bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment and validation of a predictive nomogram for gestational diabetes mellitus during early pregnancy term: A retrospective study
Authors: Li Luman , Zhu Quan , Wang Zihan , Tao Yun , Liu Huanyu , Tang Fei , Liu Song-Mei , Zhang Yuanzhen
Published: February 2023

Objective

This study aims to develop and evaluate a predictive nomogram for early assessment risk factors of gestational diabetes mellitus (GDM) during early pregnancy term, so as to help early clinical management and intervention.

Methods

A total of 824 pregnant women at Zhongnan Hospital of Wuhan University and Maternal and Child Health Hospital of Hubei Province from 1 February 2020 to 30 April 2020 were enrolled in a retrospective observational study and comprised the training dataset. Routine clinical and laboratory information was collected; we applied least absolute shrinkage and selection operator (LASSO) logistic regression and multivariate ROC risk analysis to determine significant predictors and establish the nomogram, and the early pregnancy files (gestational weeks 12–16, n = 392) at the same hospital were collected as a validation dataset. We evaluated the nomogram via the receiver operating characteristic (ROC) curve, C-index, calibration curve, and decision curve analysis (DCA).

Results

We conducted LASSO analysis and multivariate regression to establish a GDM nomogram during the early pregnancy term; the five selected risk predictors are as follows: age, blood urea nitrogen (BUN), fibrinogen-to-albumin ratio (FAR), blood urea nitrogen-to-creatinine ratio (BUN/Cr), and blood urea nitrogen-to-albumin ratio (BUN/ALB). The calibration curve and DCA present optimal predictive power. DCA demonstrates that the nomogram could be applied clinically.

Conclusion

An effective nomogram that predicts GDM should be established in order to help clinical management and intervention at the early gestational stage.
A novel conditional survival nomogram for monitoring real-time prognosis of non-metastatic triple-negative breast cancer
Authors: Meng Xiangdi , Cai Yuanyuan , Chang Xiaolong , Guo Yinghua
Published: February 2023

Background

Conditional survival (CS) is defined as the possibility of further survival after patients have survived for several years since diagnosis. This may be highly valuable for real-time prognostic monitoring, especially when considering individualized factors. Such prediction tools were lacking for non-metastatic triple-negative breast cancer (TNBC). Therefore, this study estimated CS and developed a novel CS-nomogram for real-time prediction of 10-year survival.

Methods

We recruited 32,836 non-metastatic TNBC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2019), who were divided into training and validation groups according to a 7:3 ratio. The Kaplan-Meier method estimated overall survival (OS), and the CS was calculated using the formula CS(y|x) =OS(y+x)/OS(x), where OS(x) and OS(y+x) were the survival of x- and (x+y)-years, respectively. The least absolute shrinkage and selection operator (LASSO) regression identified predictors to develop the CS-nomogram.

Results

CS analysis reported gradual improvement in real-time survival over time since diagnosis, with 10-year OS updated annually from an initial 69.9% to 72.8%, 78.1%, 83.0%, 87.0%, 90.3%, 93.0%, 95.0%, 97.0%, and 98.9% (after 1-9 years of survival, respectively). The LASSO regression identified age, marriage, race, T status, N status, chemotherapy, surgery, and radiotherapy as predictors of CS-nomogram development. This model had a satisfactory predictive performance with a stable 10-year time-dependent area under the curves (AUCs) between 0.75 and 0.86.

Conclusions

Survival of non-metastatic TNBC survivors improved dynamically and non-linearly with survival time. The study developed a CS-nomogram that provided more accurate prognostic data than traditional nomograms, aiding clinical decision-making and reducing patient anxiety.
Investigating characteristics of the long-term settlement of railway embankments in warm permafrost areas
Authors: Xu Yuezhen , Shen Mingde , Zhou Zhiwei , Ma Wei , Li Guoyu , Chen Dun
Published: February 2023

Introduction: The embankment in the permafrost zone of the Qinghai–Tibet Railway (QTR) faces the problem of permafrost degradation, especially in the warm and ice-rich permafrost areas. The settlement deformation of the embankment is more serious in these areas.

Methods: This study systematically investigates the settlement deformation characteristics during 16 operational years of three types of typical roadbed structures. The traditional embankment (TE), U-shaped crushed-rock embankment (UCRE), and crushed-rock revetment embankment (CRRE) are the roadbed structures. The long-term monitoring ground temperature and deformation data of the embankment section along the QTR in warm permafrost areas from 2005 to 2020 are utilized in analysis.

Results and Discussion: This study focuses on the influence law of the roadbed structure form, shady–sunny slope effect, and temperature field change on the settlement of the roadbed. The results indicated that the two types of the crushed-rock embankment (CRE) of the long-term cumulative settlement are less than 50% of the cumulative settlement of the TE, and the impact on controlling the settlement is significant. The annual settlements of the three types of embankment structures are related to the artificial permafrost table (APT) and influenced by cyclical climate change at the regional scale. The annual growth rate of the settlement at the left and right shoulders of the UCRE as a result of the effect of the shady–sunny slope does not vary considerably as the number of operational years increases. The impact of the shady–sunny slope on the CRRE for the various settlements before 2008 was negligible. After 2008, the thermal disturbance to the embankment temperature field induced by the preconstruction and the effect of shady–sunny slopes decreased gradually as the number of operational years increased. In some years of operation, a thawed interlayer in the TE and CRRE greatly affected the embankment settlement acceleration. The settlement growth rate of the TE is related to the decline of the artificial permafrost table (APT). During the operational years, there was no thawed interlayer in the UCRE. The development of the settlement rate is unaffected by the temperature field for either the left or right embankment shoulder.
The reproductive behavior of Neotropical dung beetles
Authors: Huerta Carmen , Cruz-Rosales Magdalena , González-Vainer Patricia , Chamorro-Florescano Ivette , Rivera José D. , Favila Mario E.
Published: February 2023

Dung beetles display complex reproductive behaviors involving sexual findings, sexual recognition, fighting for mates and food used for nesting, sperm competition, and parental care. Over the past 40 years, significant advances have been made regarding the knowledge of various aspects of the sexual and nesting behavior of Neotropical dung beetles. However, human activities modify the natural habitats of dung beetles at an alarming rate, affecting food availability and altering the ecological functions performed by the species in their different habitats. A deeper understanding of the reproductive behavior of dung beetles may contribute significantly in understanding the evolutionary diversification of these insects and their response to environmental changes. The present study reviews and analyzes studies regarding the sexual and reproductive behavior of Neotropical dung beetle species under field and laboratory conditions. We gathered 132 studies and 146 species; 42% of the available data were based on field observations, 23% on laboratory observations, 30% under both field and laboratory conditions, and 5% unspecified. Our review detected significant knowledge, geographic, and habitat gaps regarding the reproductive behavior of Neotropical dung beetles. Based on our findings, we propose future research goals and alternative methods to measure the behavioral responses of Neotropical dung beetles to the impacts of human activities.
Development of bread wheat (Triticum aestivum L) variety HD3411 following marker-assisted backcross breeding for drought tolerance
Authors: Kumar Prashanth K. C. , Bellundagi Amasiddha , Krishna Hari , Mallikarjuna Mallana Gowdra , Thimmappa Ramya K. , Rai Neha , Shashikumara P. , Sinha Nivedita , Jain Neelu , Singh Pradeep K. , Singh Gyanendra Pratap , Prabhu Kumble Vinod
Published: February 2023

Marker-assisted backcross breeding enables selective insertion of targeted traits into the genome to improve yield, quality, and stress resistance in wheat. In the current investigation, we transferred four drought tolerance quantitative trait loci (QTLs) controlling traits, viz canopy temperature, normalized difference vegetative index, chlorophyll content, and grain yield from the drought-tolerant donor line, C306, into a popular high-yielding, drought-sensitive variety, HD2733. Marker-assisted selection coupled with stringent phenotypic screening was used to advance each generation. This study resulted in 23 improved lines carrying combinations of four drought tolerance QTLs with a range of 85.35%–95.79% background recovery. The backcross-derived lines gave a higher yield under moisture-deficit stress conditions compared with the recipient parent. They also showed higher phenotypic mean values for physiological traits and stability characteristics of HD2733. A promising genotype, HD3411, derived from this cross was identified for release after national multi-location coordinating trials under the All India Coordinated Wheat Improvement Project. Our study is a prime example of the advantages of precision breeding using integrating markers and phenotypic selection to develop new cultivars with desirable traits like drought tolerance.
Sub genomic analysis of SARS-CoV-2 using short read amplicon-based sequencing
Authors: Koh Lian Chye Winston , Seow Yiqi , Kong Kiat Whye , Lau Ming Li Lalita , Kumar Shoban Krishna , Yan Gabriel , Lee Chun Kiat , Yan Benedict , Tambyah Paul Anantharajah , Hoon Shawn
Published: February 2023

The novel coronavirus disease 2019 (COVID-19) pandemic poses a serious public health risk. In this report, we present a modified sequencing workflow using short tiling (280bp) amplicons library preparation method paired with Illumina’s iSeq100 desktop sequencer. We demonstrated the utility of our workflow in identifying gapped reads that capture characteristics of subgenomic RNA junctions within our patient cohort. These analytical and library preparation approaches allow a versatile, small footprint and decentralized deployment that can facilitate comprehensive genetics characterizations during outbreaks. Based on the sequencing data, Taqman assays were designed to accurately capture the quantity of subgenomic ORF5 and ORF7a RNA from patient samples and demonstrated utility in tracking subgenomic titres in patient samples when combined with a standard COVID-19 qRT-PCR assay.
Differing prevalence of microcephaly and macrocephaly in male and female fetuses
Authors: Brawley Amalia M. , Schaefer Eric W. , Lucarelli Elizabeth , Ural Serdar H. , Chuang Cynthia H. , Hwang Wenke , Paul Ian M. , Daymont Carrie
Published: February 2023

Objective

To compare the proportion of female and male fetuses classified as microcephalic (head circumference [HC] < 3rd percentile) and macrocephalic (>97th percentile) by commonly used sex-neutral growth curves.

Methods

For fetuses evaluated at a single center, we retrospectively determined the percentile of the first fetal HC measurement between 16 and 0/7 and 21–6/7 weeks using the Hadlock, Intergrowth-21st, and NICHD growth curves. The association between sex and the likelihood of being classified as microcephalic or macrocephalic was evaluated with logistic regression.

Results

Female fetuses (n = 3,006) were more likely than male fetuses (n = 3,186) to be classified as microcephalic using the Hadlock (0.4% male, 1.4% female; odds ratio female vs. male 3.7, 95% CI [1.9, 7.0], p < 0.001), Intergrowth-21st (0.5% male, 1.6% female; odds ratio female vs. male 3.4, 95% CI [1.9, 6.1], p < 0.001), and NICHD (0.3% male, 1.6% female; odds ratio female vs. male 5.6, 95% CI [2.7, 11.5], p < 0.001) curves. Male fetuses were more likely than female fetuses to be classified as macrocephalic using the Intergrowth-21st (6.0% male, 1.5% female; odds ratio male vs. female 4.3, 95% CI [3.1, 6.0], p < 0.001) and NICHD (4.7% male, 1.0% female; odds ratio male vs. female 5.1, 95% CI [3.4, 7.6], p < 0.001) curves. Very low proportions of fetuses were classified as macrocephalic using the Hadlock curves (0.2% male, < 0.1% female; odds ratio male vs. female 6.6, 95% CI [0.8, 52.6]).

Conclusion

Female fetuses were more likely to be classified as microcephalic, and male fetuses were more likely to be classified as macrocephalic. Sex-specific fetal head circumference growth curves could improve interpretation of fetal head circumference measurements, potentially decreasing over- and under-diagnosis of microcephaly and macrocephaly based on sex, therefore improving guidance for clinical decisions. Additionally, the overall prevalence of atypical head size varied using three growth curves, with the NICHD and Intergrowth-21st curves fitting our population better than the Hadlock curves. The choice of fetal head circumference growth curves may substantially impact clinical care.
Giant phagocytes (Gφ) and neutrophil-macrophage hybrids in human carotid atherosclerotic plaques – An activated phenotype
Authors: Lavie Lena , Si-on Erez , Hoffman Aaron
Published: February 2023

Introduction

A small subpopulation of CD66b+ neutrophils with extended lifespan and immensely large size was identified in vitro. They internalized dead neutrophil remnants and cellular debris, transforming them into giant phagocytes (Gφ) resembling macrophage-foam cells with a massive lipid content and CD68+ scavenger receptor expression. Thus, we sought to investigate if similar CD66b+ neutrophils with altered morphology and functions exist in inflammatory/atherosclerotic conditions in vivo, by using human carotid atherosclerotic plaques.

Methods

Thirty-three plaques were obtained from 31 patients undergoing endarterectomy. Carotid plaques were analyzed for CD markers by immunohistochemistry and immunofluorescence and quantitatively analyzed by confocal microscopy. Intra-plaque lipids were stained with Oil Red O.

Results

Plaque CD66b+ neutrophils co-expressed myeloperoxidase (MPO)+ and neutrophil elastase (NE)+. Also, co-expression of CD66b+/CD68+, CD66b+/CD36+, CD66b+/vascular-endothelial-growth- factor (VEGF)+ and 3-nitrotyrosine (3-NT)+/NE+ was noted. Similarly, macrophages co-expressed CD163+/CD68+, CD163+/VEGF+ and CD163+/3-NT+. Both cell types were predominantly localized in lipid-rich areas and stained for lipids. CD66b+ and CD163+ expressions were highly positively correlated with each other and each with CD68+, and 3-NT+. Morphologically, CD66+ cells were big, had a rounded nucleus, and resembled macrophage-foam cell morphology as well as that of Gφ in vitro. To clarify whether CD66b+ and CD163+ cells represent two distinct plaque-populations, plaques were double-stained for CD66b/CD163 co-localization. A third of the plaques was negative for CD66b/CD163 co-localization. Other plaques had a low co-localization, but in few plaques, co-localization was high, collectively, indicating that in some of plaques there were two distinct cell populations, those resembling Gφ, and those co-expressing CD66b+/CD163+, demonstrating a hybrid neutrophil-macrophage phenotype. Interestingly, CD66b+/CD163+ co-localization was highly positively correlated with the oxidant 3-NT, hence, supporting trans-differentiation of CD66b+ cells to CD163+ Cells. Conversely, phagocytosis of dead neutrophils by macrophages might have also occurred.

Discussion

Thus, we conclude that in some of the plaques CD66b+ cells might represent cells resembling Gφ that developed in prolonged culture conditions. Yet, CD66b+/CD163+ co-expressing cells represent a new neutrophil-macrophage hybrid population of unknown transitioning point, possibly by adopting macrophage markers or contrariwise. Nonetheless, the significance and functions of these cells in plaque biology or other inflammatory/atherosclerotic conditions should be unveiled.
The endoparasite Perkinsus olseni affecting the Mediterranean mussels (Mytilus galloprovincialis) in the Italian and Spanish waters: A new possible threat for mussel aquaculture and wild animal population
Authors: Carella Francesca , Fernandez Tejedor Margarita , Villari Grazia , Andree Karl Blyth , De Vico Gionata
Published: February 2023

Dinoflagellates belonging to the Perkinsus genus are OIE (World Organization for animal Health)-listed pathogens extremely virulent for clams and oysters in many marine ecosystems throughout the world. During the monitoring activities of the Mediterranean mussel (Mytilus galloprovincialis) in Campania region (Italy), the presence of typical trophozoites of Perkinsus sp. was observed in mussels from farms and natural banks. Simultaneously, following mussel mortality in the Spanish waters of Catalonia, histopathological studies revealed the presence of the same parasite. Although perkinsosis is an endemic disease in clams in Italy (with prevalence from 40 to 80%), there are no reports to date of its presence in Mediterranean mussels and of the effect on this species. For this study, histopathology, Ray’s Fluid Thioglycollate Medium (RFTM), and molecular diagnostics with conventional Polimerase Chain Reaction (PCR) and qPCR were performed. In samples from Italy, histopathology in the mussel from one farm revealed a prevalence of 26% in February 2019, 40% in February 2020, 16% in November 2020, and 23% in April 2021. In a natural bank, Perkinsus was also detected in May 2020 but in lower prevalence. In Spain, in July 2020, the presence of the parasite was 20% in one site and 10% in a second site and related to animal mortality. In both areas, Perkinsus sp. elicited multiple inflammatory capsules of different size or infiltrates at the level of the digestive gland and gonad. Molecular diagnostics of the Internal Transcriber Spacer (ITS) region of the rDNA (ITS1, 5.8S, and ITS2) showed a 97% similarity of P. olseni from Italy with samples from New Zealand, Australia, and Uruguay and in bivalves such as Pitar rostrata, Astrovenus sp., and Haliotis sp., whereas in Spain the identity was 99% samples from South Korean venerids such as Anadara granosa. Phylogenetic analysis group together P. olseni from Italian and Spanish mussels but place them distant from other P. olseni described in the clams from Europe (Italy, France, and Spain). Direct impact of transboundary animal diseases in aquaculture constitutes a serious consequence for export living animals and their products, as well for international trade. This compromises food security, also causing a high socioeconomic impact on aquaculture exporting nations. P. olseni is a generalist pathogen able to infect different bivalve species, possibly passing from clams to oysters and mussels. Recognized international organizations should take this into account in the view of possible cross-infection. Other studies are needed to define pathogen virulence in this species.
Thermal investigation into the Oldroyd-B hybrid nanofluid with the slip and Newtonian heating effect: Atangana–Baleanu fractional simulation
Authors: Ali Qasim , Amir Muhammad , Raza Ali , Khan Umair , Eldin Sayed M. , Alotaibi Abeer M. , Elattar Samia , Abed Ahmed M.
Published: February 2023

The significance of thermal conductivity, convection, and heat transportation of hybrid nanofluids (HNFs) based on different nanoparticles has enhanced an integral part in numerous industrial and natural processes. In this article, a fractionalized Oldroyd-B HNF along with other significant effects, such as Newtonian heating, constant concentration, and the wall slip condition on temperature close to an infinitely vertical flat plate, is examined. Aluminum oxide (Al2O3) and ferro-ferric oxide (Fe3O4) are the supposed nanoparticles, and water (H2O) and sodium alginate (C6H9NaO7) serve as the base fluids. For generalized memory effects, an innovative fractional model is developed based on the recently proposed Atangana–Baleanu time-fractional (AB) derivative through generalized Fourier and Fick’s law. This Laplace transform technique is used to solve the fractional governing equations of dimensionless temperature, velocity, and concentration profiles. The physical effects of diverse flow parameters are discussed and exhibited graphically by Mathcad software. We have considered 0.15≤α≤0.85,2≤Pr⁡≤9,5≤Gr≤20,0.2≤ϕ1,ϕ2≤0.8,3.5≤Gm≤8, 0.1≤ Sc ≤0.8, and 0.3≤λ1,λ2≤1.7. Moreover, for validation of our present results, some limiting models, such as classical Maxwell and Newtonian fluid models, are recovered from the fractional Oldroyd-B fluid model. Furthermore, comparing the results between Oldroyd-B, Maxwell, and viscous fluid models for both classical and fractional cases, Stehfest and Tzou numerical methods are also employed to secure the validity of our solutions. Moreover, it is visualized that for a short time, temperature and momentum profiles are decayed for larger values of α, and this effect is reversed for a long time. Furthermore, the energy and velocity profiles are higher for water-based HNFs than those for the sodium alginate-based HNF.
Mature cystic extragonadal teratoma in Douglas’ pouch: Case report and literature review
Authors: Yang Yun , Zhao Mengru , Chen Mengyue , Tang Huimin , Qin Zhenyue , Liu Junling , Wang Huihui , Bao Mingyue , Chen Jiming , Xia Bairong
Published: February 2023

Teratomas often occur in the gonads, while Extragonadal mature cystic teratomas are reported occasionally, with the most common site being the omentum. Teratoma in the Douglas sac is extremely rare. we report a rare case of mature cystic Teratoma in the Douglas sac in a 71-year-old woman who underwent laparoscopic surgery. A cyst with a diameter of approximately 6 cm from Douglas was found during surgery, and the mass was separated from both ovaries. Microscopically, the cyst was a mature cystic teratoma that did not originate from the ovary.
The efficacy of pericapsular nerve group block for postoperative analgesia in patients undergoing hip surgery: A systematic review and meta-analysis of randomized controlled trials
Authors: Yu Liang , Shen Xiaojuan , Liu He
Published: February 2023

Background

As an optional regional anesthesia approach, pericapsular nerve group (PENG) block has been successfully utilized to manage pain for hip surgeries without affecting motor function. The present meta-analysis aimed to verify the efficacy of PENG block for postoperative analgesia in patients undergoing hip surgery.

Methods

A total of 497 academic articles were identified after a systematic search in the databases of PubMed, Embase, Web of Science, and Cochrane Library up to 25 August 2022. The primary outcome was postoperative 24-h morphine consumption. Secondary outcomes included the time of the first request for rescue analgesia, static and dynamic pain scores 6 and 24 h after surgery, and incidence of postoperative nausea and vomiting (PONV). We calculated mean differences (MDs) with 95% confidence intervals (CIs) for postoperative 24-h morphine consumption, time of the first request for rescue analgesia, static and dynamic pain scores 6 and 24 h after surgery, and odds ratios (ORs) with 95% CIs for incidence of PONV. The chi-square test was used for heterogeneity analysis, and heterogeneity was assessed by I2. Statistical analysis was performed using Review Manager 5.4.

Results

Numerous electronic databases were searched, and finally, nine studies were identified. There was no significant difference in morphine consumption during the postoperative 24 h [MD: −2.57, 95% CI: (−5.42, 0.27), P = 0.08] and the time of the first request for rescue analgesia [MD: 1.79, 95% CI: (−1.06, 4.64), P = 0.22] between the PENG block and control groups. PENG block did not reveal a significant difference in 6 h [MD: −0.17, 95% CI: (−0.92, 0.57), P = 0.65] [MD: −0.69, 95% CI: (−1.58, 0.21), P = 0.13] and 24 h [MD: −0.25, 95% CI: (−1.54, 1.05), P = 0.71], [MD: 0.05, 95% CI: (−0.84, 0.93), P = 0.91] static and dynamic pain scores compared with other nerve block methods. Moreover, the two groups have a similar risk of PONV (OR: 1.29, 95% CI = 0.53–3.10, P = 0.57).

Conclusion

This review shows that PENG block can act as an alternative multimodal analgesia for hip surgery, and compared with the other kinds of nerve block, there was no significant difference in the postoperative analgesic effect of PENG block.

Systematic review registration

Supplementary Datasheet 1, identifier: CRD 42022356496.
Toward waterborne protozoa detection using sensing technologies
Authors: Nemati Sara , Shalileh Farzaneh , Mirjalali Hamed , Omidfar Kobra
Published: February 2023

Drought and limited sufficient water resources will be the main challenges for humankind during the coming years. The lack of water resources for washing, bathing, and drinking increases the use of contaminated water and the risk of waterborne diseases. A considerable number of waterborne outbreaks are due to protozoan parasites that may remain active/alive in harsh environmental conditions. Therefore, a regular monitoring program of water resources using sensitive techniques is needed to decrease the risk of waterborne outbreaks. Wellorganized point-of-care (POC) systems with enough sensitivity and specificity is the holy grail of research for monitoring platforms. In this review, we comprehensively gathered and discussed rapid, selective, and easy-to-use biosensor and nanobiosensor technologies, developed for the early detection of common waterborne protozoa.
A review of the peripheral proprioceptive apparatus in the larynx
Authors: Hernández-Morato Ignacio , Yu Victoria X. , Pitman Michael J.
Published: February 2023

The larynx is an organ of the upper airway that participates in breathing, glutition, voice production, and airway protection. These complex functions depend on vocal fold (VF) movement, facilitated in turn by the action of the intrinsic laryngeal muscles (ILM). The necessary precise and near-instantaneous modulation of each ILM contraction relies on proprioceptive innervation of the larynx. Dysfunctional laryngeal proprioception likely contributes to disorders such as laryngeal dystonia, dysphagia, vocal fold paresis, and paralysis. While the proprioceptive system in skeletal muscle derived from somites is well described, the proprioceptive circuitry that governs head and neck structures such as VF has not been so well characterized. For over two centuries, researchers have investigated the question of whether canonical proprioceptive organs, muscle spindles, and Golgi tendon organs, exist in the ILM, with variable findings. The present work is a state-of-the-art review of the peripheral component of laryngeal proprioception, including current knowledge of canonical and possible alternative proprioceptive circuitry elements in the larynx.
Electrical stimulation therapy for peripheral nerve injury
Authors: Ni Lingmei , Yao Zhao , Zhao Yifan , Zhang Tianfang , Wang Jie , Li Siyue , Chen Zuobing
Published: February 2023

Peripheral nerve injury is common and frequently occurs in extremity trauma patients. The motor and sensory impairment caused by the injury will affect patients' daily life and social work. Surgical therapeutic approaches don't assure functional recovery, which may lead to neuronal atrophy and hinder accelerated regeneration. Rehabilitation is a necessary stage for patients to recover better. A meaningful role in non-pharmacological intervention is played by rehabilitation, through individualized electrical stimulation therapy. Clinical studies have shown that electrical stimulation enhances axon growth during nerve repair and accelerates sensorimotor recovery. According to different effects and parameters, electrical stimulation can be divided into neuromuscular, transcutaneous, and functional electrical stimulation. The therapeutic mechanism of electrical stimulation may be to reduce muscle atrophy and promote muscle reinnervation by increasing the expression of structural protective proteins and neurotrophic factors. Meanwhile, it can modulate sensory feedback and reduce neuralgia by inhibiting the descending pathway. However, there are not many summary clinical application parameters of electrical stimulation, and the long-term effectiveness and safety also need to be further explored. This article aims to explore application methodologies for effective electrical stimulation in the rehabilitation of peripheral nerve injury, with simultaneous consideration for fundamental principles of electrical stimulation and the latest technology. The highlight of this paper is to identify the most appropriate stimulation parameters (frequency, intensity, duration) to achieve efficacious electrical stimulation in the rehabilitation of peripheral nerve injury.
The impact of vasomotion on analysis of rodent fMRI data
Authors: Lambers Henriette , Wachsmuth Lydia , Lippe Chris , Faber Cornelius
Published: February 2023

Introduction

Small animal fMRI is an essential part of translational research in the cognitive neurosciences. Due to small dimensions and animal physiology preclinical fMRI is prone to artifacts that may lead to misinterpretation of the data. To reach unbiased translational conclusions, it is, therefore, crucial to identify potential sources of experimental noise and to develop correction methods for contributions that cannot be avoided such as physiological noise. Aim of this study was to assess origin and prevalence of hemodynamic oscillations (HDO) in preclinical fMRI in rat, as well as their impact on data analysis.

Methods

Following the development of algorithms for HDO detection and suppression, HDO prevalence in fMRI measurements was investigated for different anesthetic regimens, comprising isoflurane and medetomidine, and for both gradient echo and spin echo fMRI sequences. In addition to assessing the effect of vasodilation on HDO, it was studied if HDO have a direct neuronal correlate using local field potential (LFP) recordings. Finally, the impact of HDO on analysis of fMRI data was assessed, studying both the impact on calculation of activation maps as well as the impact on brain network analysis. Overall, 303 fMRI measurements and 32 LFP recordings were performed in 71 rats.

Results

In total, 62% of the fMRI measurements showed HDO with a frequency of (0.20 ± 0.02) Hz. This frequent occurrence indicated that HDO cannot be generally neglected in fMRI experiments. Using the developed algorithms, HDO were detected with a specificity of 95%, and removed efficiently from the signal time courses. HDO occurred brain-wide under vasoconstrictive conditions in both small and large blood vessels. Vasodilation immediately interrupted HDO, which, however, returned within 1 h under vasoconstrictive conditions. No direct neuronal correlate of HDO was observed in LFP recordings. HDO significantly impacted analysis of fMRI data, leading to altered cluster sizes and F-values for activated voxels, as well as altered brain networks, when comparing data with and without HDO.

Discussion

We therefore conclude that HDO are caused by vasomotion under certain anesthetic conditions and should be corrected during fMRI data analysis to avoid bias.
Bilateral transcranial direct current stimulation may be a feasible treatment of Parkinsonian tremor
Authors: Zhang Bin , Huang Feifei , Liu Jun , Zhang Dingguo
Published: February 2023

Background

Parkinsonian tremor is a common pathological tremor that affects over 6 million people worldwide. It lowers patients' quality of life and threatens their career development, especially when patients' occupation requires dexterous manipulation. In spite of current available treatments in clinics, there is a lack of low-cost, low side-effect, effective solutions for Parkinsonian tremor. Transcranial direct current stimulation (tDCS) may be an alternative treatment.

Objective

In this research, we explored the immediate effect of tDCS with a novel bilateral electrode setup over Parkinsonian tremor. In such a bilateral setup, the cathode was placed over the primary cortex contralateral to the more affected side of Parkinsonian tremor while the anode symmetrically over the other hemisphere. It was designed as a modification to the traditional cathodal setup. The performance of this bilateral setup was compared with three other setups including anodal setup, cathodal setup, and sham (control).

Methods

A randomized, sham-controlled, double-blind, crossover experiment was carried out over 13 qualified patients diagnosed with idiopathic Parkinson's disease (PD). Before and after the stimulus of each tDCS setup, subjects were tested before and after tDCS with four measures, including the Unified Parkinson's Disease Rating Scale (UPDRS), Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), Purdue Pegboard Test (PPT) and a self-design Continuous Tremor Signal Assessment (CTSA). Tremor intensity calculated from CTSA data were regarded as the primary outcome of the experiment.

Results

Statistical results of CTSA, FTMTRS and PPT showed both bilateral tDCS and cathodal tDCS effectively suppressed Parkinsonian tremor. A quantitative comparison of the effect in tremor suppression indicated the optimal suppressive effect was obtained with bilateral tDCS. Based on the results of UPDRS, anodal tDCS was found to benefit subjects' overall performance the most, however, it had little effect in improving Parkinsonian tremor, as revealed by the results of other evaluations.

Conclusion

Our study suggests a beneficial immediate effect of bilateral tDCS in Parkinsonian tremor suppression. In addition, we assume there may be an underlying interhemispheric unbalance of cortical excitability which contributes to Parkinsonian tremor genesis.

Clinical trial registration

Identifier: ChiCTR2100054804.
Sporadic spinal psammomatous malignant melanotic nerve sheath tumor: A case report and literature review
Authors: Bonomo Giulio , Gans Alessandro , Mazzapicchi Elio , Rubiu Emanuele , Alimonti Paolo , Eoli Marica , Paterra Rosina , Pollo Bianca , Iess Guglielmo , Restelli Francesco , Falco Jacopo , Acerbi Francesco , Schiariti Marco Paolo , Ferroli Paolo , Broggi Morgan
Published: February 2023

Background

Sporadic Spinal Psammomatous Malignant Melanotic Nerve Sheath Tumor (SSP-MMNST) is a rare subgroup of peripheral nerve sheath tumors arising along the spine. Only a few reports of SSP-MMNST have been described. In this paper, we review the literature on SSP-MMNST focusing on clinical, and diagnostic features, as well as investigating possible pathogenetic mechanisms to better implement therapeutic strategies. We also report an illustrative case of a young female presenting with cervicobrachial pain due to two SSP-MMNSTs arising from C5-6 right spinal roots.

Case description

We report a case of a 28-year-old woman presenting with right arm weakness and dysesthesia. Clinical examination and neuroimaging were performed, and, following surgical removal of both lesions, a histological diagnosis of SSP-MMNST was obtained.

Results

The literature review identified 21 eligible studies assessing 23 patients with SSP-MMNST, with a mean onset age of 41 years and a slight male gender preference. The lumbar district was the most involved spinal segment. Gross-total resection (GTR) was the treatment of choice in all amenable cases, followed in selected cases with residual tumor by adjuvant radiotherapy or chemotherapy. The metastatic and recurrence rates were 31.58% and 36.8%, respectively.

Conclusion

Differently from common schwannomas, MMNST represents a rare disease with known recurrence and metastatization propensity. As reported in our review, SSP-MMNST has a greater recurrence rate when compared to other forms of spinal MMNST, raising questions about the greater aggressiveness of the former. We also found that residual disease is related to a higher risk of systemic disease spreading. This metastatic potential, usually associated with primary lumbar localization, is characterized by a slight male prevalence. Indeed, whenever GTR is unachievable, considering the higher recurrence rate, adjuvant radiation therapy should be taken into consideration.
An updated portrait of monocyte-macrophages in classical Hodgkin lymphoma
Authors: Ferrarini Isacco , Bernardelli Andrea , Lovato Ester , Schena Alberto , Krampera Mauro , Visco Carlo
Published: February 2023

Classical Hodgkin lymphoma (cHL) is a unique neoplastic ecosystem characterized by a heterogeneous immune infiltrate surrounding the rare malignant Hodgkin Reed-Sternberg cells. Though less abundant than T-cells, tumor-infiltrating macrophages play a pivotal role in supporting HRS survival through cell-to-cell and paracrine interactions. Traditional immunohistochemistry based upon the M1-M2 dichotomy yielded controversial results about the composition, functional role and prognostic impact of macrophages in cHL. More recent studies exploiting single-cell technologies and image analyses have highlighted the heterogeneity and the peculiar spatial arrangement of the macrophagic infiltrate, with the most immunosuppressive subpopulations lying in close proximity of HRS cells and the most tumor-hostile subsets kept far away from the neoplastic niches. High-throughput analysis of peripheral blood mononuclear cells in cHL patients have also identified a novel, potentially cytotoxic, subpopulation predicting better response to PD-1 blockade. This review examines the phenotypic profile, spatial localization and clinical impact of tumor-infiltrating macrophages and circulating monocytes in cHL, providing an up-do-date portrait of these innate immune cells with possible translational applications.
Gut microbiota composition alteration analysis and functional categorization in children with growth hormone deficiency
Authors: Huang Congfu , Meng Dongming , Li Yinhu , Lu Shiyang , Yang Wei , Wu Bin , Chen Shufen , Yang Zhenyu , Liu Haiying
Published: February 2023

Objective

To study changes in the composition and functions of the gut microbiota (GM) in children with growth hormone deficiency (GHD) using high-throughput sequencing.

Methods

Thirty-three children with GHD diagnosed in Longgang District Maternity and Child Health Hospital were included in the disease group and 24 healthy children of the same age comprised the control group. Total DNA was extracted and amplified from stool samples obtained from all subjects. High-throughput sequencing was used to analyze the GM composition and functions.

Results

The GM from the two groups of children showed significant differences in α-diversity (P < 0.05). In comparison with the control group, the abundance of the phylum Bacteroidetes was significantly higher (45.96% vs. 65.71%) while the Firmicutes count was significantly lower (47.09% vs. 25.20%). At the genus level, the abundance of Prevotella in the disease group was significantly higher (3.16% vs. 20.67%) and that of Lachnospiracea incertae sedis, Clostridium XlVa, and Megamonas was lower (6.576% vs. 1.75%; 4.51% vs. 0.80%; 5.08% vs. 2.02%, respectively). GM functions, including those involved in membrane_transport, energy_metabolism, poorly_characterized, metabolism_of_cofactors_and_vitamins, glycan_biosynthesis_and_metabolism, transcription, folding,_sorting,_and_degradation, were significantly altered in the disease group. The abundance of various GM components was correlated with endocrine hormone levels.

Conclusion

Significant alterations in the GM are seen in children with growth hormone deficiency, which may affect both energy metabolism and the levels of endocrine hormones, potentially leading to growth restriction.
Cuscutae semen alleviates CUS-induced depression-like behaviors in mice via the gut microbiota-neuroinflammation axis
Authors: Hou Lanwei , Yang Liu , Zhu Caiting , Miao Jingyu , Zhou Wenjuan , Tang Yuchun , Meng Haiwei , Liu Shuwei
Published: February 2023

Introduction: Major depressive disorder is a mental disease with complex pathogenesis and treatment mechanisms involving changes in both the gut microbiota and neuroinflammation. Cuscutae Semen (CS), also known as Chinese Dodder seed, is a medicinal herb that exerts several pharmacological effects. These include neuroprotection, anti-neuroinflammation, the repair of synaptic damage, and the alleviation of oxidative stress. However, whether CuscutaeSemen exerts an antidepressant effect remains unknown.

Methods: In this study, we evaluated the effect of CS on chronic unpredictable stress (CUS)-induced depression-like behaviors in mice by observing changes in several inflammatory markers, including proinflammatory cytokines, inflammatory proteins, and gliocyte activation. Meanwhile, changes in the gut microbiota were analyzed based on 16 S rRNA sequencing results. Moreover, the effect of CS on the synaptic ultrastructure was detected by transmission electron microscopy.

Results: We found that the CS extract was rich in chlorogenic acid and hypericin. And CS relieved depression-like behaviors in mice exposed to CUS. Increased levels of cytokines (IL-1β and TNF-α) and inflammatory proteins (NLRP3, NF-κB, and COX-2) induced by CUS were reversed after CS administration. The number of astrocytes and microglia increased after CUS exposure, whereas they decreased after CS treatment. Meanwhile, CS could change the structure of the gut microbiota and increase the relative abundance of Lactobacillus. Moreover, there was a significant relationship between several Lactobacilli and indicators of depression-like behaviors and inflammation. There was a decrease in postsynaptic density after exposure to CUS, and this change was alleviated after CS treatme.

Conclusion: This study found that CS treatment ameliorated CUS-induced depression-like behaviors and synaptic structural defects in mice via the gut microbiota-neuroinflammation axis. And chlorogenic acid and hypericin may be the main active substances for CS to exert antidepressant effects.
A small molecule inhibitor of Notch1 modulates stemness and suppresses breast cancer cell growth
Authors: Saran Uttara , Chandrasekaran Balaji , Tyagi Ashish , Shukla Vaibhav , Singh Amandeep , Sharma Arun K. , Damodaran Chendil
Published: February 2023

Although breast cancer stem cells (BCSCs) are well characterized, molecularly targeting and eradicating this sub-population remains a challenge in the clinic. Recent studies have explored several signaling pathways that govern stem cell activation: We and others established that the Notch1 signaling plays a significant role in the proliferation, survival, and differentiation of BCSCs. Earlier, we reported that a newly developed small molecule, ASR490, binds to the negative regulatory region (NRR: The activation switch of the Notch receptor) of Notch1. In vitro results demonstrated that ASR490 significantly inhibited BCSCs (ALDH+ and CD44+/CD24–) and breast cancer (BC) growth at nM concentrations, and subsequently inhibited the colony- and mammosphere-forming abilities of BCSCs and BCs. ASR490 downregulated the expressions of Notch1 intracellular domain (NICD: The active form of Notch1) and its downstream effectors Hey1 and HES1. Inhibition of Notch1-NICD facilitated autophagy-mediated growth inhibition by triggering the fusion of autophagosome and autolysosome in BCSCs. ASR490 was found to be non-toxic to healthy cells as compared to existing Notch1 inhibitors. Moreover, oral administration of ASR490 abrogated BCSC and BC tumor growth in the in vivo xenograft models. Together our results indicate that ASR490 is a potential therapeutic agent that inhibits BC tumor growth by targeting and abolishing Notch1 signaling in BCSCs and BC cells.
Alteration of speed-of-sound by fixatives and tissue processing methods in scanning acoustic microscopy
Authors: Tamura Kazuki , Ito Kazuyo , Yoshida Sachiko , Mamou Jonathan , Miura Katsutoshi , Yamamoto Seiji
Published: February 2023

The elasticity of biological tissues is one of the physical characteristics of tissues and has attracted attention as a clinical diagnostic parameter. The elasticity can be determined on the microscopic scale with speed of sound (SoS) measurements using acoustic microscopy. In SoS measurements, a thin-sliced section is attached to a glass slide in the same manner as a light microscopic specimen. There are two main methods for preparing thin sections: paraffin-embedding and frozen-section. The frozen-section method requires fewer processing steps from sectioning to measurement and is considered to reduce artifacts in the sample compared with the paraffin-embedding method. Both methods need fixatives to keep tissue structures. Many reports of measurements using frozen sections are focused on soft tissues with relatively high protein contents. In this study, we determined the SoS in thin sections of four types of organs (brain, heart, liver, and kidney) prepared using two different methods (paraffin-embedding and frozen-section) and four different chemical fixatives (formalin, Karnovsky fixative (KF) 0.5% and 2.0% glutaraldehyde, and ethanol). The SoS in heart and liver samples prepared using KF showed good agreement with reported values for raw samples. For samples fixed with KF, the SoS increased as the glutaraldehyde concentration increased from 0.5% to 2.0%. A brain tumor sample was processed with KF 0.5%, and the SoS in the tumor was significantly higher than that in the non-tumor area. The results confirmed that it is possible to measure the SoS in brain samples with low protein contents using appropriate fixatives.
The SHI irradiation induced transition to negative dielectric constant phase in K2Bi4Ti4WO18
Authors: Sharma Vipul K. , Kumawat Ashish K. , Rathore Satyapal S. , Sulania Indra , Meena R. C. , Kedia S. K. , Nathawat Dr. Rashi
Published: February 2023

In present communication, a new Aurivillius family compound K2Bi4Ti4WO18 was synthesized, and the impact of swift heavy ion (SHI), Ni+11 irradiation on its surface and dielectric properties has been studied in detail. The phase formation in this complex oxide, and crystallization to B2cb symmetry was confirmed by the X-ray diffraction. However, post irradiation the XRD, SEM and AFM studies shows the surface amorphization, in agreement with the theoretical calculations. Furthermore, the effect of irradiation was also observed in the bulk dielectric properties as the system transform to a phase with negative dielectric constant above 350 K in the radio frequencies. This transition is in correlation with significant change in other dielectric parameters such enhancement in AC conductivity, a helical Nyquist plot and multiple dielectric relaxations. This conspicuous changes in the dielectric response post irradiation is attributed to the SHI induced defect formation, modification of energy barriers and their consequences on the electronic structure. Thus, current study suggests that the dielectric properties of Aurivillius K2Bi4Ti4WO18 could be tailored by ion irradiation and opens a new possibility of tuning functional properties.