bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorescence based HTS-compatible ligand binding assays for dopamine D3 receptors in baculovirus preparations and live cells
Authors: Tahk Maris-Johanna , Laasfeld Tõnis , Meriste Elo , Brea Jose , Loza Maria Isabel , Majellaro Maria , Contino Marialessandra , Sotelo Eddy , Rinken Ago
Published: March 2023

Dopamine receptors are G-protein-coupled receptors that are connected to severe neurological disorders. The development of new ligands targeting these receptors enables gaining a deeper insight into the receptor functioning, including binding mechanisms, kinetics and oligomerization. Novel fluorescent probes allow the development of more efficient, cheaper, reliable and scalable high-throughput screening systems, which speeds up the drug development process. In this study, we used a novel Cy3B labelled commercially available fluorescent ligand CELT-419 for developing dopamine D3 receptor-ligand binding assays with fluorescence polarization and quantitative live cell epifluorescence microscopy. The fluorescence anisotropy assay using 384-well plates achieved Z’ value of 0.71, which is suitable for high-throughput screening of ligand binding. The assay can also be used to determine the kinetics of both the fluorescent ligand as well as some reference unlabeled ligands. Furthermore, CELT-419 was also used with live HEK293-D3R cells in epifluorescence microscopy imaging for deep-learning-based ligand binding quantification. This makes CELT-419 quite a universal fluorescence probe which has the potential to be also used in more advanced microscopy techniques resulting in more comparable studies.
Alternative ATPase domain interactions in eukaryotic Hsp70 chaperones
Authors: Ben-Khoud Yassin , Chen Chao-Sheng , Ali Maruf M. U.
Published: March 2023

Hsp70 molecular chaperones are essential components for maintaining protein homeostasis within cells. They interact with substrate or client proteins in a well characterised fashion that is regulated by ATP and supported by co-chaperones. In eukaryotes there is a vast array of Hsp70 isoforms that may facilitate adaption to a particular cellular compartment and distinct biological role. Emerging data indicate a novel type of interaction between Hsp70 and client protein that does not fit with the classical Hsp70 ATP regulated substrate mechanism. In this review, we highlight Hsp70 ATPase domain interactions with binding partners from various biological systems that we refer to as Hsp70 ATPase alternative binding proteins or HAAB proteins. We identify common mechanistic features that may define how Hsp70 operates when associating with proteins in this alternative HAAB mode of action.
Natural essential oils derived from herbal medicines: A promising therapy strategy for treating cognitive impairment
Authors: Shi Ai , Long Yu , Ma Yin , Yu Shuang , Li Dan , Deng Jie , Wen Jing , Li Xiaoqiu , Wu Yuanyuan , He Xiaofang , Hu Yue , Li Nan , Hu Yuan
Published: March 2023

Cognitive impairment (CI), mainly Alzheimer’s disease (AD), continues to increase in prevalence and is emerging as one of the major health problems in society. However, until now, there are no first-line therapeutic agents for the allopathic treatment or reversal of the disease course. Therefore, the development of therapeutic modalities or drugs that are effective, easy to use, and suitable for long-term administration is important for the treatment of CI such as AD. Essential oils (EOs) extracted from natural herbs have a wide range of pharmacological components, low toxicity, and wide sources, In this review, we list the history of using volatile oils against cognitive disorders in several countries, summarize EOs and monomeric components with cognitive improvement effects, and find that they mainly act by attenuating the neurotoxicity of amyloid beta, anti-oxidative stress, modulating the central cholinergic system, and improving microglia-mediated neuroinflammation. And combined with aromatherapy, the unique advantages and potential of natural EOs in the treatment of AD and other disorders were discussed. This review hopes to provide scientific basis and new ideas for the development and application of natural medicine EOs in the treatment of CI.
White matter hyperintensity mediating gait disorders in iNPH patients via neurofilament light chain
Authors: Yang Lu , Yang Fuxia , Deng Yao , Yan Aijuan , Wei Wenshi , Fang Xuhao
Published: March 2023

Purpose

This study aimed to analyze the differences in regional white matter hyperintensities (WMH) volume and cerebrospinal fluid biomarker levels between idiopathic normal pressure hydrocephalus (iNPH) patients with or without gait disorder.

Methods

Forty-eight iNPH patients undergoing bypass surgery and 20 normal senile individuals were included. The LST toolkit was used to segment all MRI fluid attenuation inversion images and quantify the WMH volume in each brain region. Cerebrospinal fluid was collected from all individuals and measured for concentrations of Aβ, t-tau, p-tau, and neurofilament light chain (NfL). Patients with iNPH were followed up for 1 year and divided categorized into a gait disorder improvement group and no improvement group according to the 3 m round-trip test time parameter improvement by more than 10%.

Results

We found that WMH in all areas of iNPH patients was higher than that in the control group. CSF levels of Aβ, t-tau, and p-tau were lower than those in the control group, while NfL levels were higher than those in the control group. The gait (+) group NfL level was higher than that in gait (−), and there were no statistical differences in Aβ, t-tau, and p-tau levels. The gait (+) group of frontal and parietal lobe WMH volume PVH above the gait (−) group. The mediating effect model analysis showed that PVH might affect the gait disorder of iNPH patients through NfL. A 1-year follow-up of the patients after the bypass surgery found that 24 of the 35 patients in the gait (+) group had improvements, while 11 had no significant improvements. The comparison of CSF marker levels between the two groups showed that the CSF NfL level in the improved group was lower than that in the non-improved group. The WMH volume and PVH in the frontal–parietal lobe of the improved group were lower than those of the non-improved group.

Conclusion

iNPH patients have more serious frontoparietal and periventricular white matter lesions, and WMH volume in the frontoparietal may mediate the occurrence of gait disorder in iNPH patients through the increase of NfL level.
Electrical impedance myography combined with quantitative assessment techniques in paretic muscle of stroke survivors: Insights and challenges
Authors: Gong Ze , Lo Wai Leung Ambrose , Wang Ruoli , Li Le
Published: March 2023

Aging is a non-modifiable risk factor for stroke and the global burden of stroke is continuing to increase due to the aging society. Muscle dysfunction, common sequela of stroke, has long been of research interests. Therefore, how to accurately assess muscle function is particularly important. Electrical impedance myography (EIM) has proven to be feasible to assess muscle impairment in patients with stroke in terms of micro structures, such as muscle membrane integrity, extracellular and intracellular fluids. However, EIM alone is not sufficient to assess muscle function comprehensively given the complex contributors to paretic muscle after an insult. This article discusses the potential to combine EIM and other common quantitative methods as ways to improve the assessment of muscle function in stroke survivors. Clinically, these combined assessments provide not only a distinct advantage for greater accuracy of muscle assessment through cross-validation, but also the physiological explanation on muscle dysfunction at the micro level. Different combinations of assessments are discussed with insights for different purposes. The assessments of morphological, mechanical and contractile properties combined with EIM are focused since changes in muscle structures, tone and strength directly reflect the muscle function of stroke survivors. With advances in computational technology, finite element model and machine learning model that incorporate multi-modal evaluation parameters to enable the establishment of predictive or diagnostic model will be the next step forward to assess muscle function for individual with stroke.
Detrimental effects of soluble α-synuclein oligomers at excitatory glutamatergic synapses
Authors: Ferrari Elena , Salvadè Michela , Zianni Elisa , Brumana Marta , DiLuca Monica , Gardoni Fabrizio
Published: March 2023

Introduction

Oligomeric and fibrillar species of the synaptic protein α-synuclein are established key players in the pathophysiology of Parkinson’s disease and other synucleinopathies. Increasing evidence in the literature points to prefibrillar oligomers as the main cytotoxic species driving dysfunction in diverse neurotransmitter systems even at early disease stages. Of note, soluble oligomers have recently been shown to alter synaptic plasticity mechanisms at the glutamatergic cortico-striatal synapse. However, the molecular and morphological detrimental events triggered by soluble α-synuclein aggregates that ultimately lead to excitatory synaptic failure remain mostly elusive.

Methods

In the present study, we aimed to clarify the effects of soluble α-synuclein oligomers (sOligo) in the pathophysiology of synucleinopathies at cortico-striatal and hippocampal excitatory synapses. To investigate early defects of the striatal synapse in vivo, sOligo were inoculated in the dorsolateral striatum of 2-month-old wild-type C57BL/6J mice, and molecular and morphological analyses were conducted 42 and 84 days post-injection. In parallel, primary cultures of rat hippocampal neurons were exposed to sOligo, and molecular and morphological analyses were performed after 7 days of treatment.

Results

In vivo sOligo injection impaired the post-synaptic retention of striatal ionotropic glutamate receptors and decreased the levels of phosphorylated ERK at 84 days post-injection. These events were not correlated with morphological alterations at dendritic spines. Conversely, chronic in vitro administration of sOligo caused a significant decrease in ERK phosphorylation but did not significantly alter post-synaptic levels of ionotropic glutamate receptors or spine density in primary hippocampal neurons.

Conclusion

Overall, our data indicate that sOligo are involved in pathogenic molecular changes at the striatal glutamatergic synapse, confirming the detrimental effect of these species in an in vivo synucleinopathy model. Moreover, sOligo affects the ERK signaling pathway similarly in hippocampal and striatal neurons, possibly representing an early mechanism that anticipates synaptic loss.
The L1 cell adhesion molecule constrains dendritic spine density in pyramidal neurons of the mouse cerebral cortex
Authors: Murphy Kelsey E. , Wade Sarah D. , Sperringer Justin E. , Mohan Vishwa , Duncan Bryce W. , Zhang Erin Y. , Pak Yubin , Lutz David , Schachner Melitta , Maness Patricia F.
Published: March 2023

A novel function for the L1 cell adhesion molecule, which binds the actin adaptor protein Ankyrin was identified in constraining dendritic spine density on pyramidal neurons in the mouse neocortex. In an L1-null mouse mutant increased spine density was observed on apical but not basal dendrites of pyramidal neurons in diverse cortical areas (prefrontal cortex layer 2/3, motor cortex layer 5, visual cortex layer 4. The Ankyrin binding motif (FIGQY) in the L1 cytoplasmic domain was critical for spine regulation, as demonstrated by increased spine density and altered spine morphology in the prefrontal cortex of a mouse knock-in mutant (L1YH) harboring a tyrosine (Y) to histidine (H) mutation in the FIGQY motif, which disrupted L1-Ankyrin association. This mutation is a known variant in the human L1 syndrome of intellectual disability. L1 was localized by immunofluorescence staining to spine heads and dendrites of cortical pyramidal neurons. L1 coimmunoprecipitated with Ankyrin B (220 kDa isoform) from lysates of wild type but not L1YH forebrain. This study provides insight into the molecular mechanism of spine regulation and underscores the potential for this adhesion molecule to regulate cognitive and other L1-related functions that are abnormal in the L1 syndrome.
Upper limb home-based robotic rehabilitation in chronic stroke patients: A pilot study
Authors: Bressi Federica , Campagnola Benedetta , Cricenti Laura , Santacaterina Fabio , Miccinilli Sandra , Di Pino Giovanni , Fiori Francesca , D'Alonzo Marco , Di Lazzaro Vincenzo , Ricci Lorenzo , Capone Fioravante , Pacilli Alessandra , Sterzi Silvia , Bravi Marco
Published: March 2023

Introduction

Robotic therapy allow to propose sessions of controlled and identical exercises, customizing settings, and characteristics on the individual patient. The effectiveness of robotic assisted therapy is still under study and the use of robots in clinical practice is still limited. Moreover, the possibility of treatment at home allows to reduce the economic costs and time to be borne by the patient and the caregiver and is a valid tool during periods of pandemic such as covid. The aim of this study is to assess whether a robotic home-based treatment rehabilitation using the iCONE robotic device has effects on a stroke population, despite the chronic condition of patients involved and the absence of a therapist next to the patient while performing the exercises.

Materials and methods

All patients underwent an initial (T0) and final (T1) assessment with the iCONE robotic device and clinical scales. After T0 evaluation, the robot was delivered to the patient's home for 10 days of at-home treatment (5 days a week for 2 weeks).

Results

Comparison between T0 and T1 evaluations revealed some significant improvements in robot-evaluated indices such as Independence and Size for the Circle Drawing exercise and Movement Duration for Point-to-Point exercise, but also in the MAS of the elbow. From the analysis of the acceptability questionnaire, a general appreciation of the robot emerged: patients spontaneously asked for the addition of further sessions and to continue therapy.

Discussion

Telerehabilitation of patients suffering from a chronic stroke is an area that is still little explored. From our experience, this is one of the first studies to carry out a telerehabilitation with these characteristics. The use of robots can become a method to reduce the rehabilitation health costs, to ensure continuity of care, and to arrive in more distant places or where the availability of resources is limited.

Conclusion

From the data obtained, this rehabilitation seems to be promising for this population. Moreover, promoting the recovery of the upper limb, iCONE can improve patient's quality of life. It would be interesting to conduct RCT studies to compare a conventional treatment in structure with a robotic telematics treatment.
Electrically-evoked oscillating calcium transients in mono- and co-cultures of iPSC glia and sensory neurons
Authors: Lawson Jennifer , LaVancher Elijah , DeAlmeida Mauricio , Black Bryan James
Published: March 2023

Activated glia are known to exhibit either neuroprotective or neurodegenerative effects, depending on their phenotype, while participating in chronic pain regulation. Until recently, it has been believed that satellite glial cells and astrocytes are electrically slight and process stimuli only through intracellular calcium flux that triggers downstream signaling mechanisms. Though glia do not exhibit action potentials, they do express both voltage- and ligand-gated ion channels that facilitate measurable calcium transients, a measure of their own phenotypic excitability, and support and modulate sensory neuron excitability through ion buffering and secretion of excitatory or inhibitory neuropeptides (i.e., paracrine signaling). We recently developed a model of acute and chronic nociception using co-cultures of iPSC sensory neurons (SN) and spinal astrocytes on microelectrode arrays (MEAs). Until recently, only neuronal extracellular activity has been recorded using MEAs with a high signal-to-noise ratio and in a non-invasive manner. Unfortunately, this method has limited compatibility with simultaneous calcium transient imaging techniques, which is the most common method for monitoring the phenotypic activity of astrocytes. Moreover, both dye-based and genetically encoded calcium indicator imaging rely on calcium chelation, affecting the culture’s long-term physiology. Therefore, it would be ideal to allow continuous and simultaneous direct phenotypic monitoring of both SNs and astrocytes in a high-to-moderate throughput non-invasive manner and would significantly advance the field of electrophysiology. Here, we characterize astrocytic oscillating calcium transients (OCa2+Ts) in mono- and co-cultures of iPSC astrocytes as well as iPSC SN-astrocyte co-cultures on 48 well plate MEAs. We demonstrate that astrocytes exhibit OCa2+Ts in an electrical stimulus amplitude- and duration-dependent manner. We show that OCa2+Ts can be pharmacologically inhibited with the gap junction antagonist, carbenoxolone (100 μM). Most importantly, we demonstrate that both neurons and glia can be phenotypically characterized in real time, repeatedly, over the duration of the culture. In total, our findings suggest that calcium transients in glial populations may serve as a stand-alone or supplemental screening technique for identifying potential analgesics or compounds targeting other glia-mediated pathologies.
The effect of noise on the cortical activity patterns of speech processing in adults with single-sided deafness
Authors: Han Ji-Hye , Lee Jihyun , Lee Hyo-Jeong
Published: March 2023

The most common complaint in people with single-sided deafness (SSD) is difficulty in understanding speech in a noisy environment. Moreover, the neural mechanism of speech-in-noise (SiN) perception in SSD individuals is still poorly understood. In this study, we measured the cortical activity in SSD participants during a SiN task to compare with a speech-in-quiet (SiQ) task. Dipole source analysis revealed left hemispheric dominance in both left- and right-sided SSD group. Contrary to SiN listening, this hemispheric difference was not found during SiQ listening in either group. In addition, cortical activation in the right-sided SSD individuals was independent of the location of sound whereas activation sites in the left-sided SSD group were altered by the sound location. Examining the neural-behavioral relationship revealed that N1 activation is associated with the duration of deafness and the SiN perception ability of individuals with SSD. Our findings indicate that SiN listening is processed differently in the brains of left and right SSD individuals.
Safety and precision of frontal trajectory of lateral habenula deep brain stimulation surgery in treatment-resistant depression
Authors: Cui Zhiqiang , Jiang Chao , Hu Chunhua , Tian Ye , Ling Zhipei , Wang Jian , Fan Tengteng , Hao Hongwei , Wang Zhiyan , Li Luming
Published: March 2023

Introduction

The lateral habenula (LHb) is a promising deep brain stimulation (DBS) target for treatment-resistant depression (TRD). However, the optimal surgical trajectory and its safety of LHb DBS are lacking.

Methods

We reported surgical trajectories for the LHb in six TRD patients treated with DBS at the General Hospital of the Chinese People's Liberation Army between April 2021 and May 2022. Pre-operative fusions of magnetic resonance imaging (MRI) and computed tomography (CT) were conducted to design the implantation trajectory of DBS electrodes. Fusions of MRI and CT were conducted to assess the safety or precision of LHb DBS surgery or implantable electrodes locations.

Results

Results showed that the optimal entry point was the posterior middle frontal gyrus. The target coordinates (electrode tips) were 3.25 ± 0.82 mm and 3.25 ± 0.82 mm laterally, 12.75 ± 0.42 mm and 13.00 ± 0.71 mm posterior to the midpoint of the anterior commissure–posterior commissure (AC-PC) line, and 1.83 ± 0.68 mm and 1.17 ± 0.75 mm inferior to the AC-PC line in the left and right LHb, respectively. The “Ring” angles (relative to the AC-PC level on the sagittal section plane) of the trajectories to the left and right LHb were 51.87° ± 6.67° and 52.00° ± 7.18°, respectively. The “Arc” angles (relative to the midline of the sagittal plane) were 33.82° ± 3.39° and 33.55° ± 3.72°, respectively. Moreover, there was small deviation of actual from planned target coordinates. No patient had surgery-, disease- or device-related adverse events during the perioperative period.

Conclusion

Our results suggested that LHb-DBS surgery via frontal trajectory is safe, accurate, and feasible. This is an applicable work to report in detail the target coordinates and surgical path of human LHb-DBS. It has of great clinical reference value to treat more cases of LHb-DBS for TRD.
Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH): Study protocol for a multi-centered two-arm randomized adaptive trial
Authors: Ratcliff Jonathan J. , Hall Alex J. , Porto Edoardo , Saville Benjamin R. , Lewis Roger J. , Allen Jason W. , Frankel Michael , Wright David W. , Barrow Daniel L. , Pradilla Gustavo
Published: March 2023

Background

Intracerebral hemorrhage (ICH) is a potentially devastating condition with elevated early mortality rates, poor functional outcomes, and high costs of care. Standard of care involves intensive supportive therapy to prevent secondary injury. To date, there is no randomized control study demonstrating benefit of early evacuation of supratentorial ICH.

Methods

The Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) Trial was designed to evaluate the minimally invasive trans-sulcal parafascicular surgery (MIPS) approach, a technique for safe access to deep brain structures and ICH removal using the BrainPath® and Myriad® devices (NICO Corporation, Indianapolis, IN). ENRICH is a multi-centered, two-arm, randomized, adaptive comparative-effectiveness study, where patients are block randomized by ICH location and Glasgow Coma Score (GCS) to early ICH evacuation using MIPS plus standard guideline-based management vs. standard management alone to determine if MIPS results in improved outcomes defined by the utility-weighted modified Rankin score (UWmRS) at 180 days as the primary endpoint. Secondary endpoints include clinical and economic outcomes of MIPS using cost per quality-adjusted life years (QALYs). The inclusion and exclusion criteria aim to capture a broad group of patients with high risk of significant morbidity and mortality to determine optimal treatment strategy.

Discussion

ENRICH will result in improved understanding of the benefit of MIPS for both lobar and deep ICH affecting the basal ganglia. The ongoing study will lead to Level-I evidence to guide clinicians treatment options in the management of acute treatment of ICH.

Trial registration

This study is registered with clinicaltrials.gov (Identifier: NCT02880878).
The role of autoimmune antibodies to predict secondary autoimmunity in patients with relapsing-remitting multiple sclerosis treated with alemtuzumab: A nationwide prospective survey
Authors: Sandgren Sofia , Novakova Lenka , Axelsson Markus , Amirbeagi Firoozeh , Kockum Ingrid , Olsson Tomas , Malmestrom Clas , Lycke Jan
Published: March 2023

Background

Alemtuzumab (ALZ) is an immune reconstitution therapy for treating relapsing-remitting multiple sclerosis (RRMS). However, ALZ increases the risk of secondary autoimmune diseases (SADs).

Objective

We explored whether the detection of autoimmune antibodies (auto-Abs) could predict the development of SADs.

Methods

We included all patients with RRMS in Sweden who initiated ALZ treatment (n = 124, 74 female subjects) from 2009 to 2019. The presence of auto-Abs was determined in plasma samples obtained at the baseline and at 6, 12, and 24 months of follow-up, as well as in a subgroup of patients (n = 51), it was determined in plasma samples obtained at the remaining 3-month intervals up to 24 months. Monthly blood tests, urine tests, and the assessment of clinical symptoms were performed for monitoring safety including that of SADs.

Results

Autoimmune thyroid disease (AITD) developed in 40% of patients, within a median follow-up of 4.5 years. Thyroid auto-Abs were detected in 62% of patients with AITD. The presence of thyrotropin receptor antibodies (TRAbs) at the baseline increased the risk of AITD by 50%. At 24 months, thyroid auto-Abs were detected in 27 patients, and 93% (25/27) developed AITD. Among patients without thyroid auto-Abs, only 30% (15/51) developed AITD (p < 0.0001). In the subgroup of patients (n = 51) with more frequent sampling for auto-Abs, 27 patients developed ALZ-induced AITD, and 19 of them had detectable thyroid auto-Abs prior to the AITD onset, with a median interval of 216 days. Eight patients (6.5%) developed non-thyroid SAD, and none had detectable non-thyroid auto-Abs.

Conclusion

We conclude that monitoring thyroid auto-Abs, essentially TRAbs, may improve the surveillance of AITD associated with ALZ treatment. The risk for non-thyroid SADs was low, and monitoring non-thyroid auto-Abs did not seem to provide any additional information for predicting non-thyroid SADs.
Manual lesion segmentations for traumatic brain injury characterization
Authors: Bennett Alexis , Garner Rachael , Morris Michael D. , La Rocca Marianna , Barisano Giuseppe , Cua Ruskin , Loon Jordan , Alba Celina , Carbone Patrick , Gao Shawn , Pantoja Asenat , Khan Azrin , Nouaili Noor , Vespa Paul , Toga Arthur W. , Duncan Dominique
Published: March 2023

Traumatic brain injury (TBI) often results in heterogenous lesions that can be visualized through various neuroimaging techniques, such as magnetic resonance imaging (MRI). However, injury burden varies greatly between patients and structural deformations often impact usability of available analytic algorithms. Therefore, it is difficult to segment lesions automatically and accurately in TBI cohorts. Mislabeled lesions will ultimately lead to inaccurate findings regarding imaging biomarkers. Therefore, manual segmentation is currently considered the gold standard as this produces more accurate masks than existing automated algorithms. These masks can provide important lesion phenotype data including location, volume, and intensity, among others. There has been a recent push to investigate the correlation between these characteristics and the onset of post traumatic epilepsy (PTE), a disabling consequence of TBI. One motivation of the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is to identify reliable imaging biomarkers of PTE. Here, we report the protocol and importance of our manual segmentation process in patients with moderate-severe TBI enrolled in EpiBioS4Rx. Through these methods, we have generated a dataset of 127 validated lesion segmentation masks for TBI patients. These ground-truths can be used for robust PTE biomarker analyses, including optimization of multimodal MRI analysis via inclusion of lesioned tissue labels. Moreover, our protocol allows for analysis of the refinement process. Though tedious, the methods reported in this work are necessary to create reliable data for effective training of future machine-learning based lesion segmentation methods in TBI patients and subsequent PTE analyses.
Excessive self-grooming, gene dysregulation and imbalance between the striosome and matrix compartments in the striatum of Shank3 mutant mice
Authors: Ferhat Allain-Thibeault , Verpy Elisabeth , Biton Anne , Forget Benoît , De Chaumont Fabrice , Mueller Florian , Le Sourd Anne-Marie , Coqueran Sabrina , Schmitt Julien , Rochefort Christelle , Rondi-Reig Laure , Leboucher Aziliz , Boland Anne , Fin Bertrand , Deleuze Jean-François , Boeckers Tobias M. , Ey Elodie , Bourgeron Thomas
Published: March 2023

Autism is characterized by atypical social communication and stereotyped behaviors. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are detected in 1–2% of patients with autism and intellectual disability, but the mechanisms underpinning the symptoms remain largely unknown. Here, we characterized the behavior of Shank3Δ11/Δ11 mice from 3 to 12 months of age. We observed decreased locomotor activity, increased stereotyped self-grooming and modification of socio-sexual interaction compared to wild-type littermates. We then used RNAseq on four brain regions of the same animals to identify differentially expressed genes (DEGs). DEGs were identified mainly in the striatum and were associated with synaptic transmission (e.g., Grm2, Dlgap1), G-protein-signaling pathways (e.g., Gnal, Prkcg1, and Camk2g), as well as excitation/inhibition balance (e.g., Gad2). Downregulated and upregulated genes were enriched in the gene clusters of medium-sized spiny neurons expressing the dopamine 1 (D1-MSN) and the dopamine 2 receptor (D2-MSN), respectively. Several DEGs (Cnr1, Gnal, Gad2, and Drd4) were reported as striosome markers. By studying the distribution of the glutamate decarboxylase GAD65, encoded by Gad2, we showed that the striosome compartment of Shank3Δ11/Δ11 mice was enlarged and displayed much higher expression of GAD65 compared to wild-type mice. Altogether, these results indicate altered gene expression in the striatum of Shank3-deficient mice and strongly suggest, for the first time, that the excessive self-grooming of these mice is related to an imbalance in the striatal striosome and matrix compartments.
Orexinergic neurons modulate stress coping responses in mice
Authors: Kim Jae Gon , Ea Ji Yun , Yoon Bong-June
Published: March 2023

Stress is a critical precipitating factor for major depression. However, individual responses to the same stressor vary widely, possibly owing to individual variations in stress resilience. Nevertheless, the factors that determine stress susceptibility and resilience remain poorly understood. Orexin neurons have been implicated in the control of stress-induced arousal. Therefore, we investigated whether orexin-expressing neurons are involved in the regulation of stress resilience in male mice. We found that the level of c-fos expression was significantly different in susceptible versus resilient mice in the learned helplessness test (LHT). Furthermore, activating orexinergic neurons induced resilience in the susceptible group, and this resilience was also consistently observed in other behavioral tests. However, activating orexinergic neurons during the induction period (during inescapable stress exposure) did not affect stress resilience in the escape test. In addition, analyses using pathway-specific optic stimulation revealed that activating orexinergic projections to the medial part of the nucleus accumbens (NAc) alone mediated a decrease in anxiety but was not sufficient to induce resilience in the LHT. Collectively, our data suggest that orexinergic projections to multiple targets control diverse and flexible stress-related behaviors in response to various stressors.
Characterization of donkey-meat flavor profiles by GC–IMS and multivariate analysis
Authors: Man Limin , Ren Wei , Sun Mengqi , Du Yanrui , Chen Han , Qin Huaxiu , Chai Wenqiong , Zhu Mingxia , Liu Guiqin , Wang Changfa , Li Mengmeng
Published: March 2023

The distinctive flavor compounds of donkey meat are unknown. Accordingly, in the present study, the volatile compounds (VOCs) in the meat from SanFen (SF) and WuTou (WT) donkeys were comprehensively analyzed by gas chromatography–ion mobility spectrometry (GC-IMS) combined with multivariate analysis. A total of 38 VOCs, of which 33.33% were ketones, 28.89% were alcohols, 20.00% were aldehydes, and 2.22% were heterocycles, were identified. Ketones and alcohols were significantly more abundant for SF than for WT, whereas aldehydes showed the opposite trend. The donkey meats from the two strains were well differentiated using topographic plots, VOC fingerprinting, and multivariate analysis. A total of 17 different VOCs were identified as potential markers for distinguishing the different strains, including hexanal-m, 3-octenal, oct-1-en-3-ol, and pentanal-d. These results indicate that GC–IMS combined with multivariate analysis is a convenient and powerful method for characterizing and discriminating donkey meat.
Prognostic nutritional index and prognosis of patients with coronary artery disease: A systematic review and meta-analysis
Authors: Zhang Shengjing , Wang Huanfen , Chen Saiya , Cai Shengsheng , Zhou Shigeng , Wang Congling , Ni Xiuyuan
Published: March 2023

Background

This review assessed if prognostic nutritional index (PNI) can predict mortality and major adverse cardiac events (MACE) in coronary artery disease (CAD) patients.

Methods

PubMed, Web of Science, Scopus, and Embase were searched up to 1st November 2022 for all types of studies reporting adjusted associations between PNI and mortality or MACE in CAD patients. A random-effect meta-analysis was conducted for PNI as categorical or continuous variable. Subgroup analysis were conducted for multiple confounders.

Results

Fifteen studies with 22,521 patients were included. Meta-analysis found that low PNI was a significant predictor of mortality in CAD patients as compared to those with high PNI (HR: 1.67 95% CI: 1.39, 2.00 I2 = 95% p < 0.00001). Increasing PNI scores were also associated with lower mortality (HR: 0.94 95% CI: 0.91, 0.97 I2 = 89% p = 0.0003). Meta-analysis demonstrated that patients with low PNI had significantly higher incidence of MACE (HR: 1.57 95% CI: 1.08, 2.28 I2 = 94% p = 0.02) and increasing PNI was associated with lower incidence of MACE (HR: 0.84 95% CI: 0.72, 0.92 I2 = 97% p = 0.0007). Subgroup analyses showed mixed results.

Conclusion

Malnutrition assessed by PNI can independently predict mortality and MACE in CAD patients. Variable PNI cut-offs and high inter-study heterogeneity are major limitations while interpreting the results. Further research focusing on specific groups of CAD and taking into account different cut-offs of PNI are needed to provide better evidence.

Systematic Review Registration

No CRD42022365913 https://www.crd.york.ac.uk/prospero/.
Review on the health-promoting effect of adequate selenium status
Authors: Sun Ying , Wang Zhineng , Gong Pin , Yao Wenbo , Ba Qian , Wang Hui
Published: March 2023

Selenium is an essential microelement involved in various biological processes. Selenium deficiency increases the risk of human immunodeficiency virus infection, cancer, cardiovascular disease, and inflammatory bowel disease. Selenium possesses anti-oxidant, anti-cancer, immunomodulatory, hypoglycemic, and intestinal microbiota-regulating properties. The non-linear dose-response relationship between selenium status and health effects is U-shaped; individuals with low baseline selenium levels may benefit from supplementation, whereas those with acceptable or high selenium levels may face possible health hazards. Selenium supplementation is beneficial in various populations and conditions; however, given its small safety window, the safety of selenium supplementation is still a subject of debate. This review summarizes the current understanding of the health-promoting effects of selenium on the human body, the dietary reference intake, and evidence of the association between selenium deficiency and disease.
The learning curve on uniportal video-assisted thoracoscopic lobectomy with the help of postoperative review of videos
Authors: Song Zuodong , Yuan Yu , Cheng Chao , Luo Qingquan , Cheng Xinghua
Published: March 2023

Objectives

Video-assisted thoracoscopic lobectomy has become the preferred surgical approach in experienced centers, and uniportal approaches are becoming increasingly used. But the uniportal approach is still not widely applied presumably due to the learning difficulties of this complex procedure. The use of surgical videos may be helpful to accelerate the learning of this new techniques as in other fields. In this study, we aimed to analyze the learning curve of uniportal video-assisted thoracoscopic lobectomy with the help of postoperative review of videos.

Methods

114 patients with early-stage lung cancer who underwent uniportal video-assisted thoracoscopic lobectomy performed from 2020 to 2021 were reviewed in this study. We recorded the operation video for each patient and reviewed all the videos after surgery. The learning curves were assessed using cumulative sum analysis and the collected data of perioperative outcomes were assessed.

Results

The CUMSUM curve showed its inflection points were around case 38 and 53. It was less compared with previous studies, which about 57–140 cases are needed to attain the proficient phase. The perioperative outcomes were similar in each phase, which included intraoperative blood loss (79.00 ± 26.70 vs 70.67 ± 26.64 vs 70.56 ± 27.23, p=0.0119), the length of hospital stay (3.60 ± 1.52 days vs. 3.23 ± 0.90 days vs. 3.06 ± 0.88 days, p=0.053), the rate of prolonged air leak and conversion to open thoracotomy. There was also no significant difference in the numbers and station of lymph node dissection among the three phases.

Conclusions

Uniportal video-assisted thoracoscopic lobectomy is a safe and reliable approach. Recording and reviewing the operation video could help the surgeon to improve deficiencies and refine the procedure.
Obesity and cancer: Mouse models used in studies
Authors: Zhang Bo-Tao , Xu Jia-Ying , Wang Wei , Zeng Yang , Jiang Jun
Published: March 2023

There is increasing evidence that obesity is associated with the occurrence and development of malignant tumors. When studying the relationship between obesity and malignant tumors, it is very important to choose an appropriate animal model. However, BALB/c nude mice and other animals commonly used to study tumor xenograft (human-derived tumor cell lines) transplantation models are difficult to induce obesity, while C57BL/6 mice and other model animals commonly used for obesity research are not suitable for tumor xenograft transplantation. Therefore, it is difficult to replicate both obesity and malignancy in animal models at the same time. This review summarizes several experimental animal models and protocols that can simultaneously induce obesity and tumor xenografts.
Risk factors for the recurrence of cervical cancer using MR-based T1 mapping: A pilot study
Authors: Liu Jie , Li Shujian , Cao Qinchen , Zhang Yong , Nickel Marcel Dominik , Wu Yanglei , Zhu Jinxia , Cheng Jingliang
Published: March 2023

Objectives

This study aimed to identify risk factors for recurrence in patients with cervical cancer (CC) through quantitative T1 mapping.

Methods

A cohort of 107 patients histopathologically diagnosed with CC at our institution between May 2018 and April 2021 was categorized into surgical and non-surgical groups. Patients in each group were further divided into recurrence and non-recurrence subgroups depending on whether they showed recurrence or metastasis within 3 years of treatment. The longitudinal relaxation time (native T1) and apparent diffusion coefficient (ADC) value of the tumor were calculated. The differences between native T1 and ADC values of the recurrence and non-recurrence subgroups were analyzed, and receiver operating characteristic (ROC) curves were drawn for parameters with statistical differences. Logistic regression was performed for analysis of significant factors affecting CC recurrence. Recurrence-free survival rates were estimated by Kaplan–Meier analysis and compared using the log-rank test.

Results

Thirteen and 10 patients in the surgical and non-surgical groups, respectively, showed recurrence after treatment. There were significant differences in native T1 values between the recurrence and non-recurrence subgroups in the surgical and non-surgical groups (P<0.05); however, there was no difference in ADC values (P>0.05). The areas under the ROC curve of native T1 values for discriminating recurrence of CC after surgical and non-surgical treatment were 0.742 and 0.780, respectively. Logistic regression analysis indicated that native T1 values were risk factors for tumor recurrence in the surgical and non-surgical groups (P=0.004 and 0.040, respectively). Compared with cut-offs, recurrence-free survival curves of patients with higher native T1 values of the two groups were significantly different from those with lower ones (P=0.000 and 0.016, respectively).

Conclusion

Quantitative T1 mapping could help identify CC patients with a high risk of recurrence, supplementing information on tumor prognosis other than clinicopathological features and providing the basis for individualized treatment and follow-up schemes.
Comparison of the second-line treatments for patients with small cell lung cancer sensitive to previous platinum-based chemotherapy: A systematic review and Bayesian network analysis
Authors: Shi Hekai , Guo Nuojin , Zhao Zeming , Liu Ligang , Ni Tianyi , Zhang Jinye , Lu Yingjie
Published: March 2023

Objective

It remains unclear what the best second-line treatment is for patients with small-cell lung cancer sensitive to previous platinum-based chemotherapy.

Methods

We systematically screened randomized controlled trials from several online databases. The primary outcome was objective response rate (ORR), and the secondary outcomes were disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and hematological complications graded 3 to 5. The efficacy of included treatments was ranked by surface under the cumulative ranking curve (SUCRA) value.

Results

We included eleven trials involving 1560 patients in quantitative analysis. Triple chemotherapy containing platinum (TP, combination of cisplatin, etoposide, and irinotecan) was associated with favorable ORR (intravenous topotecan vs TP; odds ratio: 0.13, 95% CI:0.03-0.63; SUCRA, 0.94) and PFS (vs intravenous topotecan; hazard ratio, 0.5; 95% CI: 0.25-0.99; SUCRA, 0.90). Belotecan ranked highest for OS (SUCRA, 0.90), while intravenous topotecan plus Ziv-aflibercept ranked highest for DCR (SUCRA, 0.75). TP was more likely to cause anemia and thrombocytopenia while intravenous topotecan plus Ziv-aflibercept resulted in most neutrocytopenia.

Conclusion

TP is the first recommendation for the second-line treatment of sensitive relapsed SCLC. TP achieved priority in ORR and PFS with the most frequent adverse effects in anemia and thrombocytopenia. For patients who cannot tolerate the hematological adverse effects of triple chemotherapy, amrubicin is an optional option. Amrubicin had relatively good ORR and PFS, accompanied by fewer hematological complications. The rechallenge of the platinum doublet is inferior to amrubicin in ORR, DCR, and PFS. Oral topotecan has a similar effect compared with IV topotecan, but oral topotecan was associated with slightly higher safety and less stress in nursing. Belotecan contributed to the best PFS with slightly better safety but was not ideal in other outcomes.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358256.
Factors influencing health professionals' use of high-flow nasal cannula therapy for infants with bronchiolitis – A qualitative study
Authors: O’Brien Sharon L. , Haskell Libby , Tavender Emma J. , Wilson Sally , Borland Meredith L. , Oakley Ed , Dalziel Stuart R. , Gill Fenella J.
Published: March 2023

Aim

To explore the factors influencing the use of high-flow nasal cannula (HFNC) therapy for infants with bronchiolitis.

Design

Qualitative approach using semi-structured interviews.

Methods

The semi-structured interviews (face-to-face or virtual) were conducted between September 2020 and February 2021. Deductive content analysis was used to map key influencing factors for use of HFNC therapy to the Theoretical Domains Framework (TDF).

Results

Nineteen interviews were undertaken before reaching thematic saturation (7 nurses, 12 doctors) in emergency departments and paediatric wards from four purposively selected hospitals in Australia and New Zealand. Influencing factors were mapped to eight domains in the TDF with 21 themes identified. Main findings included: (1) Health professionals' expectations of HFNC therapy on patient deterioration, work of breathing and oxygenation; (2) Staff emotions relating to concern and anxiety about deterioration and “need to do something”; (3) Social influences from other health professionals and parents and (4) Environmental factors relating to logistics of care and patient transfer considerations. These factors, combined with the ready availability of HFNC equipment and health professionals having the required skills to administer the therapy, contributed to its initiation.

Conclusion

Individual/personal and contextual/environmental factors contribute to the use of HFNC therapy for infants with bronchiolitis. It is evident these influences contribute substantially to increased use, despite evidence-based guidelines recommending a more nuanced approach to this therapy. These findings will inform a targeted implementation intervention to promote evidence-based use of HFNC therapy in infants with bronchiolitis.
Chemoprophylaxis for the prevention of tuberculosis in kidney transplant recipients: A systematic review and meta-analysis
Authors: Yuan Zhihui , Chao Sheng , Xu Yuan , Niu Yulin
Published: March 2023

Background:A systematic review and meta-analysis was performed to investigate the efficacy and safety of isoniazid (INH) prophylaxis to prevent tuberculosis (TB) infection in kidney transplant recipients (KTRs).

Methods:Web of Science, SCOPUS, and PubMed were searched to identify relevant studies that compared the effects among patients who received INH prophylaxis after transplantation.

Results:A total of 13 studies (involving 6,547 KTRs) were included in our analysis. We found that the risk of active TB infection (RR: 0.35, 95%CI 0.27–0.45,p< 0.01) for KTRs was lower in the INH treatment group than in those without prophylaxis. However, there was no significant difference between the two groups in mortality (RR: 0.93, 95%CI 0.67–1.28,p= 0.64), acute rejection (RR: 0.82, 95%CI 0.44–1.51,p= 0.52), and hepatotoxicity (RR: 1.25, 95%CI 0.94–1.65,p= 0.12).

Conclusion:Isoniazid prophylaxis is a safe and effective for KTRs on reactivation of latent TB infection.