bluuebunny/crossref_metadata_2025 huggingface dataset:
Physician distribution across China’s cities: regional variations
Authors: Yu Xuexin , Zhang Wei , Liang Jersey
Published: July 2021

Background

Distribution of physicians is a key component of access to health care. Although there is extensive research on urban-rural disparities in physician distribution, limited attention has been directed to the heterogeneity across urban areas. This research depicts variations in physician density across over 600 cities in the context of China’s rapid urbanization.

Methods

Data came from National Census Surveys and China statistical yearbooks, 2000–2003, and 2010–2013. Cities were characterized in terms of not only administrative level but also geographic regions and urban agglomerations. We analyzed variations in physician supply by applying generalized estimating equations with an ordinal logistic linking function.

Results

Although overall physician density increased between 2003 and 2013, with population and socioeconomic attributes adjusted, physician density declined in urban China. On average, urban districts had a higher physician density than county-level cities, but there were regional variations. Cities in urban agglomerations and those outsides did not differ in physician density.

Conclusion

Despite the reduced inequality between 2003 and 2013, the growth in physician density did not appear to be commensurate with the changes in population health demand. Assessment in physician distribution needs to take into account heterogeneity in population and socioeconomic characteristics.
Exposure to environmental phenols and parabens, and relation to body mass index, eczema and respiratory outcomes in the Norwegian RHINESSA study
Authors: Vindenes Hilde Kristin , Svanes Cecilie , Lygre Stein Håkon Låstad , Real Francisco Gomez , Ringel-Kulka Tamar , Bertelsen Randi Jacobsen
Published: July 2021

Background

Many phenols and parabens are applied in cosmetics, pharmaceuticals and food, to prevent growth of bacteria and fungi. Whether these chemicals affect inflammatory diseases like allergies and overweight is largely unexplored. We aimed to assess the associations of use of personal care products with urine biomarkers levels of phenols and paraben exposure, and whether urine levels (reflecting body burden of this chemical exposures) are associated with eczema, rhinitis, asthma, specific IgE and body mass index.

Methods

Demographics, clinical variables, and self-report of personal care products use along with urine samples were collected concurrently from 496 adults (48% females, median age: 28 years) and 90 adolescents (10–17 years of age) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan (TCS), triclocarban (TCC), parabens and benzophenone-3, bisphenols and dichlorophenols (DCP) were quantified by mass spectrometry.

Results

Detection of the urine biomarkers varied according to chemical type and demographics. TCC was detected in 5% of adults and in 45% of adolescents, while propyl (PPB) and methyl (MPB) parabens were detected in 95% of adults and in 94% (PPB) and 99% (MPB) of adolescents. Women had higher median urine concentrations of phenolic chemicals and reported a higher frequency of use of personal care products than men. Urine concentration of MPB increased in a dose-dependent manner with increased frequency of use of several cosmetic products. Overall, urinary biomarker levels of parabens were lower in those with current eczema. The biomarker concentrations of bisphenol S was higher in participants with positive specific IgE and females with current asthma, but did not differ by eczema or rhinitis status. MPB, ethylparaben (EPB), 2,4-DCP and TCS were inversely related to BMI in adults; interaction by gender were not significant.

Conclusions

Reported frequency of use of personal care products correlated very well with urine biomarker levels of paraben and phenols. Several chemicals were inversley related to BMI, and lower levels of parabens was observed for participants with current eczema. There is a need for further studies of health effects of chemicals from personal care products, in particular in longitudinally designed studies.
The blocking effect of the glycoprotein IIb/IIIa receptor in the mouse model of asthma
Authors: Kim Seo-Hee , Trinh Hoang Kim Tu , Park Hae-Sim , Shin Yoo Seob
Published: July 2021

Background

It is apparent that the interaction between platelets and eosinophils plays a critical role in the activation of allergic inflammation. We investigated whether blocking of the glycoprotein (GP) IIb/IIIa receptor can attenuate allergic inflammation and airway hyperresponsiveness through inhibition of platelet–eosinophil aggregation (PEA) in asthma.

Methods

BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 0 and 14, followed by 3 nebulized OVA challenges on days 28–30. On each challenge day, 5 mg/kg tirofiban was administered intraperitoneally 30 min before the challenge. Mice were assessed for airway hyperresponsiveness (AHR), airway inflammation, and the degree of PEA. Finally, the activation levels of platelets and eosinophils were evaluated.

Results

Tirofiban treatment decreased AHR and eosinophilic inflammation in Bronchoalveolar Lavage (BAL) fluid. This treatment also reduced the levels of interleukin (IL)-4, IL-5, and IL-13 in BAL fluid and airway inflammatory cell infiltration in histological evaluation. Interestingly, the blocking of the GP IIb/IIIa receptor more reduced PEA in both blood and lung tissue of tirofiban-treated mice than in those of the positive control mice, and both eosinophilic and platelet activations were attenuated in tirofiban-treated mice.

Conclusions

The blocking of GP IIb/IIIa receptor with tirofiban can attenuate AHR and airway inflammation through the inhibition of PEA and activation.
The value of restaging CT following neoadjuvant chemotherapy for resectable gastric cancer. A population-based study
Authors: Sandø Alina Desiree , Fougner Reidun , Grønbech Jon Erik , Bringeland Erling Audun
Published: July 2021

Background

Response evaluation following neoadjuvant chemotherapy (NAC) in gastric cancer is debated. The aim of this study was to investigate the value of UICC-downstaging as mode of response evaluation following a MAGIC-style regimen of NAC.

Methods

Retrospective, population-based study on consecutive patients with resectable gastric adenocarcinoma receiving NAC from 2007 to 2016. CT-scan was obtained at diagnosis (rTNM) and repeated following NAC (yrTNM) to evaluate response in terms of downstaging. Further, yrTNM stage was crosstabulated to pathologic stage (ypTNM) to depict correlation between radiologic and pathologic assessment.

Results

Of 171 patients receiving NAC, 169 were available for response evaluation. For TNM-stages, 43% responded, 50% had stable disease and 7% progressed at CT. Crosstabulating yrTNM stage to ypTNM stage, 24% had concordant stages, with CT overstaging 38% and understaging 38% of the tumours, Cohen kappa ƙ = 0,06 (95%CI 0.004–0.12). Similar patterns of discordance were found for T-stages and N-stages separately. For M-category, restaging CT detected 12 patients with carcinomatosis, with an additional 14 diagnosed with carcinomatosis only at operation. No patient developed parenchymal or extra abdominal metastases, and none developed locally non-resectable tumour during delivery of NAC. Restaging CT with response evaluation was not able to stratify patients into groups of different long-term survival rates based on response mode.

Conclusions

Routine CT-scan following NAC is of limited value. Accuracy of CT staging compared to final pathologic stage is poor, and radiologic downstaging as measure of response evaluation is unreliable and unable to discriminate long-term survival rates based on response mode.
Correlation between hypoxia-inducible factor-1α C1772T/G1790A polymorphisms and head and neck cancer risk: a meta-analysis
Authors: Wu Ting , Zhang Zhong-ti , Li Lin , Liu Ru-yue , Bei Bao-ting
Published: July 2021

Objective

This meta-analysis was implemented to evaluate the association between hypoxia-inducible factor-1α (HIF-1α) C1772T/G1790A polymorphisms and susceptibility to head and neck cancer (HNC).

Material and methods

This meta-analysis has been registered on PROSPERO platform (CRD42021257309). The PubMed, Embase and Web of Science databases were searched to retrieve eligible published papers. STATA software was used to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to assess the correlation strength.

Results

Our results demonstrated that the HIF-1α C1772T polymorphism was significantly related to an increased HNC risk (OR = 2.27, 95% CI = 1.17–4.42 for the homozygous model; OR = 11.53, 95% CI = 1.11–120.4 for the recessive model), especially in Caucasians (OR = 2.16, 95% CI = 1.09–4.27 for the homozygous model; OR = 2.28, 95% CI = 1.15–5.51 for the recessive model). Similarly, a remarkable correlation was discovered between the G1790A polymorphism and HNC risk (OR = 72.11, 95% CI = 2.08–2502.4 for the homozygous model; OR = 58.05, 95% CI = 1.70–1985.77 for the recessive model). Moreover, in the subgroup analysis by source of controls, a statistically significant correlation was discovered in the population-based (PB) subgroup (OR = 9.43, 95% CI = 1.20–73.9 for allelic model; OR = 72.11, 95% CI = 2.08–2502.4 for the homozygous model; OR = 3.22, 95% CI = 1.28–8.08 for the heterozygous model; OR = 7.83, 95% CI = 1.48–41.37 for the dominant model; OR = 58.05, 95% CI = 1.70–1985.8 for the recessive model) but not in the hospital-based (HB) subgroup.

Conclusion

Our study found that both HIF-1α C1772T and G1790A polymorphisms might be a higher risk of HNC, especially in the Caucasian group with the C1772T polymorphism.
Rebuilding to shape a better future: the role of young professionals in the public health workforce
Authors: Wong Brian Li Han , Siepmann Ines , Chen Tara T. , Fisher Shelby , Weitzel Tobias S. , Nathan Naomi L. , Saminarsih Diah S.
Published: July 2021

The COVID-19 pandemic has made clear the extreme needs of the public health workforce. As societies discuss how to build up the capacity and infrastructure of their systems, it is crucial that young professionals are involved. Previous attempts to incorporate young professionals into the public health workforce have wrestled with inaccessibility, tokenisation, and a lack of mentorship, leading to a loss of potential workforce members and a non-representative workforce that reinforces systemic societal exclusion of diverse young people. These barriers must be addressed through robust mentorship structures, intentional recruitment and continuous support, as well as genuine recognition of the contributions of young professionals to build the sustainable, interdisciplinary, unified public health that is necessary for the future.
The role of PD-L1 in the immune dysfunction that mediates hypoxia-induced multiple organ injury
Authors: Sun Yang , Tan Jin , Miao Yuyang , Zhang Qiang
Published: July 2021

Hypoxia is a pathological condition common to many diseases, although multiple organ injuries induced by hypoxia are often overlooked. There is increasing evidence to suggest that the hypoxic environment may activate innate immune cells and suppress adaptive immunity, further stimulating inflammation and inhibiting immunosurveillance. We found that dysfunctional immune regulation may aggravate hypoxia-induced tissue damage and contribute to secondary injury. Among the diverse mechanisms of hypoxia-induced immune dysfunction identified to date, the role of programmed death-ligand 1 (PD-L1) has recently attracted much attention. Besides leading to tumour immune evasion, PD-L1 has also been found to participate in the progression of the immune dysfunction which mediates hypoxia-induced multiple organ injury. In this review, we aimed to summarise the role of immune dysfunction in hypoxia-induced multiple organ injury, the effects of hypoxia on the cellular expression of PD-L1, and the effects of upregulated PD-L1 expression on immune regulation. Furthermore, we summarise the latest information pertaining to the involvement, diagnostic value, and therapeutic potential of immunosuppression induced by PD-L1 in various types of hypoxia-related diseases, including cancers, ischemic stroke, acute kidney injury, and obstructive sleep apnoea.
Neural basis of implicit cognitive reappraisal in panic disorder: an event-related fMRI study
Authors: Wang Hai-Yang , Xu Guo-Qing , Ni Ming-Fei , Zhang Cui-Hong , Li Xue-Lin , Chang Yi , Sun Xiao-Pei , Zhang Bing-Wei
Published: July 2021

Background

Panic disorder (PD) is thought to be related with deficits in emotion regulation, especially in cognitive reappraisal. According to the cognitive model, PD patients’ intrinsic and unconscious misappraisal strategies are the cause of panic attacks. However, no studies have yet been performed to explore the underlying neuromechanism of cognitive reappraisal that occur on an unconscious level in PD patients.

Methods

Twenty-six patients with PD and 25 healthy controls (HC) performed a fully-verified event-block design emotional regulation task aimed at investigating responses of implicit cognitive reappraisal during an fMRI scan. Participants passively viewed negatively valanced pictures that were beforehand neutrally, positively, or adversely portrayed in the task.

Results

Whole-brain analysis of fMRI data showed that PD patients exhibited less activation in the right dorsolateral prefrontal cortex (dlPFC) and right dorsomedial prefrontal cortex (dmPFC) compared to HC, but presented greater activation in parietal cortex when negative pictures were preceded by positive/neutral vs negative descriptions. Simultaneously, interactive effects of Group × Condition were observed in the right amygdala across both groups. Furthermore, activation in dlPFC and dmPFC was is negatively correlated to severity of anxiety and panic in PD when negative images were preceded by non-negative vs negative descriptions.

Conclusions

Emotional dysregulation in PD is likely the result of deficient activation in dlPFC and dmPFC during implicit cognitive reappraisal, in line with impaired automatic top-down regulation. Correlations between severity of anxiety and panic attack and activation of right dlPFC and dmPFC suggest that the failure to engage prefrontal region during implicit cognitive reappraisal might be associated wtih the severity of anxiety and panic; such functional patterns might be the target of possible treatments.
Automatically evaluating balance using machine learning and data from a single inertial measurement unit
Authors: Kamran Fahad , Harrold Kathryn , Zwier Jonathan , Carender Wendy , Bao Tian , Sienko Kathleen H. , Wiens Jenna
Published: July 2021

Background

Recently, machine learning techniques have been applied to data collected from inertial measurement units to automatically assess balance, but rely on hand-engineered features. We explore the utility of machine learning to automatically extract important features from inertial measurement unit data for balance assessment.

Findings

Ten participants with balance concerns performed multiple balance exercises in a laboratory setting while wearing an inertial measurement unit on their lower back. Physical therapists watched video recordings of participants performing the exercises and rated balance on a 5-point scale. We trained machine learning models using different representations of the unprocessed inertial measurement unit data to estimate physical therapist ratings. On a held-out test set, we compared these learned models to one another, to participants’ self-assessments of balance, and to models trained using hand-engineered features. Utilizing the unprocessed kinematic data from the inertial measurement unit provided significant improvements over both self-assessments and models using hand-engineered features (AUROC of 0.806 vs. 0.768, 0.665).

Conclusions

Unprocessed data from an inertial measurement unit used as input to a machine learning model produced accurate estimates of balance performance. The ability to learn from unprocessed data presents a potentially generalizable approach for assessing balance without the need for labor-intensive feature engineering, while maintaining comparable model performance.
Predictability of maxillary positioning: a 3D comparison of virtual and conventional orthognathic surgery planning
Authors: Quast Anja , Santander Petra , Kahlmeier Timon , Moser Norman , Schliephake Henning , Meyer-Marcotty Philipp
Published: July 2021

Background

Virtual surgery planning (VSP) is believed to reduce inaccuracies in maxillary positioning compared to conventional surgery planning (CSP) due to the elimination of face-bow transfer and laboratory steps. However, there is still a lack of comparative studies for the accuracy of splint-based maxillary positioning in CSP versus VSP. Therefore, the objective of this retrospective, observational study was to compare if splints produced by VSP and CSP reach postoperative outcomes within clinically acceptable limits.

Methods

The planned and actual postoperative results of 52 patients (VSP: n = 26; CSP: n = 26) with a mean age of 24.4 ± 6.2 years were investigated by three-dimensional (3D) alignment with planning software. The conventional treatment plan was digitized, so that the evaluation of both methods was performed in the same manner using the same coordinate system. Inaccuracies were measured by sagittal, vertical and transversal deviations of the upper central incisors and the inclination of the maxillary occlusal plane between the planned and achieved maxillary positions.

Results

Both methods demonstrated significant differences between the planned and actual outcome. The highest inaccuracies were observed in vertical impaction and midline correction. No significant differences between CSP and VSP were observed in any dimension. Errors in vertical and sagittal dimension intensified each other.

Conclusions

In conclusion, splint-based surgeries reached similar results regardless of the applied planning method and splint production.
The effectiveness of trauma care systems at different stages of development in reducing mortality: a systematic review and meta-analysis
Authors: Alharbi Rayan Jafnan , Shrestha Sumina , Lewis Virginia , Miller Charne
Published: July 2021

Background

Traumatic injury remains the leading cause of death, with more than five million deaths every year. Little is known about the comparative effectiveness in reducing mortality of trauma care systems at different stages of development. The objective of this study was to review the literature and examine differences in mortality associated with different stages of trauma system development.

Method

A systematic review of peer-reviewed population-based studies retrieved from MEDLINE, EMBASE, and CINAHL. Additional studies were identified from references of articles, through database searching, and author lists. Articles written in English and published between 2000 and 2020 were included. Selection of studies, data extraction, and quality assessment of the included studies were performed by two independent reviewers. The results were reported as odds ratio (OR) with 95 % confidence intervals (CI).

Results

A total of 52 studies with a combined 1,106,431 traumatic injury patients were included for quantitative analysis. The overall mortality rate was 6.77% (n= 74,930). When patients were treated in a non-trauma centre compared to a trauma centre, the pooled statistical odds of mortality were reduced (OR 0.74 [95% CI 0.69–0.79];p< 0.001). When patients were treated in a non-trauma system compared to a trauma system the odds of mortality rates increased (OR 1.17 [95% CI 1.10–1.24];p< 0.001). When patients were treated in a post-implementation/initial system compared to a mature system, odds of mortality were significantly higher (OR 1.46 [95% CI 1.37–1.55];p< 0.001).

Conclusion

The present study highlights that the survival of traumatic injured patients varies according to the stage of trauma system development in which the patient was treated. The analysis indicates a significant reduction in mortality following the introduction of the trauma system which is further enhanced as the system matures. These results provide evidence to support efforts to, firstly, implement trauma systems in countries currently without and, secondly, to enhance existing systems by investing in system development.

Systematic review registration number

PROSPEROCRD42019142842.
Improving early diagnosis of rare diseases using Natural Language Processing in unstructured medical records: an illustration from Dravet syndrome
Authors: Lo Barco Tommaso , Kuchenbuch Mathieu , Garcelon Nicolas , Neuraz Antoine , Nabbout Rima
Published: July 2021

Background

The growing use of Electronic Health Records (EHRs) is promoting the application of data mining in health-care. A promising use of big data in this field is to develop models to support early diagnosis and to establish natural history. Dravet Syndrome (DS) is a rare developmental and epileptic encephalopathy that commonly initiates in the first year of life with febrile seizures (FS). Age at diagnosis is often delayed after 2 years, as it is difficult to differentiate DS at onset from FS. We aimed to explore if some clinical terms (concepts) are significantly more used in the electronic narrative medical reports of individuals with DS before the age of 2 years compared to those of individuals with FS. These concepts would allow an earlier detection of patients with DS resulting in an earlier orientation toward expert centers that can provide early diagnosis and care.

Methods

Data were collected from the Necker Enfants Malades Hospital using a document-based data warehouse, Dr Warehouse, which employs Natural Language Processing, a computer technology consisting in processing written information. Using Unified Medical Language System Meta-thesaurus, phenotype concepts can be recognized in medical reports. We selected individuals with DS (DS Cohort) and individuals with FS (FS Cohort) with confirmed diagnosis after the age of 4 years. A phenome-wide analysis was performed evaluating the statistical associations between the phenotypes of DS and FS, based on concepts found in the reports produced before 2 years and using a series of logistic regressions.

Results

We found significative higher representation of concepts related to seizures’ phenotypes distinguishing DS from FS in the first phases, namely the major recurrence of complex febrile convulsions (long-lasting and/or with focal signs) and other seizure-types. Some typical early onset non-seizure concepts also emerged, in relation to neurodevelopment and gait disorders.

Conclusions

Narrative medical reports of individuals younger than 2 years with FS contain specific concepts linked to DS diagnosis, which can be automatically detected by software exploiting NLP. This approach could represent an innovative and sustainable methodology to decrease time of diagnosis of DS and could be transposed to other rare diseases.
The effectiveness of a psycho-education intervention on mental health literacy in communities affected by the COVID-19 pandemic—a cluster randomized trial of 24 villages in central Uganda—a research protocol
Authors: Akena Dickens , Kiguba Ronald , Muhwezi Wilson W. , Kwesiga Brendan , Kigozi Gwendolyne , Nakasujja Noeline , Lukwata Hafsa
Published: July 2021

Background

Literature shows a high prevalence of psychological distress (PD) as well as common mental disorders (CMD) such as major depressive disorders (MDD), generalized anxiety disorders (GAD), post-traumatic stress disorders (PTSD), and substance misuse disorders (SUD) among people exposed to disasters and pandemics like the COVID-19. Moreover, CMD are associated with increased mortality (mainly through suicide) and morbidity (loss of productivity). A number of countries have made deliberate efforts to identify and manage CMD in light of COVID-19. However, low levels of mental health literacy (MHL) manifested by the individual’s unawareness of CMD symptoms, limited human and mental health infrastructure resources, and high levels of mental illness stigma (MIS) are barriers to integration of mental health care in general health care during pandemics and epidemics such as the COVID-19.

Objectives

For the proposed study, we will determine effectiveness of a psycho-education intervention delivered by village health team (VHT) members.

Methods

We will employ a cluster randomized trial design in 24 villages in central Uganda. We will collect baseline data to and document the prevalence of MHL, PD, MDD, PTSD, GAD, and SUD. We will distribute information education and communication materials (IEC) aimed at improving MHL to 420 adult individuals in the intervention arm (n = 12 villages). In the control arm (n = 12 villages), VHTs will distribute ministry of health COVID-19 information leaflets to 420 participants. Within 7 days of distributing the materials, research assistants will conduct a follow-up interview and assess for the same parameters (MHL, PD, MDD, PTSD, GAD, and SUD). We will use an intention to treat analysis to estimate the effectiveness of the psycho-education intervention.

Discussion

Findings from this research will guide policy and practice regarding the integration of mental health services in the community in the context of epidemic preparedness and response.

Trial registration

ClinicalTrials.govNCT04616989. Registered on 05 November 2020
Risk factors associated with tick infestations on equids in Khyber Pakhtunkhwa, Pakistan, with notes on Rickettsia massiliae detection
Authors: Ali Abid , Zahid Hafsa , Zeb Ismail , Tufail Muhammad , Khan Sulaiman , Haroon Muhammad , Tufail Muhammad , Bilal Muhammad , Hussain Majid , Alouffi Abdulaziz S. , Muñoz-Leal Sebastián , Labruna Marcelo B.
Published: July 2021

Background

Studies on ticks infesting equids are lacking in various parts of the world, including Khyber Pakhtunkhwa (KP), Pakistan. The aim of this study was to investigate the diversity of ticks infesting equids, associated risk factors and rickettsial detection in ticks from equids in KP.

Methods

Inspection of 404 equid hosts from November 2018 to October 2019 resulted in the collection of 550 ticks. Data on tick-associated risk factors were collected from equid owners by means of a questionnaire. After morphological identification, partial DNA sequences of the tick mitochondrial 16S rRNA gene were used for taxonomic confirmation of species. Partial sequences of the gltA and ompA genes were used for Rickettsia detection in ticks.

Results

A total of 550 tick specimens were collected on 324 (80.2%) of the equids inspected, of which 161 were horses (50%), 145 (45%) were donkeys and 18 were mules (5%). The ticks were identified as belonging to the following five species: Rhipicephalus microplus (341 specimens, 62% of the total ticks), Rh. haemaphysaloides (126, 23%), Rh. turanicus (39, 7%), Rh. sanguineus (s.l.) (33, 6%) and Hyalomma anatolicum (11, 2%). The most prevalent tick life stage was adult females (279, 51%) followed by adult males (186, 34%) and nymphs (85, 15%). Higher tick infestations were observed on male equids (relative risk [RR] 0.7432, P < 0.0005) and adult equids (RR 1.268, P < 0.0020). Ticks were frequently attached to the axial region of horses (55, 21%), sternum of donkeys (44, 21%) and belly of mules (19, 23%) (P < 0.04). Temporal patterns of tick infestation in association with temperature and humidity were highly significant (P < 0.05). Risk factors, such as animal housing (P < 0.0003), living management (P < 0.006), grazing type (P < 0.01) and location in hilly areas (P < 0.02), significantly enhanced the chances for tick infestation. Tick species analyzed in this study were phylogenetically related to species from Afghanistan, China, South Africa and Taiwan. Partial sequences of the gltA and ompA genes obtained from Rh. microplus and Rh. haemaphysaloides were 100% identical to the spotted fever group pathogen Rickettsia massiliae.

Conclusions

Equids exposed to significant risk factors were infected by one or more of at least five tick species in KP, Pakistan, and some of the ticks harbored the human pathogen R. massiliae.

Graphical abstract
Synchronous and metachronous malignant melanomas arising in a human immunodeficiency virus-positive patient after the commencement of highly active antiretroviral therapy treatment: a case report
Authors: Paul Sharad P. , Briggs Simon , Hitchcock Michael
Published: July 2021

Background

We present an unusual case of a patient who developed four melanomas within a few months of diagnosis with human immunodeficiency virus and commencement of highly active antiretroviral therapy therapy. The patient had no previous history of melanoma, and previous skin checks were normal.

Case presentation

A 50-year-old Caucasian male drainlayer with Fitzpatrick type 2 skin presented for a routine skin examination. He had been diagnosed with human immunodeficiency virus 4 months earlier and commenced on highly active antiretroviral therapy therapy. He was found to have three melanomas (melanoma in situ stage) on excision biopsies, and when he presented for wider excisions of these sites a few weeks later, another new melanoma in situ was found. He had no other medical history of note, and no symptoms to report. He is being followed up 3-monthly.

Conclusions

This case of a human immunodeficiency virus-positive person presenting with four cutaneous melanomas—occurring in both synchronous and metachronous fashion within a 4-month period—is being presented both for its uniqueness and also to highlight the increased need for close skin surveillance in human immunodeficiency virus-positive patients.
Adipose mesenchymal stem cells combined with platelet-rich plasma accelerate diabetic wound healing by modulating the Notch pathway
Authors: Ebrahim Nesrine , Dessouky Arigue A. , Mostafa Ola , Hassouna Amira , Yousef Mohamed M. , Seleem Yasmin , El Gebaly Eman Abd El Aziz M. , Allam Mona M. , Farid Ayman Samir , Saffaf Bayan A. , Sabry Dina , Nawar Ahmed , Shoulah Ahmed A. , Khalil Ahmed H. , Abdalla Sami F. , El-Sherbiny Mohamed , Elsherbiny Nehal M. , Salim Rabab F.
Published: July 2021

Background

Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due to its high content of growth factors. However, its application is limited due to the rapid degradation of growth factors. The present study aimed to evaluate the efficacy of combined adipose-derived mesenchymal stem cells (ADSCs) and PRP therapy in promoting diabetic wound healing in relation to the Notch signaling pathway.

Methods

Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic), diabetic, PRP-treated, ADSC-treated, and PRP+ADSCs-treated groups]. The effect of individual and combined therapy was evaluated by assessing wound closure rate, epidermal thickness, dermal collagen, and angiogenesis. Moreover, gene and protein expression of key elements of the Notch signaling pathway (Notch1, Delta-like canonical Notch ligand 4 (DLL4), Hairy Enhancer of Split-1 (Hes1), Hey1, Jagged-1), gene expression of angiogenic marker (vascular endothelial growth factor and stromal cell-derived factor 1) and epidermal stem cells (EPSCs) related gene (ß1 Integrin) were assessed.

Results

Our data showed better wound healing of PRP+ADSCs compared to their individual use after 7 and 14 days as the combined therapy caused reepithelialization and granulation tissue formation with a marked increase in area percentage of collagen, epidermal thickness, and angiogenesis. Moreover, Notch signaling was significantly downregulated, and EPSC proliferation and recruitment were enhanced compared to other treated groups and diabetic groups.

Conclusions

These data demonstrated that PRP and ADSCs combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and EPSC proliferation.
Scintigraphic tracking of 99mTechnetium-labelled equine peripheral blood-derived mesenchymal stem cells after intravenous, intramuscular, and subcutaneous injection in healthy dogs
Authors: Beerts Charlotte , Brondeel Carlien , Pauwelyn Glenn , Depuydt Eva , Tack Liesa , Duchateau Luc , Xu Yangfeng , Saunders Jimmy H. , Peremans Kathelijne , Spaas Jan H.
Published: July 2021

Background

Mesenchymal stem cell treatments in dogs have been investigated as a potential innovative alternative to current conventional therapies for a variety of conditions. So far, the precise mode of action of the MSCs has yet to be determined. The aim of this study was to gain more insights into the pharmacokinetics of MSCs by evaluating their biodistribution in healthy dogs after different injection routes.

Methods

Three different studies were performed in healthy dogs to evaluate the biodistribution pattern of radiolabelled equine peripheral blood-derived mesenchymal stem cells following intravenous, intramuscular and subcutaneous administration in comparison with free 99mTechnetium. The labelling of the equine peripheral blood-derived mesenchymal stem cells was performed using stannous chloride as a reducing agent. Whole-body scans were obtained using a gamma camera during a 24-h follow-up.

Results

The labelling efficiency ranged between 59.58 and 83.82%. Free 99mTechnetium accumulation was predominantly observed in the stomach, thyroid, bladder and salivary glands, while following intravenous injection, the 99mTechnetium-labelled equine peripheral blood-derived mesenchymal stem cells majorly accumulated in the liver throughout the follow-up period. After intramuscular and subcutaneous injection, the injected dose percentage remained very high at the injection site.

Conclusions

A distinct difference was noted in the biodistribution pattern of the radiolabelled equine peripheral blood-derived mesenchymal stem cells compared to free 99mTechnetium indicating equine peripheral blood-derived mesenchymal stem cells have a specific pharmacokinetic pattern after systemic administration in healthy dogs. Furthermore, the biodistribution pattern of the used xenogeneic equine peripheral blood-derived mesenchymal stem cells appeared to be different from previously reported experiments using different sources of mesenchymal stem cells.
Glycemic control by umbilical cord-derived mesenchymal stem cells promotes effects of fasting-mimicking diet on type 2 diabetic mice
Authors: Zhao Na , Gao Ying-Feng , Bao Lei , Lei Jing , An Huan-Xiao , Pu Feng-Xing , Cheng Rui-Ping , Chen Ji , Ni Hua , Sui Bing-Dong , Ji Fan-Pu , Hu Cheng-Hu
Published: July 2021

Background

Hepatic steatosis is a big hurdle to treat type 2 diabetes (T2D). Fasting-mimicking diet (FMD) has been shown to be an effective intervention in dyslipidemia of T2D. However, fasting may impair the normal glucose metabolism. Human umbilical cord-derived mesenchymal stem cell (UC-MSC) transplantation has been discovered to regulate immune reactions and reduce hyperglycemia in diabetes. However, the effect of UC-MSCs on improving the lipid metabolism disorder is not quite satisfactory. We have investigated the efficacy comparison and interaction between FMD and UC-MSC infusion, aiming to establish effective T2D therapies and explore its mechanism.

Methods

C57/BL6 mice were fed with high-fat diet (HFD) to induce a diet-induced obese (DIO) mouse model. Leptin receptor-deficient (db/db) mice were used for follow-up experiments. DIO or db/db mice were divided into 4 groups: phosphate buffer saline (PBS), UC-MSCs, FMD, and UC-MSCs + FMD. At the end of the study period, mice were fasted and sacrificed, with the measurement of physiological and biochemical indexes. In addition, the fresh liver, skin, and white adipose tissue were analyzed by histology.

Results

FMD restored the lipid metabolism in DIO mice, whereas its capacity to rescue hyperglycemia was uncertain. Infusion of UC-MSCs was effective in T2D glycemic control but the impact on dyslipidemia was insufficient. Furthermore, both the glucose and the lipid alterations of DIO and db/db mice recovered after UC-MSCs combined with FMD. It was proved that UC-MSCs promoted FMD effects on ameliorating hyperglycemia and restoring the lipid metabolism in T2D mice, while FMD had little promotion effect on UC-MSCs. Mechanistically, we discovered that UC-MSC infusion significantly modulated systematic inflammatory microenvironment, which contributed to concerted actions with FMD.

Conclusions

We established a strategy that combined UC-MSC infusion and FMD and was effective in treating T2D, which provided potential approaches for developing novel clinical T2D therapies.
Comparison of mesenchymal stromal cells from peritoneal dialysis effluent with those from umbilical cords: characteristics and therapeutic effects on chronic peritoneal dialysis in uremic rats
Authors: Du Yangchun , Zong Ming , Guan Qiunong , Huang Zhongli , Zhou Lan , Cai Jing , da Roza Gerald , Wang Hao , Qi Hualin , Lu Yiping , Du Caigan
Published: July 2021

Background

A long-term of peritoneal dialysis (PD) using a hypertonic PD solution (PDS) leads to patient’s peritoneal membrane (PM) injury, resulting in ultrafiltration failure (UFF) and PD drop-out. Our previous study shows that PD effluent-derived mesenchymal stromal cells (pMSCs) prevent the PM injury in normal rats after repeated exposure of the peritoneal cavity to a PDS. This study was designed to compare the cytoprotection between pMSCs and umbilical cord-derived MSCs (UC-MSCs) in the treatment of both PM and kidney injury in uremic rats with chronic PD.

Methods

5/6 nephrectomized (5/6Nx) Sprague Dawley rats were intraperitoneally (IP) injected Dianeal (4.25% dextrose, 10 mL/rat/day) and were treated with pMSCs or umbilical cord (UC)-MSCs (approximately 2 × 106/rat/week, IP). Ultrafiltration was determined by IP injection of 30 mL of Dianeal (4.25% dextrose) with 1.5-h dewell time, and kidney failure by serum creatinine (SCr) and blood urea nitrogen (BUN). The structure of the PM and kidneys was assessed using histology. Gene expression was examined using quantitative reverse transcription PCR, and protein levels using flow cytometric and Western blot analyses.

Results

We showed a slight difference in the morphology between pMSCs and UC-MSCs in plastic dishes, and significantly higher expression levels of stemness-related genes (NANOG, OCT4, SOX2, CCNA2, RAD21, and EXO1) and MSCs surface markers (CD29, CD44, CD90 and CD105) in UC-MSCs than those in pMSCs, but no difference in the differentiation to chondrocytes, osteocytes or adipocytes. pMSC treatment was more effective than UC-MSCs in the protection of the MP and remnant kidneys in 5/6Nx rats from PDS-induced injury, which was associated with higher resistance of pMSCs than UC-MSCs to uremic toxins in culture, and more reduction of peritoneal mesothelial cell death by the secretome from pMSCs than from UC-MSCs in response to PDS exposure. The secretome from both pMSCs and UC-MSCs similarly inactivated NOS2 in activated THP1 cells.

Conclusions

As compared to UC-MSCs, pMSCs may more potently prevent PDS-induced PM and remnant kidney injury in this uremic rat model of chronic PD, suggesting that autotransplantation of ex vivo-expanded pMSCs may become a promising therapy for UFF and deterioration of remnant kidney function in PD patients.
Influence of the mesenchymal stromal cell source on the hematopoietic supportive capacity of umbilical cord blood-derived CD34+-enriched cells
Authors: Bucar Sara , Branco André Dargen de Matos , Mata Márcia F. , Milhano João Coutinho , Caramalho Íris , Cabral Joaquim M. S. , Fernandes-Platzgummer Ana , da Silva Cláudia L.
Published: July 2021

Background

Umbilical cord blood (UCB) is a clinically relevant alternative source of hematopoietic stem/progenitor cells (HSPC). To overcome the low cell number per UCB unit, ex vivo expansion of UCB HSPC in co-culture with mesenchymal stromal cells (MSC) has been established. Bone marrow (BM)-derived MSC have been the standard choice, but the use of MSC from alternative sources, less invasive and discardable, could ease clinical translation of an expanded CD34+ cell product. Here, we compare the capacity of BM-, umbilical cord matrix (UCM)-, and adipose tissue (AT)-derived MSC, expanded with/without xenogeneic components, to expand/maintain UCB CD34+-enriched cells ex vivo.

Methods

UCB CD34+-enriched cells were isolated from cryopreserved mononuclear cells and cultured for 7 days over an established feeder layer (FL) of BM-, UCM-, or AT-derived MSC, previously expanded using fetal bovine serum (FBS) or fibrinogen-depleted human platelet lysate (HPL) supplemented medium. UCB cells were cultured in serum-free medium supplemented with SCF/TPO/FLT3-L/bFGF. Fold increase in total nucleated cells (TNC) as well as immunophenotype and clonogenic potential (cobblestone area-forming cells and colony-forming unit assays) of the expanded hematopoietic cells were assessed.

Results

MSC from all sources effectively supported UCB HSPC expansion/maintenance ex vivo, with expansion factors (in TNC) superior to 50x, 70x, and 80x in UCM-, BM-, and AT-derived MSC co-cultures, respectively. Specifically, AT-derived MSC co-culture resulted in expanded cells with similar phenotypic profile compared to BM-derived MSC, but resulting in higher total cell numbers. Importantly, a subpopulation of more primitive cells (CD34+CD90+) was maintained in all co-cultures. In addition, the presence of a MSC FL was essential to maintain and expand a subpopulation of progenitor T cells (CD34+CD7+). The use of HPL to expand MSC prior to co-culture establishment did not influence the expansion potential of UCB cells.

Conclusions

AT represents a promising alternative to BM as a source of MSC for co-culture protocols to expand/maintain HSPC ex vivo. On the other hand, UCM-derived MSC demonstrated inferior hematopoietic supportive capacity compared to MSC from adult tissues. Despite HPL being considered an alternative to FBS for clinical-scale manufacturing of MSC, further studies are needed to determine its impact on the hematopoietic supportive capacity of these cells.
Ferulic acid inhibits LPS-induced apoptosis in bovine mammary epithelial cells by regulating the NF-κB and Nrf2 signalling pathways to restore mitochondrial dynamics and ROS generation
Authors: Liu Mingjiang , Zhang Chi , Xu Xiaolong , Zhao Xin , Han Ziyi , Liu Dandan , Bo Ruonan , Li Jingui , Liu Zongping
Published: July 2021

In bovine mammary epithelial cells (BMECs), a cascade of inflammatory reactions induced by lipopolysaccharide (LPS) has been shown to result in cell injury and apoptosis. The present study aims to reveal the protective effect of ferulic acid (FA) on LPS-induced BMEC apoptosis and explore its potential molecular mechanisms. First, we showed that FA had low cytotoxicity to BMECs and significantly decreased cell apoptosis and the proinflammatory response induced by LPS. Next, FA blocked LPS-induced oxidative stress by restoring the balance of the redox state and inhibiting mitochondrial dysfunction, the main contributor to LPS-induced apoptosis and ROS generation. Furthermore, the relief of inflammation and redox disturbance in the FA preconditioning group were accompanied by weaker NF-κB activation, enhanced Nrf2 activation and maintained cell viability compared to the LPS group. When BMECs were treated with FA alone, we observed that Nrf2 activation was induced before the inhibition of NF-κB activation and that the Keap1–Nrf2 relationship was disturbed. We concluded that FA prevented LPS-induced BMEC apoptosis by reversing the dominant relationship between NF-κB and Nrf2.
Early warning of bloodstream infection in elderly patients with circulating microparticles
Authors: Liu Tingting , Wang Jiang , Yuan Yaping , Wu Jionghe , Wang Chao , Gu Yueqin , Li Hongxia
Published: July 2021

Background

The difficulty of early diagnosis of bloodstream infection in the elderly patients leads to high mortality. Therefore, it is essential to determine some new methods of early warning of bloodstream infection in the elderly patients for timely adjustment of treatment and improvement of prognosis.

Methods

Patients aged over 65 years with suspected bloodstream infections were included and divided into bloodstream infection (BSI) and non-bloodstream infection (non-BSI) groups based on blood culture results. The morphology of microparticles (MPs) was observed by using transmission electron microscopy, and the number of MPs was dynamically monitored by flow cytometry.

Results

A total of 140 patients were included in the study: 54 in the BSI group and 86 in the non-BSI group. Total MPs (T-MPs) ≥ 6000 events/µL (OR, 7.693; 95% CI 2.944–20.103, P < 0.0001), neutrophil-derived MPs (NMPs) ≥ 500 events/µL (OR, 12.049; 95% CI 3.574–40.623, P < 0.0001), and monocyte counts ≤ 0.4 × 109/L (OR, 3.637; 95% CI 1.415–9.348, P = 0.007) within 6 h of fever were independently associated with bloodstream infection in the elderly patients. We also developed an early warning model for bloodstream infection in the elderly patients with an area under the curve of 0.884 (95% CI 0.826–0.942, P < 0.0001), sensitivity of 86.8%, specificity of 76.5%, positive predictive value of 70.8%, and negative predictive value of 89.8%.

Conclusion

The early warning model of bloodstream infection based on circulating T-MPs, NMPs, and monocyte counts within 6 h of fever in the elderly patients was helpful in early detection of bloodstream infection and therefore promptly adjustment of treatment plan.
Computer wireless network integration technology in equipment state data collection
Authors: Ma Lixin
Published: July 2021

The paper introduces a handheld integrated power data acquisition and analysis equipment based on a computer wireless network mobile platform, an intelligent transportation inspection box. The intelligent transportation inspection box acts as a bridge between the transportation inspection work site side and the power grid company center to realize data and resource sharing between the site and center sides. The application of intelligent operation and inspection boxes based on computer wireless network integration technology is essential for improving the professional and intelligent level of on-site operation and maintenance, improving the efficiency of operation and inspection work and the ability to control equipment status, strengthening state maintenance and auxiliary decision-making, and promoting the construction of smart grids significance.
Closed-form pricing formula for foreign equity option with credit risk
Authors: Kim Donghyun , Yoon Ji-Hun , Kim Geonwoo
Published: July 2021

Since credit risk in the over-the-counter (OTC) market has undoubtedly become very important issue, credit risk has to be considered when the options in the OTC market are priced. In this paper, we consider the valuation of foreign equity options with credit risk. In order to derive a closed-form pricing formula of this option, we adopt the partial differential equation (PDE) approach and use the Mellin transform method to solve the PDE. Specifically, triple Mellin transforms are used, and the pricing formula is presented as 3-dimensional normal cumulative distribution functions. Finally, we verify that our closed-form formula is accurate by comparing it with the numerical result from the Monte-Carlo simulation.
Successful treatment of acquired reactive perforating collagenosis with itraconazole
Authors: Ye Binrong , Cao Yi , Liu Yeqiang
Published: July 2021

Background

Acquired reactive perforating collagenosis (ARPC) is a rare form of transepithelial elimination in which altered collagen is extruded through the epidermis.

Case presentation

A 23-year-old male presented with cup-like ulcerated lesions on his limbs since 3 months. A series of serological and immunological tests showed no abnormalities. A diagnosis of ARPC was based on skin biopsy findings. The patient was cured using treatment with itraconazole for 8 weeks, in the absence of a fungal infection.

Conclusions

The anti-inflammatory and anti-angiogenic effects of itraconazole can have good therapeutic benefits for ARPC.