bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of the host genetic factors, hypercholesterolemia and diabetes with mild influenza in an Iranian population
Authors: Mehrbod Parvaneh , Eybpoosh Sana , Farahmand Behrokh , Fotouhi Fatemeh , Khanzadeh Alishahi Majid
Published: March 2021

Background

Variation in host genetic factors may result in variation in the host immune response to the infection. Some chronic diseases may also affect individuals’ susceptibility to infectious diseases. The aim of this study was to evaluate the association of the host genetic factors mostly involved in inflammation, as well as hypercholesterolemia and diabetes with mild flu in an Iranian population.

Methods

In this cross-sectional study, nasopharyngeal swab samples were collected from 93 patients referred to primary care centers of Markazi, Semnan, and Zanjan provinces (central Iran) due to flu-like symptoms between March 2015 and December 2018. Of these, PCR test identified 49 influenza A/H1N1 and 44 flu-negative individuals. Twelve single-nucleotide polymorphisms (SNPs) in RPAIN, FCGR2A, MBL-2, CD55, C1QBP, IL-10, TNF-α and an unknown gene were genotyped using iPLEX GOLD SNP genotyping analysis. Hypercholesterolemia and diabetes status was determined based on the physician diagnosis. Association of the host genetic variants, hypercholesterolemia and diabetes with mild A/H1N1 flu was assessed with univariable and multivariable logistic regression analysis as implemented in Stata software (v.14). Statistical tests were considered as significant at 0.05 levels.

Results

Frequency of diabetes and hypercholesterolemia, as well as participants mean age was significantly higher in the flu-negative rather than the flu-positive group. Of 12 SNPs, nine did not show any significant association with mild flu in our study (rs1801274, rs1800451, rs2564978, rs361525, rs1800450, rs1800871, rs1800872, rs1800896, rs1800629). Possessing G vs. A allele in two SNPs (rs3786054 and rs8070740) was associated with a threefold increase in the chance of mild flu when compared to flu-negative patients (95% CI: 1.1, 22.0). Possessing C allele (vs. A) in the rs9856661 locus also increased the chance of mild flu up to 2 folds (95% CI: 1.0, 10.0).

Conclusion

The results showed that possessing the G allele in either rs3786054 or rs8070740 loci in C1QBP and RPAIN genes, respectively, increased the risk of H1N1 infection up to 3.3 folds, regardless of the patient’s age, BMI, diabetes, and hypercholesterolemia. Complementary functional genomic studies would shed more light on the underlying mechanism of human immunity associated with these genetic markers. The identified genetic factors may have the same role in susceptibility to similar respiratory infections with RNA viruses, like SARS, MERS and COVID-19. Future genetic association studies targeting these RNA viruses, especially COVID-19 is recommended. Studies on other ethnic groups would also shed light on possible ethnic variations in genetic susceptibility to respiratory RNA viruses.

Trial registryIR.PII.REC.1399.063
Disease-associated metabolic alterations that impact satellite cells and muscle regeneration: perspectives and therapeutic outlook
Authors: Joseph Josiane , Doles Jason D.
Published: March 2021

Many chronic disease patients experience a concurrent loss of lean muscle mass. Skeletal muscle is a dynamic tissue maintained by continuous protein turnover and progenitor cell activity. Muscle stem cells, or satellite cells, differentiate (by a process called myogenesis) and fuse to repair and regenerate muscle. During myogenesis, satellite cells undergo extensive metabolic alterations; therefore, pathologies characterized by metabolic derangements have the potential to impair myogenesis, and consequently exacerbate skeletal muscle wasting. How disease-associated metabolic disruptions in satellite cells might be contributing to wasting is an important question that is largely neglected. With this review we highlight the impact of various metabolic disruptions in disease on myogenesis and skeletal muscle regeneration. We also discuss metabolic therapies with the potential to improve myogenesis, skeletal muscle regeneration, and ultimately muscle mass.
Chronic exposure to PM2.5 aggravates SLE manifestations in lupus-prone mice
Authors: Yariwake Victor Yuji , Torres Janaína Iannicelli , dos Santos Amandda Rakell Peixoto , Freitas Sarah Cristina Ferreira , De Angelis Kátia , Farhat Sylvia Costa Lima , Câmara Niels Olsen Saraiva , Veras Mariana Matera
Published: March 2021

Background

Air pollution causes negative impacts on health. Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations and multifactorial etiology. Recent studies suggest that air pollution can trigger SLE and induce disease activity. However, this association has not been deeply investigated. Thus, the aim of this study was to evaluate whether exposure to fine particulate matter (PM2.5) exacerbates SLE manifestations, focusing on renal complications, in a lupus-prone animal model. Female NZBWF1 mice were exposed daily to 600 μg/m3of inhaled concentrated ambient particles (CAP) or filtered air (FA). Survival rate, body weight, weight of organs (kidney, spleen, thymus, liver and heart), blood cell count, proteinuria, kidney stereology, renal histopathology, gene expression and oxidative stress were analyzed.

Results

Female NZBW mice exposed to CAP showed decreased survival, increased circulating neutrophils, early onset of proteinuria and increased kidney weight with renal cortex enlargement when compared to NZBW mice exposed to FA.

Conclusions

This work shows that air pollution aggravates some SLE manifestations in lupus-prone mice. These results reinforce the need of reducing air pollutant levels in order to promote a better quality of life for individuals diagnosed with SLE.
K-seq, an affordable, reliable, and open Klenow NGS-based genotyping technology
Authors: Ziarsolo Peio , Hasing Tomas , Hilario Rebeca , Garcia-Carpintero Victor , Blanca Jose , Bombarely Aureliano , Cañizares Joaquin
Published: March 2021

Background

K-seq, a new genotyping methodology based on the amplification of genomic regions using two steps of Klenow amplification with short oligonucleotides, followed by standard PCR and Illumina sequencing, is presented. The protocol was accompanied by software developed to aid with primer set design.

Results

As the first examples, K-seq in species as diverse as tomato, dog and wheat was developed. K-seq provided genetic distances similar to those based on WGS in dogs. Experiments comparing K-seq and GBS in tomato showed similar genetic results, although K-seq had the advantage of finding more SNPs for the same number of Illumina reads. The technology reproducibility was tested with two independent runs of the tomato samples, and the correlation coefficient of the SNP coverages between samples was 0.8 and the genotype match was above 94%. K-seq also proved to be useful in polyploid species. The wheat samples generated specific markers for all subgenomes, and the SNPs generated from the diploid ancestors were located in the expected subgenome with accuracies greater than 80%.

Conclusion

K-seq is an open, patent-unencumbered, easy-to-set-up, cost-effective and reliable technology ready to be used by any molecular biology laboratory without special equipment in many genetic studies.
New paradigms for the treatment of lysosomal storage diseases: targeting the endocannabinoid system as a therapeutic strategy
Authors: Schuchman Edward H. , Ledesma Maria D. , Simonaro Calogera M.
Published: March 2021

Over the past three decades the lysosomal storage diseases have served as model for rare disease treatment development. While these efforts have led to considerable success, important challenges remain. For example, no treatments are currently approved for nearly two thirds of all lysosomal diseases, and there is limited impact of the existing drugs on the central nervous system. In addition, the costs of these therapies are extremely high, in part due to the fact that drug development has focused on a “single hit” approach – i.e., one drug for one disease. To overcome these obstacles researchers have begun to focus on defining common disease mechanisms in the lysosomal diseases, particularly in the central nervous system, with the hope of identifying drugs that might be used in several lysosomal diseases rather than an individual disease. With this concept in mind, herein we review a new potential treatment approach for the lysosomal storage diseases that focuses on modulation of the endocannabinoid system. We provide a short introduction to lysosomal storage diseases and the endocannabinoid system, followed by a brief review of data supporting this concept.
Learning about stress from building, drilling and flying: a scoping review on team performance and stress in non-medical fields
Authors: Dijkstra Femke S. , Renden Peter G. , Meeter Martijn , Schoonmade Linda J. , Krage Ralf , van Schuppen Hans , de la Croix Anne
Published: March 2021

Background

Teamwork is essential in healthcare, but team performance tends to deteriorate in stressful situations. Further development of training and education for healthcare teams requires a more complete understanding of team performance in stressful situations. We wanted to learn from others, by looking beyond the field of medicine, aiming to learn about a) sources of stress, b) effects of stress on team performance and c) concepts on dealing with stress.

Methods

A scoping literature review was undertaken. The three largest interdisciplinary databases outside of healthcare, Scopus, Web of Science and PsycINFO, were searched for articles published in English between 2008 and 2020. Eligible articles focused on team performance in stressful situations with outcome measures at a team level. Studies were selected, and data were extracted and analysed by at least two researchers.

Results

In total, 15 articles were included in the review (4 non-comparative, 6 multi- or mixed methods, 5 experimental studies). Three sources of stress were identified: performance pressure, role pressure and time pressure. Potential effects of stress on the team were: a narrow focus on task execution, unclear responsibilities within the team and diminished understanding of the situation. Communication, shared knowledge and situational awareness were identified as potentially helpful team processes. Cross training was suggested as a promising intervention to develop a shared mental model within a team.

Conclusion

Stress can have a significant impact on team performance. Developing strategies to prevent and manage stress and its impact has the potential to significantly increase performance of teams in stressful situations. Further research into the development and use of team cognition in stress in healthcare teams is needed, in order to be able to integrate this ‘team brain’ in training and education with the specific goal of preparing professionals for team performance in stressful situations.
The implications of complexity, systems thinking and philosophy for pediatricians
Authors: Ehrich Jochen , Manemann Jürgen , Tasic Velibor , DeSanto Natale Gaspare
Published: March 2021

National service systems in child healthcare are characterized by diversity and complexity. Primary, secondary, tertiary and quaternary healthcare services create complex networks covering pediatric subspecialties, psychology, sociology, economics and politics. Can pediatrics exist without philosophy? Does the absence of integrating philosophical perspectives during conceptualization of pediatric care contribute to deficiencies in the service systems structuring child healthcare? Philosophy offers new ways of complex systems thinking in scientific and clinical pediatrics. Philosophy could improve coping strategies on different levels when dealing with ethics of research projects, individual child healthcare and crises of healthcare service systems. Boundary and ultimate situations experienced by severely sick children require help, hope and resilience. Patients and families as well as pediatricians and other caregivers must act in concert. All of them may benefit from consulting with philosophers. The aim of this article is to point out the risks of a strict separation of scientific insight and sensory experience affecting child healthcare in our modern society, which is dominated by technology, competition and lack of equity and time.
Population genetic structure of the Asian bush mosquito, Aedes japonicus (Diptera, Culicidae), in Belgium suggests multiple introductions
Authors: Smitz Nathalie , De Wolf Katrien , Deblauwe Isra , Kampen Helge , Schaffner Francis , De Witte Jacobus , Schneider Anna , Verlé Ingrid , Vanslembrouck Adwine , Dekoninck Wouter , Meganck Kenny , Gombeer Sophie , Vanderheyden Ann , De Meyer Marc , Backeljau Thierry , Werner Doreen , Müller Ruth , Van Bortel Wim
Published: March 2021

Background

Aedes japonicus japonicus has expanded beyond its native range and has established in multiple European countries, including Belgium. In addition to the population located at Natoye, Belgium, locally established since 2002, specimens were recently collected along the Belgian border. The first objective of this study was therefore to investigate the origin of these new introductions, which were assumed to be related to the expansion of the nearby population in western Germany. Also, an intensive elimination campaign was undertaken at Natoye between 2012 and 2015, after which the species was declared to be eradicated. This species was re-detected in 2017, and thus the second objective was to investigate if these specimens resulted from a new introduction event and/or from a few undetected specimens that escaped the elimination campaign.

Methods

Population genetic variation at nad4 and seven microsatellite loci was surveyed in 224 and 68 specimens collected in Belgium and Germany, respectively. German samples were included as reference to investigate putative introduction source(s). At Natoye, 52 and 135 specimens were collected before and after the elimination campaign, respectively, to investigate temporal changes in the genetic composition and diversity.

Results

At Natoye, the genotypic microsatellite make-up showed a clear difference before and after the elimination campaign. Also, the population after 2017 displayed an increased allelic richness and number of private alleles, indicative of new introduction(s). However, the Natoye population present before the elimination programme is believed to have survived at low density. At the Belgian border, clustering results suggest a relation with the western German population. Whether the introduction(s) occur via passive human-mediated ground transport or, alternatively, by natural spread cannot be determined yet from the dataset.

Conclusion

Further introductions within Belgium are expected to occur in the near future, especially along the eastern Belgian border, which is at the front of the invasion of Ae. japonicus towards the west. Our results also point to the complexity of controlling invasive species, since 4 years of intense control measures were found to be not completely successful at eliminating this exotic at Natoye.

Graphical Abstract
Prevalence and associated factors of uncontrolled hyperlipidemia among Thai patients with diabetes and clinical atherosclerotic cardiovascular diseases: a cross-sectional study
Authors: Lertwanichwattana Teeraboon , Rangsin Ram , Sakboonyarat Boonsub
Published: March 2021

Objectives

The research aimed to determine the prevalence and associated factors of uncontrolled hyperlipidemia among Thai patients with the disease and Clinical ASCVD.

Results

A total of 1,527 Thai diabetic patients with a history of ASCVD were included in the study. Uncontrolled hyperlipidemia was detected among 1,216 patients (79.6%; 95% CI 77.6–81.7). The independent factors associated with uncontrolled hyperlipidemia included being female (adjusted odds ratio (AORs); 1.5, 95% CI 1.2–2.0), using thiazolidinedione (AORs; 1.7, 95% CI 1.1–2.7), community hospital (AORs; 4.3, 95% CI 1.0–18.0) and BMI level at 18.5–22.9 kg/m2 (AORs; 2.2, 95% CI 1.2–4.0), 23.0–24.9 kg/m2 (AORs; 1.8 95% CI 0.9–3.3), 25.0–29.9 kg/m2 (AORs; 2.3 95% CI 1.3–4.3) and ≥ 30 kg/m2 (AORs; 2.5 95% CI 1.3–4.9).
Addison’s disease associated with hypokalemia: a case report
Authors: Abdalla M. , Dave J. A. , Ross I. L.
Published: March 2021

Background

Primary adrenal insufficiency (Addison's disease) is a rare medical condition usually associated with hyperkalemia or normokalemia. We report a rare case of Addison's disease, coexisting with hypokalemia, requiring treatment.

Case presentation

In this case, a 42-year-old man was admitted to the intensive care unit with a history of loss of consciousness and severe hypoglycemia. His blood tests showed metabolic acidosis, low concentrations of cortisol 6 nmol/L (normal 68–327 nmol/L), and high plasma adrenocorticotropic hormone 253 pmol/L (normal 1.6–13.9 pmol/L), and he was diagnosed with primary adrenal insufficiency. Surprisingly, his serum potassium was low, 2.3 mmol/L (normal 3.5–5.1 mmol/L), requiring replacement over the course of his admission. Computed tomography scan of the adrenal glands showed features suggestive of unilateral adrenal tuberculosis. Investigations confirmed renal tubulopathy. The patient responded favorably to cortisol replacement, but never required fludrocortisone.

Conclusions

Coexistence of hypokalemia with Addison’s disease is unusual. We recommend investigation of the cause of hypokalemia in its own right, if it occurs with primary adrenal insufficiency.
Long non-coding RNA LNC_000641 regulates pseudorabies virus replication
Authors: Fang Linlin , Gao Yanni , Liu Xing , Bai Juan , Jiang Ping , Wang XianWei
Published: March 2021

Long non-coding RNAs (lncRNAs) are a new arm of gene regulatory mechanism as discovered by sequencing techniques and follow-up functional studies. The lncRNAs regulation of pseudorabies virus (PRV) infection has rarely been reported so far. Using RNA sequencing analysis, 225 lncRNAs with significant altered expressions in 3D4/21 cells infected with PRV (ZJ01) were identified. Five lncRNAs upregulated in PRV-infected cells were verified in cells infected with different PRV strains by qRT-PCR. By down- and up-regulation of lnc641, the accelerating effect of lnc641 on PRV replication was confirmed. Furthermore, we found that lnc641 regulated PRV replication by inhibiting the JAK-STAT1 pathway. This study suggests that lnc641 could be a new host factor target for developing antiviral therapies against PRV infection.
Numaswitch: an efficient high-titer expression platform to produce peptides and small proteins
Authors: Nguyen Bach-Ngan , Tieves Florian , Rohr Thomas , Wobst Hilke , Schöpf Felix S. , Solano Jóse D. Montoya , Schneider Julia , Stock Janpeter , Uhde Andreas , Kalthoff Thomas , Jaeger Karl Erich , Schmitt Lutz , Schwarz Christian
Published: March 2021

The production of peptides as active pharmaceutical ingredients (APIs) by recombinant technologies is of emerging interest. A reliable production platform, however, is still missing due the inherent characteristics of peptides such as proteolytic sensitivity, aggregation and cytotoxicity. We have developed a new technology named Numaswitch solving present limitations. Numaswitch was successfully employed for the production of diverse peptides and small proteins varying in length, physicochemical and functional characteristics, including Teriparatide, Linaclotide, human β-amyloid and Serum amyloid A3. Additionally, the potential of Numaswitch for a cost-efficient commercial production is demonstrated yielding > 2 g Teriparatide per liter fermentation broth in a quality meeting API standard.
Nonlocal boundary value problems for ψ-Hilfer fractional-order Langevin equations
Authors: Nuchpong Cholticha , Ntouyas Sotiris K. , Vivek Devaraj , Tariboon Jessada
Published: March 2021

In the paper, we study a boundary value problem for a class ofψ-Hilfer fractional-order Langevin equations with multi-point integral boundary conditions. Existence and uniqueness results are established by using well-known fixed point theorems. Examples illustrating the main results are also included.
Lyapunov stability analysis for nonlinear delay systems under random effects and stochastic perturbations with applications in finance and ecology
Authors: Almutairi Abdulwahab , El-Metwally H. , Sohaly M. A. , Elbaz I. M.
Published: March 2021

This manuscript is involved in the study of stability of the solutions of functional differential equations (FDEs) with random coefficients and/or stochastic terms. We focus on the study of different types of stability of random/stochastic functional systems, specifically, stochastic delay differential equations (SDDEs). Introducing appropriate Lyapunov functionals enables us to investigate the necessary conditions for stochastic stability, asymptotic stochastic stability, asymptotic mean square stability, mean square exponential stability, global exponential mean square stability, and practical uniform exponential stability. Some examples with numerical simulations are presented to strengthen the theoretical results. Using our theoretical study, important aspects of epidemiological and ecological mathematical models can be revealed. In ecology, the dynamics of Nicholson’s blowflies equation is studied. Conditions of stochastic stability and stochastic global exponential stability of the equilibrium point at which the blowflies become extinct are investigated. In finance, the dynamics of the Black–Scholes market model driven by a Brownian motion with random variable coefficients and time delay is also studied.
Barriers to implementing antimicrobial stewardship programs in three low- and middle-income country tertiary care settings: findings from a multi-site qualitative study
Authors: Rolfe Robert , Kwobah Charles , Muro Florida , Ruwanpathirana Anushka , Lyamuya Furaha , Bodinayake Champica , Nagahawatte Ajith , Piyasiri Bhagya , Sheng Tianchen , Bollinger John , Zhang Chi , Ostbye Truls , Ali Shamim , Drew Richard , Kussin Peter , Anderson Deverick J. , Woods Christopher W. , Watt Melissa H. , Mmbaga Blandina T. , Tillekeratne L. Gayani
Published: March 2021

Background

Antimicrobial resistance has been named as one of the top ten threats to public health in the world. Hospital-based antimicrobial stewardship programs (ASPs) can help reduce antimicrobial resistance. The purpose of this study was to determine perceived barriers to the development and implementation of ASPs in tertiary care centers in three low- and middle-income countries (LMICs).

Methods

Interviews were conducted with 45 physicians at tertiary care hospitals in Sri Lanka (n = 22), Kenya (12), and Tanzania (11). Interviews assessed knowledge of antimicrobial resistance and ASPs, current antimicrobial prescribing practices, access to diagnostics that inform antimicrobial use, receptiveness to ASPs, and perceived barriers to implementing ASPs. Two independent reviewers coded the interviews using principles of applied thematic analysis, and comparisons of themes were made across the three sites.

Results

Barriers to improving antimicrobial prescribing included prohibitively expensive antimicrobials, limited antimicrobial availability, resistance to changing current practices regarding antimicrobial prescribing, and limited diagnostic capabilities. The most frequent of these barriers in all three locations was limited drug availability. Many physicians in all three sites had not heard of ASPs before the interviews. Improved education was a suggested component of ASPs at all three sites. The creation of guidelines was also recommended, without prompting, by interviewees at all three sites. Although most participants felt microbiological results were helpful in tailoring antibiotic courses, some expressed distrust of laboratory culture results. Biomarkers like erythrocyte sedimentation rate and c-reactive protein were not felt to be specific enough to guide antimicrobial therapy. Despite limited or no prior knowledge of ASPs, most interviewees were receptive to implementing protocols that would include documentation and consultation with ASPs regarding antimicrobial prescribing.

Conclusions

Our study highlighted several important barriers to implementing ASPs that were shared between three tertiary care centers in LMICs. Improving drug availability, enhancing availability of and trust in microbiologic data, creating local guidelines, and providing education to physicians regarding antimicrobial prescribing are important steps that could be taken by ASPs in these facilities.
Observing UT1-UTC with VGOS
Authors: Haas Rüdiger , Varenius Eskil , Matsumoto Saho , Schartner Matthias
Published: March 2021

We present first results for the determination of UT1-UTC using the VLBI Global Observing System (VGOS). During December 2019 through February 2020, a series of 1 h long observing sessions were performed using the VGOS stations at Ishioka in Japan and the Onsala twin telescopes in Sweden. These VGOS-B sessions were observed simultaneously to standard legacy S/X-band Intensive sessions. The VGOS-B data were correlated, post-correlation processed, and analysed at the Onsala Space Observatory. The derived UT1-UTC results were compared to corresponding results from standard legacy S/X-band Intensive sessions (INT1/INT2), as well as to the final values of the International Earth Rotation and Reference Frame Service (IERS), provided in IERS Bulletin B. The VGOS-B series achieves 3–4 times lower formal uncertainties for the UT1-UTC results than standard legacy S/X-band INT series. The RMS agreement w.r.t. to IERS Bulletin B is slightly better for the VGOS-B results than for the simultaneously observed legacy S/X-band INT1 results, and the VGOS-B results have a small bias only with the smallest remaining standard deviation.
Automatic Segmentation and 3D Printing of A-shaped Manikins using a Bounding Box and Body-feature Points
Authors: Jung Jin Young , Chee Seonkoo , Sul In Hwan
Published: March 2021

A novel algorithm for 3D-printing technology was proposed to generate large-scale objects, especially A-shaped manikins or 3D human body scan data. Most of the conventional 3D printers have a finite printing volume, and it is the users’ work to convert the target object into a printable size. In this study, an automatic three-step segmentation strategy was applied to the raw manikin mesh data until the final pieces had a smaller size than the 3D printer’s maximum printing volume, which is generally called “beam length”. Human body feature point information was adopted for fashion and textile researchers to easily specify the desired cutting positions. A simple bounding box, especially orienting bounding box, and modified Boolean operator were proposed to extract the specified segments with computational stability. The proposed method was applied to graphically synthesized manikin data, and 1/8, 1/4, and 1/2 scale manikins were successfully printed, minimizing the amount of support structure.
DL-3-n-butylphthalide improved physical and learning and memory performance of rodents exposed to acute and chronic hypobaric hypoxia
Authors: Xu Gang , Shi Yi-Kun , Sun Bin-Da , Liu Lu , E. Guo-Ji , He Shu , Zhang Jian-Yang , Liu Bao , Hu Qiu , Chen Jian , Gao Yu-Qi , Zhang Er-Long
Published: March 2021

Background

Studies have revealed the protective effect of DL-3-n-butylphthalide (NBP) against diseases associated with ischemic hypoxia. However, the role of NBP in animals with hypobaric hypoxia has not been elucidated. This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia.

Methods

Sprague-Dwaley rats and Kunming mice administered with NBP (0, 60, 120, and 240 mg/kg for rats and 0, 90, 180, and 360 mg/kg for mice) were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined. Then, the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments, conducted at 5800 m for 3 days or 20 days, to evaluate changes in physical functions. The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment, conducted at 5800 m for 6 days or 27 days, to evaluate changes in learning and memory function. ATP levels were measured in the gastrocnemius muscle and malonaldehyde (MDA), superoxide dismutase (SOD), hydrogen peroxide (H2O2), glutathione peroxidase (GSH-Px), and lactate were detected in sera of rats, and routine blood tests were also performed.

Results

Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability. The time and distance to exhaustion for mice (NBP, 90 mg/kg) and time to exhaustion for rats (NBP, 120 and 240 mg/kg) significantly increased under conditions of acute hypoxia compared with control group. NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia. Moreover, 240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia. Furthermore, the levels of MDA and H2O2 decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia. Additionally, ATP levels in the gastrocnemius muscle significantly increased, while lactate levels in sera significantly decreased.

Conclusion

NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.
A case of 18 years disease-free survival after combined pancreatoduodenectomy and hemicolectomy for carcinosarcoma of the transverse colon
Authors: Ohwada Susumu , Moro Amika , Amit Nair , Sasaki Kazunari , Sakurai Shinji , Takada-Owada Atsuko , Izumi Masaru , Nakano Yuhei , Kashima Yasushige , Matsuyama Hideki
Published: March 2021

Background

Ascertaining the origin of large tumors located in the region of the pancreas head and adjacent mesocolon can pose a challenge preoperatively. En bloc pancreatoduodenectomy with hemicolectomy is often required towards curative tumor resection (R0) of malignant tumors in this region.

Case presentation

Herein we report a case of a 48-year-old man with two contiguous masses each 5 cm in size, located in the pancreatic head. The masses were detected incidentally by abdominal ultrasonography at an annual health check. Endoscopic biopsies revealed inflammation with no malignancy. Cross-sectional imaging showed the tumor direct invasion of the uncinate process of the pancreas, and the third portion of the duodenum. Based on imaging, a malignant submucosal tumor originating from mesenchymal cells in the mesentery of the transverse colon was made preoperatively. The mass required en bloc pancreatoduodenectomy, right hemicolectomy, and resection of the superior mesenteric vein. The final pathology was carcinosarcoma of the transverse colon. The patient survived 18 years after surgery without recurrence.

Conclusions

Malignant tumors located in the region of the pancreas head should be considered for an en bloc curative tumor resection and adjuvant chemotherapy treatments offered that might be beneficial for carcinosarcoma.
Contributing factors to the total fertility rate declining trend in the Middle East and North Africa: a systemic review
Authors: Pourreza Aboulghasem , Sadeghi Ahmad , Amini-Rarani Mostafa , Khodayari-Zarnaq Rahim , Jafari Hasan
Published: March 2021

Background

The total fertility rate (TFR) in the Middle East and North Africa has experienced a declining trend in recent years. Accordingly, the present study was conducted to provide a clear picture of the most critical factors affecting the TFR decline in this region.

Methods

This study was a systematic review between the years 2000 and 2016. The different databases like Cochrane, PubMed, Scopus, and Science Direct and the Google Scholar search engine were used. At first, 270 articles and then 18 articles were selected and meticulously read for the final analysis.

Results

The results indicated a declining trend in the TFR in the Middle East and North Africa, as in other parts of the world. Regarding the causes of this declining trend, several factors were identified and categorized into five main factors of health care-related, cultural, economic, social, and political.

Conclusions

While taking advantage of the experiences, it is necessary to identify the five main factors and their related issues and hence consider them in the population policy-making.
The expansive effects of polyamines on the metabolism and virulence of Streptococcus pneumoniae
Authors: Nanduri Bindu , Swiatlo Edwin
Published: March 2021

Polyamines are common intracellular metabolites of nearly all cells, and their conservation across a vast diversity of cells suggests critical roles for these compounds in cellular physiology. Most intracellular polyamines are associated with RNA and, subsequently, polyamines have significant effects on transcription and translation. Putrescine and spermidine are the most common polyamines in bacteria. Intracellular polyamine pools in bacteria are tightly controlled by both de novo synthesis and transport. Polyamine homeostasis is emerging as a critical parameter of multiple pathways and physiology with substantial impact on bacterial pathogenesis, including the important human pathogenStreptococcus pneumoniae. Modulation of polyamine metabolism in pneumococci is an important regulator of central metabolism. It has broad effects on virulence factors such as capsule as well as stress responses that ultimately impact the survival of pneumococcus in a host. Polyamine transport protein as a single antigen or in combination with other pneumococcal proteins is shown to be an efficacious immunogen that protects against nasopharyngeal colonization, and invasive disease. A comprehensive description of polyamine metabolic pathways and their intersection with pneumococcal pathogenesis will undoubtedly point to novel approaches for treatment and prevention of pneumococcal disease.
Effect of carbon-to-nitrogen ratio on high-rate nitrate removal in an upflow sludge blanket reactor for polluted raw water pre-treatment application
Authors: How Seow Wah , Ting Choo Xiang , Yap Jing Ying , Kwang Ching Yi , Tan Chee Keong , Yoochatchaval Wilasinee , Syutsubo Kazuaki , Chua Adeline Seak May
Published: March 2021

The drinking water treatment plants (DWTPs) in the developing countries urgently need an efficient pre-treatment for nitrate (NO3−) removal to cope with the increasing NO3−pollution in raw water. An upflow sludge blanket (USB) reactor applied for NO3−removal from domestic wastewater may be adopted by the DWTPs. However, studies on the optimal carbon-to-nitrogen ratio (C/N) and operation of USB reactor at short hydraulic retention times (HRT) for high-rate polluted raw water pre-treatment are lacking. In this study, we first investigated the optimal C/N for biological NO3−removal in a sequencing batch reactor (SBR). An USB reactor was then operated with the optimal C/N for pre-treating synthetic raw water contaminated with NO3−(40 mg N L− 1) to monitor the NO3−removal performance and to examine opportunities for reducing the HRT. After operating the SBR with designed C/N of 4, 3 and 2 g C g− 1N, we selected C/N of 3 g C g− 1N as the optimal ratio due to the lower carbon breakthrough and nitrite (NO2−) accumulation in the SBR. The USB reactor achieved complete NO3−and NO2−removal with a lower designed C/N of 2 g C g− 1N due to the longer sludge retention time when compared with that of SBR (10 d). The high specific denitrification rate (18.7 ± 3.6 mg N g− 1mixed liquor volatile suspended solids h− 1) suggested a possible HRT reduction to 36 min. We successfully demonstrated an USB reactor for high-rate NO3−removal, which could be a promising technology for DWTPs to pre-treat raw water sources polluted with NO3−.
Retraction Note: Patelloplasty in total knee arthroplasty with circumpatellar denervation versus without denervation – a randomized prospective study
Authors: Deekshith S. R. K. , Reddy K. J. , Raviteja R.
Published: March 2021

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s42836-021-00076-6.
Antilithiatic effect of C. dactylon, E. officinalis, K. pinnata, and B. nutans ethyl acetate fraction on glyoxylate-induced nephrolithiasis
Authors: Bigoniya Papiya , Sohgaura Atul Kumar , Shrivastava Birendra
Published: March 2021

Background

The plants Cynodon dactylon (C. dactylon), Emblica officinalis (E. officinalis), Kalanchoe pinnata (K. pinnata), and Bambusa nutans (B. nutans) have been reported to possess diuretic and antiurolithiatic potential against ethylene glycol and ammonium chloride along with in vitro calcium oxalate (CaOx) crystal growth inhibition property. Our previous research publications reported a rich presence of antioxidative phytocompounds like polyphenols and flavonoids in ethyl acetate fractions of these plants. This present study aims to explore antiurolithiatic potential of C. dactylon, E. officinalis, K. pinnata, and B. nutans ethyl acetate fraction following 7 days of sodium glyoxalate treatment on mice.

Results

Sodium glyoxylate treatment caused significant (P < 0.01–0.001) reduction in the urine magnesium and creatinine and elevation in oxalate, citrate, calcium, and phosphate levels. Ethyl acetate fraction of K. pinnata and B. nutans showed a highly significant antilithiatic effect by increasing urine volume, normalizing disrupted urine parameters, increasing LDH level, and decreasing kidney tissue oxalate content. E. officinalis and K. pinnata ethyl acetate fraction treatment showed a pronounced reversal of tubular dilation and damage of epithelial cell in kidney tissue with very less inflammatory cell infiltration.

Conclusion

The results signify the protective effect of K. pinnata and B. nutans ethyl acetate fraction rich with polyphenol and flavonoid on glyoxylate induced oxidative cell damage and morphological changes in mouse kidneys.
Predictive geologic mapping from geophysical data using self-organizing maps: A case study from Baie Verte, Newfoundland, Canada
Authors: Carter-McAuslan Angela , Farquharson Colin
Published: March 2021

Self-organizing maps (SOMs) are a type of unsupervised artificial neural networks clustering tool. SOMs are used to cluster large multivariate data sets. They can identify patterns and trends in the geophysical maps of an area and generate proxy geology maps, known as remote predictive mapping. We have applied SOMs to magnetic, radiometric, and gravity data sets compiled from multiple modern and legacy data sources over the Baie Verte Peninsula, Newfoundland, Canada. The regional and local geologic maps available for this area and knowledge from numerous geologic studies has enabled the accuracy of SOM-based predictive mapping to be assessed. Proxy geology maps generated by primary clustering directly from the SOMs and secondary clustering using a k-means approach reproduced many geologic units identified by previous traditional geologic mapping. Of the combinations of data sets tested, the combination of magnetic data, primary radiometric data and their ratios, and Bouguer gravity data gave the best results. We found that using reduced-to-the-pole residual intensity or using the analytic signal as the magnetic data were equally useful. The SOM process was unaffected by gaps in the coverage of some of the data sets. The SOM results could be used as input into k-means clustering because this method requires no gaps in the data. The subsequent k-means clustering resulted in more meaningful proxy geology maps than were created by the SOM alone. In regions where the geology is poorly known, these proxy maps can be useful in targeting where traditional, on-the-ground geologic mapping would be most beneficial, which can be especially useful in parts of the world where access is difficult and expensive.
Comparing psychotropic medication prescribing in personality disorder between general mental health and psychological services: retrospective cohort study
Authors: Kadra-Scalzo Giouliana , Garland Jacqueline , Miller Stephen , Chang Chin-Kuo , Fok Marcella , Hayes Richard D. , Moran Paul , Shetty Hitesh , Young Allan H. , Stewart Robert
Published: March 2021

Background

Although no drugs are licensed for the treatment of personality disorder, pharmacological treatment in clinical practice remains common.

Aims

This study aimed to estimate the prevalence of psychotropic drug use and associations with psychological service use among people with personality disorder.

Method

Using data from a large, anonymised mental healthcare database, we identified all adult patients with a diagnosis of personality disorder and ascertained psychotropic medication use between 1 August 2015 and 1 February 2016. Multivariable logistic regression models were constructed, adjusting for sociodemographic, clinical and service use factors, to examine the association between psychological services use and psychotropic medication prescribing.

Results

Of 3366 identified patients, 2029 (60.3%) were prescribed some form of psychotropic medication. Patients using psychological services were significantly less likely to be prescribed psychotropic medication (adjusted odds ratio 0.48, 95% CI 0.39–0.59, P<0.001) such as antipsychotics, benzodiazepines and antidepressants. This effect was maintained following several sensitivity analyses. We found no difference in the risk for mood stabiliser (adjusted odds ratio 0.79, 95% CI 0.57–1.10, P = 0.169) and multi-class psychotropic use (adjusted odds ratio 0.80, 95% CI 0.60–1.07, P = 0.133) between patients who did and did not use psychological services.

Conclusions

Psychotropic medication prescribing is common in patients with personality disorder, but significantly less likely in those who have used psychological services. This does not appear to be explained by differences in demographic, clinical and service use characteristics. There is a need to develop clear prescribing guidelines and conduct research in clinical settings to examine medication effectiveness for this population.
Development of Machine Learning Algorithms for the Prediction of Financial Toxicity in Localized Breast Cancer Following Surgical Treatment
Authors: Sidey-Gibbons Chris , Pfob André , Asaad Malke , Boukovalas Stefanos , Lin Yu-Li , Selber Jesse Creed , Butler Charles E. , Offodile Anaeze Chidiebele
Published: March 2021

PURPOSE

Financial burden caused by cancer treatment is associated with material loss, distress, and poorer outcomes. Financial resources exist to support patients but identification of need is difficult. We sought to develop and test a tool to accurately predict an individual's risk of financial toxicity based on clinical, demographic, and patient-reported data prior to initiation of breast cancer treatment.

PATIENTS AND METHODS

We surveyed 611 patients undergoing breast cancer therapy at MD Anderson Cancer Center. We collected data using the validated COmprehensive Score for financial Toxicity (COST) patient-reported outcome measure alongside other financial indicators (credit score, income, and insurance status). We also collected clinical and perioperative data. We trained and tested an ensemble of machine learning (ML) algorithms (neural network, regularized linear model, support vector machines, and a classification tree) to predict financial toxicity. Data were randomly partitioned into training and test samples (2:1 ratio). Predictive performance was assessed using area-under-the-receiver-operating-characteristics-curve (AUROC), accuracy, sensitivity, and specificity.

RESULTS

In our test sample (N = 203), 48 of 203 women (23.6%) reported significant financial burden. The algorithm ensemble performed well to predict financial burden with an AUROC of 0.85, accuracy of 0.82, sensitivity of 0.85, and specificity of 0.81. Key clinical predictors of financial burden from the linear model were neoadjuvant therapy (βregularized, .11) and autologous, rather than implant-based, reconstruction (βregularized, .06). Notably, radiation and clinical tumor stage had no effect on financial burden.

CONCLUSION

ML models accurately predicted financial toxicity related to breast cancer treatment. These predictions may inform decision making and care planning to avoid financial distress during cancer treatment or enable targeted financial support. Further research is warranted to validate this tool and assess applicability for other types of cancer.
Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL
Authors: Shah Nirali N. , Lee Daniel W. , Yates Bonnie , Yuan Constance M. , Shalabi Haneen , Martin Staci , Wolters Pamela L. , Steinberg Seth M. , Baker Eva H. , Delbrook Cindy P. , Stetler-Stevenson Maryalice , Fry Terry J. , Stroncek David F. , Mackall Crystal L.
Published: March 2021

PURPOSE

CD19 chimeric antigen receptor (CD19-CAR) T cells induce high response rates in children and young adults (CAYAs) with B-cell acute lymphoblastic leukemia (B-ALL), but relapse rates are high. The role for allogeneic hematopoietic stem-cell transplant (alloHSCT) following CD19-CAR T-cell therapy to improve long-term outcomes in CAYAs has not been examined.

METHODS

We conducted a phase I trial of autologous CD19.28ζ-CAR T cells in CAYAs with relapsed or refractory B-ALL. Response and long-term clinical outcomes were assessed in relation to disease and treatment variables.

RESULTS

Fifty CAYAs with B-ALL were treated (median age, 13.5 years; range, 4.3-30.4). Thirty-one (62.0%) patients achieved a complete remission (CR), 28 (90.3%) of whom were minimal residual disease−negative by flow cytometry. Utilization of fludarabine/cyclophosphamide–based lymphodepletion was associated with improved CR rates (29/42, 69%) compared with non–fludarabine/cyclophosphamide–based lymphodepletion (2/8, 25%; P = .041). With median follow-up of 4.8 years, median overall survival was 10.5 months (95% CI, 6.3 to 29.2 months). Twenty-one of 28 (75.0%) patients achieving a minimal residual disease−negative CR proceeded to alloHSCT. For those proceeding to alloHSCT, median overall survival was 70.2 months (95% CI, 10.4 months to not estimable). The cumulative incidence of relapse after alloHSCT was 9.5% (95% CI, 1.5 to 26.8) at 24 months; 5-year EFS following alloHSCT was 61.9% (95% CI, 38.1 to 78.8).

CONCLUSION

We provide the longest follow-up in CAYAs with B-ALL after CD19-CAR T-cell therapy reported to date and demonstrate that sequential therapy with CD19.28ζ-CAR T cells followed by alloHSCT can mediate durable disease control in a sizable fraction of CAYAs with relapsed or refractory B-ALL (ClinicalTrials.gov identifier: NCT01593696 ).