bluuebunny/crossref_metadata_2025 huggingface dataset:
ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer
Authors: Yi Hanxi , Lu Wangxing , Liu Fan , Zhang Guoqing , Xie Feifan , Liu Wenjie , Wang Lei , Zhou Wenhu , Cheng Zeneng
Published: May 2021

Background

Reactive oxygen species (ROS)-responsive drug delivery systems (DDSs) are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve spatially and temporally controllable and accurate drug release in tumor sites based on ROS-responsive DDSs. To solve this problem, we designed a nanosystem combined photodynamic therapy (PDT) and ROS-responsive chemotherapy.

Methods

Indocyanine green (ICG), an ROS trigger and photosensitizer, and pB-DOX, a ROS-responsive prodrug of doxorubicin (DOX), were coencapsulated in polyethylene glycol modified liposomes (Lipo/pB-DOX/ICG) to construct a combination therapy nanosystem. The safety of nanosystem was assessed on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, target cell toxicity, and combined treatment effect were estimated on human breast cancer cells MDA-MB-231. In vivo biodistribution, biosafety assessment, and combination therapy effects were investigated based on MDA-MB-231 subcutaneous tumor model.

Results

Compared with DOX·HCl, Lipo/pB-DOX/ICG showed higher safety on normal cells. The toxicity of target cells of Lipo/pB-DOX/ICG was much higher than that of DOX·HCl, Lipo/pB-DOX, and Lipo/ICG. After endocytosis by MDA-MB-231 cells, Lipo/pB-DOX/ICG produced a large amount of ROS for PDT by laser irradiation, and pB-DOX was converted to DOX by ROS for chemotherapy. The cell inhibition rate of combination therapy reached up to 93.5 %. After the tail vein injection (DOX equivalent of 3.0 mg/kg, ICG of 3.5 mg/kg) in mice bearing MDA-MB-231 tumors, Lipo/pB-DOX/ICG continuously accumulated at the tumor site and reached the peak at 24 h post injection. Under irradiation at this time point, the tumors in Lipo/pB-DOX/ICG group almost disappeared with 94.9 % tumor growth inhibition, while those in the control groups were only partially inhibited. Negligible cardiotoxicity and no treatment-induced side effects were observed.

Conclusions

Lipo/pB-DOX/ICG is a novel tool for on-demand drug release at tumor site and also a promising candidate for controllable and accurate combinatorial tumor therapy.
Intracranial VCAM1 at time of mechanical thrombectomy predicts ischemic stroke severity
Authors: Maglinger Benton , Sands Madison , Frank Jacqueline A. , McLouth Christopher J. , Trout Amanda L. , Roberts Jill M. , Grupke Stephen , Turchan-Cholewo Jadwiga , Stowe Ann M. , Fraser Justin F. , Pennypacker Keith R.
Published: May 2021

Background

Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy.

Methods

The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical analysis of plasma proteomics used independent sample t tests, correlations, linear regression, and robust regression models to determine network signaling and predictors of clinical outcomes. Data and network analyses were performed using IBM SPSS Statistics, SAS v 9.4, and STRING V11.

Results

Increased systemic (p<0.001) and intracranial (p=0.013) levels of VCAM1 were associated with the presence of hypertension. Intracranial VCAM1 was positively correlated to both infarct volume (p=0.032; r=0.34) and edema volume (p=0.026; r=0.35). The %∆ in NIHSS from admittance to discharge was found to be significantly correlated to both systemic (p=0.013; r = −0.409) and intracranial (p=0.011; r = −0.421) VCAM1 levels indicating elevated levels of systemic and intracranial VCAM1 are associated with reduced improvement of stroke severity based on NIHSS from admittance to discharge. STRING-generated analyses identified biologic functional descriptions as well as function-associated proteins from the predictive models of infarct and edema volume.

Conclusions

The current study provides novel data on systemic and intracranial VCAM1 in relation to stroke comorbidities, stroke severity, functional outcomes, and the role VCAM1 plays in complex protein-protein signaling pathways. These data will allow future studies to develop predictive biomarkers and proteomic targets for drug development to improve our ability to treat a devastating pathology.
Strategies to promote the implementation of Screening, Brief Intervention, and Referral to Treatment (SBIRT) in healthcare settings: a scoping review
Authors: Thoele Kelli , Moffat Laura , Konicek Stephanie , Lam-Chi Monika , Newkirk Erica , Fulton Janet , Newhouse Robin
Published: May 2021

Background

Screening, brief intervention, and referral to treatment (SBIRT), is an approach for the prevention and treatment of substance use disorders, but is often underutilized in healthcare settings. Although the implementation of SBIRT is challenging, the use of multi-faceted and higher intensity strategies are more likely to result in the successful incorporation of SBIRT into practice in primary care settings. SBIRT may be used in different healthcare settings, and the context for implementation and types of strategies used to support implementation may vary by setting. The purpose of this scoping review is to provide an overview regarding the use of strategies to support implementation of SBIRT in all healthcare settings and describe the associated outcomes.

Methods

A scoping review was conducted using CINAHL Complete, HealthBusiness FullTEXT, PsycINFO, PubMed, and Embase to search for articles published in English prior to September 2019. The search returned 462 citations, with 18 articles included in the review. Two independent reviewers extracted data from each article regarding the theory, design, timeline, location, setting, patient population, substance type, provider, sample size and type, implementation strategies, and implementation outcomes. The reviewers entered all extracted data entered into a table and then summarized the results.

Results

Most of the studies were conducted in the United States in primary care or emergency department settings, and the majority of studies focused on SBIRT to address alcohol use in adults. The most commonly used strategies to support implementation included training and educating stakeholders or developing stakeholder interrelationships. In contrast, only a few studies engaged patients or consumers in the implementation process. Efforts to support implementation often resulted in an increase in screening, but the evidence regarding the brief intervention is less clear, and most studies did not assess the reach or adoption of the referral to treatment.

Discussion

In addition to summarizing the strategies used to increase reach and adoption of SBIRT in healthcare settings, this scoping review identified multiple gaps in the literature. Two major gaps include implementation of SBIRT in acute care settings and the application of implementation theories to inform healthcare efforts to enable use of SBIRT.
How therapists and patients need to develop a clinical feedback system after 18 months of use in a practice-research network: a qualitative study
Authors: Moltu Christian , McAleavey Andrew A. , Helleseth Marianne M. , Møller Geir Helge , Nordberg Sam S.
Published: May 2021

Background

A personalized computer-adaptive system for clinical feedback and routine outcome monitoring in mental health, Norse Feedback aims to bridge the needs for standardized and idiographic measures in ordinary practice.

Methods

Item response theory analyses of completed treatment processes (n = 800) informed a qualitative study comprising individual in-depth interviews and focus groups with patients (n = 9) and clinicians (n = 10). The research question was: How do clinicians and patients contribute to developing a clinical feedback system in a continuous process aimed at refining its clinical usefulness?

Results

We conducted thematic analyses and found five themes: 1. Added clinical needs, 2. Needs for re-organizing the clinician report, 3.Needs for differentiation of clinical content, 4. User-interface needs, and 5. Item level suggestions.

Conclusion

In this article, we detail resulting needs for continuous adaptation to practice, and discuss implications of the concrete experiences with the Norse action research program for the larger field of ROM/CFS implementation.
Functional mapping of androgen receptor enhancer activity
Authors: Huang Chia-Chi Flora , Lingadahalli Shreyas , Morova Tunc , Ozturan Dogancan , Hu Eugene , Yu Ivan Pak Lok , Linder Simon , Hoogstraat Marlous , Stelloo Suzan , Sar Funda , van der Poel Henk , Altintas Umut Berkay , Saffarzadeh Mohammadali , Le Bihan Stephane , McConeghy Brian , Gokbayrak Bengul , Feng Felix Y. , Gleave Martin E. , Bergman Andries M. , Collins Colin , Hach Faraz , Zwart Wilbert , Emberly Eldon , Lack Nathan A.
Published: May 2021

Background

Androgen receptor (AR) is critical to the initiation, growth, and progression of prostate cancer. Once activated, the AR binds to cis-regulatory enhancer elements on DNA that drive gene expression. Yet, there are 10–100× more binding sites than differentially expressed genes. It is unclear how or if these excess binding sites impact gene transcription.

Results

To characterize the regulatory logic of AR-mediated transcription, we generated a locus-specific map of enhancer activity by functionally testing all common clinical AR binding sites with Self-Transcribing Active Regulatory Regions sequencing (STARRseq). Only 7% of AR binding sites displayed androgen-dependent enhancer activity. Instead, the vast majority of AR binding sites were either inactive or constitutively active enhancers. These annotations strongly correlated with enhancer-associated features of both in vitro cell lines and clinical prostate cancer samples. Evaluating the effect of each enhancer class on transcription, we found that AR-regulated enhancers frequently interact with promoters and form central chromosomal loops that are required for transcription. Somatic mutations of these critical AR-regulated enhancers often impact enhancer activity.

Conclusions

Using a functional map of AR enhancer activity, we demonstrated that AR-regulated enhancers act as a regulatory hub that increases interactions with other AR binding sites and gene promoters.
Super-resolution visualization and modeling of human chromosomal regions reveals cohesin-dependent loop structures
Authors: Hao Xian , Parmar Jyotsana J. , Lelandais Benoît , Aristov Andrey , Ouyang Wei , Weber Christian , Zimmer Christophe
Published: May 2021

Background

The 3D organization of the chromatin fiber in cell nuclei plays a key role in the regulation of gene expression. Genome-wide techniques to score DNA-DNA contacts, such as Hi-C, reveal the partitioning of chromosomes into epigenetically defined active and repressed compartments and smaller “topologically associated” domains. These domains are often associated with chromatin loops, which largely disappear upon removal of cohesin. Because most Hi-C implementations average contact frequencies over millions of cells and do not provide direct spatial information, it remains unclear whether and how frequently chromatin domains and loops exist in single cells.

Results

We combine 3D single-molecule localization microscopy with a low-cost fluorescence labeling strategy that does not denature the DNA, to visualize large portions of single human chromosomes in situ at high resolution. In parallel, we develop multi-scale, whole nucleus polymer simulations, that predict chromatin structures at scales ranging from 5 kb up to entire chromosomes. We image chromosomes in G1 and M phase and examine the effect of cohesin on interphase chromatin structure. Depletion of cohesin leads to increased prevalence of loose chromatin stretches, increased gyration radii, and reduced smoothness of imaged chromatin regions. By comparison to model predictions, we estimate that 6–25 or more purely cohesin-dependent chromatin loops coexist per megabase of DNA in single cells, suggesting that the vast majority of the genome is enclosed in loops.

Conclusion

Our results provide new constraints on chromatin structure and showcase an affordable non-invasive approach to study genome organization in single cells.
Cellular and transcriptomic analyses reveal two-staged chloroplast biogenesis underpinning photosynthesis build-up in the wheat leaf
Authors: Loudya Naresh , Mishra Priyanka , Takahagi Kotaro , Uehara-Yamaguchi Yukiko , Inoue Komaki , Bogre Laszlo , Mochida Keiichi , López-Juez Enrique
Published: May 2021

Background

The developmental gradient in monocot leaves has been exploited to uncover leaf developmental gene expression programs and chloroplast biogenesis processes. However, the relationship between the two is barely understood, which limits the value of transcriptome data to understand the process of chloroplast development.

Results

Taking advantage of the developmental gradient in the bread wheat leaf, we provide a simultaneous quantitative analysis for the development of mesophyll cells and of chloroplasts as a cellular compartment. This allows us to generate the first biologically-informed gene expression map of this leaf, with the entire developmental gradient from meristematic to fully differentiated cells captured. We show that the first phase of plastid development begins with organelle proliferation, which extends well beyond cell proliferation, and continues with the establishment and then the build-up of the plastid genetic machinery. The second phase is marked by the development of photosynthetic chloroplasts which occupy the available cellular space. Using a network reconstruction algorithm, we predict that known chloroplast gene expression regulators are differentially involved across those developmental stages.

Conclusions

Our analysis generates both the first wheat leaf transcriptional map and one of the most comprehensive descriptions to date of the developmental history of chloroplasts in higher plants. It reveals functionally distinct plastid and chloroplast development stages, identifies processes occurring in each of them, and highlights our very limited knowledge of the earliest drivers of plastid biogenesis, while providing a basis for their future identification.
Serosurvey and associated risk factors of anti-Toxocara spp. antibodies in bovines from slaughterhouses of southeastern Brazil
Authors: Giudice Paula Andreia Fabris , Lescano Susana Angélica Zevallos , Gonzáles William Henry Roldan , Giuffrida Rogério , Bandeira Fernanda Nobre , Kmetiuk Louise Bach , Pires dos Santos Andrea , Biondo Alexander Welker , Santarém Vamilton Alvares
Published: May 2021

Background

Toxocariasis, caused by a nematode species of the genus Toxocara, has been described as one of the most prevalent zoonotic helminthiases worldwide. Human transmission may occur by ingesting Toxocara spp. larvae from raw or undercooked meat or organs; however, no comprehensive serosurvey study has been conducted to date investigating the role of cattle as paratenic hosts. The aim of the study reported here was to assess the prevalence of anti-Toxocara spp. antibodies and associated risk factors in bovines from two slaughterhouses located in Presidente Prudente, southeastern Brazil.

Methods

Blood samples were collected and tested by indirect enzyme-linked immunosorbent assay (ELISA). Cattle farmers voluntarily responded to an epidemiologic questionnaire.

Results

Overall, 213 of the 553 (38.5%) bovine samples were assessed as seropositive for anti-Toxocara spp. antibodies by indirect ELISA. Multivariate analysis revealed that the source of beef cattle and the presence of dogs or cats at the farm were associated with seropositivity. The use of feedlot systems was associated with lower likelihood of seropositivity.

Conclusions

These results indicate a high level of anti-Toxocara seropositivity in slaughterhouse cattle, with potentially contaminated meat posing an infection risk to humans. In addition, the presence of dogs and cats where the slaughtered beef cattle were raised was statistically associated with bovine seropositivity, probably due to the overlapping environment at the farm and the lack of pet deworming. The use of feedlot systems was a protective factor likely due to the absence of dog and cat contact, elevated feeding troughs that avoid contact with contaminated soil or grass, and younger age at slaughter of feedlot cattle. In summary, bovines may be used as environmental sentinels of Toxocara spp. contamination, and high seropositivity of slaughterhouse cattle may indicate a potential risk of human toxocariasis through the ingestion of raw or undercooked contaminated meat.

Graphical Abstract
Double anus in an Ixodes scapularis nymph, a medically important tick vector
Authors: Taank Vikas , Lattanzio Frank A. , Sultana Hameeda , Neelakanta Girish
Published: May 2021

Background

Ixodes scapularis ticks are medically important arthropod vectors that transmit several pathogens to humans. The observations of morphological abnormalities, including nanism, missing leg, extra leg, and gynandromorphism, have been reported in these ticks. In this study, we report the presence of two anuses in a laboratory-reared I. scapularis nymph.

Results

Larval ticks were allowed to feed on mice and to molt to nymphs. Two anuses were observed in one of the freshly molted nymphs. Stereo and scanning electron microscopy confirmed the presence of two anuses in one nymph within a single anal groove.

Conclusions

This report confirms the rare occurrence of double anus in I. scapularis.

Graphical Abstract
The analysis of some special results of a Lasota–Wazewska model with mixed variable delays
Authors: Yazgan Ramazan , Tunç Osman
Published: May 2021

This study is about getting some conditions that guarantee the existence and uniqueness of the weighted pseudo almost periodic (WPAP) solutions of a Lasota–Wazewska model with time-varying delays. Some adequate conditions have been obtained for the existence and uniqueness of the WPAP solutions of the Lasota–Wazewska model, which we dealt with using some differential inequalities, the WPAP theory, and the Banach fixed point theorem. Besides, an application is given to demonstrate the accuracy of the conditions of our main results.
Proteomic analyses on the browning of shade-dried Thompson seedless grape
Authors: Liu Fengjuan , Huang Wenshu , Feng Zuoshan , Tao Yongxia , Fan Yingying , He Weizhong , Li XiaoLi , Fang Xiaotong , Wang Cheng , Bai Yujia
Published: May 2021

China is one of the main producers in the worldwide raisin market. Most China’s raisins are produced in Xinjiang where the Thompson seedless grape (Vitis vinifera L.cv.Thompson seedless) is the main variety of green raisin. However, the browning of Thompson seedless grape during drying has been well-acknowledged as the primary factor affecting the development of the raisin industry. Data independent acquisition (DIA)-based protein profiling was performed on fresh and shade-dried Thompson seedless grapes. As a result, 5431 proteins were identified, among which the amounts of 739 proteins in fresh grape were found to be significantly different with those in dried grape. The functional annotation based on the Blast2GO showed that the ‘organic substance metabolic process’, ‘regulation of molecular function’, ‘enzyme regulator activity’, and ‘isomerase activity’ related proteins became very active during browning. Further analyses revealed that the browning-related proteins, which with significant different amounts in fresh and in dried grapes, are primarily involved in the phenylpropanoid biosynthesis, tyrosine metabolism, phenylalanine metabolism, oxidative phosphorylation metabolism, plutathione metabolism, peroxisome pathway, and fatty acid degradation. And five random differential proteins were verified with parallel reaction monitoring (PRM). The PRM results were in agreement with the DIA data. The main browning-related proteins of Thompson seedless grape were identified in this study. Their properties were tested, and their roles in the browning mechanism were indicated. This will lay base to a better understanding on the enzymatic browning of Thompson seedless grape, and it will also provide guidance for controlling the quality of Thompson seedless grapes in industry.
Urban planning and the market of development rights in Italy: learning from Milan
Authors: Serra Sergio
Published: May 2021

In recent years, the influence of neoliberal principles has led to an experimental application of new market-oriented approaches in the field of urban studies, in order to achieve different objectives of public interest, from the compensation of land use restrictions to the acquisition of areas for public services. Also in Italy, the use of equalization and non-financial compensation mechanisms has been influenced by internationally consolidated models, such as the Transfer of Development Rights programs (TDR). The key issue concerns the legal autonomy of development rights from land ownership, allowing their trade in the municipal market and thus, in theory, balancing private and public benefits. The scientific debate focuses on the several opportunities, in terms of planning effectiveness and flexibility, but also envisages the risk to generate unfairness, deregulation and other speculations. The paper aims to assess the positive and negative impacts of a generalized use of TDR in the urban governance and in the real estate market, adopting a case study research method. The experience of Milan has been investigated, analyzing the municipal registry of development rights. The results highlight strengths and weaknesses of the market of development rights application, in particular the risk of encouraging real estate speculation, in the same way as financial markets. Conclusions suggest the need of a more effective integration of market-based tools in the planning and regulatory framework, avoiding that their uncontrolled use could weaken the role of public authority in the local government.
Fundamental underpinnings of simulation education: describing a four-component instructional design approach to healthcare simulation fellowships
Authors: Meguerdichian Michael J. , Bajaj Komal , Walker Katie
Published: May 2021

Although in 2020, there are more than 120 healthcare simulation fellowships established globally, there is a paucity of literature on how to design fellowship programs most effectively, to equip graduates with the knowledge, skills, and attitudes of a competent simulation educator. Offering a systematic structure to approach simulation fellowship programmatic design may aid in better achieving program goals. In this manuscript, we present the application of the 4-component instructional design model as a blueprint to the development of Simulation Education Fellowships. We offer examples used at the NYC Health + Hospitals simulation fellowship to illustrate how the 4-component model informs fellowship program design which promotes the development of a simulation educator. This manuscript will provide a roadmap to designing curricula and assessment practices including self-reflective logbooks to focus the path toward achieving desired skills and shape future conversations around programmatic development.
Prevalence and factors associated with intestinal schistosomiasis and human fascioliasis among school children in Amhara Regional State, Ethiopia
Authors: Bekana Teshome , Berhe Nega , Eguale Tadesse , Aemero Mulugeta , Medhin Girmay , Tulu Begna , G/hiwot Yirgalem , Liang Song , Hu Wei , Erko Berhanu
Published: May 2021

Background

Schistosomiasis and fascioliasis are digenean parasitic infections and are among the neglected tropical diseases that have both medical and veterinary importance. They are found mainly in areas having limited access to safe water supply and improved sanitation.

Methods

A cross-sectional study was conducted to determine the prevalence of Schistosoma mansoni and Fasciola species infections and to identify associated risk factors among school children in Amhara Regional State, Ethiopia. Stool specimens were collected from 798 children (419 males, 379 females) and processed using Kato-Katz and formol-ether concentration techniques. A semi-structured questionnaire was used to collect socio-demographic and other exposure information to explore potential risk factors for the infections.

Results

The overall prevalence of S. mansoni and Fasciola species infections was 25.6% (95% confidence interval (CI): 22.5-28.6) and 5.5% (95% CI: 3.9-7.1), respectively. S. mansoni was present in all surveyed schools with the prevalence ranging from 12.8% (16/125; 95% CI = 5.6-20.0) to 39.7% (64/161; 95% CI = 32.2-47.2) while Fasciola species was identified in five schools with the prevalence ranging from 2.5% (4/160; 95% CI = 0.001–4.9) to 9.8% (13/133; 95% CI = 4.7–14.8). The prevalence of S. mansoni infection was significantly associated with swimming in rivers (Adjusted odds ratio (AOR): 1.79, 95% CI, 1.22–2.62; P=0.003), bathing in open freshwater bodies (AOR, 2.02; 95% CI, 1.39–2.94; P<0.001) and engaging in irrigation activities (AOR, 1.69; 95% CI, 1.19-2.39; P=0.004), and was higher in children attending Addis Mender (AOR, 2.56; 95% CI, 1.20–5.46; P=0.015 ) and Harbu schools (AOR, 3.53; 95% CI, 1.64–7.59; P=0.001). Fasciola species infection was significantly associated with consumption of raw vegetables (AOR, 2.47; 95% CI, 1.23-4.97; P=0.011) and drinking water from unimproved sources (AOR, 2.28; 95% CI, 1.11–4.70; P=0.026).

Conclusion

Both intestinal schistosomiasis and human fascioliasis are prevalent in the study area, affecting school children. Behaviors and access to unimproved water and sanitation are among significant risk factors. The findings are instrumental for targeted interventions.
The relationship of HLA-G 14-bp insertion/deletion genetic polymorphism to the risk of multiple sclerosis and its clinical phenotypes
Authors: Farghaly Wafaa M. , Saad Eldien Heba M. , Sayed Mohammed A. , Elnady Hassan M. , Khodeary Ashraf , Abdel-Gawad Abdelhady R. , El-Tallawy Hamdy N. , Abdellatif Mohammed G. , Alhewaig Hazem K.
Published: May 2021

Background

Human leukocyte antigen (HLA)-G molecule has been suggested to have a potential immunomodulatory role in multiple sclerosis (MS). Genetic variant sites of HLA-G molecule have been reported to be associated with autoimmune diseases. Identifying the genetic risk factors of MS may help in preventive strategies and anticipating disease progression. The aim of this work was to investigate the effect of HLA-G 14-base-pair insertion/deletion (14-bp INS/DEL) genetic polymorphism on MS risk and clinical characteristics and to observe the clinical characteristics of the MS patients’ group. The study included 48 MS patients and 50 cross-matched healthy controls, who were recruited from Sohag and Assiut university hospitals. Genetic testing (14-bp Ins/Del gene polymorphism) using polymerase chain reaction (PCR) was performed for patients and control groups. All patients had a detailed clinical assessment and have undergone measurement of disability using the Expanded Disability Status Scale (EDSS).

Results

No statistically significant difference was found between MS patients and healthy controls (HC) in genotypic and allelic frequencies of HLA-G 14-bp INS/DEL polymorphism (P=0.305). No significant association was found between HLA-G 14-bp INS/DEL polymorphism genotypes and clinical characteristics or degree of disability of MS patients. The most frequent presenting symptoms of MS were motor symptoms. Fatigue was the most reported symptom along the course of MS disease.

Conclusion

Although it has been long known that HLA-G represents an important MS susceptibility locus, in this study, no significant relation could be detected between the 14-bp INS/DEL polymorphism genotype and MS susceptibility. MS risk susceptibility may be not linked to a single allele but may depend on the combination of different polymorphic genetic sites. In this study, the lack of genetic susceptibility may be attributed to ethnic factor.
Spontaneous gastric perforation: is it really common?
Authors: Hashim Imran , Talat Nabila , Iqbal Asif , Choudhary Muhammad Saleem , Haider Naveed , Nayyer Sajid Iqbal , Sharif Muhammad , Wasti Arslan Raza , Ahmad Sarfraz
Published: May 2021

Background

Neonatal gastric perforation (NGP) is a rare, serious, and life-threatening condition which needs early recognition with prompt intervention for better prognosis. Its etiology is not yet well established, but multiple speculations have been put forth for its etiopathogenesis. Few most considered are traumatic, spontaneous, or secondary to inflammatory process like necrotizing enterocolitis. This study describes the etiological and prognostic factors for patients with NGP in our experience at a single center.

Results

A total of 46 neonates were included. Male gender predominated with M:F being 1.7:1. Most (n=36) neonates presented within 10 days of life whereas 8 neonates presented within 15 days. At presentation, gas under diaphragm was the most common radiologic finding in 25 (54.3%) neonates. On exploratory laparotomy, it was found that greater curvature was involved in maximum number of cases (n=27), followed by lesser curvature and anterior and posterior walls of the stomach. Most of perforations were within 1–5 cm in size. Gastrorrhaphy was done in all cases, and in two cases, feeding jejunostomy was done along with repair for feeding purpose. Finally, spontaneous NGP was diagnosed in 30 (60.8%), and NEC patches on other parts of the intestine were seen in 11 patients. Postoperatively, 28 neonates developed complications in the form of sepsis (n=13), wound infection (n=10), and burst abdomen (n=5). Regarding clinical outcome, 27 (58.7%) were discharged from the hospital whereas 19 (39.3%) patients died.

Conclusion

Our results show that spontaneous NGP is most commonly associated with NEC in our population, usually affecting the greater curvature. We observed a high mortality rate; however, good ICU care may improve the survival.
Efficient snapshot-free reverse time migration and computation of multiparameter gradients in full-waveform inversion
Authors: Robertsson Johan O. A. , Andersson Fredrik , Plessix René-Édouard
Published: May 2021

Computing images in reverse time migration and model parameter gradients from adjoint wavefields in full-waveform inversion (FWI) requires the correlation of a forward-propagated wavefield with another reverse-propagated wavefield. Although in theory only two wavefield propagations are required, one forward propagation and one reverse propagation, it requires storing the forward-propagated wavefield as a function of time to carry out the correlations, which is associated with significant input/output (I/O) cost. Alternatively, three wavefield propagations can be carried out to reverse propagate the forward-propagated wavefield in tandem with the reverse-propagated wavefield. We have determined how highly accurate reverse time migrated images and FWI model parameter gradients for anisotropic elastic FWI can be efficiently computed without significant disk I/O using two wavefield propagations by means of the principle of superposition.
Runge-Kutta discontinuous Galerkin method for solving wave equations in 2D isotropic and anisotropic poroelastic media at low frequencies
Authors: He Xijun , Yang Dinghui , Zhou Yanjie , Yang Lei , Huang Xueyuan
Published: May 2021

We have developed a Runge-Kutta discontinuous Galerkin (RKDG) method for solving wave equations in isotropic and anisotropic poroelastic media at low frequencies. First, the 2D Biot’s two-phase equations are transformed into a first-order system with dissipation. Then, the system is discretized by using the discontinuous Galerkin method with a third-order Runge-Kutta time discretization. The numerical stability conditions for solving porous equations are also investigated. We test several examples to validate our method in isotropic and anisotropic poroelastic media. Comparisons of seismic responses with the finite-difference method on fine grids show the correctness of this method. Moreover, the numerical results indicate that the RKDG method can provide clear fast P-, slow P-, and S-waves for anisotropic poroelastic media on coarse meshes. Also, a two-layer porous model, a poroelastic-elastic model with horizontal interface, and an isotropic-anisotropic poroelastic model with sinusoidal interface demonstrate that our method can deal with complex wave propagation. Therefore, the simulation results show that RKDG is an accurate and stable method for solving Biot’s equations.
Structural initiation along the frontal fold-thrust system in the western Indo-Burman Range: Implications for the tectonostratigraphic evolution of the Hatia Trough (Bengal Basin)
Authors: Abdullah Rashed , Hossain Md. Shahadat , Aktar Md. Soyeb , Hossain Mohammad Moinul , Khanam Farida
Published: May 2021

The Bengal Basin accommodates an extremely thick Cenozoic sedimentary succession that derived from the uplifted Himalayan and Indo-Burman Orogenic Belts in response to the subduction of the Indian Plate beneath the Eurasian and Burmese Plates. The Hatia Trough is a proven petroleum province that occupies much of the southern Bengal Basin. However, the style of deformation, kinematics, and possible timing of structural initiation in the Hatia Trough and the relationship of this deformation to the frontal fold-thrust system in the outer wedge (namely, the Chittagong Tripura Fold Belt) of the Indo-Burman subduction system to the east are largely unknown. Therefore, we have carried out a structural interpretation across the eastern Hatia Trough and the western Chittagong Tripura Fold Belt based on 2D seismic reflection data. Our result suggests that the synkinematic packages correspond to the Pliocene Tipam Group and the Pleistocene Dupitila Formation. This implies that the structural development in the western Chittagong Tripura Fold Belt took place from the Pliocene. In the Hatia Trough, the timing of structural activation is slightly later (since the Plio-Pleistocene). In general, fold intensity and structural complexity gradually increase toward the east. The presence of reverse faults with minor strike-slip motion along the frontal thrust system in the outer wedge is also consistent with the regional transpressional structures of the Indo-Burman subduction system. However, to the west, there is no evidence for strike-slip deformation in the Hatia Trough. The restored sections indicate that the amount of east–west shortening in the Hatia Trough is very low (maximum 1.2%). In contrast, to the east, the amount of shortening is high (maximum 13.5%) in the western margin of the Chittagong Tripura Fold Belt. In both areas, the key trapping mechanism includes anticlinal traps, although stratigraphic and combinational traps are possible, but this requires further evaluation.
Psychological health problems among Syrians during war and the COVID-19 pandemic: national survey
Authors: Mohsen Fatema , Bakkar Batoul , Melhem Sara , Aldakkak Samar , Mchantaf Dana , Marrawi Marah , Latifeh Youssef
Published: May 2021

This study aims to assess the prevalence of depression and anxiety during the COVID-19 outbreak embedded within the war in Syria. A web-based cross-sectional survey design was employed. The 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder scale revealed a high prevalence of depressive (n = 3326; 83.4%) and anxiety symptoms (n = 2777; 69.6%) among the 3989 participants. Multivariable logistic regression analysis was performed to identify factors associated with depression and anxiety. There is an urgent need within the healthcare system in Syria to provide mental healthcare to alleviate acute mental health disturbances and associated physical health perceptions among Syrians.
Rates of treatment-resistant schizophrenia from first-episode cohorts: systematic review and meta-analysis
Authors: Siskind Dan , Orr Stacy , Sinha Surabhi , Yu Ou , Brijball Bhavna , Warren Nicola , MacCabe James H , Smart Sophie E , Kisely Steve
Published: May 2021

Background

Treatment-resistant schizophrenia (TRS) is associated with high levels of functional impairment, healthcare usage and societal costs. Cross-sectional studies may overestimate TRS rates because of selection bias.

Aims

We aimed to quantify TRS rates by using first-episode cohorts to improve resource allocation and clozapine access.

Method

We undertook a systematic review of TRS rates among people with first-episode psychosis and schizophrenia, with a minimum follow-up of 8 weeks. We searched PubMed, PsycINFO, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews, and meta-analysed TRS rates from included studies.

Results

Twelve studies were included, totalling 11 958 participants; six studies were of high quality. The rate of TRS was 22.8% (95% CI 19.1–27.0%, P < 0.001) among all first-episode cohorts and 24.4% (95% CI 19.5–30.0%, P < 0.001) among first-episode schizophrenia cohorts. Subgroup sensitivity analyses by location of recruitment, TRS definition, study quality, time of data collection and retrospective versus prospective data collection did not lead to statistically significant differences in heterogeneity. In a meta-regression, duration of follow-up and percentage drop-out did not significantly affect the overall TRS rate. Men were 1.57 times more likely to develop TRS than women (95% CI 1.11–2.21, P = 0.010).

Conclusions

Almost a quarter of people with first-episode psychosis or schizophrenia will develop TRS in the early stages of treatment. When including people with schizophrenia who relapse despite initial response and continuous treatment, rates of TRS may be as high as a third. These high rates of TRS highlight the need for improved access to clozapine and psychosocial supports.
Effect of Medicaid Expansion on Receipt of Definitive Treatment and Time to Treatment Initiation by Racial and Ethnic Minorities and at Minority-Serving Hospitals: A Patient-Level and Facility-Level Analysis of Breast, Colon, Lung, and Prostate Cancer
Authors: Nguyen David-Dan , Paciotti Marco , Marchese Maya , Cole Alexander P. , Cone Eugene B. , Kibel Adam S. , Ortega Gezzer , Lipsitz Stuart R. , Weissman Joel S. , Trinh Quoc-Dien
Published: May 2021

PURPOSE:

We sought to investigate the association between Medicaid expansion under the Affordable Care Act and access to stage-appropriate definitive treatment for breast, colon, non–small-cell lung, and prostate cancer for underserved racial and ethnic minorities and at minority-serving hospitals (MSHs).

METHODS:

We conducted a retrospective, difference-in-differences study including minority patients with nonmetastatic breast, colon, non–small-cell lung, and prostate cancer and patients treated at MSHs between the age of 40 and 64, with tumors at stages eligible for definitive treatment from the National Cancer Database. We not only defined non-Hispanic Black and Hispanic cancer patients as racial and ethnic minorities but also report findings for non-Hispanic Black cancer patients separately. We examined the effect of Medicaid expansion on receipt of stage-appropriate definitive therapy, time to treatment initiation (TTI) within 30 days of diagnosis, and TTI within 90 days of diagnosis.

RESULTS:

Receipt of definitive treatment for minorities in expansion states did not change compared with minority patients in nonexpansion states. The proportion of racial and ethnic minorities in expansion states receiving treatment within 30 days increased (difference-in-differences: +3.62%; 95% CI, 1.63 to 5.61; P < .001) compared with minority patients in nonexpansion states; there was no change for TTI within 90 days. Analysis focused on Black cancer patients yielded similar results. In analyses stratified by MSH status, there was no change in receipt of definitive therapy, TTI within 30 days, and TTI within 90 days when comparing MSHs in expansion states with MSHs in nonexpansion states.

CONCLUSION:

In our cohort of cancer patients with treatment-eligible disease, we found no significant association between Medicaid expansion and changes in receipt of definitive treatment for breast, prostate, lung, and colon cancer for racial and ethnic minorities and at MSHs. Medicaid expansion was associated with improved TTI at the patient level for racial and ethnic minorities, but not at the facility level for MSHs. Targeted interventions addressing the needs of MSHs are still needed to continue mitigating national facility–level disparities in cancer outcomes.
Two definitions of maximally ψ-epistemic ontological model and preparation non-contextuality
Authors: Pan A. K.
Published: May 2021

An ontological model is termed as maximallyψ-epistemic if the overlap between any two quantum states is fully accounted for by the overlap of their respective probability distributions of ontic states. However, in the literature, there exist two different mathematical definitions (termed here as 1MψE and 2MψE) that capture the equivalent notion of maximalψ-epistemicity. In this work, we provide three theorems to critically examine the connections between preparation non-contextuality and the aforementioned two definitions of maximalψ-epistemicity. In theorem 1, we provide a simple and direct argument of an existing proof to demonstrate that the mixed state preparation non-contextuality implies the first definition of maximalψ-epistemicity. In theorem 2, we prove that the second definition of maximalψ-epistemicity implies pure-state preparation non-contextuality. If both the definitions capture the equivalent notion of maximalψ-epistemicity, then from the aforementioned two theorems one infers that the mixed-state preparation non-contextuality implies pure-state preparation non-contextuality. But, in theorem 3, we demonstrate that the mixed-state preparation non-contextuality in an ontological model implies pure-state contextuality and vice versa. This leads one to conclude that 1MψE and 2MψE capture inequivalent notions of maximalψ-epistemicity. The implications of our results and their connections to other no-go theorems are discussed.
Einstein-Gauss-Bonnet gravity with rational nonlinear electrodynamics
Authors: Kruglov S. I.
Published: May 2021

We obtain an exact spherically symmetric and magnetically charged black hole solution in 4D Einstein-Gauss-Bonnet gravity coupled with rational nonlinear electrodynamics. The thermodynamics of our model is studied. We calculate the Hawking temperature and the heat capacity of the black hole. The phase transitions occur in the point where the Hawking temperature possesses an extremum. We show that black holes are thermodynamically stable at some range of event horizon radii when the heat capacity is positive. The logarithmic correction to the Bekenstein-Hawking entropy is obtained.
Glycemic Patterns Are Distinct in Post-Bariatric Hypoglycemia After Gastric Bypass (PBH-RYGB)
Authors: Lee Daniel , Dreyfuss Jonathan M , Sheehan Amanda , Puleio Alexa , Mulla Christopher M , Patti Mary Elizabeth
Published: May 2021

Context

Severe hypoglycemia with neuroglycopenia, termed post-bariatric hypoglycemia (PBH). typically occurs postprandially, but it is also reported after activity or mid-nocturnally.

Objective

To quantify glycemia, glycemic variability, and magnitude/duration of low sensor glucose (SG) values in patients with PBH after Roux-en-Y gastric bypass (PBH-RYGB).

Methods

This retrospective analysis of data from an academic medical center included individuals with PBH-RYGB (n = 40), reactive hypoglycemia without gastrointestinal surgery (Non-Surg Hypo, n = 20), prediabetes (Pre-DM, n = 14), newly diagnosed T2D (n = 5), and healthy controls (HC, n = 38). Masked continuous glucose monitoring (Dexcom G4) was used to assess patterns over 24 hours, daytime (6 am–midnight) and nighttime (midnight–6 am). Prespecified measures included mean and median SG, variability, and percent time at thresholds of sensor glucose.

Results

Mean and median SG were similar for PBH-RYGB and HC (mean: 99.8 ± 18.6 vs 96.9 ± 10.2 mg/dL; median: 93.0 ± 14.8 vs 94.5 ± 7.4 mg/dL). PBH-RYGB had a higher coefficient of variation (27.3 ± 6.8 vs 17.9 ± 2.4%, P < 0.0001) and range (154.5 ± 50.4 vs 112.0 ± 26.7 mg/dL, P < 0.0001). Nadir was lowest in PBH-RYGB (42.5 ± 3.7 vs HC 49.0 ± 11.9 mg/dL, P = 0.0046), with >2-fold greater time with SG < 70 mg/dL vs HC (7.7 ± 8.4 vs 3.2 ± 4.1%, P = 0.0013); these differences were greater at night (12.6 ± 16.9 vs 1.0 ± 1.5%, P < 0.0001). Non-Surg Hypo also had 4-fold greater time with SG < 70 at night vs HC (SG < 70: 4.0 ± 5.9% vs 1.0 ± 1.5%), but glycemic variability was not increased.

Conclusion

Patients with PBH-RYGB experience higher glycemic variability and frequency of SG < 70 compared to HC, especially at night. These data suggest that additional pathophysiologic mechanisms beyond prandial changes contribute to PBH.
ALDH2 rs671 Is Associated With Elevated FPG, Reduced Glucose Clearance and Hepatic Insulin Resistance in Japanese Men
Authors: Takeno Kageumi , Tamura Yoshifumi , Kakehi Saori , Kaga Hideyoshi , Kawamori Ryuzo , Watada Hirotaka
Published: May 2021

Context

A recent meta-analysis of genome-wide association studies data from East Asians identified aldehyde dehydrogenase 2 (ALDH2) rs671 as a susceptibility variant for type 2 diabetes in males.

Objective

To investigate the association between ALDH2 rs671 and metabolic characteristics.

Methods

We studied 94 nonobese, nondiabetic, Japanese men. Using a 2-step hyperinsulinemic-euglycemic clamp, we evaluated insulin sensitivity in muscle and liver. Intrahepatic lipid and fat distribution were measured using 1H-magnetic resonance spectroscopy and magnetic resonance imaging, respectively. We divided participants into a risk-carrying group with ALDH2 rs671 G/G (n = 53) and a nonrisk-carrying group with ALDH2 rs671 G/A or A/A (n = 41).

Results

The risk-carrying group had significantly higher levels of alcohol consumption (18.4 [interquartile range, IQR, 10.4-48.9]) vs 12.1 (IQR, 1.3-29.0) g/day; P = .003), elevated fasting plasma glucose (FPG) (97.5 ± 7.9 vs 93.5 ± 6.2 mg/dL; P = .010), lower hepatic insulin sensitivity (61.7 ± 20.5% vs 73.1 ± 15.9%; P = .003), and lower fasting glucose clearance (0.84 ± 0.8 dL·m–2·min–1 vs 0.87 ± 0.09 dL·m–2·min–1; P = .047) than the nonrisk-carrying group, while insulin resistance in muscle and body fat distribution were similar. The single linear correlation analysis revealed significant correlations between alcohol consumption and hepatic insulin sensitivity (r = –0.262, P = .011), fasting glucose clearance (r = –0.370, P < .001), or FPG (r = 0.489, P < .001). The multiple regression analysis revealed that both ALDH2 rs671 G/G genotype and alcohol consumption were significant independent correlates for hepatic insulin sensitivity, whereas only alcohol consumption was a significant independent correlate for fasting glucose clearance.

Conclusion

Our data suggest that high-alcohol intake–dependent and independent hepatic insulin resistance and reduced fasting glucose clearance due to high alcohol intake could be a relatively upstream metabolic abnormality in ALDH2 rs671 G/G carriers.