bluuebunny/crossref_metadata_2025 huggingface dataset:
A profile of research on the parasitic trypanosomatids and the diseases they cause
Authors: Horn David
Published: January 2022

The parasitic trypanosomatids cause lethal and debilitating diseases, the leishmaniases, Chagas disease, and the African trypanosomiases, with major impacts on human and animal health. Sustained research has borne fruit by assisting efforts to reduce the burden of disease and by improving our understanding of fundamental molecular and cell biology. But where has the research primarily been conducted, and which research areas have received the most attention? These questions are addressed below using publication and citation data from the past few decades.
The orphan drug dichloroacetate reduces amyloid beta-peptide production whilst promoting non-amyloidogenic proteolysis of the amyloid precursor protein
Authors: Parkin Edward T. , Hammond Jessica E. , Owens Lauren , Hodges Matthew D.
Published: January 2022

The amyloid cascade hypothesis proposes that excessive accumulation of amyloid beta-peptides is the initiating event in Alzheimer’s disease. These neurotoxic peptides are generated from the amyloid precursor protein via sequential cleavage by β- and γ-secretases in the ’amyloidogenic’ proteolytic pathway. Alternatively, the amyloid precursor protein can be processed via the ’non-amyloidogenic’ pathway which, through the action of the α-secretase a disintegrin and metalloproteinase (ADAM) 10, both precludes amyloid beta-peptide formation and has the additional benefit of generating a neuroprotective soluble amyloid precursor protein fragment, sAPPα. In the current study, we investigated whether the orphan drug, dichloroacetate, could alter amyloid precursor protein proteolysis. In SH-SY5Y neuroblastoma cells, dichloroacetate enhanced sAPPα generation whilst inhibiting β–secretase processing of endogenous amyloid precursor protein and the subsequent generation of amyloid beta-peptides. Over-expression of the amyloid precursor protein partly ablated the effect of dichloroacetate on amyloidogenic and non-amyloidogenic processing whilst over-expression of the β-secretase only ablated the effect on amyloidogenic processing. Similar enhancement of ADAM-mediated amyloid precursor protein processing by dichloroacetate was observed in unrelated cell lines and the effect was not exclusive to the amyloid precursor protein as an ADAM substrate, as indicated by dichloroacetate-enhanced proteolysis of the Notch ligand, Jagged1. Despite altering proteolysis of the amyloid precursor protein, dichloroacetate did not significantly affect the expression/activity of α-, β- or γ-secretases. In conclusion, dichloroacetate can inhibit amyloidogenic and promote non-amyloidogenic proteolysis of the amyloid precursor protein. Given the small size and blood-brain-barrier permeability of the drug, further research into its mechanism of action with respect to APP proteolysis may lead to the development of therapies for slowing the progression of Alzheimer’s disease.
Organic dry pea (Pisum sativum L.) biofortification for better human health
Authors: Thavarajah Dil , Lawrence Tristan J. , Powers Sarah E. , Kay Joshua , Thavarajah Pushparajah , Shipe Emerson , McGee Rebecca , Kumar Shiv , Boyles Rick
Published: January 2022

A primary criticism of organic agriculture is its lower yield and nutritional quality compared to conventional systems. Nutritionally, dry pea (Pisum sativum L.) is a rich source of low digestible carbohydrates, protein, and micronutrients. This study aimed to evaluate dry pea cultivars and advanced breeding lines using on-farm field selections to inform the development of biofortified organic cultivars with increased yield and nutritional quality. A total of 44 dry pea entries were grown in two USDA-certified organic on-farm locations in South Carolina (SC), United States of America (USA) for two years. Seed yield and protein for dry pea ranged from 61 to 3833 kg ha-1 and 12.6 to 34.2 g/100 g, respectively, with low heritability estimates. Total prebiotic carbohydrate concentration ranged from 14.7 to 26.6 g/100 g. A 100-g serving of organic dry pea provides 73.5 to 133% of the recommended daily allowance (%RDA) of prebiotic carbohydrates. Heritability estimates for individual prebiotic carbohydrates ranged from 0.27 to 0.82. Organic dry peas are rich in minerals [iron (Fe): 1.9–26.2 mg/100 g; zinc (Zn): 1.1–7.5 mg/100 g] and have low to moderate concentrations of phytic acid (PA:18.8–516 mg/100 g). The significant cultivar, location, and year effects were evident for grain yield, thousand seed weight (1000-seed weight), and protein, but results for other nutritional traits varied with genotype, environment, and interactions. “AAC Carver,” “Jetset,” and “Mystique” were the best-adapted cultivars with high yield, and “CDC Striker,” “Fiddle,” and “Hampton” had the highest protein concentration. These cultivars are the best performing cultivars that should be incorporated into organic dry pea breeding programs to develop cultivars suitable for organic production. In conclusion, organic dry pea has potential as a winter cash crop in southern climates. Still, it will require selecting diverse genetic material and location sourcing to develop improved cultivars with a higher yield, disease resistance, and nutritional quality.
Effects of adipose-derived stromal cells and endothelial progenitor cells on adipose transplant survival and angiogenesis
Authors: Gan Fengshan , Liu Liu , Zhou Qingzhu , Huang Wenli , Huang Xinwei , Zhao Xian
Published: January 2022

Background

A paracrine mechanism is thought to mediate the proangiogenic capacity of adipose-derived stromal/stem cells (ASCs). However, the precise mechanism by which ASCs promote the formation of blood vessels by endothelial progenitor cells (EPCs) is unclear.

Methods

The EPCs-ASCs cocultures prepared in different ratios were subjected to tube formations assay to verify whether ASCs could directly participate in the tube genesis. The supernatant from cultured ASCs was used to stimulate EPCs to evaluate the effects on the angiogenic property of EPCs, as well as capacity for migration and invasion. A coculture model with transwell chamber were used to explore the regulation of angiogenesis markers expression in EPCs by ASCs. We then mixed ASCs with EPCs and transplanted them with adipose tissue into nude mice to evaluate the effects on angiogenesis in adipose tissue grafts.

Results

In the EPCs-ASCs cocultures, the tube formation was significantly decreased as the relative abundance of ASCs increased, while the ASCs was found to migrate and integrated into the agglomerates formed by EPCs. The supernatant from ASCs cultures promoted the migration and invasion of EPCs and the ability to form capillary-like structures. The expression of multiple angiogenesis markers in EPCs were significantly increased when cocultured with ASCs. In vivo, ASCs combined with EPC promoted vascularization in the fat transplant. Immunofluorescence straining of Edu and CD31 indicated that the Edu labeled EPC did not directly participate in the vascularization inside the fat tissue.

Conclusions

ADSC can participate in the tube formation of EPC although it cannot form canonical capillary structures. Meanwhile, Soluble factors secreted by ASCs promotes the angiogenic potential of EPCs. ASCs paracrine signaling appears to promote angiogenesis by increasing the migration and invasion of EPCs and simultaneously upregulating the expression of angiogenesis markers in EPCs. The results of in vivo experiments showed that ASCs combined with EPCs significantly promote the formation of blood vessels in the fat implant. Remarkably, EPCs may promote angiogenesis by paracrine regulation of endogenous endothelial cells (ECs) rather than direct participation in the formation of blood vessels.
Quantifying relations and similarities of the meteorological parameters among the weather stations in the Alberta Oil Sands region
Authors: Deshmukh Dhananjay , Ahmed M. Razu , Dominic John Albino , Zaghloul Mohamed S. , Gupta Anil , Achari Gopal , Hassan Quazi K.
Published: January 2022

Our objective was to quantify the similarity in the meteorological measurements of 17 stations under three weather networks in the Alberta oil sands region. The networks were for climate monitoring under the water quantity program (WQP) and air program, including Meteorological Towers (MT) and Edge Sites (ES). The meteorological parameters were air temperature (AT), relative humidity (RH), solar radiation (SR), barometric pressure (BP), precipitation (PR), and snow depth (SD). Among the various measures implemented for finding correlations in this study, we found that the use of Pearson’s coefficient (r) and absolute average error (AAE) would be sufficient. Also, we applied the percent similarity method upon considering at least 75% of the value in finding the similarity between station pairs. Our results showed that we could optimize the networks by selecting the least number of stations (for each network) to describe the measure-variability in meteorological parameters. We identified that five stations are sufficient for the measurement of AT, one for RH, five for SR, three for BP, seven for PR, and two for SD in the WQP network. For the MT network, six for AT, two for RH, six for SR, and four for PR, and the ES network requires six for AT, three for RH, six for SR, and two for BP. This study could potentially be critical to rationalize/optimize weather networks in the study area.
Characteristics and outcome of children with renal tumors in the Netherlands: The first five-year’s experience of national centralization
Authors: Roy Prakriti , van Peer Sophie E. , de Witte Martin M. , Tytgat Godelieve A. M. , Karim-Kos Henrike E. , van Grotel Martine , van de Ven Cees P. , Mavinkurve-Groothuis Annelies M. C. , Merks Johannes H. M. , Kuiper Roland P. , Hol Janna A. , Janssens Geert O. R. , de Krijger Ronald R. , Jongmans Marjolijn C. J. , Drost Jarno , van der Steeg Alida F. W. , Littooij Annemieke S. , Wijnen Marc H. W. A. , van Tinteren Harm , van den Heuvel-Eibrink Marry M.
Published: January 2022

Around 6% of all childhood malignancies represent renal tumors, of which a majority includes Wilms tumor (WT). Although survival rates have improved over the last decades, specific patients are still at risk for adverse outcome. In the Netherlands, since 2015, pediatric oncology care for renal tumors has been centralized in the Princess Máxima Center for Pediatric Oncology. Here, we describe experiences of the first 5 years of centralized care and explore whether this influences the epidemiological landscape by comparing data with the Netherlands Cancer Registry (NCR). We identified all patients <19 years with a renal mass diagnosed between 01-01-2015 and 31-12-2019 in the Princess Máxima Center. Epidemiology, characteristics and management were analyzed. We identified 164 patients (including 1 patient who refused consent for registration), in our center with a suspicion of a renal tumor. The remaining 163 cases included WT (n = 118)/cystic partially differentiated nephroblastoma (n = 2)/nephrogenic rests only (n = 6) and non-WT (n = 37). In this period, the NCR included 138 children, 1 17-year-old patient was not referred to the Princess Máxima Center. Central radiology review (before starting treatment) was performed in 121/163 patients, and central pathology review in 148/152 patients that underwent surgery. Treatment stratification, according to SIOP/EpSSG protocols was pursued based on multidisciplinary consensus. Preoperative chemotherapy was administered in 133 patients, whereas 19 patients underwent upfront surgery. Surgery was performed in 152 patients, and from 133 biomaterial was stored. Centralization of care for children with renal tumors led to referral of all but 1 new renal tumor cases in the Netherlands, and leads to referral of very rare subtypes not registered in the NCR, that benefit from high quality diagnostics and multidisciplinary decision making. National centralization of care led to enhanced development of molecular diagnostics and other innovation-based treatments for the future.
Parallel simulation and optimization framework of supplies production processes for unconventional emergencies
Authors: Zhu Dan , Wei Yaoyao , Huang Hainan , Xie Tian
Published: January 2022

The outbreak of unconventional emergencies leads to a surge in demand for emergency supplies. How to effectively arrange emergency production processes and improve production efficiency is significant. The emergency manufacturing systems are typically complex systems, which are difficult to be analyzed by using physical experiments. Based on the theory of Random Service System (RSS) and Parallel Emergency Management System (PeMS), a parallel simulation and optimization framework of production processes for surging demand of emergency supplies is constructed. Under this novel framework, an artificial system model paralleling with the real scenarios is established and optimized by the parallel implementation processes. Furthermore, a concrete example of mask shortage, which occurred at Huoshenshan Hospital in the COVID-19 pandemic, verifies the feasibility of this method.
A model for sustainable, partnership-based telehealth services in rural India: An early process evaluation from Tuver village, Gujarat
Authors: Ramanadhan Shoba , Ganapathy Krishnan , Nukala Lovakanth , Rajagopalan Subramaniya , Camillus John C.
Published: January 2022

Background

Telehealth can improve access to high-quality healthcare for rural populations in India. However, rural communities often have other needs, such as sanitation or employment, to benefit fully from telehealth offerings, highlighting a need for systems-level solutions. A Business of Humanity approach argues that innovative solutions to wicked problems like these require strategic decision-making that attends to a) humaneness, e.g., equity and safety and b) humankind, or the needs and potential of large and growing markets comprised of marginalized and low-income individuals. The approach is expected to improve economic performance and long-term value creation for partners, thus supporting sustainability.

Methods

A demonstration project was conducted in Tuver, a rural and tribal village in Gujarat, India. The project included seven components: a partnership that emphasized power-sharing and complementary contributions; telehealth services; health promotion; digital services; power infrastructure; water and sanitation; and agribusiness. Core partners included the academic partner, local village leadership, a local development foundation, a telehealth provider, and a design-build contractor. This early process evaluation relies on administrative data, field notes, and project documentation and was analyzed using a case study approach.

Results

Findings highlight the importance of taking a systems perspective and engaging inter-sectoral partners through alignment of values and goals. Additionally, the creation of a synergistic, health-promoting ecosystem offers potential to support telehealth services in the long-term. At the same time, engaging rural, tribal communities in the use of technological advances posed a challenge, though local staff and intermediaries were effective in bridging disconnects.

Conclusion

Overall, this early process evaluation highlights the promise and challenges of using a Business of Humanity approach for coordinated, sustainable community-level action to improve the health and well-being of marginalized communities.
Suicidal behaviors among Bangladeshi university students: Prevalence and risk factors
Authors: Rasheduzzaman M. , al-Mamun Firoj , Hosen Ismail , Akter Tahmina , Hossain Moazzem , Griffiths Mark D. , Mamun Mohammed A.
Published: January 2022

Background

Bangladeshi university students are considered to be highly suicide-prone compared to other populations and cohorts. However, no prior epidemiological studies have assessed the suicidality (i.e., past-year suicidal ideation [SI], lifetime suicide plan [SP], and lifetime suicide attempt [SA]) among Bangladeshi students, including the variables such as past-year stressful life events and family mental health history. This is arguably a major knowledge gap in the country. Therefore, the present study investigated the prevalence and associated risk factors for suicidal behaviors among Bangladeshi university students.

Methods

A cross-sectional study was conducted utilizing a convenience sampling method among a total of 1844 university students between October and November 2019. Data were collected based on the information related to socio-demographics, perceived health-related questions, past-year stressful life events, family mental health history, and suicidal behaviors (i.e., SI, SP, and SA). Chi-square tests and binary logistic regressions were used to analyze the data utilizing SPSS statistical software.

Results

The prevalence of past-year suicidal ideation, lifetime suicide plans, and suicide attempts were 13.4%, 6.0%, and 4.4%, respectively. Females reported significantly higher suicidal behavior than males (i.e., 20.6% vs.10.2% SI; 9% vs. 4.6% SP; and 6.4% vs.3.6% SA). Risk factors for SI were being female, year of academic study, residing in an urban area, using psychoactive substances, experiencing both past year physical and mental illness, experiencing any type of stressful past-year life events, experiencing campus ragging (i.e., senior students abusing, humiliating and/or harassing freshers or more junior students), experiencing family mental illness history, and having family suicide attempt history. SP was associated with several factors including being female, year of academic study, using psychoactive substance, experiencing both past-year physical and mental illness, and experiencing any type of stressful past-year life events. Risk factors for SA were being female, year of academic study, using psychoactive substances, experiencing past-year mental illness, experiencing any type of stressful past-year life events, and having family suicide attempt history.

Conclusions

University students appear to be a vulnerable group for experiencing suicidal behaviors. The present findings warrant rigorous action and early intervention programs such as counseling and other mental health professional services by university authorities. Longitudinal studies are highly recommended involving countrywide representative samples.
Case-control study of adverse childhood experiences and multiple sclerosis risk and clinical outcomes
Authors: Horton Mary K. , McCurdy Shannon , Shao Xiaorong , Bellesis Kalliope , Chinn Terrence , Schaefer Catherine , Barcellos Lisa F.
Published: January 2022

Background

Adverse childhood experiences (ACEs) are linked to numerous health conditions but understudied in multiple sclerosis (MS). This study’s objective was to test for the association between ACEs and MS risk and several clinical outcomes.

Methods

We used a sample of adult, non-Hispanic MS cases (n = 1422) and controls (n = 1185) from Northern California. Eighteen ACEs were assessed including parent divorce, parent death, and abuse. Outcomes included MS risk, age of MS onset, Multiple Sclerosis Severity Scale score, and use of a walking aid. Logistic and linear regression estimated odds ratios (ORs) (and beta coefficients) and 95% confidence intervals (CIs) for ACEs operationalized as any/none, counts, individual events, and latent factors/patterns.

Results

Overall, more MS cases experienced ≥1 ACE compared to controls (54.5% and 53.8%, respectively). After adjusting for sex, birthyear, and race, this small difference was attenuated (OR = 1.01, 95% CI: 0.87, 1.18). There were no trends of increasing or decreasing odds of MS across ACE count categories. Consistent associations between individual ACEs between ages 0–10 and 11–20 years and MS risk were not detected. Factor analysis identified five latent ACE factors, but their associations with MS risk were approximately null. Age of MS onset and other clinical outcomes were not associated with ACEs after multiple testing correction.

Conclusion

Despite rich data and multiple approaches to operationalizing ACEs, no consistent and statistically significant effects were observed between ACEs with MS. This highlights the challenges of studying sensitive, retrospective events among adults that occurred decades before data collection.
Emergency department utilization for substance use disorders and mental health conditions during COVID-19
Authors: Venkatesh Arjun K. , Janke Alexander T. , Kinsman Jeremy , Rothenberg Craig , Goyal Pawan , Malicki Caitlin , D’Onofrio Gail , Taylor Andrew , Hawk Kathryn
Published: January 2022

Background

As the emergency department (ED) has evolved into the de-facto site of care for a variety of substance use disorder (SUD) presentations, trends in ED utilization are an essential public health surveillance tool. Changes in ED visit patterns during the COVID-19 pandemic may reflect changes in access to outpatient treatment, changes in SUD incidence, or the unintended effects of public policy to mitigate COVID-19. We use a national emergency medicine registry to describe and characterize trends in ED visitation for SUDs since 2019.

Methods

We included all ED visits identified in a national emergency medicine clinical quality registry, which included 174 sites across 33 states with data from January 2019 through June 2021. We defined SUD using ED visit diagnosis codes including: opioid overdose and opioid use disorder (OUD), alcohol use disorders (AUD), and other SUD. To characterize changes in ED utilization, we plotted the 3-week moving average ratio of visit counts in 2020 and 2021 as compared to visit counts in 2019.

Findings

While overall ED visits declined in the early pandemic period and had not returned to 2019 baseline by June 2021, ED visit counts for SUD demonstrated smaller declines in March and April of 2020, so that the proportion of overall ED visits that were for SUD increased. Furthermore, in the second half of 2020, ED visits for SUD returned to baseline, and increased above baseline for OUD ever since May 2020.

Conclusions

We observe distinct patterns in ED visitation for SUDs over the course of the COVID-19 pandemic, particularly for OUD for which ED visitation barely declined and now exceeds previous baselines. These trends likely demonstrate the essential role of hospital-based EDs in providing 24/7/365 care for people with SUDs and mental health conditions. Allocation of resources must be directed towards the ED as a de-facto safety net for populations in crisis.
Baseline procalcitonin as a predictor of bacterial infection and clinical outcomes in COVID-19: A case-control study
Authors: Atallah Natalie J. , Warren Hailey M. , Roberts Matthew B. , Elshaboury Ramy H. , Bidell Monique R. , Gandhi Ronak G. , Adamsick Meagan , Ibrahim Maryam K. , Sood Rupali , Bou Zein Eddine Savo , Cobler-Lichter Matthew J. , Alexander Natalie J. , Timmer Kyle D. , Atallah Christine J. , Viens Adam L. , Panossian Vahe S. , Scherer Allison K. , Proctor Teddie , Smartt Sherrie , Letourneau Alyssa R. , Paras Molly L. , Johannes Sascha , Wiemer Jan , Mansour Michael K.
Published: January 2022

Purpose

Coronavirus disease-2019 (COVID-19) is associated with a wide spectrum of clinical symptoms including acute respiratory failure. Biomarkers that can predict outcomes in patients with COVID-19 can assist with patient management. The aim of this study is to evaluate whether procalcitonin (PCT) can predict clinical outcome and bacterial superinfection in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Methods

Adult patients diagnosed with SARS-CoV-2 by nasopharyngeal PCR who were admitted to a tertiary care center in Boston, MA with SARS-CoV-2 infection between March 17 and April 30, 2020 with a baseline PCT value were studied. Patients who were presumed positive for SARS-CoV-2, who lacked PCT levels, or who had a positive urinalysis with negative cultures were excluded. Demographics, clinical and laboratory data were extracted from the electronic medical records.

Results

324 patient charts were reviewed and grouped by clinical and microbiologic outcomes by day 28. Baseline PCT levels were significantly higher for patients who were treated for true bacteremia (p = 0.0005) and bacterial pneumonia (p = 0.00077) compared with the non-bacterial infection group. Baseline PCT positively correlated with the NIAID ordinal scale and survival over time. When compared to other inflammatory biomarkers, PCT showed superiority in predicting bacteremia.

Conclusions

Baseline PCT levels are associated with outcome and bacterial superinfection in patients hospitalized with SARS-CoV-2.
Loneliness among people with severe mental illness during the COVID-19 pandemic: Results from a linked UK population cohort study
Authors: Heron Paul , Spanakis Panagiotis , Crosland Suzanne , Johnston Gordon , Newbronner Elizabeth , Wadman Ruth , Walker Lauren , Gilbody Simon , Peckham Emily
Published: January 2022

Aim/Goal/Purpose

Population surveys underrepresent people with severe mental ill health. This paper aims to use multiple regression analyses to explore perceived social support, loneliness and factor associations from self-report survey data collected during the Covid-19 pandemic in a sample of individuals with severe mental ill health.

Design/Methodology/Approach

We sampled an already existing cohort of people with severe mental ill health. Researchers contacted participants by phone or by post to invite them to take part in a survey about how the pandemic restrictions had impacted health, Covid-19 experiences, perceived social support, employment and loneliness. Loneliness was measured by the three item UCLA loneliness scale.

Findings

In the pandemic sub-cohort, 367 adults with a severe mental ill health diagnosis completed a remote survey. 29–34% of participants reported being lonely. Loneliness was associated with being younger in age (adjusted OR = -.98, p = .02), living alone (adjusted OR = 2.04, p = .01), high levels of social and economic deprivation (adjusted OR = 2.49, p = .04), and lower perceived social support (B = -5.86, p < .001). Living alone was associated with lower perceived social support. Being lonely was associated with a self-reported deterioration in mental health during the pandemic (adjusted OR = 3.46, 95%CI 2.03–5.91).

Practical implications

Intervention strategies to tackle loneliness in the severe mental ill health population are needed. Further research is needed to follow-up the severe mental ill health population after pandemic restrictions are lifted to understand perceived social support and loneliness trends.

Originality

Loneliness was a substantial problem for the severe mental ill health population before the Covid-19 pandemic but there is limited evidence to understand perceived social support and loneliness trends during the pandemic.
Immune correlates of Mycobacterium Tuberculosis patients in Zambia stratified by HIV serostatus and level of immunity-a cross-sectional analytical laboratory based study
Authors: Lungu Patrick , Njelesani Evarist , Sukwa Thomas , Ngalamika Owen , Munsaka Sody , Kilembe William , Lakhi Shabir , Mwaba Peter
Published: January 2022

Background

People living with HIV (PLHIV) co-infected with tuberculosis (TB) have a distinct clinical presentation and poorer treatment outcomes compared to HIV-seronegative TB patients. Excluding low CD4 count, innate immune factors associated with TB are not fully elucidated. We, therefore, characterised and compared the expression of IL-6, TNF-α, IFN-γ, and IL-10 in whole blood of treatment naïve TB patients stimulated with heat-killed Mycobacterium tuberculosis stratified by HIV status and the level of CD4 count.

Results

We recruited 39 HIV seropositive and 31 HIV seronegative TB patients. Median (IQR) age was 35(28–42) years and 31(25–36) years respectively, and a majority had pulmonary tuberculosis i.e. 38(95%) and 30(97%), respectively. The two groups were significantly different in the distribution of CD4 count, 563 [465–702.5 cells/mm3] vs 345 [157–483 cell/mm3] in HIV negative vs HIV positive respectivelyp= <0.001. Post stimulation, the expression of IL-6 in HIV negative TB patients was significantly higher than in the HIV positive 16,757366 [8,827–23,686 pg/ml] vs. 9,508 [5,514–15,008 pg/ml], respectively;p= 0.0360. TNF-α and IFN-γ were highly expressed in HIV negative TB patients compared to the HIV positive though not statistically significant. We only observed higher expression of IL-6 in HIV negative patients in comparison to the HIV positive when stratified by level of CD4 counts as < 500 and ≥ 500 cell/mm3for both cohorts. 21,953 [8,990–24,206 pg/ml] vs 9,505 [5,400–15,313 pg/ml],pvalue = 0.0585 in patients with CD4 count < 500 cell/mm3and 13,168 [7,087–22,584 pg/ml] vs 10,413 [7,397–14,806 pg/ml],pvalue = 0.3744 for patients with CD4 count of ≥ 500 cell/mm3 respectively. We found a positive pairwise correlation between TNF-α -alpha and IL-6 in both HIV positive and HIV negative patients, r = 0.61 (95% CI 0.36–0.72;p< 0.0001) and r = 0.48 (95% CI 0.15–0.68;p= 0.005) respectively. The IFNγ/IL-10 ratio was higher in HIV negative when compared to HIV positive individuals, 0.052 [0.0–0.28] vs 0.007 [0–0.32] respectively;p= 0.05759. IL-6 independently reduced the probability of TB/HIV, Adjusted odds ratio 0.99,pvalue 0.007.

Conclusions

This study suggests that HIV seronegative TB patients have a higher pro-inflammatory response to MTB than HIV seropositive TB patients. Further, it also shows that the level of CD4 influences immunomodulation. The findings suggest that the difference in cytokine expression may be responsible for the distinct patterns of TB presentation between HIV positive and HIV negative patient.
Ramadan is not associated with increased infection risk in Pakistani and Bangladeshi populations: Findings from controlled interrupted time series analysis of UK primary care data
Authors: Almulhem Munerah , Thayakaran Rasiah , Hanif Shahjehan , Gooden Tiffany , Thomas Neil , Hazlehurst Jonathan , Tahrani Abd A. , Hanif Wasim , Nirantharakumar Krishnarajah
Published: January 2022

Background

The effect of fasting on immunity is unclear. Prolonged fasting is thought to increase the risk of infection due to dehydration. This study describes antibiotic prescribing patterns before, during, and after Ramadan in a primary care setting within the Pakistani and Bangladeshi populations in the UK, most of whom are Muslims, compared to those who do not observe Ramadan.

Method

Retrospective controlled interrupted time series analysis of electronic health record data from primary care practices. The study consists of two groups: Pakistanis/Bangladeshis and white populations. For each group, we constructed a series of aggregated, daily prescription data from 2007 to 2017 for the 30 days preceding, during, and after Ramadan, respectively.

Findings

Controlling for the rate in the white population, there was no evidence of increased antibiotic prescription in the Pakistani/Bangladeshi population during Ramadan, as compared to before Ramadan (IRR: 0.994; 95% CI: 0.988–1.001, p = 0.082) or after Ramadan (IRR: 1.006; 95% CI: 0.999–1.013, p = 0.082).

Interpretation

In this large, population-based study, we did not find any evidence to suggest that fasting was associated with an increased susceptibility to infection.
Patient-reported outcomes among people living with HIV on single- versus multi-tablet regimens: Data from a real-life setting
Authors: Degroote Sophie , Vandekerckhove Linos , Vogelaers Dirk , Vanden Bulcke Charlotte
Published: January 2022

Background

The use of single-tablet regimens (STRs) in HIV treatment is ubiquitous. However, reintroducing the (generic) components as multi-tablet regimens (MTRs) could be an interesting cost-reducing strategy. It is essential to involve patient-reported outcome measures (PROs) to examine the effects of such an approach. Hence, this study compared PROs of people living with HIV taking an STR versus a MTR in a real world setting.

Materials and methods

This longitudinal study included 188 people living with HIV. 132 remained on a MTR and 56 switched to an STR. At baseline, months 1-3-6-12-18 and 24, participants filled in questionnaires on health-related quality of life (HRQoL), depressive symptoms, HIV symptoms, neurocognitive complaints (NCC), treatment satisfaction and adherence. Generalized linear mixed models and generalized estimation equations mixed models were built.

Results

Clinical parameters and PROs of the two groups were comparable at baseline. Neurocognitive complaints and treatment satisfaction did differ over time among the groups. In the STR-group, the odds of having NCC increased monthly by 4,1% as compared to the MTR-group (p = 0.035). Moreover, people taking an STR were more satisfied with their treatment after 6 months: the median change score was high: 24 (IQR 7,5–29). Further, treatment satisfaction showed a contrary evolution in the groups: the estimated state score of the STR-group increased by 3,3 while it decreased by 0,2 in the MTR-group (p = 0.003). No differences over time between the groups were observed with regard to HRQoL, HIV symptoms, depressive symptoms and adherence.

Conclusions

Neurocognitive complaints were more frequently reported among people on an STR versus MTR. This finding contrasts with the higher treatment satisfaction in the STR-group over time. The long-term effects of both PROs should guide the decision-making on STRs vs. (generic) MTRs.
A structured additive modeling of diabetes and hypertension in Northeast India
Authors: Marbaniang Strong P. , Chungkham Holendro Singh , Lhungdim Hemkhothang
Published: January 2022

Background

Multiple factors are associated with the risk of diabetes and hypertension. In India, they vary widely even from one district to another. Therefore, strategies for controlling diabetes and hypertension should appropriately address local risk factors and take into account the specific causes of the prevalence of diabetes and hypertension at sub-population levels and in specific settings. This paper examines the demographic and socioeconomic risk factors as well as the spatial disparity of diabetes and hypertension among adults aged 15–49 years in Northeast India.

Methods

The study used data from the Indian Demographic Health Survey, which was conducted across the country between 2015 and 2016. All men and women between the ages of 15 and 49 years were tested for diabetes and hypertension as part of the survey. A Bayesian geo-additive model was used to determine the risk factors of diabetes and hypertension.

Results

The prevalence rates of diabetes and hypertension in Northeast India were, respectively, 6.38% and 16.21%. The prevalence was higher among males, urban residents, and those who were widowed/divorced/separated. The functional relationship between household wealth index and diabetes and hypertension was found to be an inverted U-shape. As the household wealth status increased, its effect on diabetes also increased. However, interestingly, the inverse was observed in the case of hypertension, that is, as the household wealth status increased, its effect on hypertension decreased. The unstructured spatial variation in diabetes was mainly due to the unobserved risk factors present within a district that were not related to the nearby districts, while for hypertension, the structured spatial variation was due to the unobserved factors that were related to the nearby districts.

Conclusion

Diabetes and hypertension control measures should consider both local and non-local factors that contribute to the spatial heterogeneity. More importance should be given to efforts aimed at evaluating district-specific factors in the prevalence of diabetes within a region.
Evaluation of SARS-CoV-2 entry, inflammation and new therapeutics in human lung tissue cells
Authors: Grau-Expósito Judith , Perea David , Suppi Marina , Massana Núria , Vergara Ander , Soler Maria José , Trinite Benjamin , Blanco Julià , García-Pérez Javier , Alcamí José , Serrano-Mollar Anna , Rosado Joel , Falcó Vicenç , Genescà Meritxell , Buzon Maria J.
Published: January 2022

The development of physiological models that reproduce SARS-CoV-2 infection in primary human cells will be instrumental to identify host-pathogen interactions and potential therapeutics. Here, using cell suspensions directly from primary human lung tissues (HLT), we have developed a rapid platform for the identification of viral targets and the expression of viral entry factors, as well as for the screening of viral entry inhibitors and anti-inflammatory compounds. The direct use of HLT cells, without long-term cell culture and in vitro differentiation approaches, preserves main immune and structural cell populations, including the most susceptible cell targets for SARS-CoV-2; alveolar type II (AT-II) cells, while maintaining the expression of proteins involved in viral infection, such as ACE2, TMPRSS2, CD147 and AXL. Further, antiviral testing of 39 drug candidates reveals a highly reproducible method, suitable for different SARS-CoV-2 variants, and provides the identification of new compounds missed by conventional systems, such as VeroE6. Using this method, we also show that interferons do not modulate ACE2 expression, and that stimulation of local inflammatory responses can be modulated by different compounds with antiviral activity. Overall, we present a relevant and rapid method for the study of SARS-CoV-2.
Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection
Authors: Sohail Aaqib , Iqbal Azeem A. , Sahini Nishika , Chen Fangfang , Tantawy Mohamed , Waqas Syed F.H. , Winterhoff Moritz , Ebensen Thomas , Schultz Kristin , Geffers Robert , Schughart Klaus , Preusse Matthias , Shehata Mahmoud , Bähre Heike , Pils Marina C. , Guzman Carlos A. , Mostafa Ahmed , Pleschka Stephan , Falk Christine , Michelucci Alessandro , Pessler Frank
Published: January 2022

Excessive inflammation is a major cause of morbidity and mortality in many viral infections including influenza. Therefore, there is a need for therapeutic interventions that dampen and redirect inflammatory responses and, ideally, exert antiviral effects. Itaconate is an immunomodulatory metabolite which also reprograms cell metabolism and inflammatory responses when applied exogenously. We evaluated effects of endogenous itaconate and exogenous application of itaconate and its variants dimethyl- and 4-octyl-itaconate (DI, 4OI) on host responses to influenza A virus (IAV). Infection induced expression of ACOD1, the enzyme catalyzing itaconate synthesis, in monocytes and macrophages, which correlated with viral replication and was abrogated by DI and 4OI treatment. In IAV-infected mice, pulmonary inflammation and weight loss were greater in Acod1-/- than in wild-type mice, and DI treatment reduced pulmonary inflammation and mortality. The compounds reversed infection-triggered interferon responses and modulated inflammation in human cells supporting non-productive and productive infection, in peripheral blood mononuclear cells, and in human lung tissue. All three itaconates reduced ROS levels and STAT1 phosphorylation, whereas AKT phosphorylation was reduced by 4OI and DI but increased by itaconate. Single-cell RNA sequencing identified monocytes as the main target of infection and the exclusive source of ACOD1 mRNA in peripheral blood. DI treatment silenced IFN-responses predominantly in monocytes, but also in lymphocytes and natural killer cells. Ectopic synthesis of itaconate in A549 cells, which do not physiologically express ACOD1, reduced infection-driven inflammation, and DI reduced IAV- and IFNγ-induced CXCL10 expression in murine macrophages independent of the presence of endogenous ACOD1. The compounds differed greatly in their effects on cellular gene homeostasis and released cytokines/chemokines, but all three markedly reduced release of the pro-inflammatory chemokines CXCL10 (IP-10) and CCL2 (MCP-1). Viral replication did not increase under treatment despite the dramatically repressed IFN responses. In fact, 4OI strongly inhibited viral transcription in peripheral blood mononuclear cells, and the compounds reduced viral titers (4OI>Ita>DI) in A549 cells whereas viral transcription was unaffected. Taken together, these results reveal itaconates as immunomodulatory and antiviral interventions for influenza virus infection.
Séneca: ¿creador de los derechos del hombre?
Authors: Rodríguez Magariños Faustino Gudín
Published: January 2022

A nuestro juicio, los derechos humanos en su configuración contemporánea se estructuran sobre dos ejes: de un lado, en el aspecto pasivo, la dignidad humana entendida como barrera infranqueable que todos deben respetar y, de otro, en el lado activo, el sentimiento de empatía hacia el otro. Para llegar a este punto se ha producido un largo recorrido que ha ido configurando una idea que se cimenta en el que quizás sea el principio jurídico y ético más básico: «neminem laedere».
Bajo nuestra óptica, la lucha por los derechos humanos en cualquiera de sus dimensiones equivale a la disputa por la defensa de la dignidad humana dado que este concepto parece amalgamar y dar soporte a todos los demás. La concepción moderna de la dignidad humana es tributaria de la labor de Séneca que la desarrolla hasta darle un contenido muy paralelo y similar al de hoy en día y su visión cambia el modo de ver a nuestros semejantes, primero en el Imperio romano, más siendo completada su labor un milenio más tarde con la llegada del humanismo y el iluminismo.
Los dispositivos de geolocalización del trabajador como medio de prueba en el proceso laboral
Authors: Valle Muñoz Francisco Andrés
Published: January 2022

Los dispositivos de geolocalización del trabajador son un instrumento tecnológico de que dispone el empresario para controlar la prestación de trabajo, pero, a su vez, son un medio de prueba para acreditar incumplimientos contractuales del trabajador en el seno del proceso laboral. En el presente estudio se analiza el valor de los dispositivos de geolocalización como medio de prueba en el proceso laboral sobre la base de abordar tres grandes temas: el primero de ellos es el relativo a su licitud, sobre todo cuando la información contenida en ellos se obtiene con vulneración de derechos fundamentales del trabajador como son el derecho a la intimidad y el derecho a la protección de datos de carácter personal, y, ligado con lo anterior, los efectos que ello conlleva en la sanción impuesta por el empresario al trabajador; el segundo tema está relacionado con la naturaleza jurídica autónoma o no de este medio de prueba y su calificación como prueba electrónica o digital y no como prueba documental; y el tercero de ellos está relacionado con la prueba sobre la autenticidad y exactitud de la información contenida en dichos dispositivos, y el recurso a otros medios probatorios alternativos para constatar tales circunstancias.
A short review on passive strategies applied to minimise the building
cooling loads in hot locations
Authors: Al-Yasiri Qudama , Szabó Márta
Published: January 2022

Cooling and air-conditioning systems are responsible for the highest
energy consumption in buildings located in hot areas. This high share does
not only increase the building energy demand cost but also increases the
environmental impact, the topmost awareness of the modern era. The
development of traditional systems and reliance on renewable technologies
have increased drastically in the last century but still lacks economic
concerns. Passive cooling strategies have been introduced as a successful
option to mitigate the energy demand and improve energy conservation in
buildings. This paper shed light on some passive strategies that could be
applied to minimise building cooling loads to encourage the movement
towards healthier and more energy-efficient buildings. For this purpose,
seven popular passive technologies have been discussed shortly:
multi-panned windows, shading devices, insulations, green roofing, phase
change materials, reflective coatings, and natural ventilation using the
windcatcher technique. The analysis of each strategy has shown that the
building energy could be improved remarkably. Furthermore, adopting more
passive strategies can significantly enhance the building thermal comfort
even under severe weather conditions.
Analog and digital modeling of sound and impaired periodontal
supporting tissues during mechanical testing
Authors: Szabó Veronika T. , Szabó Balázs , Tarjányi Tamás , Szőke-Trenyik Eszter , Szabó Balázs P. , Fráter Márk
Published: January 2022

Periodontitis is one of the most common conditions affecting oral
health among adults, posing a great challenge for both patients and also
for dentists aiming to treat this disease. In severe stages such
deterioration of the supporting tissues, namely the periodontal ligaments
and the bone, can occur, which will affect the biomechanical behavior and
therefore the longevity and survival of the affected teeth. In order to be
able to plan both periodontal and subsequent restorative treatment
properly, valid modelling of the current clinical situation is advised. The
aim of the present article is to comprehensively discuss possible analog
and digital modeling methods of periodontally affected teeth and the
periodontal structures surrounding them. Modelling possibilities can serve
later as the basis of mechanical load, digital finite element studies, and
also aid clinical treatment planning.
Coronavirus: A Practicing Veterinarian Prospective
Authors: Ayaz Muhammad Mazhar , Nazir Muhammad Mudasser , Akhtar Muhammad Saleem , Aziz Mubashir , Niaz Kamal , Ahmad Tanveer , Ahmad Haroon , Sheikh Ahsan Sattar
Published: January 2022

COVID19 is posing threat cosmopolitically encompassing more than 200 countries and making threat to entire population globally as pandemic. The cats, dogs and bovine are at threat which are close partner to human population. The veterinarians specially practicing are at risk when they encounter the sick animals. This study focus to the Pakistani veterinarian where animal population is under estimated or sometimes census is not performed. As Current population of domestic animals in Pakistan consist of 23.34 million buffaloes, 22.42 million cattle, 24.24 million sheep, 49.14 million goats, and with a huge population of dogs and cats without official census which may pose a threat to innocent population and even more a practicing veterinarian and veterinary paramedics are more at threat, if god forbids. There is need for further investigation its role and zoonotic perspective. Regarding practicing field veterinarians fighting without weapons against mass destructing pathogen and making vulnerability on wide.
On the anniversary of Galina A. Melnichenko, Academician of the Russian Academy of Sciences
Authors: Editorial Article
Published: January 2022

Galina Afanasyevna Melnichenko is a well-known Russian endocrinologist-researcher, academician of the Russian Academy of Sciences, author and head of fundamental and applied research. G.A. Melnichenko is one of the leaders in creating a methodology for organizing the endocrinological service of the Russian Federation. G.A. Melnichenko made a great contribution to the formation of modern ideas about the role of autoimmune and iodine deficiency states in the development of thyroid pathology. Leading Russian specialist in diseases of the hypothalamic-pituitary system, orphan endocrinopathies, adrenal pathology, multiple endocrine neoplasia syndromes.