bluuebunny/crossref_metadata_2025 huggingface dataset:
Dextroamphetamine Treatment in Children With Hypothalamic Obesity
Authors: van Schaik Jiska , Welling Mila S. , de Groot Corjan J. , van Eck Judith P. , Juriaans Alicia , Burghard Marcella , Oude Ophuis Sebastianus B. J. , Bakker Boudewijn , Tissing Wim J. E. , Schouten-van Meeteren Antoinette Y. N. , van den Akker Erica L. T. , van Santen Hanneke M.
Published: March 2022

Introduction

Hypothalamic obesity (HO) in children has severe health consequences. Lifestyle interventions are mostly insufficient and currently no drug treatment is approved for children with HO. Amphetamines are known for their stimulant side-effect on resting energy expenditure (REE) and suppressing of appetite. Earlier case series have shown positive effects of amphetamines on weight in children with acquired HO. We present our experiences with dextroamphetamine treatment in the, up to now, largest cohort of children with HO.

Methods

A retrospective cohort evaluation was performed of children with HO treated with dextroamphetamine at two academic endocrine pediatric clinics. Off-label use of dextroamphetamine was initiated in patients with progressive, therapy-resistant acquired or congenital HO. Anthropometrics, REE, self-reported (hyperphagic) behavior and energy level, and side effects were assessed at start and during treatment.

Results

Nineteen patients with a mean age of 12.3 ± 4.0 years had been treated with dextroamphetamine. In two patients, ΔBMI SDS could not be evaluated due to short treatment duration or the simultaneous start of extensive lifestyle treatment. Mean treatment duration of the 17 evaluated patients was 23.7 ± 12.7 months. Fourteen patients (n = 10 with acquired HO, n = 4 with congenital HO) responded by BMI decline or BMI stabilization (mean ΔBMI SDS of -0.6 ± 0.8, after a mean period of 22.4 ± 10.5 months). In three patients, BMI SDS increased (mean ΔBMI SDS of +0.5 ± 0.1, after a mean period of 29.7 ± 22.6 months). In 11 responders, measured REE divided by predicted REE increased with +8.9%. Thirteen patients (68.4%) reported decreased hyperphagia, improvement of energy level and/or behavior during treatment. Two patients developed hypertension during treatment, which resulted in dosage adjustment or discontinuation of treatment. Twelve children continued treatment at last moment of follow-up.

Conclusion

In addition to supportive lifestyle interventions, dextroamphetamine treatment may improve BMI in children with HO. Furthermore, dextroamphetamines have the potential to decrease hyperphagia and improve resting energy expenditure, behavior, and energy level. In patients with acquired HO, these effects seem to be more pronounced when compared to patients with congenital HO. Future studies are needed to support these results.
Active Cable Sheath Current-Based Protection Scheme for an Offshore HVAC Wind Transmission System
Authors: Zhao Yang , Liu Qing , Xia Rong , Shang Yingqiang
Published: March 2022

Due to the complex sending terminal structure of offshore wind transmission systems, conventional on-line monitoring-based protection cannot work well. The electromagnetic transient faults are also difficult to locate due to a short time span with fast characteristics that are affected by various power electronic devices and control algorithms. To solve the aforementioned problems, a new offshore wind transmission line protection scheme based on active detection of submarine cable sheath current is proposed. This method uses a normalized coding cooperation to realize the risk levels and failure locations of the transient defects, and then the sheath currents become a characteristic input data source, which can build a clear system protection boundary. Case studies using MATLAB and ATP simulations are carried out, where three types of transient faults represented by sheath currents are studied, i.e., loss of electrical continuity of grounding device, short circuit of segmented metal sheath of cable joint, and water immersion of junction box. Testing results illustrated that the proposed method could achieve fast fault detection and precise fault location of the electromagnetic transients. Moreover, compared with conventional wind farm protection techniques, it only needs to add few signal injection modules with high sampling frequency into the submarine optical fibers.
Plankton Diversity in Tropical Wetlands Under Different Hydrological Conditions (Lake Tana, Ethiopia)
Authors: Kahsay Abrehet , Lemmens Pieter , Triest Ludwig , De Meester Luc , Kibret Mulugeta , Verleyen Elie , Adgo Enyew , Wondie Ayalew , Stiers Iris
Published: March 2022

Plankton is an integral part of wetland biodiversity and plays a vital role in the functioning of wetlands. Diversity patterns of plankton in wetlands and factors structuring its community composition are poorly understood, albeit important for identifying areas for restoration and conservation. Here we investigate patterns in local and regional plankton richness and taxonomic and functional community composition in riverine papyrus swamps, river mouth wetlands, and lacustrine wetlands in the Lake Tana sub-basin, Ethiopia. Data on phytoplankton, zooplankton, and environmental variables were collected from 12 wetlands during the dry and wet seasons of 2018. Redundancy analysis, and linear mixed effect models, were used to investigate differences in local environmental conditions and variation in plankton community richness and composition between wetland types. We also assessed the ecological uniqueness of the plankton community by calculating the contribution of a single wetland: local contributions to overall beta diversity (LCBD) and contributions of individual species (SCBD) to overall beta diversity (BDTotal). Beta regression models were used to investigate the relationships of LCBD and SCBD to environmental variables, wetland, and taxa characteristics. A total of 85 phytoplankton taxa, distributed among 18 Reynolds functional groups, and 57 zooplankton taxa were observed over the entire set of samples. Local plankton taxon richness was significantly higher in riverine papyrus swamps (mean taxa of 30 phytoplankton and 21 zooplankton) compared to river mouth wetlands (mean taxa of 27 phytoplankton and 13 zooplankton). Several local environmental variables and the composition of the plankton community differed significantly between the three wetland types. The highest phytoplankton ecological uniqueness (LCBD) was detected in lacustrine wetlands, whereas the riverine papyrus swamps had the highest zooplankton ecological uniqueness. Based on our analyses, we recommend protecting the wetlands with high LCBD values and stress the importance of various wetland types for preserving the diverse plankton communities of Lake Tana wetlands.
Chip Off the Old Block: Generation, Development, and Ancestral Concepts of Heredity
Authors: Poczai Péter , Santiago-Blay Jorge A.
Published: March 2022

Heredity is such a fundamental concept that it is hard to imagine a world where the connection between parents and offspring is not understood. Three hundred years ago thinking of the phenomenon of heredity bore on a cluster of distinct philosophical questions inherited from antiquity concerning the nature and origin of substances or beings that lacked biological meaning. We are reminded of this philosophical heritage by the fact that in the 18th century the study of reproduction, embryology and development was referred to as “the science of generation”. It is now clear that reproduction, the biological process by which parents produce offspring, is a fundamental feature of all life on Earth. Heredity, the transmission of traits from parents to offspring via sexual or asexual reproduction, allows differences between individuals to accumulate and evolve through natural selection. Genetics is the study of heredity, and in particular, variation of fundamental units responsible for heredity. Ideas underlying this theory evolved in considerably different and unrelated ways across a number of knowledge domains, including philosophy, medicine, natural history, and breeding. The fusion of these different domains into a single comprehensive theory in 19th century biology was a historically and culturally interdependent process, thus examining genetic prehistory should unravel these entanglements. The major goal of our review is tracing the various threads of thought that gradually converged into our contemporary understanding of heredity.
The Programmed Death-1 Pathway Counter-Regulates Inflammation-Induced Osteoclast Activity in Clinical and Experimental Settings
Authors: Greisen Stinne R. , Kragstrup Tue W. , Thomsen Jesper Skovhus , Hørslev-Pedersen Kim , Hetland Merete Lund , Stengaard-Pedersen Kristian , Østergaard Mikkel , Ørnbjerg Lykke , Junker Peter , Sharpe Arlene H. , Freeman Gordon J. , Hvid Malene , Moestrup Søren K. , Hauge Ellen Margrethe , Deleuran Bent
Published: March 2022

Objective

The programmed death-1 (PD-1) pathway is essential for maintaining self-tolerance and plays an important role in autoimmunity, including rheumatoid arthritis (RA). Here, we investigated how membrane-bound and soluble (s)PD-1 influence bone homeostasis during chronic inflammation, exemplified in RA.

Methods

Bone mineral density and bone microstructure were examined in PD-1 and PD-L1 knockout (KO) mice and compared with wild-type (WT) mice. Receptor activator of nuclear factor kappa-B ligand (RANKL) was measured in serum, and the expression examined on activated bone marrow cells. Osteoclast formation was examined in cells from murine spleen and bone marrow and from human synovial fluid cells. sPD-1 was measured in chronic and early (e)RA patients and correlated to markers of disease activity and radiographic scores.

Results

PD-1 and PD-L1 KO mice showed signs of osteoporosis. This was supported by a significantly reduced trabecular bone volume fraction and deteriorated microstructure, as well as increased osteoclast formation and an increased RANKL/OPG ratio. The recombinant form of sPD-1 decreased osteoclast formationin vitro, but was closely associated with disease activity markers in eRA patients. Sustained elevated sPD-1 levels indicated ongoing inflammation and were associated with increased radiographic progression.

Conclusion

The PD-1 pathway is closely associated with bone homeostasis, and lacking members of this pathway causes a deteriorated bone structure. The immunological balance in the microenvironment determines how the PD-1 pathway regulates osteoclast formation. In eRA patients, sPD-1 may serve as a biomarker, reflecting residual but clinically silent disease activity and radiographic progression.
Plasmodium falciparum-Specific Memory B-Cell and Antibody Responses Are Associated With Immunity in Children Living in an Endemic Area of Kenya
Authors: Jahnmatz Peter , Nyabundi Diana , Sundling Christopher , Widman Linnea , Mwacharo Jedidah , Musyoki Jennifer , Otieno Edward , Ahlborg Niklas , Bejon Philip , Ndungu Francis M. , Färnert Anna
Published: March 2022

Identifying the mechanism of naturally acquired immunity against Plasmodium falciparum malaria could contribute to the design of effective malaria vaccines. Using a recently developed multiplexed FluoroSpot assay, we assessed cross-sectional pre-existing memory B-cells (MBCs) and antibody responses against six well known P. falciparum antigens (MSP-119, MSP-2 (3D7), MSP-2 (FC27), MSP-3, AMA-1 and CSP) and measured their associations with previous infections and time to clinical malaria in the ensuing malaria season in Kenyan children. These children were under active weekly surveillance for malaria as part of a long-term longitudinal malaria immunology cohort study, where they are recruited from birth. After performing Cox regression analysis, we found that children with a breadth of three or more antigen-specific MBC or antibody responses at the baseline had a reduced risk for malaria in the ensuing P. falciparum transmission season. Specifically, MBC responses against AMA-1, MSP-2 (3D7) and MSP-3, as well as antibody responses to MSP-2 (3D7) and MSP-3 were prospectively associated with a reduced risk for malaria. The magnitude or breadth of MBC responses were however not correlated with the cumulative number of malaria episodes since birth. We conclude that increased breadth for merozoite antigen-specific MBC and antibody responses is associated with protection against malaria.
PDK4 Inhibition Ameliorates Melatonin Therapy by Modulating Cerebral Metabolism and Remyelination in an EAE Demyelinating Mouse Model of Multiple Sclerosis
Authors: Ghareghani Majid , Farhadi Zahra , Rivest Serge , Zibara Kazem
Published: March 2022

We recently showed that melatonin ameliorates the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, efficiency of melatonin therapy was associated with side effects, manifested by slowing down of remyelination, through increasing the inhibitory effects of brain pyruvate dehydrogenase kinase-4 (PDK-4) on pyruvate dehydrogenase complex (PDC), a key enzyme in fatty acid (FA) synthesis during remyelination. In this study, we investigated the metabolic profile of FA synthesis using combination therapy of melatonin and diisopropylamine dichloroacetate (DADA), a PDK4 inhibitor, in EAE mice. Disease progression was monitored by recording the disability scores. Immunological, oligodendrogenesis and metabolic factors were also evaluated. Results showed that combination therapy of melatonin and DADA significantly reduced EAE disability scores, compared to melatonin, whereas DADA alone did not have any effect. In addition, co-therapy inhibited pro-inflammatory while increasing anti-inflammatory cytokines, significantly better than melatonin alone. Moreover, administration of combination drugs recovered the declined expression of oligodendrocytic markers in EAE, more potently than melatonin. Furthermore, co-therapy affected cerebral energy metabolism by significantly reducing lactate levels while increasing N-acetylaspartate (NAA) and 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase (HMGCR) levels. Finally, while melatonin increased lactate and PDK4 expression levels and greatly reduced PDC activity, co-therapy significantly restored PDC function while reducing the lactate levels. In summary, administration of melatonin with DADA increased the efficiency of melatonin treatment by eliminating the inhibitory effects of PDK4 on PDC’s function, a critical step for proper FA synthesis during remyelination.
Climate-Related Vulnerability and Risk Assessment of Main Ocean Uses: An Overview
Authors: Fernandes Miguel , Vieira da Silva Carina , Frazão Santos Catarina
Published: March 2022

Vulnerability and risk analyses have been increasingly used in a wide variety of contexts to support ocean management and planning processes. Depending on the context, such analyses may focus on different dimensions, spatial scales, and hazards. In the particular context of climate change, the variability inherent to the developed assessments has led to the emergence of numerous methodological frameworks, allowing for advances in the field while raising uncertainties on applied concepts, definitions, and approaches. In the present study, we developed a systematic literature review to analyze and discuss the key concepts, methodologies, and limitations of existing vulnerability and risk assessments of main ocean uses to global climate change. We analyzed over 314 scientific references regarding the elements considered in the analysis (e.g., exposure, sensitivity, adaptive capacity), dimensions (e.g., ecological, economic, social), type of indicators (e.g., quantitative, qualitative), maritime activities, climate-related drivers of change, and spatial scales. Results show that most vulnerability and risk assessments address fisheries and marine conservation, and that sea-level rise and extreme events are the most frequently considered climate-related drivers of change. The main identified limitations pertain to the level of subjectivity and the tremendous variety of concepts, areas of expertise, and systems addressed in such studies. We highlight that further research is needed particularly on the development of cross-sectoral studies and integrative approaches, using multiple indicators and frameworks. There is also a need for assessments explicitly designed to support ocean planning and integrated marine management processes. Review processes such as the present one provide a “big picture,” allowing for a global view on complex topics, and contributing to advances in the field.
Adaptive Network Design for Multiple Gliders Observation of Mesoscale Eddy
Authors: Gao Zhanwen , Chen Ge , Song Yang , Zheng Jie , Ma Chunyong
Published: March 2022

With its excellent endurance, good maneuverability and track controllability, glider has become one of the important equipment to obtain ocean field data. The network observation of multiple gliders will be the main approach of ocean observation in the future. However, how to plan the glider path in a reasonable way and how to design the optimal observation network consisting of multiple gliders in an eddy have not been well solved. As an effort to tackle this problem, an adaptive network design algorithm for multiple gliders in mesoscale eddies observation which referred as “Optimal Sampling” is proposed in this paper. Simulation experiments of tracking a target eddy in the South China Sea (SCS) show that the proposed algorithm cannot only realize the adaptive network design for multiple gliders, but also ensure the uniform sampling inside the eddy. Compared with the traditional method which samples eddy along a fixed path, the observation data obtained by the solution proposed in this paper are more valuable to describe the essential temperature characteristics of eddies. The residual errors computed from the interpolation of the sampled field is also smaller.
Cross-Shelf Exchange in the Southwestern Atlantic Shelf: Climatology and Extreme Events
Authors: Berden Giuliana , Piola Alberto R. , Palma Elbio D.
Published: March 2022

The variability and drivers of the cross-shelf exchanges between the Southwestern Atlantic shelf and the open ocean from 30 to 40°S are analyzed using a high-resolution ocean model reanalysis at daily resolution. The model's performance was first evaluated using altimetry data, and independent mooring and hydrographic data collected in the study area. Model transports are in overall good agreement with all other estimates. The record-mean (1993–2018) cross-shore transport is offshore, 2.09 ± 1.60 Sv. 73% of the shelf-open ocean exchange occurs in the vicinity of Brazil-Malvinas Confluence (~38°S) and 20% near 32°S. This outflow is mostly contributed by northward alongshore transport through 40°S (63%) and the remaining by southward transport through 30°S (37%). The cross-shore flow presents weak seasonal variations, with a maximum in austral summer, and high variability at subannual and weekly time scales. The latter is mainly associated with abrupt wind changes generated by synoptic atmospheric systems. Alongshore wind variations set up sea-level changes in the inner shelf which in turn drive large anomalies in the associated geostrophic alongshore flow. The difference in inner shelf sea-level anomalies at 30 and 40°S is a good indicator of cross-shelf exchange at seasonal and shorter time scales. Episodes of extreme offshore transport that reach up to 9.45 Sv and last about 2 days are driven by convergence of these alongshore flows over the shelf. Large exports of shelf waters lead to freshening of the upper open ocean as revealed by in-situ and satellite observations. In contrast, onshore extreme events drive open ocean water intrusions of up to 6.53 Sv and last <4 days. These inflows, particularly the subtropical waters from the Brazil Current, induce a substantial salinification of the outer shelf.
Piloting a Regional Scale Ocean Literacy Survey in Fife
Authors: Spoors Felicity , Leakey Chris D. B. , James Mark A.
Published: March 2022

Ocean Literacy (OL) encapsulates the journey of improved awareness of marine and coastal issues, to the adoption of clear values and attitudes based on that knowledge, and intentional lifestyle and other personal choices at an individual and societal level. Understanding a community or group’s position in this transition enables institutions, such as universities, charities or civil society organisations, to target their public engagement efforts to make progress toward a healthier marine environment. To gather a baseline of OL in Fife, Scotland, an online survey was launched to residents of the Local Authority Area, between the 8th May and 30th June 2021. Responses indicated widespread uncertainty about solutions to marine and coastal problems, prompting the promotion of a solutions-based focus for public engagement efforts, particularly regarding local issues. While there was common agreement that the government, businesses and citizens could be doing more to advance the health of the marine environment and climate, only 55% of respondents had already made some changes to their lifestyles with the intention to continue at the point of survey. Some barriers evidently remain. Concern for the marine environment, climate and future generations largely govern the desire to alter behaviour to reap the desired benefits which include the enjoyment of nature, cultural heritage and aids to mental health. Taking a “nested approach” to OL surveying (regional surveys within a national framework) is likely to improve response rates and amplify the voices of rural and coastal communities. Furthermore, the OL surveying platform may opportunistically serve as a useful tool for investigating public priorities in the early stages of marine planning and policy development.
Corneal in vivo Confocal Microscopy for Assessment of Non-Neurological Autoimmune Diseases: A Meta-Analysis
Authors: Gu Yuxiang , Liu Xin , Yu Xiaoning , Qin Qiyu , Yu Naiji , Ke Weishaer , Wang Kaijun , Chen Min
Published: March 2022

Purpose

This study aimed to evaluate the features of corneal nerve with in vivo confocal microscopy (IVCM) among patients with non-neurological autoimmune (NNAI) diseases.

Methods

We systematically searched PubMed, Web of Science, and Cochrane Central Register of Controlled Trials for studies published until May 2021. The weighted mean differences (WMDs) of corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), tortuosity, reflectivity, and beadings per 100 μm with a 95% CI between NNAI and control group were analyzed using a random-effects model.

Results

The results showed 37 studies involving collective totals of 1,423 patients and 1,059 healthy controls were ultimately included in this meta-analysis. The pooled results manifested significantly decreased CNFL (WMD: −3.94, 95% CI: −4.77–−3.12), CNFD (WMD: −6.62, 95% CI: −8.4–−4.85), and CNBD (WMD: −9.89, 95% CI: −14–−5.79) in NNAI patients. In addition, the NNAI group showed more tortuous corneal nerve (WMD: 1.19, 95% CI:0.57–1.81). The comparison between NNAI patients and healthy controls in beadings per 100 μm corneal nerve length was inconsistent. No significant difference was found in the corneal nerve fiber reflectivity between NNAI and the control group (WMD: −0.21, 95% CI: −0.65–0.24, P = 0.361).

Conclusions

The parameters and morphology of corneal nerves observed by IVCM proved to be different in NNAI patients from healthy controls, suggesting that IVCM may be a non-invasive technique for identification and surveillance of NNAI diseases.
Treatment Guidelines for Atopic Dermatitis Since the Approval of Dupilumab: A Systematic Review and Quality Appraisal Using AGREE-II
Authors: Ghazal Stephanie , Ridha Zainab , D'Aguanno Kathleen , Nassim David , Quaiattini Andrea , Netchiporouk Elena , Poulin Yves , Kalia Sunil , Marcoux Danielle , Piguet Vincent , Jack Carolyn
Published: March 2022

Introduction

Since its approval for adults with moderate-to-severe atopic dermatitis (AD) in 2017, dupilumab has been incorporated into clinical practice guidelines (CPGs). However, recommendations differ internationally, and the quality assessment of their development is unclear.

Objective

We aimed to systematically review and appraise the quality of CPGs for adult AD reported since 2017 and map the recommendations for dupilumab initiation relative to conventional systemic therapy (CST).

Materials and Methods

A literature search was conducted in June 2020 in MEDLINE, EMBASE, SCOPUS, and CINAHL. Twelve CPGs were retrieved. Methodological quality was assessed using the validated Appraisal of Guidelines for Research & Evaluation II tool (AGREE-II). Recommendations were extracted and compared.

Results

AGREE-II median scores per domain of the CPGs were (%, r = range): scope/purpose, 78% (50–96); stakeholder involvement, 54% (28–85); rigor of development, 39% (21–63); clarity of presentation, 85% (69–100); applicability, 27% (6–51); and editorial independence, 76% (42–100). Neither met the threshold of 70% quality criteria for rigor of development nor the applicability domains. Three CPGs met the criteria for recommendation without modification. CPGs' approach to dupilumab initiation was as follows: second line, preferred over CST and nbUVB (n = 1/12 CPG); second line, equivalent to CST or nbUVB (n = 3/12 CPGs); third line, after nbUVB or CST (n = 5/12 CPGs); and fourth line after nbUVB and CST (n = 2/12). No consensus was reached for n = 1/12 CPG.

Conclusion and Relevance

Dupilumab is now incorporated into CPGs for adult AD. These CPGs exhibited good quality in scope/purpose, clarity, and editorial independence domains. However, none met AGREE-II criteria for methodological rigor/applicability. Gaps were found in mechanisms for updates, facilitators/barriers, resource implications, and stakeholder involvement. Only n = 3/12 CPGs met quality criteria for recommendation without modifications. Of these, two favored a conservative sequential approach for the initiation of dupilumab relative to CST, while one did not reach consensus. Our findings highlight divergent recommendations AD treatment, underlining a need to incorporate quality criteria into future guideline development.
Case Report: Analysis of Plasma Extracellular Vesicles in a Triple Negative Spindle-Cell Metaplastic Breast Cancer Patient
Authors: Vannini Ivan , Urbini Milena , Melloni Mattia , Rossi Tania , Gallerani Giulia , Palleschi Michela , Azzali Irene , Puccetti Maurizio , Martinelli Giovanni , Fabbri Francesco
Published: March 2022

Metaplastic breast cancer (MpBC) is a rare tumor representing 1% of all breast malignancies. The prognosis of this histologic subtype is actually poor and there are no current clear-cut therapeutic guidelines. Hence, despite its uniqueness, its aggressive prognostic profile strongly encourages further studies to identify new markers and therapeutic targets. Herein, we report a case of 32-years-old patient affected with of triple negative spindle-shaped MpBC. The research of molecular targets on the primary tumor did not allow performing an effective therapeutic choice. Extracellular Vesicles (EVs) are under intense study as new potential pathophysiological markers and targets for therapeutic applications, in different tumors for their role in tumor onset, progression and aggressiveness. Here, we examined the involvement of EVs in this case, to look into the MpBC microenvironment willing to identify new potential molecular targets, pathways of aggressiveness, and markers of prognosis and therapeutic efficacy. Firstly, we characterized MpBC patient EV dimensions and surface proteins. Moreover, we analyzed the EV RNA cargo supposed to be delivered to nearby and distant recipient cells. Interestingly, we observed a dysregulation EV-contained miRNAs, which could determine an increased expression of oncogenes in the tumor microenvironment, probably enabling cancer progression. These data suggest that the characterization of miRNA cargo of EVs could be important for the identification of new markers and for the application of future new target therapies.
Immunogenicity and Safety of COVID-19 Vaccines in Patients Receiving Renal Replacement Therapy: A Systematic Review and Meta-Analysis
Authors: Ma Becky Mingyao , Tam Anthony Raymond , Chan Kam Wa , Ma Maggie Kam Man , Hung Ivan Fan Ngai , Yap Desmond Yat Hin , Chan Tak Mao
Published: March 2022

Background

Systematic data on the efficacy and safety of COVID-19 vaccine in patients on renal replacement therapy (RRT) remains limited. We conducted a meta-analysis on the efficacy and safety of COVID-19 vaccine in patients on RRT.

Methods

Eligible studies were identified by systematic literature search in four electronic databases. Twenty-seven studies (4,264 patients) were included for meta-analysis. 99% patients received mRNA vaccine.

Results

Patients on RRT showed inferior seropositivity after two-dosed COVID-19 vaccine, 44% lower than the general population. Kidney transplant recipients (KTRs) had significantly lower seropositivity than patients on haemodialysis (HD) or peritoneal dialysis (PD) (26.1 vs. 84.3% and 92.4% respectively, p < 0.001 for both). Compared with healthy controls, KTRs, HD and PD patients were 80% (95% CI: 62–99%), 18% (95% CI: 9–27%) and 11% (95% CI: 1–21%) less likely to develop antibodies after vaccination (p < 0.001, <0.001 and 0.39 respectively). In KTRs, every 1% increase in using mycophenolate was associated with 0.92% reduction in seropositivity (95% CI: −1.68, −0.17, p = 0.021) at population level. The overall adverse event rate attributed to vaccination was 2.1%. Most events were mild.

Conclusion

Patients on RRT, particularly KTRs, had significantly reduced antibody response after two-dosed COVID-19 vaccination. Vaccination is generally well tolerated.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42021261879.
Situs Inversus Totalis on 18F-FDG PET/CT: A Case Report and a Literature Review
Authors: Liu Xu-Sheng , Wu Rui-Min , Wan Hua-Bing , Chen Yi-Jia , Tan Fan , Zeng Dao-Bing , Yang Yi , Pei Zhi-Jun
Published: March 2022

A 62-year-old female patient with pathologically confirmed left lung small cell neuroendocrine carcinoma. The patient was referred to our positron emission tomography (PET)/CT center to look for possible metastatic diseases. After fasting for 8 h, the fasting blood glucose level of the patient was 7.1 mmol/L. The patient was intravenously injected with a 6.42 mCi (238 MBq) 18F-fluorodeoxyglucose (FDG) imaging agent. After the patient rested for 1 h, we scanned the patient with SIEMENS Biograph mCT 64 PET/CT camera. In addition to lung tumors and lymph node diseases, abnormal tracer uptake in the patient's thyroid was also found. PET/CT also showed situs inversus totalis of the patient, including the dextrocardia, liver on the left side, stomach, and spleen on the right side of the patient's body. The identification of anatomical variations and abnormalities by PET/CT imaging is very important to develop the best treatment for lung cancer.
Follow-Up Study of Subdermal Low-Echoic Lesions in the Ischial Region in Wheelchair Users With Spinal Cord Injuries
Authors: Kawasaki Shinji , Nishimura Yukihide , Kouda Ken , Umemoto Yasunori , Kinoshita Tokio , Hashizaki Takamasa , Kawanishi Makoto , Nakamura Taro , Tajima Fumihiro
Published: March 2022

Objective:

To follow up patients with spinal cord injuries with subdermal low-echoic lesions in the ischial region for abnormalities after 1 year.

Design

A retrospective cohort study.

Setting

A Japanese rehabilitation center.

Participants

We included patients with chronic spinal cord injuries and subdermal low-echoic lesions who underwent routine inspection and palpation examinations (n = 7).

Interventions

Education on pressure injury and instruction on pressure relief and seating was provided and the patients were followed up for abnormalities after 1 year. Self-reports were obtained on wheelchair sitting time, and interface pressure was recorded while the patients were seated on the wheelchair. Interface pressure measurements at the bilateral ischial regions were recorded with a force-sensitive application pressure mapping system.

Outcome Measures

The primary outcome was the presence of subdermal low-echoic lesions in the bilateral ischial regions on ultrasonography at the 1-year follow-up examination. Secondary outcomes included wheelchair sitting time and interface pressure in the bilateral ischial regions.

Results

Of the 10 areas that showed subdermal low-echoic lesions on ultrasonography, nine had improved after 1 year. One area that did not improve was an open wound. At the follow-up examination, the pressure duration was reduced in all patients, and the interface pressure could be reduced in 5/7 patients.

Conclusions

This is the first study to follow up with patients having spinal cord injuries and subdermal low-echoic lesions in the ischial region using ultrasonography. The low-echoic lesions improved within 1 year by reducing the pressure duration and interface pressure. Pressure injury prevention in patients with spinal cord injuries relies on the early detection of skin abnormalities, and education and instruction to change self-management behaviors are recommended.
Red Flags, Prognostic Impact, and Management of Patients With Cardiac Amyloidosis and Aortic Valve Stenosis: A Systematic Review and Meta-Analysis
Authors: Myasoedova Veronika A. , Conte Maddalena , Valerio Vincenza , Moschetta Donato , Massaiu Ilaria , Petraglia Laura , Leosco Dario , Poggio Paolo , Parisi Valentina
Published: March 2022

Background

Cardiac amyloidosis (CA) has been recently recognized as a condition frequently associated with aortic stenosis (AS). The aim of this study was to evaluate: the main characteristics of patients with AS with and without CA, the impact of CA on patients with AS mortality, and the effect of different treatment strategies on outcomes of patients with AS with concomitant CA.

Materials and Methods

A detailed search related to CA in patients with AS and outcomes was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies enrolling 1,988 subjects (1,658 AS alone and 330 AS with CA) were included in the qualitative and quantitative analysis of main patients with AS characteristics with and without CA, difference in mortality, and treatment strategy.

Results

The prevalence of CA resulted in a mean of 15.4% and it was even higher in patients with AS over 80 years old (18.2%). Patients with the dual diagnosis were more often males, had lower body mass index (BMI), were more prone to have low flow, low gradient with reduced left ventricular ejection fraction AS phenotype, had higher E/A and E/e', and greater interventricular septum hypertrophy. Lower Sokolow–Lyon index, higher QRS duration, higher prevalence of right bundle branch block, higher levels of N-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were significantly associated with CA in patients with AS. Higher overall mortality in the 178 patients with AS + CA in comparison to 1,220 patients with AS alone was observed [odds ratio (OR) 2.25, p = 0.004]. Meta-regression analysis showed that younger age and diabetes were associated with overall mortality in patients with CS with CA (Z-value −3.0, p = 0.003 and Z-value 2.5, p = 0.013, respectively). Finally, patients who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) had a similar overall mortality risk, but lower than medication-treated only patients.

Conclusion

Results from our meta-analysis suggest that several specific clinical, electrocardiographic, and echocardiographic features can be considered “red flags” of CA in patients with AS. CA negatively affects the outcome of patients with AS. Patients with concomitant CA and AS benefit from SAVR or TAVI.
Application of Transcriptomics for Predicting Protein Interaction Networks, Drug Targets and Drug Candidates
Authors: Kankanige Dulshani , Liyanage Liwan , O'Connor Michael D.
Published: March 2022

Protein interaction pathways and networks are critically-required for a vast range of biological processes. Improved discovery of candidate druggable proteins within specific cell, tissue and disease contexts will aid development of new treatments. Predicting protein interaction networks from gene expression data can provide valuable insights into normal and disease biology. For example, the resulting protein networks can be used to identify potentially druggable targets and drug candidates for testing in cell and animal disease models. The advent of whole-transcriptome expression profiling techniques—that catalogue protein-coding genes expressed within cells and tissues—has enabled development of individual algorithms for particular tasks. For example,: (i) gene ontology algorithms that predict gene/protein subsets involved in related cell processes; (ii) algorithms that predict intracellular protein interaction pathways; and (iii) algorithms that correlate druggable protein targets with known drugs and/or drug candidates. This review examines approaches, advantages and disadvantages of existing gene expression, gene ontology, and protein network prediction algorithms. Using this framework, we examine current efforts to combine these algorithms into pipelines to enable identification of druggable targets, and associated known drugs, using gene expression datasets. In doing so, new opportunities are identified for development of powerful algorithm pipelines, suitable for wide use by non-bioinformaticians, that can predict protein interaction networks, druggable proteins, and related drugs from user gene expression datasets.
Reforming Nitrate Metabolism for Enhancing L-Arginine Production in Corynebacterium crenatum Under Oxygen Limitation
Authors: Huang Mingzhu , Zhu Lingfeng , Feng Lin , Zhan Li , Zhao Yue , Chen Xuelan
Published: March 2022

Various amino acids are widely manufactured using engineered bacteria. It is crucial to keep the dissolved oxygen at a certain level during fermentation, but accompanied by many disadvantages, such as high energy consumption, reactive oxygen species, and risk of phage infections. Thus, anaerobic production of amino acids is worth attempting. Nitrate respiration systems use nitrate as an electron acceptor under anoxic conditions, which is different from the metabolism of fermentation and can produce energy efficiently. Herein, we engineered Corynebacterium crenatum to enhance L-arginine production under anaerobic conditions through strengthening nitrate respiration and reforming nitrogen flux. The construction of mutant strain produced up to 3.84 g/L L-arginine under oxygen limitation with nitrate, and this value was 131.33% higher than that produced by the control strain under limited concentrations of oxygen without nitrate. Results could provide fundamental information for improving L-arginine production by metabolic engineering of C. crenatum under oxygen limitation.
The Spatial Landscape of the Bacterial Community and Bile Acids in the Digestive Tract of Patients With Bile Reflux
Authors: Yang Ni , Xu Jun , Wang Xuemei , Chen Ning , Su Lin , Liu Yulan
Published: March 2022

Background

Bile reflux can lead to inflammation and increased intestinal metaplasia. Since bile acids can influence the gastrointestinal environment, it is possible that bile reflux may alter the gastric microbiota and potentially the oral or gut microbiota. Bile acids have a very complex interrelationship with microbiota. We aimed to explore the characteristics of the digestive tract microbiota and bile acids profile in bile reflux patients.

Methods

This study included 20 chronic gastritis patients with bile reflux and 20 chronic gastritis patients without bile reflux. Saliva, gastric fluid, and fecal samples were collected for bile acid testing. Buccal mucosal swabs, gastric mucosal tissues, and feces were collected for bacteria detection. The UPLC-MS/MS examined bile acids profiles. 16S rRNA gene sequencing was used to analyze the bacterial profile.

Results

Bilirubin in the blood increased in bile reflux patients. No other clinical factors were identified to be significantly associated with bile reflux. 12-DHCA, 6,7-diketo LCA, and βHDCA decreased while TUDCA increased in saliva of bile reflux patients. Streptococcus, Capnocytophaga, Neisseria, and Actinobacillus decreased in oral mucosa of bile reflux patients while Helicobacter, Prevotella, and Veillonella increased. Gastric bile acid levels were generally higher in bile reflux patients. Gastric mucosal microbiota was highly stable. The changes in fecal bile acids were insignificant. Bifidobacterium, Prevotella_2, Ruminococcus, Weissella, Neisseria, and Akkermansia decreased in fecal samples from bile reflux patients; while Alloprevotella, Prevotella_9, Parabacteroides, and Megamonas increased.

Conclusion

Our results demonstrate that bile reflux significantly alters the oral, gastric, and intestinal bile acids profiles but only influences the oral and gut microbiota composition. These findings indicate that bile reflux can modulate the gastrointestinal microbiota in a site-specific manner.
Current Therapy and Therapeutic Targets for Microsporidiosis
Authors: Wei Junhong , Fei Zhihui , Pan Guoqing , Weiss Louis M. , Zhou Zeyang
Published: March 2022

Microsporidia are obligate intracellular, spore-forming parasitic fungi which are grouped with the Cryptomycota. They are both opportunistic pathogens in humans and emerging veterinary pathogens. In humans, they cause chronic diarrhea in immune-compromised patients and infection is associated with increased mortality. Besides their role in pébrine in sericulture, which was described in 1865, the prevalence and severity of microsporidiosis in beekeeping and aquaculture has increased markedly in recent decades. Therapy for these pathogens in medicine, veterinary, and agriculture has become a recent focus of attention. Currently, there are only a few commercially available antimicrosporidial drugs. New therapeutic agents are needed for these infections and this is an active area of investigation. In this article we provide a comprehensive summary of the current as well as several promising new agents for the treatment of microsporidiosis including: albendazole, fumagillin, nikkomycin, orlistat, synthetic polyamines, and quinolones. Therapeutic targets which could be utilized for the design of new drugs are also discussed including: tubulin, type 2 methionine aminopeptidase, polyamines, chitin synthases, topoisomerase IV, triosephosphate isomerase, and lipase. We also summarize reports on the utility of complementary and alternative medicine strategies including herbal extracts, propolis, and probiotics. This review should help facilitate drug development for combating microsporidiosis.
Understanding the Role of SARS-CoV-2 ORF3a in Viral Pathogenesis and COVID-19
Authors: Zhang Jiantao , Ejikemeuwa Amara , Gerzanich Volodymyr , Nasr Mohamed , Tang Qiyi , Simard J. Marc , Zhao Richard Y.
Published: March 2022

The ongoing SARS-CoV-2 pandemic has shocked the world due to its persistence, COVID-19-related morbidity and mortality, and the high mutability of the virus. One of the major concerns is the emergence of new viral variants that may increase viral transmission and disease severity. In addition to mutations of spike protein, mutations of viral proteins that affect virulence, such as ORF3a, also must be considered. The purpose of this article is to review the current literature on ORF3a, to summarize the molecular actions of SARS-CoV-2 ORF3a, and its role in viral pathogenesis and COVID-19. ORF3a is a polymorphic, multifunctional viral protein that is specific to SARS-CoV/SARS-CoV-2. It was acquired from β-CoV lineage and likely originated from bats through viral evolution. SARS-CoV-2 ORF3a is a viroporin that interferes with ion channel activities in host plasma and endomembranes. It is likely a virion-associated protein that exerts its effect on the viral life cycle during viral entry through endocytosis, endomembrane-associated viral transcription and replication, and viral release through exocytosis. ORF3a induces cellular innate and pro-inflammatory immune responses that can trigger a cytokine storm, especially under hypoxic conditions, by activating NLRP3 inflammasomes, HMGB1, and HIF-1α to promote the production of pro-inflammatory cytokines and chemokines. ORF3a induces cell death through apoptosis, necrosis, and pyroptosis, which leads to tissue damage that affects the severity of COVID-19. ORF3a continues to evolve along with spike and other viral proteins to adapt in the human cellular environment. How the emerging ORF3a mutations alter the function of SARS-CoV-2 ORF3a and its role in viral pathogenesis and COVID-19 is largely unknown. This review provides an in-depth analysis of ORF3a protein’s structure, origin, evolution, and mutant variants, and how these characteristics affect its functional role in viral pathogenesis and COVID-19.
CRISPR Detection and Research on Screening Mutant Gene TTN of Moyamoya Disease Family Based on Whole Exome Sequencing
Authors: Xiao Yilei , Liu Weidong , Hao Jiheng , Jiang Qunlong , Wang Xingbang , Yu Donghu , Zhang Liyong , Dong Zhaogang , Wang Jiyue
Published: March 2022

Moyamoya disease (MMD) has a high incidence in Asian populations and demonstrates some degree of familial clustering. Whole-exome sequencing (WES) is useful in establishing key related genes in familial genetic diseases but is time-consuming and costly. Therefore, exploring a new method will be more effective for the diagnosis of MMD. We identified familial cohorts showing MMD susceptibility and performed WES on 5 affected individuals to identify susceptibility loci, which identified point mutation sites in the titin (TTN) gene (rs771533925, rs559712998 and rs72677250). Moreover, TTN mutations were not found in a cohort of 50 sporadic MMD cases. We also analyzed mutation frequencies and used bioinformatic predictions to reveal mutation harmfulness, functions and probabilities of disease correlation, the results showed that rs771533925 and rs72677250 were likely harmful mutations with GO analyses indicating the involvement of TTN in a variety of biological processes related to MMD etiology. CRISPR-Cas12a assays designed to detect TTN mutations provided results consistent with WES analysis, which was further confirmed by Sanger sequencing. This study recognized TTN as a new familial gene marker for moyamoya disease and moreover, demonstrated that CRISPR-Cas12a has the advantages of rapid detection, low cost and simple operation, and has broad prospects in the practical application of rapid detection of MMD mutation sites.