bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: Bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral?
Authors: Yuan Ziyun , Xiang Lei , Liu Ran , Yue Wei
Published: May 2023

Background

The middle cerebellar peduncle (MCP) is the most common site associated with hearing impairment in acute ischaemic stroke. Narrowing or occlusion of the vertebrobasilar artery due to atherosclerosis is thought to be the main pathogenesis of MCP infarction. Most previous reports of MCP infarction have not been clear whether the patient's hearing impairment is localized to the center or periphery.

Case presentation

We report 44-year-old man with vertigo, tinnitus, and bilateral sudden sensorineural hearing loss (SSNHL) as the first symptoms. Pure Tone Audiogram revealed complete hearing loss in both ears. Acute bilateral MCP infarction was diagnosed by repeated brain magnetic resonance imaging (MRI). The brainstem auditory evoked potential (BAEP) and the electrocochleography were normal. The otoacoustic emissions showed binaural cochlear dysfunctions. After the antiplatelet, lipid-lowering, steroids and hyperbaric oxygen therapy, the pure-tone average (PTA) showed a clear improvement with 67 decibels (dB) on the right and 73 dB on the left at the 3-month follow-up.

Conclusion

Vertebrobasilar diseases due to atherosclerosis should be routinely considered in middle-aged and elderly patients with vascular risk factors and bilateral hearing loss. Bilateral SSNHL can be a prodrome of acute MCP infarction and it can be peripheral. Brain MRI, brain magnetic resonance angiogram (MRA), brain and neck computed tomography angiography (CTA), BAEP, otoacoustic emissions, and Pure Tone Audiogram help to localize and qualify the diagnosis. Bilateral SSNHL localized to the periphery usually improves better and has a good prognosis. Early detection of hearing loss and intervention can help patients recover.
Policy analysis in the field of rare diseases in China: a combined study of content analysis and Bibliometrics analysis
Authors: Li Xiaotao , Wu Lan , Yu Lina , He Youqin , Wang Min , Mu Yan
Published: May 2023

Introduction

The Chinese government has made significant strides in addressing the needs of individuals affected by rare diseases in recent years. This paper aims to provide a comprehensive analysis of national rare disease policies in China from 2009 to 2022, using a mixed-methods approach.

Methods

A two-dimensional analytical framework, which includes policy tools and policy themes, is introduced to analyze the rare disease policies comprehensively. Drawing on the policy tools theory proposed by Rothwell and Zegveld, this paper evaluates the tools used in rare disease policies. Co-word analyses and network analyses are employed to identify key themes in rare disease policies and collaboration among government departments.

Results

The rare disease policy landscape in China is undergoing rapid growth, with an increasing number of government departments involved in policy formulation. However, further collaboration between departments is needed to strengthen these policies. Environment-based and supply-based tools are preferred in rare disease policies. The policy themes can be grouped into four categories: (1) Registration, Approval and Supply of Rare Disease Drugs, (2) Construction of Diagnosis and Treatment System for Rare Diseases, (3) Development and Genericization of Rare Disease Drugs, and (4) Social Security for Patients with Rare Diseases.

Discussion

The study provides valuable insights into the current state of rare disease policies in China and offers suggestions for policy improvement. The results show that the Chinese government has made efforts to address the needs of individuals affected by rare diseases, but there is still room for improvement. The collaboration between government departments needs to be strengthened to achieve better rare disease policies. The findings of this study have implications for other countries with similar healthcare systems and can contribute to a better understanding of the impact of rare disease policies on public health.
Mitochondrial genome diversity of Balamuthia mandrillaris revealed by a fatal case of granulomatous amoebic encephalitis
Authors: Law Cherie Tsz-Yiu , Nivesvivat Thirapa , Xiong Qing , Kulkeaw Kasem , Shi Ling , Ruenchit Pichet , Suwanpakdee Detchvijitr , Suwanpakdee Piradee , Tongkrajang Nongnat , Sarasombath Patsharaporn T. , Tsui Stephen Kwok-Wing
Published: May 2023

Introduction

Balamuthia (B.) mandrillaris is a free-living amoeba that can cause rare yet fatal granulomatous amoebic encephalitis (GAE). However, efficacious treatment for GAE is currently unavailable, especially when genomic studies on B. mandrillaris are limited.

Methods

In this study, B. mandrillaris strain KM-20 was isolated from the brain tissue of a GAE patient, and its mitochondrial genome was de novo assembled using high-coverage Nanopore long reads and Illumina short reads.

Results and Discussion

Phylogenetic and comparative analyses revealed a range of diversification in the mitochondrial genome of KM-20 and nine other B. mandrillaris strains. According to the mitochondrial genome alignment, one of the most variable regions was observed in the ribosomal protein S3 (rps3), which was caused by an array of novel protein tandem repeats. The repeating units in the rps3 protein tandem region present significant copy number variations (CNVs) among B. mandrillaris strains and suggest KM-20 as the most divergent strain for its highly variable sequence and highest copy number in rps3. Moreover, mitochondrial heteroplasmy was observed in strain V039, and two genotypes of rps3 are caused by the CNVs in the tandem repeats. Taken together, the copy number and sequence variations of the protein tandem repeats enable rps3 to be a perfect target for clinical genotyping assay for B. mandrillaris. The mitochondrial genome diversity of B. mandrillaris paves the way to investigate the phylogeny and diversification of pathogenic amoebae.
Using natricine snakes to test how prey type and size affect predatory behaviors and performance
Authors: Gripshover Noah D. , Jayne Bruce C.
Published: May 2023

Introduction

Predation is a complex process for which behavior, morphology, and size of both predator and prey can affect the success and effectiveness of the predator. For predators such as snakes that swallow prey whole, gape ultimately limits prey size, but the behaviors used to select, capture, and consume prey and attributes of the prey can also affect maximal prey size. For example, swallowing live, struggling prey is difficult, but using coiling or envenomation to restrain or kill prey has evolved repeatedly in snakes.

Methods

To test the potential benefits of these behaviors, we manipulated the type and size of prey, and determined how stereotyped predatory behavior was in a snake species (Liodytes rigida) that uses both coiling and envenomation to restrain and immobilize its formidable prey of crayfish. We also studied a close relative (Liodytes pygaea) that eats fish and salamanders to gain insights into the evolution of these traits.

Results

For L. rigida, envenomation of hard-shell crayfish via their soft underside was very stereotyped (100% of feedings). Envenomation of soft-shell crayfish was less frequent (59% of feedings) but became more likely both with increased relative prey size and increased time after molt (hardness). L. rigida coiled more for hard-shell than soft-shell crayfish (77% vs. 30%). The probability of coiling was unaffected by prey size, but it increased with increased time after molt for the soft-shell crayfish. Liodytes rigida waited to swallow crayfish until they were completely immobile in 75% and 37% of the feedings with hard- and soft-shelled crayfish, respectively. Even with large prey L. pygaea never used coiling or envenomation, whereas previous studies of L. alleni, the sister species of L. rigida, observed non-lethal coiling without envenomation when eating hard-shell crayfish.

Discussion

Our findings for the Liodytes clade of three species suggest that coiling evolved ancestral to the crayfish specialists (L. alleni; L. rigida), and envenomation by L. rigida subsequently evolved as an additional means of subduing formidable prey. The proximate benefits observed for coiling and envenomation in L. rigida support the evolutionary scenario that both traits evolved to enhance the feeding performance for more formidable prey.
An advanced bionic knee joint mechanism with neural network controller
Authors: Xu Changxian , Sun Zhongbo , Wang Chen , Wu Xiujun , Li Binglin , Zhao Liming
Published: May 2023

In this article, a tensegrity-based knee mechanism is studied for developing a high-efficiency rehabilitation knee exoskeleton. Moreover, the kinematics and dynamics models of the knee mechanism are explored for bringing about further improvement in controller design. In addition, to estimate the performance of the bionic knee joint, based on the limit function of knee patella, the limit position functionality of the bionic knee joint is developed for enhancing the bionic property. Furthermore, to eliminate the noise item and other disturbances that are constantly generated in the rehabilitation process, a noise-tolerant zeroing neural network (NTZNN) algorithm is utilized to establish the controller. This indicates that the controller shows an anti-noise performance; hence, it is quite unique from other bionic knee mechanism controllers. Eventually, the anti-noise performance and the calculation of the precision of the NTZNN controller are verified through several simulation and contrast results.
Development of network oscillations through adolescence in male and female rats
Authors: Sibilska Sonia , Mofleh Rola , Kocsis Bernat
Published: May 2023

The primary aim of this research was to study the developmental trajectory of oscillatory synchronization in neural networks of normal healthy rats during adolescence, corresponding to the vulnerable age of schizophrenia prodrome in human. To monitor the development of oscillatory networks through adolescence we used a “pseudo-longitudinal” design. Recordings were performed in terminal experiments under urethane anesthesia, every day from PN32 to PN52 using rats-siblings from the same mother, to reduce individual innate differences between subjects. We found that hippocampal theta power decreased and delta power in prefrontal cortex increased through adolescence, indicating that the oscillations in the two different frequency bands follow distinct developmental trajectories to reach the characteristic oscillatory activity found in adults. Perhaps even more importantly, theta rhythm showed age-dependent stabilization toward late adolescence. Furthermore, sex differences was found in both networks, more prominent in the prefrontal cortex compared with hippocampus. Delta increase was stronger in females and theta stabilization was completed earlier in females, in postnatal days PN41-47, while in males it was only completed in late adolescence. Our finding of a protracted maturation of theta-generating networks in late adolescence is overall consistent with the findings of longitudinal studies in human adolescents, in which oscillatory networks demonstrated a similar pattern of maturation.
microRNA-dependent regulation of gene expression in GABAergic interneurons
Authors: Kołosowska Karolina Anna , Schratt Gerhard , Winterer Jochen
Published: May 2023

Information processing within neuronal circuits relies on their proper development and a balanced interplay between principal and local inhibitory interneurons within those circuits. Gamma-aminobutyric acid (GABA)ergic inhibitory interneurons are a remarkably heterogeneous population, comprising subclasses based on their morphological, electrophysiological, and molecular features, with differential connectivity and activity patterns. microRNA (miRNA)-dependent post-transcriptional control of gene expression represents an important regulatory mechanism for neuronal development and plasticity. miRNAs are a large group of small non-coding RNAs (21–24 nucleotides) acting as negative regulators of mRNA translation and stability. However, while miRNA-dependent gene regulation in principal neurons has been described heretofore in several studies, an understanding of the role of miRNAs in inhibitory interneurons is only beginning to emerge. Recent research demonstrated that miRNAs are differentially expressed in interneuron subclasses, are vitally important for migration, maturation, and survival of interneurons during embryonic development and are crucial for cognitive function and memory formation. In this review, we discuss recent progress in understanding miRNA-dependent regulation of gene expression in interneuron development and function. We aim to shed light onto mechanisms by which miRNAs in GABAergic interneurons contribute to sculpting neuronal circuits, and how their dysregulation may underlie the emergence of numerous neurodevelopmental and neuropsychiatric disorders.
Evaluation of perception threshold and pain in patients with Parkinson’s disease using PainVision®
Authors: Kurihara Kanako , Fujioka Shinsuke , Mishima Takayasu , Tsuboi Yoshio
Published: May 2023

Introduction

Pain is one of the most frequent non-motor symptoms occurring in patients with Parkinson’s disease (PD). Traditionally, the Visual Analog Pain Scale (VAS), Numerical Rating Scale (NRS), and Wong-Baker Faces Pain Rating Scale (FRS) have been used for clinical pain assessment, but these assessments are subjective at best. In contrast, PainVision® is a perceptual/pain analyzer that can quantitatively evaluate pain as “pain intensity” based on “current perception threshold” and “pain equivalent current.” We evaluated the current perception threshold in all PD patients and pain intensity in PD patients with pain using PainVision®.

Methods

We recruited 48 patients with PD (PwPD) with pain and 52 PwPD without pain. For patients with pain, we measured current perception threshold, pain equivalent current, and pain intensity using PainVision®, in addition to evaluation by VAS, NRS, and FRS. For patients without pain, only current perception threshold was measured.

Results

There was no correlation with either VAS or FRS, whereas only weak correlation was identified for NRS (γ = −0.376) with pain intensity. Current perception threshold was positively correlated with duration of the disease (γ = 0.347) and the Hoehn and Yahr stage (γ = 0.259). As a quantitative evaluation of pain, pain intensity by PainVision® does not correlate with conventional subjective pain assessments.

Discussion

This new quantitative evaluation method of pain may be suitable as an evaluation tool for future intervention research. Current perception threshold in PwPD was related to the duration and severity of the disease and may be involved in peripheral neuropathy associated with PD.
A TTFS-based energy and utilization efficient neuromorphic CNN accelerator
Authors: Yu Miao , Xiang Tingting , P. Srivatsa , Chu Kyle Timothy Ng , Amornpaisannon Burin , Tavva Yaswanth , Miriyala Venkata Pavan Kumar , Carlson Trevor E.
Published: May 2023

Spiking neural networks (SNNs), which are a form of neuromorphic, brain-inspired AI, have the potential to be a power-efficient alternative to artificial neural networks (ANNs). Spikes that occur in SNN systems, also known as activations, tend to be extremely sparse, and low in number. This minimizes the number of data accesses typically needed for processing. In addition, SNN systems are typically designed to use addition operations which consume much less energy than the typical multiply and accumulate operations used in DNN systems. The vast majority of neuromorphic hardware designs support rate-based SNNs, where the information is encoded by spike rates. Generally, rate-based SNNs can be inefficient as a large number of spikes will be transmitted and processed during inference. One coding scheme that has the potential to improve efficiency is the time-to-first-spike (TTFS) coding, where the information isn't presented through the frequency of spikes, but instead through the relative spike arrival time. In TTFS-based SNNs, each neuron can only spike once during the entire inference process, and this results in high sparsity. The activation sparsity of TTFS-based SNNs is higher than rate-based SNNs, but TTFS-based SNNs have yet to achieve the same accuracy as rate-based SNNs. In this work, we propose two key improvements for TTFS-based SNN systems: (1) a novel optimization algorithm to improve the accuracy of TTFS-based SNNs and (2) a novel hardware accelerator for TTFS-based SNNs that uses a scalable and low-power design. Our work in TTFS coding and training improves the accuracy of TTFS-based SNNs to achieve state-of-the-art results on the MNIST and Fashion-MNIST datasets. Meanwhile, our work reduces the power consumption by at least 2.4×, 25.9×, and 38.4× over the state-of-the-art neuromorphic hardware on MNIST, Fashion-MNIST, and CIFAR10, respectively.
Spotlights on adult patients with pediatric-type diffuse gliomas in accordance with the 2021 WHO classification of CNS tumors
Authors: Chen Wenlin , Jin Shanmu , Liu Qianshu , Wang Hai , Xia Yu , Guo Xiaopeng , Guo Siying , Wang Yaning , Shi Yixin , Liu Delin , Li Yilin , Wang Yuekun , Xing Hao , Li Junlin , Wu Jiaming , Liang Tingyu , Qu Tian , Li Huanzhang , Yang Tianrui , Zhang Kun , Wang Yu , Ma Wenbin
Published: May 2023

Introduction

The fifth edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors released in 2021 formally defines pediatric-type diffuse gliomas. However, there is still little understanding of pediatric-type diffuse gliomas, and even less attention has been paid to adult patients. Therefore, this study describes the clinical radiological, survival, and molecular features of adult patients with pediatric-type glioma.

Methods

Adult patients who underwent surgery from January 2011 to January 2022, classified as pediatric-type glioma, were included in this study. Clinical, radiological, histopathological, molecular pathological, and survival data were collected for analysis.

Results

Among 596 adult patients, 20 patients with pediatric-type glioma were screened, including 6 with diffuse astrocytoma, MYB- or MYBL1-altered, 2 with diffuse midline glioma, H3 K27-altered, and 12 with diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype. Pediatric high-grade glioma (pHGG) frequently showed tumor enhancement, peritumoral edema, and intratumoral necrosis. Adult patients with pHGG showed a longer life expectancy than adult patients with glioblastoma. Common molecular alterations included chromosome alterations and CDKN2A/B, PIK3CA, and PTEN, while altered KMT5B and MET were found to affect the overall survival.

Conclusion

Our study demonstrated adult patients with pediatric-type glioma. Notably, our research aims to expand the current understanding of adult patients with pediatric-type diffuse gliomas. Furthermore, personalized therapies consisting of targeted molecular inhibitors for MET and VEGFA may exhibit beneficial effects in the corresponding population.
A survey and perspective on neuromorphic continual learning systems
Authors: Mishra Richa , Suri Manan
Published: May 2023

With the advent of low-power neuromorphic computing systems, new possibilities have emerged for deployment in various sectors, like healthcare and transport, that require intelligent autonomous applications. These applications require reliable low-power solutions for sequentially adapting to new relevant data without loss of learning. Neuromorphic systems are inherently inspired by biological neural networks that have the potential to offer an efficient solution toward the feat of continual learning. With increasing attention in this area, we present a first comprehensive review of state-of-the-art neuromorphic continual learning (NCL) paradigms. The significance of our study is multi-fold. We summarize the recent progress and propose a plausible roadmap for developing end-to-end NCL systems. We also attempt to identify the gap between research and the real-world deployment of NCL systems in multiple applications. We do so by assessing the recent contributions in neuromorphic continual learning at multiple levels—applications, algorithms, architectures, and hardware. We discuss the relevance of NCL systems and draw out application-specific requisites. We analyze the biological underpinnings that are used for acquiring high-level performance. At the hardware level, we assess the ability of the current neuromorphic platforms and emerging nano-device-based architectures to support these algorithms in the presence of several constraints. Further, we propose refinements to continual learning metrics for applying them to NCL systems. Finally, the review identifies gaps and possible solutions that are not yet focused upon for deploying application-specific NCL systems in real-life scenarios.
Prefrontal activation during dual-task seated stepping and walking performed by subacute stroke patients with hemiplegia
Authors: Nosaka Shinnosuke , Imada Ken , Saita Kazuya , Okamura Hitoshi
Published: May 2023

Objectives

This study examined prefrontal cortex (PFC) activation during dual-task seated stepping and walking performed by subacute stroke patients with hemiplegia and evaluated the relationship between PFC activation, frontal lobe functions, and dual-task interference.

Methods

Patients with functional ambulation category (FAC) scores ≤ 2 comprised the seated stepping task group. Those with FAC scores > 2 comprised the walking task group. There were 11 patients in the seated stepping task group (mean age, 65.3±12.2 years; age range, 55-73.5 years; 7 male and 4 female patients; time since stroke onset, 45.7±9.9 days) and 11 patients in the walking task group (mean age, 65.6±15.2 years; age range, 49.5-74.5 years; 7 male and 4 female patients; time since stroke onset, 57.5±18.3 days). Both groups completed the Frontal Assessment Battery (FAB). The seated stepping task group performed the following three tasks: cognitive task (CT), normal seated stepping (NSS), and dual-task seated stepping (DTSS). The walking task group completed the following tasks: CT, normal walking (NW), and dual-task walking (DTW). The CT was a letter fluency task; this letter fluency task was simultaneously performed during seated stepping (DTSS) and walking (DTW). Changes in the oxygenated hemoglobin (O2Hb) concentration and deoxygenated hemoglobin concentration during the tasks were measured using near-infrared spectroscopy (Pocket NIRS HM; Dynasense Inc., Japan). The number of steps, walking speed, and percentage of correct responses to the CT were recorded.

Results

The results showed that DTSS activated the PFC significantly more than performing a single task and that NSS was associated with a significantly higher difference in the hemoglobin concentration when compared to that associated with the CT, which was a single task. In the walking task group, PFC activation was significantly higher during DTW, NW, and CT (in that order), and O2Hb concentrations were significantly higher in the contralesional hemisphere than in the ipsilesional hemisphere during all tasks. Associations between PFC activation, FAB scores, and dual-task interference in the seated task group indicated significant positive correlations between FAB scores and cognitive performance with dual-task interference.

Conclusion

DTSS may be an effective means of activating the PFC of patients with difficulty walking.
Neurons innervating both the central amygdala and the ventral tegmental area encode different emotional valences
Authors: Liu Anqi , Cheng Yuelin , Huang Ju
Published: May 2023

Mammals are frequently exposed to various environmental stimuli, and to determine whether to approach or avoid these stimuli, the brain must assign emotional valence to them. Therefore, it is crucial to investigate the neural circuitry mechanisms involved in the mammalian brain’s processing of emotional valence. Although the central amygdala (CeA) and the ventral tegmental area (VTA) individually encode different or even opposing emotional valences, it is unclear whether there are common upstream input neurons that innervate and control both these regions, and it is interesting to know what emotional valences of these common upstream neurons. In this study, we identify three major brain regions containing neurons that project to both the CeA and the VTA, including the posterior bed nucleus of the stria terminalis (pBNST), the pedunculopontine tegmental nucleus (PPTg), and the anterior part of the basomedial amygdala (BMA). We discover that these neural populations encode distinct emotional valences. Activating neurons in the pBNST produces positive valence, enabling mice to overcome their innate avoidance behavior. Conversely, activating neurons in the PPTg produces negative valence and induces anxiety-like behaviors in mice. Neuronal activity in the BMA, on the other hand, does not influence valence processing. Thus, our study has discovered three neural populations that project to both the CeA and the VTA and has revealed the distinct emotional valences these populations encode. These results provide new insights into the neurological mechanisms involved in emotional regulation.
SZT2 variants associated with partial epilepsy or epileptic encephalopathy and the genotype-phenotype correlation
Authors: Luo Sheng , Ye Xing-Guang , Jin Liang , Li Huan , He Yun-Yan , Guan Bao-Zhu , Gao Liang-Di , Liang Xiao-Yu , Wang Peng-Yu , Lu Xin-Guo , Yan Hong-Jun , Li Bing-Mei , Chen Yong-Jun , Liu Zhi-Gang
Published: May 2023

Background

Recessive SZT2 variants are reported to be associated with developmental and epileptic encephalopathy 18 (DEE-18) and occasionally neurodevelopment abnormalities (NDD) without seizures. This study aims to explore the phenotypic spectrum of SZT2 and the genotype-phenotype correlation.

Methods

Trios-based whole-exome sequencing was performed in patients with epilepsy. Previously reported SZT2 mutations were systematically reviewed to analyze the genotype-phenotype correlations.

Results

SZT2 variants were identified in six unrelated cases with heterogeneous epilepsy, including one de novo null variant and five pairs of biallelic variants. These variants had no or low frequencies in controls. All missense variants were predicted to alter the hydrogen bonds with surrounding residues and/or protein stability. The three patients with null variants exhibited DEE. The patients with biallelic null mutations presented severe DEE featured by frequent spasms/tonic seizures and diffuse cortical dysplasia/periventricular nodular heterotopia. The three patients with biallelic missense variants presented mild partial epilepsy with favorable outcomes. Analysis of previously reported cases revealed that patients with biallelic null mutations presented significantly higher frequency of refractory seizures and earlier onset age of seizure than those with biallelic non-null mutations or with biallelic mutations containing one null variant.

Significance

This study suggested that SZT2 variants were potentially associated with partial epilepsy with favorable outcomes without NDD, expanding the phenotypic spectrum of SZT2. The genotype-phenotype correlation helps in understanding the underlying mechanism of phenotypic variation.
Hippocampal beta rhythms as a bridge between sensory learning and memory-guided decision-making
Authors: Miles Jesse Thomas , Kidder Kevan Scott , Mizumori Sheri J. Y.
Published: May 2023

A pillar of systems neuroscience has been the study of neural oscillations. Research into these oscillations spans brain areas, species, and disciplines, giving us common ground for discussing typically disparate fields of neuroscience. In this review, we aim to strengthen the dialog between sensory systems research and learning and memory systems research by examining a 15–40 Hz oscillation known as the beta rhythm. Starting with foundational observations based largely in olfactory systems neuroscience, we review evidence suggesting beta-based activity may extend across sensory systems generally, as well as into the hippocampus and areas well known for coordinating decisions and memory-guided behaviors. After evaluating this work, we propose a framework wherein the hippocampal beta oscillation and its diverse coupling with other brain areas can support both sensory learning and memory-guided decision-making. Using this framework, we also propose circuitries that may support these processes, and experiments to test our hypothesis.
Deep-learning-based automatic segmentation and classification for craniopharyngiomas
Authors: Yan Xiaorong , Lin Bingquan , Fu Jun , Li Shuo , Wang He , Fan Wenjian , Fan Yanghua , Feng Ming , Wang Renzhi , Fan Jun , Qi Songtao , Jiang Changzhen
Published: May 2023

Objective

Neuronavigation and classification of craniopharyngiomas can guide surgical approaches and prognostic information. The QST classification has been developed according to the origin of craniopharyngiomas; however, accurate preoperative automatic segmentation and the QST classification remain challenging. This study aimed to establish a method to automatically segment multiple structures in MRIs, detect craniopharyngiomas, and design a deep learning model and a diagnostic scale for automatic QST preoperative classification.

Methods

We trained a deep learning network based on sagittal MRI to automatically segment six tissues, including tumors, pituitary gland, sphenoid sinus, brain, superior saddle cistern, and lateral ventricle. A deep learning model with multiple inputs was designed to perform preoperative QST classification. A scale was constructed by screening the images.

Results

The results were calculated based on the fivefold cross-validation method. A total of 133 patients with craniopharyngioma were included, of whom 29 (21.8%) were diagnosed with type Q, 22 (16.5%) with type S and 82 (61.7%) with type T. The automatic segmentation model achieved a tumor segmentation Dice coefficient of 0.951 and a mean tissue segmentation Dice coefficient of 0.8668 for all classes. The automatic classification model and clinical scale achieved accuracies of 0.9098 and 0.8647, respectively, in predicting the QST classification.

Conclusions

The automatic segmentation model can perform accurate multi-structure segmentation based on MRI, which is conducive to clearing tumor location and initiating intraoperative neuronavigation. The proposed automatic classification model and clinical scale based on automatic segmentation results achieve high accuracy in the QST classification, which is conducive to developing surgical plans and predicting patient prognosis.
Association of RANKL and EGFR gene expression with bone metastases in patients with metastatic non-small cell lung cancer
Authors: Brouns Anita J.W.M. , Hendriks Lizza E.L. , Robbesom-van den Berge Iris J. , Driessen Annemariek J.H.M. , Roemen Guido M.J.M. , van Herpen Britt L.J. , Dekkers Zoë , Heitzer Bas , Leunissen Daphne J.G. , Moonen Laura , Lunde Ragnar , Westenend Marcel , van Driel Marjolein , Speel Ernst-Jan M. , Dingemans Anne-Marie C.
Published: May 2023

Introduction

Bone metastases are frequent in patients with non-small cell lung cancer (NSCLC). The receptor activator of Nuclear Factor κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is important in bone metastases development. Furthermore, epidermal growth factor receptor (EGFR) signaling promotes osteoclast formation and stimulation. The understanding of the biological mechanism of bone metastases development might have implications for treatment strategies. Therefore, we studied whether there is an association between EGFR, RANKL, RANK and OPG gene expression in the tumor and presence of bone metastases in patients with NSCLC.

Methods

From an updated multicenter study, including patients with EGFR mutated (EGFR+), Kirsten rat sarcoma (KRAS+) and EGFR/KRAS wildtype metastatic NSCLC, all patients with available formalin-fixed paraffin-embedded (FFPE) tumor samples were selected. Ribonucleic Acid (RNA) was isolated from these samples and gene expressions of EGFR, RANKL, OPG and RANKL were determined via quantitative Polymerase Chain Reaction (qPCR). Data on demographics, histology and molecular subtyping, sample origin, presence of bone metastasis, SREs and bone progression were collected. Primary endpoint was relation between EGFR, RANK, RANKL, OPG gene expression, RANKL: OPG ratio and bone metastases.

Results

In 73/335 (32% EGFR+, 49% KRAS+, 19% EGFR/KRAS wildtype) samples from unique patients, gene expression analysis could be performed. Of these 73 patients, 46 (63%) had bone metastases at diagnosis or developed bone metastases during the disease course. No association was found between EGFR expression and presence of bone metastases. Patients with bone metastases had a significantly higher RANKL expression and RANKL: OPG ratio compared to those without. An increased RANKL: OPG ratio resulted in a 1.65x increased risk to develop bone metastases, especially in the first 450 days after diagnosis of metastatic NSCLC.

Conclusion

Increased RANKL gene expression and RANKL: OPG ratio, but not EGFR expression, was associated with presence of bone metastases. Additionally, an increased RANKL: OPG gene ratio was associated with a higher incidence of bone metastases development.
Ongoing complete response after treatment cessation with dabrafenib, trametinib, and cetuximab as third-line treatment in a patient with advanced BRAFV600E mutated, microsatellite-stable colon cancer: A case report and literature review
Authors: Piringer Gudrun , Decker Jörn , Trommet Vera , Kühr Thomas , Heibl Sonja , Dörfler Konrad , Thaler Josef
Published: May 2023

Metastatic BRAFV600E mutated colorectal cancer is associated with poor overall survival and modest effectiveness to standard therapies. Furthermore, survival is influenced by the microsatellite status. Patients with microsatellite-stable and BRAFV600E mutated colorectal cancer have the worst prognosis under the wide range of genetic subgroups in colorectal cancer. Herein, we present a patient case of an impressive therapeutic efficacy of dabrafenib, trametinib, and cetuximab as later-line therapy in a 52-year-old woman with advanced BRAFV600E mutated, microsatellite-stable colon cancer. This patient achieved a complete response after 1 year of triple therapy. Due to skin toxicity grade 3 and recurrent urinary tract infections due to mucosal toxicity, a therapy de-escalation to dabrafenib and trametinib was performed, and the double therapy was administered for further 41 months with ongoing complete response. For 1 year, the patient was off therapy and is still in complete remission.
Radiation doses to mediastinal organs at risk in early-stage unfavorable Hodgkin lymphoma– a risk stratified analysis of the GHSG HD17 trial
Authors: Oertel Michael , Hering Dominik , Baues Christian , Kittel Christopher , Fuchs Michael , Kriz Jan , Kröger Kai , Vordermark Dirk , Herfarth Klaus , Engenhart-Cabillic Rita , Lukas Peter , Haverkamp Uwe , Borchmann Peter , Eich Hans Theodor
Published: May 2023

Introduction

The German Hodgkin Study Group (GHSG) HD17 trial established the omission of radiotherapy (RT) for patients with early-stage unfavorable Hodgkin lymphoma being PET-negative after 2 cycles of BEACOPP escalated plus 2 cycles of ABVD. This patient group reveals heterogeneity in characteristics and disease extent which prompted us to perform a decisive dosimetric analysis according to GHSG risk factors. This may help to tailor RT individually balancing risks and benefits.

Methods

For quality assurance, RT-plans were requested from the treating facilities (n= 141) and analyzed centrally. Dose-volume histograms were scanned either paper-based or digitally to obtain doses to mediastinal organs. These were registered and compared according to GHSG risk factors.

Results

Overall, RT plans of 176 patients were requested, 139 of which had dosimetric information on target volumes within the mediastinum. Most of these patients were stage II (92.8%), had no B-symptoms (79.1%) and were aged < 50 years (89.9%). Risk factors were present in 8.6% (extranodal involvement), 31.7% (bulky disease), 46.0% (elevated erythrocyte sedimentation rate) and 64.0% (three involved areas), respectively. The presence of bulky disease significantly affected the mean RT doses to the heart (p=0.005) and to the left lung (median: 11.3 Gy vs. 9.9 Gy; p=0.042) as well as V5 of the right and left lung, respectively (median right lung: 67.4% vs. 51.0%; p=0.011; median left lung: 65.9% vs. 54.2%; p=0.008). Significant differences in similar organs at risk parameters could be found between the sub-cohorts with the presence or absence of extranodal involvement, respectively. In contrast, an elevated erythrocyte sedimentation rate did not deteriorate dosimetry significantly. No association of any risk factor with radiation doses to the female breast was found.

Conclusion

Pre-chemotherapy risk factors may help to predict potential RT exposure to normal organs and to critically review treatment indication. Individualized risk-benefit evaluations for patients with HL in early-stage unfavorable disease are mandatory.
Maternal and perinatal outcomes of low-dose aspirin plus low-molecular-weight heparin therapy on antiphospholipid antibody-positive pregnant women with chronic hypertension
Authors: Long Shangqin , Zhang Liren , Li Xiaodong , He Yongjie , Wen Xin , Xu Nannan , Li Xiaoqing , Wang Jingmin
Published: May 2023

Objectives

Positive antiphospholipid antibodies (aPLs) and chronic hypertension (CH) in pregnancy are important causes of maternal and neonatal morbidity and mortality. However, there are no relevant studies on the treatment of aPL-positive pregnant women with CH. This study aimed to determine the effect of low-dose aspirin (LDA) plus low-molecular-weight heparin (LMWH) on maternal and perinatal outcomes in persistently aPL-positive pregnant women with CH.

Methods

This study was performed at the First Affiliated Hospital of Dalian Medical University in Liaoning, China, from January 2018 to December 2021. Pregnant women diagnosed CH and persistently positive aPL who had no autoimmune disease such as systemic lupus erythematosus, antiphospholipid syndrome were recruited and divided into control group (LDA and LWMH were not used), LDA group (LDA was used) and LDA plus LMWH group (both LDA and LMWH were used) according to whether they use LDA and/or LMWH. A total of 81 patients were enrolled, including 40 patients in the control group, 19 patients in the LDA group, and 22 patients in the LDA plus LMWH group. The maternal and perinatal outcomes of LDA plus LMWH therapy were analysed.

Results

Compared with control group, the rate of severe preeclampsia in LDA group (65.00% vs. 31.58%, p = 0.016) and LDA plus LMWH group (65.00% vs. 36.36%, p = 0.030) had a statistically significant reduction. Compared with control group, the rate of fetal loss in LDA group (35.00% vs. 10.53%, p = 0.014) and LDA plus LMWH group (35.00% vs. 0.00%, p = 0.002) had a statistically significant reduction. Compared with control group, the rate of live birth in LDA group (65.00% vs. 89.74%, p = 0.048) and LDA plus LMWH group (65.00% vs. 100.00%, p = 0.002) had a statistically significant increased. Compared withcontrol group, the incidence of early-onset preeclampsia (47.50% vs. 36.84%, p = 0.008) and early-onset severe preeclampsia (47.50% vs. 13.64%, p = 0.001) in the LDA plus LMWH group decreased and were statistically different. Furthermore, we also found that LDA or LDA plus LMWH hadn't increase the rate of blood loss and placental abruption.

Conclusion

Both LDA and LDA combined with LMWH could decrease the incidence of severe preeclampsia, decrease the rate of foetal loss, increase the rate of live birth. However, LDA plus LWMH could reduce and delay the onset of severe preeclampsia, prolong the gestational age and increase the rate of full-term delivery, improve the maternal and perinatal outcomes.
Management of hypocalcemia following thyroid surgery in children
Authors: Romera Andrea , Barragán Lourdes , Álvarez-Baena Lucía , Sanjuán Erika , Ordóñez Javier , García-Casillas María Antonia , Mora Marina , Sanz María
Published: May 2023

Introduction

Pediatric post-thyroidectomy hypocalcemia management varies significantly from hospital to hospital. The current study has two aims: first, we evaluate demographic data in all pediatric patients submitted to thyroid surgery in our Spanish tertiary hospital over 20 years; secondly, we describe the way that hypocalcemia was diagnosed and treated in that period and present a multidisciplinary protocol for perioperative management of this condition.

Methods

This is a retrospective and observational study of all patients from 0 to 16 years old who underwent thyroid surgery from 2000 to 2020 at our institution. Demographic, surgical and electrolyte data were recorded from the electronic database.

Results

From 2000 to 2016, pediatric thyroid surgery at our institution was performed on 33 patients without a consistent approach or standard electrolyte management. A protocol for perioperative management of these patients was introduced in 2017, and applied to 13 patients. In 2019, the protocol was assessed and updated following a case of symptomatic hypocalcemia. From 2000 to 2016, 47 pediatric patients in all underwent thyroid surgery. We registered eight asymptomatic hypocalcemias. One child developed symptomatic hypocalcemia. Two patients have permanent hypoparathyroidism.

Discussion

Our incidence of general complications following thyroidectomy was low; hypocalcemia was the most prevalent. All the cases of hypocalcemia submitted to the protocol were identified early by iPTH measurements. Intraoperative iPTH levels and percentage drop from baseline could help stratify patients according to their risk of hypocalcemia. High risk patients require immediate postoperative supplementation, including calcitriol and calcium carbonate.
Case report: Muscle involvement in a Chinese patient with TRNT1-related disorder
Authors: Wei Cui-Jie , Liu Yi-Dan , Yang Yan-Ling , Wu Yuan , Liu Jie-Yu , Chang Xing-Zhi , Hua Ying , Liu Yu-He , Xiong Hui
Published: May 2023

The TRNT1 gene encodes tRNA nucleotidyltransferase 1, which catalyzes the addition of cytosine-cytosine-adenosine (CCA) to the ends of cytoplasmic and mitochondrial tRNAs. The most common clinical phenotype associated with TRNT1 is autosomal recessive sideroblastic anemia with B-cell immunodeficiency, periodic fever, and developmental delay (SIFD). Muscle involvement has rarely been reported in TRNT1-related disorders. Here we report a Chinese patient with incomplete SIFD and hyperCKemia, and explored the skeletal muscle pathological changes. The patient was a 3-year-old boy with sensorineural hearing loss, sideroblastic anemia, and developmental delay since infancy. At the age of 11 months, significantly increased levels of creatine kinase were noted, accompanied by mild muscle weakness. Whole-exome sequencing revealed compound heterozygous variants of the TRNT1 gene, c.443C > T (p.Ala148Val) and c.692C > G (p.Ala231Gly), in the patient. Western blot showed a decreased expression of TRNT1 and cytochrome c oxidase subunit IV (COX IV) in the skeletal muscle of the patient. Electron microscopy observation of skeletal muscle pathology revealed abnormal mitochondria of various sizes and shapes, supporting a diagnosis of mitochondrial myopathy. The present case indicates that in addition to the classic SIFD phenotype, TRNT1 mutations can cause mitochondrial myopathy, a rare clinical phenotype of TRNT1-related disorders.
Assessment of left heart dysfunction to predict doxorubicin cardiotoxicity in children with lymphoma
Authors: Chen Jiaqi , Cheng Chunyue , Fan Li , Xu Xiaochuan , Chen Jing , Feng Yang , Tang Yi , Yang Chunjiang
Published: May 2023

Objectives

The objectives of this study were to assess the changes in the left myocardial function after chemotherapy for childhood lymphoma and observe the predictive or monitor value for cancer treatment-related cardiac dysfunction (CTRCD) by speckle-tracking echocardiography.

Methods

A total of 23 children with histopathological diagnoses of lymphoma were included, with age-matched normal controls. Comparative analysis of clinical serological tests and left heart strain parameters in children with lymphoma, including left ventricular global longitudinal strain (LVGLS); global myocardial work (GMW) indices, which include global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency; and the LS of subendocardial, middle, and subepicardial layer myocardium during left ventricular systole were measured: left atrial strain of reservoir phase (LASr), left atrial strain of conduit phase (LAScd), and left atrial strain of contraction phase (LASct).

Results

One-way ANOVA showed that GLS, GWI, GCW, LASr, and LAScd were closely associated with CTRCD and multivariate logistic regression analysis showed that GLS was the most sensitive predictor for detecting patients at lofty risk of anthracycline-related cardiotoxicity. Both before and after chemotherapy, GLS in the left ventricle showed a pattern of basal segment < middle segment < apical segment and subepicardial < middle < subendocardial layer (p < 0.05), and the degree of decrease also showed a regular pattern of epicardial layer < middle layer < subendocardial layer while the difference was not significant (p > 0.05). After chemotherapy, maximum flow rate in early mitral relaxation/left atrial systolic maximum flow rate (E/A) and left atrial volume index of each group were in the normal range, and the values of LASr, LAScd, and LASct slightly increased in the second cycle and decreased significantly in the fourth cycle after chemotherapy, reaching the lowest level; LASr and LAScd were positively correlated with GLS.

Conclusion

LVGLS is a more sensitive and earlier indicator to predict CTRCD compared with conventional echocardiography-related parameters and serological markers, and GLS of each myocardial layer showed a certain regularity. Left atrial strain can be used for early monitoring of cardiotoxicity in children with lymphoma after chemotherapy.
Nutrition in children with exocrine pancreatic insufficiency
Authors: Zheng Yuhua , Mostamand Shikib
Published: May 2023

Exocrine pancreatic insufficiency (EPI) is a condition defined as pancreatic loss of exocrine function, including decreased digestive enzymes and bicarbonate secretion, which leads to maldigestion and malabsorption of nutrients. It is a common complication in many pancreatic disorders. If left undiagnosed, EPI can cause poor digestion of food, chronic diarrhea, severe malnutrition and related complications. Nutritional status and fat-soluble vitamins should be carefully assessed and monitored in patients with EPI. Early diagnosis of EPI is clinically important for appropriate nutritional support and initiating pancreatic enzyme replacement therapy (PERT) which could significantly improve patient outcomes. The evaluation of nutritional status and related unique management in children with EPI will be discussed in this review.