bluuebunny/crossref_metadata_2025 huggingface dataset:
Progression of histological lesions after ABO incompatible kidney transplantation
Authors: Guy Pierre , Delas Audrey , Esposito Laure , Cointault Olivier , Colombat Magali , Congy-Jolivet Nicolas , Raynaud Marc , Kamar Nassim , Del Bello Arnaud
Published: October 2022

Recent large meta-analyses suggested a poorer long-term patients’ and grafts’ outcomes after ABO incompatible (ABOi) living-donor kidney transplantation (LDKT) compared to ABO compatible LDKT. However, little is known about the long-term histological pattern after ABOi LDKT. We compared the histological features observed on protocol biopsies from 03/11 to 11/19 in 94 ABOi LDKT (including 14 with preformed Donor Specific Antibodies, pDSAs), 27 LDKT ABO compatible (ABOc) with pDSAs, and 21 ABOc without pDSAs) during the first five years post transplantation. During the first 5 years post-transplantation, a progression of chronic lesions (patients with a ci >0 raised from 11% to 65%, p<0.0001, patients with a ct >0 raised from 29% to 78%, p<0.0001) was observed in ABOi LDKT without pDSAs. Histological patterns of evolution were comparable to those observed in ABOc kidney transplant patients. Microvascular inflammation was lower in ABOi LDKT without pDSAs compared to those with pDSAs (ABOi or ABOc). At last follow-up, 28 months, IQR (15-48) post-transplantation, 29 patients (36%) had a severe graft dysfunction (defined by a CKD-epi eGFR < 30 mL/min/1.73m²). The donor age was a predictive factor for the development of severe kidney allograft dysfunction at last follow-up (HR= 1.05, 95% CI [1.05-1.10], p= 0.03).

Hence, long-term histological analysis of ABOi LDKT shows only an increase of chronic interstitial and tubular atrophy changes, without active lesions. These data confirm that ABOi LDKT programs can be securely developed.
Case report: Senescence as mechanism of resistance to Pembrolizumab in a Lymphoma patient who failed CD19-Targeted CAR-T cell therapy
Authors: De Matteis Serena , Casadei Beatrice , Lolli Ginevra , Dicataldo Michele , Barbato Francesco , Dan Elisa , Paccagnella Andrea , Sinigaglia Barbara , Bertuzzi Clara , Arcari Annalisa , Zazzeroni Luca , Bernuzzi Patrizia , Laprovitera Noemi , Storci Gianluca , Bertuccio Salvatore Nicola , Ferracin Manuela , Bonafè Massimiliano , Zinzani Pier Luigi , Bonifazi Francesca
Published: October 2022

Background

T cells engineered to target CD19 antigen on neoplastic B cells represent the most striking example of CAR-T cell therapy. The success rate of this therapy is affected by several limitations: target antigen loss, and/or acquisition of a senescent/exhausted phenotype by CAR and non-CAR T cells.

Case presentation

We report on a patient affected by refractory Diffuse Large B-cell Lymphoma who was resistant to CAR T-cell therapy and to two cycles post CAR-T of pembrolizumab (PBZ) due to the evolution into a B-cell Hodgkin-like lymphoma. Owing to the CD30 expression and the Hodgkin-like phenotype, the patient was ultimately treated with Brentuximab-Vedotin and finally underwent remission. Upon PBZ treatment, 100% of circulating CAR-T+ cells showed a persistent CD8+ senescent/exhausted phenotype, while an increase in the percentage of senescent cells was found in the non-CAR CD8+ T cells compartment.

Conclusions

PBZ is not able to reinvigorate exhausted CAR+ T cells and to confer durable clinical response. We hypothesize that the phenomenon is due to the senescent phenotype of CAR+ T cells, which did not allow PBZ-induced reactivation and proliferative rescue. The phenomenon, together with the loss of CAR-T target CD19 and the shift of non-CAR CD8+ T cells towards a senescent phenotype likely contributed to set up an immune landscape with poor antitumor capacity.
The IOP lowering effects of “planning” selective laser trabeculoplasty in open angle glaucoma
Authors: Chu Yi-Ching , Chang Pei-Yao , Wang Jia-Kang , Huang Tzu-Lun , Hsu Yung-Ray
Published: October 2022

Purpose

To investigate whether the planning of selective laser trabeculoplasty (SLT) influences the intraocular pressure (IOP) in patients with open angle glaucoma (OAG).

Methods

In this retrospective case-control study conducted on patients with OAG who planned to undergo SLT treatment (SLT group) or a visual field examination (VF group), we collected the demographic data, IOP on the planning day and on the scheduled day of the SLT treatment or VF examination. ΔIOP was defined as the IOP change between the planning day and the scheduled day. We used multivariable regression analyses and linear mixed model to evaluate the association between the abovementioned factors and ΔIOP in the VF group and the treatment eye (SLTt) and fellow eye (SLTf) of the SLT group.

Results

One hundred and fifty-three eyes of 102 patients with OAG were included, of which 51 patients in the SLT group and 51 patients in the VF group. The ΔIOP was −1.92 ± 2.77 mmHg in the SLTt, −0.65 ± 2.47 mmHg in the SLTf and −0.08 ± 1.73 mmHg in the VF group (P < 0.05). Both multivariable regression analysis between the VF and SLTt group and linear mixed model in the SLT group showed significant negative association between the ΔIOP and SLT arrangement (P < 0.05). There was no significant association between ΔIOP and age, gender, baseline IOP, IOP fluctuation, nor SE.

Conclusions

The IOP was significantly reduced in patients with OAG after “planning” of SLT treatment, even without actual performing the laser treatment in our retrospective case-control study.
Milder outcomes of SARS-CoV-2 genetically confirmed reinfections compared to primary infections with the delta variant: A retrospective case-control study
Authors: Suljič Alen , Sočan Maja , Mrzel Maja , Lunar Maja M. , Korva Miša , Štorman Alenka , Prosenc Katarina , Janežič Sandra , Žohar-Čretnik Tjaša , Zupanič Tina , Poljak Mario , Avšič-Županc Tatjana
Published: October 2022

Background

SARS-CoV-2 infection does not confer long immunity. However, studies suggest that prior infection is associated with lower risk of reinfection and milder outcomes of recurrent infections. The aims of this retrospective observational case-control study were to describe the clinical and molecular characteristics of genetically confirmed Delta reinfection cases and to assess the potential protective role of preceding infection on the severity of reinfection.

Methods

We used next generation sequencing (NGS) to explore if cases with two positive real time RT-PCR tests > 90 days apart were infected with a different SARS-CoV-2 variant. Cases with confirmed reinfection between August 1st and October 31st, 2021 (the Delta wave) in Slovenia were matched 1:4 by age, sex and timeframe (week of positive test) with individuals with primary infection. Sociodemographic and epidemiologic data, vaccination status, and data on hospitalization and outcome of infection were retrieved from several centralized and standardized national databases. Additional epidemiologic surveys were performed on a limited number of cases and controls.

Results

We identified 628 cases of genetically confirmed reinfection during the study period and matched them with 2,512 control subjects with Delta primary infection. Primary infections in individuals with reinfection were mainly caused by B.1.258.17 (51.1%), followed by B.1.1.7 (15.1%) and reinfection was detected on average 271 days after primary infection (range 101–477 days). Our results show a substantially lower probability of hospitalization in cases with reinfection compared with controls (OR: 0.21, p = 0.017), but no significant difference was observed in intensive care unit admission and deaths. We observed a significantly lower proportion of vaccinated individuals among cases compared to controls (4.5% vs. 28.2%), suggesting that hybrid immunity leads to lower probability of reinfection. Detailed analysis of the temporal distribution of variants, responsible for reinfections, showed no significant differences in reinfection potential.

Conclusion

Reinfection with the SARS-CoV-2 Delta variant resulted in fewer hospitalizations compared to the primary Delta infection, suggesting that primary infection may, to some extent, produce at least short lasting protective immunity. This study provides additional insight into the reinfection dynamics that may allow appropriate public health measures to be taken in subsequent waves of the COVID-19 pandemic.
Differential retention of adalimumab and etanercept biosimilars compared to originator treatments: Results of a retrospective French multicenter study
Authors: Larid Guillaume , Baudens Guy , Dandurand Alexis , Coquerelle Pascal , Goeb Vincent , Guyot Marie Hélène , Marguerie Laurent , Maury Frédéric , Veillard Eric , Houvenagel Eric , Salmon Jean-Hugues , Flipo René-Marc , Gervais Elisabeth
Published: October 2022

Objectives

Previous studies demonstrated equivalence in terms of efficacy and safety of biosimilars (bsDMARDs) compared to original treatments (boDMARDs) and in switching situations. Less is known about what happens when initiating a bsDMARD in a molecule naïve patient. The objectives of our study were to compare the retention of treatment of subcutaneous boDMARDs and bsDMARDs globally, depending on the disease [rheumatoid arthritis (RA), spondyloarthritis (SpA), or psoriatic arthritis (PsA)], molecule [etanercept (ETN) or adalimumab (ADA)], line of treatment, or presence of citrate in the context of first use of each molecule (namely initiation) and to analyze treatment retention’s predictive factors.

Materials and methods

This multicenter retrospective study used data from shared medical records of the RIC-FRANCE network, encompassing the prescription of hospital rheumatologists and attached practitioners, of patients with RA, SpA, or PsA, with the starting ETN between 03/10/2016 and 31/07/2020, or ADA between 23/10/2018 and 31/07/2020. Clinical data were collected from medical records. Retention analysis was performed using Kaplan–Meier curves and the log-rank test. Retention’s predictive factors were analyzed using Cox proportional-hazard ratio.

Results

Eight hundred forty-five prescriptions were analyzed: 340 boDMARDs and 505 bsDMARDs. About 57% of prescriptions concerned women. The mean age was 51.8 years. About 38% were prescriptions for RA, 16% for PsA, and 46% for SpA. An increase in the initiation over time was observed for both ETN and ADA. The retention rate of bsDMARDs was superior to boDMARDs’ one (39 vs. 23 months; p = 0.045). When molecules are compared, the difference was significant only for ETN (45 vs. 19 months for boDMARD; p = 0.0265). When comparing diseases, the difference in favor of bsDMARDs was significant in patients with RA only (p = 0.041). Citrated treatments displayed better retention compared to citrate-free treatments (p = 0.0137). Multivariable analysis of predictive factors for the cessation of treatment found shorter disease duration, boDMARD prescription, hospital practitioner prescription, late line of treatment, and female sex as significant. More side effects were observed with boDMARDs, especially more infections (17.8% vs. 7.8%).

Conclusion

Even if bsDMARDs’ prescription increases over time, its penetration rate is still below expectations. bsDMARDs displayed better retention compared to boDMARDs, especially for ETN, and in patients with RA. Citrated treatments had better retention. Prescription by a full-time hospital-based rheumatologist is associated with poorer retention.
Research of cervical microbiota alterations with human papillomavirus infection status and women age in Sanmenxia area of China
Authors: Hu Jintao , Wu Yuhan , Quan Lili , Yang Wenjuan , Lang Jidong , Tian Geng , Meng Bo
Published: October 2022

Background

Human papillomavirus (HPV) infection is the leading cause of cervical cancer. More and more studies discovered that cervical microbiota (CM) composition correlated with HPV infection and the development of cervical cancer. However, more studies need to be implemented to clarify the complex interaction between microbiota and the mechanism of disease development, especially in a specific area of China.

Materials and methods

In this study, 16S rDNA sequencing was applied on 276 Thin-prep Cytologic Test (TCT) samples of patients from the Sanmenxia area. Systematical analysis of the microbiota structure, diversity, group, and functional differences between different HPV infection groups and age groups, and co-occurrence relationships of the microbiota was carried out.

Results

The major microbiota compositions of all patients includeLactobacillus iners,Escherichia coli,Enterococcus faecalis, andAtopobium vaginaeat species level, andStaphylococcus,Lactobacillus,Gardnerella,Bosea,Streptococcus, andSneathiain genus level. Microbiota diversity was found significantly different between HPV-positive (Chao1 index: 98.8869,p< 0.01), unique-268 infected (infections with one of the HPV genotype 52, 56, or 58, 107.3885,p< 0.01), multi-268 infected (infections with two or more of HPV genotype 52, 56, and 58, 97.5337,p= 0.1012), other1 (94.9619,p< 0.05) groups and HPV-negative group (83.5299). Women older than 60 years old have higher microbiota diversity (108.8851,p< 0.01,n= 255) than younger women (87.0171,n= 21). The abundance ofGardnerellaandAtopobium vaginaewas significantly higher in the HPV-positive group than in the HPV-negative group, whileBurkholderiaceaeandMycoplasmawere more abundant in the unique-268 group compared to the negative group.Gamma-proteobacteriaandPseudomonaswere found more abundant in older than 60 patients than younger groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) analysis revealed the effects on metabolism by microbiota that the metabolism of cells, proteins, and genetic information-related pathways significantly differed between HPV-negative and positive groups. In contrast, lipid metabolism, signal transduction, and cell cycle metabolism pathway significantly differed between multi-268 and negative groups.

Conclusion

The HPV infection status and age of women were related to CM’s diversity and function pathways. The complex CM co-occurrent relationships and their mechanism in disease development need to be further investigated.
The plasmid-encoded lactose operon plays a vital role in the acid production rate of Lacticaseibacillus casei during milk beverage fermentation
Authors: Li Xiaoxia , Zhai Zhengyuan , Hao Yanling , Zhang Ming , Hou Caiyun , He Jingjing , Shi Shaoqi , Zhao Zhi , Sang Yue , Ren Fazheng , Wang Ran
Published: October 2022

Lacticaseibacillus casei is used extensively in the fermented milk-beverage industry as a starter culture. Acid production capacity during fermentation is the main criterion for evaluating starters although it is strain-dependent. In this study, the acid production rates of 114 L. casei strains were determined and then classified into high acid (HC), medium acid (MC), and low acid (LC) groups. Comparative genomics analysis found that the lac operon genes encoding the phosphoenolpyruvate-lactose phosphotransferase system (PTSLac) were located on plasmids in the HC strains; however, it is notable that the corresponding operons were located on the chromosome in LC strains. Real-time PCR analysis showed that the copy numbers of lac operon genes in HC strains were between 3.1 and 9.3. To investigate the relationship between copy number and acid production rate, the lac operon cluster of the HC group was constitutively expressed in LC strains. The resulting copy numbers of lac operon genes were between 15.8 and 18.1; phospho-β-galactosidase activity increased by 1.68–1.99-fold; and the acid production rates increased by 1.24–1.40-fold, which enhanced the utilization rate of lactose from 17.5 to 42.6% in the recombinant strains. The markedly increased expression of lac operon genes increased lactose catabolism and thereby increased the acid production rate of L. casei.
Glutathione deficiency in the pathogenesis of SARS-CoV-2 infection and its effects upon the host immune response in severe COVID-19 disease
Authors: Labarrere Carlos A. , Kassab Ghassan S.
Published: October 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 19 (COVID-19) has numerous risk factors leading to severe disease with high mortality rate. Oxidative stress with excessive production of reactive oxygen species (ROS) that lower glutathione (GSH) levels seems to be a common pathway associated with the high COVID-19 mortality. GSH is a unique small but powerful molecule paramount for life. It sustains adequate redox cell signaling since a physiologic level of oxidative stress is fundamental for controlling life processes via redox signaling, but excessive oxidation causes cell and tissue damage. The water-soluble GSH tripeptide (γ-L-glutamyl-L-cysteinyl-glycine) is present in the cytoplasm of all cells. GSH is at 1–10 mM concentrations in all mammalian tissues (highest concentration in liver) as the most abundant non-protein thiol that protects against excessive oxidative stress. Oxidative stress also activates the Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) redox regulator pathway, releasing Nrf2 to regulate the expression of genes that control antioxidant, inflammatory and immune system responses, facilitating GSH activity. GSH exists in the thiol-reduced and disulfide-oxidized (GSSG) forms. Reduced GSH is the prevailing form accounting for >98% of total GSH. The concentrations of GSH and GSSG and their molar ratio are indicators of the functionality of the cell and its alteration is related to various human pathological processes including COVID-19. Oxidative stress plays a prominent role in SARS-CoV-2 infection following recognition of the viral S-protein by angiotensin converting enzyme-2 receptor and pattern recognition receptors like toll-like receptors 2 and 4, and activation of transcription factors like nuclear factor kappa B, that subsequently activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) expression succeeded by ROS production. GSH depletion may have a fundamental role in COVID-19 pathophysiology, host immune response and disease severity and mortality. Therapies enhancing GSH could become a cornerstone to reduce severity and fatal outcomes of COVID-19 disease and increasing GSH levels may prevent and subdue the disease. The life value of GSH makes for a paramount research field in biology and medicine and may be key against SARS-CoV-2 infection and COVID-19 disease.
Phenotypic and genotypic characterization of antimicrobial resistance profiles in Salmonella isolated from waterfowl in 2002–2005 and 2018–2020 in Sichuan, China
Authors: Guan Ying , Li Yanwan , Li Jin , Yang Zhishuang , Zhu Dekang , Jia Renyong , Liu Mafeng , Wang Mingshu , Chen Shun , Yang Qiao , Wu Ying , Zhang Shaqiu , Gao Qun , Ou Xumin , Mao Sai , Huang Juan , Sun Di , Tian Bin , Cheng Anchun , Zhao Xinxin
Published: October 2022

Salmonella enterica is a widespread foodborne pathogen with concerning antimicrobial resistance (AMR). Waterfowl are a major source of Salmonella transmission, but there are few systematic studies on Salmonella prevalence in waterfowl species. In this study, 126 Salmonella isolates (65 collected in 2018–2020 and 61 collected in 2002–2005) were obtained from waterfowl samples in Sichuan, China. Their serotypes, pulsed-field gel electrophoresis (PFGE) types, and phenotypic and genotypic AMR profiles were systematically examined. The isolates were distributed in 7 serotypes, including serovars Enteritidis (46.0%), Potsdam (27.8%), Montevideo (7.9%), Cerro (6.3%), Typhimurium (4.8%), Kottbus (4.0%) and Apeyeme (3.2%). Their PFGE characteristics were diverse; all isolates were distributed in four groups (cutoff value: 60.0%) and 20 clusters (cutoff value: 80.0%). Moreover, all isolates were multidrug resistant, and high rates of AMR to lincomycin (100.0%), rifampicin (100.0%), sulfadiazine (93.7%), erythromycin (89.7%), ciprofloxacin (81.0%), and gentamicin (75.4%) were observed. Finally, 49 isolates were subjected to whole-genome sequencing, and a wide variety of AMR genes were found, including multiple efflux pump genes and specific resistance genes. Interestingly, the tet(A)/tet(B) and catII resistance genes were detected in only isolates obtained in the first collection period, while the gyrA (S83F, D87N and D87G) and gyrB (E466D) mutations were detected at higher frequencies in the isolates obtained in the second collection period, supporting the findings that isolates from different periods exhibited different patterns of resistance to tetracycline, chloramphenicol and nalidixic acid. In addition, various incompatible plasmid replicon fragments were detected, including Col440I, Col440II, IncFIB, IncFII, IncX1, IncX9, IncI1-I and IncI2, which may contribute to the horizontal transmission of AMR genes and provide competitive advantages. In summary, we demonstrated that the Salmonella isolates prevalent in Sichuan waterfowl farms exhibited diverse serotypes, multiple AMR phenotypes and genotypes, and AMR changes over time, indicating their potential risks to public health.
Leguminous cover crops and soya increased soil fungal diversity and suppressed pathotrophs caused by continuous cereal cropping
Authors: Yu Shuting , Wang Tianshu , Meng Yili , Yao Shuihong , Wang Li , Zheng Haotian , Zhou Yanzheng , Song Zewei , Zhang Bin
Published: October 2022

The enrichment of soil-borne fungal pathogens and a high input of mineral fertilizer in the continuous cropping of cereal crops have raised a concern about soil health deterioration. Conversion of continuous cereal cropping to a legume-involved system alters the soil fungal community. However, when a leguminous cover crop is grown with a succeeding legume grain crop such as soya (Glycine max L. Merril), the effects on the soil fungal community when two legumes are involved in the crop system remain unclear. Thus, the effects of the cover crop on the soil fungal community under a succession of soya and a succession of maize (Zea mays L.) were clarified: a continuous wheat (Triticum aestivum L.)–maize cropping system was converted to new rotation systems with three cover crop treatments: leguminous vetch (Vicia sativa L.), a mixture of vetch and rye (Secale cereale L.), and fallow, succeeded by soya or maize in this study. The soil fungal community at the harvest of soya and maize were determined using high-throughput sequencing of ITS2 amplicons. Compared to a wheat–maize rotation system, all of the new rotation systems that involved leguminous crops or fallow increased the soil fungal diversity and suppressed pathotrophs by reducing the soil NH4+, NO3−, available K, and available P concentrations. Different cover crops changed the fungal community composition, but their effect was overwhelmed by the strong effect of succeeding soya, which induced minor shifts among the cover crop treatments under soya than maize. The Vetch–Soya system exhibited the highest fungal diversity, which have been due to an increase of symbiotrophs. Replacing wheat with mixed vetch and rye most greatly suppressed the pathotrophs, and this suppression effect was stronger when succeeded by maize than by soya. These results showed the short-term benefits of legume–legume succession and legume–cereal mixed cover crops for increasing fungal diversity and suppressing pathotrophs. Further study is needed to examine the long-term effects of Vetch–Soya on the accumulation of legume-associated pathogens.
Tailored light emission from color centers in nanodiamond using self-assembled photonic crystals
Authors: Sharma Sachin , Ashish  , Nair Rajesh V.
Published: October 2022

The defect centers in solid-state materials especially the nitrogen-vacancy (NV) centers in diamond have shown a tremendous potential for their utilization in quantum technology applications. However, they exhibit certain drawbacks such as the feeble zero phonon line with huge phonon contribution and the higher lifetime values. Here, we present a novel approach to control the spontaneous emission from NV centers in nanodiamond using engineered self-assembled photonic crystals. Using two complimentary emission measuring geometries at room temperature, we show a 63% suppression and 17% enhancement of NV center emission intensity using photonic stopgap, supported with simulations. The emission rates are modified in a broad spectral range of NV center emission and are consistent with the Barnett–Loudon sum rule. The results are crucial for emerging quantum technologies using NV centers in diamond.
Comparison of vacuum pressures and suction forces generated by different pump systems for aspiration thrombectomy
Authors: Kim Sum , Lee Jong Young
Published: October 2022

Objective

Aspiration thrombectomy is used to treat endovascular stroke treatment by clot removal through vacuum and suction forces. We aimed to investigate the pressures and suction forces generated by different pump systems for aspiration.

Methods

Vacuum pressure was measured using a vacuum gauge with a closed tip for a 60cc syringe and aspiration pumps. Using an artificial thrombus made from polyvinyl alcohol hydrogel and latex membrane, we assessed the catheter tip force generated on an artificial thrombus using 5Fr Sofia and 6Fr Sofia PLUS intermediate catheters combined with Penumbra Jet Engine or Stryker Medela AXS Universal Aspiration Set. Subsequently, we calculated the catheter tip forces based on the pressure [catheter tip size (force = area × pressure)], and compared with the measured catheter tip force.

Results

The 60cc syringe generated the highest vacuum pressure. Among the automatic pumps, the Penumbra jet engine generated the highest vacuum pressure. The catheter tip forces on the artificial thrombus and latex membrane were 18.5 ± 1.70 and 8.0 ± 1.23 gf, respectively, and 13.9 ± 1.37 and 5.6 ± 0.83 gf, respectively using the 5 Fr Sofia with the Penumbra Jet Engine and the Stryker Medela AXS Universal Aspiration Set, respectively. The corresponding values for the 6 Fr Sofia PLUS with the Penumbra Jet Engine and Stryker Medela AXS Universal Aspiration Set were 39.7 ± 3.88 and 20.7 ± 0.92 gf and 25.4 ± 4.96 and 18.0 ± 0.84 gf. For a constant catheter diameter and the automatic pump, the catheter tip force was significantly larger in the artificial thrombus than latex membrane (p < 0.001, ANOVA).

Conclusion

The catheter diameter, vacuum pressure, and clot softness are positively correlated with the catheter tip force.
Effects of transcranial direct current stimulation on motor skills learning in healthy adults through the activation of different brain regions: A systematic review
Authors: Qi Shuo , Liang Zhiqiang , Wei Zhen , Liu Yu , Wang Xiaohui
Published: October 2022

Objective

This systematic review aims to analyze existing literature of the effects of transcranial direct current stimulation (tDCS) on motor skills learning of healthy adults and discuss the underlying neurophysiological mechanism that influences motor skills learning.

Methods

This systematic review has followed the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The PubMed, EBSCO, and Web of Science databases were systematically searched for relevant studies that were published from database inception to May 2022. Studies were included based on the Participants, Intervention, Comparison, Outcomes, and Setting inclusion strategy. The risk of bias was evaluated by using the Review manager 5.4 tool. The quality of each study was assessed with the Physiotherapy Evidence Database (PEDro) scale.

Results

The electronic search produced 142 studies. Only 11 studies were included after filtering. These studies performed well in terms of distribution, blinding availability and selective reporting. They reported that tDCS significantly improved motor skills learning. The main outcomes measure were the improvement of the motor sequence tasks and specific motor skills. Nine studies showed that tDCS interventions reduced reaction time to complete motor sequence tasks in healthy adults and two studies showed that tDCS interventions improved golf putting task performance.

Conclusion

The included studies showed that tDCS can help healthy adults to improve the motor skills learning by activating different brain regions, such as the primary motor cortex, left dorsolateral prefrontal cortex and right cerebellum. However, the number of included studies was limited, and the sample sizes were small. Therefore, more studies are urgently needed to validate the results of current studies and further explore the underlying neurophysiological mechanisms of tDCS in the future.
Changes in primary somatosensory cortex following allogeneic hand transplantation or autogenic hand replantation
Authors: Philip Benjamin A. , Valyear Kenneth F. , Cirstea Carmen M. , Baune Nathan A. , Kaufman Christina , Frey Scott H.
Published: October 2022

Former amputees who undergo allogeneic hand transplantation or autogenic hand replantation (jointly, “hand restoration”) present a unique opportunity to measure the range of post-deafferentation plastic changes in the nervous system, especially primary somatosensory cortex (S1). However, few such patients exist, and previous studies compared single cases to small groups of typical adults. Here, we studied 5 individuals (n = 8 sessions: a transplant with 2 sessions, a transplant with 3 sessions, and three replants with 1 session each). We used functional magnetic resonance imaging (fMRI) to measure S1 responsiveness to controlled pneumatic tactile stimulation delivered to each patient's left and right fingertips and lower face. These data were compared with responses acquired from typical adults (n = 29) and current unilateral amputees (n = 19). During stimulation of the affected hand, patients' affected S1 (contralateral to affected hand) responded to stimulation in a manner similar both to amputees and to typical adults. The presence of contralateral responses indicated grossly typical S1 function, but responses were universally at the low end of the range of typical variability. Patients' affected S1 showed substantial individual variability in responses to stimulation of the intact hand: while all patients fell within the range of typical adults, some patient sessions (4/8) had substantial ipsilateral responses similar to those exhibited by current amputees. Unlike hand restoration patients, current amputees exhibited substantial S1 reorganization compared to typical adults, including bilateral S1 responses to stimulation of the intact hand. In all three participant groups, we assessed tactile localization by measuring individuals' ability to identify the location of touch on the palm and fingers. Curiously, while transplant patients improved their tactile sensory localization over time, this was uncorrelated with changes in S1 responses to tactile stimuli. Overall, our results provide the first description of cortical responses to well-controlled tactile stimulation after hand restoration. Our case studies indicate that hand restoration patients show S1 function within the range of both typical adults and amputees, but with low-amplitude and individual-specific responses that indicate a wide range of potential cortical neurological changes following de-afferentation and re-afferentation.
PAMPAS: A PsychoAcoustical Method for the Perceptual Analysis of multidimensional Sonification
Authors: Ziemer Tim , Schultheis Holger
Published: October 2022

The sonification of data to communicate information to a user is a relatively new approach that established itself around the 1990s. To date, many researchers have designed their individual sonification from scratch. There are no standards in sonification design and evaluation. But researchers and practitioners have formulated several requirements and established several methods. There is a wide consensus that psychoacocustics could play an important role in the sonification design and evaluation phase. But this requires a) an adaption of psychoacoustic methods to the signal types of sonification and b) a preparation of the sonification for the psychoacoustic experiment procedure. In this method paper, we present a PsychoAcoustical Method for the Perceptual Analysis of multidimensional Sonification (PAMPAS) dedicated to the researchers of sonification. A well-defined and well-established, efficient, reliable, and replicable just noticeable difference (JND) experiment using the maximum likelihood procedure (MLP) serves as the basis to achieve perceptual linearity of parameter mapping during the sonification design stage and to identify and quantify perceptual effects during the sonification evaluation stage, namely the perceptual resolution, hysteresis effects and perceptual interferences. The experiment results are scores from standardized data space and a standardized procedure. These scores can serve to compare multiple sonification designs of a single researcher or even among different research groups. This method can supplement other sonification designs and evaluation methods from a perceptual viewpoint.
Assessing the contrast sensitivity function in myopic parafovea: A quick contrast sensitivity functions study
Authors: Xu Zixuan , Zhuang Yijing , Chen Zhipeng , Hou Fang , Chan Lily Y. L. , Feng Lei , Ye Qingqing , He Yunsi , Zhou Yusong , Jia Yu , Yuan Junpeng , Lu Zhong-Lin , Li Jinrong
Published: October 2022

Purpose

Compare peripheral contrast sensitivity functions (CSF) between myopes and emmetropes to reveal potential myogenic risks during emmetropization.

Materials and methods

This observational, cross-sectional, non-consecutive case study included data from 19 myopes (23.42 ± 4.03 years old) and 12 emmetropes (22.93 ± 2.91 years old) who underwent central and peripheral quick CSF (qCSF) measurements. Summary CSF metrics including the cut-off spatial frequency (cut-off SF), area under log CSF (AULCSF), low-, intermediate-, and high-spatial-frequency AULCSFs (l-, i-, and h-SF AULCSFs), and log CS at 19 SFs in the fovea and 15 peripheral locations (superior, inferior, temporal, and nasal quadrants at 6, 12, 18, and 24° eccentricities, excluding the physiological scotoma at 18°) were analyzed with 3-way and 4-way between-subjects analysis of variance (ANOVA) (α = 0.05).

Results

Three-way ANOVA showed that myopes had significantly increased AULCSF at 6° (mean difference, 0.08; 95% CI, 0.02–0.13; P = 0.007) and 12° (mean difference, 0.09; 95% CI, 0.03–0.14; P = 0.003). Log CS at all 19 SFs were higher in the myopia group compared to the normal group (mean differencesuperior, 0.02; 95% CI, 0.01–0.20; P = 0.02 and mean differenceinferior, 0.11; 95% CI, 0.02–0.21; P = 0.01) at 12°. The h-SF AULCSF at 6° (mean differenceinferior, 1.27; 95% CI, 0.32–2.22; P = 0.009) and i-SF AULCSF at 12° (mean differencesuperior, 5.31; 95% CI, 4.35–6.27; P < 0.001; mean differenceinferior, 1.14; 95% CI, 0.19–2.10; P = 0.02) were higher in myopia vs. normal group.

Conclusion

We found myopia increased contrast sensitivity in superior and inferior visual field locations at 6° parafoveal and 12° perifoveal regions of the retina. The observation of increased contrast sensitivities within the macula visual field in myopia might provide important insights for myopia control during emmetropization.
Glial functions in the blood-brain communication at the circumventricular organs
Authors: Miyata Seiji
Published: October 2022

The circumventricular organs (CVOs) are located around the brain ventricles, lack a blood-brain barrier (BBB) and sense blood-derived molecules. This review discusses recent advances in the importance of CVO functions, especially glial cells transferring periphery inflammation signals to the brain. The CVOs show size-limited vascular permeability, allowing the passage of molecules with molecular weight <10,000. This indicates that the lack of an endothelial cell barrier does not mean the free movement of blood-derived molecules into the CVO parenchyma. Astrocytes and tanycytes constitute a dense barrier at the distal CVO subdivision, preventing the free diffusion of blood-derived molecules into neighboring brain regions. Tanycytes in the CVOs mediate communication between cerebrospinal fluid and brain parenchyma via transcytosis. Microglia and macrophages of the CVOs are essential for transmitting peripheral information to other brain regions via toll-like receptor 2 (TLR2). Inhibition of TLR2 signaling or depletion of microglia and macrophages in the brain eliminates TLR2-dependent inflammatory responses. In contrast to TLR2, astrocytes and tanycytes in the CVOs of the brain are crucial for initiating lipopolysaccharide (LPS)-induced inflammatory responses via TLR4. Depletion of microglia and macrophages augments LPS-induced fever and chronic sickness responses. Microglia and macrophages in the CVOs are continuously activated, even under normal physiological conditions, as they exhibit activated morphology and express the M1/M2 marker proteins. Moreover, the microglial proliferation occurs in various regions, such as the hypothalamus, medulla oblongata, and telencephalon, with a marked increase in the CVOs, due to low-dose LPS administration, and after high-dose LPS administration, proliferation is seen in most brain regions, except for the cerebral cortex and hippocampus. A transient increase in the microglial population is beneficial during LPS-induced inflammation for attenuating sickness response. Transient receptor potential receptor vanilloid 1 expressed in astrocytes and tanycytes of the CVOs is responsible for thermoregulation upon exposure to a warm environment less than 37°C. Alternatively, Nax expressed in astrocytes and tanycytes of the CVOs is crucial for maintaining body fluid homeostasis. Thus, recent findings indicate that glial cells in the brain CVOs are essential for initiating neuroinflammatory responses and maintaining body fluid and thermal homeostasis.
Repeated psychological stress, chronic vicarious social defeat stress, evokes irritable bowel syndrome-like symptoms in mice
Authors: Yoshioka Toshinori , Ohashi Misaki , Matsumoto Kenjiro , Omata Tomoki , Hamano Takumi , Yamazaki Mayuna , Kimiki Sayaka , Okano Kotaro , Kobayashi Riho , Yamada Daisuke , Hada Noriyasu , Kato Shinichi , Saitoh Akiyoshi
Published: October 2022

Increasing evidence has demonstrated that emotional states and intestinal conditions are inter-connected in so-called “brain–gut interactions.” Indeed, many psychiatric disorders are accompanied by gastrointestinal symptoms, such as the irritable bowel syndrome (IBS). However, the functional connection remains elusive, partly because there are few useful experimental animal models. Here, we focused on a highly validated animal model of stress-induced psychiatric disorders, such as depression, known as the chronic vicarious social defeat stress (cVSDS) model mice, which we prepared using exposure to repeated psychological stress, thereafter examining their intestinal conditions. In the charcoal meal test and the capsaicin-induced hyperalgesia test, cVSDS model mice showed a significantly higher intestinal transit ratio and increased visceral pain-related behaviors, respectively. These changes persisted over one month after the stress session. On the other hand, the pathological evaluations of the histological and inflammatory scores of naive and cVSDS model mice did not differ. Furthermore, keishikashakuyakuto—a kampo medicine clinically used for the treatment of IBS—normalized the intestinal motility change in cVSDS model mice. Our results indicate that cVSDS model mice present IBS-like symptoms such as chronic intestinal peristaltic changes and abdominal hyperalgesia without organic lesion. We therefore propose the cVSDS paradigm as a novel animal model of IBS with wide validity, elucidating the correlation between depressive states and intestinal abnormalities.
Quantitative evaluation of diaphragmatic motion during forced breathing in chronic obstructive pulmonary disease patients using dynamic chest radiography
Authors: Chen Jianghong , Zhong Zhaohui , Wang Wei , Yu Ganggang , Zhang Tingting , Wang Zhenchang
Published: October 2022

Objective

To quantitatively evaluate the bilateral diaphragmatic motion difference during forced breathing between chronic obstructive pulmonary disease (COPD) patients and healthy individuals using dynamic chest radiography technique.

Methods

This prospective study included the COPD patients (n: 96, f/m: 17/79, age: 66 ± 8 years old) and healthy individuals (n: 50, f/m: 42/8, age: 53 ± 5 years old) that underwent dynamic chest radiography with a flat panel X-ray detector system during forced breathing in a standing position. After analyzing the excursions, duration and velocity of diaphragmatic motion were automatically calculated using the postprocessing software. The parameters of diaphragmatic motion including excursion, duration, velocity, inhalation/exhalation times were assessed in all subjects for both diaphragms. The correlation between lung function parameters and diaphragmatic motion excursions were further evaluated.

Results

The excursions of diaphragmatic motion in COPD patients were significantly decreased in COPD patients compared with healthy individuals during forced breathing (P < 0.05). The excursion in COPD patients was 35.93 ± 13.07 mm vs. 41.49 ± 12.07 mm in healthy individuals in the left diaphragm, and 32.05 ± 12.29 mm in COPD patients vs. 36.88 ± 10.96 mm in healthy individuals in the right diaphragm. The duration of diaphragmatic motion significantly decreased in COPD patients, compared with the healthy individuals (P < 0.05). The inhalation time in COPD patients was 2.03 ± 1.19 s vs. 2.53 ± 0.83 s in healthy individuals in the left diaphragm and 1.94 ± 1.32 s in COPD patients vs. 2.23 ± 1.21 s in healthy individuals in the right diaphragm. The exhalation time was 4.77 ± 1.32 s in COPD patients vs. 6.40 ± 2.73 s in healthy individuals in the left diaphragm and 4.94 ± 3.30 s in COPD patients vs. 6.72 ± 2.58 s in healthy individuals in the right diaphragm. The peak velocity of diaphragmatic motion showed no significant difference between COPD and healthy groups. The excursions of bilateral diaphragmatic motion showed moderate correlation with FEV1/FVC (r = 0.44, P < 0.001). Multi-linear regression analysis showed that the excursions of bilateral diaphragm are significantly associated with COPD occurrence (P < 0.05).

Conclusion

The excursions and duration of diaphragmatic motion during forced breathing are significantly decreased in COPD patients, compared with healthy individuals. Our study showed that precise bilateral diaphragmatic motion activity can be evaluated by dynamic chest radiography.
Characterization of plasma metabolites and proteins in patients with herpetic neuralgia and development of machine learning predictive models based on metabolomic profiling
Authors: Zhou Ruihao , Li Jun , Zhang Yujun , Xiao Hong , Zuo Yunxia , Ye Ling
Published: October 2022

Herpes zoster (HZ) is a localized, painful cutaneous eruption that occurs upon reactivation of the herpes virus. Postherpetic neuralgia (PHN) is the most common chronic complication of HZ. In this study, we examined the metabolomic and proteomic signatures of disease progression in patients with HZ and PHN. We identified differentially expressed metabolites (DEMs), differentially expressed proteins (DEPs), and key signaling pathways that transition from healthy volunteers to the acute or/and chronic phases of herpetic neuralgia. Moreover, some specific metabolites correlated with pain scores, disease duration, age, and pain in sex dimorphism. In addition, we developed and validated three optimal predictive models (AUC > 0.9) for classifying HZ and PHN from healthy individuals based on metabolic patterns and machine learning. These findings may reveal the overall metabolomics and proteomics landscapes and proposed the optimal machine learning predictive models, which provide insights into the mechanisms of HZ and PHN.
Mesenchymal stromal cells for the treatment of Alzheimer’s disease: Strategies and limitations
Authors: Regmi Shobha , Liu Daniel Dan , Shen Michelle , Kevadiya Bhavesh D. , Ganguly Abantika , Primavera Rosita , Chetty Shashank , Yarani Reza , Thakor Avnesh S.
Published: October 2022

Alzheimer’s disease (AD) is a major cause of age-related dementia and is characterized by progressive brain damage that gradually destroys memory and the ability to learn, which ultimately leads to the decline of a patient’s ability to perform daily activities. Although some of the pharmacological treatments of AD are available for symptomatic relief, they are not able to limit the progression of AD and have several side effects. Mesenchymal stem/stromal cells (MSCs) could be a potential therapeutic option for treating AD due to their immunomodulatory, anti-inflammatory, regenerative, antioxidant, anti-apoptotic, and neuroprotective effects. MSCs not only secret neuroprotective and anti-inflammatory factors to promote the survival of neurons, but they also transfer functional mitochondria and miRNAs to boost their bioenergetic profile as well as improve microglial clearance of accumulated protein aggregates. This review focuses on different clinical and preclinical studies using MSC as a therapy for treating AD, their outcomes, limitations and the strategies to potentiate their clinical translation.
Electroacupuncture alleviates orofacial allodynia and anxiety-like behaviors by regulating synaptic plasticity of the CA1 hippocampal region in a mouse model of trigeminal neuralgia
Authors: Jia Yu-Zhi , Li Hai-Tao , Zhang Guang-Ming , Wu Hong-Yun , Zhang Si-Shuo , Zhi Hong-Wei , Wang Ya-Han , Zhu Jing-Wen , Wang Yi-Fan , Xu Xiang-Qing , Tian Cai-Jun , Cui Wen-Qiang
Published: October 2022

Objective

Trigeminal neuralgia (TN), one of the most severe and debilitating chronic pain conditions, is often accompanied by mood disorders, such as anxiety and depression. Electroacupuncture (EA) is a characteristic therapy of Traditional Chinese Medicine with analgesic and anxiolytic effects. This study aimed to investigate whether EA ameliorates abnormal TN orofacial pain and anxiety-like behavior by altering synaptic plasticity in the hippocampus CA1.

Materials and methods

A mouse infraorbital nerve transection model (pT-ION) of neuropathic pain was established, and EA or sham EA was used to treat ipsilateral acupuncture points (GV20-Baihui and ST7-Xiaguan). Golgi–Cox staining and transmission electron microscopy (TEM) were administrated to observe the changes of synaptic plasticity in the hippocampus CA1.

Results

Stable and persistent orofacial allodynia and anxiety-like behaviors induced by pT-ION were related to changes in hippocampal synaptic plasticity. Golgi stainings showed a decrease in the density of dendritic spines, especially mushroom-type dendritic spines, in hippocampal CA1 neurons of pT-ION mice. TEM results showed that the density of synapses, membrane thickness of the postsynaptic density, and length of the synaptic active zone were decreased, whereas the width of the synaptic cleft was increased in pT-ION mice. EA attenuated pT-ION-induced orofacial allodynia and anxiety-like behaviors and effectively reversed the abnormal changes in dendritic spines and synapse of the hippocampal CA1 region.

Conclusion

EA modulates synaptic plasticity of hippocampal CA1 neurons, thereby reducing abnormal orofacial pain and anxiety-like behavior. This provides evidence for a TN treatment strategy.