bluuebunny/crossref_metadata_2025 huggingface dataset:
Species diversity pattern and its drivers of the understory herbaceous plants in a Chinese subtropical forest
Authors: Tian Kai , Chai Pengtao , Wang Yunquan , Chen Lei , Qian Haiyuan , Chen Shengwen , Mi Xiangcheng , Ren Haibao , Ma Keping , Chen Jianhua
Published: January 2023

Understory herbaceous plants are an important component of forest ecosystems, playing important roles in species diversity and forest dynamics in forests. However, the current understanding of the biodiversity of forest communities is mostly from woody plants, and knowledge of community structure and species diversity for understory herbaceous plants remains scarce. In a subtropical forest in China, we investigated understory vascular herbaceous diversity from 300 plots (5 × 5 m) in the main growing season. In this study, we analyzed the community structure and diversity pattern of the understory herbaceous community and linked the species diversity pattern to both abiotic and biotic environments. We found a rich diversity of understory herbaceous communities in this forest (81 species belonging to 55 genera), and floristic elements at the genus level were dominated by tropical elements, followed by temperate elements. The diversity pattern of the understory herbaceous showed a significant habitat preference, with the highest diversity in the lowland valleys and then followed by in middle slopes. In addition, herbaceous diversity was significantly affected by both abiotic factors (such as terrain convexity) and biotic factors (such as the diversity of surrounding woody plants). Our study indicated that species diversity of understory herbaceous showed a remarkable habitat preference, such as lowland valleys, and highlighted the importance of both abiotic and biotic environments in driving herbaceous diversity patterns in the subtropical forest understory.
Forest-clearing to create early-successional habitats: Questionable benefits, significant costs
Authors: Kellett Michael J. , Maloof Joan E. , Masino Susan A. , Frelich Lee E. , Faison Edward K. , Brosi Sunshine L. , Foster David R.
Published: January 2023

A campaign is underway to clear established forests and expand early-successional habitats—also called young forest, pre-forest, early seral, or open habitats—with the intention of benefitting specific species. Coordinated by federal and state wildlife agencies, and funded with public money, public land managers work closely with hunting and forestry interests, conservation organizations, land trusts, and private landowners toward this goal. While forest-clearing has become a major focus in the Northeast and Upper Great Lakes regions of the U.S., far less attention is given to protecting and recovering old-forest ecosystems, the dominant land cover in these regions before European settlement. Herein we provide a discussion of early-successional habitat programs and policies in terms of their origins, in the context of historical baselines, with respect to species’ ranges and abundance, and as they relate to carbon accumulation and ecosystem integrity. Taken together, and in the face of urgent global crises in climate, biodiversity, and human health, we conclude that public land forest and wildlife management programs must be reevaluated to balance the prioritization and funding of early-successional habitat with strong and lasting protection for old-growth and mature forests, and, going forward, must ensure far more robust, unbiased, and ongoing monitoring and evaluation.
Clinical impact of exome sequencing in the setting of a general pediatric ward for hospitalized children with suspected genetic disorders
Authors: Kagan Maayan , Semo-Oz Rotem , Ben Moshe Yishay , Atias-Varon Danit , Tirosh Irit , Stern-Zimmer Michal , Eliyahu Aviva , Raas-Rothschild Annick , Bivas Maayan , Shlomovitz Omer , Chorin Odelia , Rock Rachel , Tzadok Michal , Ben-Zeev Bruria , Heimer Gali , Bolkier Yoav , Gruber Noah , Dagan Adi , Bar Aluma Bat El , Pessach Itai M. , Rechavi Gideon , Barel Ortal , Pode-Shakked Ben , Anikster Yair , Vivante Asaf
Published: January 2023

Background: Genetic conditions contribute a significant portion of disease etiologies in children admitted to general pediatric wards worldwide. While exome sequencing (ES) has improved clinical diagnosis and management over a variety of pediatric subspecialties, it is not yet routinely used by general pediatric hospitalists. We aim to investigate the impact of exome sequencing in sequencing-naive children suspected of having monogenic disorders while receiving inpatient care.

Methods: We prospectively employed exome sequencing in children admitted to the general pediatric inpatient service at a large tertiary medical center in Israel. Genetic analysis was triggered by general and/or subspecialist pediatricians who were part of the primary inpatient team. We determined the diagnostic yield among children who were referred for exome sequencing and observed the effects of genetic diagnosis on medical care.

Results: A total of fifty probands were evaluated and exome sequenced during the study period. The most common phenotypes included were neurodevelopmental (56%), gastrointestinal (34%), and congenital cardiac anomalies (24%). A molecular diagnosis was reached in 38% of patients. Among seven patients (37%), the molecular genetic diagnosis influenced subsequent clinical management already during admission or shortly following discharge.

Conclusion: We identified a significant fraction of genetic etiologies among undiagnosed children admitted to the general pediatric ward. Our results support that early application of exome sequencing may be maximized by pediatric hospitalists’ high index of suspicion for an underlying genetic etiology, prompting an in-house genetic evaluation. This framework should include a multidisciplinary co-management approach of the primary care team working alongside with subspecialties, geneticists and bioinformaticians.
Identification of COL4A4 variants in Chinese patients with familial hematuria
Authors: Gao Yanan , Yuan Lamei , Yuan Jinzhong , Yang Yan , Wang Jiangang , Chen Yong , Zhang Hao , Ai Yinze , Deng Hao
Published: January 2023

Background: Benign familial hematuria and Alport syndrome are common causes of familial hematuria among children and young adults, which are attributable to variants in the collagen type IV alpha chain genes, COL4A3, COL4A4, or COL4A5. The study was conducted to identify the underlying genetic causes in patients with familial hematuria.

Methods: Two unrelated Han-Chinese pedigrees with familial hematuria were recruited for this study. Whole exome sequencing was combined with in silico analysis to identify potential genetic variants, followed by variant confirmation by Sanger sequencing. Reverse transcription, PCR, and Sanger sequencing were performed to evaluate the effect of the detected splicing variant on mRNA splicing.

Results: A novel heterozygous splicing c.595-1G>A variant and a known heterozygous c.1715G>C variant in the collagen type IV alpha 4 chain gene (COL4A4) were identified and confirmed in patients of pedigree 1 and pedigree 2, respectively. Complementary DNA analysis indicated this splicing variant could abolish the canonical splice acceptor site and cause a single nucleotide deletion of exon 10, which was predicted to produce a truncated protein.

Conclusions: The two COL4A4 variants, c.595-1G>A variant and c.1715G>C (p.Gly572Ala) variant, were identified as the genetic etiologies of two families with familial hematuria, respectively. Our study broadened the variant spectrum of the COL4A4 gene and explained the possible pathogenesis, which will benefit clinical management and genetic counseling.
Single-cell RNA sequencing reveals intratumoral heterogeneity and potential mechanisms of malignant progression in prostate cancer with perineural invasion
Authors: Zhang Bao , Wang Shenghan , Fu Zhichao , Gao Qiang , Yang Lin , Lei Zhentao , Shi Yuqiang , Le Kai , Xiong Jie , Liu Siyao , Zhang Jiali , Su Junyan , Chen Jing , Liu Mengyuan , Niu Beifang
Published: January 2023

Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.

Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition of tumor tissues. The differently expressed genes among each cluster were identified by EdgeR. GO enrichment analysis was used to understand the roles of genes within the clusters. Pseudotime cell trajectory was used to reveal the molecular pathways underlying cell fate decisions and identify genes whose expression changed as the cells underwent transition. We applied CellPhoneDB to identify cell-cell interactions among the epithelial and neural cells in PNI-PCa.

Results: Analysis of the ∼17,000 single-cell transcriptomes in three PNI prostate cancer tissues, we identified 12 major cell clusters, including neural cells and two epithelial subtypes with different expression profiles. We found that basal/intermediate epithelial cell subtypes highly expressed PCa progression-related genes, including PIGR, MMP7, and AGR2. Pseudotime trajectory analysis showed that luminal epithelial cells could be the initiating cells and transition to based/intermediate cells. Gene ontology (GO) enrichment analysis showed that pathways related to cancer progressions, such as lipid catabolic and fatty acid metabolic processes, were significantly enriched in basal/intermediate cells. Our analysis also suggested that basal/intermediate cells communicate closely with neural cells played a potential role in PNI-PCa progression.

Conclusion: These results provide our understanding of PNI-PCa cellular heterogeneity and characterize the potential role of basal/intermediate cells in the PNI-PCa progression.
Global trends in research of immune cells associated with hypertensive disorders of pregnancy: A 20-year bibliometric analyses (from 2001 to 2021)
Authors: Wang Yue , Li Baoxuan , Tong Fei
Published: January 2023

Background

A growing evidence suggests that immune cells play a significant role in the pathogenesis of hypertensive disorders of pregnancy (HDP).Over the past 20 years, several studies have been conducted on the role of immune cells in hypertensive disorders of pregnancy. This study used bibliometric analysis to assess research hotspots and future trends in studies on immune cells in hypertensive disorders of pregnancy.

Methods

We extracted all relevant literature on immune cells and hypertensive disorders of pregnancy from the Web of Science core collection for the period of 2001 to 2021. We used VOS Viewer, CiteSpace, R-bibliometrix and Python for bibliometric analysis.

Results

We identified 2,388 records published in 593 journals by 9,886 authors from 2,174 universities/institutions in 91 countries/regions. The number of publications tended to increase over time, with the highest number of publications in 2021, up to 205. The USA was the country with the most publications. UNIVERSITY OF MISSISSIPPI was the most influential institution. Lamarca B, Romero R, and Saito S were the most prolific authors. Finally, three research hotspot clusters were identified based on keywords, which reflected the role of immune cells in the development of hypertensive disorders of pregnancy, the current research status,and predicted hot spots for future research.

Conclusions

Our study systematically analyzed the role of immune cells in the pathogenesis of hypertensive disorders of pregnancy in the last 20 years. Our results indicated that immune cells, such as T cells, natural killer (NK) cells,and macrophages, and the cytokines released such as TNF-α, IFN-γ in the maternal circulation and at the maternal-fetal interface would influence the development of hypertensive disorders of pregnancy and we need further investigate the role of individual immune cells and translational studies to provide new therapeutic perspectives to mitigate adverse perinatal outcomes due to hypertensive disorders of pregnancy. In conclusion, bibliometric studies provide a general overview of immune cells in the study of hypertensive disorders of pregnancy.
Retrospective analysis on the immunopotentiating mechanism of an emulsion-based vaccine adjuvant on human antigen presenting cells
Authors: Bonam Srinivasa Reddy , Platenburg Peter Paul , Bayry Jagadeesh
Published: January 2023

We retrospectively analyzed the immunopotentiating mechanism of an oil-in-water (O/W) emulsion-based vaccine adjuvant LiteVax™ Adjuvant (LVA) that contains CMS (Maltose 4’-monosulphate 1,2,3,6,2’,3’,6’-heptadecanoic acid ester), squalane, Tween 80 in phosphate buffered saline. Despite being effective in animal models, the immunological mechanisms by which LVA exerts adjuvant function are not known. As dendritic cells (DC) are key for initiating and propagating the immune response, we have investigated the effect of LVA and of its components on the DC function. We show that CMS but not LVA significantly enhances the expression of DC activation-associated markers, cytokine secretion, and CD4+ T cell responses. On the other hand, CMS ZERO [non-sulphated sucrose fatty acid esters (ZERO)], used as a control, had no such activity. Our data identified the unique nature of CMS in LVA, and propose that LVA acts as a delivery system, and CMS acts as an immunostimulatory agent.
Perceptions of practitioners on the importance and achievement of research and social implementation activities on marine and freshwater carbon
Authors: Watanabe Satoshi , Maruya Yasuyuki , Yano Shinichiro , Nakayama Keisuke
Published: January 2023

Research and social implementation related to carbon in marine and freshwater ecosystems are increasingly gaining emphasis in the global quest to achieve carbon neutrality. It is important not only to advance academic research, but also to solve practical problems for improved understanding, maintenance, and dissemination of information on carbon in marine or freshwater areas. In this study, we conducted a questionnaire survey of participants in activities related to carbon in marine or freshwater areas in Japan to clarify which issues were considered important and their understanding of the degree to which activities related to carbon in marine or freshwater areas had been achieved. Based on the responses to all questions, 77.9% of respondents, on average, among the practitioners in marine areas recognized the importance of the program strongly, while 46.5% recognized that the degree of achievement was insufficient. This tendency was more pronounced for carbon in freshwater than in marine areas(72.2% and 48.6%, respectively). The results, grouped by respondent attributes, revealed that the perception of importance and level of achievement varied depending on the organization of the activity, age, and years of knowledge of carbon in marine and/or freshwater areas. Practitioners with greater experience and those working on specific implementations perceived implementation-related aspects as more important and less accomplished than academic ones. This study provides valuable insights into the research aspects of carbon in marine and/or freshwater areas to achieve carbon neutrality.
Enhanced proliferation in a prawn embryonic primary cell culture ectopically expressing mutated Ras
Authors: Sudarshan Gurucharan , Weil Simy , Rotem-Dai Noa , Manor Rivka , Greenshpan Yariv , Goldstein Oron , Sharabi Omri , Aflalo Eliahu D. , Ofir Rivka , Rosental Benyamin , Gazit Roi , Sagi Amir
Published: January 2023

Crustacean cell line immortalization has gained a great deal of attention in recent decades for both scientific and applied reasons. Our goal in this study was to advance the state of art towards establishing an immortalized cell line by improving the proliferation rates of primary cells isolated from embryos of the giant freshwater prawn Macrobrachium rosenbergii by using a lentivirus expressing the Ras oncogene. The choice of Ras derived from its involvement in various cellular pathways, such as cell growth, differentiation, and survival, and its use as a tool for in-vitro immortalization, e.g., a specific mutated Ras (RasV12) was used to generate an arthropod cell line. Complementarily, in-silico screening of M. rosenbergii transcriptomic libraries for Ras expression indicated that Ras is already expressed at very early stages of embryo development. In the current study, we transduced primary M. rosenbergii embryonic cells with a lentivirus expressing RasV12 by using the white spot syndrome virus (WSSV IE1) promoter. Expression and sequencing (as followed by sequencing cDNA, confocal microscopy and FACS analysis) of the mutated Ras in the transduced cells confirmed that the lentivirus was successfully integrated into the genome. The lenti-MrRas transduction rate was 23% in the total primary cell population and more than 80% in a sub-population of cells with high granularity. Proliferation of lenti-MrRas transfected cells was enhanced to almost 1200% of the seeding density by the end of our experiment (18 days), which was double that of the control. We were thus successful in enhancing the longevity of embryonic primary cell cultures by ectopic expression of the mutated Ras protein, but the improvement was not sufficient for immortalization.
Design, characterization and preliminary usability testing of a portable robot for unsupervised therapy of hand function
Authors: Ranzani Raffaele , Albrecht Martin , Haarman Claudia J. W. , Koh Emily , Devittori Giada , Held Jeremia P. O. , Tönis Frederik J. , Gassert Roger , Lambercy Olivier
Published: January 2023

Introduction:There is evidence that increasing therapy dose after stroke might promote recovery. Unfortunately, in clinical practice, therapy dose is limited by financial and organizational constraints. Simple robotic devices could be used without supervision in the clinic or at home to increase dose without requiring additional resources. For this purpose, we developed HandyBot, a portable three-degrees-of-freedom end-effector haptic device to perform sensorimotor task-oriented therapy of hand function (i.e., grasping, forearm pronosupination, wrist flexion-extension) in different environments.

Methods:We present the mechatronic design of the device and its technical evaluation in terms of workspace, dynamics (i.e., max end-effector velocity, acceleration and force), sensing (i.e., position, velocity and force resolution) and haptic performance (i.e., transparency, maximum stable impedance range, rigid contact rendering accuracy). In addition, its feasibility and usability (in terms of System Usability Scale (SUS)) were assessed in a single-session experiment with four subjects with chronic stroke that tested the HandyBot therapy platform (i.e., haptic device with a graphical/physical user interface and a set of therapy exercises) while simulating unsupervised use (i.e., the subject used the device independently while a therapist was only observing the session).

Results:HandyBot showed hardware and control performances comparable to other less portable therapy devices for hand function (e.g., 94% accuracy in stiffness rendering, low apparent mass of 0.2 kg in transparency mode), making it a suitable platform for the implementation of sensorimotor therapy exercises. HandyBot showed good platform usability in terms of SUS (i.e., above 75 out of 100 for device and graphical user interfaces, above 65 out of 100 for the exercises) when tested in simulated unsupervised settings. These tests underlined minor design improvements that should be considered to allow using such a device in uncontrolled settings.

Discussion:HandyBot is a novel robot for hand rehabilitation after stroke that revealed high-quality hardware and haptic performance. HandyBot was usable for stroke patients at first exposure for (simulated) unsupervised robot-assisted sensorimotor therapy of hand function. This therapy approach combined with this novel portable robotic device has the potential to help increase therapy dose and decrease therapy-associated costs (e.g., therapist time to therapy time ratio) in different environments.
Efficacy and safety of ciprofol for agitation and delirium in the ICU: A multicenter, single-blind, 3-arm parallel randomized controlled trial study protocol
Authors: Liu Guo Liang , Wu Guo Zhi , Ge Dong , Zhou Heng Jie , Cui Song , Gao Kai , Sun Wei Jia , Yu Dong Hai , Liu Si Bo , Liu Jin Jie
Published: January 2023

Background

Agitation is very common in the intensive care unit (ICU). The causes include pain, delirium, underlying disease, withdrawal syndrome, and some drug treatments. The practical goal of ICU treatment is to find an appropriate sedation regimen to reduce pain, restlessness, and delirium. Previous trials have examined the use of dexmedetomidine, but no trials have evaluated the efficacy and safety of ciprofol, a new sedative drug.

Methods

This study was a multicenter, single-blind, 3-arm parallel randomized controlled trial. ICU patients aged ≥ 18 years with agitation and delirium who met the eligibility criteria were included. The main outcome was the proportion of patients who needed additional study medication or midazolam due to agitation within 4 h after the first intravenous injection of the study medication. The secondary outcomes included the pass rate as indicated by a Richmond Agitation-Sedation Scale (RASS) score < +1, the effectiveness rate of improving delirium symptoms, the number of recurrences of agitation within 24 h, the incidence of rescue treatment, the dose and cost of analgesic and sedative drugs, the length and cost of ICU stay, and the 30-day survival period. The safety evaluation included the incidence of adverse events (hypotension, bradycardia, hypoxia, etc.) and the rate of endotracheal intubation. The subjects were randomly assigned to receive ciprofol, dexmedetomidine, or normal saline at a ratio of 1:1:1. The rates of additional drug administration within 4 h after the first injection of the study drug in the three groups were 40, 50, and 90%, respectively. A total sample size of 81 subjects was required to reach 90% power and an α of 0.05. Considering a 20% loss rate, 102 patients were enrolled and randomly assigned to the three groups in equal proportions.

Ethics and communication

This trial was approved by the Ethics Committee of Dalian Municipal Central Hospital. The communication plan includes presentations at scientific conferences, scientific publications, and presentations to the public through non-professional media.

Clinical trial registration

www.ClinicalTrials.gov, identifier ChiCTR220006 2799.
Novel models for early prediction and prevention of acute respiratory distress syndrome in patients following hepatectomy: A clinical translational study based on 1,032 patients
Authors: Wang Xiaoqiang , Zhang Hongyan , Zong Ruiqing , Yu Weifeng , Wu Feixiang , Li Yiran
Published: January 2023

Background

Acute respiratory distress syndrome (ARDS) is a serious organ failure and postoperative complication. However, the incidence rate, early prediction and prevention of postoperative ARDS in patients undergoing hepatectomy remain unidentified.

Methods

A total of 1,032 patients undergoing hepatectomy between 2019 and 2020, at the Eastern Hepatobiliary Surgery Hospital were included. Patients in 2019 and 2020 were used as the development and validation cohorts, respectively. The incidence rate of ARDS was assessed. A logistic regression model and a least absolute shrinkage and selection operator (LASSO) regression model were used for constructing ARDS prediction models.

Results

The incidence of ARDS was 8.8% (43/490) in the development cohort and 5.7% (31/542) in the validation cohort. Operation time, postoperative aspartate aminotransferase (AST), and postoperative hemoglobin (Hb) were all critical predictors identified by the logistic regression model, with an area under the curve (AUC) of 0.804 in the development cohort and 0.752 in the validation cohort. Additionally, nine predictors were identified by the LASSO regression model, with an AUC of 0.848 in the development cohort and 0.786 in the validation cohort.

Conclusion

We reported the incidence of ARDS in patients undergoing hepatectomy and developed two simple and practical prediction models for early predicting postoperative ARDS in patients undergoing hepatectomy. These tools may improve clinicians’ ability to early estimate the risk of postoperative ARDS and timely prevent its emergence.
1,4-dihydroxy quininib modulates the secretome of uveal melanoma tumour explants and a marker of oxidative phosphorylation in a metastatic xenograft model
Authors: Slater Kayleigh , Bosch Rosa , Smith Kaelin Francis , Jahangir Chowdhury Arif , Garcia-Mulero Sandra , Rahman Arman , O’Connell Fiona , Piulats Josep M. , O’Neill Valerie , Horgan Noel , Coupland Sarah E. , O’Sullivan Jacintha , Gallagher William M. , Villanueva Alberto , Kennedy Breandán N.
Published: January 2023

Uveal melanoma (UM) is an intraocular cancer with propensity for liver metastases. The median overall survival (OS) for metastatic UM (MUM) is 1.07 years, with a reported range of 0.84–1.34. In primary UM, high cysteinyl leukotriene receptor 1 (CysLT1) expression associates with poor outcomes. CysLT1 antagonists, quininib and 1,4-dihydroxy quininib, alter cancer hallmarks of primary and metastatic UM cell lines in vitro. Here, the clinical relevance of CysLT receptors and therapeutic potential of quininib analogs is elaborated in UM using preclinical in vivo orthotopic xenograft models and ex vivo patient samples. Immunohistochemical staining of an independent cohort (n = 64) of primary UM patients confirmed high CysLT1 expression significantly associates with death from metastatic disease (p = 0.02; HR 2.28; 95% CI 1.08–4.78), solidifying the disease relevance of CysLT1 in UM. In primary UM samples (n = 11) cultured as ex vivo explants, 1,4-dihydroxy quininib significantly alters the secretion of IL-13, IL-2, and TNF-α. In an orthotopic, cell line-derived xenograft model of MUM, 1,4-dihydroxy quininib administered intraperitoneally at 25 mg/kg significantly decreases ATP5B expression (p = 0.03), a marker of oxidative phosphorylation. In UM, high ATP5F1B is a poor prognostic indicator, whereas low ATP5F1B, in combination with disomy 3, correlates with an absence of metastatic disease in the TCGA-UM dataset. These preclinical data highlight the diagnostic potential of CysLT1 and ATP5F1B in UM, and the therapeutic potential of 1,4-dihydroxy quininib with ATP5F1B as a companion diagnostic to treat MUM.
Patterns and factors associated with pneumococcal vaccination in a prospective cohort of 1,697 patients with rheumatoid arthritis
Authors: Thomas Konstantinos , Lazarini Argyro , Kaltsonoudis Evripidis , Voulgari Paraskevi V. , Drosos Alexandros A. , Repa Argyro , Sali Ainour Molla Ismail , Sidiropoulos Prodromos , Tsatsani Panagiota , Gazi Sousana , Fragkiadaki Kalliopi , Tektonidou Maria G. , Sfikakis Petros P. , Katsimbri Pelagia , Boumpas Dimitrios , Argyriou Evangelia , Boki Kyriaki A. , Karagianni Konstantina , Katsiari Christina , Evangelatos Gerasimos , Iliopoulos Alexios , Grika Eleftheria P. , Vlachoyiannopoulos Panagiotis G. , Dimitroulas Theodoros , Garyfallos Alexandros , Melissaropoulos Konstantinos , Georgiou Panagiotis , Georganas Constantinos , Vounotrypidis Periklis , Ntelis Konstantinos , Areti Maria , Kitas George D. , Vassilopoulos Dimitrios
Published: January 2023

Introduction

Patients with rheumatoid arthritis (RA) are at increased risk for serious infections. Pneumococcal vaccination is among the most important preventive measures, however, vaccine uptake is suboptimal. We explored the rate and factors associated with pneumococcal vaccination in a contemporary RA cohort.

Materials and methods

Multi-center, prospective, RA cohort study in Greece. Patient and disease characteristics and influenza and pneumococcal vaccinations were documented at baseline and 3 years later.

Results

One thousand six hundred and ninety-seven patients were included and 34.5% had already received at least one pneumococcal vaccine at baseline. Among 1,111 non-vaccinated patients, 40.1% received pneumococcal vaccination during follow-up, increasing the vaccine coverage to 60.8%. By multivariate analysis, positive predictors for pneumococcal vaccination included prescription of influenza vaccine (OR = 33.35, 95% CI: 18.58–59.85), history of cancer (OR = 2.35, 95% CI: 1.09–5.06), bDMARD use (OR = 1.85, 95% CI: 1.29–2.65), seropositivity (OR = 1.47, 95% CI: 1.05–2.05), and high disease activity (DAS28-ESR, OR = 1.33, 95% CI: 1.17–1.51). Male sex (OR = 0.65, 95% CI: 0.43–0.99) was a negative predictor for pneumococcal vaccination during follow-up.

Discussion

Despite increasing rates of pneumococcal vaccine coverage, 40% of RA patients remain unvaccinated. Severe disease, bDMARD use, comorbidities, and more importantly flu vaccination were the most significant factors associated with pneumococcal vaccination, emphasizing the currently unmet need for cultivating a “vaccination culture” in RA patients.
Comparative effectiveness of acupuncture in sham-controlled trials for knee osteoarthritis: A systematic review and network meta-analysis
Authors: Lee Boram , Kim Tae-Hun , Birch Stephen , Alraek Terje , Lee Hye Won , Nielsen Arya , Wieland L. Susan , Lee Myeong Soo
Published: January 2023

Objectives

Although many trials have assessed the effect of acupuncture on knee osteoarthritis (KOA), its efficacy remains controversial. Sham acupuncture techniques are regarded as representative control interventions in acupuncture trials and sometimes incorporate the use of sham devices (base units) to support a non-penetrating needle. To achieve successful blinding, these trials also use acupuncture base units in the verum acupuncture group. Base units are not used in real-world clinical settings. We aimed to assess the effect sizes of verum and sham acupuncture for KOA in sham-controlled trials with or without base units.

Methods

A total of 10 electronic databases for randomized controlled trials (RCTs) comparing the efficacy of verum manual acupuncture and sham acupuncture for the treatment of KOA were searched for articles published before April 12, 2022. The primary outcome was pain intensity, and the secondary outcomes included physical function. The first assessment after the end of treatment was chosen for analysis. Effect sizes are reported as standardized mean differences (SMDs) with 95% confidence intervals (95% CIs). The risk of bias was assessed using the Cochrane risk of bias tool, and publication bias was evaluated using a funnel plot and Egger’s test. The quality of evidence for estimates was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach.

Results

Fifteen RCTs were included. There was generally a low risk of bias except for the difficulty in blinding acupuncture therapists (performance bias). Compared to verum acupuncture in sham-controlled trials using base units, verum acupuncture in sham-controlled trials without base units was more effective for improving pain (SMD −0.56, 95% CI −1.09 to −0.03) and function (SMD −0.73, 95% CI −1.36 to −0.10) in KOA. The quality of evidence for network estimates was moderate to low due to the risk of bias and imprecision.

Conclusion

These findings suggest that verum acupuncture in different types of sham-controlled trials has different effect sizes for KOA. Because base units are not used in clinical settings, the results of verum acupuncture in sham-controlled trials with base units need to be interpreted carefully.

Systematic review registration

https://www.researchregistry.com/browse-the-registry#registryofsystematicreviewsmeta-analyses/registryofsystematicreviewsmeta-analysesdetails/6269f962606c5e001fd8790c/, identifier reviewregistry1351.
Case report: Sotrovimab, remdesivir and nirmatrelvir/ritonavir combination as salvage treatment option in two immunocompromised patients hospitalized for COVID-19
Authors: Baldi Federico , Dentone Chiara , Mikulska Malgorzata , Fenoglio Daniela , Mirabella Michele , Magnè Federica , Portunato Federica , Altosole Tiziana , Sepulcri Chiara , Giacobbe Daniele Roberto , Uras Chiara , Scavone Graziana , Taramasso Lucia , Orsi Andrea , Cittadini Giuseppe , Filaci Gilberto , Bassetti Matteo
Published: January 2023

COVID-19 in immunocompromised patients is difficult to treat. SARS-CoV-2 interaction with the host immune system and the role of therapy still remains only partly understood. There are no data regarding the use of monoclonal antibodies and the combination of two antivirals in fighting viral replication and disease progression. We report the cases of two patients, both treated with rituximab for non-Hodgkin lymphoma and granulomatosis with polyangiitis, respectively, and both hospitalized for COVID-19 with positive SARS-CoV-2 RNAemia, who were successfully treated with a salvage combination therapy with sotrovimab, remdesivir and nirmatrelvir/ritonavir.
Gut-muscle crosstalk. A perspective on influence of microbes on muscle function
Authors: Chew Weixuan , Lim Yen Peng , Lim Wee Shiong , Chambers Edward S. , Frost Gary , Wong Sunny Hei , Ali Yusuf
Published: January 2023

Our gastrointestinal system functions to digest and absorb ingested food, but it is also home to trillions of microbes that change across time, nutrition, lifestyle, and disease conditions. Largely commensals, these microbes are gaining prominence with regards to how they collectively affect the function of important metabolic organs, from the adipose tissues to the endocrine pancreas to the skeletal muscle. Muscle, as the biggest utilizer of ingested glucose and an important reservoir of body proteins, is intricately linked with homeostasis, and with important anabolic and catabolic functions, respectively. Herein, we provide a brief overview of how gut microbiota may influence muscle health and how various microbes may in turn be altered during certain muscle disease states. Specifically, we discuss recent experimental and clinical evidence in support for a role of gut-muscle crosstalk and include suggested underpinning molecular mechanisms that facilitate this crosstalk in health and diseased conditions. We end with a brief perspective on how exercise and pharmacological interventions may interface with the gut-muscle axis to improve muscle mass and function.
Clinical genome editing to treat sickle cell disease—A brief update
Authors: Zarghamian Parinaz , Klermund Julia , Cathomen Toni
Published: January 2023

Sickle cell disease (SCD) is one of the most common hemoglobinopathies. Due to its high prevalence, with about 20 million affected individuals worldwide, the development of novel effective treatments is highly warranted. While transplantation of allogeneic hematopoietic stem cells (HSC) is the standard curative treatment approach, a variety of gene transfer and genome editing strategies have demonstrated their potential to provide a prospective cure for SCD patients. Several stratagems employing CRISPR-Cas nucleases or base editors aim at reactivation of γ-globin expression to replace the faulty β-globin chain. The fetal hemoglobin (HbF), consisting of two α-globin and two γ-globin chains, can compensate for defective adult hemoglobin (HbA) and reverse the sickling of hemoglobin-S (HbS). Both disruption of cis-regulatory elements that are involved in inhibiting γ-globin expression, such as BCL11A or LRF binding sites in the γ-globin gene promoters (HBG1/2), or the lineage-specific disruption of BCL11A to reduce its expression in human erythroblasts, have been demonstrated to reestablish HbF expression. Alternatively, the point mutation in the HBB gene has been corrected using homology-directed repair (HDR)-based methodologies. In general, genome editing has shown promising results not only in preclinical animal models but also in clinical trials, both in terms of efficacy and safety. This review provides a brief update on the recent clinical advances in the genome editing space to offer cure for SCD patients, discusses open questions with regard to off-target effects induced by the employed genome editors, and gives an outlook of forthcoming developments.
Case report: Kimura's disease with minimal degenerative glomerulopathy without eosinophil infiltration responds to mycophenolate mofetil treatment
Authors: Han Qing , Han Jie , Wang Weitao , Gao Jie , Qiao Youzhen , Jia Junfeng , Zhang Kui , Zheng Zhaohui , Zhu Ping
Published: January 2023

Kimura's disease (KD) is a rare chronic progressive immune inflammatory disease. The etiology is unknown and manifests as a chronic inflammatory process, which is more common in young Asian men. The clinical manifestations are painless subcutaneous swelling of the head and neck and periauricular lymphadenopathy, which is slow growing and has a benign course. KD may involve the kidney, and pathological examination revealed eosinophil infiltration in the renal tissue. Proteinuria has been reported in 12–16% of KD cases, and about 60–70% of KD patients will develop nephrotic proteinuria. KD is easily confused with nephrotic syndrome, because KD does not have specific clinical manifestations, laboratory and imaging, and early misdiagnosis is easy. We report a case of KD that was biopsy-proven to have minimal lesion glomerulopathy after ~11 years. In this report, we describe a clinical case of KD with nephrotic syndrome, but there's no eosinophil infiltration in the kidneys. The clinical manifestations of KD recurrence were bilateral eyelid edema, bilateral lower limb swelling, and massive proteinuria in response to mycophenolate mofetil treatment (1.5 g).
Clinical characteristics and outcomes of critically ill coronavirus disease 2019 patients in Malaysia during the first wave: A multi-center observational study (COVIDICU-MY)
Authors: Ab Rahman Noor Iftitah , Yunos Nor’azim Mohd , Atan Rafidah , Mariapun Jeevitha , Ab Rahman Mohd Ali‘Imran , Ismail Abdul Jabbar , Deva Shanti Rudra
Published: January 2023

Background

Coronavirus disease 2019 (COVID-19) emerged with a wide range of clinical presentations; Malaysia was not spared from its impact. This study describes the clinical characteristics of COVID-19 patients admitted to intensive care unit, their clinical course, management, and hospital outcomes.

Methods

COVIDICU-MY is a retrospective analysis of COVID-19 patients from 19 intensive care units (ICU) across Malaysia from 1 March 2020 to 31 May 2020. We collected epidemiological history, demographics, clinical comorbidities, laboratory investigations, respiratory and hemodynamic values, management, length of stay and survival status. We compared these variables between survival and non-survival groups.

Results

A total of 170 critically ill patients were included, with 77% above 50 years of age [median age 60, IQR (51–66)] and 75.3% male. Hypertension, diabetes mellitus, hyperlipidemia, chronic cardiac disease, and chronic kidney disease were most common among patients. A high Simplified Acute Physiology Score (SAPS) II score [median 45, IQR (34–49)] and Sequential Organ Failure Assessment (SOFA) score [median 8, IQR (6–11)] were associated with mortality. Patients were profoundly hypoxic with a median lowest PaO2/FiO2 ratio of 150 (IQR 99–220) at admission. 91 patients (53.5%) required intubation on their first day of admission, out of which 38 died (73.1% of the hospital non-survivors). Our sample had more patients with moderate Acute Respiratory Distress Syndrome (ARDS), 58 patients (43.9%), compared to severe ARDS, 33 patients (25%); with both ARDS classification groups contributing to 25 patients (54.4%) and 11 patients (23.9%) of the non-survival group, respectively. Cumulative fluid balance over 24 h was higher in the non-survival group with significant differences on Day 3 (1,953 vs. 622 ml, p < 0.05) and Day 7 of ICU (3,485 vs. 830 ml, p < 0.05). Patients with high serum creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and low lymphocyte count throughout the stay also had a higher risk of mortality. The hospital mortality rate was 30.6% in our sample.

Conclusion

We report high mortality amongst critically ill patients in intensive care units in Malaysia, at 30.6%, during the March to May 2020 period. High admission SAPS II and SOFA, and severe hypoxemia and high cumulative fluid balance were associated with mortality. Higher creatinine, urea, lactate dehydrogenase, aspartate aminotransferase and d-dimer, and lymphopenia were observed in the non-survival group.
Case report: Thrombotic microangiopathy concomitant with macrophage activation syndrome in systemic lupus erythematosus refractory to conventional treatment successfully treated with eculizumab
Authors: Yamaguchi Makoto , Mizuno Masashi , Kitamura Fumiya , Iwagaitsu Shiho , Nobata Hironobu , Kinashi Hiroshi , Banno Shogo , Asai Akimasa , Ishimoto Takuji , Katsuno Takayuki , Ito Yasuhiko
Published: January 2023

Thrombotic microangiopathy (TMA) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). Macrophage activation syndrome (MAS) is also a rare, life-threatening hyperinflammatory condition that is comorbid with SLE. However, the association between TMA and MAS in patients with SLE has rarely been assessed, and the difficulty of diagnosing these conditions remains prevalent. The efficacy of eculizumab has been reported for SLE patients whose conditions are complicated with TMA. However, no study has investigated the therapeutic efficacy of eculizumab for TMA concomitant with SLE-associated MAS. Herein, we report the first case of TMA concomitant with SLE-associated MAS that was initially refractory to conventional immunosuppressive therapy but showed remarkable recovery after eculizumab treatment. Furthermore, we evaluated serum syndecan-1 and hyaluronan levels, which are biomarkers of endothelial damage. We found that these levels decreased after the administration of eculizumab, suggesting that TMA was the main pathology of the patient. This case illustrates that it is important to appropriately assess the possibility of TMA during the course of SLE-associated MAS and consider the use of eculizumab as necessary.
Clinical efficacy of acupuncture for pain relief from renal colic: A meta-analysis and trial sequence analysis
Authors: Chen Hsiao-Tien , Kuo Cheng-Feng , Hsu Chin-Chia , Lai Li-Chun , Cheng Ai-Chin , Sun Cheuk-Kwan , Hung Kuo-Chuan
Published: January 2023

Background

This meta-analysis aimed at investigating the efficacy of acupuncture for relieving renal colic and reducing the risk of analgesic-related complications.

Methods

Randomized controlled trials (RCTs) comparing the efficacy of acupuncture (acupuncture group) with conventional interventions (control group) were screened from MEDLINE, EMBASE, Cochrane library databases, China Knowledge Network (CNKI), and Airiti Library till July 15, 2022. The primary outcome was the rate of effective pain relief (response rate), while secondary outcomes included the time of onset of pain relief, visual analog scale (VAS) at 30–60 min and risk of side effects.

Results

Thirteen eligible studies involving 1,212 participants published between 1992 and 2021 were analyzed. Compared with the control group, patients receiving acupuncture had a higher overall response rate [risk ratio (RR) = 1.12, 95% CI: 1.05–1.19, p = 0.0002, I2 = 41%, 1,136 patients] (primary outcome) and a faster pain relief [MD = −10.74 min, 95% CI: −12.65 to −8.82, p < 0.00001, I2 = 87%, 839 patients]. Patients receiving acupuncture had a lower pain score [MD = −0.65, 95% CI: −1.09 to −0.21, p = 0.21, I2 = 55%, 327 patients] and risk of side effects (RR = 0.11, 95% CI: 0.04–0.26, p < 0.00001, I2 = 0, 314 patients) compared to those receiving conventional interventions. Results from trial sequence analysis revealed sufficient evidence supporting the beneficial effects of acupuncture on response rate, time to pain relief, and pain score at 30–60 min.

Conclusion

Compared with conventional analgesic-based interventions, acupuncture can more efficiently relieve renal colic with fewer adverse effects. The limited number and quality of included studies warrant more clinical RCTs to support our findings.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022346714.
Disease clearance in ulcerative colitis: Setting the therapeutic goals for future in the treatment of ulcerative colitis
Authors: Ramos Laura , Teo-Loy Jeny , Barreiro-de Acosta Manuel
Published: January 2023

Ulcerative colitis, one of the phenotypic patterns of inflammatory bowel disease, should be considered a progressive disease with an increased risk of complications if intestinal inflammation is not adequately controlled. The advent of new lines of treatment for this condition has changed and expanded the therapeutic goals to modify its natural history and evolution. The concept of “disease clearance” in ulcerative colitis aims to achieve clinical and biological remission as well as mucosal healing (endoscopic, histological, and in future molecular) in these patients. This review provides the available data on each of the goals of disease clearance in ulcerative colitis to be considered for application in clinical practice in the coming years.
Intergenerational transmission of parental risky health behaviors in Chinese children: Are there socioeconomic status differences?
Authors: Yu Zexuan , Qin Wen , Li Jiajia
Published: January 2023

Background

Risky health behaviors in childhood, including smoking, alcohol consumption, and having a poor diet, are the major sources of non-communicable diseases in adulthood. This study aimed to examine how parents affect children's risky health behaviors and whether intergenerational transmission differs based on socioeconomic status (SES).

Methods

Data were extracted from the 1991–2015 China Health and Nutrition Survey (CHNS). Smoking (n = 5,946), alcohol consumption (n = 7,821), and sugar-sweetened beverages (SSBs) consumption (n = 3,537) were used as proxies for risky health behaviors in children. A binary choice model for panel data with a random-effect specification was employed to examine whether risky health behaviors can be transmitted from parents to their children. Subsequently, we conducted a seemingly unrelated estimation test (SUEST) to explore the differences in parental transmission between the different SES groups.

Results

We found strong intergenerational persistence of smoking, alcohol drinking, and SSBs drinking behaviors, except for the mothers' smoking behavior. Mothers had a greater influence on children's alcohol drinking and SSBs drinking behaviors than fathers both in urban and rural areas and in different SES groups. The intergenerational transmission of SSBs drinking behavior exhibited a decreasing trend with increasing SES for both urban and rural families. In urban areas, mothers' alcohol drinking behavior has a decreasing trend with increasing education level, occupation, and income; however, in rural areas, the influence of mothers' alcohol drinking behavior occurred in the same direction with increasing education level and occupation type. In rural areas, the influence of fathers' drinking and smoking behaviors on children appears to mostly increase with increasing SES. Meanwhile, the influence of such behaviors among urban fathers would decrease with increasing SES.

Conclusion

Parents' behaviors and SES can influence the initiation of risky health behaviors in their offspring. Thus, to promote healthy behaviors, policymakers can introduce health education programs for parents, particularly for those living in rural areas and with a low SES.