Contemporary Management of Pediatric Brainstem Tumors.

Brain tumors are the second most common malignancy in childhood. Around 15-20% of pediatric brain tumors occur in the brainstem. The most common type of brainstem tumor are diffuse tumors in the ventral pons, whereas focal tumors tend to arise from the midbrain, medulla, and dorsal pons. Glioma is the most common pathological entity. Contemporary management consists of surgery, radiotherapy, chemotherapy, and other adjuvant treatment. Surgical options range from biopsy to radical excision. Biopsy can be performed for diagnostic and prognostic purposes, or in the setting of clinical trials, mainly for diffuse intrinsic pontine gliomas. For focal tumors, surgeons need to carefully balance clinical outcomes against possible neurological sequelae in order to achieve maximal safe resection. Radiotherapy is essential for control of high-grade tumors and may be applied to residual or recurrent low-grade tumors. Proton therapy may provide similar efficacy and less neurotoxicity in comparison to conventional photon therapy. Oncological treatment continues to evolve from conventional chemotherapy to targeted therapy, immunotherapy, and other novel treatment methods and holds great potential as adjuvant therapy for pediatric brainstem tumors.

Whole-exome sequencing identified genes known to be responsible for retinitis pigmentosa in 28 Chinese families.

Purpose: Retinitis pigmentosa (RP) is a group of highly heterogenetic inherited retinal degeneration diseases. Molecular genetic diagnosis of RP is quite challenging because of the complicated disease-causing mutation spectrum. The aim of this study was to explore the mutation spectrum in Chinese RP patients using next-generation sequencing technology and to explore the genotype-phenotype relationship. Method: In this study, a cost-effective strategy using whole-exome sequencing (WES) was employed to address the genetic diagnosis of 28 RP families in China. One to two patients and zero to two healthy relatives were sequenced in each family. All mutations in WES data that passed through the filtering procedure were searched in relation to 662 gene defects that can cause vision-associated phenotypes (including 89 RP genes in the RetNet Database). All patients visiting the outpatient department received comprehensive ophthalmic examinations. Result: Twenty-five putative pathogenic mutations of 12 genes were detected by WES and were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including the 12 following genes: USH2A, CYP4V2, PRPF31, RHO, RP1, CNGA1, CNGB1, EYS, PRPF3, RP2, RPGR, and TOPORS. Three families were rediagnosed as having Bietti crystalline dystrophy (BCD). USH2A (4/20, 20%) and CYP4V2 (3/20, 15%) were found to be the most frequent mutated genes. Seven novel mutations were identified in this research, including mutations in USH2A1, USH2A2, PRPF31, RP2, TOPORS, CNGB1, and RPGR. Phenotype and genotype relationships in the 12 RP genes were analyzed, which revealed later disease onset and more severe visual function defects in CYP4V2. Conclusion: Twenty-five putative pathogenic mutations of 12 genes were detected by WES, and these were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including seven novel mutations. USH2A and CYP4V2 were found to be the most frequent genes in this research. Phenotype and genotype relationships were revealed, and the mutation spectrum of RP in Chinese populations was expanded in this research, which may benefit future cutting-edge therapies.

Methylation- and homologous recombination deficiency-related mutant genes predict the prognosis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a lung cancer subtype with poor prognosis. We investigated the prognostic value of methylation- and homologous recombination deficiency (HRD)-associated gene signatures in LUAD. METHODS: Data on RNA sequencing, somatic mutations, and methylation were obtained from TCGA database. HRD scores were used to stratify patients with LUAD into high and low HRD groups and identify differentially mutated and expressed genes (DMEGs). Pearson correlation analysis between DMEGs and methylation yielded methylation-associated DMEGs. Cox regression analysis was used to construct a prognostic model, and the distribution of clinical features in the high- and low-risk groups was compared. RESULTS: Patients with different HRD scores showed different DNA mutation patterns. There were 272 differentially mutated genes and 6294 differentially expressed genes. Fifty-seven DMEGs were obtained; the top 10 upregulated genes were COL11A1, EXO1, ASPM, COL12A1, COL2A1, COL3A1, COL5A2, DIAPH3, CAD, and SLC25A13, while the top 10 downregulated genes were C7, ERN2, DLC1, SCN7A, SMARCA2, CARD11, LAMA2, ITIH5, FRY, and EPHB6. Forty-two DMEGs were negatively correlated with 259 methylation sites. Gene ontology and pathway enrichment analysis of the DMEGs revealed enrichment of loci involved in extracellular matrix-related remodeling and signaling. Six out of the 42 methylation-associated DMEGs were significantly associated with LUAD prognosis and included in the prognostic model. The model effectively stratified high- and low-risk patients, with the high-risk group having more patients with advanced stage disease. CONCLUSION: We developed a novel prognostic model for LUAD based on methylation and HRD. Methylation-associated DMEGs may function as biomarkers and therapeutic targets for LUAD. Further studies are needed to elucidate their roles in LUAD carcinogenesis.

Choroidal vascular changes in retinitis pigmentosa patients detected by optical coherence tomography angiography.

BACKGROUND: To evaluate choroidal vascular changes, including choriocapillaris (CC) and middle/large choroidal vessels, in retinitis pigmentosa (RP) patients using wide-angle optical coherence tomography angiography (OCTA) and to determine whether changes in the choroidal vascularity have a relationship with visual function and retinal structural changes. METHODS: 34 patients with a confirmed diagnosis of RP and 48 controls were recruited. All patients underwent detailed ophthalmologic and imaging examinations, including two types of OCTA (Optovue, 3 × 3 mm, 6 × 6 mm; VG-200, 12 × 12 mm). CC defects were defined according to the choroidal vascular structure in five degrees. To evaluate middle and large choroidal vascular changes, the choroidal vascularity index (CVI), which was the luminance volume to the total choroidal volume, was used. RESULTS: Defects of choroidal vascularity of RP eyes were detected in comparison to control eyes. The defects were observed in the CC layer with a concentric or lobular pattern at different degrees. CVI, which was used to reflect middle/large choroidal vascularity, decreased in the perifoveal, pararetinal and periretinal regions in the RP eyes. CC defects degree were correlated with the BCVA (p = 0.001, r = - 0.556), the Humphrey indexes (mean deviation, MD, p < 0.001, r = - 0.673; PVF, p = 0.003, r = - 0.639; 10° mean sensitivity, 10° MS, p = 0.002, r = - 0.651) and microperimetry index (mean sensitivity, MS, p < 0.001, r = - 0.807). The preserved CC area (mean value: 28.65 ± 12.50 mm2) was negatively correlated with MS measured by microperimetry (p = 0.005, r = - 0.449). Ordinary regression analysis revealed that the CC defect degree was associated with the CVI of perifovea (p = 0.002, 95% CI: - 102.14 to - 24.01), the EZ length (p = 0.006, 95% CI: - 0.006 to - 0.001) and the VAD (vascular area density) of the DCP (deep capillary plexus) in the fovea (p = 0.022, 95% CI: 0.038-0.478). No correlations were detected between BCVA and CVI in any retinal regions. No correlations were found between the CVI and the VAD in any retinal regions. CONCLUSION: The choroidal vascularity was widely defected in RP. Choriocapillaris and middle/large choroidal vascularity defects were correlated with each other. Visual function and retinal structural changes were found to be associated with choriocapillaris defects but not with middle/large choroidal vascular defects.

An Effective Sensor Deployment Scheme that Ensures Multilevel Coverage of Wireless Sensor Networks with Uncertain Properties.

The coverage problem is a fundamental problem for almost all applications in wireless sensor networks (WSNs). Many applications even impose the requirement of multilevel (k) coverage of the region of interest (ROI). In this paper, we consider WSNs with uncertain properties. More precisely, we consider WSNs under the probabilistic sensing model, in which the detection probability of a sensor node decays as the distance between the target and the sensor node increases. The difficulty we encountered is that there is no unified definition of k-coverage under the probabilistic sensing model. We overcome this difficulty by proposing a "reasonable" definition of k-coverage under such a model. We propose a sensor deployment scheme that uses less number of deployed sensor nodes while ensuring good coverage qualities so that (i) the resultant WSN is connected and (ii) the detection probability satisfies a predefined threshold p th , where 0 < p th < 1 . Our scheme uses a novel "zone 1 and zone 1-2" strategy, where zone 1 and zone 2 are a sensor node's sensing regions that have the highest and the second highest detection probability, respectively, and zone 1-2 is the union of zones 1 and 2. The experimental results demonstrate the effectiveness of our scheme.

[Identification of a Novel Mutation of EPB41 Gene in a Family Affected with Hereditary Elliptocytosis].

OBJECTIVE: To analyse potential genetic cause of a family affected with hereditary elliptocytosis （HE）. METHODS: Peripheral blood samples from this HE family were collected. Targeted capture and high-throughput sequencing of 4 813 genetic disease-associated genes was performed in four members of the family. Possible causative genetic variation was obtained and further confirmed by Sanger sequencing. Fifty healthy control subjects were recruited for detection of the candidate variation. RESULTS: High-throughput sequencing detected a nonsense mutation c.1215G>A（p.Trp405Ter）in exon 13 of the EPB41 gene in the proband and his mother presenting with moderate anemia. The pathogenicity of this loss-of-function mutation is very strong, because the G→A transition leads to introduce the premature stop codon instead of tryptophan codon at position 405, which producing a truncating protein with loss of important functional domains. This causative mutation is extremely rare in the population, and it has not yet been reported. The grandmother of the proband was heterozygous for the same mutation. Genotype-phenotype cosegregation was observed in this family. This mutation was not found in the 50 unrelated healthy controls. CONCLUSION: The c.1215G>A mutation of the EPB41 gene probably accounts for the disease in this HE family. This study reports a pathogenic EPB41 mutation in a Chinese HE family for the first time.

The role of sacral laminoplasty in the management of spina bifida and sacral cystic lesions: case series.

OBJECTIVE: Although laminae are not viewed as essential structures for spinal integrity, in the sacrum the anatomical weakness and gravity makes it a vulnerable area for CSF accumulation and expansion. The congenital or postoperative defects of sacral laminae, such as in patients with spina bifida, make this area more susceptible to forming progressive dural ectasia, pseudomeningocele, or expansile arachnoid cyst (Tarlov cyst). In addition, adhesions between the dura and surrounding soft tissue after laminectomy can cause some local symptoms, which are difficult to relieve. The authors propose that sacral laminoplasty with titanium mesh can provide a rigid support and barrier to resolve these sacral lesions and local symptoms. METHODS: From January 2016 to December 2017, patients with progressive CSF-containing lesions in the sacral area and defective sacral laminae were included in the study. After repair of the lesion, the authors performed sacral laminoplasty with titanium mesh in each patient. Subsequently, the soft tissue and skin were closed primarily. RESULTS: A total of 6 patients were included. Four patients with repaired myelomeningocele had progressive dural ectasia. One patient with lipomyelomeningocele previously underwent detethering surgery and developed postoperative pseudomeningocele. One patient had a symptomatic Tarlov cyst. Four of these 6 cases presented with low-back pain and local tenderness. During follow-up, ranging from 13 to 37 months, all 6 patients experienced no recurrence of dural ectasia or pseudomeningocele and were free from local symptoms. CONCLUSIONS: Sacral laminoplasty with titanium mesh is a safe and effective procedure for treating progressive sacral dural ectasia and refractory pseudomeningocele, preventing CSF leakage as well as relieving local symptoms that may occur years after previous surgery for spina bifida.

Cognitive emotion regulation strategies among Chinese adolescents having unprotected sex: a latent profile analysis.

The association between cognitive emotion regulation strategy use and adolescents' risk behavior has long been emphasized. To identify coping profiles of Chinese adolescents having unprotected sex and to examine the characteristics and associations among those subgroups, 541 adolescents (age, 14-19 years) were screened from secondary schools in 10 Chinese cities. By latent profile analysis (LPA), the participants were identified into three latent profiles: the low reaction profile (LRP, N = 70), the medium reaction profile (MRP, N = 369), and the high reaction profile (HRP, N = 102) based on nine subscales of the Cognitive Emotion Regulation Questionnaire (CERQ). By one-way analysis of variance, chi-square tests, and multivariate logistic regression analysis, we found that: the HRP has the highest level of using eight strategies and the lowest unprotected sex, meanwhile the LRP has the lowest level of using nine strategies and the highest unprotected sex among three groups (both p < .05). The low response coping was more prevalent among boys and younger students. It indicates that more active cognitive coping, using both adaptive and maladaptive strategies, may associate with less unprotected sex. The programs of enhancing active copying may be targeted in interventions aiming to reduce adolescent unprotected sex.

Limitations of the endonasal endoscopic approach in treating olfactory groove meningiomas. A systematic review.

OBJECTIVE: To review current management strategies for olfactory groove meningioma (OGM)s and the recent literature comparing endoscopic endonasal (EEA) with traditional transcranial (TCA) approaches. METHODS: A PubMed search of the recent literature (2011-2016) was performed to examine outcomes following EEA and TCA for OGM. The extent of resection, visual outcome, postoperative complications and recurrence rates were analyzed using percentages and proportions, the Fischer exact test and the Student's t-test using Graphpad PRISM 7.0Aa (San Diego, CA) software. RESULTS: There were 444 patients in the TCA group with a mean diameter of 4.61 (±1.17) cm and 101 patients in the EEA group with a mean diameter of 3.55 (± 0.58) cm (p = 0.0589). GTR was achieved in 90.9% (404/444) in the TCA group and 70.2% (71/101) in the EEA group (p < 0.0001). Of the patients with preoperative visual disturbances, 80.7% (21/26) of patients in the EEA cohort had an improvement in vision compared to 12.83%(29/226) in the TCA group (p < 0.0001). Olfaction was lost in 61% of TCA and in 100% of EEA patients. CSF leaks and meningitis occurred in 25.7% and 4.95% of EEA patients and 6.3% and 1.12% of TCA patients, respectively (p < 0.0001; p = 0.023). CONCLUSIONS: Our updated literature review demonstrates that despite more experience with endoscopic resection and skull base reconstruction, the literature still supports TCA over EEA with respect to the extent of resection and complications. EEA may be an option in selected cases where visual improvement is the main goal of surgery and postoperative anosmia is acceptable to the patient or in medium-sized tumors with existing preoperative anosmia. Nevertheless, based on our results, it seems more prudent at this time to use TCA for the majority of OGMs.

Transtubular excisional biopsy as a rescue for a non-diagnostic stereotactic needle biopsy-case report and literature review.

Stereotactic needle biopsy, a standard of care for acquiring deep-seated pathology, has limitations and risks in some situations. We present an uncommon case with basal ganglia dematiaceous mycetoma. Due to the firm consistency of the lesion, the initial stereotactic needle biopsy failed to provide a diagnosis. In a second operation, transtubular excisional biopsy was successfully performed to remove the entire mycetoma. We reviewed recent case series of transtubular approaches to deep-seated brain lesions and suggest this method could be a rescue for a non-diagnostic stereotactic needle biopsy and even may be the approach of choice in some cases.

Predictors and incidence of orthostatic headache associated with lumbar drain placement following endoscopic endonasal skull base surgery.

BACKGROUND: Orthostatic headache (OH) is a potential complication of lumbar drainage (LD) usage. The incidence and risk factors for OH with the use of lumbar drainage during endoscopic endonasal procedures have not been documented. OBJECTIVE: To investigate the incidence of post-procedure OHs associated with placement of LD in patients undergoing endoscopic endonasal procedures. METHODS: We prospectively noted the placement of LDs in a consecutive series of endoscopic endonasal skull base surgeries. Charts were retrospectively reviewed, and patients were divided into two groups: those with OH and those without. The patient demographics, drain durations, imaging findings of intracranial hypotension, pathologies and need for a blood patch were compared between the two groups. RESULTS: Two hundred forty-nine patients were included in the study. Seven patients (2.8%) suffered post-dural puncture OH, which was mild to moderate and disappeared 2-8 days (median 3 days) after treatment. Blood patches were used in four patients. Significant predisposing factors were age (33.0 vs. 53.5, P = 0.014) and a strong trend for female gender (85.7% vs. 47.9%, P = 0.062). BMI and drain duration were not significant. Postoperative intracranial hypotension was diagnosed radiographically in 43% of OH patients and in 5.4% of those without OH (P = 0.003). Four (1.6%) patients required treatment with an epidural blood patch. CONCLUSION: OH associated with intracranial hypotension in patients undergoing endoscopic endonasal procedures with LDs is an infrequent complication seen more commonly in young female patients. Radiographic signs of intracranial hypotension are a specific but not sensitive test for OH.

Alteration of RhoA Prenylation Ameliorates Cardiac and Vascular Remodeling in Spontaneously Hypertensive Rats.

BACKGROUND: In our previous study, farnesyl pyrophosphate synthase (FPPS) was shown to be increased in spontaneously hypertensive rats (SHR) and in mice with angiotensin-II induced cardiac hypertrophy. Overexpression of FPPS induced cardiac hypertrophy and fibrosis in mice, accompanied by an increase in the synthesis of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). In the present study, we investigated the mechanisms of reversing cardiovascular remodeling in SHR by inhibiting FPPS. METHODS AND RESULTS: Six-week-old rats were given vehicle or an FPPS inhibitor (alendronate, 100 ug/kg/d) daily for twelve weeks by osmotic mini-pump. The results demonstrated that FPPS inhibition attenuated cardiac hypertrophy and fibrosis in SHR as shown by the heart weight to body weight ratio, echocardiographic parameters, and histological examination. In addition, FPPS inhibition attenuated aortic remodeling as shown by reduced media thickness, media cross-sectional area and collagen of the aorta as well as SBP, DBP, MBP. Furthermore, 12 weeks of alendronate treatment significantly decreased FPP and GGPP levels, RhoA activation and geranylgeranylation in the heart and aorta, all of which were significantly upregulated in SHR compared with normotensive Wistar-Kyoto rats. CONCLUSION: Taken together, these results indicate that chronic treatment with alendronate decreases the development of cardiac and aortic remodeling, by a pathway which involves inhibition of the geranylgeranylation and activation of RhoA.

The association of APOC4 polymorphisms with premature coronary artery disease in a Chinese Han population.

BACKGROUND: Hypercholesterolemia arising from abnormal lipid metabolism is one of the critical risk factors for coronary artery disease (CAD), however the roles of genetic variants in lipid metabolism-related genes on premature CAD (≤ 60 years old) development still require further investigation. We herein genotyped four single nucleotide polymorphisms (SNPs) in lipid metabolism-related genes (rs1132899 and rs5167 in APOC4, rs1801693 and rs7765781 in LPA), aimed to shed light on the influence of these SNPs on individual susceptibility to early-onset CAD. METHODS: Genotyping of the four SNPs (rs1132899, rs5167, rs1801693 and rs7765781) was performed in 224 premature CAD cases and 297 control subjects (≤ 60 years old) using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. The association of these SNPs with premature CAD was performed with SPSS software. RESULTS: Multivariate logistic regression analysis showed that C allele (OR = 1.50, P = 0.027) and CC genotype (OR = 2.84, P = 0.022) of APOC4 rs1132899 were associated with increased premature CAD risk, while the other three SNPs had no significant effect. Further stratified analysis uncovered a more evident association with the risk of premature CAD among male subjects (C allele, OR = 1.65, and CC genotype, OR = 3.33). CONCLUSIONS: Our data provides the first evidence that APOC4 rs1132899 polymorphism was associated with an increased risk of premature CAD in Chinese subjects, and the association was more significant among male subjects.

The LRP6 rs2302685 polymorphism is associated with increased risk of myocardial infarction.

BACKGROUND: Abnormal lipids is one of the critical risk factors for myocardial infarction (MI), however the role of genetic variants in lipid metabolism-related genes on MI pathogenesis still requires further investigation. We herein genotyped three SNPs (LRP6 rs2302685, LDLRAP1 rs6687605, SOAT1 rs13306731) in lipid metabolism-related genes, aimed to shed light on the influence of these SNPs on individual susceptibility to MI. METHODS: Genotyping of the three SNPs (rs2302685, rs6687605 and rs13306731) was performed in 285 MI cases and 650 control subjects using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. The association of these SNPs with MI and lipid profiles was performed with SPSS software. RESULTS: Multivariate logistic regression analysis showed that C allele (OR = 1.62, P = 0.039) and the combined CT/CC genotype (OR = 1.67, P = 0.035) of LRP6 rs2302685 were associated with increased MI risk, while the other two SNPs had no significant effect. Further stratified analysis uncovered a more evident association with MI risk among younger subjects (≤60 years old). Fascinatingly, CT/CC genotype of rs2302685 conferred increased LDL-C levels compared to TT genotype (3.0 mmol/L vs 2.72 mmol/L) in younger subjects. CONCLUSIONS: Our data provides the first evidence that LRP6 rs2302685 polymorphism is associated with an increased risk of MI in Chinese subjects, and the association is more evident among younger individuals, which probably due to the elevated LDL-C levels.

The neuromuscular control for lower limb exoskeleton- a 50-year perspective.

Historically, impaired lower limb function has resulted in heavy health burden and large economic loss in society. Although experts from various fields have put large amounts of effort into overcoming this challenge, there is still not a single standard treatment that can completely restore the lost limb function. During the past half century, with the advancing understanding of human biomechanics and engineering technologies, exoskeletons have achieved certain degrees of success in assisting and rehabilitating patients with loss of limb function, and therefore has been spotlighted in both the medical and engineering fields. In this article, we review the development milestones of lower limb exoskeletons as well as the neuromuscular interactions between the device and wearer throughout the past 50 years. Fifty years ago, the lower-limb exoskeletons just started to be devised. We review several prototypes and present their designs in terms of structure, sensor and control systems. Subsequently, we introduce the development milestones of modern lower limb exoskeletons and discuss the pros and cons of these differentiated devices. In addition, we summarize current important neuromuscular control systems and sensors; and discuss current evidence demonstrating how the exoskeletons may affect neuromuscular control of wearers. In conclusion, based on our review, we point out the possible future direction of combining multiple current technologies to build lower limb exoskeletons that can serve multiple aims.

Clinical Characteristics of Infants with Symptomatic Congenital and Postnatal Cytomegalovirus Infection-An 11-Year Multicenter Cohort Study in Taiwan.

(1) Background: Cytomegalovirus (CMV) infection is a prevalent viral disease among infants. The prevalence typically ranges from 0.2% to 2.4% among all newborns. There are limited data regarding the demographic characteristics of infants with symptomatic CMV infections. (2) Methods: In this retrospective cohort study using the Chang Gung Memorial Hospital multicenter database, infants with CMV infection determined by a positive urine culture, positive blood polymerase chain reaction assay or positive immunoglobulin M result for CMV from 2011 through 2021 were included. Clinical characteristics at initial diagnosis, management and outcomes were investigated. Congenital CMV (cCMV) infection is diagnosed within three weeks after birth; postnatal CMV (pCMV) is diagnosed when CMV is detected after the first 3 weeks of life. (3) Results: Among the 505 CMV-infected infants identified, 272 were included in the analysis. According to the age at initial presentation, 21 infants had cCMV infection and 251 had pCMV infection. Higher incidences of prematurity and being small for gestational age and a lower Z score for weight at diagnosis were observed in the cCMV group. While thrombocytopenia (61.9%) was the leading presentation in the cCMV group, hepatitis (59.8%) and prolonged jaundice (21.9%) were more common in the pCMV group. (4) Conclusions: Utilizing an 11-year multicenter database, we demonstrated the characteristics of infants with CMV infection in Taiwan and highlighted the demographic disparities and differing symptoms between the cCMV and pCMV groups. These findings emphasize the necessity for future research to refine screening policies, explore treatment options, and establish follow-up protocols for affected infants.

Clonal Complex 12 Serotype Ib Streptococcus agalactiae Strain Causing Complicated Sepsis in Neonates: Clinical Features and Genetic Characteristics.

Streptococcus agalactiae (group B Streptococcus [GBS]) is well known to cause serious diseases in infants. A serotype Ib GBS strain has recently emerged and become prevalent in Southeast Asia. We aimed to investigate the clinical and genetic characteristics of this strain. All neonates with invasive GBS diseases from a tertiary-level medical center in Taiwan between 2003 and 2020 were analyzed. The capsule serotyping, multilocus sequence typing, and antimicrobial resistance analyses were performed on all the invasive GBS isolates, and whole-genome sequencing (WGS) was performed specifically on the type Ib GBS strain. A total of 188 neonates with invasive GBS disease during the study period were identified. The type Ib GBS strain accounted for 7.4% (n = 14) of neonatal GBS invasive diseases. Almost all type Ib GBS isolates belonged to sequence type 12 (13/14, 92.9%) and clonal complex 12. Neonates with type Ib GBS disease had a significantly higher rate of complicated sepsis (10/14, 71.4%; P < 0.05) and sepsis-attributable mortality (6/14, 42.9%; P < 0.05). Additionally, type Ib GBS isolates had significantly higher rates of resistance to erythromycin and clindamycin (both 100%; P < 0.05) than other GBS serotypes. WGS revealed the presence of an ~75-kb integrative and conjugative element, ICESag37, comprising multiple antibiotic resistance and virulence genes, and PI-1 plus PI-2a were noted in all type Ib serotype 12 (ST12) GBS isolates; these isolates may be responsible for its high invasiveness and antimicrobial resistance rates. The genomic characteristics of the type Ib clonal complex 12 (CC12) GBS strain may account for the high illness severity associated with this strain and its antibiotic resistance. Continuous monitoring and advanced strategies to control the spread of type Ib CC12 GBS should be considered. IMPORTANCE A type Ib ST12 GBS strain is not a common isolate in neonatal invasive diseases and has been ignored for a long time. However, the recent literature and our data showed that such a GBS strain is associated with a significantly higher risk of severe sepsis, higher illness severity, and a significantly higher rate of sepsis-attributable mortality. This study found a novel gene cluster, including the presence of ICESag37 and specific pilus genes, carrying multiple antimicrobial resistance and virulence genes, which may be responsible for the clinical characteristics. Because of the higher mortality and severity of illness, we concluded that continuous monitoring of the type Ib ST12 GBS strain is warranted in the future.

Porous Carbon Composite Generated from Silk Fibroins and Graphene for Supercapacitors.

Hierarchical porous heteroatom-doped carbon composites were developed by carbonization followed by KOH activation process, with natural silkworm cocoon and chemical exfoliated graphene sheets as starting materials. The introduction of graphene sheets offers more hierarchical micro/meso porosities, a low charge-transfer resistance, and a large BET surface area of ∼1281.8 m2 g-1, which are responsible for the fast charge/discharge kinetics and the high rate capability compared with those of single silk fibroins-derived carbon materials. The silk fiber provides a high level of heteroatom functionalities (∼2.54% N and ∼21.3% O), which are desirable for high faradaic pseudocapacitance. The as-prepared carbon composite exhibited a high specific capacitance of 290 F g-1 with good rate capability and cycling stability. The symmetric supercapacitors yielded a high value of energy density of 12.9 W h kg-1 at a power density of 95 W kg-1 with a 1.45 V voltage range in 1 M KOH aqueous electrolytes.

A Proposed Algorithm for Managing Cerebral Proliferative Angiopathy.

OBJECTIVE: Cerebral proliferative angiopathy (CPA) is a rare disease, characterized by a large vascular nidus, diffuse angiogenesis, and intermingled normal brain tissue. Conservative treatment, endovascular intervention, indirect revascularization, and radiotherapy have been applied to treat this disease. However, some cases deteriorate even after non-conservative treatment, and there has been no standard of treatment for this disease so far. In order to build a better treatment strategy, we review literature, present our case and propose an algorithm for managing CPA. METHODS: Following the PRISMA principle, we systemically reviewed literature discussing CPA. A case successfully managed with multi-modal treatment is also illustrated. RESULTS: A total of 23 articles with 74 cases of CPA were found. Thirty-three patients received single-modal management. These 33 cases include 24 receiving endovascular intervention, 7 receiving indirect revascularization, and 2 receiving radiotherapy. Three of the 33 patients deteriorated clinically, and 1 expired. We present a 6-year-old boy with left hemispheric CPA receiving indirect revascularization, followed by 2 consecutive courses of stereotactic radiosurgery targeting arteriovenous shunts in the left basal ganglia and arteriovenous shunts around the olfactory groove. In the follow-up period of more than 4 years, good collateral formation, improved perilesional perfusion, CPA shrinkage, and symptom relief were all achieved. CONCLUSIONS: Based on our literature review and case, we propose an algorithm for the management of CPA and emphasize that multi-modal treatment is necessary for most CPA cases.

Clinical and Microbiological Characteristics of Neonates with Candidemia and Impacts of Therapeutic Strategies on the Outcomes.

Neonatal candidemia is associated with significant morbidities and a high mortality rate. We aimed to investigate the clinical characteristics of Candida bloodstream infections in neonates and the impact of therapeutic strategies on the outcomes. We identified all the neonates with candidemia from a medical center in Taiwan over an 18-year period (2003−2021) and analyzed them. Clinical isolates were confirmed by DNA sequencing, and antifungal susceptibility testing was performed. The prognostic factors associated with clinical treatment failure (30-day, all-cause mortality and persistent candidemia > 72 h after antifungal agents) and in-hospital mortality were analyzed using logistic regression modeling. A total of 123 neonates with 139 episodes of candidemia were included in the study. The median (IQR) gestational age and birth weight of the neonates with candidemia were 29.0 (26.0−35.0) weeks and 1104.0 (762.0−2055) g, respectively. The most common Candida spp. was Candida albicans (n = 57, 41.0%), followed by C. parapsilosis (n = 44, 31.7%), Candida guilliermondii (n = 12, 8.6%), and C. glabrata (n = 11, 7.9%). The overall susceptibility to fluconazole was 81.3%, and the resistant rates against other antifungal agents were less than 3%. The cumulative mortality rate at 7 and 30 days after the first episode of candidemia was 11.3% and 32.3%, respectively. The overall in-hospital mortality rate was 42.3%. The treatment outcomes did not change over the study period and were not affected by delayed initiation of antifungal agents. Multivariate analysis showed that delayed catheter removal (odds ratio [OR], 5.54; 95% confidence interval [CI]: 1.93−15.86, p = 0.001), septic shock (OR, 7.88; 95% CI: 2.83−21.93, p < 0.001), and multiple chronic comorbidities (OR, 8.71; 95% CI: 1.82−41.81, p = 0.007) were independently associated with the final in-hospital mortality. We concluded that the overall mortality of neonatal candidemia has remained consistently high over the past decade. Prompt early catheter removal and an aggressive treatment strategy for neonatal candidemia with septic shock would be critical to improving patient outcomes.