bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of soluble CD80 in patients with soft tissue tumors
Authors: Matsuyama Yumi , Asanuma Kunihiro , Yoshida Keisuke , Hagi Tomohito , Iino Takahiro , Nakamura Tomoki , Sudo Akihiro
Published: September 2022

Background

Immune checkpoint protein (ICP), which is a central factor group of the immune system, has been reported to have a correlation between the degree of its expression and the prognosis of patients with malignant tumors, and many inhibitors have appeared as therapeutic targets. On the other hand, a soluble form of ICP in circulating blood induced systemic immunosuppression. In this study, we investigated the relationship between the soluble form of CD80 (sCD80) which is a ligand for the inhibitory system CTLA-4, in blood, and clinicopathological parameters in patients with soft tissue tumors.

Methods

A total of 119 patients with primary soft tissue tumors were enrolled in this study. The sCD80 levels were measured by enzyme immunoassay.

Results

There were no significant differences in sCD80 levels between benign (34) and soft tissue sarcoma (STS) patients (85). In STS, the high-sCD80 group had significantly lower metastasis-free survival (MS) and lower overall survival (OS) than the low-sCD80 group at 5 years using the log-rank test (OS: high > 404 pg/mL, low ≤ 404 pg/mL, MS: high > 531 pg/ml, low ≤ 531 pg/ml). On multivariate Cox proportional hazard analysis, the high-sCD80 group had significant differences in 5MS and 5OS compared to the low-sCD80 group.

Conclusions

In conclusion, sCD80 may negatively affect systemic immune circumstances, in STS, and may have potential as a therapeutic target.
Resveratrol protection against IL-1β-induced chondrocyte damage via the SIRT1/FOXO1 signaling pathway
Authors: Liang ChuanCai , Xing Hengte , Wang ChenYu , Xu XiongFeng , Hao Yarong , Qiu Bo
Published: September 2022

Purpose

Osteoarthritis (OA) is a common joint disease characterized by cartilage degeneration, synovial inflammation, osteophytes, and subchondral osteosclerosis. This study investigated the effects of resveratrol (RES) on extracellular matrix (ECM), autophagy, and apoptosis in OA pathogenesis via the SIRT1/FOXO1 pathway.

Methods

The microenvironment of OA chondrocytes was stimulated in vitro by adding 10 ng/mL of IL-1β to primary Wistar rat chondrocyte. Western blotting, immunofluorescence, quantitative real-time PCR, and transmission electron microscopy (TEM) were used for analysis.

Results

In the presence of IL-1β, RES increased the expression of silent information regulator (SIR) 1 protein and the phosphorylation level of forkhead transcription factor (FOXO) 1. It also promoted chondrocyte autophagy, increased the expression of SOX9 and aggrecan, inhibited chondrocyte apoptosis and matrix breakdown, and protected chondrocytes from IL-1β damage. After a SIRT1 inhibitor or FOXO1 inhibitor was added, the protective effect of RES on chondrocytes was significantly weakened. Our results suggest that RES regulates the ECM metabolism, autophagy, and apoptosis of OA chondrocytes through the SIRT1/FOXO1 pathway to ameliorate IL-1β-induced chondrocyte injury.

Conclusion

RES protects chondrocytes from IL-1β-induced damage by activating SIRT1/FOXO1 signaling and holds potential in OA treatment.
Social pharmaceutical innovation and alternative forms of research, development and deployment for drugs for rare diseases
Authors: Douglas Conor M. W. , Aith Fernando , Boon Wouter , de Neiva Borba Marina , Doganova Liliana , Grunebaum Shir , Hagendijk Rob , Lynd Larry , Mallard Alexandre , Mohamed Faisal Ali , Moors Ellen , Oliveira Claudio Cordovil , Paterson Florence , Scanga Vanessa , Soares Julino , Raberharisoa Vololona , Kleinhout-Vliek Tineke
Published: September 2022

Rare diseases are associated with difficulties in addressing unmet medical needs, lack of access to treatment, high prices, evidentiary mismatch, equity, etc. While challenges facing the development of drugs for rare diseases are experienced differently globally (i.e., higher vs. lower and middle income countries), many are also expressed transnationally, which suggests systemic issues. Pharmaceutical innovation is highly regulated and institutionalized, leading to firmly established innovation pathways. While deviating from these innovation pathways is difficult, we take the position that doing so is of critical importance. The reason is that the current model of pharmaceutical innovation alone will not deliver the quantity of products needed to address the unmet needs faced by rare disease patients, nor at a price point that is sustainable for healthcare systems. In light of the problems in rare diseases, we hold that re-thinking innovation is crucial and more room should be provided for alternative innovation pathways. We already observe a significant number and variety of new types of initiatives in the rare diseases field that propose or use alternative pharmaceutical innovation pathways which have in common that they involve a diverse set of societal stakeholders, explicitly address a higher societal goal, or both. Our position is that principles of social innovation can be drawn on in the framing and articulation of such alternative pathways, which we term heresocial pharmaceutical innovation(SPIN), and that it should be given more room for development. As an interdisciplinary research team in the social sciences, public health and law, the cases of SPIN we investigate are spread transnationally, and include higher income as well as middle income countries. We do this to develop a better understanding of the social pharmaceutical innovation field’s breadth and to advance changes ranging from the bedside to system levels. We seek collaborations with those working in such projects (e.g., patients and patient organisations, researchers in rare diseases, industry, and policy makers). We aim to add comparative and evaluative value to social pharmaceutical innovation, and we seek to ignite further interest in these initiatives, thereby actively contributing to them as a part of our work.
The impact of the COVID-19 pandemic on Fabry Disease Patients: an examination of Mood Status, Therapy Adherence, and COVID-19 infection
Authors: Karaca Cebrail , Dincer Mevlut Tamer , Ozcan Seyda Gul , Sarac Betul , Ahmadzada Saffa , Alagoz Selma , Bakir Alev , Kiykim Ertugrul , Trabulus Sinan , Seyahi Nurhan
Published: September 2022

Background

Fabry disease (FD) is a rare metabolic disorder, in which a lifelong enzyme replacement therapy (ERT) constitutes the cornerstone of disease-specific therapy. In this study, we examined the effects of the COVID-19 pandemic and lockdown measures on the management of FD patients.

Methods

We collected data in three main domains; mood status, adherence to ERT, and COVID-19 infection. We used the Hospital Anxiety and Depression Scale (HADS) to evaluate the mood statuses of FD patients and the Morisky Medication Adherence Scale (MMAS) and the Medication Adherence Report Scale (MARS) to assess patients’ adherence to non-disease specific therapy. We also examined a control group to compare the mood status data.

Results

A total of 67 FD patients (males: 47.8%, mean age: 37.0 years) were recruited to the study, of which 58 were receiving ERT. Both the HADS depression and anxiety scores were higher in the control group compared to FD patients. During the first wave of the pandemic, 25 patients reported to have missed an infusion for a mean of 2.3 ± 1.7 doses and half of the patients had adopted a home-based infusion treatment regimen. COVID-19 infection developed in 25 patients, of which one died. The majority of our patients (71.6%) have had at least one shot of the vaccine.

Conclusion

We found that FD patients were more resilient to the negative psychological effects of lockdown. Traumatic growth may be an important factor in explaining this finding. Government-supported home therapy programs might be beneficial for FD patients to increase the therapy adherence.
Clinical, cytogenetic, and genomic analyses of an Ecuadorian subject with Klinefelter syndrome, recessive hemophilia A, and 1;19 chromosomal translocation: a case report
Authors: Gaviria Anibal , Cadena-Ullauri Santiago , Cevallos Francisco , Guevara-Ramirez Patricia , Ruiz-Pozo Viviana , Tamayo-Trujillo Rafael , Paz-Cruz Elius , Zambrano Ana Karina
Published: September 2022

Background

Hemophilia A is considered one of the most common severe hereditary disorders. It is an X-linked recessive disease caused by a deficiency or lack of function of the blood clotting factor VIII. Klinefelter syndrome is a genetic disorder that affects male individuals due to one or more extra X chromosomes, present in all cells or with mosaicism. The aneuploidy is due to either mitotic or meiotic chromosome non-disjunction. Chromosomal translocations are a group of genome abnormalities in which a region or regions of a chromosome break and are transferred to a nonhomologous chromosome or a new location in the same chromosome.

Case presentation

Our subject was born in Ecuador at 36 weeks of gestation by vaginal delivery. At 3 months old, the Factor VIII activity measure showed a 23.7% activity indicating a diagnosis of mild hemophilia A. At 1 year old, the karyotype showed an extra X chromosome, consistent with a diagnosis of Klinefelter syndrome, and a translocation between the long arms of chromosomes 1 and 19, at positions q25 and q13, respectively.

Conclusions

Klinefelter syndrome and hemophilia are a rare combination. In the present case report, the subject presents both, meaning that he has inherited one X chromosome from the father and one X chromosome from the mother. Since the father has severe hemophilia A; and the subject presents a below 40% Factor VIII activity, a skewed X inactivation is suggested. Additionally, the proband presents a translocation with the karyotype 47,XXY,t(1;19)(q25;q13). No similar report with phenotypic consequences of the translocation was found. The present report highlights the importance of a correct diagnosis, based not only on the clinical manifestations of a disease but also on its genetic aspects, identifying the value of integrated diagnostics. The subject presents three different genetic alterations, Klinefelter syndrome, hemophilia A, and a 1;19 chromosomal translocation.
Learning and visualizing chronic latent representations using electronic health records
Authors: Chushig-Muzo David , Soguero-Ruiz Cristina , Miguel Bohoyo Pablo de , Mora-Jiménez Inmaculada
Published: September 2022

Background

Nowadays, patients with chronic diseases such as diabetes and hypertension have reached alarming numbers worldwide. These diseases increase the risk of developing acute complications and involve a substantial economic burden and demand for health resources. The widespread adoption of Electronic Health Records (EHRs) is opening great opportunities for supporting decision-making. Nevertheless, data extracted from EHRs are complex (heterogeneous, high-dimensional and usually noisy), hampering the knowledge extraction with conventional approaches.

Methods

We propose the use of the Denoising Autoencoder (DAE), a Machine Learning (ML) technique allowing to transform high-dimensional data into latent representations (LRs), thus addressing the main challenges with clinical data. We explore in this work how the combination of LRs with a visualization method can be used to map the patient data in a two-dimensional space, gaining knowledge about the distribution of patients with different chronic conditions. Furthermore, this representation can be also used to characterize the patient’s health status evolution, which is of paramount importance in the clinical setting.

Results

To obtain clinical LRs, we considered real-world data extracted from EHRs linked to the University Hospital of Fuenlabrada in Spain. Experimental results showed the great potential of DAEs to identify patients with clinical patterns linked to hypertension, diabetes and multimorbidity. The procedure allowed us to find patients with the same main chronic disease but different clinical characteristics. Thus, we identified two kinds of diabetic patients with differences in their drug therapy (insulin and non-insulin dependant), and also a group of women affected by hypertension and gestational diabetes. We also present a proof of concept for mapping the health status evolution of synthetic patients when considering the most significant diagnoses and drugs associated with chronic patients.

Conclusion

Our results highlighted the value of ML techniques to extract clinical knowledge, supporting the identification of patients with certain chronic conditions. Furthermore, the patient’s health status progression on the two-dimensional space might be used as a tool for clinicians aiming to characterize health conditions and identify their more relevant clinical codes.
MeCP2 deficiency impairs motor cortical circuit flexibility associated with motor learning
Authors: Yue Yuanlei , Ash Ryan T. , Boyle Natalie , Kinter Anna , Li Yipeng , Zeng Chen , Lu Hui
Published: September 2022

Loss of function mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MECP2) cause Rett syndrome (RTT), a postnatal neurological disorder. The loss of motor function is an important clinical feature of RTT that manifests early during the course of the disease. RTT mouse models with mutations in the murine orthologous Mecp2 gene replicate many human phenotypes, including progressive motor impairments. However, relatively little is known about the changes in circuit function during the progression of motor deficit in this model. As the motor cortex is the key node in the motor system for the control of voluntary movement, we measured firing activity in populations of motor cortical neurons during locomotion on a motorized wheel-treadmill. Different populations of neurons intermingled in the motor cortex signal different aspects of the locomotor state of the animal. The proportion of running selective neurons whose activity positively correlates with locomotion speed gradually decreases with weekly training in wild-type mice, but not in Mecp2-null mice. The fraction of rest-selective neurons whose activity negatively correlates with locomotion speed does not change with training in wild-type mice, but is higher and increases with the progression of locomotion deficit in mutant mice. The synchronization of population activity that occurs in WT mice with training did not occur in Mecp2-null mice, a phenotype most clear during locomotion and observable across all functional cell types. Our results could represent circuit-level biomarkers for motor regression in Rett syndrome.
Henoch-Schönlein purpura following COVID-19 vaccine in a child: a case report
Authors: Casini Francesca , Magenes Vittoria Carlotta , De Sanctis Marina , Gattinara Maurizio , Pandolfi Marco , Cambiaghi Stefano , Zuccotti Gian Vincenzo , Fabiano Valentina
Published: September 2022

Background

Henoch-Schönlein purpura (HSP) is an IgA-mediated small vessel vasculitis, typical of childhood. It’s a self-limiting disease and it affects different systems. HSP is characterized by dermatological, abdominal, joint and renal clinical manifestations. This condition usually occurs upon infections, mainly upper respiratory tract ones, medications, vaccinations and malignancies.

Case presentation

We describe the case of a 11 year-old girl who developed a urticarial rash 12 days after the first dose of Pfizer-BioNTech BNT16B2b2 mRNA vaccine and a clear picture of Henoch Schönlein purpura 5 days after administration of the second dose of the same vaccine.

Conclusion

To our knowledge, this is the first description of a pediatric patient with Henoch-Schönlein purpura occurring in association with vaccination against COVID-19.
Integrating temporal single-cell gene expression modalities for trajectory inference and disease prediction
Authors: Ranek Jolene S. , Stanley Natalie , Purvis Jeremy E.
Published: September 2022

Background

Current methods for analyzing single-cell datasets have relied primarily on static gene expression measurements to characterize the molecular state of individual cells. However, capturing temporal changes in cell state is crucial for the interpretation of dynamic phenotypes such as the cell cycle, development, or disease progression. RNA velocity infers the direction and speed of transcriptional changes in individual cells, yet it is unclear how these temporal gene expression modalities may be leveraged for predictive modeling of cellular dynamics.

Results

Here, we present the first task-oriented benchmarking study that investigates integration of temporal sequencing modalities for dynamic cell state prediction. We benchmark ten integration approaches on ten datasets spanning different biological contexts, sequencing technologies, and species. We find that integrated data more accurately infers biological trajectories and achieves increased performance on classifying cells according to perturbation and disease states. Furthermore, we show that simple concatenation of spliced and unspliced molecules performs consistently well on classification tasks and can be used over more memory intensive and computationally expensive methods.

Conclusions

This work illustrates how integrated temporal gene expression modalities may be leveraged for predicting cellular trajectories and sample-associated perturbation and disease phenotypes. Additionally, this study provides users with practical recommendations for task-specific integration of single-cell gene expression modalities.
Overestimation of benefit when clinical trials stop early: a simulation study
Authors: Liu Sharon , Garrison Scott R.
Published: September 2022

Background

Stopping trials early because of a favourable interim analysis can exaggerate benefit. This study simulated trials typical of those stopping early for benefit in the real world and estimated the degree to which early stopping likely overestimates benefit.

Methods

From 1 million simulated trials, we selected those trials that exceeded interim stopping criteria, and compared apparent benefit when stopped with the true benefit used to generate the data. Each simulation randomly assigned period of observation, number of subjects, and control event rate using normal distributions centred on the same parameters in a template trial typical of real-world “truncated” (i.e. stopped for benefit) trials. The intervention’s true relative risk reduction (RRR) was also randomized, and assumed 1% of drugs have a warfarin-like effect (60% RRR), 5% a statin-like effect (35% RRR), 39% an ASA-like effect (15% RRR), 50% no effect (0% RRR), and that 5% would cause harm (modelled as a 20% relative risk increase). Trials had a single interim analysis and a z-value for stopping of 2.782 (O’Brien-Fleming threshold). We also modelled (1) a large truncated trial based on the SPRINT blood pressure trial (using SPRINT’s parameters and stopping criteria) and (2) the same typical truncated trials if they instead went to completion as planned with no interim analysis.

Results

For typical truncated trials, the true RRR was roughly 2/3 the observed RRR at the time of stopping. RRR was overestimated by an absolute 14.9% (median, IQR 6.4–24.6) in typical truncated trials, by 5.3% (IQR −0.1 to 11.4) in the same trials if instead carried to completion, and by 2.3% (IQR 0.98–1.09) in large SPRINT-like trials. For all models, to keep the absolute RRR overestimate below 5%, 250 events were required.

Conclusion

Simulated trials typical of those stopping early for benefit overestimate the true relative risk reduction by roughly 50% (i.e. the true RRR was 2/3 of the observed value). Overestimation was much smaller, and likely unimportant, when simulating large SPRINT-like trials stopping early. Whether trials were large or small, stopped early or not, a minimum 250 events were needed to avoid overestimating relative risk reduction by an absolute 5% or more.
Higher amoebic and metronidazole resistant forms of Blastocystis sp. seen in schizophrenic patients
Authors: Franklin Freddy , Rajamanikam Arutchelvan , Raju Chandramathi Samudi , Gill Jesjeet Singh , Francis Benedict , Sy-Cherng Luke Woon , Kumar Suresh
Published: September 2022

Background

Blastocystis sp. is one of the most common colonisers of the intestinal tract that demonstrate strong interaction with accompanying gut bacteria. Previously, the protozoan isolated from individuals with irritable bowel syndrome (IBS) showed altered phenotypic features suggesting that it can be triggered to become pathogenic. Previous studies reported altered gut microbiota and high prevalence of Blastocystis sp. in schizophrenia patients. However, the phenotypic characteristics of Blastocystis sp. isolated from individuals with SZ have yet to be described.

Methods

In this study, faecal samples from 50 patients with severe schizophrenia (SZ) and 100 non-schizophrenic (NS) individuals were screened for Blastocystis sp. infection. Positive isolates were subjected to genotypic and phenotypic characterization.

Results

We found that 12 out of 50 (24%) SZ and 5 out of 100 (5%) NS individuals were detected Blastocystis sp. positive using both in vitro culture and PCR method with no significant association to age and gender. Out of the 15 sequenced isolates, ST3 was the most prevalent subtype (66.7%) followed by ST1 (20%) and ST6 (13.3%). The isolates from SZ individuals demonstrated significant slower growth rate (34.9 ± 15.6 h) and larger range of cell diameter (3.3–140 µm). We detected higher amoebic forms and metronidazole resistance among SZ isolates with variation in cell surface glycoprotein where 98% of cells from SZ showed consistent medium to high binding affinity (+ 2 to + 3) to Concavalin A staining compared to NS isolates that demonstrated only 76% high lectin (+ 3) binding affinity. Cysteine and serine protease levels were predominantly found among SZ isolates. We also demonstrate the presence of metalloprotease in Blastocystis sp. especially among NS isolates. Introduction of solubilised antigens from SZ isolates increased the cell proliferation of HCT116 cells by two fold when compared to NS isolates.

Conclusion

Our findings demonstrated Blastocystis sp. isolated from SZ individuals showed variation in phenotype specifically in morphology and drug resistance. The findings indicate that the gut environment (SZ and NS) and treatment of SZ could have influenced the phenotype of Blastocystis sp.

Graphical Abstract
Factors secreted by monosodium urate crystal-stimulated macrophages promote a proinflammatory state in osteoblasts: a potential indirect mechanism of bone erosion in gout
Authors: Naot Dorit , Pool Bregina , Chhana Ashika , Gao Ryan , Munro Jacob T. , Cornish Jillian , Dalbeth Nicola
Published: September 2022

Background

Tophi are lesions commonly present at sites of bone erosion in gout-affected joints. The tophus comprises a core of monosodium urate (MSU) crystals surrounded by soft tissue that contains macrophages and other immune cells. Previous studies found that MSU crystals directly reduce osteoblast viability and function. The aim of the current study was to determine the indirect, macrophage-mediated effects of MSU crystals on osteoblasts.

Methods

Conditioned medium from the RAW264.7 mouse macrophage cell line cultured with MSU crystals was added to the MC3T3-E1 mouse osteoblastic cell line. Conditioned medium from the THP-1 human monocytic cell line cultured with MSU crystals was added to primary human osteoblasts (HOBs). Matrix mineralization was assessed by von Kossa staining. Gene expression was determined by real-time PCR, and concentrations of secreted factors were determined by enzyme-linked immunosorbent assay.

Results

In MC3T3-E1 cells cultured for 13 days in an osteogenic medium, the expression of the osteoblast marker genesCol1a1,Runx2,Sp7,Bglap,Ibsp, andDmp1was inhibited by a conditioned medium from MSU crystal-stimulated RAW264.7 macrophages. Mineral staining of MC3T3-E1 cultures on day 21 confirmed the inhibition of osteoblast differentiation. In HOB cultures, the effect of 20 h incubation with a conditioned medium from MSU crystal-stimulated THP-1 monocytes on osteoblast gene expression was less consistent. Expression of the genes encoding cyclooxygenase-2 and IL-6 and secretion of the proinflammatory mediators PGE2and IL-6 were induced in MC3T3-E1 and HOBs incubated with conditioned medium from MSU crystal-stimulated macrophages/monocytes. However, inhibition of cyclooxygenase-2 activity and PGE2secretion from HOBs indicated that this pathway does not play a major role in mediating the indirect effects of MSU crystals in HOBs.

Conclusions

Factors secreted from macrophages stimulated by MSU crystals attenuate osteoblast differentiation and induce the expression and secretion of proinflammatory mediators from osteoblasts. We suggest that bone erosion in joints affected by gout results from a combination of direct and indirect effects of MSU crystals.
How do responses vary between mothers and their daughters on measuring daughter’s self-rated health (SRH): a study among school-going adolescent girls in the primary setting of Varanasi, India
Authors: Patel Ratna , Bansod Dhananjay W.
Published: September 2022

Objective

How self-rated health (SRH) varies when the response on SRH is recorded from the respondent herself (adolescent girl) and her mother on her behalf. This study examines the prevalence of SRH among adolescent girls from her point of view as well as from her mother’s point of view. This insight could help us interpret the differences in opinion of girls and their mothers while measuring the girls’ self-rated health.

Results

Almost one-fifth (19.4%) of the girls reported poor SRH. In contrast, only one in eight mothers (12.3%) could report their daughters under the category of poor SRH. Nearly one-third (76.5%) of the mothers reported their daughter’s SRH as good when daughters themselves rated poorly on SRH and another one-tenth (9.6%) reported their daughter’s SRH as poor when daughters themselves categorized in the good SRH category [χ2 = 9.900; p < 0.002]. More than 90 percent of the Rich and Middle wealth index women, women in the household with only daughters and no son, women whose husbands had higher education, women with higher secondary education, and non-working women visualized their daughter’s SRH as good when daughters themselves reported poor SRH.
Characterization of the fatty acid profile in the ventral midbrain of mice exposed to dietary imbalance between omega-6 and omega-3 fatty acids during specific life stages
Authors: Sakayori Nobuyuki , Katakura Masanori , Setogawa Susumu , Sugita Makoto , Kobayashi Kazuto
Published: September 2022

Objective

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients. Dietary imbalance between these PUFAs, in particular high in n-6 PUFAs and low in n-3 PUFAs (n-6high/n-3low), is common in modern society. We have previously reported that C57BL/6 mouse male offspring derived from mothers exposed to an n-6high/n-3low diet during the gestation had an augmented ventral midbrain dopamine system in adulthood; however, the fatty acid composition in this brain region has not yet been investigated. This follow-up study aims to characterize the fatty acid profile of the ventral midbrain of mice exposed to the n-6high/n-3low diet during specific life stages.

Results

n-6 PUFAs, especially linoleic acid, were increased in the ventral midbrain of offspring exposed to the n-6high/n-3low diet during the gestation compared to those exposed to a well-balanced control diet throughout life. On the other hand, n-3 PUFAs, especially docosahexaenoic acid, were decreased in the ventral midbrain of offspring exposed to the n-6high/n-3low diet during the gestation, lactation, or postweaning period compared to those exposed to the control diet throughout life. Thus, exposure to the n-6high/n-3low diet in pregnancy increases linoleic acid and that in any life stage decreases docosahexaenoic acid in the offspring's ventral midbrain.
Solar maculopathy secondary to sunlight exposure reflected from the screen of mobile devices: two case reports
Authors: Marticorena Joaquín , Honrubia Ana , Ascaso Javier
Published: September 2022

Background

Solar maculopathy is a well described clinical entity that usually occurs in patients that have gazed directly the sun. In this report we describe the first two cases of solar maculopathy in individuals exposed to sunlight reflected from the screen of mobile devices in the absence of direct sun gaze.

Cases description

Case 1. A 30-year-old Caucasic man presented with bilateral metamorphopsia, central scotoma and decreased visual acuity two days after being reading for four hours with his tablet computer in a terrace of a ski center. Case 2. A 20-year-old Caucasic woman was examined for bilateral decrease of visual acuity and central scotoma after being at the beach the day before and reading with her mobile phone for 3 hours. Both patients denied gazing directly to sunlight at any moment. In each case, exploration revealed fundus and OCT images compatible with the typical features of solar maculopathy. After 2 years of follow-up, in absence of any specific treatment, Case 1 had a complete resolution of the fundus alterations, while Case 2 still presented defects of the outer retinal layers. In both cases, an exposure to sunlight reflected from the screen of their mobile devices was documented in environments where solar radiation is thought to be augmented.

Conclusion

Sunlight reflection from a display screen needs to be considered as a possible risk factor for increased solar radiation and a subsequent risk of solar maculopathy.
Synovial membrane-derived mesenchymal progenitor cells from osteoarthritic joints in dogs possess lower chondrogenic-, and higher osteogenic capacity compared to normal joints
Authors: Teunissen M. , Ahrens N. S. , Snel L. , Narcisi R. , Kamali S. A. , van Osch G. J. V. M. , Meij B. P. , Mastbergen S. C. , Sivasubramaniyan K. , Tryfonidou M. A.
Published: September 2022

Background

Synovial membrane-derived mesenchymal progenitor cells (SM-MPCs) are a promising candidate for the cell-based treatment of osteoarthritis (OA) considering their in vitro and in vivo capacity for cartilage repair. However, the OA environment may adversely impact their regenerative capacity. There are no studies for canine (c)SM-MPCs that compare normal to OA SM-MPCs, even though dogs are considered a relevant animal model for OA. Therefore, this study compared cSM-MPCs from normal and OA synovial membrane tissue to elucidate the effect of the OA environment on MPC numbers, indicated by CD marker profile and colony-forming unit (CFU) capacity, and the impact of the OA niche on tri-lineage differentiation.

Methods

Normal and OA synovial membrane were collected from the knee joints of healthy dogs and dogs with rupture of the cruciate ligaments. The synovium was assessed by histopathological OARSI scoring and by RT-qPCR for inflammation/synovitis-related markers. The presence of cSM-MPCs in the native tissue was further characterized with flow cytometry, RT-qPCR, and immunohistochemistry, using the MPC markers; CD90, CD73, CD44, CD271, and CD34. Furthermore, cells isolated upon enzymatic digestion were characterized by CFU capacity, and a population doublings assay. cSM-MPCs were selected based on plastic adherence, expanded to passage 2, and evaluated for the expression of MPC-related surface markers and tri-lineage differentiation capacity.

Results

Synovial tissue collected from the OA joints had a significantly higher OARSI score compared to normal joints, and significantly upregulated inflammation/synovitis markers S100A8/9, IL6, IL8, and CCL2. Both normal and OA synovial membrane contained cells displaying MPC properties, including a fibroblast-like morphology, CFU capacity, and maintained MPC marker expression over time during expansion. However, OA cSM-MPCs were unable to differentiate towards the chondrogenic lineage and had low adipogenic capacity in contrast to normal cSM-MPCs, whereas they possessed a higher osteogenic capacity. Furthermore, the OA synovial membrane contained significantly lower percentages of CD90+, CD44+, CD34+, and CD271+ cells.

Conclusions

The OA environment had adverse effects on the regenerative potential of cSM-MPCs, corroborated by decreased CFU, population doubling, and chondrogenic capacity compared to normal cSM-MPCs. OA cSM-MPCs may be a less optimal candidate for the cell-based treatment of OA than normal cSM-MPCs.
Human umbilical cord blood mononuclear cells transplantation for perinatal brain injury
Authors: Xi Yufeng , Yue Guang , Gao Shuqiang , Ju Rong , Wang Yujia
Published: September 2022

Perinatal brain injury is a leading cause of death and disability in children. Hypoxic-ischemic encephalopathy in full term infants, and white matter injury in premature infants are most known brain injury in perinatal period. Human umbilical cord blood mononuclear cells contain hematopoietic stem cells, mesenchymal stem cells, endothelial progenitor cells, lymphocytes, monocytes, and so on. Human umbilical cord blood mononuclear cells have many biological functions, such as nerve and vascular regeneration, anti-apoptosis, anti-inflammation, and immune regulation. Human umbilical cord blood mononuclear cells transplantation has achieved significant efficacy and safety in animal and clinical trials for the treatment of perinatal brain injury. We will review human umbilical cord blood mononuclear cells transplantation for perinatal brain injury in this review.
Sexual dimorphism of leptin and adiposity in children between 0 and 10 years: a systematic review and meta-analysis
Authors: Ortega-Avila Jose Guillermo , García-Muñoz Harry , Segura Ordoñez Alejandro , Salazar Contreras Blanca C.
Published: September 2022

Background

Differences in adolescents and adults by sex in blood levels of leptin and adiposity have been described; however, it is not yet clear if these differences arise from the prepubertal stage in subjects with a normal-weight. Therefore, we examine whether there are differences by sex in levels of blood leptin and adiposity in children with a normal-weight between 0 and 10 years old.

Methods

Search strategy: eligible studies were obtained from three electronic databases (Ovid, Embase and LILACS) and contact with experts. Selection criteria: healthy children up to 10 years of age with normal-weight according to age.

Data collection and analyses: data were extracted by four independent reviewers using a predesigned data collection form. For the analysis, we stratified according to age groups (newborns, 0.25–0.5 years, 3–5.9 years, 6–7.9 years, 8–10 years). The statistical analysis was performed in the R program.

Results

Of the initially identified 13,712 records, 21 were selected in the systematic review and meta-analysis. The sex was associated with the overall effect on blood leptin (pooled MD = 1.72 ng/mL, 95% CI: 1.25–2.19) and body fat percentage (pooled MD = 3.43%, 95% CI: 2.53–4.33), being both higher in girls. This finding was consistent in the majority of age groups.

Conclusion

The results of our meta-analyses support the sexual dimorphism in circulating blood leptin and body fat percentage between girls and boys with normal-weight from prepuberty.
Evaluation of alpaca tracheal explants as an ex vivo model for the study of Middle East respiratory syndrome coronavirus (MERS-CoV) infection
Authors: Te Nigeer , Rodon Jordi , Creve Rhea , Pérez Mónica , Segalés Joaquim , Vergara-Alert Júlia , Bensaid Albert
Published: September 2022

Middle East respiratory syndrome coronavirus (MERS-CoV) poses a serious threat to public health. Here, we established an ex vivo alpaca tracheal explant (ATE) model using an air-liquid interface culture system to gain insights into MERS-CoV infection in the camelid lower respiratory tract. ATE can be infected by MERS-CoV, being 103 TCID50/mL the minimum viral dosage required to establish a productive infection. IFNs and antiviral ISGs were not induced in ATE cultures in response to MERS-CoV infection, strongly suggesting that ISGs expression observed in vivo is rather a consequence of the IFN induction occurring in the nasal mucosa of camelids.
Differential gene expression analysis of common target genes for the detection of SARS-CoV-2 using real time-PCR
Authors: Valadan Reza , Golchin Soheila , Alizadeh-Navaei Reza , Haghshenas Mohammadreza , Zargari Mehryar , Mousavi Tahoora , Ghamati Mohammad
Published: September 2022

COVID-19 currently is the main cause of the severe acute respiratory disease and fatal outcomes in human beings worldwide. Several genes are used as targets for the detection of SARS-CoV-2, including the RDRP, N, and E genes. The present study aimed to determine the RDRP, N, and E genes expressions of SARS-CoV- 2 in clinical samples. For this purpose, 100 SARS-CoV-2 positive samples were collected from diagnostic laboratories of Mazandaran province, Iran. After RNA extraction, the real-time reverse transcription PCR (real-time RT-PCR) assay was performed for differential gene expressions’ analysis of N, E, and RDRP. The threshold cycle (Ct) values for N, RDRP, and E targets of 100 clinical samples for identifying SARS-CoV-2 were then evaluated using quantitative real-time PCR (qRT-PCR). This result suggests N gene as a potential target for the detection of the SARS-CoV‐2, since it was observed to be highly expressed in the nasopharyngeal or oropharynges of COVID-19 patients (P < 0.0001). Herein, we showed that SARS-CoV- 2 genes were differentially expressed in the host cells. Therefore, to reduce obtaining false negative results and to increase the sensitivity of the available diagnostic tests, the target genes should be carefully selected based on the most expressed genes in the cells.
Maintenance of tRNA and elongation factors supports T3SS proteins translational elongations in pathogenic bacteria during nutrient starvation
Authors: Sun Yue , Shao Xiaolong , Zhang Yingchao , Han Liangliang , Huang Jiadai , Xie Yingpeng , Liu Jingui , Deng Xin
Published: September 2022

Background

Sufficient nutrition contributes to rapid translational elongation and protein synthesis in eukaryotic cells and prokaryotic bacteria. Fast synthesis and accumulation of type III secretion system (T3SS) proteins conduce to the invasion of pathogenic bacteria into the host cells. However, the translational elongation patterns of T3SS proteins in pathogenic bacteria under T3SS-inducing conditions remain unclear. Here, we report a mechanism of translational elongation of T3SS regulators, effectors and structural protein in four model pathogenic bacteria (Pseudomonas syringae, Pseudomonas aeruginosa, Xanthomonas oryzae and Ralstonia solanacearum) and a clinical isolate (Pseudomonas aeruginosa UCBPP-PA14) under nutrient-limiting conditions. We proposed a luminescence reporter system to quantitatively determine the translational elongation rates (ERs) of T3SS regulators, effectors and structural protein under different nutrient-limiting conditions and culture durations.

Results

The translational ERs of T3SS regulators, effectors and structural protein in these pathogenic bacteria were negatively regulated by the nutrient concentration and culture duration. The translational ERs in 0.5× T3SS-inducing medium were the highest of all tested media. In 1× T3SS-inducing medium, the translational ERs were highest at 0 min and then rapidly decreased. The translational ERs of T3SS regulators, effectors and structural protein were inhibited by tRNA degradation and by reduced levels of elongation factors (EFs).

Conclusions

Rapid translational ER and synthesis of T3SS protein need adequate tRNAs and EFs in nutrient-limiting conditions. Numeric presentation of T3SS translation visually indicates the invasion of bacteria and provides new insights into T3SS expression that can be applied to other pathogenic bacteria.
Presentation attack detection and biometric recognition in a challenge-response formalism
Authors: Haasnoot Erwin , Spreeuwers Luuk J. , Veldhuis Raymond N. J.
Published: September 2022

Presentation attack detection (PAD) is used to mitigate the dangers of theweakest link problemin biometric recognition, in which failure modes of one application affect the security of all other applications. Strong PAD methods are therefore a must, and we believe biometric challenge-response protocols (BCRP) form an underestimated part of this ecosystem. In this paper, we conceptualize what BCRPs are, and we propose a descriptive formalism and categorization for working with them. We validate the categorization against existing literature that we classified to be describing BCRPs. Lastly, we discuss how strong BCRPs provide advantages over PAD methods, specifically in the protection of individual applications and the protection ofotherapplications from inadvertent leaks in BCRP applications. We note that research in BCRPs is fragmented, and our intent for the proposed formalism and categorization are to give focus and direction to research efforts into biometric challenge-response protocols.
A new fair-efficient spectrum allocation scheme for the LTE and WiFi coexistence platform
Authors: Kim Sungwook
Published: September 2022

Long-term evolution (LTE) carrier aggregation with the unlicensed WiFi spectrum band has been pointed out as a good solution to handle the rapidly increasing wireless data traffic amounts. With both LTE and WiFi networks, the investigation of their coexistence is a hot research topic of active interest, primarily driven by industry and academia. In this study, we investigate a new spectrum allocation scheme for the LTE/WiFi coexistence platform. To maximize the system throughput while guaranteeing a relative fairness between heterogeneous networks, we adopt the cooperative game paradigm to design our novel scheme. According to the basic ideas of Proportional Nash bargaining solution (PNBS) and Zhang’s group bargaining solution (ZGBS), we can leverage a mutual consensus to provide a fair-efficient solution for the LTE/WiFi spectrum sharing problem. Based on the online interactive bargaining approach, network agents work together to effectively share the LTE and WiFi spectrum resources. Under dynamically changing network environments, it is an essential approach to find the relevant trade-off between conflicting requirements, i.e., fairness and efficiency. Validated by simulation results, our proposed scheme can provide important insights into the LTE/WiFi system operations. Finally, we forecast further research trends on the basis of our conclusion.
Pathways and approaches for scaling-up of community-based management of acute malnutrition programs through the lens of complex adaptive systems in South Sudan
Authors: Renzaho Andre M. N. , Dachi Gilbert , Ategbo Eric , Chitekwe Stanley , Doh Daniel
Published: September 2022

Background

Funds for community-based management of acute malnutrition (CMAM) programs are short-term in nature. CMAM programs are implemented in countries with weak policies and health systems and are primarily funded by donors. Beyond operational expansion, their institutionalisation and alignment with governments’ priorities are poorly documented. The study aimed to identify pathway opportunities and approaches for horizontal and vertical scaling up of CMAM programs in South Sudan.

Methods

The study was conducted in South Sudan between August and September 2021 using an online qualitative survey with 31 respondents from policy and implementing organisations. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework guided the study’s design. It was self-administered through the Qualtrics platform. We used Qualitative Content Analysis supported by the Nvivo coding process. A deductive a priori template of codes approach was complemented by a data-driven inductive approach to develop the second level of interpretive understanding.

Results

Findings from the study demonstrate that the emphasis of CMAM programs was horizontal scaling up, characterised by geographic distribution and coverage as well as operational expansion. Main challenges have included unsustainable funding models, the inadequacy of existing infrastructure, high operational costs, cultural beliefs, and access-related barriers. Factor impacting access to CMAM programs have been geographical terrains, safety, and security concerns. Vertical scaling up, which emphasises institutional and ownership strengthening through a sound policy, regulatory, and fiscal environment, received relatively little attention. Nutrition supplies are not part of the government’s essential drug list and there is limited or no budgetary allocation for nutrition programs by the government in national budgets and fiscal strategies. Factors constraining vertical scalability have included weak government systems and capacity, a lack of advocacy and lobbying opportunities, and an apparent lack of exits strategies.

Conclusion

Addressing the scalability problems of CMAM programs in South Sudan demands a delicate balancing act that prioritises both horizontal and vertical scalability. Government and political leadership that harness multidisciplinary and multi-sectoral coordination are required. There is a need to increase policy commitment to malnutrition and associated budgetary allocation, emphasise local resource mobilisation, and ensure financial sustainability of integrating CMAM programs into the existing health and welfare system.
Effect of the preoperative physical status on postoperative nausea and vomiting risk: a matched cohort study
Authors: Kim Jong Ho , Kim Haewon , Yoo Kookhyun , Hwang Sung Mi , Lim So Young , Lee Jae Jun , Kwon Young Suk
Published: September 2022

Background

The American Society of Anesthesiologists Physical Status Classification System is commonly used for preoperative assessment. Patient physical status before surgery can play an important role in postoperative nausea and vomiting. However, the relationship between the physical status classification and postoperative nausea and vomiting has not been well defined.

Methods

Adults aged ≥ 18 years who underwent procedures under anesthesia between 2015 and 2020 were included in the study. We analyzed the relationship of postoperative nausea and vomiting with physical status classification score using propensity score matching and Cox hazard regression. Differences in intraoperative use of vasopressor and inotropes and invasive monitoring were investigated according to the classification.

Results

A total of 163,500 patients were included in the study. After matching, classification 1 versus 2 included 43,400 patients; 1 versus ≤ 3, 13,287 patients; 2 versus ≤ 3, 23,530 patients (absolute standardized difference, 0–0.06). Patients with physical status classification ≤ 3 had a significantly lower postoperative nausea and vomiting risk than those with classification 1–2 (physical status classification 1 vs. ≤ 3, hazard ratio 0.76 [0.71–0.82], P < 0.001; 2 versus ≤ 3, hazard ratio 0.86 [0.82–0.91], P < 0.001). Intraoperative use of vasopressor or inotrope and invasive monitoring were noted more in the high physical status classification than the low physical status classification (absolute standardized difference [0.19–1.25]).

Conclusion

There were differences in intraoperative invasive monitoring and use of vasopressor or inotrope among the classifications, and a score of 3 or higher reduced the risk of postoperative nausea and vomiting more than a score of 1–2.