bluuebunny/crossref_metadata_2025 huggingface dataset:
Methacrylate Polymers With “Flipped External” Ester Groups: A Review
Authors: Kumar Dhiraj , Bolskar Robert D. , Mutreja Isha , Jones Robert S.
Published: June 2022

Current resin composites have favorable handling and upon polymerization initial physical properties that allow for efficient material replacement of removed carious tooth structure. Dental resin composites have long-term durability limitations due to the hydrolysis of ester bonds within the methacrylate-based polymer matrix. This article outlines the importance of ester bonds positioned internal to the carbon–carbon double bond in current methacrylate monomers. Water and promiscuous salivary/bacterial esterase activity can initiate ester bond hydrolysis that can sever the polymer backbone throughout the material. Recent studies have custom synthesized, with the latest advances in modern organic chemical synthesis, a novel molecule named ethylene glycol bis (ethyl methacrylate) (EGEMA). EGEMA was designed to retain the reactive acrylate units. Upon intermolecular polymerization of vinyl groups, EGEMA ester groups are positioned outside the backbone of the polymer chain. This review highlights an investigation into the degradation resistance of EGEMA using buffer, esterase, and microbial storage assays. Material samples of EGEMA had superior final physical and mechanical properties than traditional ethylene glycol dimethacrylate (EGDMA) in all degradation assays. Integrating bioinformatics-based biodegradation predictions to the experimental results of storage media analyzed by LC/GC-MS revealed that hydrolysis of EGEMA generated small amounts of ethanol while preserving the strength-bearing polymer backbone. Prior studies support an investigation into additional custom-synthesized methacrylate polymers with “flipped external” ester groups. The long-term goal is to improve clinical durability compared to current methacrylates while retaining the inherent advantages of acrylic-based chemistry, which may ease the implementation of these novel methacrylates into clinical practice.
Performing Meaningful Movement Analysis From Publicly Available Videos Using Free Software – A Case of Acrobatic Sports
Authors: Kong Pui Wah , Sim Alexiaa , Chiam Melody J.
Published: June 2022

This paper illustrates how movement analysis could be performed using publicly available videos and freeware to generate meaningful information for sports practitioners and researchers. Using acrobatic sports as a case, we performed kinematic analysis on 206 YouTube videos of high-level competitions in diving and gymnastics using Kinovea. Results revealed good to excellent inter-rater reliability of variables analyzed. Significant differences in angular speed (p < 0.001, η2p = 0.213) and flight time (p < 0.001, η2p = 0.928) were found among eight different events. Divers had longer flight time (p < 0.001, η2p = 0.569) and were somersaulting faster than gymnasts (p = 0.021, η2p = 0.026). Angular speed was higher in tuck than pike somersaults (p < 0.001, η2p = 0.214). Shorter the flight time was significantly correlated with faster angular speed (rho = −0.533, p < 0.001) in gymnastics events. Coaches and scientists can consider applying the proposed method to monitor the athletes’ performance and to identify errors (e.g., insufficient flight time). The kinematics measurements can also be used to guide the transition plan across different apparatus and categories (e.g., 10-m platform to 3-m springboard). In conclusion, the present study highlights the potential of using readily available information and open-source freeware to generate scientific data for sports applications. Such data analysis approach can accommodate a wide range of video qualities, is easily accessible, and not restricted by situations such as social distancing, quarantine, lockdown or other restrictive measures.
Advances in Immune Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma
Authors: Chen Yue , Hu Haoyue , Yuan Xianglei , Fan Xue , Zhang Chengda
Published: June 2022

Hepatocellular carcinoma (HCC) is usually diagnosed in an advanced stage and has become the second deadliest type of cancer worldwide. The systemic treatment of advanced HCC has been a challenge, and for decades was limited to treatment with tyrosine kinase inhibitors (TKIs) until the application of immune checkpoint inhibitors (ICIs) became available. Due to drug resistance and unsatisfactory therapeutic effects of monotherapy with TKIs or ICIs, multi-ICIs, or the combination of ICIs with antiangiogenic drugs has become a novel strategy to treat advanced HCC. Antiangiogenic drugs mostly include TKIs (sorafenib, lenvatinib, regorafenib, cabozantinib and so on) and anti-vascular endothelial growth factor (VEGF), such as bevacizumab. Common ICIs include anti-programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1), including nivolumab, pembrolizumab, durvalumab, and atezolizumab, and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), including tremelimumab and ipilimumab. Combination therapies involving antiangiogenic drugs and ICIs or two ICIs may have a synergistic action and have shown greater efficacy in advanced HCC. In this review, we present an overview of the current knowledge and recent clinical developments in ICI-based combination therapies for advanced HCC and we provide an outlook on future prospects.
Global Expansion of Jeffrey’s Insights: Jeffrey Modell Foundation’s Genetic Sequencing Program for Primary Immunodeficiency
Authors: Quinn Jessica , Modell Vicki , Johnson Britt , Poll Sarah , Aradhya Swaroop , Orange Jordan S. , Modell Fred
Published: June 2022

Genetic disorders that impair the immune system, known as Primary Immunodeficiencies (PI), include over 450 single-gene inborn errors of immunity. Timely and appropriate diagnosis and treatment is vital to quality of life (QOL) and sometimes survival, as patients are susceptible to frequent, persistent, severe, and sometimes life-threatening infections or autoimmunity. Suspected PI patients that do not have a genetic diagnosis often endure a prolonged, onerous, inefficient, and expensive experience, known as a diagnostic odyssey. The resulting diagnostic delay prohibits proper disease management and treatment, causing unnecessary distress and diminished QOL. Next-generation sequencing (NGS) offers relief from the distress of the diagnostic odyssey, but because of cost and barriers to access, it is regularly unobtainable. The Jeffrey Modell Foundation (JMF) introduced “Jeffrey’s Insights”, a no-charge genetic sequencing pilot program, in January 2019 for patients within the Jeffrey Modell Centers Network (JMCN) with an underlying PI, but no genetic diagnosis. Building on the success of the pilot program, JMF expanded it globally to more than 400 Centers in the JMCN in early 2020. The most current version of Invitae’s PI Panel available was used for this program. All participating clinicians were invited to complete a brief questionnaire assessing prior impediments to access and post-sequencing alterations in disease management and treatment. A total of 1,398 patients were tested, with 20.3% receiving a molecular diagnosis and many more receiving helpful diagnostic leads. Results obtained from genetic sequencing led to an alteration of clinical diagnosis, disease management, treatment, and genetic counseling in 39%, 38%, 35%, and 53% of patients, respectively. The global expansion of this program further underscores the crucial need for NGS for PI, along with its efficiency and potential cost savings. The results of this program to date further define rationale for the availability of comprehensive diagnostic NGS for patients with PI when requisitioned by an expert immunologist.
Demographic, Clinical and Laboratory Characteristics of Ocular Syphilis: 6-Years Case Series Study From an Eye Center in East-China
Authors: Sun Chuan-bin , Liu Geng-hao , Wu Rong , Liu Zhe
Published: June 2022

Purpose

To report the demographic, clinical, and laboratory characteristics of ocular syphilis based on a 6-year case series study from an eye center in East-China.

Methods

A total of 131 cases (191 eyes) of ocular syphilis and the annual number of total syphilis cases from January 2016 to December 2021, were included in this study. Detailed medical records including systemic and ophthalmic medical history, a complete ophthalmic examination, color fundus photography, B-type ultrasound, fundus fluorescein angiography (FFA), spectral domain optical coherence tomography (SD-OCT), laboratory tests of the serum and cerebrospinal fluid (CSF) samples, as well as visual field test and orbital or cranial MRI in cases with suspected optic neuritis or optic atrophy, were collected and analyzed. Pearson Chi-square or Fisher’s exact tests was used for statistics analysis.

Results

Of the 131 cases with ocular syphilis, 86 cases were in men and 6 cases had a past medical history or systemic manifestation of syphilis. HIV was found in only 2 of 70 cases undergoing serum HIV test. The average age was 54.0 years, ranging from 26–85 years. The average percentage of ocular syphilis out from the total syphilis cases was 5.1%, the average titer of serum rapid plasma regain (RPR) at presentation was 1:32, ranging from 1:1–1:512. The most predominant manifestation of ocular syphilis was posterior uveitis, followed by optic neuritis, optic atrophy, panuveitis, retinal vasculitis, and retinitis. The median of BCVA of all 191 eyes was 20/200 (ranging from no light perception to 20/20), and 20/40 (ranging from no light perception to 20/20) at presentation and final follow-up, respectively. Ocular syphilis with active inflammation responded well to penicillin therapy, no matter the initial visual acuity, ocular disease type, or RPR titers, as long as it was diagnosed early and treated properly and promptly. However, cases with optic atrophy, acute retinal necrosis, late diagnosis, permanent disruption, or loss of outer segment of photoreceptors of macular retina on SD-OCT showed poor visual improvement after therapy.

Conclusions

Early diagnosis of ocular syphilis is still challenging in clinical practice and syphilis tests should be routinely performed in patients with uveitis, retinitis, optic neuritis, and optic atrophy.
Nucleocapsid Specific Diagnostics for the Detection of Divergent SARS-CoV-2 Variants
Authors: Isaacs Ariel , Amarilla Alberto A. , Aguado Julio , Modhiran Naphak , Albornoz Eduardo A. , Baradar Alireza A. , McMillan Christopher L. D. , Choo Jovin J. Y. , Idris Adi , Supramaniam Aroon , McMillan Nigel A. J. , Muller David A. , Young Paul R. , Woodruff Trent M. , Wolvetang Ernst J. , Chappell Keith J. , Watterson Daniel
Published: June 2022

Since the start of the COVID-19 pandemic, multiple waves of SARS-CoV-2 variants have emerged. Of particular concern is the omicron variant, which harbors 28 mutations in the spike glycoprotein receptor binding and N-terminal domains relative to the ancestral strain. The high mutability of SARS-CoV-2 therefore poses significant hurdles for development of universal assays that rely on spike-specific immune detection. To address this, more conserved viral antigens need to be targeted. In this work, we comprehensively demonstrate the use of nucleocapsid (N)-specific detection across several assays using previously described nanobodies C2 and E2. We show that these nanobodies are highly sensitive and can detect divergent SARS-CoV-2 ancestral, delta and omicron variants across several assays. By comparison, spike-specific antibodies S309 and CR3022 only disparately detect SARS-CoV-2 variant targets. As such, we conclude that N-specific detection could provide a standardized universal target for detection of current and emerging SARS-CoV-2 variants of concern.
Association of Total Calcium With Serum Uric Acid Levels Among United States Adolescents Aged 12–19 Years: A Cross-Sectional Study
Authors: Gu Fang , Luo Xiaoming , Jin Xiaoli , Cai Changshou , Zhao Wenyan
Published: June 2022

Aims

Evidence of a link between total calcium (CA) and serum uric acid (SUA) is absent in adolescents. Thus, this study aimed to determine the relationship between total CA levels and SUA levels in United States adolescents.

Methods

A cross-sectional study analyzed a sample composed of 8,309 United States adolescents aged 12–19 years from the National Health and Nutrition Examination Survey database (1999–2006 survey cycle). Multivariable linear regression analyses and multivariable logistic regression analyses were used to assess the correlation of total CA with SUA levels and hyperuricemia. Furthermore, the dose-response relationship of total CA and SUA levels was analyzed using smooth curve fitting (penalized spline method).

Results

According to multivariable linear regression analysis, every 1 mg/dL increase in total CA level is associated with a 0.33 mg/dL (β = 0.33, 95% CI: 0.27–0.40, p < 0.001) increase in SUA. Multivariable logistic regression analyses showed that every 0.1 mg/dL increase in total CA level is linked with an 8% increased risk of hyperuricemia (OR = 1.08, 95% CI: 1.06–1.10, p < 0.001). The analyses of smooth curve fitting revealed that total CA levels were linearly correlated with SUA levels (Pnon–linearity = 0.152). The results were highly stable in all subgroups. The interaction analysis results presented that race/ethnicity had an interactive role in associating total CA with SUA levels.

Conclusions

In United States adolescents, total CA levels were linearly and positively correlated with SUA levels.
Biogenic Synthesis of Zinc Nanoparticles, Their Applications, and Toxicity Prospects
Authors: Rani Simran , Kumar Pradeep , Dahiya Priyanka , Dang Amita Suneja , Suneja Pooja
Published: June 2022

Nanofertilizers effectively deliver the micronutrients besides reducing the phytotoxicity and environmental damage associated with chemical fertilizers. Zinc, an essential micronutrient, is significant for chloroplast development, activation of certain enzymes, and primary metabolism. Nano zinc oxide (ZnO) is the most widely used zinc nanoparticle. Concerns regarding the toxicity of conventional physical and chemical methods of synthesizing the nanoparticles have generated the need for a green approach. It involves the biogenic synthesis of metallic nanoparticles using plants and microorganisms. Microbe-mediated biogenic synthesis of metallic nanoparticles is a bottom-up approach in which the functional biomolecules of microbial supernatant reduce the metal ions into its nanoparticles. This review discusses the biological synthesis of nano-ZnO from microorganisms and related aspects such as the mechanism of synthesis, factors affecting the same, methods of application, along with their role in conferring drought stress tolerance to the plants and challenges involved in their large-scale synthesis and applications.
Biomaterials and Electroactive Bacteria for Biodegradable Electronics
Authors: Bonné Robin , Wouters Koen , Lustermans Jamie J. M. , Manca Jean V.
Published: June 2022

The global production of unrecycled electronic waste is extensively growing each year, urging the search for alternatives in biodegradable electronic materials. Electroactive bacteria and their nanowires have emerged as a new route toward electronic biological materials (e-biologics). Recent studies on electron transport in cable bacteria—filamentous, multicellular electroactive bacteria—showed centimeter long electron transport in an organized conductive fiber structure with high conductivities and remarkable intrinsic electrical properties. In this work we give a brief overview of the recent advances in biodegradable electronics with a focus on the use of biomaterials and electroactive bacteria, and with special attention for cable bacteria. We investigate the potential of cable bacteria in this field, as we compare the intrinsic electrical properties of cable bacteria to organic and inorganic electronic materials. Based on their intrinsic electrical properties, we show cable bacteria filaments to have great potential as for instance interconnects and transistor channels in a new generation of bioelectronics. Together with other biomaterials and electroactive bacteria they open electrifying routes toward a new generation of biodegradable electronics.
Cross Task Modality Alignment Network for Sketch Face Recognition
Authors: Guo Yanan , Cao Lin , Du Kangning
Published: June 2022

The task of sketch face recognition refers to matching cross-modality facial images from sketch to photo, which is widely applied in the criminal investigation area. Existing works aim to bridge the cross-modality gap by inter-modality feature alignment approaches, however, the small sample problem has received much less attention, resulting in limited performance. In this paper, an effective Cross Task Modality Alignment Network (CTMAN) is proposed for sketch face recognition. To address the small sample problem, a meta learning training episode strategy is first introduced to mimic few-shot tasks. Based on the episode strategy, a two-stream network termed modality alignment embedding learning is used to capture more modality-specific and modality-sharable features, meanwhile, two cross task memory mechanisms are proposed to collect sufficient negative features to further improve the feature learning. Finally, a cross task modality alignment loss is proposed to capture modality-related information of cross task features for more effective training. Extensive experiments are conducted to validate the superiority of the CTMAN, which significantly outperforms state-of-the-art methods on the UoM-SGFSv2 set A, set B, CUFSF, and PRIP-VSGC dataset.
WHOPPA Enables Parallel Assessment of Leucine-Rich Repeat Kinase 2 and Glucocerebrosidase Enzymatic Activity in Parkinson’s Disease Monocytes
Authors: Wallings Rebecca L. , Hughes Laura P. , Staley Hannah A. , Simon Zachary D. , McFarland Nikolaus R. , Alcalay Roy N. , Garrido Alicia , Martí María José , Sarró Eduardo Tolosa , Dzamko Nicolas , Tansey Malú Gámez
Published: June 2022

Both leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GCase) are promising targets for the treatment of Parkinson’s disease (PD). Evidence suggests that both proteins are involved in biological pathways involving the lysosome. However, studies to date have largely investigated the enzymes in isolation and any relationship between LRRK2 and GCase remains unclear. Both enzymes are highly expressed in peripheral blood monocytes and have been implicated in immune function and inflammation. To facilitate the standardized measurement of these readouts in large cohorts of samples collected from persons with PD across the globe, we developed and optimized a sample collection and processing protocol with parallel flow cytometry assays. Assay parameters were first optimized using healthy control peripheral blood mononuclear cells (PBMCs), and then LRRK2 and GCase activities were measured in immune cells from persons with idiopathic PD (iPD). We tested the ability of this protocol to deliver similar results across institutes across the globe, and named this protocol the Wallings-Hughes Optimized Protocol for PBMC Assessment (WHOPPA). In the application of this protocol, we found increased LRRK2 levels and stimulation-dependent enzymatic activity, and decreased GBA index in classical iPD monocytes, as well as increased cytokine release in PD PBMCs. WHOPPA also demonstrated a strong positive correlation between LRRK2 levels, pRab10 and HLA-DR in classical monocytes from subjects with iPD. These data support a role for the global use of WHOPPA and expression levels of these two PD-associated proteins in immune responses, and provide a robust assay to determine if LRRK2 and GCase activities in monocytes have potential utility as reliable and reproducible biomarkers of disease in larger cohorts of subjects with PD.
Elevated Lipoprotein-Associated Phospholipase A2 Is Associated With Intracranial Atherosclerosis
Authors: Wang Yuan , Liu Gang , Song Haiqing , Cao Catherine , Ji Xunming , Cao Guodong
Published: June 2022

Background

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory factor in the pathogenesis of atherosclerotic plaque and is associated with an increased risk of ischemic stroke. Whether Lp-PLA2 is associated with stenosis subtypes in acute ischemic stroke (AIS) has not been investigated.

Methods

A total of 126 eligible AIS patients were divided into four groups: (1) no cerebral artery stenosis (NCS); (2) intracranial artery stenosis (ICAS); (3) extracranial artery stenosis (ECAS); and (4) combined intracranial and extracranial artery stenosis (IECS). Associations between serum Lp-PLA2 levels and the stenosis subtypes were assessed.

Results

The ICAS group had a lower frequency of dyslipidemia as compared to the NCS group and the IECS group (35.3% vs. 70% vs. 71.8%, respectively, p = 0.001) and was more likely to be symptomatic than the ECAS group (76.5% vs. 43.8%, respectively, p = 0.014). Lp-PLA2 levels in the ICAS group were 112.2 ± 66.8 μg/L which are, higher than those in the NCS, ECAS, and IECS groups (81.7 ± 38.5, 106.1 ± 57.8, 89.3 ± 52.2 μg/L, respectively, p = 0.025). In the third and fourth quartiles of Lp-PLA2 levels, stenosis had occurred more frequently in the ICAS group than in the other three groups (third Q: 50.0% vs. 3.1% vs. 28.1% vs. 18.8%, p = 0.002; fourth Q: 48.4% vs. 16.1% vs. 25.8% vs. 9.7%, p = 0.014). Lp-PLA2 levels were higher in patients with more or severe stenosis in the ICAS group.

Conclusions

Elevated Lp-PLA2 levels were differentially associated with increased risk in AIS patients with ICAS compared to those with ECAS or no stenosis. Lp-PLA2 may be a promising biomarker and potential therapeutic target for ICAS.
Different Roles of the Left and Right Ventrolateral Prefrontal Cortex in Cognitive Reappraisal: An Online Transcranial Magnetic Stimulation Study
Authors: Cheng Si , Qiu Xiufu , Li Sijin , Mo Licheng , Xu Feng , Zhang Dandan
Published: June 2022

The ventrolateral prefrontal cortex (VLPFC) plays a pivotal role in cognitive reappraisal. Previous studies suggested a functional asymmetry of the bilateral VLPFC, but the evidence is still insufficient during cognitive reappraisal. In this study, we conducted an online single-pulse transcranial magnetic stimulation (spTMS) to investigate the causal and distinct roles of the left and right VLPFC in reappraisal. Participants were instructed to reappraise (down-regulate) or attend to pictures depicting social exclusion scenarios while the spTMS was applied over the left or right VLPFC of the participants’ brains. The results showed that spTMS of either the left or the right VLPFC would increase reappraisal difficulty. Meanwhile, the outcome of reappraisal (measured by self-reported negative feelings) significantly deteriorated when the right (but not the left) VLPFC was temporally interrupted by spTMS, while the verbal fluency during oral reporting of the reappraisal strategy was significantly reduced when the left VLPFC was interrupted by spTMS. Taken together, these findings provide causal evidence for the involvement of left and right VLPFC with distinct roles: while the left VLPFC is responsible for the linguistic especially semantic process of generating and selecting appraisals according to the goal of emotion regulation, the right VLPFC plays a critical role in inhibiting inappropriate negative emotions and thoughts generated by the effective scenarios. These findings deepen our understanding of the neurocognitive mechanism of emotion regulation.
Case Report: Prolonged Effects of Short-Term Transcranial Magnetic Stimulation on EEG Biomarkers, Spectral Power, and Seizure Frequency
Authors: Starnes Keith , Britton Jeffrey W. , Burkholder David B. , Suchita Iffat A. , Gregg Nicholas M. , Klassen Bryan T. , Lundstrom Brian Nils
Published: June 2022

Transcranial magnetic stimulation (TMS) is a non-invasive modality of focal brain stimulation in which a fluctuating magnetic field induces electrical currents within the cortex. It remains unclear to what extent TMS alters EEG biomarkers and how EEG biomarkers may guide treatment of focal epilepsy. We present a case of a 48-year-old man with focal epilepsy, refractory to multiple medication trials, who experienced a dramatic reduction in seizures after targeting the area of seizure onset within the left parietal-occipital region with low-frequency repetitive TMS (rTMS). Prior to treatment, he experienced focal seizures that impacted cognition including apraxia at least 50–60 times daily. MRI of the brain showed a large focal cortical dysplasia with contrast enhancement involving the left occipital-parietal junction. Stimulation for 5 consecutive days was well-tolerated and associated with a day-by-day reduction in seizure frequency. In addition, he was monitored with continuous video EEG, which showed continued and progressive changes in spectral power (decreased broadband power and increased infraslow delta activity) and a gradual reduction in seizure frequency and duration. One month after initial treatment, 2-day ambulatory EEG demonstrated seizure-freedom and MRI showed resolution of focal contrast enhancement. He continues to receive 2–3 days of rTMS every 2–4 months. He was seizure-free for 6 months, and at last follow-up of 17 months was experiencing auras approximately every 2 weeks without progression to disabling seizures. This case demonstrates that rTMS can be a well-tolerated and effective means of controlling medication-refractory seizures, and that EEG biomarkers change gradually in a fashion in association with seizure frequency. TMS influences cortical excitability, is a promising non-invasive means of treating focal epilepsy, and has measurable electrophysiologic effects.
Diagnostic Value of Multimodal Intraoperative Neuromonitoring by Combining Somatosensory-With Motor-Evoked Potential in Posterior Decompression Surgery for Thoracic Spinal Stenosis
Authors: Liu Tun , Yan Liang , Qi Huaguang , Luo Zhenguo , Liu Xuemei , Yuan Tao , Dong Buhuai , Zhao Yuanting , Zhao Songchuan , Li Houkun , Liu Zhian , Wu Xucai , Wang Fei , Wang Wentao , Huang Yunfei , Wang Gang
Published: June 2022

Background

Intraoperative neuromonitoring (IONM) has become an increasingly essential technique in spinal surgery. However, data on the diagnostic value of IONM in predicting impending postoperative neurological deficits (PONDs) for patients who underwent posterior decompression surgery for thoracic spinal stenosis (TSS) are limited. Furthermore, patients who are at the highest risk of waveform changes during the surgery remain unknown. Our purpose was to (1) assess the diagnostic accuracy of IONM by combining somatosensory-evoked potential (SSEP) with motor-evoked potential (MEP) in predicting PONDs for patients who underwent the surgery and (2) identify the independent risk factors correlated with IONM changes in our study population.

Methods

A total of 326 consecutive patients who underwent the surgery were identified and analyzed. We collected the following data: (1) demographic and clinical data; (2) IONM data; and (3) outcome data such as details of PONDs, and recovery status (complete, partial, or no recovery) at the 12-month follow-up visit.

Results

In total, 27 patients developed PONDs. However, 15, 6, and 6 patients achieved complete recovery, partial recovery, and no recovery, respectively, at the 12-month follow-up. SSEP or MEP change monitoring yielded better diagnostic efficacy in predicting PONDs as indicated by the increased sensitivity (96.30%) and area under the receiver operating characteristic (ROC) curve (AUC) value (0.91). Only one neurological deficit occurred without waveform changes. On multiple logistic regression analysis, the independent risk factors associated with waveform changes were as follows: preoperative moderate or severe neurological deficits (p = 0.002), operating in the upper- or middle-thoracic spinal level (p = 0.003), estimated blood loss (EBL) ≥ 400 ml (p < 0.001), duration of symptoms ≥ 3 months (p < 0.001), and impairment of gait (p = 0.001).

Conclusion

Somatosensory-evoked potential or MEP change is a highly sensitive and moderately specific indicator for predicting PONDs in posterior decompression surgery for TSS. The independent risks for IONM change were as follows: operated in upper- or middle-thoracic spinal level, presented with gait impairment, had massive blood loss, moderate or severe neurological deficits preoperatively, and had a longer duration of symptoms.

Clinical Trial Registration

[http://www.chictr.org.cn]; identifier [ChiCTR 200003 2155].
Suppression of Neuronal Firing Following Antidromic High-Frequency Stimulations on the Neuronal Axons in Rat Hippocampal CA1 Region
Authors: Yuan Yue , Feng Zhouyan , Yang Gangsheng , Ye Xiangyu , Wang Zhaoxiang
Published: June 2022

High-frequency stimulation (HFS) of electrical pulses has been used to treat certain neurological diseases in brain with commonly utilized effects within stimulation periods. Post-stimulation effects after the end of HFS may also have functions but are lack of attention. To investigate the post-stimulation effects of HFS, we performed experiments in the rat hippocampal CA1 region in vivo. Sequences of 1-min antidromic-HFS (A-HFS) were applied at the alveus fibers. To evaluate the excitability of the neurons, separated orthodromic-tests (O-test) of paired pulses were applied at the Schaffer collaterals in the period of baseline, during late period of A-HFS, and following A-HFS. The evoked potentials of A-HFS pulses and O-test pulses were recorded at the stratum pyramidale and the stratum radiatum of CA1 region by an electrode array. The results showed that the antidromic population spikes (APS) evoked by the A-HFS pulses persisted through the entire 1-min period of 100 Hz A-HFS, though the APS amplitudes decreased significantly from the initial value of 9.9 ± 3.3 mV to the end value of 1.6 ± 0.60 mV. However, following the cessation of A-HFS, a silent period without neuronal firing appeared before the firing gradually recovered to the baseline level. The mean lengths of both silent period and recovery period of pyramidal cells (21.9 ± 22.9 and 172.8 ± 91.6 s) were significantly longer than those of interneurons (11.2 ± 8.9 and 45.6 ± 35.9 s). Furthermore, the orthodromic population spikes (OPS) and the field excitatory postsynaptic potentials (fEPSP) evoked by O-tests at ∼15 s following A-HFS decreased significantly, indicating the excitability of pyramidal cells decreased. In addition, when the pulse frequency of A-HFS was increased to 200, 400, and 800 Hz, the suppression of neuronal activity following A-HFS decreased rather than increased. These results indicated that the neurons with axons directly under HFS can generate a post-stimulation suppression of their excitability that may be due to an antidromic invasion of axonal A-HFS to somata and dendrites. The finding provides new clues to utilize post-stimulation effects generated in the intervals to design intermittent stimulations, such as closed-loop or adaptive stimulations.
The P300 Auditory Event-Related Potential May Predict Segregation of Competing Speech by Bimodal Cochlear Implant Listeners
Authors: Tao Duo-Duo , Zhang Yun-Mei , Liu Hui , Zhang Wen , Xu Min , Galvin John J. , Zhang Dan , Liu Ji-Sheng
Published: June 2022

Compared to normal-hearing (NH) listeners, cochlear implant (CI) listeners have greater difficulty segregating competing speech. Neurophysiological studies have largely investigated the neural foundations for CI listeners' speech recognition in quiet, mainly using the P300 component of event-related potentials (ERPs). P300 is closely related to cognitive processes involving auditory discrimination, selective attention, and working memory. Different from speech perception in quiet, little is known about the neurophysiological foundations for segregation of competing speech by CI listeners. In this study, ERPs were measured for a 1 vs. 2 kHz contrast in 11 Mandarin-speaking bimodal CI listeners and 11 NH listeners. Speech reception thresholds (SRTs) for a male target talker were measured in steady noise or with a male or female masker. Results showed that P300 amplitudes were significantly larger and latencies were significantly shorter for the NH than for the CI group. Similarly, SRTs were significantly better for the NH than for the CI group. Across all participants, P300 amplitude was significantly correlated with SRTs in steady noise (r = −0.65, p = 0.001) and with the competing male (r = −0.62, p = 0.002) and female maskers (r = −0.60, p = 0.003). Within the CI group, there was a significant correlation between P300 amplitude and SRTs with the male masker (r = −0.78, p = 0.005), which produced the most informational masking. The results suggest that P300 amplitude may be a clinically useful neural correlate of central auditory processing capabilities (e.g., susceptibility to informational masking) in bimodal CI patients.
Examining the Role of Socioeconomic Status and Maternal Sensitivity in Predicting Functional Brain Network Connectivity in 5-Month-Old Infants
Authors: Chajes Johanna R. , Stern Jessica A. , Kelsey Caroline M. , Grossmann Tobias
Published: June 2022

Infancy is a sensitive period of human brain development that is plastically shaped by environmental factors. Both proximal factors, such as sensitive parenting, and distal factors, such as socioeconomic status (SES), are known predictors of individual differences in structural and functional brain systems across the lifespan, yet it is unclear how these familial and contextual factors work together to shape functional brain development during infancy, particularly during the first months of life. In the current study, we examined pre-registered hypotheses regarding the interplay between these factors to assess how maternal sensitivity, within the broader context of socioeconomic variation, relates to the development of functional connectivity in long-range cortical brain networks. Specifically, we measured resting-state functional connectivity in three cortical brain networks (fronto-parietal network, default mode network, homologous-interhemispheric connectivity) using functional near-infrared spectroscopy (fNIRS), and examined the associations between maternal sensitivity, SES, and functional connectivity in a sample of 5-month-old infants and their mothers (N = 50 dyads). Results showed that all three networks were detectable during a passive viewing task, and that maternal sensitivity was positively associated with functional connectivity in the default mode network, such that infants with more sensitive mothers exhibited enhanced functional connectivity in this network. Contrary to hypotheses, we did not observe any associations of SES with functional connectivity in the brain networks assessed in this study. This suggests that at 5 months of age, maternal sensitivity is an important proximal environmental factor associated with individual differences in functional connectivity in a long-range cortical brain network implicated in a host of emotional and social-cognitive brain processes.
Enhancement of Frequency-Specific Hemodynamic Power and Functional Connectivity by Transcranial Photobiomodulation in Healthy Humans
Authors: Truong Nghi Cong Dung , Wang Xinlong , Wanniarachchi Hashini , Liu Hanli
Published: June 2022

Transcranial photobiomodulation (tPBM) has been considered a safe and effective brain stimulation modality being able to enhance cerebral oxygenation and neurocognitive function. To better understand the underlying neurophysiological effects of tPBM in the human brain, we utilized a 111-channel functional near infrared spectroscopy (fNIRS) system to map cerebral hemodynamic responses over the whole head to 8-min tPBM with 1,064-nm laser given on the forehead of 19 healthy participants. Instead of analyzing broad-frequency hemodynamic signals (0–0.2 Hz), we investigated frequency-specific effects of tPBM on three infra-slow oscillation (ISO) components consisting of endogenic, neurogenic, and myogenic vasomotions. Significant changes induced by tPBM in spectral power of oxygenated hemoglobin concentration (Δ[HbO]), functional connectivity (FC), and global network metrics at each of the three ISO frequency bands were identified and mapped topographically for frequency-specific comparisons. Our novel findings revealed that tPBM significantly increased endogenic Δ[HbO] powers over the right frontopolar area near the stimulation site. Also, we demonstrated that tPBM enabled significant enhancements of endogenic and myogenic FC across cortical regions as well as of several global network metrics. These findings were consistent with recent reports and met the expectation that myogenic oscillation is highly associated with endothelial activity, which is stimulated by tPBM-evoked nitric oxide (NO) release.
miRNA Involvement in Cerebral Ischemia-Reperfusion Injury
Authors: Neag Maria-Adriana , Mitre Andrei-Otto , Burlacu Codrin-Constantin , Inceu Andreea-Ioana , Mihu Carina , Melincovici Carmen-Stanca , Bichescu Marius , Buzoianu Anca-Dana
Published: June 2022

Cerebral ischemia reperfusion injury is a debilitating medical condition, currently with only a limited amount of therapies aimed at protecting the cerebral parenchyma. Micro RNAs (miRNAs) are small, non-coding RNA molecules that via the RNA-induced silencing complex either degrade or prevent target messenger RNAs from being translated and thus, can modulate the synthesis of target proteins. In the neurological field, miRNAs have been evaluated as potential regulators in brain development processes and pathological events. Following ischemic hypoxic stress, the cellular and molecular events initiated dysregulate different miRNAs, responsible for long-terming progression and extension of neuronal damage. Because of their ability to regulate the synthesis of target proteins, miRNAs emerge as a possible therapeutic strategy in limiting the neuronal damage following a cerebral ischemic event. This review aims to summarize the recent literature evidence of the miRNAs involved in signaling and modulating cerebral ischemia-reperfusion injuries, thus pointing their potential in limiting neuronal damage and repair mechanisms. An in-depth overview of the molecular pathways involved in ischemia reperfusion injury and the involvement of specific miRNAs, could provide future perspectives in the development of neuroprotective agents targeting these specific miRNAs.
Deleterious Variation in BR Serine/Threonine Kinase 2 Classified a Subtype of Autism
Authors: Deng Jingxin , Wang Yi , Hu Meixin , Lin Jia , Li Qiang , Liu Chunxue , Xu Xiu
Published: June 2022

Recently, deleterious variants in the BR serine/threonine kinase 2 (BRSK2) gene have been reported in patients with autism spectrum disorder (ASD), suggesting that BRSK2 is a new high-confidence ASD risk gene, which presents an opportunity to understand the underlying neuropathological mechanisms of ASD. In this study, we performed clinical and neurobehavioral evaluations of a proband with a de novo non-sense variant in BRSK2 (p.R222X) with other reported BRSK2 mutant patients. To validate BRSK2 as an ASD risk gene, we generated a novel brsk2b-deficient zebrafish line through CRISPR/Cas9 and characterized its morphological and neurobehavioral features as well as performed molecular analysis of neurogenesis-related markers. The proband displayed typical ASD behaviors and language and motor delay, which were similar to other published BRSK2 mutant patients. Morphologically, brsk2b–/– larvae exhibited a higher embryonic mortality and rate of pericardium edema, severe developmental delay, and depigmentation as well as growth retardation in the early developmental stage. Behaviorally, brsk2b–/– zebrafish displayed significantly decreased activity in open field tests and enhanced anxiety levels in light/dark tests and thigmotaxis analysis. Specifically, brsk2b–/– zebrafish showed a prominent reduction of social interaction with peers and disrupted social cohesion among homogeneous groups. Molecularly, the mRNA expression levels of homer1b (a postsynaptic density scaffolding protein), and mbpa, mpz, and plp1b (molecular markers of oligodendrocytes and myelination) were increased in the brain tissues of adult brsk2b–/– zebrafish, while the expression level of isl1a, a marker of motor neurons, was decreased. Taken together, for the first time, we established a novel brsk2b-deficient zebrafish model that showed prominent ASD-like behaviors. In addition, the disturbed mRNA expression levels of neurogenesis-related markers implied that the processes of postsynaptic signaling as well as oligodendrocytes and myelination may be involved. This discovery may suggest a path for further research to identify the underlying neuropathological mechanisms between BRSK2 and ASD.
Extraction of Gelatin From Poultry Byproduct: Influence of Drying Method on Structural, Thermal, Functional, and Rheological Characteristics of the Dried Gelatin Powder
Authors: Rather Jahangir A. , Majid Syed Darakshan , Dar Aamir Hussain , Amin Tawheed , Makroo H. A. , Mir Shabir Ahmad , Barba Francisco J. , Dar B. N.
Published: June 2022

The poultry processing industrial wastes are rich sources of gelatin protein, which can be utilized for various industrial sectors. The present investigation was conducted to evaluate the effect of freeze-drying (FD) and hot air drying (HAD) on the physicochemical, structural, thermal, and functional characteristics of chicken feet gelatin. The yield (%) of extracted FD and HAD gelatin was 14.7 and 14.5%, respectively. The gelatin samples showed lower percent transmittance in the UV region. The FTIR bands were at 3,410–3,448 cm−1, 1,635 cm−1, 1,527–334 cm−1, and 1,242–871 cm−1 representing amide-A, amide-I, amide-II, and amide-III bands, respectively. The water activity of HAD was higher (0.43) than in FD (0.21) samples and pH were 5.23 and 5.14 for HAD and FD samples, respectively. The flow index (n) of 6.67% gelatin solutions was 0.104 and 0.418 with consistency coefficient (k) of 37.94 and 31.68 for HAD and FD samples, respectively. The HAD sample shows higher gel strength (276 g) than the FD samples (251 g). The foaming capacity (FC) and foaming stability (FS) of FD samples were 81 and 79.44% compared to 62 and 71.28% for HAD, respectively. The emulsion capacity and emulsion stability of HAD gelatin were higher at 53.47 and 52.66% than FD gelatin. The water holding capacity (WHC) and oil binding capacity (OBC) of FD were lower, that is, 14.3 and 5.34 mL/g compared to HAD gelatin having 14.54 and 6.2 mL/g WHC and OBC, respectively. Hence, the present study indicated that gelatin samples can be utilized in various food products for enhancing functionality and can be used for developing edible packaging materials.
DigiMir Test: Establishing a Novel Pipeline for MiR-371a Quantification Using Droplet Digital PCR in Liquid Biopsies From Testicular Germ Cell Tumor Patients
Authors: Sequeira José Pedro , Lobo João , Constâncio Vera , Brito-Rocha Tiago , Carvalho-Maia Carina , Braga Isaac , Maurício Joaquina , Henrique Rui , Jerónimo Carmen
Published: June 2022

Testicular germ cell tumors (TGCTs) are the most common cancers in young-adult male patients aged between 15 and 39 years. Hsa-miR-371a-3p is currently the most reliable biomarker for diagnosis and monitoring of these patients non-invasively in liquid biopsies, and it is destined to be introduced in the clinic due to improved performance compared to the classical serum tumor markers available. Current studies have focused on real-time quantitative PCR (RT-qPCR) protocols for its determination; still, some challenges remain, since these protocols often require preamplification steps (costly and time-consuming), and report relative levels normalized to a housekeeping microRNA, not always performed the same way. Droplet digital PCR (ddPCR) shows the promise to overcome these challenges, skipping normalization and preamplifications, but has hardly been explored in the field of TGCTs. In this work, we provide a report of a ddPCR-based pipeline for the quantification of hsa-miR-371a-3p (the DigiMir pipeline) and compare it with two RT-qPCR protocols. A total of 107 plasma samples were investigated in the validation setting. The DigiMir pipeline detected TGCTs in a manner representative of tumor burden, with a sensitivity and specificity of 94% and 100%, respectively, outperforming the combined sensitivity of all three classical serum tumor markers (61.5%). Therefore, in this proof-of-concept investigation, we have shown that the DigiMir pipeline constitutes a new promising methodology to accurately report hsa-miR-371a-3p in the clinical setting.
Predictors of Lung Adenocarcinoma With Leptomeningeal Metastases: A 2022 Targeted-Therapy-Assisted molGPA Model
Authors: Zhang Milan , Tong Jiayi , Ma Weifeng , Luo Chongliang , Liu Huiqin , Jiang Yushu , Qin Lingzhi , Wang Xiaojuan , Yuan Lipin , Zhang Jiewen , Peng Fuhua , Chen Yong , Li Wei , Jiang Ying
Published: June 2022

Objective

To explore prognostic indicators of lung adenocarcinoma with leptomeningeal metastases (LM) and provide an updated graded prognostic assessment model integrated with molecular alterations (molGPA).

Methods

A cohort of 162 patients was enrolled from 202 patients with lung adenocarcinoma and LM. By randomly splitting data into the training (80%) and validation (20%) sets, the Cox regression and random survival forest methods were used on the training set to identify statistically significant variables and construct a prognostic model. The C-index of the model was calculated and compared with that of previous molGPA models.

Results

The Cox regression and random forest models both identified four variables, which included KPS, LANO neurological assessment, TKI therapy line, and controlled primary tumor, as statistically significant predictors. A novel targeted-therapy-assisted molGPA model (2022) using the above four prognostic factors was developed to predict LM of lung adenocarcinoma. The C-indices of this prognostic model in the training and validation sets were higher than those of the lung-molGPA (2017) and molGPA (2019) models.

Conclusions

The 2022 molGPA model, a substantial update of previous molGPA models with better prediction performance, may be useful in clinical decision making and stratification of future clinical trials.
Breast Pumps and Mastitis in Breastfeeding Women: Clarifying the Relationship
Authors: Mitoulas Leon R. , Davanzo Riccardo
Published: June 2022

Mastitis is a debilitating condition that can impact around 20% of mothers and is characterized by fever, flu-like symptoms and tender, swollen areas of the breasts. Despite the emerging evidence that breast milk dysbiosis is an underlying cause of mastitis, breast pumps have been implicated as a predisposing risk factor in the pathophysiology of mastitis in breastfeeding mothers. Previous studies have suggested that the use of a breast pump increases a mother's risk for developing mastitis, however, incidence rates of mastitis over the stages of lactation do not match breast pump usage rates. Furthermore, breast pumps, even when used at low vacuum, still promote some breast drainage, thus avoiding milk stasis, which is considered a key factor in the development of mastitis. As a consequence, these data suggest that the literature association of breast pumps with mastitis is more a case of reverse causation and not direct association. Moreover, it is important to note that breast pumps are actually a part of the conservative management of mastitis. In combination, these data show that the breast pump should not be considered a driver in the pathophysiology of mastitis in women.