in the selective refinement of early LCIC connectivity. Multiple-labeling studies for a variety of established MGC markers (CD11b, CX3CR1, Iba1, TMEM119) indicate significant MGC heterogeneity in the LCIC as its compartments and segregated multisensory maps emerge. Marker colocalization was the exception rather than the rule, suggesting that unique MGC subpopulations exist in the LCIC and perhaps serve distinct developmental roles. Potential mechanisms whereby microglia sculpt early multisensory LCIC maps and how such activity/inactivity may underlie certain neurodevelopmental conditions, including autism spectrum disorder and schizophrenia, are discussed.