bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial community structural response to variations in physicochemical features of different aquifers
Authors: Dai Heng , Zhang Yiyu , Fang Wen , Liu Juan , Hong Jun , Zou Chaowang , Zhang Jin
Published: February 2023

Introduction

The community structure of groundwater microorganisms has a significant impact on groundwater quality. However, the relationships between the microbial communities and environmental variables in groundwater of different recharge and disturbance types are not fully understood.

Methods

In this study, measurements of groundwater physicochemical parameters and 16S rDNA high-throughput sequencing technology were used to assess the interactions between hydrogeochemical conditions and microbial diversity in Longkou coastal aquifer (LK), Cele arid zone aquifer (CL), and Wuhan riverside hyporheic zone aquifer (WH). Redundancy analysis indicated that the primary chemical parameters affecting the microbial community composition were NO3–, Cl–, and HCO3–.

Results

The species and quantity of microorganisms in the river–groundwater interaction area were considerably higher than those in areas with high salinity [Shannon: WH (6.28) > LK (4.11) > CL (3.96); Chao1: WH (4,868) > CL (1510) > LK (1,222)]. Molecular ecological network analysis demonstrated that the change in microbial interactions caused by evaporation was less than that caused by seawater invasion under high-salinity conditions [(nodes, links): LK (71,192) > CL (51,198)], whereas the scale and nodes of the microbial network were greatly expanded under low-salinity conditions [(nodes, links): WH (279,694)]. Microbial community analysis revealed that distinct differences existed in the classification levels of the different dominant microorganism species in the three aquifers.

Discussion

Environmental physical and chemical conditions selected the dominant species according to microbial functions. Gallionellaceae, which is associated with iron oxidation, dominated in the arid zones, while Rhodocyclaceae, which is related to denitrification, led in the coastal zones, and Desulfurivibrio, which is related to sulfur conversion, prevailed in the hyporheic zones. Therefore, dominant local bacterial communities can be used as indicators of local environmental conditions.
Alterations in metabolome and microbiome signatures provide clues to the role of antimicrobial peptide KT2 in ulcerative colitis
Authors: Nan Qiong , Ye Yan , Tao Yan , Jiang Xinyi , Miao Yinglei , Jia Jie , Miao Jiarong
Published: February 2023

Introduction

Ulcerative colitis (UC) is an inflammatory disease of the intestinal tract with unknown etiology. Both genetic and environmental factors are involved in the occurrence and development of UC. Understanding changes in the microbiome and metabolome of the intestinal tract is crucial for the clinical management and treatment of UC.

Methods

Here, we performed metabolomic and metagenomic profiling of fecal samples from healthy control mice (HC group), DSS (Dextran Sulfate Sodium Salt) -induced UC mice (DSS group), and KT2-treated UC mice (KT2 group).

Results and Discussion

In total, 51 metabolites were identified after UC induction, enriched in phenylalanine metabolism, while 27 metabolites were identified after KT2 treatment, enriched in histidine metabolism and bile acid biosynthesis. Fecal microbiome analysis revealed significant differences in nine bacterial species associated with the course of UC, including Bacteroides, Odoribacter, and Burkholderiales, which were correlated with aggravated UC, and Anaerotruncus, Lachnospiraceae, which were correlated with alleviated UC. We also identified a disease-associated network connecting the above bacterial species with UC-associated metabolites, including palmitoyl sphingomyelin, deoxycholic acid, biliverdin, and palmitoleic acid. In conclusion, our results indicated that Anaerotruncus, Lachnospiraceae, and Mucispirillum were protective species against DSS-induced UC in mice. The fecal microbiomes and metabolomes differed significantly among the UC mice and KT2-treated and healthy-control mice, providing potential evidence for the discovery of biomarkers of UC.
Dynamic state of plasmid genomic architectures resulting from XerC/D-mediated site-specific recombination in Acinetobacter baumannii Rep_3 superfamily resistance plasmids carrying blaOXA-58- and TnaphA6-resistance modules
Authors: Giacone Lucía , Cameranesi M. Marcela , Sanchez Rocío I. , Limansky Adriana S. , Morán-Barrio Jorgelina , Viale Alejandro M.
Published: February 2023

The acquisition of blaOXA genes encoding different carbapenem-hydrolyzing class-D β-lactamases (CHDL) represents a main determinant of carbapenem resistance in the nosocomial pathogen Acinetobacter baumannii. The blaOXA-58 gene, in particular, is generally embedded in similar resistance modules (RM) carried by plasmids unique to the Acinetobacter genus lacking self-transferability. The ample variations in the immediate genomic contexts in which blaOXA-58-containing RMs are inserted among these plasmids, and the almost invariable presence at their borders of non-identical 28-bp sequences potentially recognized by the host XerC and XerD tyrosine recombinases (pXerC/D-like sites), suggested an involvement of these sites in the lateral mobilization of the gene structures they encircle. However, whether and how these pXerC/D sites participate in this process is only beginning to be understood. Here, we used a series of experimental approaches to analyze the contribution of pXerC/D-mediated site-specific recombination to the generation of structural diversity between resistance plasmids carrying pXerC/D-bounded blaOXA-58- and TnaphA6-containing RM harbored by two phylogenetically- and epidemiologically-closely related A. baumannii strains of our collection, Ab242 and Ab825, during adaptation to the hospital environment. Our analysis disclosed the existence of different bona fide pairs of recombinationally-active pXerC/D sites in these plasmids, some mediating reversible intramolecular inversions and others reversible plasmid fusions/resolutions. All of the identified recombinationally-active pairs shared identical GGTGTA sequences at the cr spacer separating the XerC- and XerD-binding regions. The fusion of two Ab825 plasmids mediated by a pair of recombinationally-active pXerC/D sites displaying sequence differences at the cr spacer could be inferred on the basis of sequence comparison analysis, but no evidence of reversibility could be obtained in this case. The reversible plasmid genome rearrangements mediated by recombinationally-active pairs of pXerC/D sites reported here probably represents an ancient mechanism of generating structural diversity in the Acinetobacter plasmid pool. This recursive process could facilitate a rapid adaptation of an eventual bacterial host to changing environments, and has certainly contributed to the evolution of Acinetobacter plasmids and the capture and dissemination of blaOXA-58 genes among Acinetobacter and non-Acinetobacter populations co-residing in the hospital niche.
Spatio-temporal connectivity of the aquatic microbiome associated with cyanobacterial blooms along a Great Lake riverine-lacustrine continuum
Authors: Crevecoeur Sophie , Edge Thomas A. , Watson Linet Cynthia , Watson Susan B. , Greer Charles W. , Ciborowski Jan J. H. , Diep Ngan , Dove Alice , Drouillard Kenneth G. , Frenken Thijs , McKay Robert Michael , Zastepa Arthur , Comte Jérôme
Published: February 2023

Lake Erie is subject to recurring events of cyanobacterial harmful algal blooms (cHABs), but measures of nutrients and total phytoplankton biomass seem to be poor predictors of cHABs when taken individually. A more integrated approach at the watershed scale may improve our understanding of the conditions that lead to bloom formation, such as assessing the physico-chemical and biological factors that influence the lake microbial community, as well as identifying the linkages between Lake Erie and the surrounding watershed. Within the scope of the Government of Canada’s Genomics Research and Development Initiative (GRDI) Ecobiomics project, we used high-throughput sequencing of the 16S rRNA gene to characterize the spatio-temporal variability of the aquatic microbiome in the Thames River–Lake St. Clair-Detroit River–Lake Erie aquatic corridor. We found that the aquatic microbiome was structured along the flow path and influenced mainly by higher nutrient concentrations in the Thames River, and higher temperature and pH downstream in Lake St. Clair and Lake Erie. The same dominant bacterial phyla were detected along the water continuum, changing only in relative abundance. At finer taxonomical level, however, there was a clear shift in the cyanobacterial community, with Planktothrix dominating in the Thames River and Microcystis and Synechococcus in Lake St. Clair and Lake Erie. Mantel correlations highlighted the importance of geographic distance in shaping the microbial community structure. The fact that a high proportion of microbial sequences found in the Western Basin of Lake Erie were also identified in the Thames River, indicated a high degree of connectivity and dispersal within the system, where mass effect induced by passive transport play an important role in microbial community assembly. Nevertheless, some cyanobacterial amplicon sequence variants (ASVs) related to Microcystis, representing less than 0.1% of relative abundance in the upstream Thames River, became dominant in Lake St. Clair and Erie, suggesting selection of those ASVs based on the lake conditions. Their extremely low relative abundances in the Thames suggest additional sources are likely to contribute to the rapid development of summer and fall blooms in the Western Basin of Lake Erie. Collectively, these results, which can be applied to other watersheds, improve our understanding of the factors influencing aquatic microbial community assembly and provide new perspectives on how to better understand the occurrence of cHABs in Lake Erie and elsewhere.
QsvR and OpaR coordinately repress biofilm formation by Vibrio parahaemolyticus
Authors: Zhang Miaomiao , Xue Xingfan , Li Xue , Wu Qimin , Zhang Tingting , Yang Wenhui , Hu Lingfei , Zhou Dongsheng , Lu Renfei , Zhang Yiquan
Published: February 2023

Mature biofilm formation by Vibrio parahaemolyticus requires exopolysaccharide (EPS), type IV pili, and capsular polysaccharide (CPS). Production of each is strictly regulated by various control pathways including quorum sensing (QS) and bis-(3′–5′)-cyclic di-GMP (c-di-GMP). QsvR, an AraC-type regulator, integrates into the QS regulatory cascade via direct control of the transcription of the master QS regulators, AphA and OpaR. Deletion of qsvR in wild-type or opaR mutant backgrounds altered the biofilm formation by V. parahaemolyticus, suggesting that QsvR may coordinate with OpaR to control biofilm formation. Herein, we demonstrated both QsvR and OpaR repressed biofilm-associated phenotypes, c-di-GMP metabolism, and the formation of V. parahaemolyticus translucent (TR) colonies. QsvR restored the biofilm-associated phenotypic changes caused by opaR mutation, and vice versa. In addition, QsvR and OpaR worked coordinately to regulate the transcription of EPS-associated genes, type IV pili genes, CPS genes and c-di-GMP metabolism-related genes. These results demonstrated how QsvR works with the QS system to regulate biofilm formation by precisely controlling the transcription of multiple biofilm formation-associated genes in V. parahaemolyticus.
Effect of deposit chemistry on microbial community structure and activity: Implications for under-deposit microbial corrosion
Authors: Diaz-Mateus Maria A. , Salgar-Chaparro Silvia J. , Machuca Laura L. , Farhat Hanan
Published: February 2023

Introduction

The deposition of solid particles carried by production fluids from oil and gas companies in horizontal surfaces of different assets has shown to cause severe localised corrosion. Sand, one of the most common deposits in the energy sector pipelines, is frequently mixed with crude, oil, asphaltenes, corrosion inhibitors, and other organic compounds. For this reason, they might favour the metabolic activity of native microbial communities. This study aimed to determine the impact of sand-deposit chemical composition on the microbial community structure and functional attributes of a multispecies consortium recovered from an oilfield and the resulting risk of under-deposit microbial corrosion of carbon steel.

Methods

Sand deposits recovered from an oil pipeline were used in their raw form and compared against the same deposits exposed to heat treatment to remove organic compounds. A four-week immersion test in a bioreactor filled with synthetic produced water and a two-centimeter layer of sand was set up to assess corrosion and microbial community changes.

Results

The raw untreated deposit from the field containing hydrocarbons and treatment chemicals resulted in a more diverse microbial community than its treated counterpart. Moreover, biofilms developed in the raw sand deposit exhibited higher metabolic rates, with functional profile analysis indicating a predominance of genes associated with xenobiotics degradation. Uniform and localized corrosion were more severe in the raw sand deposit compared to the treated sand.

Discussion

The complex chemical composition of the untreated sand might have represented an additional source of energy and nutrients to the microbial consortium, favoring the development of different microbial genera and species. The higher corrosion rate obtained under the untreated sand suggests that MIC occurred due to syntrophic relationships between sulphate reducers or thiosulphate reducers and fermenters identified in the consortium.
Untargeted metabolomics and quantification analysis reveal the shift of chemical constituents between instant dark teas individually liquid-state fermented by Aspergillus cristatus, Aspergillus niger, and Aspergillus tubingensis
Authors: Liao Si-yu , Zhao Yi-qiao , Jia Wen-bao , Niu Li , Bouphun Tunyaluk , Li Pin-wu , Chen Sheng-xiang , Chen Wei , Tang Dan-dan , Zhao Yue-ling , Zou Yao , Zhu Ming-zhi , Xu Wei
Published: February 2023

Instant dark teas (IDTs) were individually liquid-state fermented using the fungi Aspergillus cristatus, Aspergillus niger, and Aspergillus tubingensis. To understand how the chemical constituents of IDTs were affected by the fungi, samples were collected and measured by liquid chromatography-tandem mass-tandem mass spectrometry (LC-MS/MS). Untargeted metabolomics analysis revealed that 1,380 chemical constituents were identified in positive and negative ion modes, and 858 kinds of chemical components were differential metabolites. Through cluster analysis, IDTs were different from the blank control, and their chemical constituents mostly included carboxylic acids and their derivatives, flavonoids, organooxygen compounds, and fatty acyls. And the metabolites of IDTs fermented by A. niger and A. tubingensis had a high degree of similarity and were classified into one category, which showed that the fungus used to ferment is critical to the formation of certain qualities of IDTs. The biosynthesis of flavonoids and phenylpropanoid, which involved nine different metabolites such as p-coumarate, p-coumaroyl-CoA, caffeate, ferulate, naringenin, kaempferol, leucocyanidin, cyanidin, and (-)-epicatechin, were significant pathways influencing the quality formation of IDTs. Quantification analysis indicated that the A. tubingensis fermented-IDT had the highest content of theaflavin, theabrownin, and caffeine, while the A. cristatus fermented-IDT had the lowest content of theabrownin, and caffeine. Overall, the results provided new insights into the relationship between the quality formation of IDTs and the microorganisms used in liquid-state fermentation.
Health disparities in aging: Improving dementia care for Black women
Authors: Findley Caleigh A. , Cox MaKayla F. , Lipson Adam B. , Bradley RaTasha , Hascup Kevin N. , Yuede Carla , Hascup Erin R.
Published: February 2023

In the United States, 80% of surveyed Black patients report experiencing barriers to healthcare for Alzheimer’s disease and related dementias (ADRD), delaying the time-sensitive treatment of a progressive neurodegenerative disease. According to the National Institute on Aging, Black study participants are 35% less likely to be given a diagnosis of ADRD than white participants, despite being twice as likely to suffer from ADRD than their white counterparts. Prior analysis of prevalence for sex, race, and ethnicity by the Centers for Disease Control indicated the highest incidence of ADRD in Black women. Older (≥65 years) Black women are at a disproportionately high risk for ADRD and yet these patients experience distinct inequities in obtaining clinical diagnosis and treatment for their condition. To that end, this perspective article will review a current understanding of biological and epidemiological factors that underlie the increased risk for ADRD in Black women. We will discuss the specific barriers Black women face in obtaining access to ADRD care, including healthcare prejudice, socioeconomic status, and other societal factors. This perspective also aims to evaluate the performance of intervention programs targeted toward this patient population and offer possible solutions to promote health equity.
Pentad: A reproducible cytoarchitectonic protocol and its application to parcellation of the human hippocampus
Authors: Williams Emily M. , Rosenblum Emma W. , Pihlstrom Nicole , Llamas-Rodríguez Josué , Champion Samantha , Frosch Matthew P. , Augustinack Jean C.
Published: February 2023

Introduction

The hippocampus is integral for learning and memory and is targeted by multiple diseases. Neuroimaging approaches frequently use hippocampal subfield volumes as a standard measure of neurodegeneration, thus making them an essential biomarker to study. Collectively, histologic parcellation studies contain various disagreements, discrepancies, and omissions. The present study aimed to advance the hippocampal subfield segmentation field by establishing the first histology based parcellation protocol, applied to n = 22 human hippocampal samples.

Methods

The protocol focuses on five cellular traits observed in the pyramidal layer of the human hippocampus. We coin this approach the pentad protocol. The traits were: chromophilia, neuron size, packing density, clustering, and collinearity. Subfields included were CA1, CA2, CA3, CA4, prosubiculum, subiculum, presubiculum, parasubiculum, as well as the medial (uncal) subfields Subu, CA1u, CA2u, CA3u, and CA4u. We also establish nine distinct anterior-posterior levels of the hippocampus in the coronal plane to document rostrocaudal differences.

Results

Applying the pentad protocol, we parcellated 13 subfields at nine levels in 22 samples. We found that CA1 had the smallest neurons, CA2 showed high neuronal clustering, and CA3 displayed the most collinear neurons of the CA fields. The border between presubiculum and subiculum was staircase shaped, and parasubiculum had larger neurons than presubiculum. We also demonstrate cytoarchitectural evidence that CA4 and prosubiculum exist as individual subfields.

Discussion

This protocol is comprehensive, regimented and supplies a high number of samples, hippocampal subfields, and anterior-posterior coronal levels. The pentad protocol utilizes the gold standard approach for the human hippocampus subfield parcellation.
Bilateral ankle deformities affects gait kinematics in chronic stroke patients
Authors: Kim Hogene , Cho Ji-Eun , Seo Kyeong-Jun , Lee Jooyoung
Published: February 2023

Objectives

Stroke patients suffer from ankle joint deformities due to spastic ankle muscles. This study evaluated the viability of using 3D scanned surface images of the feet of stroke victims to visually assess the deformities of a hemiparetic foot and investigated the influences of deformed ankle joints on gait kinematics.

Methods

A total of 30 subjects with stroke-induced hemiparesis and 11 age-matched healthy controls completed the clinical assessments. We analyzed their feet's morphometric characteristics using a 3D scanner, identified convenient anthropometric measurements, and conducted gait trials on even and uneven terrains. The 3D foot morphometric characteristics were evaluated using the geometric morphometrics method (GMM).

Results

Results showed that there were significant differences in bilateral foot shapes between the chronic stroke patients and healthy controls and between the paretic and non-paretic sides in the chronic stroke patients. In stroke patients, those with the smaller medial malleoli's vertical tilt angles showed significantly different ankle ranges of motion of dorsi-/plantar flexion during gaits on uneven terrains (p = 0.009). In addition, those with the greater medial malleoli's vertical tilt angles showed significantly different ankle ranges of motion of inversion/eversion during gaits on even and uneven terrains (p < 0.05).

Conclusion

Using 3D scanning technology, bilateral morphometric changes in the feet of chronic stroke patients were shown by GMM and the simple anthropometric measurements identified its shape deformities in the feet. Their possible effects on gait kinematics while walking on uneven terrains were investigated. Current methodology can be potentially useful in applying conventional productions of clinically manufactured, patient-fitted ankle-foot-orthosis in orthotics and prosthetics, and in detecting various unidentified pathological deformities in the feet.
Pathogenic free-living amoebic encephalitis from 48 cases in China: A systematic review
Authors: Chen Xiang-Ting , Zhang Qian , Wen Si-Yuan , Chen Fei-Fei , Zhou Chang-Qing
Published: February 2023

Background

Free-living amoebae (FLA) including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris can become pathogenic and cause severe cerebral infections, named primary amoebic meningoencephalitis (PAM), granulomatous amoebic encephalitis (GAE), and balamuthia amoebic encephalitis (BAE), respectively. FLA encephalitis has been reported across China, but the clinical data descriptions and analytical results of these different reports vary widely. Currently, no consensus treatment has been established. We conduct a systematic review to evaluate the exposure location, clinical symptoms, diagnosis, treatment, and prognosis of three FLA encephalitis and aim to reveal the differences between three FLA encephalitis in China.

Methods

We used MEDLINE (PubMed interface), EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang database, and China Biology Medicine disc (CBMdisc) databases for literatures published and manually retrieve the hospital records of our hospital. The search time was up to August 30, 2022, with no language restrictions.

Results

After excluding possible duplicate cases, a total of 48 patients of three FLA encephalitis were collected. One from the medical records of our hospital and 47 patients from 31 different studies. There were 11 patients of PAM, 10 patients of GAE, and 27 patients of BAE. The onset of PAM is mostly acute or subacute, and the clinical symptoms are acute and fulminant hemorrhagic meningoencephalitis. Most patients with GAE and BAE have an insidious onset and a chronic course. A total of 21 BAE patients (77.8%) had skin lesions before onset of symptoms. Additionally, 37 cases (77.1%) were diagnosed with FLA encephalitis before death. And there were 4 of PAM, 2 of GAE, and 10 of BAE diagnosed using next generation sequencing. No single agent can be proposed as the ideal therapy by itself. Only 6 cases were successfully treated.

Conclusions

This review provides an overview of the available data and studies of FLA encephalitis in China and identify some potential differences. FLA encephalitis is a rare but pathogenic infection, and physicians should early identify this encephalitis to improve survival.
Management of carotid cavernous fistulas: A single center experience
Authors: Alatzides Georgios Luca , Opitz Marcel , Li Yan , Goericke Sophia , Oppong Marvin Darkwah , Frank Benedikt , Eckstein Anja Katrin , Köhrmann Martin , Wrede Karsten , Forsting Michael , Wanke Isabel , Deuschl Cornelius
Published: February 2023

Purpose

Multimodal endovascular therapy (EVT) of carotid cavernous fistula (CCF) with different approaches and a variety of available embolization material enable high occlusion rates with good clinical and functional outcome but until now there is still little evidence available. This retrospective single-center study aims to evaluate EVT of CCF with different neuroendovascular techniques regarding occlusion rates, complications and outcomes.

Materials and methods

From 2001 to 2021 59 patients with CCF were treated at our tertiary university hospital. Patient records and all imaging data including angiograms were reviewed for demographic and epidemiological data, symptoms, fistula type, number of EVTs, complications of EVT, type of embolic materials, occlusion rates and recurrences.

Results

Etiology of the CCF were spontaneous (41/59, 69.5%) post-traumatic (13/59, 22%) and ruptured cavernous aneurysms (5/59, 8.5%). Endovascular therapy was completed in one session in 74.6% (44/59). Transvenous access was most frequent (55.9% 33/59) followed by transarterial catheterization in 33.9% (20/59) and a combination of both (6/59, 10.2%). Exclusively coils were used in 45.8% (27/59), a combination of ethylene vinyl alcohol (EVOH) copolymer (Onyx) and coils in 42.4% (25/59). Complete obliteration was achieved in 96.6% of patients (57/59) with an intraprocedural-related complication rate of 5.1% (3/59) and no mortality.

Conclusion

Endovascular therapy of CCF has been shown to be safe and effective with high cure rates and low rates of intraprocedural complications and morbidity even in complex scenarios.
Late neurological consequences of SARS-CoV-2 infection: New challenges for the neurologist
Authors: Korchut Agnieszka , Rejdak Konrad
Published: February 2023

Objective

In this study, a systematic review of the literature was performed to study the frequency of neurological symptoms and diseases in adult patients with COVID-19 that may be late consequences of SARS-CoV-2 infection.

Methods

Relevant studies were identified through electronic explorations of Scopus, PubMed, and Google Scholar. We followed PRISMA guidelines. Data were collected from studies where the diagnosis of COVID-19 was confirmed and its late neurological consequences occurred at least 4 weeks after initial SARS-CoV-2 infection. Review articles were excluded from the study. Neurological manifestations were stratified based on frequency (above 5, 10, and 20%), where the number of studies and sample size were significant.

Results

A total of 497 articles were identified for eligible content. This article provides relevant information from 45 studies involving 9,746 patients. Fatigue, cognitive problems, and smell and taste dysfunctions were the most frequently reported long-term neurological symptoms in patients with COVID-19. Other common neurological issues were paresthesia, headache, and dizziness.

Conclusion

On a global scale of patients affected with COVID-19, prolonged neurological problems have become increasingly recognized and concerning. Our review might be an additional source of knowledge about potential long-term neurological impacts.
Restoring the missing person to personalized medicine and precision psychiatry
Authors: Gómez-Carrillo Ana , Paquin Vincent , Dumas Guillaume , Kirmayer Laurence J.
Published: February 2023

Precision psychiatry has emerged as part of the shift to personalized medicine and builds on frameworks such as the U.S. National Institute of Mental Health Research Domain Criteria (RDoC), multilevel biological “omics” data and, most recently, computational psychiatry. The shift is prompted by the realization that a one-size-fits all approach is inadequate to guide clinical care because people differ in ways that are not captured by broad diagnostic categories. One of the first steps in developing this personalized approach to treatment was the use of genetic markers to guide pharmacotherapeutics based on predictions of pharmacological response or non-response, and the potential risk of adverse drug reactions. Advances in technology have made a greater degree of specificity or precision potentially more attainable. To date, however, the search for precision has largely focused on biological parameters. Psychiatric disorders involve multi-level dynamics that require measures of phenomenological, psychological, behavioral, social structural, and cultural dimensions. This points to the need to develop more fine-grained analyses of experience, self-construal, illness narratives, interpersonal interactional dynamics, and social contexts and determinants of health. In this paper, we review the limitations of precision psychiatry arguing that it cannot reach its goal if it does not include core elements of the processes that give rise to psychopathological states, which include the agency and experience of the person. Drawing from contemporary systems biology, social epidemiology, developmental psychology, and cognitive science, we propose a cultural-ecosocial approach to integrating precision psychiatry with person-centered care.
The efficacy and safety of acupuncture therapy for sciatica: A systematic review and meta-analysis of randomized controlled trails
Authors: Zhang Zhihui , Hu Tingting , Huang Peiyan , Yang Mengning , Huang Zheng , Xia Yawen , Zhang Xinchang , Zhang Xiaolin , Ni Guangxia
Published: February 2023

Background and objective

Sciatica is a common type of neuropathic pain disease which poses a huge financial burden to the patient. For patients with sciatica, acupuncture has been recommended as an effective method for pain relief, while there is currently a lack of sufficient evidence to support its efficacy and safety. In this review, we aimed to critically assess the published clinical evidence on the efficacy and safety of acupuncture therapy for treating sciatica.

Methods

An extensive literature search strategy was established in seven databases from their inception to 31 March 2022. Two independent reviewers performed the literature search, identification, and screening. Data extraction was performed on studies that meet the inclusion criteria, and a further quality assessment was performed according to the Cochrane Handbook and Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) recommendations. Summary Risk ratio (RR) and standardized mean differences (SMDs) with 95% confidence interval (CI) were calculated using the fixed-effects or the random-effects model. Heterogeneity in effect size across studies was explored using the subgroup analysis and the sensitivity analysis. The quality of evidence was estimated following the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Results

A total of 30 randomized controlled trials (RCTs) involving 2,662 participants were included in the meta-analysis. The results of the integration of clinical outcomes showed that the clinical efficacy of acupuncture was superior to that of medicine treatment (MT) in improving the total effective rate (relative risk (RR) = 1.25, 95% confidence interval (CI) [1.21, 1.30]; moderate certainty of evidence), reducing the Visual Analog Scale (VAS) pain score (standardized mean difference (SMD) = −1.72, 95% CI [-2.61, −0.84]; very low certainty of evidence), increasing pain threshold (SMD = 2.07, 95% CI [1.38, 2.75]; very low certainty of evidence), and decreasing recurrence rate (RR = 0.27, 95% CI [0.13, 0.56]; low certainty of evidence). In addition, a few adverse events (RR = 0.38, 95% CI [0.19, 0.72]; moderate certainty of evidence) were reported during the intervention, which indicated that acupuncture was a safe treatment option.

Conclusions

Acupuncture therapy is an effective and safe treatment for patients with sciatica, and it can be considered a suitable replacement for medicine treatment (MT). However, given the high heterogeneity and a low methodological quality of previous studies, future RCTs should be well-designed according to the rigorous methodology.

Systematic review registration

International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) (https://inplasy.com/register/), identifier [INPLASY202240060].
Electrical nerve stimulation for sensory-neural pathway reconstruction in upper-limb amputees
Authors: Wang Yingying , Liu Hongyu , Zeng Peiying , Ji Lingchao , Zhou Yaqi , Zhou Liufang , Tao Yuan
Published: February 2023

Introduction

The loss of the neural sensory function pathways between the stump limbs and the brain greatly impacts the rehabilitation of limb function and the daily lives of amputees. Non-invasive physical stressors, such as mechanical pressure and transcutaneous electrical nerve stimulation (TENS), could be potential solutions for recovering somatic sensations in amputees. Previous studies have shown that stimulating the residual or regenerated nerves in the stumps of some amputees can produce phantom hand sensations. However, the results are inconclusive due to unstable physiological responses caused by inaccurate stimulus parameters and positions.

Methods

In this study, we developed an optimal TENS strategy by mapping the distribution of the nerves in the stump skin that elicitsphantom sensations known as a “phantom hand map.” We evaluated the effectiveness and stability of the confirmed stimulus configuration in a long-term experiment using single- and multi-stimulus paradigms. Additionally, we evaluated the evoked sensations by recording electroencephalograms (EEG) and analyzing brain activities.

Results

The results demonstrated that various types of intuitive sensations for amputees could be stably induced by adjusting TENS frequencies, particularly at 5 and 50 Hz. At these frequencies, 100% stability of sensory types was achieved when the stimuli were applied to two specific locations on the stump skin. Furthermore, at these locations, the stability of sensory positions was 100% across different days. Moreover, the evoked sensations were objectively supported by specific patterns of event-related potentials in brain responses.

Discussion

This study provides an effective method for developing and evaluating physical stressor stimulus strategies, which could play an important role in the somatosensory rehabilitation of amputees and other patients suffering from somatomotor sensory dysfunction. The paradigm developed in this study can provide effective guidelines for stimulus parameters in physical and electrical nerve stimulation treatments for a variety of symptoms related to neurological disorders.
Low and high carbohydrate isocaloric diets on performance, fat oxidation, glucose and cardiometabolic health in middle age males
Authors: Prins Philip J. , Noakes Timothy D. , Buga Alex , D’Agostino Dominic P. , Volek Jeff S. , Buxton Jeffrey D. , Heckman Kara , Jones Dalton W. , Tobias Naomi E. , Grose Holly M. , Jenkins Anna K. , Jancay Kelli T. , Koutnik Andrew P.
Published: February 2023

High carbohydrate, low fat (HCLF) diets have been the predominant nutrition strategy for athletic performance, but recent evidence following multi-week habituation has challenged the superiority of HCLF over low carbohydrate, high fat (LCHF) diets, along with growing interest in the potential health and disease implications of dietary choice. Highly trained competitive middle-aged athletes underwent two 31-day isocaloric diets (HCLF or LCHF) in a randomized, counterbalanced, and crossover design while controlling calories and training load. Performance, body composition, substrate oxidation, cardiometabolic, and 31-day minute-by-minute glucose (CGM) biomarkers were assessed. We demonstrated: (i) equivalent high-intensity performance (@∼85%VO2max), fasting insulin, hsCRP, and HbA1cwithout significant body composition changes across groups; (ii) record high peak fat oxidation rates (LCHF:1.58 ± 0.33g/min @ 86.40 ± 6.24%VO2max; 30% subjects > 1.85 g/min); (iii) higher total, LDL, and HDL cholesterol on LCHF; (iv) reduced glucose mean/median and variability on LCHF. We also found that the 31-day mean glucose on HCLF predicted 31-day glucose reductions on LCHF, and the 31-day glucose reduction on LCHF predicted LCHF peak fat oxidation rates. Interestingly, 30% of athletes had 31-day mean, median and fasting glucose > 100 mg/dL on HCLF (range: 111.68-115.19 mg/dL; consistent with pre-diabetes), also had the largest glycemic and fat oxidation response to carbohydrate restriction. These results: (i) challenge whether higher carbohydrate intake is superior for athletic performance, even during shorter-duration, higher-intensity exercise; (ii) demonstrate that lower carbohydrate intake may be a therapeutic strategy to independently improve glycemic control, particularly in those at risk for diabetes; (iii) demonstrate a unique relationship between continuous glycemic parameters and systemic metabolism.
Oral ketone esters acutely improve myocardial contractility in post-hospitalized COVID-19 patients: A randomized placebo-controlled double-blind crossover study
Authors: Wodschow Helena Zander , Davidovski Filip Søskov , Christensen Jacob , Lassen Mats Christian Højbjerg , Skaarup Kristoffer Grundtvig , Nygaard Hanne , Møller Niels , Rungby Jørgen , Biering-Sørensen Tor , Rossing Peter , Jensen Nicole Jacqueline , Laursen Jens Christian
Published: February 2023

Background

COVID-19 is associated with subclinical myocardial injury. Exogenous ketone esters acutely improve left myocardial function in healthy participants and patients with heart failure, but the effects have not been investigated in participants previously hospitalized for COVID-19.

Methods

This is a randomized placebo-controlled double-blind crossover study comparing a single oral ketone ester dose of 395 mg/kg with placebo. Fasting participants were randomized to either placebo in the morning and oral ketone ester in the afternoon or vice versa. Echocardiography was performed immediately after intake of the corresponding treatment. Primary outcome was left ventricular ejection fraction (LVEF). Secondary outcomes were absolute global longitudinal strain (GLS), cardiac output and blood oxygen saturation. Linear mixed effects models were used to assess differences.

Results

We included 12 participants previously hospitalized for COVID-19 with a mean (±SD) age of 60 ± 10 years. The mean time from hospitalization was 18 ± 5 months. Oral ketone esters did not increase LVEF between placebo and oral ketone ester [mean difference: −0.7% (95% CI −4.0 to 2.6%), p = 0.66], but increased GLS [1.9% (95% CI: 0.1 to 3.6%), p = 0.04] and cardiac output [1.2 L/min (95% CI: −0.1 to 2.4 L/min), p = 0.07], although non-significant. The differences in GLS remained significant after adjustment for change in heart rate (p = 0.01). There was no difference in blood oxygen saturation. Oral ketone esters increased blood ketones over time (peak level 3.1 ± 4.9 mmol/L, p < 0.01). Ketone esters increased blood insulin, c-peptide, and creatinine, and decreased glucose and FFA (all p ≤ 0.01) but did not affect glucagon, pro-BNP, or troponin I levels (all p > 0.05).

Conclusion

In patients previously hospitalized with COVID-19, a single oral dose of ketone ester had no effect on LVEF, cardiac output or blood oxygen saturation, but increased GLS acutely.

Clinical trial registration

https://clinicaltrials.gov/, identifier NCT04377035.
Resveratrol analog, triacetylresveratrol, a potential immunomodulator of lung adenocarcinoma immunotherapy combination therapies
Authors: He Jian , Qiu Nianxiang , Zhou Xianchao , Meng Mei , Liu Zixue , Li Jingquan , Du Shiyu , Sun Zhiqiang , Wang Hui
Published: February 2023

Introduction

Resveratrol, an activator for longevity regulatory genes-sirtuin family (SIRTs) and Sirtuin 2 (SIRT2) is an important factor of SIRTs which demonstrated biological function in cancers, but the underlying mechanism is unrevealed.

Methods

We investigated the mRNA and protein levels of SIRT2 in a variety of cancers and the potential role for clinical prognosis, as well as analysed the association between the gene and immune infiltration in various cancers. And an analysis of two types of lung cancer was conducted to construct a systematic prognostic landscape. Finally, putative binding site of the triacetylresveratrol bound to SIRT2 was built from homology modeling.

Results and discussion

We concluded that higher mRNA and protein levels of SIRT2 affected prognosis in various types of cancers, especially in LUAD cohorts. In addition, SIRT2 is linked with a better overall survival (OS) in LUAD patients. Further research suggested a possible explanation for this phenotype might be that SIRT2 mRNA levels are positively correlated with infiltrating status of multiple immunocytes in LU-AD but not LUSC, i.e. SIRT2 expression may contribute to the recruitment of CD8+T cell, CD4+ T cell, T cell CD4+ memory resting, Tregs, T cell NK and positively correlated to the expression of PD-1, also excluding neutrophil, T cell CD8+ naïve and B cell plasma cells in LUAD. We found that triacetyl-resveratrol demonstrated the most potent agonist efficiency to SIRT2 and the EC 50 as low as 142.79 nM. As a result, SIRT2 appears to be a promising novel biomarker for prognosis prediction in patients with LUAD and triacetylresveratrol might be a potential immunomodulator of LUAD to anti-PD-1 based immunotherapy combination therapies.
Combinatory analysis of immune cell subsets and tumor-specific genetic variants predict clinical response to PD-1 blockade in patients with non-small cell lung cancer
Authors: Dutta Nikita , Rohlin Anna , Eklund Ella A. , Magnusson Maria K. , Nilsson Frida , Akyürek Levent M. , Torstensson Per , Sayin Volkan I. , Lundgren Anna , Hallqvist Andreas , Raghavan Sukanya
Published: February 2023

Objectives

Immunotherapy by blocking programmed death protein-1 (PD-1) or programmed death protein-ligand1 (PD-L1) with antibodies (PD-1 blockade) has revolutionized treatment options for patients with non-small cell lung cancer (NSCLC). However, the benefit of immunotherapy is limited to a subset of patients. This study aimed to investigate the value of combining immune and genetic variables analyzed within 3–4 weeks after the start of PD-1 blockade therapy to predict long-term clinical response.

Materials and methodology

Blood collected from patients with NSCLC were analyzed for changes in the frequency and concentration of immune cells using a clinical flow cytometry assay. Next-generation sequencing (NGS) was performed on DNA extracted from archival tumor biopsies of the same patients. Patients were categorized as clinical responders or non-responders based on the 9 months’ assessment after the start of therapy.

Results

We report a significant increase in the post-treatment frequency of activated effector memory CD4+ and CD8+ T-cells compared with pre-treatment levels in the blood. Baseline frequencies of B cells but not NK cells, T cells, or regulatory T cells were associated with the clinical response to PD-1 blockade. NGS of tumor tissues identified pathogenic or likely pathogenic mutations in tumor protein P53, Kirsten rat sarcoma virus, Kelch-like ECH-associated protein 1, neurogenic locus notch homolog protein 1, and serine/threonine kinase 11, primarily in the responder group. Finally, multivariate analysis of combined immune and genetic factors but neither alone, could discriminate between responders and non-responders.

Conclusion

Combined analyses of select immune cell subsets and genetic mutations could predict early clinical responses to immunotherapy in patients with NSCLC and after validation, can guide clinical precision medicine efforts.
A novel signature constructed by super-enhancer-related genes for the prediction of prognosis in hepatocellular carcinoma and associated with immune infiltration
Authors: Wei Xueyan , Zhou Zihan , Long Meiying , Lin Qiuling , Qiu Moqin , Chen Peiqin , Huang Qiongguang , Qiu Jialin , Jiang Yanji , Wen Qiuping , Liu Yingchun , Li Runwei , Nong Cunli , Guo Qian , Yu Hongping , Zhou Xianguo
Published: February 2023

Background

Super-enhancer (SE) refers to a regulatory element with super transcriptional activity, which can enrich transcription factors and drive gene expression. SE-related genes play an important role in the pathogenesis of malignant tumors, including hepatocellular carcinoma (HCC).

Methods

The SE-related genes were obtained from the human super-enhancer database (SEdb). Data from the transcriptome analysis and related clinical information with HCC were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. The upregulated SE-related genes from TCGA-LIHC were identified by the DESeq2R package. Multivariate Cox regression analysis was used to construct a four-gene prognostic signature. According to the median risk score, HCC patients were divided into high-risk and low-risk group patients.

Results

The Kaplan-Meier (KM) curve showed that a significantly worse prognosis was found for the high-risk group (P<0.001). In the TCGA-LIHC dataset, the area under the curve (AUC) values were 0.737, 0.662, and 0.667 for the model predicting overall survival (OS) over 1-, 3-, and 5- years, respectively, indicating the good prediction ability of our prediction model. This model’s prognostic value was further validated in the LIRI-JP dataset and HCC samples (n=65). Furthermore, we found that higher infiltration level of M0 macrophages and upregulated of CTLA4 and PD1 in the high-risk group, implying that immunotherapy could be effective for those patients.

Conclusion

These results provide further evidence that the unique SE-related gene model could accurately predict the prognosis of HCC.
Effect of EGFR-TKIs combined with craniocerebral radiotherapy on the prognosis of EGFR-mutant lung adenocarcinoma patients with brain metastasis: A propensity-score matched analysis
Authors: Deng Guangchuan , Tan Xiaojing , Li Yankang , Zhang Yingyun , Wang Qi , Li Jianbin , Li Zhenxiang
Published: February 2023

Background and Purpose

Epidermal growth factor receptor (EGFR)-mutant lung cancers are associated with a high risk of developing brain metastases (BM). Craniocerebral radiotherapy is a cornerstone for the treatment of BM, and EGFR-TKIs act on craniocerebral metastases”. However, whether EGFR-TKIs combined with craniocerebral radiotherapy can further increase the efficacy and improve the prognosis of patients is unclear. This study aimed to evaluate the difference in efficacy between targeted-therapy alone and targeted-therapy combined with radiotherapy in EGFR-mutant lung adenocarcinoma patients with BM.

Materials and Methods

A total of 291 patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutations were enrolled in this retrospective cohort study. Propensity score matching (PSM) was conducted using a nearest-neighbor algorithm (1:1) to adjust for demographic and clinical covariates. Patients were divided into two groups: EGFR-TKIs alone and EGFR-TKIs combined with craniocerebral radiotherapy. Intracranial progression-free survival (iPFS) and overall survival (OS) were calculated. Kaplan–Meier analysis was used to compare iPFS and OS between the two groups. Brain radiotherapy included WBRT, local radiotherapy, and WBRT+Boost.

Results

The median age at diagnosis was 54 years (range: 28–81 years). Most patients were female (55.9%) and non-smokers (75.5%). Fifty-one pairs of patients were matched using PSM. The median iPFS for EGFR-TKIs alone (n=37) and EGFR-TKIs+craniocerebral radiotherapy (n=24) was 8.9 and 14.7 months, respectively. The median OS for EGFR-TKIs alone (n=52) and EGFR-TKIs+craniocerebral radiotherapy (n=52) was 32.1 and 45.3 months, respectively.

Conclusion

In EGFR-mutant lung adenocarcinoma patients with BM, targeted therapy combined with craniocerebral radiotherapy is an optimal treatment.