bluuebunny/crossref_metadata_2025 huggingface dataset:
Viability, yield and expansion capability of feline MSCs obtained from subcutaneous and reproductive organ adipose depots
Authors: Wysong Amy , Ortiz Priscilla , Bittel Douglas , Ott Lindsey , Karanu Francis , Filla Michael , Stehno-Bittel Lisa
Published: July 2021

Background

The source of multipotent stromal cells (MSC) can have a significant influence on the health and expansion capacity of the cells. As the applications for allogeneic MSCs in the treatment of feline diseases increase, the location of the initial donor tissue must be analyzed. To date, comparisons have only been made between feline MSCs collected from bone marrow or abdominal fat. This is the first report to compare cells obtained from different adipose depots in the cat with a focus on clinically relevant donor tissues. The tissue was collected from 34 healthy cats undergoing spaying (fat around the ovaries and uterine horn) or subcutaneous fat collected during surgical procedures.

Results

The amount of starting material is essential to isolate sufficient MSCs. The total tissue yield from the subcutaneous fat was significantly greater than could be obtained from around the reproductive organs, leading to 3 times more MSCs per donor. However, the concentration of MSCs obtained from reproductive fat was higher than from subcutaneous fat. In addition, the viability of the MSCs from the reproductive fat was significantly higher than the subcutaneous fat. Since most spaying occurs in young cats (under 18 months) reproductive fat was collected from adult cats during spaying, illustrating that age did not alter the yield or viability of the MSCs. When sufficient tissue was collected, it was digested either mechanically or enzymatically. Mechanical digestion further decreased the viability and yield of MSCs from subcutaneous fat compared to enzymatic digestion. Biomarkers of stem cell characterization, expansion capacity and function were detected using qPCR. CD70, CD90 and CD105 were all expressed in high levels in the 3 groups. However, the reproductive fat had higher levels of CD73 with the mechanically digested subcutaneous fat having the least. Gata6 was detected in all samples while Sox2 and Sox17 were also detected with higher quantities found in the enzymatically digested subcutaneous fat. Negative control genes of Gata4 and Pdx1 showed no detection prior to 50 cycles. During the first three passages, age of the donor, location of the donor tissue, or digestion protocol had no effect on cell culture doubling times or cell viability.

Conclusions

While MSCs from reproductive fat had superior cells/tissue weight and initial viability, there were still dramatically fewer cells obtained compared to subcutaneous fat due to the limited amount of tissue surrounding the reproductive organs. Further, in P1-P3 cultures there were no differences noted in doubling time or cell viability between tissue obtained from reproductive or subcutaneous fat depots.
Neutralization of IL-33 modifies the type 2 and type 3 inflammatory signature of viral induced asthma exacerbation
Authors: Warren Kristi J. , Poole Jill A. , Sweeter Jenea M. , DeVasure Jane M. , Dickinson John D. , Peebles R. Stokes , Wyatt Todd A.
Published: July 2021

Background

Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation.

Methods

Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry.

Results

While thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 h after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVA-treated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 h after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well.

Conclusions

Taken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 neutralization in RSV-induced asthma exacerbation.
Impact of organic carbon acquisition on growth and functional biomolecule production in diatoms
Authors: Marella Thomas Kiran , Bhattacharjya Raya , Tiwari Archana
Published: July 2021

Diatoms are unicellular photosynthetic protists which constitute one of the most successful microalgae contributing enormously to global primary productivity and nutrient cycles in marine and freshwater habitats. Though they possess the ability to biosynthesize high value compounds like eicosatetraenoic acid (EPA), fucoxanthin (Fx) and chrysolaminarin (Chrl) the major bottle neck in commercialization is their inability to attain high density growth. However, their unique potential of acquiring diverse carbon sources via varied mechanisms enables them to adapt and grow under phototrophic, mixotrophic as well as heterotrophic modes. Growth on organic carbon substrates promotes higher biomass, lipid, and carbohydrate productivity, which further triggers the yield of various biomolecules. Since, the current mass culture practices primarily employ open pond and tubular photobioreactors for phototrophic growth, they become cost intensive and economically non-viable. Therefore, in this review we attempt to explore and compare the mechanisms involved in organic carbon acquisition in diatoms and its implications on mixotrophic and heterotrophic growth and biomolecule production and validate how these strategies could pave a way for future exploration and establishment of sustainable diatom biorefineries for novel biomolecules.
Perceived physical health outcomes of direct-acting antiviral treatment for hepatitis C: a qualitative study
Authors: Goutzamanis Stelliana , Horyniak Danielle , Doyle Joseph S. , Hellard Margaret , Higgs Peter ,   on behalf of the Treatment and Prevention Study group
Published: July 2021

Background

Novel health promotion and treatment uptake initiatives will be necessary to ensure Australia meets 2030 hepatitis C elimination targets. Increasing treatment uptake will be assisted by a better understanding of the treatment experience and patient-perceived benefits. This study describes the perceived physical health benefits from direct-acting antiviral (DAA) hepatitis C treatment among people who inject drugs in Melbourne, Australia.

Methods

Twenty participants were recruited from a community treatment trial and community health clinics. Semi-structured interviews were performed with each participant before, during and following treatment. Interviews focused on treatment experiences, attitudes and motivations. Interviews were recorded, transcribed and thematically analysed.

Results

Two themes relating to the physical experience of treatment developed; intersection between physical and mental health and “maybe it’s working”. Participants reported various physical benefits, most prominently, reduced fatigue. Reductions in fatigue resulted in instant and meaningful changes in everyday life. Some participants did experience side effects, which they described as mild. Experiencing noticeable physical benefits during treatment was perceived as validation that treatment was working.

Conclusion

Physical health benefits of DAA treatment may have carry-on effects on cognitive, emotional or social wellbeing and should be incorporated into how treatment is promoted to those who require it.
Overexpressed MPS-1 contributes to endometrioma development through the NF-κB signaling pathway
Authors: Liu Yang , Ma Junyan , Zhang Liqi , Lin Jun , Liu Xiaohua
Published: July 2021

Background

Endometriosis is a benign gynecological disease that shares some characteristics with malignant tumors and affects approximately 10% of women of reproductive age. Endometrioma refers to endometriosis that appears in the ovary. Metallopanstimulin-1 (MPS-1) is a component of the 40S subunit of ribosomes that has extra-ribosomal functions that contribute to the development of diseases. This study aimed to explore the expression pattern and role of MPS-1 in endometrioma development.

Methods

Quantitative real time polymerase chain reaction, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay were used to determine the expression of MPS-1 in patients with endometrioma. Following the successful knockdown of MPS-1 by siRNA, CCK-8 assays, flow cytometry, and transwell assays were performed to detect ectopic endometrial stromal cells (EcESCs) proliferation, the rate of apoptosis, and cell cycle, migration, and invasion, respectively. Western blotting was used to explore the effect of MPS-1 knockdown on protein levels in the NF-κB signaling pathway.

Results

The expression of MPS-1 was significantly higher in endometrioma and the serum of endometrioma patients than in the patients without endometriosis. In addition, the downregulation of MPS-1 expression inhibited EcESCs proliferation, migration, and invasion. This downregulation led to the arrest of the EcESCs cycle in the G0/G1 phase and apoptosis and depressed the NF-κB signaling pathway.

Conclusion

MPS-1 can regulate EcESCs proliferation, motility, invasion, apoptosis, and cell cycle via the NF-κB signaling pathway in endometrioma. This may contribute to the formation or development of endometriotic foci. This study suggests the potential role of MPS-1 in the pathogenesis of endometriosis and enabled further research into the use of MPS-1 in the clinical diagnosis of endometrioma.
Educational needs of medical practitioners about medical billing: a scoping review of the literature
Authors: Faux Margaret , Adams Jon , Wardle Jonathan
Published: July 2021

Introduction

The World Health Organization has suggested the solution to health system waste caused by incorrect billing and fraud is policing and prosecution. However, a growing body of evidence suggests leakage may not always be fraudulent or corrupt, with researchers suggesting medical practitioners may sometimes struggle to understand increasingly complex legal requirements around health financing and billing transactions, which may be improved through education. To explore this phenomenon further, we undertook a scoping review of the literature to identify the medical billing education needs of medical practitioners and whether those needs are being met.

Methods

Eligible records included English language materials published between 1 January 2000 and 4 May 2020. Searches were conducted on MEDLINE, PubMed, Google Scholar, CINAHL, LexisNexis and Heinonline.

Results

We identified 74 records as directly relevant to the search criteria. Despite undertaking a comprehensive, English language search, with no country restrictions, studies meeting the inclusion criteria were limited to three countries (Australia, Canada, US), indicating a need for further work internationally. The literature suggests the education needs of medical practitioners in relation to medical billing compliance are not being met and medical practitioners desire more education on this topic. Evidence suggests education may be effective in improving medical billing compliance and reducing waste in health systems. There is broad agreement amongst medical education stakeholders in multiple jurisdictions that medical billing should be viewed as a core competency of medical education, though there is an apparent inertia to include this competency in medical education curricula. Penalties for non-compliant medical billing are serious and medical practitioners are at risk of random audits and investigations for breaches of sometimes incomprehensible, and highly interpretive regulations they may never have been taught.

Conclusion

Despite acknowledged significance of waste in health systems due to poor practitioner knowledge of billing practices, there has been very little research to date on education interventions to improve health system efficiency at a practitioner level.
The effect of IL-2 stimulation and treatment of TRPM3 on channel co-localisation with PIP2 and NK cell function in myalgic encephalomyelitis/chronic fatigue syndrome patients
Authors: Eaton-Fitch Natalie , Cabanas Hélène , du Preez Stanley , Staines Donald , Marshall-Gradisnik Sonya
Published: July 2021

Background

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a serious multifactorial disorder. The origin remains ambiguous, however reduced natural killer (NK) cell cytotoxicity is a consistent immunological feature of ME/CFS. Impaired transient receptor potential melastatin 3 (TRPM3), a phosphatidylinositol dependent channel, and impaired calcium mobilisation have been implicated in ME/CFS pathology. This investigation aimed to examine the localisation of TRPM3 at the NK cell plasma membrane and co-localisation with phosphatidylinositol 4,5-bisphosphate (PIP2). The effect of IL-2 priming and treatment using pregnenolone sulfate (PregS) and ononetin on TRPM3 co-localisation and NK cell cytotoxicity in ME/CFS patients and healthy controls (HC) was also investigated.

Methods

NK cells were isolated from 15 ME/CFS patients and 15 age- and sex-matched HC. Immunofluorescent technique was used to determine co-localisation of TRPM3 with the NK cell membrane and with PIP2of ME/CFS patients and HC. Flow cytometry was used to determine NK cell cytotoxicity. Following IL-2 stimulation and treatment with PregS and ononetin changes in co-localisation and NK cell cytotoxicity were measured.

Results

Overnight treatment of NK cells with PregS and ononetin resulted in reduced co-localisation of TRPM3 with PIP2and actin in HC. Co-localisation of TRPM3 with PIP2in NK cells was significantly reduced in ME/CFS patients compared with HC following priming with IL-2. A significant increase in co-localisation of TRPM3 with PIP2was reported following overnight treatment with ononetin within ME/CFS patients and between groups. Baseline NK cell cytotoxicity was significantly reduced in ME/CFS patients; however, no changes were observed following overnight incubation with IL-2, PregS and ononetin between HC and ME/CFS patients. IL-2 stimulation significantly enhanced NK cell cytotoxicity in HC and ME/CFS patients.

Conclusion

Significant changes in co-localisation suggest PIP2-dependent TRPM3 function may be impaired in ME/CFS patients. Stimulation of NK cells with IL-2 significantly enhanced cytotoxic function in ME/CFS patients demonstrating normal function compared with HC. A crosstalk exists between IL-2 and TRPM3 intracellular signalling pathways which are dependent on Ca2+influx and PIP2. While IL-2R responds to IL-2 binding in vitro, Ca2+dysregulation and impaired intracellular signalling pathways impede NK cell function in ME/CFS patients.
Knowledge and determinants of women’s knowledge on vertical transmission of HIV and AIDS in South Africa
Authors: Darteh Eugene Kofuor Maafo , Abraham Susanna Aba , Seidu Abdul-Aziz , Chattu Vijay Kumar , Yaya Sanni
Published: July 2021

Background

HIV/AIDS is still one of the major public health concerns globally. It is one of the major contributory causes of deaths among women in the reproductive age (15–49 years) and has resulted in about 14 million orphaned children globally. Knowledge of Mother-to Child transmission is one of the strategies to fight against HIV. This study, therefore, sought to assess the knowledge and determinants of women’s knowledge on vertical transmission of HIV and AIDS in their reproductive age in South Africa.

Methods

Data were obtained from the South Africa Demographic and Health Survey (SADHS) 2016. Both descriptive (frequencies and percentages) and inferential analysis (multilevel mixed-effects complementary log–log regression model) were conducted and the statistical significance was set at p < 0.05.

Results

The prevalence of knowledge of mother to child transmission of HIV and AIDS during pregnancy, delivery, breastfeeding and at least knowledge of one source are 87.0%, 81.1%, 80.3% and 91.4% respectively. At the individual level, those with secondary [AOR = 1.28, CI = 1.04,1.57] and higher [AOR = 1.55, CI = 1.21,1.99], those who read newspaper less than once a week [AOR = 1.16, CI = [1.05,1.28], at least once a week [AOR = 1.14, CI = 1.04,1.25], and those who listen to the radio less than once a week [AOR = 1.22, CI = 1.03,1.43] had higher odds of knowledge on MTCT of HIV and AIDS. However, those with parity 0 [AOR = 0.73, CI = [0.63,0.85] had lower odds of knowledge of MTCT of HIV and AIDS compared with those with parity 4 or more. At the contextual level, those in the poorest wealth quintile [AOR = 0.82,CI = 0.69,0.97] had lower odds of having knowledge of MTCT of HIV and AIDS. Those in the urban areas [AOR = 1.17, CI = [1.04,1.31], those in Limpopo [AOR = 1.35, CI = [1.12,1.64], Gauteng [AOR = 1.35, CI = [1.12,1.62] and North west[AOR = 1.49, CI = [1.22,1.81] had higher odds of knowledge of mother to child transmission of HIV and AIDS.

Conclusion

The study has demonstrated that there is relatively high knowledge of mother to child transmission of HIV and AIDS in South Africa. The factors associated with the knowledge are educational level, exposure to mass media, parity, wealth status, place of residence and the region of residence. To further increase the knowledge, it is imperative to adopt various messages and target respondents in different part of SSA through the mass media channels. This should be done taking cognizant of the rural–urban variations and socio-economic status.
Further considerations about “Detection and identification of enteroviruses circulating in children with acute gastroenteritis in Pará State, Northern Brazil (2010–2011)”
Authors: Machado Raiana Scerni , de Sousa Ivanildo Pedro , Monteiro Jacqueline Cortinhas , Ferreira James Lima , dos Santos Alves Jainara Cristina , Tavares Fernando Neto
Published: July 2021

On the detection and identification of enteroviruses circulating in children with acute gastroenteritis in Brazil: reply to Luchs, A. Comments on Detection and identification of enteroviruses circulating in children with acute gastroenteritis in Pará State, Northern Brazil (2010–2011).
Longitudinal changes in compliance, oxygenation and ventilatory ratio in COVID-19 versus non-COVID-19 pulmonary acute respiratory distress syndrome
Authors: Beloncle François , Studer Antoine , Seegers Valérie , Richard Jean-Christophe , Desprez Christophe , Fage Nicolas , Merdji Hamid , Pavlovsky Bertrand , Helms Julie , Cunat Sibylle , Mortaza Satar , Demiselle Julien , Brochard Laurent , Mercat Alain , Meziani Ferhat
Published: July 2021

Background

Differences in physiology of ARDS have been described between COVID-19 and non-COVID-19 patients. This study aimed to compare initial values and longitudinal changes in respiratory system compliance (CRS), oxygenation parameters and ventilatory ratio (VR) in patients with COVID-19 and non-COVID-19 pulmonary ARDS matched on oxygenation.

Methods

135 patients with COVID-19 ARDS from two centers were included in a physiological study; 767 non-COVID-19 ARDS from a clinical trial were used for the purpose of at least 1:2 matching. A propensity-matching was based on age, severity score, oxygenation, positive end-expiratory pressure (PEEP) and pulmonary cause of ARDS and allowed to include 112 COVID-19 and 198 non-COVID pulmonary ARDS.

Results

The two groups were similar on initial oxygenation. COVID-19 patients had a higher body mass index, higherCRSat day 1 (median [IQR], 35 [28–44] vs 32 [26–38] ml cmH2O−1,p = 0.037). At day 1,CRSwas correlated with oxygenation only in non-COVID-19 patients; 61.6% and 68.2% of COVID-19 and non-COVID-19 pulmonary ARDS were still ventilated at day 7 (p = 0.241). Oxygenation became lower in COVID-19 than in non-COVID-19 patients at days 3 and 7, whileCRSbecame similar. VR was lower at day 1 in COVID-19 than in non-COVID-19 patients but increased from day 1 to 7 only in COVID-19 patients. VR was higher at days 1, 3 and 7 in the COVID-19 patients ventilated using heat and moisture exchangers compared to heated humidifiers. After adjustment on PaO2/FiO2, PEEP and humidification device,CRSand VR were found not different between COVID-19 and non-COVID-19 patients at day 7. Day-28 mortality did not differ between COVID-19 and non-COVID-19 patients (25.9% and 23.7%, respectively,p = 0.666).

Conclusions

For a similar initial oxygenation, COVID-19 ARDS initially differs from classical ARDS by a higherCRS, dissociated from oxygenation.CRSbecome similar for patients remaining on mechanical ventilation during the first week of evolution, but oxygenation becomes lower in COVID-19 patients.

Trial registration: clinicaltrials.gov NCT04385004
Higher versus lower positive end-expiratory pressure in patients without acute respiratory distress syndrome: a meta-analysis of randomized controlled trials
Authors: Pettenuzzo Tommaso , Boscolo Annalisa , De Cassai Alessandro , Sella Nicolò , Zarantonello Francesco , Persona Paolo , Pasin Laura , Landoni Giovanni , Navalesi Paolo
Published: July 2021

Background

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the association of higher positive end-expiratory pressure (PEEP), as opposed to lower PEEP, with hospital mortality in adult intensive care unit (ICU) patients undergoing invasive mechanical ventilation for reasons other than acute respiratory distress syndrome (ARDS).

Methods

We performed an electronic search of MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, CINAHL, and Web of Science from inception until June 16, 2021 with no language restrictions. In addition, a research-in-progress database and grey literature were searched.

Results

We identified 22 RCTs (2225 patients) comparing higher PEEP (1007 patients) with lower PEEP (991 patients). No statistically significant association between higher PEEP and hospital mortality was observed (risk ratio 1.02, 95% confidence interval 0.89–1.16; I2 = 0%, p = 0.62; low certainty of evidence). Among secondary outcomes, higher PEEP was associated with better oxygenation, higher respiratory system compliance, and lower risk of hypoxemia and ARDS occurrence. Furthermore, barotrauma, hypotension, duration of ventilation, lengths of stay, and ICU mortality were similar between the two groups.

Conclusions

In our meta-analysis of RCTs, higher PEEP, compared with lower PEEP, was not associated with mortality in patients without ARDS receiving invasive mechanical ventilation. Further large high-quality RCTs are required to confirm these findings.
Transcriptome and genome evolution during HER2-amplified breast neoplasia
Authors: Lu Peipei , Foley Joseph , Zhu Chunfang , McNamara Katherine , Sirinukunwattana Korsuk , Vennam Sujay , Varma Sushama , Fehri Hamid , Srivastava Arunima , Zhu Shirley , Rittscher Jens , Mallick Parag , Curtis Christina , West Robert
Published: July 2021

Background

The acquisition of oncogenic drivers is a critical feature of cancer progression. For some carcinomas, it is clear that certain genetic drivers occur early in neoplasia and others late. Why these drivers are selected and how these changes alter the neoplasia’s fitness is less understood.

Methods

Here we use spatially oriented genomic approaches to identify transcriptomic and genetic changes at the single-duct level within precursor neoplasia associated with invasive breast cancer. We study HER2 amplification in ductal carcinoma in situ (DCIS) as an event that can be both quantified and spatially located via fluorescence in situ hybridization (FISH) and immunohistochemistry on fixed paraffin-embedded tissue.

Results

By combining the HER2-FISH with the laser capture microdissection (LCM) Smart-3SEQ method, we found that HER2 amplification in DCIS alters the transcriptomic profiles and increases diversity of copy number variations (CNVs). Particularly, interferon signaling pathway is activated by HER2 amplification in DCIS, which may provide a prolonged interferon signaling activation in HER2-positive breast cancer. Multiple subclones of HER2-amplified DCIS with distinct CNV profiles are observed, suggesting that multiple events occurred for the acquisition of HER2 amplification. Notably, DCIS acquires key transcriptomic changes and CNV events prior to HER2 amplification, suggesting that pre-amplified DCIS may create a cellular state primed to gain HER2 amplification for growth advantage.

Conclusion

By using genomic methods that are spatially oriented, this study identifies several features that appear to generate insights into neoplastic progression in precancer lesions at a single-duct level.
An individual randomised efficacy trial of autologous blood products, leukocyte and platelet-rich fibrin (L-PRF), to promote ulcer healing in leprosy in Nepal: the TABLE trial protocol
Authors: Napit Indra B. , Shrestha Dilip , Bishop Jon , Choudhury Sopna , Dulal Santosh , Gill Paramjit , Gkini Eleni , Gwyther Holly , Hagge Deanna A. , Neupane Karuna , Sartori Jo , Slinn Gemma , Watson Samuel I. , Lilford Richard
Published: July 2021

Background

Leprosy is curable with multidrug therapy and treatment in the early stages can prevent disability. However, local nerve damage can lead to injury and consequently recurring and disfiguring ulcers. The aim of this study is to evaluate the treatment of leprosy ulcers using an autologous blood product; leukocyte and platelet-rich fibrin (L-PRF) to promote healing.

Methods

This is a single-centre study in the Anandaban Hospital, The Leprosy Mission Nepal, Kathmandu, Nepal. Consenting patients (n=130) will be individually randomised in a single-blinded, controlled trial. Participants will be 18 years of age or older, admitted to the hospital with a clean, dry and infection-free chronic foot ulcer between 2 and 20 cm2 in size. If the ulcer is infected, it will be treated before enrolment into the study. The intervention involves the application of leukocyte and platelet-rich fibrin (L-PRF) matrix on the ulcer beds during twice-weekly dressing changes. Controls receive usual care in the form of saline dressings only during their twice-weekly dressing changes. Primary outcomes are the rate of healing assessed using standardised photographs by observers blind to allocated treatment, and time to complete re-epithelialization. Follow-up is at 6 months from randomisation.

Discussion

This research will provide valuable information on the clinical and cost-effectiveness of L-PRF in the treatment of leprosy ulcers. An additional benefit is the evaluation of the effects of treatment on quality of life for people living with leprosy ulcers. The results will improve our understanding of the scalability of this treatment across low-income countries for ulcer healing in leprosy and potentially other conditions such as diabetic ulcers.

Trial registration

ISRCTN14933421. Registered on 16 June 2020
Charged aerosol detector response modeling for fatty acids based on experimental settings and molecular features: a machine learning approach
Authors: Pawellek Ruben , Krmar Jovana , Leistner Adrian , Djajić Nevena , Otašević Biljana , Protić Ana , Holzgrabe Ulrike
Published: July 2021

The charged aerosol detector (CAD) is the latest representative of aerosol-based detectors that generate a response independent of the analytes’ chemical structure. This study was aimed at accurately predicting the CAD response of homologous fatty acids under varying experimental conditions. Fatty acids from C12 to C18 were used as model substances due to semivolatile characterics that caused non-uniform CAD behaviour. Considering both experimental conditions and molecular descriptors, a mixed quantitative structure–property relationship (QSPR) modeling was performed using Gradient Boosted Trees (GBT). The ensemble of 10 decisions trees (learning rate set at 0.55, the maximal depth set at 5, and the sample rate set at 1.0) was able to explain approximately 99% (Q2: 0.987, RMSE: 0.051) of the observed variance in CAD responses. Validation using an external test compound confirmed the high predictive ability of the model established (R2: 0.990, RMSEP: 0.050). With respect to the intrinsic attribute selection strategy, GBT used almost all independent variables during model building. Finally, it attributed the highest importance to the power function value, the flow rate of the mobile phase, evaporation temperature, the content of the organic solvent in the mobile phase and the molecular descriptors such as molecular weight (MW), Radial Distribution Function—080/weighted by mass (RDF080m) and average coefficient of the last eigenvector from distance/detour matrix (Ve2_D/Dt). The identification of the factors most relevant to the CAD responsiveness has contributed to a better understanding of the underlying mechanisms of signal generation. An increased CAD response that was obtained for acetone as organic modifier demonstrated its potential to replace the more expensive and environmentally harmful acetonitrile.
A case–control study on the association of intestinal flora with ulcerative colitis
Authors: Tang Yin-hua , Liu Hong-cheng , Song Guang , Wu Tian-tian , Zhao Ying , Shi Li-jun
Published: July 2021

The association between intestinal flora and ulcerative colitis (UC) was studied in order to provide a basis and method for clinical treatment. Fresh fecal samples were collected from 30 active UC patients and 10 healthy controls. The intestinal flora DNA from each sample was extracted and 16S rRNA gene sequencing was carried out using HiSeq platform to identify the intestinal flora in fecal samples. The richness and diversity of intestinal flora in UC patients were significantly lower than those in healthy control group (P < 0.05). Significant differences were observed between the intestinal flora-species of UC patients and healthy controls. Synergistetes (P < 0.01) and Firmicutes (P < 0.05), along with probiotics Veillonella (P < 0.01), Ruminococcus and Coprococcus (P < 0.05) in the UC patients were lower than that in the healthy controls significantly. Furthermore, compared with the control group, Tenericutes (P < 0.01) and intestinal pathogenic bacteria, including Bacteroides (P < 0.01), Escherichia and Sutterella (P < 0.05) were significantly increased. The incidence of UC is significantly associated with the changes in intestinal flora. Changes in intestinal flora may lead to a decrease in the diversity of intestinal flora or to the enrichment of a particular intestinal flora.
Maternal supplementation with phytogenic additives influenced the faecal microbiota and reproductive potential in sows
Authors: Nowland Tanya L. , Stanley Dragana , Kirkwood Roy N. , Torok Valeria A. , Bajagai Yadav S. , Gannon Neil J. , Plush Kate J.
Published: July 2021

Sows undergo physiological stress during gestation and lactation, potentially leading to enteric dysbiosis and reduced reproductive potential. Phytogenic additives (PFs) may improve performance via their antioxidant, anti-inflammatory and antimicrobial properties. This study determined whether the provision of a gestation/lactation diet containing PAs would alter the gastrointestinal microbiota of sows and their piglets, and improve performance. Sows received a commercial diet throughout gestation and lactation (CTR; n = 64), a commercial diet throughout gestation and a diet containing PAs in lactation (CTR-PA; n = 63) or a commercial diet containing PAs in gestation and lactation (PA; n = 90). Sows were weighed and backfat recorded after mating and at entry and exit from the farrowing house and piglets were weighed on days 1 and 21 of life. Faecal samples collected from sows at farrowing house entry and piglets at 21 and 35 d were subjected to 16 S rRNA gene amplicon analysis. The addition of PAs to sow diets resulted in more piglets born (P = 0.03), however, it did not improve the number of liveborn piglets (P = 0.14). There were no differences in sow weight, P2 backfat depth or lactation feed intake observed. PAs had no effect on piglet weight or survival to weaning but did alter the faecal microbiota of sows, and this change was observed in piglets at 21 and 35 d. PA supplementation to sows has the potential to increase litter size, while also potentially influencing gastrointestinal tract health of the sow and piglets reared.
Pathological alterations in the gastrointestinal tract of a porcine model of DMD
Authors: Zou Xiaodong , Ouyang Hongsheng , Pang Daxin , Han Renzhi , Tang Xiaochun
Published: July 2021

Background

Patients with Duchenne muscular dystrophy (DMD) develop severe skeletal and cardiac muscle pathologies, which result in premature death. Therefore, the current therapeutic efforts are mainly targeted to correct dystrophin expression in skeletal muscle and heart. However, it was reported that DMD patients may also exhibit gastrointestinal and nutritional problems. How the pathological alterations in gastrointestinal tissues contribute to the disease are not fully explored.

Results

Here we employed the CRISPR/Cas9 system combined with somatic nuclear transfer technology (SCNT) to establish a porcine model of DMD and explored their pathological alterations. We found that genetic disruption of dystrophin expression led to morphological gastrointestinal tract alterations, weakened the gastrointestinal tract digestion and absorption capacity, and eventually led to malnutrition and gastric dysfunction in the DMD pigs.

Conclusions

This work provides important insights into the pathogenesis of DMD and highlights the need to consider the gastrointestinal dysfunction as an additional therapeutic target for DMD patients.
National and regional trends in MRI utilization in the face of the ongoing COVID-19 pandemic
Authors: Luxenburg Osnat , Saban Mor , Myers Vicki , Vaknin Sharona , Boldor Noga , Wilf-Miron Rachel
Published: July 2021

Background and purpose

Marked reductions in imaging exams have been documented during the COVID-19 pandemic. The study aimed to examine the effect of the two waves of COVID-19 on magnetic resonance imaging (MRI) utilization at the national and regional level.

Materials and methods

A retrospective-archive study was conducted in Israel, comparing March–December 2020 with March–December 2018 and 2019. Data on MRI utilization were obtained from the national MRI registry, while data on confirmed COVID-19 cases, by place of residence, were obtained from the Israeli Ministry of Health open COVID-19 database.

Results

The number and rate of MRI examinations decreased during the first COVID-19 wave, with the steepest drop in April 2020: 47.5% relative decrease compared to April 2019, and 42.2% compared to 2018. This was followed by a compensatory increase between the waves and a return to almost pre-pandemic levels of use, with just a modest decrease, during the second, more intense COVID wave, compared with the previous year. Existing differences between regions increased during the pandemic. The rate ratio of MRI exams between Tel-Aviv and the Northern periphery increased from 2.89 in April 2019 to 3.94 in April 2020. Jerusalem metropolitan region, with the largest burden of COVID disease, demonstrated only a modest decrease (1%) in MRI utilization during the first 10 months of the pandemic.

Conclusions

At the national level, time trends in reduced MRI utilization followed the first wave of COVID-19, and were accompanied by increased regional disparities. These changes were not explained by differences in the burden of COVID-19 disease but might be explained by unequal distribution of MRI scanners among regions. Reduced utilization was not evident during the second wave, nor at the beginning of the third wave, despite higher COVID-19 case load, demonstrating adaptation to the new normal. Patterns of MRI utilization might help policy-makers and healthcare managers predict the behavior of imaging as well as other sectors, such as elective surgical procedures, during an ongoing pandemic. This forecast might help to manage the lasting effects of the pandemic, including extended waiting times, in the months and years following its remission. In preparation for future national emergencies, timely and detailed data on MRI utilization can serve as a “sensor” for a wide array of diagnostic and interventional medical activities, providing policy-makers with an updated snapshot to guide their response at the regional and national levels.
Leveraging discrete modulation and liquid metal antennas for interference reduction
Authors: Baig Mirza Uzair , Elassy Kareem S. , Høst-Madsen Anders , Ohta Aaron T. , Shiroma Wayne A. , Nosratinia Aria
Published: July 2021

Recent progress in the understanding of the behavior of the interference channel has led to valuable insights: first, discrete signaling has been discovered to have tangible benefits in the presence of interference,
especially when one does not wish to decode the interfering signal, i.e., the interference is treated as noise, and second, the capacity of the interference channel as a function of the interference link gains is now understood to be highly irregular, i.e., non-monotonic and discontinuous. This work addresses these two issues in an integrated and interdisciplinary manner: it utilizes discrete signaling to approach the capacity of the interference channel by developing lower bounds on the mutual information under discrete modulation and treating interference as noise, subject to an outage set, and addresses the issue of sensitivity to link gains with a liquid metal reconfigurable antenna to avoid the aforementioned outage sets. Simulations illustrate the effectiveness of our approach.
New coincidence point results for generalized graph-preserving multivalued mappings with applications
Authors: Hammad Hasanen A. , De la Sen Manuel , Agarwal Praveen
Published: July 2021

This research aims to investigate a novel coincidence point (cp) of generalized multivalued contraction (gmc) mapping involved a directed graph in b-metric spaces (b-ms). An example and some corollaries are derived to strengthen our main theoretical results. We end the manuscript with two important applications, one of them is interested in finding a solution to the system of nonlinear integral equations (nie) and the other one relies on the existence of a solution to fractional integral equations (fie).
COVID-19 vaccination associated severe immune thrombocytopenia
Authors: Shah Syed Raza Ali , Dolkar Sherpa , Mathew Jacob , Vishnu Prakash
Published: July 2021

Background

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has emerged as a deadliest global pandemic after its identification in December 2019 in Wuhan, China resulting in more than three million deaths worldwide. Recently FDA issued emergency authorization for three vaccines for prevention of COVID-19. Here in, we report three cases of severe immune thrombocytopenia (ITP) following COVID-19 vaccination and their clinical course.

Case presentations

Case #1: 53 year old male with past medical history of Crohn’s disease was admitted for myalgias and diffuse petechial rash 8 days after receiving second dose of Pfizer-BioNTech COVID-19 vaccine. A complete blood test showed a platelet count of 2 × 109/L. Patient did not have a prior history of thrombocytopenia and other causes of thrombocytopenia were ruled out by history and pertinent lab data. He received two doses of intravenous immunoglobulin and oral dexamethasone for 4 days resulting in normalization of platelet counts.

Case #2: 67 year male with past medical history of chronic ITP in remission was admitted for melena 2 days after receiving his first dose of Pfizer-BioNTech COVID-19 vaccine. A complete blood test showed a platelet count of 2 × 109/L. Physical exam showed generalized petechiae. There was no history of recent flares of ITP and patient had normal platelet counts following his splenectomy 4 years ago. He received two doses of IVIG and oral dexamethasone for 4 days with gradual improvement in platelet counts.

Case #3: 59 year old female with past medical history of chronic ITP secondary to SLE was admitted for bloody diarrhea 2 days after receiving her first dose of Johnson and Johnson COVID-19 vaccine. Physical exam was unremarkable. A complete blood test showed platelet count of 64 × 109/L which dropped to 27 × 109/L during hospital course. She received oral dexamethasone for 4 days with improvement in platelet counts.

Conclusion

COVID-19 vaccination induced ITP has been recently acknowledged. However, given very few cases and limited data, currently there are no guidelines for management of ITP caused by COVID-19 vaccine as well as vaccination of people with predisposing conditions.
Simultaneous degradation of two mycotoxins enabled by a fusion enzyme in food-grade recombinant Kluyveromyces lactis
Authors: Xia Yu , Wu Zifeng , He Rui , Gao Yahui , Qiu Yangyu , Cheng Qianqian , Ma Xiaoyuan , Wang Zhouping
Published: July 2021

Aflatoxin B1 (AFB1) and zearalenone (ZEN) are two predominant mycotoxins ubiquitously found in corn, peanuts, and other grains, which pose a great threat to human health. Therefore, safe and effective methods for detoxification of these mycotoxins are urgently needed. To achieve simultaneous degradation of multiple mycotoxins, a fusion enzyme ZPF1 was constructed by linking zearalenone hydrolase and manganese peroxidase with a linker peptide GGGGS. This fusion enzyme was secretory expressed successfully in the newly constructed food-grade recombinant strain Kluyveromyces lactis GG799(pKLAC1-ZPF1), and was investigated with the mycotoxins degradation efficiency in two reaction systems. Results showed that both AFB1 and ZEN can be degraded by ZPF1 in reaction system 1 (70.0 mmol/L malonic buffer with 1.0 mmol/L MnSO4, 0.1 mmol/L H2O2, 5.0 µg/mL AFB1 and ZEN, respectively) with the ratios of 46.46% and 38.76%, respectively. In reaction system 2 (50.0 mmol/L Tris–HCl, with 5.0 µg/mL AFB1 and ZEN, respectively), AFB1 cannot be degraded while ZEN can be degraded with the ratio of 35.38%. To improve the degradation efficiency of these mycotoxins, optimization of the induction and degradation conditions were fulfilled subsequently. The degradation ratios of AFB1 and ZEN by ZPF1 in reaction system 1 reached 64.11% ± 2.93% and 46.21% ± 3.17%, respectively. While in reaction system 2, ZEN was degraded by ZPF1 at a ratio of 41.45% ± 3.34%. The increases of degradation ratios for AFB1 and ZEN in reaction system 1 were 17.65% and 7.45%, respectively, while that for ZEN in reaction system 2 was 6.07%, compared with the unoptimized results.
Rare occurrence of severe blindness and deafness in Friedreich ataxia: a case report
Authors: Damásio Joana , Sardoeira Ana , Araújo Maria , Carvalho Isabel , Sequeiros Jorge , Barros José
Published: July 2021

Background

Friedreich ataxia is the most frequent hereditary ataxia worldwide. Subclinical visual and auditory involvement has been recognized in these patients, with co-occurrence of severe blindness and deafness being rare.

Case report

We describe a patient, homozygous for a 873 GAA expansion in the FXN gene, whose first symptoms appeared by the age of 8. At 22 years-old he developed sensorineural deafness, and at 26 visual impairment. Deafness had a progressive course over 11 years, until a stage of extreme severity which hindered communication. Visual acuity had a catastrophic deterioration, with blindness 3 years after visual impairment was first noticed. Audiograms documented progressive sensorineural deafness, most striking for low frequencies. Visual evoked potentials disclosed bilaterally increased P100 latency. He passed away at the age of 41 years old, at a stage of extreme disability, blind and deaf, in addition to the complete phenotype of a patient with Friedreich ataxia of more than 30 years duration.

Discussion

Severe vision loss and extreme deafness has been described in very few patients with Friedreich ataxia. Long duration, severe disease and large expanded alleles may account for such an extreme phenotype; nonetheless, the role of factors as modifying genes warrants further investigation in this subset of patients.
A totally extraperitoneal approach for endoscopic resection of a congenital prepubic sinus through the pubic symphysis
Authors: Fukuhara Masahiro , Onishi Shun , Yonemura Yusuke , Sato Tomoe , Tsutsumi Satoshi , Bandoh Toshio , Utsunomiya Tohru , Esumi Genshiro
Published: July 2021

Background

A congenital prepubic sinus (CPS) is a rare congenital anomaly in which a duct remnant extends from the skin opening near the pubic symphysis to various parts and the lesions are mostly located in the preperitoneal space. The totally extraperitoneal (TEP) approach is an operational method that provides a good field of view for the preperitoneal space. We report the CPS through the pubic symphysis in which complete resection was achieved by a TEP approach. TEP approach was minimally invasive and achieved satisfactory cosmetic outcome.

Case presentation

We herein report the case of a 13-year-old boy with a fistula opening near the dorsal penis. He was admitted to our hospital due to fever and lower abdominal pain. Abdominal ultrasonography and computed tomography revealed an abscess inside a fistula lumen on the posterior surface of the rectus abdominis muscles in the midline of the lower abdomen. Under a diagnosis of CPS, which was located in the preperitoneal space, endoscopic resection was performed by a totally extraperitoneal approach. After making an umbilical incision, the rectus abdominis muscle was excised outward to expose the preperitoneal space. A single-port system was placed in the preperitoneal space. Three 5-mm-port trocars were inserted. As the preperitoneal cavity was expanded, a sinus connecting to the pubic symphysis was confirmed. The pubic symphysis did not connect with the bladder. Because the fistula was penetrated with the pubic symphysis, the remaining caudal fistula was removed from the body surface with a small spindle-shaped incision around the fistula opening. Finally, the sinus was completely resected, with confirmation from both the cranial side and dorsal side of the pubic symphysis. We were able to perform complete resection of the CPS with good visibility and without any peritoneal damage. There were no intraoperative complications. His postoperative course was uneventful during the 1-year follow-up.

Conclusions

The TEP approach may be feasible for the resection of a CPS and may allow safe and secure resection due to good visibility, even in pediatric patients.