bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent T cell-mediated immune responses against Omicron variants after the third COVID-19 mRNA vaccine dose
Authors: Belik Milja , Liedes Oona , Vara Saimi , Haveri Anu , Pöysti Sakari , Kolehmainen Pekka , Maljanen Sari , Huttunen Moona , Reinholm Arttu , Lundberg Rickard , Skön Marika , Österlund Pamela , Melin Merit , Hänninen Arno , Hurme Antti , Ivaska Lauri , Tähtinen Paula A. , Lempainen Johanna , Kakkola Laura , Jalkanen Pinja , Julkunen Ilkka
Published: January 2023

Introduction

The prime-boost COVID-19 mRNA vaccination strategy has proven to be effective against severe COVID-19 disease and death. However, concerns have been raised due to decreasing neutralizing antibody levels after COVID-19 vaccination and due to the emergence of new immuno-evasive SARS-CoV-2 variants that may require additional booster vaccinations.

Methods

In this study, we analyzed the humoral and cell-mediated immune responses against the Omicron BA.1 and BA.2 subvariants in Finnish healthcare workers (HCWs) vaccinated with three doses of COVID-19 mRNA vaccines. We used enzyme immunoassay and microneutralization test to analyze the levels of SARS-CoV-2 specific IgG antibodies in the sera of the vaccinees and the in vitro neutralization capacity of the sera. Activation induced marker assay together with flow cytometry and extracellular cytokine analysis was used to determine responses in SARS-CoV-2 spike protein stimulated PBMCs.

Results

Here we show that within the HCWs, the third mRNA vaccine dose recalls both humoral and T cell-mediated immune responses and induces high levels of neutralizing antibodies against Omicron BA.1 and BA.2 variants. Three weeks after the third vaccine dose, SARS-CoV-2 wild type spike protein-specific CD4+ and CD8+ T cells are observed in 82% and 71% of HCWs, respectively, and the T cells cross-recognize both Omicron BA.1 and BA.2 spike peptides. Although the levels of neutralizing antibodies against Omicron BA.1 and BA.2 decline 2.5 to 3.8-fold three months after the third dose, memory CD4+ T cell responses are maintained for at least eight months post the second dose and three months post the third vaccine dose.

Discussion

We show that after the administration of the third mRNA vaccine dose the levels of both humoral and cell-mediated immune responses are effectively activated, and the levels of the spike-specific antibodies are further elevated compared to the levels after the second vaccine dose. Even though at three months after the third vaccine dose antibody levels in sera decrease at a similar rate as after the second vaccine dose, the levels of spike-specific CD4+ and CD8+ T cells remain relatively stable. Additionally, the T cells retain efficiency in cross-recognizing spike protein peptide pools derived from Omicron BA.1 and BA.2 subvariants. Altogether our results suggest durable cellmediated immunity and protection against SARS-CoV-2.
Intermediate conductance Ca2+-activated potassium channels are activated by functional coupling with stretch-activated nonselective cation channels in cricket myocytes
Authors: Numata Tomohiro , Sato-Numata Kaori , Yoshino Masami
Published: January 2023

Cooperative gating of localized ion channels ranges from fine-tuning excitation–contraction coupling in muscle cells to controlling pace-making activity in the heart. Membrane deformation resulting from muscle contraction activates stretch-activated (SA) cation channels. The subsequent Ca2+ influx activates spatially localized Ca2+-sensitive K+ channels to fine-tune spontaneous muscle contraction. To characterize endogenously expressed intermediate conductance Ca2+-activated potassium (IK) channels and assess the functional relevance of the extracellular Ca2+ source leading to IK channel activity, we performed patch-clamp techniques on cricket oviduct myocytes and recorded single-channel data. In this study, we first investigated the identification of IK channels that could be distinguished from endogenously expressed large-conductance Ca2+-activated potassium (BK) channels by adding extracellular Ba2+. The single-channel conductance of the IK channel was 62 pS, and its activity increased with increasing intracellular Ca2+ concentration but was not voltage-dependent. These results indicated that IK channels are endogenously expressed in cricket oviduct myocytes. Second, the Ca2+ influx pathway that activates the IK channel was investigated. The absence of extracellular Ca2+ or the presence of Gd3+ abolished the activity of IK channels. Finally, we investigated the proximity between SA and IK channels. The removal of extracellular Ca2+, administration of Ca2+ to the microscopic region in a pipette, and application of membrane stretching stimulation increased SA channel activity, followed by IK channel activity. Membrane stretch-induced SA and IK channel activity were positively correlated. However, the emergence of IK channel activity and its increase in response to membrane mechanical stretch was not observed without Ca2+ in the pipette. These results strongly suggest that IK channels are endogenously expressed in cricket oviduct myocytes and that IK channel activity is regulated by neighboring SA channel activity. In conclusion, functional coupling between SA and IK channels may underlie the molecular basis of spontaneous rhythmic contractions.
Identification, classification and expression analysis of the Ras superfamily genes in the Pacific white shrimp, Litopenaeus vannamei
Authors: Si Shuqing , Zhang Xiaojun , Yuan Jianbo , Zhang Xiaoxi , Yu Yang , Yang Song , Li Fuhua
Published: January 2023

The Ras superfamily of small guanosine triphosphatases (GTPases) are a large group of small GTP-binding proteins, which play crucial roles in basic cellular processes in all eukaryotes. In this study, by analyzing the gene structure, temporal and spatial expression patterns, a total of 108 Ras superfamily genes were identified in the genome of the Pacific white shrimp Litopenaeus vannamei. We found these genes included not only the classical Ras GTPase superfamily members, but also some unconventional and novel Ras GTPase proteins, which have unknown functions and unique expression patterns. All Ras superfamily genes of L. vannamei were highly conserved within the core G domain and closely related in phylogeny, but they might have two different evolutionary origins. In addition, different Ras GTPase genes exhibited distinct expression patterns in different tissues, development/molting stages and WSSV infection samples of L. vannamei, suggesting that they may have a high functional specialization, and play important roles in regulating the biological processes of cell differentiation, growth and development, immune response, etc. This study provides important clues for the structure, classification, evolution and function of Ras superfamily in shrimp.
Spatial-temporal variations of short-lived mesoscale eddies and their environmental effects
Authors: Liu Shidong , Xu Jishang , Qiao Lulu , Li Guangxue , Shi Jinghao , Ding Dong , Yu Di , Yang Xue , Pan Yufeng , Liu Siyu , Fu Xiaoshuang
Published: January 2023

Mesoscale eddies (MEs) affect the transport and redistribution of oceanic matter and energy. The long-lived and long-distance propagation of individual eddies has garnered extensive attention; however, short-lived MEs (< 7 days) have been widely overlooked. In this study, the basic features of short-lived MEs and their spatial-temporal variations in a tropical eddy-rich region were extracted and analyzed for the first time. Short-lived cyclonic and anticyclonic eddies (CEs/AEs) were found to be widespread in two eddy belts in the tropical region of the western Pacific warm pool (WPWP). The CEs and AEs were formed by the shear instability between large-scale circulations and were distributed on both sides of the North Equatorial Countercurrent, with significant differences in spatial distribution. The variations in sea surface temperature, mixed layer depth, and surface chlorophyll-a concentration in the core of the WPWP were spatially and temporally related to the development of the two eddy belts. This new insight into short-lived MEs in the tropical region contributes to our current understanding of ocean eddies. The potential impacts of short-lived MEs on climate change, global air–sea interactions, and tropical cyclone formation should receive adequate attention and further assessment in future research.
Larval settlement and metamorphosis of Mytilus coruscus in response to varying bacterial capsular polysaccharide
Authors: He Chu-Han , Zhang Wen , Hu Xiao-Meng , Yoshida Asami , Osatomi Kiyoshi , Liang Xiao , Yang Jin-Long
Published: January 2023

Marine invertebrates are the backbone of marine biodiversity and play a pivotal role in the marine ecosystem. The life cycle of most marine invertebrates includes the settlement and metamorphosis stage, which is induced by marine biofilms, but the mechanism is still enigmatic. In the present study, we constructed the capsular polysaccharide (CPS) synthesis gene capC-deleted mutant of Pseudoalteromonas marina by gene knockout and then compared the phenotype, the biofilm-forming ability, the effect on settlement and metamorphosis of Mytilus coruscus, and the exopolysaccharide and CPS levels between the mutant and the wild-type strains to explicate the relationship between bacteria and mussels. The study presented that the phenotype and biofilm-forming ability between the wild-type and ΔcapC strains had no significant difference, but the inducing activity of ΔcapC biofilms on larval settlement and metamorphosis decreased significantly (p < 0.05). Compared with the wild-type, the CPS content of ΔcapC strain significantly decreased by 38.07%, accompanied by the increase of c-di-GMP. Meanwhile, the biomass of α-polysaccharides and β-polysaccharides on ΔcapC biofilms decreased significantly (p < 0.05). Thus, the CPS synthesis gene could modulate c-di-GMP, which regulates bacterial polysaccharide secretion, and then impact larval settlement and metamorphosis of mussels. This work brings an entry point to deeply understand the interaction between bacterial polysaccharide and larval recruitment.
Case report: Subcutaneous Mycobacterium haemophilum infection in an immunocompetent patient after lipolysis injections
Authors: Ni Linan , Zou Danyang , Yang Hong , Gao Zhiqin , Yu Qian , Yang Lianjuan
Published: January 2023

Mycobacterium haemophilum is a slow-growing, aerobic mycobacterium that acts as a pathogen in immunocompromised adult patients and immunocompetent children. There are only a few rare cases in the literature describing this species as a cause of subcutaneous infections. Here, we describe a subcutaneous infection caused by M. haemophilum in an immunocompetent female after lipolysis injections at an unqualified beauty salon, suggesting that this bacteria can also be a potential causative agent of adverse events in medical aesthetics. In addition, M. haemophilum caused lesions not only at the injection sites and adjacent areas but also invaded distant sections through the subcutaneous sinus tracts. Thus, early diagnosis and appropriate treatment are vital to prevent further deterioration and improve prognosis.
Validation of a deep neural network-based algorithm supporting clinical management of adnexal mass
Authors: Reilly Gerard P. , Dunton Charles J. , Bullock Rowan G. , Ure Daniel R. , Fritsche Herbert , Ghosh Srinka , Pappas Todd C. , Phan Ryan T.
Published: January 2023

Background

Conservative management of adnexal mass is warranted when there is imaging-based and clinical evidence of benign characteristics. Malignancy risk is, however, a concern due to the mortality rate of ovarian cancer. Malignancy occurs in 10–15% of adnexal masses that go to surgery, whereas the rate of malignancy is much lower in masses clinically characterized as benign or indeterminate. Additional diagnostic tests could assist conservative management of these patients. Here we report the clinical validation of OvaWatch, a multivariate index assay, with real-world evidence of performance that supports conservative management of adnexal masses.

Methods

OvaWatch utilizes a previously characterized neural network-based algorithm combining serum biomarkers and clinical covariates and was used to examine malignancy risk in prospective and retrospective samples of patients with an adnexal mass. Retrospective data sets were assembled from previous studies using patients who had adnexal mass and were scheduled for surgery. The prospective study was a multi-center trial of women with adnexal mass as identified on clinical examination and indeterminate or asymptomatic by imaging. The performance to detect ovarian malignancy was evaluated at a previously validated score threshold.

Results

In retrospective, low prevalence (N = 1,453, 1.5% malignancy rate) data from patients that received an independent physician assessment of benign, OvaWatch has a sensitivity of 81.8% [95% confidence interval (CI) 65.1–92.7] for identifying a histologically confirmed malignancy, and a negative predictive value (NPV) of 99.7%. OvaWatch identified 18/22 malignancies missed by physician assessment. A prospective data set had 501 patients where 106 patients with adnexal mass went for surgery. The prevalence was 2% (10 malignancies). The sensitivity of OvaWatch for malignancy was 40% (95% CI: 16.8–68.7%), and the specificity was 87% (95% CI: 83.7–89.7) when patients were included in the analysis who did not go to surgery and were evaluated as benign. The NPV remained 98.6% (95% CI: 97.0–99.4%). An independent analysis set with a high prevalence (45.8%) the NPV value was 87.8% (95% CI: 95% CI: 75.8–94.3%).

Conclusion

OvaWatch demonstrated high NPV across diverse data sets and promises utility as an effective diagnostic test supporting management of suspected benign or indeterminate mass to safely decrease or delay unnecessary surgeries.
Integrated conjugative plasmid drives high frequency chromosomal gene transfer in Sulfolobus islandicus
Authors: Sanchez-Nieves Ruben L. , Zhang Changyi , Whitaker Rachel J.
Published: January 2023

Gene transfer in crenarchaea has been observed within natural and experimental populations of Sulfolobus. However, the molecular factors that govern how gene transfer and recombination manifest themselves in these populations is still unknown. In this study, we examine a plasmid-mediated mechanism of gene transfer in S. islandicus that results in localized high frequency recombination within the chromosome. Through chromosomal marker exchange assays with defined donors and recipients, we find that while bidirectional exchange occurs among all cells, those possessing the integrated conjugative plasmid, pM164, mobilize a nearby locus at a significantly higher frequency when compared to a more distal marker. We establish that traG is essential for this phenotype and that high frequency recombination can be replicated in transconjugants after plasmid transfer. Mapping recombinants through genomic analysis, we establish the distribution of recombinant tracts with decreasing frequency at increasing distance from pM164. We suggest the bias in transfer is a result of an Hfr (high frequency recombination)-like conjugation mechanism in this strain. In addition, we find recombinants containing distal non-selected recombination events, potentially mediated by a different host-encoded marker exchange (ME) mechanism.
Why should we care about astrocytes in a motor neuron disease?
Authors: Stoklund Dittlau Katarina , Van Den Bosch Ludo
Published: January 2023

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults, causing progressive degeneration of motor neurons, which results in muscle atrophy, respiratory failure and ultimately death of the patients. The pathogenesis of ALS is complex, and extensive efforts have focused on unravelling the underlying molecular mechanisms with a large emphasis on the dying motor neurons. However, a recent shift in focus towards the supporting glial population has revealed a large contribution and influence in ALS, which stresses the need to explore this area in more detail. Especially studies into astrocytes, the residential homeostatic supporter cells of neurons, have revealed a remarkable astrocytic dysfunction in ALS, and therefore could present a target for new and promising therapeutic entry points. In this review, we provide an overview of general astrocyte function and summarize the current literature on the role of astrocytes in ALS by categorizing the potentially underlying molecular mechanisms. We discuss the current efforts in astrocyte-targeted therapy, and highlight the potential and shortcomings of available models.
An improved adaptive triangular mesh-based image warping method
Authors: Tang Wei , Jia Fangxiu , Wang Xiaoming
Published: January 2023

It is of vital importance to stitch the two images into a panorama in many computer vision applications of motion detection and tracking and virtual reality, panoramic photography, and virtual tours. To preserve more local details and with few artifacts in panoramas, this article presents an improved mesh-based joint optimization image stitching model. Since the uniform vertices are usually used in mesh-based warps, we consider the matched feature points and uniform points as grid vertices to strengthen constraints on deformed vertices. Simultaneously, we define an improved energy function and add a color similarity term to perform the alignment. In addition to good alignment and minimal local distortion, a regularization parameter strategy of combining our method with an as-projective-as-possible (APAP) warp is introduced. Then, controlling the proportion of each part by calculating the distance between the vertex and the nearest matched feature point to the vertex. This ensures a more natural stitching effect in non-overlapping areas. A comprehensive evaluation shows that the proposed method achieves more accurate image stitching, with significantly reduced ghosting effects in the overlapping regions and more natural results in the other areas. The comparative experiments demonstrate that the proposed method outperforms the state-of-the-art image stitching warps and achieves higher precision panorama stitching and less distortion in the overlapping. The proposed algorithm illustrates great application potential in image stitching, which can achieve higher precision panoramic image stitching.
Implications of stimulus-induced, rhythmic, periodic, or ictal discharges (SIRPIDs) in hospitalized patients
Authors: Martinez Paola , Sheikh Irfan , Westover M. Brandon , Zafar Sahar F.
Published: January 2023

Background

Stimulus-induced electroencephalographic (EEG) patterns are commonly seen in acutely ill patients undergoing continuous EEG monitoring. Despite ongoing investigations, the pathophysiology, therapeutic and prognostic significance of stimulus-induced rhythmic, periodic or ictal discharges (SIRPIDs) and how it applies to specific pathologies remain unclear. We aimed to investigate the clinical implications of SIRPIDs in hospitalized patients.

Methods

This is a retrospective single-center study of hospitalized patients from May 2016 to August 2017. We included patients above the age of 18 years who underwent >16 h of EEG monitoring during a single admission. We excluded patients with cardiac arrest and anoxic brain injury. Demographic data were obtained as well as admission GCS, and discharge modified Rankin Score (mRS). EEGs were reviewed for background activity in addition to epileptiform, periodic, and rhythmic patterns. The presence or absence of SIRPIDs was recorded. Our outcome was discharge mRS defined as good outcome, mRS 0–4, and poor outcome mRS, 5–6.

Results

A total of 351 patients were included in the final analysis. The median age was 63 years and 175 (50%) were women. SIRPIDs were identified in 82 patients (23.4%). Patients with SIRPIDs had a median initial GCS of 12 (IQR, 6–15) and a length of stay of 12 days (IQR, 6–15). They were more likely to have absent posterior dominant rhythm, decreased reactivity, and more likely to have spontaneous periodic and rhythmic patterns and higher frequency of burst suppression. After adjusting for baseline clinical variables, underlying disease type and severity, and EEG background features, the presence of SIRPIDs was also associated with poor outcomes classified as MRS 5 or 6 (OR 4.75 [2.74–8.24] p ≤ 0.0001).

Conclusion

In our cohort of hospitalized patients excluding anoxic brain injury, SIRPIDs were identified in 23.4% and were seen most commonly in patients with primary systemic illness. We found SIRPIDs were independently associated with poor neurologic outcomes. Several studies are indicated to validate these findings and determine the risks vs. benefits of anti-seizure treatment.
S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages
Authors: Rossi Rosanna , Douglas Andrew , Gil Sara Molina , Jabrah Duaa , Pandit Abhay , Gilvarry Michael , McCarthy Ray , Prendergast James , Jood Katarina , Redfors Petra , Nordanstig Annika , Ceder Erik , Dunker Dennis , Carlqvist Jeanette , Szikora István , Thornton John , Tsivgoulis Georgios , Psychogios Klearchos , Tatlisumak Turgut , Rentzos Alexandros , Doyle Karen M.
Published: January 2023

Background and purpose

Post-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH.

Methods

We analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis.

Results

PTIH was associated with higher S100b levels in clots (0.33 [0.08–0.85] vs. 0.07 [0.02–0.27] mm2, H1 = 6.021, P = 0.014*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0–23.0] vs. 14.0 [10.5–19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1–4] vs. 1 [1–2.5], H1 = 5.995, P = 0.014*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots.

Conclusions

Higher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation.
Association between fatigue and cytokine profiles in patients with ischemic stroke
Authors: Kirchberger Inge , Meisinger Christa , Freuer Dennis , Leone Vincenza , Ertl Michael , Zickler Philipp , Naumann Markus , Linseisen Jakob
Published: January 2023

Background

Chronic fatigue is a common symptom after a stroke. Studies suggested that chronic fatigue is caused by inflammatory or immunological processes but data are limited and contradictory. Thus, the present study aimed to identify specific biomarkers associated with fatigue in post-stroke patients and replicated the findings in a population-based study.

Methods

We investigated associations between 39 circulating biomarkers of inflammation and fatigue in 327 patients after an ischemic stroke included in the Stroke Cohort Augsburg (SCHANA) study and the “Metabolism, Nutrition and Immune System in Augsburg” (MEIA) study (n = 140). The Fatigue Assessment Scale (FAS) was used to assess the severity of fatigue. The serum concentrations of the biomarkers were measured using the Bio-Plex Pro™ Human Cytokine Screening Panel (Bio-Rad, USA). Multiple linear regression models adjusted for possible confounders were used to examine associations.

Results

In patients with stroke, SCGFb was inversely associated [−1.67, 95% confidence interval (CI) (−3.05; −0.29) p = 0.018], and in healthy subjects, G-CSF was positively associated [1.56, 95% CI (0.26; 2.87), p = 0.020] with an increasing FAS-score, while SCF was positively related in both samples [1.84, 95% CI (0.27; 3.42), p = 0.022 and 1.40, 95% CI (0.29; 2.52), p = 0.015]. However, after correction for multiple testing, all of these associations lost statistical significance.

Conclusion

The present findings suggested an association between the growth factor SCF and fatigue. Future research on cytokines as possible markers of fatigue should focus on a longitudinal design including a sufficiently large number of study participants to enable testing associations between certain cytokines and sub-groups of chronic fatigue.
Non-motor symptoms in multiple system atrophy: A comparative study with Parkinson's disease and progressive supranuclear palsy
Authors: Hu Wen-Zheng , Cao Ling-Xiao , Yin Jin-Hui , Zhao Xue-Song , Piao Ying-Shan , Gu Wei-Hong , Ma Jing-Hong , Wan Zhi-Rong , Huang Yue
Published: January 2023

Background

Non-motor symptoms (NMS) are compulsory clinical features for the clinical diagnosis of multiple system atrophy (MSA), some of which precede motor symptoms onset. To date, few studies have systematically investigated NMS in MSA and the timing of presenting NMS as the disease progresses. Clinically, MSA is difficult to be differentiated from Parkinson's disease (PD) and progressive supranuclear palsy (PSP), and the differences in NMS between MSA and PD/PSP remain unclear. The aim of this study was to compare the burden of NMS between MSA and PD/PSP and to delineate the timing of NMS presentation relative to the onset of motor symptoms in MSA.

Methods

A total of 61, 87, and 30 patients with MSA, PD, and PSP, respectively, were enrolled in this study. NMS was systematically assessed in all patients using the NMS scale (NMSS), and the onset of NMS relative to the onset of motor symptoms in MSA was investigated.

Results

MSA group had higher total NMSS scores (82.15 ± 46.10) than the PD (36.14 ± 30.78) and PSP (50.30 ± 55.05) groups (p < 0.001 overall). The number distribution pattern of the NMS was significantly different among the three parkinsonian disorders (p < 0.001 overall). In total, 85.2% of patients with MSA had more than 10 NMS, which was significantly higher than PD (28.7%) and PSP (33.3%). The frequency and scores of many NMSS subdomains and symptoms were higher in MSA than in PD and PSP (all p < 0.05). Multivariate logistic regression analysis revealed that patients with fainting, lack of motivation, swallowing, and loss of sexual interest could be attributed to MSA rather than PD or PSP, while patients with loss of concentration and forgetfulness were characteristic features of PD or PSP rather than MSA. REM-sleep behavior disorder (RBD), constipation, problems having sex, and loss of sexual interest preceded the motor symptoms onset of MSA by 2.81 ± 4.51, 1.54 ± 6.32, 1.35 ± 4.70, and 0.45 ± 3.61 years, respectively.

Conclusion

The NMS spectrum in MSA differs from that of PD and PSP. Patients with MSA have a higher NMS burden than patients with PD or PSP. RBD, constipation, problems having sex, and loss of sexual interest may become early diagnostic clinical markers of MSA.
Dual ankyrinG and subpial autoantibodies in a man with well-controlled HIV infection with steroid-responsive meningoencephalitis: A case report
Authors: Bartley Christopher M. , Ngo Thomas T. , Cadwell Cathryn R. , Harroud Adil , Schubert Ryan D. , Alvarenga Bonny D. , Hawes Isobel A. , Zorn Kelsey C. , Hunyh Trung , Teliska Lindsay H. , Kung Andrew F. , Shah Shailee , Gelfand Jeffrey M. , Chow Felicia C. , Rasband Matthew N. , Dubey Divyanshu , Pittock Sean J. , DeRisi Joseph L. , Wilson Michael R. , Pleasure Samuel J.
Published: January 2023

Neuroinvasive infection is the most common cause of meningoencephalitis in people living with human immunodeficiency virus (HIV), but autoimmune etiologies have been reported. We present the case of a 51-year-old man living with HIV infection with steroid-responsive meningoencephalitis whose comprehensive pathogen testing was non-diagnostic. Subsequent tissue-based immunofluorescence with acute-phase cerebrospinal fluid revealed anti-neural antibodies localizing to the axon initial segment (AIS), the node of Ranvier (NoR), and the subpial space. Phage display immunoprecipitation sequencing identified ankyrinG (AnkG) as the leading candidate autoantigen. A synthetic blocking peptide encoding the PhIP-Seq-identified AnkG epitope neutralized CSF IgG binding to the AIS and NoR, thereby confirming a monoepitopic AnkG antibody response. However, subpial immunostaining persisted, indicating the presence of additional autoantibodies. Review of archival tissue-based staining identified candidate AnkG autoantibodies in a 60-year-old woman with metastatic ovarian cancer and seizures that were subsequently validated by cell-based assay. AnkG antibodies were not detected by tissue-based assay and/or PhIP-Seq in control CSF (N = 39), HIV CSF (N = 79), or other suspected and confirmed neuroinflammatory CSF cases (N = 1,236). Therefore, AnkG autoantibodies in CSF are rare but extend the catalog of AIS and NoR autoantibodies associated with neurological autoimmunity.
Tenecteplase vs. alteplase for treatment of acute ischemic stroke: A systematic review and meta-analysis of randomized trials
Authors: Kobeissi Hassan , Ghozy Sherief , Turfe Bilal , Bilgin Cem , Kadirvel Ramanathan , Kallmes David F. , Brinjikji Waleed , Rabinstein Alejandro A.
Published: January 2023

Background and objectives

Several randomized controlled trials (RCTs) have compared tenecteplase to alteplase for treatment of acute ischemic stroke (AIS). Yet, there is no meta-analysis that includes the latest published RCTs of 2022. We sought to compare the safety and efficacy of tenecteplase vs. alteplase for the treatment of AIS through a meta-analysis of all published RCTs.

Methods

A systematic literature review of the English language literature was conducted using PubMed, Web of Science, Scopus, and Embase. We included RCTs that focused on patients with AIS treated with tenecteplase and alteplase. Multiple reviewers screened through potential studies to identify the final papers included in our analysis. Following PRISMA guidelines, multiple authors extracted data to ensure accuracy. Data were pooled using a random-effects model.

Results

Nine trials, with 3,706 patients, compared outcomes of patients treated with tenecteplase and alteplase for AIS. Both treatments resulted in comparable rates of modified Rankin Scale (mRS) 0–1 at 90 days (RR = 1.03; 95% CI = 0.97–1.10; P-value = 0.359) and mRS 0–2 at 90 days (RR = 1.03; 95% CI = 0.87–1.22; P-value = 0.749). There was no heterogeneity among included studies regarding mRS 0–1 rates (I2 = 26%; P-value = 0.211); however, there was significant heterogeneity in mRS 0–2 rates (I2 = 71%; P-value = 0.002). Similarly, rates of mortality (RR = 0.97; 95% CI = 0.81–1.16; P-value = 0.746) and symptomatic intracranial hemorrhage (sICH) rates (RR = 1.10; 95% CI = 0.75–1.61; P-value = 0.622) were comparable in both treatment groups. There was no significant heterogeneity among included studies in either mortality (I2 = 30%; P-value = 0.181) or sICH (I2 = 0%; P-value = 0.734) rates. Further analysis comparing dosing of tenecteplase (0.1, 0.25, 0.32, and 0.4 mg/kg) yielded no significant differences for any of the endpoints (mRS 0–1, mRS 0–2, sICH, and mortality) compared to alteplase.

Discussion

Based on available evidence from completed RCTs, tenecteplase has proven similar safety and efficacy to alteplase for treatment of AIS.
Developmental and acquired brain injury have opposite effects on finger coordination in children
Authors: Mimouni-Bloch Aviva , Shaklai Sharon , Levin Moran , Ingber Moria , Karolitsky Tanya , Grunbaum Sigal , Friedman Jason
Published: January 2023

The ability to coordinate finger forces to dexterously perform tasks develops in children as they grow older. Following brain injury, either developmental (as in cerebral palsy–CP) or acquired (as in traumatic brain injury—TBI), this developmental trajectory will likely be impaired. In this study, we compared finger coordination in a group of children aged 4–12 with CP and TBI to a group of typically developing children using an isometric pressing task. As expected, deficits were observed in functional tests (Jebsen Taylor test of hand function, Box and Block test) for both groups, and children in both groups performed the pressing task less well than the control group. However, differing results were observed between the CP and TBI groups when using the uncontrolled manifold hypothesis to look at the synergy index. This index measures the relative amount of “good” (does not affect the outcome measure) and “bad” (does affect the outcome measure) variability, where in this case the outcome measure is the total force produced by the fingers. While children with CP were more variable in their performance, their synergy index was not significantly different from typically developing children, suggesting the development of compensatory strategies. In contrast, the children following TBI showed performance that got worse as a function of age (i.e., the older children with TBI performed worse than the younger children with TBI). These differences between the groups may be a result of different areas of brain injury typically observed in CP and TBI, and the different amount of time that has passed since the injury.
Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy
Authors: Fu Xuefei , Feng Shuyu , Qin Huan , Yan Lin , Zheng Caiyan , Yao Kai
Published: January 2023

Microglia are the primary resident retinal macrophages that monitor neuronal activity in real-time and facilitate angiogenesis during retinal development. In certain retinal diseases, the activated microglia promote retinal angiogenesis in hypoxia stress through neurovascular coupling and guide neovascularization to avascular areas (e.g., the outer nuclear layer and macula lutea). Furthermore, continuously activated microglia secrete inflammatory factors and expedite the loss of the blood-retinal barrier which causes irreversible damage to the secondary death of neurons. In this review, we support microglia can be a potential cellular therapeutic target in retinopathy. We briefly describe the relevance of microglia to the retinal vasculature and blood-retinal barrier. Then we discuss the signaling pathway related to how microglia move to their destinations and regulate vascular regeneration. We summarize the properties of microglia in different retinal disease models and propose that reducing the number of pro-inflammatory microglial death and conversing microglial phenotypes from pro-inflammatory to anti-inflammatory are feasible for treating retinal neovascularization and the damaged blood-retinal barrier (BRB). Finally, we suppose that the unique properties of microglia may aid in the vascularization of retinal organoids.
Ultrasound-guided anterior iliopsoas muscle space block effectively reduces intraoperative hypotension in elderly adults undergoing hip surgery: A randomised controlled trial
Authors: Teng Qingyu , Wang Chengyu , Dong Jing , Yan Hai , Chen Moxi , Xu Tao
Published: January 2023

Background

Hypotension often occurs during hip surgery in elderly adults with conventional posterior lumbosacral plexus block.

Purpose

We conducted a randomised controlled trial to determine if simple iliopsoas space block can lower the incidence of intraoperative hypotension (IOH) and provide sufficient perioperative pain relief during hip fracture surgery in elderly adults.

Methods

Patients undergoing surgery for elderly hip fracture were randomised to receive either an anterior iliopsoas space block with a lateral femoral cutaneous nerve block or a posterior lumbosacral plexus block. The primary outcome was a composite measure of IOH incidence comprising frequency, absolute and relative hypotension durations.

Results

Compared to the posterior group, the iliopsoas space block group had a decreased median frequency of IOH [1.09 (0–2. 14) vs. 3 (1.6–4.8), p = 0.001, respectively] along with lower absolute [5 (0–10) min] and relative [minutes below systolic blood pressure of 100 mmHg in % of total anaesthesia time, 6.67 (0–7.65)] duration of IOH compared to the posterior group [35 (10–45) min, p = 0.008; 37.6 (12.99–66.18), p = 0.004, respectively]. The median pain levels in the post-anaesthesia care unit and median intraoperative sufentanil usage were comparable between the iliopsoas space group [2 (1–3); 8 (6–10) μg] and posterior group [1 (0–3); 5 (5–8) μg]. Thermal imaging revealed that the limb injected with the iliopsoas space block had a higher skin temperature than the unblocked limb in the sacral plexus innervated region.

Conclusion

A single iliopsoas space block lowers the IOH incidence and provides comparable perioperative analgesia to conventional lumbosacral plexus block.

Clinical Trial Registration

Trial registration at www.chictr.org.cn (ChiCTR2100051394); registered 22 September 2021.
Comparative proteomics of human milk casein fraction collected from women of Korean and Han ethnic groups in China
Authors: Wang Cuina , Lu Yingcong , Hu Jia , Yang Yang , Cheng Jianjun , Jiang Shilong , Guo Mingruo
Published: January 2023

Introduction

Human breast milk provides neonates with indispensable nutrition and function. Milk protein is one of the main constituents of breast milk. Human milk profiles can be influenced by many factors.

Methods

The present study aimed to investigate the difference in casein isolated from mature milk of healthy mothers of Korean and Han ethnic groups in China using data-independent acquisition (DIA) proteomics.

Results

A total of 535 proteins were identified and quantified in casein fraction samples from both groups. A total of 528 proteins were annotated to 52 Gene Ontology (GO) terms, the majority (94.13%) of which were distributed in the cell and cell parts of the cellular component. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that 106 proteins were involved in 23 pathways, the greatest (36.79%) in carbohydrate metabolism. There were 39 differentially expressed proteins (DEPs)–10 upregulated and 29 downregulated–between Korean and Han milk. The GO function of blood microparticles and KEGG pathway of Staphylococcus aureus infection for DEPs were the most significantly enriched (p < 0.05). Protein-protein interaction analysis revealed a network with 23 DEPs in 47 interactions, and the fibrinogen alpha chain ranked first as the hub protein.

Discussion

These data may provide useful technical guidance for the development of specific infant foods for certain populations.
Primary breast osteosarcoma in a patient previously treated for ipsilateral invasive ductal carcinoma: An unusual case report with clinical and genomic features
Authors: Zhu Siji , Wang Haoyu , Lin Lin , Fei Xiaochun , Wu Jiayi
Published: January 2023

Primary breast osteosarcoma is a rare subtype of breast malignancy with limited clinical evidence, inadequate biological understanding, and unmet treatment consensus. Here, we report an unusual case of primary breast osteosarcoma developing in the same quadrant of the breast 2 years after initial dissection and radiation of invasive ductal carcinoma. Thorough evaluations of imaging and pathology were conducted while genomic alterations of both primary and secondary tumors, as well as peripheral blood samples, were explored through the next-generation sequencing technique. A comprehensive review of the current literature was also performed on this rare malignancy.
Tumor burden score dictates prognosis of patients with combined hepatocellular cholangiocarcinoma undergoing hepatectomy
Authors: Deng Gang , Ren Jun-kai , Wang Hai-tao , Deng Liang , Chen Zu-bing , Fan You-wen , Tang Ya-jun , Zhang Tong , Tang Di
Published: January 2023

Background

The prognostic value of the tumor burden score (TBS) in patients with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remains unknown. This study aimed to investigate the impact of TBS on long-term outcomes after surgery.

Methods

Patients who underwent radical-intent resection between June 2013 and December 2019 were retrospectively reviewed. Kaplan–Meier curves were used to analyze patient survival, and disease-free survival (DFS) and overall survival (OS) were examined in relation to TBS.

Results

A total of 178 patients were included in this study, with 119 in the training cohort and 59 in the validation cohort. Kaplan–Meier curves showed that TBS was a strong prognostic indicator in patients with cHCC-CCA. Elevated TBS was associated with poorer DFS and OS (both P-value < 0.001) and was identified as an independent prognostic indicator. In addition, the prognostic value of TBS outperformed tumor size and number alone, microvascular invasion, and lymph node invasion. The prognostic significance of TBS was confirmed by the internal validation cohort.

Conclusions

The present study suggested the significance of tumor morphology in assessing the prognosis of patients with cHCC-CCA who undergoing curative resection. The TBS is a promising prognostic index in patients with cHCC-CCA. Elevated TBS was related to a lower long-term survival rate and was identified as an independent risk factor for poor DFS and OS. Further research is needed to verify our results.
Synergistic treatment of osteosarcoma with biomimetic nanoparticles transporting doxorubicin and siRNA
Authors: Zhao Jingtong , Mu Xupeng , Hou Xuejia , Zhang Xiaowen , Li Ping , Jiang Jinlan
Published: January 2023

Introduction

Osteosarcoma tumors are the most common malignant bone tumors in children and adolescents. Their treatment usually requires surgical removal of all detectable cancerous tissue and multidrug chemotherapy; however, the prognosis for patients with unresectable or recurrent osteosarcoma is unfavorable. To make chemotherapy safer and more effective for osteosarcoma patients, biomimetic nanoparticles (NPs) camouflaged by mesenchymal stem cell membranes (MSCMs) were synthesized to induce osteosarcoma cell apoptosis by co-delivering the anticancer drug doxorubicin hydrochloride(DOX) and a small interfering RNA (siRNA). Importantly, these NPs have high biocompatibility and tumor-homing ability. This study aimed to improve the efficacy of osteosarcoma therapy by using the synergistic combination of DOX and an siRNA targeting the apoptosis suppressor gene survivin.

Methods

Biomimetic NPs (DOX/siSUR-PLGA@MSCM NPs) were synthesized by coloading DOX and survivin siRNA (siSUR) into poly (lactide-co-glycolide acid) (PLGA) via a double-emulsion solvent evaporation method. The NPs were camouflaged by MSCMs to deliver both DOX and survivin-targeting siRNA and characterized and evaluated in terms of cellular uptake, in vitro release, in vitro and in vivo antitumor effects, and biosafety.

Results

DOX/siSUR-PLGA@MSCM NPs had good tumor-homing ability due to the MSCMs modification. The drug-laden biomimetic NPs had good antitumor effects in homozygous MG63 tumor-bearing mice due to the synergistic effect of the drug combination.

Conclusion

DOX/siSUR-PLGA@MSCM NPs can show improved therapeutic effects in osteosarcoma patients due to the combination of a chemotherapeutic drug and gene therapy based on their good tumor targeting and biosafety.
Current status and future promise of next-generation poly (ADP-Ribose) polymerase 1-selective inhibitor AZD5305
Authors: Zheng Jingcao , Li Zhengyu , Min Wenjiao
Published: January 2023

The family of poly (ADP-ribose) polymerases (PARPs) consists of 17 members, which have been demonstrated as having effects on a series of cellular processes, including DNA replication and repair. PARP inhibitors (PARPi) suppress DNA repair through “PARP trapping”, thus, constitute an important treatment option for cancer nowadays. In addition, PARP inhibition and homologous recombination repair (HRR) defects are synthetically lethal, giving a promising therapeutic for homologous recombination repair deficient (HRD) tumors including BRCA mutation. However, overlapping hematologic toxicity causes PARPi to fail in combination with some first-line chemotherapies. Furthermore, recent literature has demonstrated that PARP1 inhibition and PARP1-DNA trapping are key for antitumor activity in HRD cancer models. Currently approved PARPi have shown varying levels of selectivity for the entire 17-member PARP family, hence contribute to toxicity. Together, these findings above have provided the necessity and feasibility of developing next-generation PARPi with improved selectivity for PARP1, expanding significant clinical values and wide application prospects both in monotherapy and combination with other anticancer agents. In this review, we summery the latest research of current approved PARPi, discuss the current status and future promise of next-generation PARP1-selective inhibitor AZD5305, including its reported progress up to now and anticipated impact on clinical.
Nephroprotective potential of Polyalthia longifolia roots against vancomycin-induced renal toxicity in experimental animals
Authors: Das Kuntal , Muthukumar A. , Almuqbil Mansour , Imran Mohd. , Rabaan Ali A. , Halwani Muhammad A. , Garout Mohammed , Alsaleh Abdulmonem A. , Alissa Mohammed , Alwashmi Ameen S. S. , Alshehri Ahmad A. , Alsayyah Ahmed , Bhavani Keserla , Mittal Swati , Gayathri R. , Alomar Nasser Fawzan , Rabbani Syed Imam , Basheeruddin Asdaq Syed Mohammed
Published: January 2023

This study was done to investigate the possible nephroprotective effect of an ethanolic root extract of Polyalthia Longifolia (PL) on vancomycin-induced nephrotoxicity using curative and protective models. Vancomycin (150 mg/kg, intravenous) was given to healthy Wistar albino rats in the curative model before the start of treatment, whereas the protective group received vancomycin at the conclusion of the 10-day treatment procedure. Animals were divided into six groups for both models; group I served as the normal control, while groups II, III, IV, V, and VI were kept as toxic control, standard (selenium, 6 mg/kg), LDPL (low dose of PL 200 mg/kg), HDPL (high dose of PL 400 mg/kg), and HDPL + selenium (interactive) groups, respectively. Renal biomarkers [(uric acid, creatinine, blood urea nitrogen (BUN), serum proteins], and blood electrolyte levels were measured for all tested groups. When compared to the vancomycin group, the HDPL significantly (p < 0.01) showed greater effectiveness in lowering the BUN, potassium, and calcium levels. Additionally, in the curative model, there was a significant (p < 0.05) decrease in the blood levels of uric acid, creatinine, BUN, potassium, and calcium in the animals who received the combination of selenium and HDPL. Both LDPL and HDPL did not provide any distinguishable effect in the protective model, but groups that received HDPL with selenium did provide detectable protection by significantly lowering their levels of uric acid, BUN, serum potassium, and total serum protein in comparison to the vancomycin control group. These findings indicate that, whether administered before or after renal damage is induced, the Polyalthia longifolia root extract provided only modest protection to nephrons, which require selenium support to prevent vancomycin-induced kidney damage.