The potential role of heparin-binding protein in neonatal sepsis: research progress.

Neonatal sepsis is a major global health challenge, leading to significant morbidity and mortality in newborns. The search for precise biomarkers for its early prediction in clinical settings has been ongoing, with heparin-binding protein (HBP) emerging as a promising candidate. Originating from granules in neutrophils, HBP is released into the bloodstream in response to infection and plays a pivotal role in the body's inflammatory response. Its significance extends beyond its inflammatory origins; research indicates dynamic changes in HBP levels are strongly linked to reduce in-hospital mortality, offering a prognostic advantage over existing biomarkers. Furthermore, HBP has demonstrated considerable clinical utility in the early diagnosis and stratification of neonatal sepsis, suggesting its potential as a reliable blood marker for early prediction of the disease and its severity. Its application may extend to guiding the judicious use of antibiotics in treating newborns, addressing a critical aspect of neonatal care. Despite these encouraging results, the precise clinical utility of HBP for diagnosing and treating sepsis in neonates still demands further clarification through extensive research. This review delves into the current scientific understanding of HBP's contribution to diagnosing, prognosticating, and treating neonatal sepsis, while considering its future clinical applications.

Genetic and pathophysiological insights from autopsied patient with primary familial brain calcification: novel MYORG variants and astrocytic implications.

Primary familial brain calcification (PFBC) is a genetic neurological disorder characterized by symmetric brain calcifications that manifest with variable neurological symptoms. This study aimed to explore the genetic basis of PFBC and elucidate the underlying pathophysiological mechanisms. Six patients from four pedigrees with brain calcification were enrolled. Whole-exome sequencing identified two novel homozygous variants, c.488G > T (p.W163L) and c.2135G > A (p.W712*), within the myogenesis regulating glycosidase (MYORG) gene. Cerebellar ataxia (n = 5) and pyramidal signs (n = 4) were predominant symptoms, with significant clinical heterogeneity noted even within the same family. An autopsy of one patient revealed extensive brainstem calcifications, sparing the cerebral cortex, and marked by calcifications predominantly in capillaries and arterioles. The pathological study suggested morphological alterations characterized by shortened foot processes within astrocytes in regions with pronounced calcification and decreased immunoreactivity of AQP4. The morphology of astrocytes in regions without calcification remains preserved. Neuronal loss and gliosis were observed in the basal ganglia, thalamus, brainstem, cerebellum, and dentate nucleus. Notably, olivary hypertrophy, a previously undescribed feature in MYORG-PFBC, was discovered. Neuroimaging showed reduced blood flow in the cerebellum, highlighting the extent of cerebellar involvement. Among perivascular cells constituting the blood-brain barrier (BBB) and neurovascular unit, MYORG is most highly expressed in astrocytes. Astrocytes are integral components of the BBB, and their dysfunction can precipitate BBB disruption, potentially leading to brain calcification and subsequent neuronal loss. This study presents two novel homozygous variants in the MYORG gene and highlights the pivotal role of astrocytes in the development of brain calcifications, providing insights into the pathophysiological mechanisms underlying PFBC associated with MYORG variants.

Case Report: Taking action or standing by: managing a preterm neonate at the risk of neonatal varicella by metagenomic next-generation sequencing.

Neonatal varicella is indeed a rare condition, and most infants born to mothers with varicella have a good prognosis. However, in exceptional cases, neonatal varicella can be life-threatening, particularly for preterm infants. Therefore, it is vital to make an early diagnosis or predict the risk of neonatal varicella to ensure prompt treatment and improve prognosis. This report made an effort to early predict neonatal vericalla by using metagenomic next-generation sequencing (mNGS) in a preterm infant who was at risk for vericalla infection. A preterm infant born from a mother with varicella with symptom onset at 8 days before delivery, putting the infant at risk for varicella infection. Importantly, the patient develop pneumonia and pneumothorax, and neonatal vericella was suspected. Fortunately, the use of mNGS for testing the varicella gene in the serum promptly ruled out varicella zoster virus (VZV) infection in the patient, as indicated by a negative mNGS result. Subsequent follow-up, which included a 14-day stay in the hospital followed by an additional 7 days at home, confirmed this finding. Throughout this period, the patient did not exhibit any rash or other symptoms associated with varicella. Therefore, the novel approach of using mNGS allows neonatologists to predict and promptly address potential neonatal infections. This early detection is crucial, as delayed diagnosis or treatment could pose life-threatening risks, as exemplified by the case of neonatal varicella. In such cases, neonatologists can take proactive measures instead of standing by for at-risk neonates. Furthermore, given the severity of neonatal varicella as a life-threatening condition, the early exclusion of subsequent varicella infection by mNGS can offer reassurance to both family members and healthcare professionals.

Linking LRP12 CGG repeat expansion to inherited peripheral neuropathy.

BACKGROUND: The causative genes for over 60% of inherited peripheral neuropathy (IPN) remain unidentified. This study endeavours to enhance the genetic diagnostic rate in IPN cases by conducting screenings focused on non-coding repeat expansions. METHODS: We gathered data from 2424 unrelated Japanese patients diagnosed with IPN, among whom 1555 cases with unidentified genetic causes, as determined through comprehensive prescreening analyses, were selected for the study. Screening for CGG non-coding repeat expansions in LRP12, GIPC1 and RILPL1 genes was conducted using PCR and long-read sequencing technologies. RESULTS: We identified CGG repeat expansions in LRP12 from 44 cases, establishing it as the fourth most common aetiology in Japanese IPN. Most cases (29/37) exhibited distal limb weakness, without ptosis, ophthalmoplegia, facial muscle weakness or bulbar palsy. Neurogenic changes were frequently observed in both needle electromyography (97%) and skeletal muscle tissue (100%). In nerve conduction studies, 28 cases primarily showed impairment in motor nerves without concurrent involvement of sensory nerves, consistent with the phenotype of hereditary motor neuropathy. In seven cases, both motor and sensory nerves were affected, resembling the Charcot-Marie-Tooth (CMT) phenotype. Importantly, the mean CGG repeat number detected in the present patients was significantly shorter than that of patients with LRP12-oculopharyngodistal myopathy (p<0.0001). Additionally, GIPC1 and RILPL1 repeat expansions were absent in our IPN cases. CONCLUSION: We initially elucidate LRP12 repeat expansions as a prevalent cause of CMT, highlighting the necessity for an adapted screening strategy in clinical practice, particularly when addressing patients with IPN.

Case report: Acute severe hyponatremia-induced seizures in a newborn: a community-acquired case and literature review.

Severe neonatal hyponatremia represents a critical electrolyte imbalance with potentially severe neurological outcomes, a condition rarely documented in community-acquired, full-term newborns. This report underscores a unique case of a 23-day-old, previously healthy, full-term male neonate experiencing severe hyponatremia that precipitated seizures, underscoring the urgency of prompt recognition and intervention. The neonate presented with symptoms including vomiting, groaning, chills, fixed staring, and limb tremors. Critical findings upon admission encompassed hypothermia, hypotension, tachycardia, and tachypnea accompanied by significant weight loss. The clinical presentation was marked by dehydration, lethargy, weak crying, a fixed gaze, irregular breathing, and coarse lung sounds, yet a distended abdomen, hypertonic limb movements, and recurrent seizures were observed. Immediate interventions included establishing IV access, rewarming, mechanical ventilation, seizure management, volume expansion, dopamine for circulatory support, and initiation of empirical antibiotics. Diagnostic evaluations revealed a sodium ion concentration of 105.9 mmol/L, while amplitude-integrated electroencephalography (aEEG) detected pronounced seizure activity characterized by a lack of sleep-wake rhythmicity, noticeable elevation in both the lower and upper amplitude margins, and a sustained decrease in the lower margin voltage dropping below 5 µV, presenting as sharp or serrated waveforms. The management strategy entailed rapid electrolyte normalization using hypertonic saline and sodium bicarbonate, anticonvulsant therapy, and comprehensive supportive care, with continuous aEEG monitoring until the cessation of seizures. Remarkably, by the third day, the neonate's condition had stabilized, allowing for discharge in good health 10 days post-admission. At a 16-month follow-up, the child exhibited no adverse neurological outcomes and demonstrated favorable growth and development. Our extensive review on the etiology, clinical manifestations, aEEG monitoring, characteristics of seizures induced by severe neonatal hyponatremia, treatment approaches, and the prognosis for seizures triggered by severe hyponatremia aims to deepen the understanding and enhance clinical management of this complex condition. It stresses the importance of early detection, accurate diagnosis, and customized treatment protocols to improve outcomes for affected neonates. Additionally, this review accentuates the indispensable role of aEEG monitoring in managing neonates at elevated risk for seizures. Yet, the safety and efficacy of swiftly administering hypertonic saline for correcting severe hyponatremia-induced seizures necessitate further investigation through medical research.

Alveolar Soft Tissue Sarcoma: Correlation of MRI Features With Histological Grading and Patient Prognosis.

BACKGROUND: Alveolar Soft Part Sarcoma (ASPS) is a rare, aggressive cancer whose diagnosis and treatment depend on histological grading. However, tumor variability can lead to underestimation, affecting treatment, and patient survival. OBJECTIVE: To evaluate MRI features associated with Grade III ASPS and to determine the relationship between MRI features and patient prognosis. STUDY TYPE: Retrospective analysis. SUBJECTS: Sixty-seven patients with ASPS were included with 37 males and 30 females (M/F = 1.23) follow-up and survival analysis on 50 patients. FIELD STRENGTH/SEQUENCE: A 3.0 T, T1WI-FSE, T2WI-FSE, DWI-EPI, DCE-MRI (gradient echo). ASSESSMENT: MRI features (margin, peritumoral oedema, peritumoral enhancement, necrosis, vascular flow void signal, heterogeneous signal intensity [SI] at T1WI and T2WI, ADCmean, time-intensity curve [TIC] type, distant metastasis, and bone invasion) and histological grading were independently evaluated by three radiologists and two pathologists, with Grade III considered high-grade. STATISTICAL TESTS: The chi-square or Fisher's exact test was used to assess the correlation between MRI features and histological grading. Multivariable binary logistic regression identified independent factors associated with high-grade tumors. The Kaplan-Meier method and Cox proportional hazards model were used to calculate hazard ratios for MRI features. RESULTS: Tumor necrosis, heterogeneous SI at T2WI ≥50%, and ADCmean were associated with high-grade ASPS. Tumor necrosis was an independent factors associated with local relapse-free survival (odds ratio [OR], 3.88). TIC type was associated with 5-year survival rate (OR, 2.80) and local relapse-free survival (OR, 2.69). Heterogeneous SI at T2WI ≥50% was associated with 5-year survival (OR, 4.00), local relapse-free survival (OR, 5.58), and local relapse-free survival (OR, 4.84). DATA CONCLUSION: MRI features including tumor necrosis, heterogeneity of SI at T2WI, ADCmean, and TIC type aid in assessing ASPS grading and prognosis. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

Qualitative and quantitative MRI analysis of alveolar soft part sarcoma: correlation with histological grade and Ki-67 expression.

OBJECTIVE: To investigate the correlation between MRI findings and histological features for preoperative prediction of histological grading and Ki-67 expression level in alveolar soft part sarcoma (ASPS). METHODS: A retrospective analysis was conducted on 63 ASPS patients (Jan 2017-May 2023). All patients underwent 3.0-T MRI examinations, including conventional sequences, dynamic contrast-enhanced scans with time-intensity curve analysis, and diffusion-weighted imaging with apparent diffusion coefficient (ADC) measurements. Patients were divided into low-grade (histological Grade I) and high-grade (histological Grade II/III) groups based on pathology. Immunohistochemistry was used to assess Ki-67 expression levels in ASPS. Statistical analysis included chi-square tests, Wilcoxon rank-sum test, binary logistic regression analysis, Spearman correlation analysis, and receiver operating characteristic curve analysis of various observational data. RESULTS: There were 29 low-grade and 34 high-grade patients (26 males and 37 females) and a wide age range (5-68 years). Distant metastasis, tumor enhancement characteristics, and ADC values were independent predictors of high-grade ASPS. High-grade ASPS had lower ADC values (p = 0.002), with an area under the curve (AUC), sensitivity, and specificity of 0.723, 79.4%, and 58.6%, respectively, for high-grade prediction. There was a negative correlation between ADC values and Ki-67 expression (r = -0.526; p < 0.001). When the cut-off value of ADC was 0.997 × 10-3 mm²/s, the AUC, sensitivity, and specificity for predicting high Ki-67 expression were 0.805, 65.6%, and 83.9%, respectively. CONCLUSION: Qualitative and quantitative MRI parameters are valuable for predicting histological grading and Ki-67 expression levels in ASPS. CRITICAL RELEVANCE STATEMENT: This study will help provide a more nuanced understanding of ASPS and guide personalized treatment strategies. KEY POINTS: There is limited research on assessing ASPS prognosis through MRI. Metastasis, enhancement, and ADC correlated with histological grade; ADC related to Ki-67 expression. MRI provides clinicians with valuable information on ASPS grading and proliferation activity.

Lymph node metastasis burden identifies head and neck squamous cell carcinoma patients benefiting from adjuvant chemoradiation: A propensity score-matching.

INTRODUCTION: To examine the influence of adjuvant chemoradiation therapy (CRT) on survival, stratified by varying numbers and level involved of metastatic lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Patients who underwent surgery for metastatic, negative margin HNSCC without extranodal extension were retrospectively enrolled and divided into two groups based on adjuvant therapy received: radiotherapy (RT) and CRT. The impact of RT versus CRT, stratified by the number of positive lymph nodes and the level involved, on Disease-Free Survival (DFS) and Overall Survival (OS) was analyzed. RESULTS: Following propensity score matching, a total of 580 patients were included. The burden and level of lymph node metastasis were independent predictors of poorer survival. Among patients with no more than two positive lymph nodes or involvement of levels I-III, the addition of chemotherapy to RT did not demonstrate a significant improvement in prognosis. However, in patients with three or more positive lymph nodes, CRT showed improved DFS and OS compared to RT. In patients with involvement of levels IV-V, the addition of chemotherapy to RT resulted in a significant 24 % reduction in the risk of recurrence and a 20 % decrease in the risk of death. CONCLUSION: Incorporation of adjuvant chemoradiation can lead to a favorable prognosis in patients with metastatic HNSCC. This impact was notable in cases where there were three or more positive lymph nodes or involvement of levels IV-V.

Applying the Wake-Up-like Effect to Enhance the Capabilities of Two-Dimensional Ferroelectric Field-Effect Transistors.

For traditional ferroelectric field-effect transistors (FeFETs), enhancing the polarization domain of bulk ferroelectric materials is essential to improve device performance. However, there has been limited investigation into the enhancement of polarization field in two-dimensional (2D) ferroelectric material such as CuInP2S6 (CIPS). In this study, similar to bulk ferroelectric materials, CIPS exhibited enhanced polarization field upon application of external cyclic voltage. Moreover, unlike traditional ferroelectric materials, the polarization enhancement of CIPS is not due to redistribution of the defect but rather originates from a mechanism: the long-distance migration of Cu ions. We termed this mechanism the "wake-up-like effect". After incorporating the wake-up-like effect into the graphene/CIPS/WSe2 FeFET device, we successfully increased the hysteresis window and enhanced the current on/off ratio by 4 orders of magnitude. Moreover, the FeFET yielded remarkable achievements, such as multilevel nonvolatile memory with 21 distinct conductance levels, a high on/off ratio exceeding 106, a long retention time exceeding 103 s, and neuromorphic computing with 93% accuracy at recognizing handwritten digits. Introducing the wake-up-like effect to 2D CIPS may pave the way for innovative approaches to achieve advanced multilevel nonvolatile memory and neuromorphic computing capabilities for next-generation micro-nanoelectronic devices.

Lymph node metastasis in cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The study aimed to assess the impact of parotid lymph nodes (LNs) on the prognosis of patients with cutaneous squamous cell carcinomas of the head and neck (HNcSCC), and to develop an alternative LN assessment method to enhance locoregional control (LRC) and overall survival (OS) stratification. METHODS: We retrospectively enrolled patients with surgically treated HNcSCC. Primary outcome variables were LRC and OS. The influence of parotid LNs and different LN assessment methods on prognosis was analyzed using Cox models, and comparisons were made using the C-index, Akaike Information Criterion, and Bayesian Information Criterion. RESULTS: A total of 126 patients were included. Both intraparotid and periparotid LN statuses significantly linked with prognosis. The presence of extranodal extension (ENE) in cervical LNs, rather than parotid LNs, was predictive of decreased LRC and OS. In the Cox analysis, only N3 of the AJCC N classification, when compared to N0, showed reduced LRC and OS. In comparison to N0P1, only N0P3/N1P1 and N2P2/N2P3 of the O'Brien staging system tended to predict poorer LRC, with no subgroup emerging as an independent predictor for OS. The proposed LN assessment method, based on the number of metastatic LNs and ENE status in cervical LNs, demonstrated superior performance in terms of C-index, Akaike Information Criterion, and Bayesian Information Criterion compared to other systems. CONCLUSION: Parotid LNs were significant determinants of prognosis in metastatic HNcSCC. The novel LN assessment method proposed (1-2 vs. 3-4 vs. 5 + or ENE) displayed similar survival stratification to the AJCC N and O'Brien staging systems.

Oncologic and functional results between sentinel lymph node biopsy and elective neck dissection in cT1/2N0 maxillary squamous cell carcinoma.

OBJECTIVE: To evaluate the oncologic safety and quality of life associated with the use of sentinel lymph node biopsy (SLNB) as compared to elective neck dissection (END) in patients with cT1/2N0 maxillary squamous cell carcinoma. METHODS: This study constituted a retrospective analysis of consecutively treated patients who underwent SLNB or END, with data collected prospectively. We analyzed the impact of the different neck procedures on regional control and disease-specific survival via the Cox model. Patients in both groups completed the University of Washington Quality of Life questionnaire. RESULTS: We included a total of 130 patients, with 47 receiving SLNB. In all cases, the sentinel lymph node could be identified, and of these, 5 had a positive result, yielding a sensitivity of 83.3 %, a specificity of 100 %, a false negative rate of 16.7 %, and a negative predictive value of 97.6 %. The sensitivity, specificity, false negative rate, and negative predictive value of END in detecting occult metastasis were 64.3 %, 100 %, 35.7 %, and 93.2 %, respectively. In comparison to END after propensity score matching, SLNB exhibited no significant difference in its effects on regional control (p = 0.519, HR: 1.05, 95 % CI: 0.52-1.93) and disease-specific survival (p = 0.634, HR: 1.22, 95 % CI: 0.53-1.99). Patients in SLNB group showed significantly higher mean scores of shoulder and taste domains at 3 months, 6 months, and 12 months postoperatively compared to those in END group. CONCLUSION: SLNB could act as a viable alternative to END in cT1/2N0 maxillary squamous cell carcinoma with comparable prognosis and better quality of life.

Artificial Funnel Nanochannel Device Emulates Synaptic Behavior.

Creating artificial synapses that can interact with biological neural systems is critical for developing advanced intelligent systems. However, there are still many difficulties, including device morphology and fluid selection. Based on Micro-Electro-Mechanical System technologies, we utilized two immiscible electrolytes to form a liquid/liquid interface at the tip of a funnel nanochannel, effectively enabling a wafer-level fabrication, interactions between multiple information carriers, and electron-to-chemical signal transitions. The distinctive ionic transport properties successfully achieved a hysteresis in ionic transport, resulting in adjustable multistage conductance gradient and synaptic functions. Notably, the device is similar to biological systems in terms of structure and signal carriers, especially for the low operating voltage (200 mV), which matches the biological neural potential (∼110 mV). This work lays the foundation for realizing the function of iontronics neuromorphic computing at ultralow operating voltages and in-memory computing, which can break the limits of information barriers for brain-machine interfaces.

Sentinel lymph node biopsy versus observation in high risk cutaneous squamous cell carcinoma of head and neck: a propensity score matching analysis.

Sentinel lymph node biopsy (SLNB) has gained considerable attention in the management of head and neck cutaneous squamous cell carcinoma (HNcSCC). The aim of this study was to compare the oncologic outcomes between observation and SLNB in cN0 high-risk HNcSCC patients. We retrospectively enrolled patients from the SEER database and evaluated the impact of observation versus SLNB on disease-specific survival (DSS) and overall survival (OS) using a Propensity Score Matching (PSM) analysis. A total of 9804 patients were included, with 1169 cases treated by SLNB. Successful retrieval of the sentinel lymph node was achieved in 1130 procedures. After PSM and subsequent multivariate analysis, SLNB was found to be an independent predictor for improved DSS, with a hazard ratio of 0.70 (95% confidence interval: 0.56-0.86). In patients presenting with two or three high-risk factors, SLNB was associated with better DSS (p = 0.021 and p = 0.044), but similar OS (p = 0.506 and p = 0.801) when compared to observation. However, in patients exhibiting four high-risk factors, SLNB demonstrated significantly improved DSS (p = 0.040) and OS (p = 0.028) compared to observation. Our findings suggest that SLNB is a highly feasible technique in HNcSCC and provides significant survival benefits. It is strongly recommended in patients with two or more high-risk factors, as it can help guide treatment decisions and improve patient outcomes.

Ceftriaxone-induced severe hemolytic anemia, renal calculi, and cholecystolithiasis in a 3-year-old child: a case report and literature review.

Ceftriaxone is widely used in pediatric outpatient care for its efficacy against respiratory and digestive system infections, yet its increasing association with severe immune hemolytic reactions requires heightened vigilance from pediatricians. This report details a rare and severe case of ceftriaxone-induced severe immune hemolytic anemia (IHA), hemolytic crisis, myocardial injury, liver injury, renal calculi, and cholecystolithiasis in a previously healthy 3-year-old child. The child, treated for bronchitis, experienced sudden pallor, limb stiffness, and altered consciousness following the fifth day of ceftriaxone infusion, with hemoglobin (Hb) levels precipitously dropping to 21 g/L. Immediate cessation of ceftriaxone and the administration of oxygen therapy, blood transfusion, intravenous immunoglobulin (IVIG), and corticosteroids led to a gradual recovery. Despite initial improvements, the patient's condition necessitated extensive hospital care due to complications including myocardial injury, liver injury, renal calculi, and cholecystolithiasis. After a 12-day hospital stay and a 3-month follow-up, the child showed complete normalization of Hb and liver function and resolution of calculi. In children, ceftriaxone infusion may trigger severe, potentially fatal, hemolytic reactions. Pediatricians must promptly recognize symptoms such as pallor, limb stiffness, and unresponsiveness, indicative of ceftriaxone-induced severe IHA, and immediately discontinue the drug. Effective management includes timely blood transfusion, respiratory support, IVIG administration, and corticosteroids when necessary, along with rigorous vital signs monitoring. Continued vigilance is imperative, even after cessation of ceftriaxone, to promptly address any residual adverse effects.

Neck management in cutaneous squamous cell carcinoma with parotid metastasis.

OBJECTIVE: Our objective is to assess the oncologic outcomes of observation, elective neck dissection (END), and elective neck irradiation (ENI) in the neck management of head and neck cutaneous squamous cell carcinoma (HNcSCC) with parotid metastasis (P+) and to evaluate the quality of life (QoL) of patients who received END or ENI. METHODS: Patients with P+ HNcSCC were retrospectively enrolled. The impact of observation, END, and ENI on regional control (RC) and overall survival (OS) was analyzed using Cox proportional hazards model with presentation via hazard ratio (HR) with a 95% confidence interval (CI). QoL was evaluated using the University of Washington Quality of Life questionnaire. RESULTS: A total of 134 patients were included in our analysis. In the Cox model for RC, both END and ENI had decreased HRs of 0.27 (95% CI: 0.15-0.69) and 0.34 (95% CI: 0.18-0.86), respectively, in comparison with observation. In the Cox model for OS, both END (p = 0.001, HR: 0.22, 95% CI: 0.10-0.72) and ENI (p = 0.006, HR: 0.30, 95% CI: 0.17-0.83) were superior to observation. In patients with three or more positive parotid lymph nodes, END resulted in significantly better RC (p < 0.001) and OS (p = 0.001) compared with ENI. The two groups were found to be comparable in all 12 domains of the University of Washington Quality of Life questionnaire. CONCLUSION: In the neck management of P+ HNcSCC, observation is not recommended. END is the preferred option, but ENI is an alternative method without compromise to survival or QoL, except in cases with three or more metastatic parotid lymph nodes.

A model for evaluating the performance of compulsory education inputs in ethnic areas in China.

A scientific performance evaluation model is necessary to establish a performance evaluation index system for compulsory education in ethnic areas and to conduct objective and impartial evaluations. After conducting theoretical analysis and reviewing literature, it was determined that existing educational input performance evaluation models are general and fail to reflect the unique characteristics of compulsory education development in ethnic areas of China. Therefore, this study intends to improve their self-adaptability and degree of fit. Based on the features of China's ethnic areas and the current situation of compulsory education development, a trinity evaluation model of compulsory education input performance in ethnic regions was constructed using the classical performance evaluation theoretical framework. This model includes the "implementation topic - target concept - performance dimension." The government is the main organization responsible for organizing and implementing the entire performance evaluation, with publicness and responsiveness as the value idea of evaluation. The "4E″ of enough, equity, efficiency, and effectiveness are the evaluation objectives, and input, allocation, output, and effect are the dimensions of the building of the performance evaluation index system. The "4E″ evaluation objectives are integrated into the performance evaluation dimensions and index system. The reconstructed theoretical model of performance evaluation combines universality and specificity, highlights the dual attributes of "tool-value," realizes the organic combination of internal and external performance evaluation, illustrates the overall performance evaluation process and ensures objective, fair, and accurate performance evaluation results. It provides useful guidelines for further optimizing compulsory education investment policies and promoting high-quality and well-balanced compulsory education in China's ethnic areas.

A novel homozygous HPDL variant in Japanese siblings with autosomal recessive hereditary spastic paraplegia: case report and literature review.

Biallelic variants of 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) gene have been linked to neurodegenerative disorders ranging from severe neonatal encephalopathy to early-onset spastic paraplegia. We identified a novel homozygous variant, c.340G > T (p.Gly114Cys), in the HPDL gene in two siblings with autosomal recessive hereditary spastic paraplegia (HSP). Despite sharing the same likely pathogenic variant, the older sister had pure HSP, whereas her brother had severe and complicated HSP, accompanied by early-onset mental retardation and abnormalities in magnetic resonance imaging. Given the clinical heterogeneity and potential for treatable conditions in HPDL-related diseases, we emphasize the importance of genetic testing for the HPDL gene.

Dystonia and Parkinsonism in COA7-related disorders: expanding the phenotypic spectrum.

BACKGROUND AND OBJECTIVE: Biallelic mutations in the COA7 gene have been associated with spinocerebellar ataxia with axonal neuropathy type 3 (SCAN3), and a notable clinical diversity has been observed. We aim to identify the genetic and phenotypic spectrum of COA7-related disorders. METHODS: We conducted comprehensive genetic analyses on the COA7 gene within a large group of Japanese patients clinically diagnosed with inherited peripheral neuropathy or cerebellar ataxia. RESULTS: In addition to our original report, which involved four patients until 2018, we identified biallelic variants of the COA7 gene in another three unrelated patients, and the variants were c.17A > G (p.D6G), c.115C > T (p.R39W), and c.449G > A (p.C150Y; novel). Patient 1 presented with an infantile-onset generalized dystonia without cerebellar ataxia. Despite experiencing an initial transient positive response to levodopa and deep brain stimulation, he became bedridden by the age of 19. Patient 2 presented with cerebellar ataxia, neuropathy, as well as parkinsonism, and showed a slight improvement upon levodopa administration. Dopamine transporter SPECT showed decreased uptake in the bilateral putamen in both patients. Patient 3 exhibited severe muscle weakness, respiratory failure, and feeding difficulties. A haplotype analysis of the mutation hotspot in Japan, c.17A > G (p.D6G), uncovered a common haplotype block. CONCLUSION: COA7-related disorders typically encompass a spectrum of conditions characterized by a variety of major (cerebellar ataxia and axonal polyneuropathy) and minor (leukoencephalopathy, dystonia, and parkinsonism) symptoms, but may also display a dystonia-predominant phenotype. We propose that COA7 should be considered as a new causative gene for infancy-onset generalized dystonia, and COA7 gene screening is recommended for patients with unexplained dysfunctions of the central and peripheral nervous systems.

Clinical variability associated with intronic FGF14 GAA repeat expansion in Japan.

BACKGROUND AND OBJECTIVES: The GAA repeat expansion within the fibroblast growth factor 14 (FGF14) gene has been found to be associated with late-onset cerebellar ataxia. This study aimed to investigate the genetic causes of cerebellar ataxia in patients in Japan. METHODS: We collected a case series of 940 index patients who presented with chronic cerebellar ataxia and remained genetically undiagnosed after our preliminary genetic screening. To investigate the FGF14 repeat locus, we employed an integrated diagnostic strategy that involved fluorescence amplicon length analysis polymerase chain reaction (PCR), repeat-primed PCR, and long-read sequencing. RESULTS: Pathogenic FGF14 GAA repeat expansions were detected in 12 patients from 11 unrelated families. The median size of the pathogenic GAA repeat was 309 repeats (range: 270-316 repeats). In these patients, the mean age of onset was 66.9 ± 9.6 years, with episodic symptoms observed in 56% of patients and parkinsonism in 30% of patients. We also detected FGF14 repeat expansions in a patient with a phenotype of multiple system atrophy, including cerebellar ataxia, parkinsonism, autonomic ataxia, and bilateral vocal cord paralysis. Brain magnetic resonance imaging (MRI) showed normal to mild cerebellar atrophy, and a follow-up study conducted after a mean period of 6 years did not reveal any significant progression. DISCUSSION: This study highlights the importance of FGF14 GAA repeat analysis in patients with late-onset cerebellar ataxia, particularly when they exhibit episodic symptoms, or their brain MRI shows no apparent cerebellar atrophy. Our findings contribute to a better understanding of the clinical variability of GAA-FGF14-related diseases.

Number and ratio of metastatic lymph nodes impacts the prognosis of submandibular gland cancer.

This study aimed to assess the impact of the number and ratio of metastatic lymph nodes (LNs) on prognosis in submandibular gland cancer. To this end, patients were selected from the Surveillance, Epidemiology, and End Results database retrospectively. The effect of the number and ratio of metastatic LNs and the American Joint Committee on Cancer (AJCC) N stage on disease-specific survival (DSS) and overall survival (OS) was analyzed. In addition, prognostic models based on LN evaluation methods were developed to predict the OS and DSS. A total of 914 patients were included. Binary recursive partitioning analysis determined the optimal cut-off number of metastatic LNs (0 vs. 1-2. vs. 3+). The presence of 3+ metastatic LNs carried the greatest impact on prognosis, followed by 1-2 positive LNs occurrences. The ratio of metastatic LNs was an independent factor for DSS and OS. The model had a higher likelihood ratio and C-index than those in the Cox model based on the AJCC N stage. Quantitative LN burden and ratio of metastatic LNs provides better survival stratification than the AJCC N stage.