bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracing the evolutionary history of hepatitis B virus genotype H endemic to Mexico
Authors: Jose-Abrego Alexis , Roman Sonia , Laguna-Meraz Saul , Rebello-Pinho João Renato , Justo Arevalo Santiago , Panduro Arturo
Published: May 2023

Hepatitis B virus (HBV) spreads efficiently among all human populations worldwide. HBV is classified into ten genotypes (A to J) with their geographic distribution and clinical features. In Mexico, HBV genotype H is the leading cause of hepatitis B and has been detected in indigenous populations, suggesting that HBV genotype H may be native to Mexico. However, little is known about the evolutionary history of HBV genotype H. Thus, we aimed to determine the age of HBV genotype H in Mexico using molecular dating techniques. Ninety-two HBV sequences of the reverse transcriptase (RT) domain of the polymerase gene (~1,251 bp) were analyzed; 48 were genotype H, 43 were genotype F, and the oldest HBV sequence from America was included as the root. All sequences were aligned, and the most recent common ancestor (TMRCA) time was calculated using the Bayesian Skyline Evolutionary Analysis. Our results estimate a TMRCA for the genotype H in Mexico of 2070.9 (667.5–4489.2) years before the present (YBP). We identified four major diversification events in genotype H, named H1, H2, H3, and H4. The TMRCA of H1 was 1213.0 (253.3–2638.3) YBP, followed by H2 1175.5 (557.5–2424.2) YBP, H3 949.6 (279.3–2105.0) YBP, and H4 1230.5 (336.3, 2756.7) YBP. We estimated that genotype H diverged from its sister genotype F around 8140.8 (1867.5–18012.8) YBP. In conclusion, this study found that genotype H in Mexico has an estimated age of 2070.9 (667.5–4489.2) YBP and has experienced at least four major diversification events since then.
Feed nutritional composition affects the intestinal microbiota and digestive enzyme activity of black soldier fly larvae
Authors: Chen Guozhong , Zhang Kai , Tang Wenli , Li Youzhi , Pang Junyi , Yuan Xin , Song Xiangbin , Jiang Linlin , Yu Xin , Zhu Hongwei , Wang Jiao , Zhang Jianlong , Zhang Xingxiao
Published: May 2023

Introduction

Using black soldier fly larvae (BSFLs) to treat food waste is one of the most promising environmental protection technologies.

Methods

We used high-throughput sequencing to study the effects of different nutritional compositions on the intestinal microbiota and digestive enzymes of BSF.

Results

Compared with standard feed (CK), high-protein feed (CAS), high-fat feed (OIL) and high-starch feed (STA) had different effects on the BSF intestinal microbiota. CAS significantly reduced the bacterial and fungal diversity in the BSF intestinal tract. At the genus level, CAS, OIL and STA decreased the Enterococcus abundance compared with CK, CAS increased the Lysinibacillus abundance, and OIL increased the Klebsiella, Acinetobacter and Bacillus abundances. Diutina, Issatchenkia and Candida were the dominant fungal genera in the BSFL gut. The relative abundance of Diutina in the CAS group was the highest, and that of Issatchenkia and Candida in the OIL group increased, while STA decreased the abundance of Diutina and increased that of Issatchenkia. The digestive enzyme activities differed among the four groups. The α-amylase, pepsin and lipase activities in the CK group were the highest, and those in the CAS group were the lowest or the second lowest. Correlation analysis of environmental factors showed a significant correlation between the intestinal microbiota composition and digestive enzyme activity, especially α-amylase activity, which was highly correlated with bacteria and fungi with high relative abundances. Moreover, the mortality rate of the CAS group was the highest, and that of the OIL group was the lowest.

Discussion

In summary, different nutritional compositions significantly affected the community structure of bacteria and fungi in the BSFL intestinal tract, affected digestive enzyme activity, and ultimately affected larval mortality. The high oil diet gave the best results in terms of growth, survival and intestinal microbiota diversity, although the digestive enzymes activities were not the highest.
Geographical distribution and pathogenesis of ticks and tick-borne viral diseases
Authors: Shah Taif , Li Qian , Wang Binghui , Baloch Zulqarnain , Xia Xueshan
Published: May 2023

Ticks are obligatory hematophagous arthropods that harbor and transmit infectious pathogens to humans and animals. Tick species belonging to Amblyomma, Ixodes, Dermacentor, and Hyalomma genera may transmit certain viruses such as Bourbon virus (BRBV), Dhori virus (DHOV), Powassan virus (POWV), Omsk hemorrhagic fever virus (OHFV), Colorado tick fever virus (CTFV), Crimean-Congo hemorrhagic fever virus (CCHFV), Heartland virus (HRTV), Kyasanur forest disease virus (KFDV), etc. that affect humans and certain wildlife. The tick vectors may become infected through feeding on viraemic hosts before transmitting the pathogen to humans and animals. Therefore, it is vital to understand the eco-epidemiology of tick-borne viruses and their pathogenesis to optimize preventive measures. Thus this review summarizes knowledge on some medically important ticks and tick-borne viruses, including BRBV, POWV, OHFV, CTFV, CCHFV, HRTV, and KFDV. Further, we discuss these viruses’ epidemiology, pathogenesis, and disease manifestations during infection.
Analysis of molecular characteristics of CAMP-negative Streptococcus agalactiae strains
Authors: Zhou Jie , Zhang Li , Zhang Yang , Liu Hui , Xu Kangli , Zhang Baohu , Feng Tianyuan , Yang Shucai
Published: May 2023

Background

Streptococcus agalactiae can produce CAMP factor, which can promote the β-hemolysin activity of Staphylococcus aureus, forming an arrow-shaped hemolysis enhancement zone at the intersection of the two bacterial species on a blood agar plate. This characteristic feature of Streptococcus agalactiae has led to the widespread use of the CAMP test as an identification method.

Methods

Vaginal/rectal swabs, collected from women at 35–37  weeks of pregnancy, were first inoculated into a selective enrichment broth media, then subcultured onto GBS chromogenic agar and 5% sheep blood agar sequentially. The VITEK-2 automatic identification system and MALDI-TOF MS were initially employed for identification, followed by the CAMP test. CAMP-negative strains underwent 16S rDNA and cfb gene sequence analysis, as well as bacterial multilocus sequence typing.

Results

A total of 190 strains were isolated, with 15 identified as CAMP-negative. Further 16S rDNA gene sequence analysis confirmed that all 15 strains were Streptococcus agalactiae. The MLST typing assay revealed that these 15 strains were of the ST862 type. The cfb gene was amplified and electrophoresed, but no specific fragments were found, indicating that these strains lack the CAMP factor due to cfb gene deletion. Antibiotic susceptibility tests demonstrated no resistance to penicillin, ampicillin, vancomycin and linezolid among the GBS strains. However, there are significant differences in resistance rates to tetracycline.

Conclusion

This study found that 7.9% of GBS strains isolated from the vagina/rectum of pregnant women were CAMP-negative, suggesting that the CAMP test method or primers targeting the cfb gene should not be used as the sole presumptive test for GBS identification.
The impact of primary immunization route on the outcome of infection with SARS-CoV-2 in a hamster model of COVID-19
Authors: Barrett Edward G. , Revelli David , Bakshi Chandra Shekhar , Kadish Alan , Amar Salomon
Published: May 2023

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in over 6.7 million deaths worldwide. COVID-19 vaccines administered parenterally via intramuscular or subcutaneous (SC) routes have reduced the severity of respiratory infections, hospitalization rates, and overall mortality. However, there is a growing interest in developing mucosally delivered vaccines to further enhance the ease and durability of vaccination. This study compared the immune response in hamsters immunized with live SARS-CoV-2 virus via SC or intranasal (IN) routes and assessed the outcome of a subsequent IN SARS-CoV-2 challenge. Results showed that SC-immunized hamsters elicited a dose-dependent neutralizing antibody response but of a significantly lower magnitude than that observed in IN-immunized hamsters. The IN challenge with SARS-CoV-2 in SC-immunized hamsters resulted in body weight loss, increased viral load, and lung pathology than that observed in IN-immunized and IN-challenged counterparts. These results demonstrate that while SC immunization renders some degree of protection, IN immunization induces a stronger immune response and better protection against respiratory SARS-CoV-2 infection. Overall, this study provides evidence that the route of primary immunization plays a critical role in determining the severity of a subsequent respiratory infection caused by SARS-CoV-2. Furthermore, the findings suggest that IN route of immunization may be a more effective option for COVID-19 vaccines than the currently used parenteral routes. Understanding the immune response to SARS-CoV-2 elicited via different immunization routes may help guide more effective and long-lasting vaccination strategies.
Serum chloride as a respiratory failure marker in amyotrophic lateral sclerosis
Authors: Manera Umberto , Grassano Maurizio , Matteoni Enrico , Bombaci Alessandro , Vasta Rosario , Palumbo Francesca , Torrieri Maria Claudia , Cugnasco Paolo , Moglia Cristina , Canosa Antonio , Chiò Adriano , Calvo Andrea
Published: May 2023

Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS) and occurs with great variability among patients according to different phenotypic features. Early predictors of respiratory failure in ALS are important to start non-invasive ventilation (NIV). Venous serum chloride values correlate with carbonate (HCO3-) blood levels and reflect metabolic compensation of respiratory acidosis. Despite its wide availability and low cost, few data on serum chloride as a prognostic marker exist in ALS literature. In the present study, we evaluated serum chloride values at diagnosis as prognostic biomarkers for overall survival and NIV adaptation in a retrospective center-based cohort of ALS patients. We collected all ALS patients with serum chloride assessment at diagnosis, identified through the Piemonte and Valle d’Aosta Register for ALS, evaluating the correlations among serum chloride, clinical features, and other serum biomarkers. Thereafter, time-to-event analysis was modeled to predict overall survival and NIV start. We found a significant correlation between serum chloride and inflammatory status markers, serum sodium, forced vital capacity (FVC), ALS functional rating scale-revised (ALSFRS-R) item 10 and 11, age at diagnosis, and weight loss. Time-to-event analysis confirmed both in univariate analysis and after multiple confounders’ adjustment that serum chloride value at diagnosis significantly influenced survival and time to NIV start. According to our analysis, based on a large ALS cohort, we found that serum chloride analyzed at diagnosis is a low-cost marker of impending respiratory decompensation. In our opinion, it should be added among the serum prognostic biomarkers that are able to stratify patients into different prognostic categories even when performed in the early phases of the disease.
Plp1 in the enteric nervous system is preferentially expressed during early postnatal development in mouse as DM20, whose expression appears reliant on an intronic enhancer
Authors: Patyal Pankaj , Fil Daniel , Wight Patricia A.
Published: May 2023

Recently, the myelin proteolipid protein gene (Plp1) was shown to be expressed in the glia of the enteric nervous system (ENS) in mouse. However, beyond this, not much is known about its expression in the intestine. To address this matter, we investigated Plp1 expression at the mRNA and protein levels in the intestine of mice at different ages (postnatal days 2, 9, 21, and 88). In this study, we show that Plp1 expression preferentially occurs during early postnatal development, primarily as the DM20 isoform. Western blot analysis indicated that DM20 migrated according to its formula weight when isolated from the intestine. However, mobilities of both PLP and DM20 were faster than expected when procured from the brain. The 6.2hPLP(+)Z/FL transgene, which uses the first half of the human PLP1 gene to drive expression of a lacZ reporter gene, recapitulated the developmental pattern observed with the native gene in the intestine, indicating that it can be used as a proxy for Plp1 gene expression. As such, the relative levels of β-galactosidase (β-gal) activity emanating from the 6.2hPLP(+)Z/FL transgene suggest that Plp1 expression is highest in the duodenum, and decreases successively along the segments, toward the colon. Moreover, removal of the wmN1 enhancer region from the transgene (located within Plp1 intron 1) resulted in a dramatic reduction in both transgene mRNA levels and β-gal activity in the intestine, throughout development, suggesting that this region contains a regulatory element crucial for Plp1 expression. This is consistent with earlier studies in both the central and peripheral nervous systems, indicating that it may be a common (if not universal) means by which Plp1 gene expression is governed.
Effectiveness and tolerability of perampanel monotherapy in children with newly diagnosed focal epilepsy
Authors: Zhao Fen , Ren Ying , Geng Guifu , Zhang Tong , Hu Wandong , Zhang Huan , Jin Ruifeng , Shi Jianguo , Gao Zaifen , Zhang Hongwei , Liu Yong
Published: May 2023

Objective

To examine the clinical effectiveness and tolerability of perampanel (PER) as initial monotherapy in pediatric patients with newly diagnosed focal epilepsy.

Methods

A retrospective analysis was conducted on 62 children with newly diagnosed focal epilepsy who were treated with PER at the Epilepsy Center of Jinan Children's Hospital from July 2021 to July 2022. The treatment status, prognosis, and adverse reactions were followed up for a minimum of 6 months after the initiation of PER monotherapy. The effectiveness of the patients was estimated by the PER effective rate at 3-, 6-, and 12-month follow-up evaluations and adverse reactions were also recorded. The effective rates of PER in different etiologies and epilepsy syndromes were also statistically analyzed.

Results

The effective rates of PER treatment at the different time points of evaluation were 88.7% (3 months), 79.1% (6 months), and 80.4% (12 months). With PER treatment, seizure freedom varied over time, with 61.3%, 71.0%, and 71.7% of patients at the 3-, 6-, and 12-month follow-ups, respectively. Among the etiologies of epilepsy, the effective rates of genetic etiology, structural etiology, and unknown etiology were generally above 50% at the 3-, 6-, and 12-month follow-ups. Among the epilepsy syndromes, the categories with higher treatment efficacy were self-limiting epilepsy with centrotemporal spikes (SeLECTs), self-limited epilepsy with autonomic seizures (SeLEAS), and childhood occipital visual epilepsy (COVE), with an effective rate of above 80%. Adverse events were documented in 22 patients (35.5%), but they were mild and tolerable. The most common adverse events comprised irritability, drowsiness, dizziness, and increased appetite.

Conclusion

PER has favorable effectiveness and tolerability as initial monotherapy for children with newly diagnosed focal epilepsy, which could be a potential option for long-term medication in the treatment of focal epilepsy in children. The current study provided potential evidence for PER as initial monotherapy in children with focal epilepsy in clinical practice.
Treatment of IgG4-related disease-associated hypertrophic pachymeningitis with intrathecal rituximab: a case report
Authors: Balaban Denis T. , Hutto Spencer K. , Panzarini Bruno P. , O'Shea Aileen , Varma Aditi , Jones Pamela S. , Chwalisz Bart K. , Stone John H. , Venna Nagagopal
Published: May 2023

IgG4-related disease-associated hypertrophic pachymeningitis (IgG4RD-HP) is a fibroinflammatory autoimmune disorder in which diagnosis is difficult without biopsy. Guidance on management of disease refractory to glucocorticoids and intravenous rituximab is limited. We present the case of a 68-year-old woman with IgG4RD-HP who developed sensorineural hearing loss with associated bulky basilar pachymeningeal enhancement. Her cerebrospinal fluid was inflammatory and had an elevated IgG4 concentration, strongly suggestive of IgG4RD-HP. Biopsy of involved meninges was not possible due to surgical risk. Over years she developed bilateral optic neuropathies and hydrocephalus, requiring intravenous rituximab and ventriculoperitoneal shunt. Her disease was refractory to glucocorticoids. Despite maintenance intravenous rituximab, she developed slowly progressive symptoms of intracranial hypertension and hydrocephalus with persistently inflammatory spinal fluid. Switching to intrathecal rituximab therapy led to dramatic improvement in gait and headache and reduced pachymeningeal bulk and metabolic activity. In patients with IgG4RD-HP refractory to glucocorticoids and intravenous rituximab, intrathecal rituximab may be an efficacious therapy.
Loss or gain of function? Effects of ion channel mutations on neuronal firing depend on the neuron type
Authors: Koch Nils A. , Sonnenberg Lukas , Hedrich Ulrike B. S. , Lauxmann Stephan , Benda Jan
Published: May 2023

Introduction

Clinically relevant mutations to voltage-gated ion channels, called channelopathies, alter ion channel function, properties of ionic currents, and neuronal firing. The effects of ion channel mutations are routinely assessed and characterized as loss of function (LOF) or gain of function (GOF) at the level of ionic currents. However, emerging personalized medicine approaches based on LOF/GOF characterization have limited therapeutic success. Potential reasons are among others that the translation from this binary characterization to neuronal firing is currently not well-understood—especially when considering different neuronal cell types. In this study, we investigate the impact of neuronal cell type on the firing outcome of ion channel mutations.

Methods

To this end, we simulated a diverse collection of single-compartment, conductance-based neuron models that differed in their composition of ionic currents. We systematically analyzed the effects of changes in ion current properties on firing in different neuronal types. Additionally, we simulated the effects of known mutations in KCNA1 gene encoding the KV1.1 potassium channel subtype associated with episodic ataxia type 1 (EA1).

Results

These simulations revealed that the outcome of a given change in ion channel properties on neuronal excitability depends on neuron type, i.e., the properties and expression levels of the unaffected ionic currents.

Discussion

Consequently, neuron-type specific effects are vital to a full understanding of the effects of channelopathies on neuronal excitability and are an important step toward improving the efficacy and precision of personalized medicine approaches.
Automated MRI quantification of volumetric per-muscle fat fractions in the proximal leg of patients with muscular dystrophies
Authors: Huysmans Lotte , De Wel Bram , Claeys Kristl G. , Maes Frederik
Published: May 2023

Muscular dystrophies (MD) are a class of rare genetic diseases resulting in progressive muscle weakness affecting specific muscle groups, depending on the type of disease. Disease progression is characterized by the gradual replacement of muscle tissue by fat, which can be assessed with fat-sensitive magnetic resonance imaging (MRI) and objectively evaluated by quantifying the fat fraction percentage (FF%) per muscle. Volumetric quantification of fat replacement over the full 3D extent of each muscle is more precise and potentially more sensitive than 2D quantification in few selected slices only, but it requires an accurate 3D segmentation of each muscle individually, which is time consuming when this has to be performed manually for a large number of muscles. A reliable, largely automated approach for 3D muscle segmentation is thus needed to facilitate the adoption of fat fraction quantification as a measure of MD disease progression in clinical routine practice, but this is challenging due to the variable appearance of the images and the ambiguity in the discrimination of the contours of adjacent muscles, especially when the normal image contrast is affected and diminished by the fat replacement. To deal with these challenges, we used deep learning to train AI-models to segment the muscles in the proximal leg from knee to hip in Dixon MRI images of healthy subjects as well as patients with MD. We demonstrate state-of-the-art segmentation results of all 18 muscles individually in terms of overlap (Dice score, DSC) with the manual ground truth delineation for images of cases with low fat infiltration (mean overall FF%: 11.3%; mean DSC: 95.3% per image, 84.4–97.3% per muscle) as well as with medium and high fat infiltration (mean overall FF%: 44.3%; mean DSC: 89.0% per image, 70.8–94.5% per muscle). In addition, we demonstrate that the segmentation performance is largely invariant to the field of view of the MRI scan, is generalizable to patients with different types of MD and that the manual delineation effort to create the training set can be drastically reduced without significant loss of segmentation quality by delineating only a subset of the slices.
Development of a Bayesian multimodal model to detect biomarkers in neuroimaging studies
Authors: Bhaumik Dulal K. , Wang Yue , Yen Pei-Shan , Ajilore Olusola A.
Published: May 2023

In this article, we developed a Bayesian multimodal model to detect biomarkers (or neuromarkers) using resting-state functional and structural data while comparing a late-life depression group with a healthy control group. Biomarker detection helps determine a target for treatment intervention to get the optimal therapeutic benefit for treatment-resistant patients. The borrowing strength of the structural connectivity has been quantified for functional activity while detecting the biomarker. In the biomarker searching process, thousands of hypotheses are generated and tested simultaneously using our novel method to control the false discovery rate for small samples. Several existing statistical approaches, frequently used in analyzing neuroimaging data have been investigated and compared via simulation with the proposed approach to show its excellent performance. Results are illustrated with a live data set generated in a late-life depression study. The role of detected biomarkers in terms of cognitive function has been explored.
On temporal scale-free non-periodic stimulation and its mechanisms as an infinite improbability drive of the brain’s functional connectogram
Authors: Cota Vinícius Rosa , Cançado Sérgio Augusto Vieira , Moraes Márcio Flávio Dutra
Published: May 2023

Rationalized development of electrical stimulation (ES) therapy is of paramount importance. Not only it will foster new techniques and technologies with increased levels of safety, efficacy, and efficiency, but it will also facilitate the translation from basic research to clinical practice. For such endeavor, design of new technologies must dialogue with state-of-the-art neuroscientific knowledge. By its turn, neuroscience is transitioning—a movement started a couple of decades earlier—into adopting a new conceptual framework for brain architecture, in which time and thus temporal patterns plays a central role in the neuronal representation of sampled data from the world. This article discusses how neuroscience has evolved to understand the importance of brain rhythms in the overall functional architecture of the nervous system and, consequently, that neuromodulation research should embrace this new conceptual framework. Based on such support, we revisit the literature on standard (fixed-frequency pulsatile stimuli) and mostly non-standard patterns of ES to put forward our own rationale on how temporally complex stimulation schemes may impact neuromodulation strategies. We then proceed to present a low frequency, on average (thus low energy), scale-free temporally randomized ES pattern for the treatment of experimental epilepsy, devised by our group and termed NPS (Non-periodic Stimulation). The approach has been shown to have robust anticonvulsant effects in different animal models of acute and chronic seizures (displaying dysfunctional hyperexcitable tissue), while also preserving neural function. In our understanding, accumulated mechanistic evidence suggests such a beneficial mechanism of action may be due to the natural-like characteristic of a scale-free temporal pattern that may robustly compete with aberrant epileptiform activity for the recruitment of neural circuits. Delivering temporally patterned or random stimuli within specific phases of the underlying oscillations (i.e., those involved in the communication within and across brain regions) could both potentiate and disrupt the formation of neuronal assemblies with random probability. The usage of infinite improbability drive here is obviously a reference to the “The Hitchhiker’s Guide to the Galaxy” comedy science fiction classic, written by Douglas Adams. The parallel is that dynamically driving brain functional connectogram, through neuromodulation, in a manner that would not favor any specific neuronal assembly and/or circuit, could re-stabilize a system that is transitioning to fall under the control of a single attractor. We conclude by discussing future avenues of investigation and their potentially disruptive impact on neurotechnology, with a particular interest in NPS implications in neural plasticity, motor rehabilitation, and its potential for clinical translation.
Accurate segmentation algorithm of acoustic neuroma in the cerebellopontine angle based on ACP-TransUNet
Authors: Zhang Zhuo , Zhang Xiaochen , Yang Yong , Liu Jieyu , Zheng Chenzi , Bai Hua , Ma Quanfeng
Published: May 2023

Acoustic neuroma is one of the most common tumors in the cerebellopontine angle area. Patients with acoustic neuroma have clinical manifestations of the cerebellopontine angle occupying syndrome, such as tinnitus, hearing impairment and even hearing loss. Acoustic neuromas often grow in the internal auditory canal. Neurosurgeons need to observe the lesion contour with the help of MRI images, which not only takes a lot of time, but also is easily affected by subjective factors. Therefore, the automatic and accurate segmentation of acoustic neuroma in cerebellopontine angle on MRI is of great significance for surgical treatment and expected rehabilitation. In this paper, an automatic segmentation method based on Transformer is proposed, using TransUNet as the core model. As some acoustic neuromas are irregular in shape and grow into the internal auditory canal, larger receptive fields are thus needed to synthesize the features. Therefore, we added Atrous Spatial Pyramid Pooling to CNN, which can obtain a larger receptive field without losing too much resolution. Since acoustic neuromas often occur in the cerebellopontine angle area with relatively fixed position, we combined channel attention with pixel attention in the up-sampling stage so as to make our model automatically learn different weights by adding the attention mechanism. In addition, we collected 300 MRI sequence nuclear resonance images of patients with acoustic neuromas in Tianjin Huanhu hospital for training and verification. The ablation experimental results show that the proposed method is reasonable and effective. The comparative experimental results show that the Dice and Hausdorff 95 metrics of the proposed method reach 95.74% and 1.9476 mm respectively, indicating that it is not only superior to the classical models such as UNet, PANet, PSPNet, UNet++, and DeepLabv3, but also show better performance than the newly-proposed SOTA (state-of-the-art) models such as CCNet, MANet, BiseNetv2, Swin-Unet, MedT, TransUNet, and UCTransNet.
Gene expression changes in cerebellum induced by dietary restriction
Authors: van’t Sant Lisanne J. , Birkisdóttir María B. , Ozinga Rutger A. , Gyenis Ákos , Hoeijmakers Jan H.J. , Vermeij Wilbert P. , Jaarsma Dick
Published: May 2023

Background

Dietary restriction (DR) is a well-established universal anti-aging intervention, and is neuroprotective in multiple models of nervous system disease, including models with cerebellar pathology. The beneficial effects of DR are associated with a rearrangement of gene expression that modulate metabolic and cytoprotective pathways. However, the effect of DR on the cerebellar transcriptome remained to be fully defined.

Results

Here we analyzed the effect of a classical 30% DR protocol on the transcriptome of cerebellar cortex of young-adult male mice using RNAseq. We found that about 5% of expressed genes were differentially expressed in DR cerebellum, the far majority of whom showing subtle expression changes. A large proportion of down-regulated genes are implicated in signaling pathways, in particular pathways associated with neuronal signaling. DR up regulated pathways in large part were associated with cytoprotection and DNA repair. Analysis of the expression of cell-specific gene sets, indicated a strong enrichment of DR down genes in Purkinje cells, while genes specifically associated with granule cells did not show such a preferential down-regulation.

Conclusion

Our data show that DR may have a clear effect on the cerebellar transcriptome inducing a mild shift from physiology towards maintenance and repair, and having cell-type specific effects.
Initial low-dose computed tomography screening results and summary of participant characteristics: based on the latest Chinese guideline
Authors: Zhang Zixuan , Gao Yinyan , Liu Shaohui , Ding Binrong , Zhang Xuewei , Wu Irene X. Y.
Published: May 2023

Background

Low-dose computed tomography (LDCT) has been promoted as a promising screening strategy for early detection of lung cancer. China released the latest lung cancer screening guideline in 2021. The compliance of the individuals who received LDCT for lung cancer screening with the guideline is unknown yet. It is necessary to summarize the distribution of guideline-defined lung cancer–related risk factors in the Chinese population so as to inform the selection of target population for the future lung cancer screening.

Methods

A single-center, cross-sectional study design was adopted. All participants were individuals who underwent LDCT at a tertiary teaching hospital in Hunan, China, between 1 January and 31 December 2021. LDCT results were derived along with guideline-based characteristics for descriptive analysis.

Results

A total of 5,486 participants were included. Over one-quarter (1,426, 26.0%) of the participants who received screening did not meet the guideline-defined high-risk population, even among non-smokers (36.4%). Most of the participants (4,622, 84.3%) were found to have lung nodules, while no clinical intervention was required basically. The detection rate of positive nodules varied from 46.8% to 71.2% when using different cut-off values for positive nodules. Among non-smoking women, ground glass opacity appeared to be more significantly common compared with non-smoking men (26.7% vs. 21.8%).

Conclusion

Over one-quarter of individuals who received LDCT screening did not meet the guideline-defined high-risk populations. Appropriate cut-off values for positive nodules need to be continuously explored. More precise and localized criteria for high-risk individuals are needed, especially for non-smoking women.
Erdafitinib treatment in metastatic urothelial carcinoma: a real-world analysis
Authors: Rouvinov Keren , Levanon Eran , Peer Avivit , Sarfaty Michal , Sarid David , Neiman Victoria , Grikshtas Eduard , Rosenbaum Eli , Kushnir Igal , Talmor Barak , Friger Michael , Zarbiv Yonaton , Gez Eli , Dresler Hadas , Shalata Walid , Meirovitz Amichay , Shrem Noa Shani , Yakobson Alexander , Mermershtain Wilmosh , Keizman Daniel
Published: May 2023

Background

Erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor is a standard post chemotherapy advanced treatment line for metastatic urothelial carcinoma harboring FGFR2/3 genomic alterations. It was approved based on a phase 2 clinical trial, revealing a 40% response rate, and 13.8 months overall survival. These FGFR genomic alterations are uncommon. Thus, real-world data on erdafitinb use is scant. We herein describe erdafitinib treatment outcome in a real world patient cohort.

Methods

We retrospectively reviewed the data of patients treated with erdafitinib from 9 Israeli medical centers.

Results

Twenty-five patients with metastatic urothelial carcinoma (median age 73, 64% male, 80% with visceral metastases) were treated with erdafitinib between January 2020 to October 2022. A clinical benefit (complete response 12%, partial response 32%, stable disease 12%) was seen in 56%. Median progression-free survival was 2.7 months, and median overall survival 6.73 months. Treatment related toxicity ≥ grade 3 occurred in 52%, and 32% discontinued therapy due to adverse events.

Conclusions

Erdafitinib therapy is associated with a clinical benefit in the real world setting, and associated with similar toxicity as reported in prospective clinical trials.
Comparative expression profiles of carboxylesterase orthologous CXE14 in two closely related tea geometrid species, Ectropis obliqua Prout and Ectropis grisescens Warren
Authors: Yang Fengshui , Li Yujie , Gao Mengyuan , Xia Qing , Wang Qian , Tang Meijun , Zhou Xiaogui , Guo Huawei , Xiao Qiang , Sun Liang
Published: May 2023

Insect carboxylesterases (CXEs) can be expressed in multiple tissues and play crucial roles in detoxifying xenobiotic insecticides and degrading olfactory cues. Therefore, they have been considered as an important target for development of eco-friendly insect pest management strategies. Despite extensive investigation in most insect species, limited information on CXEs in sibling moth species is currently available. The Ectropis obliqua Prout and Ectropis grisescens Warren are two closely related tea geometrid species, which share the same host of tea plant but differ in geographical distribution, sex pheromone composition, and symbiotic bacteria abundance, providing an excellent mode species for studies of functional diversity of orthologous CXEs. In this study, we focused on EoblCXE14 due to its previously reported non-chemosensory organs-biased expression. First, the EoblCXE14 orthologous gene EgriCXE14 was cloned and sequence characteristics analysis showed that they share a conserved motif and phylogenetic relationship. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to compare the expression profiles between two Ectropis spp. The results showed that EoblCXE14 was predominately expressed in E. obliqua larvae, whereas EgriCXE14 was abundant in E. grisescens at multiple developmental stages. Interestingly, both orthologous CXEs were highly expressed in larval midgut, but the expression level of EoblCXE14 in E. obliqua midgut was significantly higher than that of EgriCXE14 in E. grisescens midgut. In addition, the potential effect of symbiotic bacteria Wolbachia on the CXE14 was examined. This study is the first to provide comparative expression profiles of orthologous CXE genes in two sibling geometrid moth species and the results will help further elucidate CXEs functions and identify a potential target for tea geometrid pest control.
Relationship status and gender-related differences in response to infidelity
Authors: Kato Tsukasa , Okubo Nobutoshi
Published: May 2023

Introduction

The sexual imagination hypothesis suggests that responses to a partner’s infidelity emerge from the sociocultural factors that affect individuals’ imagining of that occurrence irrespective of biological sex, including relationship status (i.e., the experience of a serious, committed relationship). Nevertheless, evolutionary psychological perspectives predict that responses to a partner’s infidelity emerge from a sex-specific evolved innate mechanism.

Methods

A lower 2D:4D digit ratio is associated with more robust responses to a partner’s sexual infidelity. In this study, participants (660 males and 912 females) were requested to measure finger lengths, reactions to their partners’ sexual and emotional infidelity, and relationship status.

Results

A logistic regression and multiple regression analyses revealed that relationship status was uniquely associated with responses to a partner’s sexual and emotional infidelity beyond the effects of sex and 2D:4D. Those in committed relationships were more upset or distressed over their partners’ infidelity, particularly over sexual infidelity, than those not in committed relationships.

Discussion

The results supported the sexual imagination hypothesis indirectly, while evolutionary psychological perspectives were met with skepticism. Our findings implied that sex differences in jealousy result from relationship status, and that responses to partners’ infidelity are more alike than different.
Detecting ulterior motives from verbal cues in group deliberations
Authors: Dunbar Norah E. , Burgoon Judee K. , Chen Xunyu , Wang Xinran , Ge Saiying , Huang Qing , Nunamaker Jay
Published: May 2023

Introduction

Forensic interviewing entails practitioners interviewing suspects to secure valid information and elicit confessions. Such interviews are often conducted in police stations but may also occur in field settings such as border crossings, security checkpoints, bus terminals, and sports venues. Because these real-world interviews often lack experimental control and ground truth, this investigation explored whether results of non-forensic interviews generalize to forensic ones.

Methods

Organizational espionage was simulated to determine (1) what verbal signals distinguish truth from deception, (2) whether deception in groups aligns with deception in dyads, and (3) whether non-forensic venues can be generalized to forensic ones. Engaging in a mock hiring deliberation, participants (4–5 strangers) reviewed and discussed resumes of potential candidates. Surreptitiously, two group members assigned the role of “organizational spies” attempted to persuade the group to hire an inferior candidate. Each group member presented notes from an interview of “their” candidate, followed by a discussion of all candidates. Spies were to use any means possible, including deception, to persuade others to select their candidate. A financial incentive was offered for having one’s candidate chosen. The interview reports and discussions were transcribed and analyzed with SPLICE, an automated text analysis program.

Results

Deceivers were perceived as less trustworthy than truth-tellers, especially when the naïve players won but overall, deceivers were difficult for non-spies to detect even though they were seen as less trustworthy than the naïve participants. Deceivers’ language was more complex and exhibited an “echoing” strategy of repeating others’ opinions. This collusion evolved naturally, without pre-planning. No other verbal differences were evident, which suggests that the difference between spies and non-spies was subtle and difficult for truth-tellers to spot.

Discussion

Whether deception can be successfully detected hinges on a variety of factors including the deceiver’s skill to disguise and the detector’s ability to sense and process information. Furthermore, the group dynamics and communication context subtly moderate how deception manifests and influence the accuracy of detecting ulterior motives. Our future investigations could encompass non-verbal communication channels and verbal patterns rooted in content, thereby providing a more comprehensive understanding of deception detection.
The impact of early factors on persistent negative symptoms in youth at clinical high risk for psychosis
Authors: Devoe Daniel J. , Lui Lu , Cannon Tyrone D. , Cadenhead Kristin Suzanne , Cornblatt Barbara A. , Keshavan Matcheri , McGlashan Tom H. , Perkins Diana. O. , Seidman Larry J. , Stone William S. , Tsuang Ming T. , Woods Scott W. , Walker Elaine F. , Mathalon Daniel H. , Bearden Carrie E. , Addington Jean
Published: May 2023

Introduction

Persistent negative symptoms (PNS) are described as continuing moderate negative symptoms. More severe negative symptoms have been associated with poor premorbid functioning in both chronic schizophrenia and first episode psychosis patients. Furthermore, youth at clinical high risk (CHR) for developing psychosis may also present with negative symptoms and poor premorbid functioning. The aim of this current study was to: (1) define the relationship between PNS and premorbid functioning, life events, trauma and bullying, previous cannabis use, and resource utilization, and (2) to examine what explanatory variables best predicted PNS.

Method

CHR participants (N = 709) were recruited from the North American Prodrome Longitudinal Study (NAPLS 2). Participants were divided into two groups: those with PNS (n = 67) versus those without PNS (n = 673). A K-means cluster analysis was conducted to distinguish patterns of premorbid functioning across the different developmental stages. The relationships between premorbid adjustment and other variables were examined using independent samples t-tests or chi square for categorical variables.

Results

There was significantly more males in the PNS group. Participants with PNS had significantly lower levels of premorbid adjustment in childhood, early adolescence, and late adolescence, compared to CHR participants without PNS. There were no differences between the groups in terms of trauma, bullying, and resource utilization. The non-PNS group had more cannabis use and more desirable and non-desirable life events.

Conclusion

In terms of better understanding relationships between early factors and PNS, a prominent factor associated with PNS was premorbid functioning, in particular poor premorbid functioning in later adolescence.
Toward an integrative socio-cognitive approach in autism spectrum disorder: NEAR method adaptation—study protocol
Authors: Bahri Jihene , Abbes Zeineb S. , Ben Yahia Houda , Halayem Soumeyya , Jelili Selima , Hajri Melek , Amado Isabelle , Medalia Alice , Bouden Asma
Published: May 2023

Background

The cognitive impairments exhibited by people with ASD, threaten the development of social skills that are essential for establishing and maintaining harmonious social relationships. Cognitive remediation and social skills training are now considered as crucial therapeutic approaches in the management of these disorders. Several programs have already been validated and have shown improvements in social skills or cognitive performance. However, the effects of these training methods seem to be difficult to generalize to other everyday life. The aim of our study is to alleviate cognitive and social deficiencies by using a socio-cognitive framework to adapt the Neuropsychological Educational Approach to Remediation (NEAR) method for adolescents with ASD.

Methods/design

Adolescents meeting the DSM-5 criteria for ASD, older than 13 years, and following a regular school curriculum will be recruited from clinical population at the Child and Adolescent Psychiatry in Razi University Hospital-Manouba- Tunisia. Our study is an open and non-randomized controlled trial including 30 patients: NEAR group / control group. The NEAR method combines computerized cognitive exercises and bridging groups inspired from cognitive behavioral therapy. NEAR group will be divided into three groups of five patients each. The duration of the sessions will vary according to the capacities of the participants and the exchanges between them (about 60–120 min). In our study, bridging groups will be amended by adding other tasks including planning role plays and scenarios of problematic social situations in autism, taking into account cultural particularities in order to promote social skills. Computerized exercises will be enriched by adding other tasks aiming to improve the recognition and expression of facial emotions by using digital videos and photographs expressing the six basic emotions. The duration of the program will be about 6 months. All selected patients will have an assessment of cognitive function: social cognition, neurocognition and pragmatic skills, social skills, self-esteem and global functioning at baseline, 1 week after the end of the NEAR program and 6 months later.

Conclusion

This adaptive program is a promising socio-cognitive intervention that create new perspectives for adolescents with autism spectrum disorder.
Feasibility of implementing public-private mix approach for tuberculosis case management in Pokhara Metropolitan City of western Nepal: a qualitative study
Authors: Baral Sushila , Yadav Rajesh Kumar , Yadav Dipendra Kumar , Marahatta Sujan Babu , Baral Yadunath , Khadka Khim Bahadur , Thakur Sanjay Kumar , Paudel Srijana , Sharma Prabin , Pandey Sony , Shrestha Kusum , Shah Naveen Prakash , Basaula Laxman , Nagila Amar , Mahato Roshan Kumar , Ranabhat Chhabi Lal
Published: May 2023

Background

The Public-Private Mix (PPM) approach is a strategic initiative that involves engaging all private and public health care providers in the fight against tuberculosis using international health care standards. For tuberculosis control in Nepal, the PPM approach could be a milestone. This study aimed to explore the barriers to a public-private mix approach in the management of tuberculosis cases in Nepal.

Methods

We conducted key informant interviews with 20 participants, 14 of whom were from private clinics, polyclinics, and hospitals where the PPM approach was used, two from government hospitals, and four from policymakers. All data were audio-recorded, transcribed, and translated into English. The transcripts of the interviews were manually organized, and themes were generated and categorized into 1. TB case detection, 2. patient-related barriers, and 3. health-system-related barriers.

Results

A total of 20 respondents participated in the study. Barriers to PPM were identified into following three themes: (1) Obstacles related to TB case detection, (2) Obstacles related to patients, and (3) Obstacles related to health-care system. PPM implementation was challenged by following sub-themes that included staff turnover, low private sector participation in workshops, a lack of trainings, poor recording and reporting, insufficient joint monitoring and supervision, poor financial benefit, lack of coordination and collaboration, and non-supportive TB-related policies and strategies.

Conclusion

Government stakeholders can significantly benefit by applying a proactive role working with the private in monitoring and supervision. The joint efforts with private sector can then enable all stakeholders to follow the government policy, practice and protocols in case finding, holding and other preventive approaches. Future research are essential in exploring how PPM could be optimized.