bluuebunny/crossref_metadata_2025 huggingface dataset:
Design as sexual practice: The visual culture of social apps and HIV risk in Taiwan
Authors: Huang Poyao
Published: June 2022

This article explores the visual culture of social network applications (apps), using “safer-sex design” as an anchor to contemplate how different practices of looking at HIV co-constitute viral visibility. Drawing on science and technology studies and queer theories, this article traces viral visibility from its digital production through its marketization, and finally to its implications for gay men’s sexual communication in Taiwan. Through interviews with gay Taiwanese men and a social app developer and the visual analysis of Hornet, Grindr, and Scruff, this article describes how the precarity of viruses, knowledge of HIV prevention, and social stigmas against sexual minorities are brought together, staged, and made eligible (and ineligible) for public viewing. This article demonstrates how digital platform designs work to facilitate gay men’s sociosexual communication while ironically reinforcing stigmas against HIV/AIDS in Taiwan, and suggests a critical approach to the visual culture of social apps and queer health.
Numerical simulation of welding deformation and residual stress in aluminum alloy plate-to-sleeve welded joints
Authors: Zhao Shusen , Li Yanmin , You Haobing
Published: June 2022

The plate-to-sleeve welded joint is employed in the aluminum alloy spatial structure. The welding deformation and residual stress determine the dimensional accuracy and even increase the failure risk. Based on ABAQUS software and the coordinate transformation method, a finite element model with the arc weaving was developed to investigate the temperature field, welding deformation, and residual stress of an AA6061-T6 plate-to-sleeve welded joint with 8-pass. The metal inert gas welding experiment was performed with the corresponding joint, and the welding deformation and residual stresses were measured to verify the numerical results. The results show that the thermal cycle of the weaving weld and its vicinity have multiple peaks, and the time interval between two adjacent peaks is one weaving period. The deformation pattern of the joint is angular deformation. The maximum deformation is observed in the weld toe of the top surface. The longitudinal residual stress in the weld and its vicinity is high tensile stress, and that in the upper part of the sleeve is mainly compressive stress. The transverse residual stress in the weld and its vicinity of the top surface is low tensile stress, and that in the bottom surface is compressive stress. Furthermore, the evolution of the welding deformation and residual stresses attributed to subsequent weld passes was elaborated, which provides a reference for developing control schemes.
Night sweats (nocturnal hyperhidrosis) causing wrinkled (pruney) hands in a patient with SARS-CoV-2 infection
Authors: Jawad Ali SM
Published: June 2022

We report the case of a 28-year-old female who developed severe night sweated on the ninth day of SARS-CoV-2 infection with wrinkling of the fingers and palms.
A Layer Plus Approach to Implementation Research and Collaboration for Long-Acting Injectable Preexposure Prophylaxis for HIV Prevention
Authors: Pilgrim Nanlesta A. , Evans Tammeka M. , Czarnogorski Maggie
Published: June 2022

In 2020, the HIV prevention clinical trials, HPTN (HIV Prevention Trials Network) 083 and 084, reported that long-acting injectable cabotegravir (CAB-LA) for HIV prevention was statistically superior to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) in cisgender men and transgender women who have sex with men, and cisgender women. However, clinical efficacy does not translate to real-world effectiveness and clinical practice as evidenced by current global use of oral PrEP. There are ~626,000 users of PrEP, which is significantly below the 3 million goal set by UNAIDS for 2020. Implementation will be key to ensuring that CAB-LA reaches those who desire to use it. We describe the Layer Plus Approach for CAB-LA for PrEP dissemination and implementation. The “Layer” is focused on integrating CAB-LA into existing PrEP models of care and understanding the best delivery channels that could be established in existing programs. Important implications of layering include preparing health professionals to provide CAB-LA, improving access for potential users, and addressing existing PrEP structural and facility barriers. “Plus,” which accounts for the existing disparities in PrEP access and use, means expanding CAB-LA to reach individuals for whom HIV prevention options have not been accessible or who have lapsed on oral PrEP. Implications for Plus include the development of new structures, systems, policies, and processes. A key aspect to the Approach is building collaborations to aid successful implementation. The Layer Plus Approach is a simple but strategic framework or a tailored approach to guide dissemination research and implementation.
“Something Fun to Look Forward to”: Lessons From Implementing the Prescription for Health Farmers’ Market Initiative in Rural Upper Michigan
Authors: Joseph Carly A. , Seguin Michelle L.
Published: June 2022

Fruit and vegetable (FV) prescription programs are an increasingly popular community-based approach to addressing food insecurity and improving nutrition by connecting local health care and food systems. The Prescription for Health farmers’ market FV prescription program was piloted in a rural, low-access low-income Michigan community in 2017. The program enrolled 33 adult participants with chronic disease and provided weekly farmers’ market FV vouchers, educational nutrition handouts, and seasonal healthy recipes over 10 weeks. Weight, blood pressure, and the following self-rated variables were assessed pre- and post program: dietary habits, food literacy, physical health, and mental health. While most metrics remained generally unchanged, one of the strongest findings from our data included significant improvement in quality of life. Increased social interaction as a result of the attending the farmers’ market was a prominent theme from informal open-ended participant feedback. Given the ongoing public health crisis of loneliness and social isolation, this finding led us to consider the farmers’ market as an avenue for creating opportunities for meaningful social connection among participants and farmers. To this end, we discuss health outcomes of the Prescription for Health pilot program, reflect on unique aspects of implementing this program in a rural area, and explore future opportunities for farmers’ market prescription programs as an innovative form of nature-based social prescribing.
Highly Active Nano-Reactor for Responding Tumor Microenvironment and Antitumor Therapy
Authors: Zhang Shuangxia , Liu Yan , Liu Bo
Published: June 2022

The tumor microenvironment is complex and changeable, so the design of a nano-delivery system for the tumor microenvironment has attracted wide attention. Based on this, we designed an intelligent nano-reactor for the characteristics of acidic pH and hypoxia in the tumor microenvironment. Firstly, the silver nano-balls were synthesized by the biological template method, which exhibited a good photothermal conversion efficiency and can realize the photothermal treatment of tumor sites. Subsequently, the hypoxic prodrug tirapazamine (TPZ) and polydopamine (PDA) for chemotherapy were self-assembled. After PDA arrived at the tumor site (pH 5.5) from the normal physiological environment (pH 7.4), the hypoxic prodrug TPZ was released in pH response by PDA. Subsequently, TPZ selectively induced obvious cell damage under tumor hypoxia stimulation but had no toxic effect on normal cells under normal oxygen. In addition, the nano-converter was loaded with iRGD on the surface, which enhanced the targeted delivery of the nano-reactor to achieve a highly effective antitumor effect. The nano-reactor was capable of combining photothermal/chemotherapy therapy. Importantly, it can selectively kill tumor cells without damaging normal cells based on the characteristics of the tumor microenvironment, with high bio-safety and clinical transformation potential.
More What Duchenne Smiles Do, Less What They Express
Authors: Krumhuber Eva G. , Kappas Arvid
Published: June 2022

We comment on an article by Sheldon et al. from a previous issue of Perspectives (May 2021). They argued that the presence of positive emotion (Hypothesis 1), the intensity of positive emotion (Hypothesis 2), and chronic positive mood (Hypothesis 3) are reliably signaled by the Duchenne smile (DS). We reexamined the cited literature in support of each hypothesis and show that the study findings were mostly inconclusive, irrelevant, incomplete, and/or misread. In fact, there is no single (empirical) article that would unanimously support the idea that DSs function solely as indicators of felt positive affect. Additional evidence is reviewed, suggesting that DSs can be—and often are—displayed deliberately and in the absence of positive feelings. Although DSs may lead to favorable interpersonal perceptions and positive emotional responses in the observer, we propose a functional view that focuses on what facial actions—here specifically DSs—do rather than what they express.
Cycling modelling under uncontrolled outdoor conditions using a wearable sensor and different meteorological measurement methods
Authors: Millour Geoffrey , Plourde-Couture Félix , Domingue Frédéric
Published: June 2022

The aim of this study was to model the cycling displacement under uncontrolled outdoor conditions with a wearable sensor and different meteorological measurement methods. One participant completed eight courses of a distance of 9.2 ± 2.4 km with varied profiles and directions. Data were recorded every second with a power meter, a GPS and a speed sensor. The aerodynamic drag coefficient, measured by a Notio wearable sensor, and the meteorological variables provided by the Notio, a Kestrel fixed meteorological station and the OpenWeather website were integrated into the Martin mathematical model to calculate the theoretical power output. The power calculated by the model on the basis of data from Notio, Kestrel and OpenWeather were, respectively, 1 ± 4 W higher, 7 ± 15 W lower and 67 ± 111 W higher than the power measured by the sensor. The overall RMSE and R2, including 7325 data points, were 12.8 W and 0.77 ( p < 0.001), respectively, between the power output measured by the sensor and the power output modelled with the data from Notio. The use of the model with the wearable sensor was more precise mainly due to the relative wind measures at all points of the course. Therefore, the Notio can be useful for coaches to follow the evolution of the CdA of athletes on the field. Moreover, the model has the potential to predict the time of a cyclist just before a time trial in order to optimise his pacing strategy taking into account actual weather conditions.
Molecular mechanisms underlying the resistance of BRAF V600E-mutant metastatic colorectal cancer to EGFR/BRAF inhibitors
Authors: Xu Ting , Wang Xicheng , Wang Zhenghang , Deng Ting , Qi Changsong , Liu Dan , Li Yanyan , Ji Congcong , Li Jian , Shen Lin
Published: June 2022

Background:

Combinatorial inhibition of epidermal growth factor receptor (EGFR) and BRAF shows remarkable clinical benefits in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC). However, the tumor may inevitably develop resistance to the targeted therapy, thereby limiting the response rate and durability. This study aimed to determine the genetic alterations associated with intrinsic and acquired resistance to EGFR/BRAF inhibitors in BRAF V600E-mutant mCRC.

Methods:

Targeted sequencing of 520 cancer-related genes was performed in tumor tissues and in plasma samples collected from patients with BRAF V600E-mutant mCRC, who were treated with EGFR/BRAF ± MEK inhibitors, before and after the targeted treatment. Clinical benefit was defined as an objective response or a stable disease lasting longer than the median progression-free survival (PFS).

Results:

In all, 25 patients with BRAF V600E-mutant mCRC were included in this study. Those with RNF43 mutations ( n = 8) were more likely to achieve clinical benefit from EGFR/BRAF inhibitors than those with wild-type RNF43 (87.5% versus 37.5%, p = 0.034). Genetic alterations in receptor tyrosine kinase genes ( n = 6) were associated with worse PFS ( p = 0.005). Among the 23 patients whose disease progressed after the EGFR/BRAF-targeted therapy, at least one acquired resistance-related mutation was detected in 12 patients. Acquired mutations were most frequently observed in the mitogen-activated protein kinase pathway-related genes ( n = 9), including KRAS (G12D and Q61H/R), NRAS (Q61L/R/K and amplification), BRAF (amplification), and MEK1 (K57T). MET amplification and PIK3R1 Q579fs mutation emerged in three patients and one patient, respectively, after disease progression.

Conclusion:

Multiple genetic alterations are associated with clinical benefits and resistance to EGFR/BRAF inhibitors in BRAF V600E-mutant mCRC. Our findings provide novel insights into strategies for overcoming resistance to EGFR/BRAF inhibitors in patients with BRAF V600E-mutant mCRC.
Implicit and Explicit Attitudes Toward Service Robots in the Hospitality Industry: Gender Differences
Authors: Lee Kwang-Ho , Yen Chih-Lun Alan
Published: June 2022

The current study applies implicit theory as a theoretical lens to explore gender differences in explicit and implicit measures of robot attitudes, which in turn facilitates behavioral intention. In total, 108 participants assessed the modified Robot Implicit Association Test (RIAT) to complete both implicit measures of attitudes and explicit self-reported measures in randomized order. Our findings demonstrated that (a) implicit attitudes (RIAT D-scores) were significantly correlated with self-reported measures (explicit attitude, perceived technology innovativeness, and behavioral intention), (b) different patterns of explicit and implicit attitudes exist, and (c) males may have a more favorable preference toward service robots than females. These results help build theoretical and methodological foundations for service management innovation into the role of implicit attitude in hospitality firms.
Technological risks and ethical implications of using robots in long-term care
Authors: Hung Lillian , Mann Jim , Perry Jennifer , Berndt Annette , Wong Joey
Published: June 2022

Introduction

The pandemic provides a unique opportunity to examine new directions in innovative technological approaches in long-term care (LTC) homes. While robotics could enhance staff capacity to provide care, there are potential technology risks and ethical concerns involved in technology use among older people residing in communal aged care homes. This qualitative descriptive study explores the technological risks and ethical issues associated with the adoption of robots in the specific context of LTC homes.

Methods

The research team including patient and family partners employed purposive and snowballing methods to recruit 30 LTC participants: frontline interdisciplinary staff, operational leaders, residents and family members, and ethics experts in dementia care. Semi-structured interviews were conducted. Thematic analysis was performed to identify themes that capture empirical experiences and perspectives of a diverse group of LTC stakeholders about robotic use.

Results

Technological risks include safety, increased workload, privacy, cost and social justice, and human connection. The findings offer practical insights based on the LTC perspective to contribute to the robot ethics literature. We propose a list of pragmatic recommendations, focusing on six principles (ETHICS): Engagement of stakeholders, Technology benefit and risk assessment, Harm mitigation, Individual autonomy, Cultural safety and justice, Support of privacy.

Conclusions

There is both a growing interest as well as fear in using robotics in LTC. Practice leaders need to reflect on ethical considerations and engage relevant stakeholders in making technology decisions for everyday care.
Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces Versus Standard Management in the Treatment of Limb Amputation: A Systematic Review and Meta-Analysis
Authors: Yuan Morgan , Gallo Matteo , Gallo Lucas , Huynh Minh HQ , McRae Mark , McRae Matthew C. , Thoma Achilleas , Coroneos Christopher J. , Voineskos Sophocles H.
Published: June 2022

Introduction: Painful neuromas are a common postoperative complication of limb amputation often treated with secondary reinnervation. Surgical reinnervation include Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI), and can be primary and secondary. The aim of this review is to assess the effects of primary TMR/RPNI at the time of limb amputation on the incidence and intensity of post-operative neuroma and pain. Methods: This review was registered a priori on PROSPERO (CRD42021264360). A search of the following databases was performed in June 2021: Medline, EMBASE, and CENTRAL. Unpublished trials were searched using clinicaltrials.gov. All randomized and non-randomized studies assessing amputation with a reinnervation strategy (TMR, RPNI) were included. Outcomes evaluated included the incidences of painful neuroma, phantom limb pain (PLP), residual limb pain (RLP), as well as severity of pain, and Pain intensity, behavior, and interference (PROMIS). Results: Eleven studies were included in this systematic review, and five observational studies for quantitative synthesis. Observational study evidence suggests that TMR/RPNI results in a statistically significant reduction in incidence, pain scores and PROMIS scores of PLP and RLP. Decreased incidence of neuromas favored primary TMR/RPNI, but this did not achieve statistical significance (p = 0.07). Included studies had moderate to critical risk of bias. Conclusion: The observational data suggests that primary TMR/RPNI reduces incidence, pain scores and PROMIS scores of PLP and RLP. Going forward, randomized trials are warranted to evaluate this research question, particularly to improve the certainty of evidence.
Effect of Breastfeeding and Preterm Births on the Severity of Lower Respiratory Tract Infections and Associated Risk of Hospitalization in Infants and Toddlers
Authors: Demir And , Özdemir Karadas Nihal , Karadas Ulas
Published: June 2022

We studied the effect of duration of breastfeeding and history of prematurity on the duration of hospitalization in infants with lower respiratory tract infections (LRTI) because these may reflect the severity of illness as well as sizable direct and indirect healthcare costs. One hundred twenty-five patients (49 girls, 76 boys; aged 1-24 months) were hospitalized for LRTI during a period of 102 days and studied prospectively. We found a significant difference ( P = .045) between the durations of hospitalization of the 92 patients breastfed for at least six months, compared to the other group of 33 patients who were breastfed for less than six months. The durations of hospitalization among the groups with and without a history of prematurity were not statistically different ( P = .78). A history of breastfeeding for more than six months had significant effect on the duration of hospitalization, but this was not true for children with a history of preterm birth.
Approaches to Safety Evaluation of Baby Wipes
Authors: Li Ning , Dey Swatee , O’Connor Robert , Abbinante-Nissen Joan , White Jeff
Published: June 2022

Disposable baby wipes manufactured by Procter & Gamble, soft sheets bearing lotion that is balanced to maintain natural skin pH, are convenient for cleaning the diaper area and a quick cleanup on baby’s face and hands.

Objective:

Develop a rigorous safety assessment process to ensure that baby wipes are safe and gentle to skin. This process is built-in from the start of product research and development.

Methods:

A systematic, iterative approach that includes (1) exposure-based safety assessment of all raw materials for systemic and local effects, which are consistent with established risk assessment paradigms; (2) when needed, testing of finished wipes in in vitro and/or clinical studies for skin and eye irritation, contact sensitization, or mechanical effects on skin in comparison to benchmark products that have a long history of wipe safety in marketplace; (3) prospective and randomized in-use studies in babies; and (4) in-market monitoring that is an integral part of the on-going product safety assessment.

Results:

Individual approaches and/or their combination show mildness of the test wipes. Further, in-market monitoring is testimony to baby skin compatibility of baby wipes.

Conclusion:

The approaches that have been developed demonstrate the skin compatibility and/or benefits of baby wipes relative to other modes of cleaning if needed. This article describes our safety assurance program, exposure-based safety assessment, and the range of robust testing strategies and approaches that can be employed to assure the safety of baby wipes.
Evaluation of the Impact of an Education Program on Self-Reported Leadership and Management Competence Among Nurse Managers
Authors: Aqtash Salah , Alnusair Hussam , Brownie Sharon , Alnjadat Rafi , Fonbuena Mariezl , Perinchery Saleem
Published: June 2022

Background

Developing leadership and management competencies for nursing managers is critical to the effective leadership of others and driving team and organizational performance. This paper aimed to evaluate the impact of a system-wide nursing leadership quality improvement initiative in a network of four public hospitals and one specialized outpatient center in the United Arab Emirates (UAE). The initiative was designed to enhance nursing middle managers’ leadership and managerial competencies.

Methods

This is a quantitative evaluation following the Standards for Quality Improvement Reporting Excellence (SQUIRES) guidelines. Secondary Data analysis of a pre- and post-course self-assessment for 105 middle nursing managers who attended a nursing leadership quality improvement training program between December 2017 and April 2019.

Results

Following participation in this quality improvement initiative, the paired sample t-test analysis demonstrated a statistically significant difference between the pre- and post-assessments total and individual leadership domains mean scores.

Conclusion

Attending well-structured nursing leadership quality improvement programs positively enhances nurse managers’ professional abilities and perception of their management and leadership competencies. Leadership development programs should equip managers with the skills and tools to achieve their professional goals effectively and support their transition to becoming expert nurse leaders. Healthcare institutions’ ethical obligation is to provide them with the necessary resources and training to achieve this goal.
A macaque clonal hematopoiesis model demonstrates expansion of TET2-disrupted clones and utility for testing interventions
Authors: Shin Tae-Hoon , Zhou Yifan , Chen Shirley , Cordes Stefan , Grice Max Z. , Fan Xing , Lee Byung-Chul , Aljanahi Aisha A. , Hong So Gun , Vaughan Kelli L. , Mattison Julie A. , Kohama Steven G. , Fabre Margarete A. , Uchida Naoya , Demirci Selami , Corat Marcus A.F. , Métais Jean-Yves , Calvo Katherine R. , Buscarlet Manuel , Natanson Hannah , McGraw Kathy L. , List Alan F. , Busque Lambert , Tisdale John F. , Vassiliou George S. , Yu Kyung-Rok , Dunbar Cynthia E.
Published: June 2022

Individuals with age-related clonal hematopoiesis (CH) are at greater risk for hematologic malignancies and cardiovascular diseases. However, predictive preclinical animal models to recapitulate the spectrum of human CH are lacking. Through error-corrected sequencing of 56 human CH/myeloid malignancy genes, we identified natural CH driver mutations in aged rhesus macaques matching genes somatically mutated in human CH, with DNMT3A mutations being the most frequent. A CH model in young adult macaques was generated via autologous transplantation of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9–mediated gene-edited hematopoietic stem and progenitor cells (HSPCs), targeting the top human CH genes with loss-of-function (LOF) mutations. Long-term follow-up revealed reproducible and significant expansion of multiple HSPC clones with heterozygous TET2 LOF mutations, compared with minimal expansion of clones bearing other mutations. Although the blood counts of these CH macaques were normal, their bone marrows were hypercellular and myeloid-predominant. TET2-disrupted myeloid colony-forming units isolated from these animals showed a distinct hyperinflammatory gene expression profile compared with wild type. In addition, mature macrophages purified from the CH macaques showed elevated NLRP3 inflammasome activity and increased interleukin-1β (IL-1β) and IL-6 production. The model was used to test the impact of IL-6 blockage by tocilizumab, documenting a slowing of TET2-mutated expansion, suggesting that interruption of the IL-6 axis may remove the selective advantage of mutant HSPCs. These findings provide a model for examining the pathophysiology of CH and give insights into potential therapeutic interventions.
Gradient Annealing as a New Strategy to Fabricate Gradient Nanoparticle Array on Microwires
Authors: Chen Anqi , Lv You , Wu Yanyan , Zhu Yuan
Published: June 2022

Creating gradients of nanostructure on the surface has found broad applications such as enhanced optical spectroscopy, optical storage of information, and broadband solar energy harvesting. Here, a facile strategy is presented for fabricating gradient nanoparticle arrays with tunable size. It takes a ZnO:Ga microwire as the starting material, and the Ga3+ doping gradient along the microwire is induced by the high voltage applied. Such a doping gradient facilitates the formation of a temperature gradient in a Joule heating process. And this temperature gradient produced by this technique can be as high as 800 °C/mm, which could be later used for gradient annealing of thin metal films. After annealing, the thin metal films turn to gradient nanoparticle arrays. The obtained gradient nanoparticle arrays are confirmed effective in multi-wavelength surface enhanced Raman scattering enhancement.
Early donepezil monotherapy or combination with metoprolol significantly prevents subsequent chronic heart failure in rats with reperfused myocardial infarction
Authors: Li Meihua , Zheng Can , Kawada Toru , Uemura Kazunori , Inagaki Masashi , Saku Keita , Sugimachi Masaru
Published: June 2022

Despite the presence of clinical guidelines recommending that β-blocker treatment be initiated early after reperfused myocardial infarction (RMI), acute myocardial infarction remains a leading cause of chronic heart failure (CHF). In this study, we compared the effects of donepezil, metoprolol, and their combination on the progression of cardiac remodeling in rats with RMI. The animals were randomly assigned to untreated (UT), donepezil-treated (DT), metoprolol-treated (MT), and a combination of donepezil and metoprolol (DMT) groups. On day 8 after surgery, compared to the UT, the DT and DMT significantly improved myocardial salvage, owing to the suppression of macrophage infiltration and apoptosis. After the 10-week treatment, the DT and DMT exhibited decreased heart rate, reduced myocardial infarct size, attenuated cardiac dysfunction, and decreased plasma levels of brain natriuretic peptide and catecholamine, thereby preventing subsequent CHF. These results suggest that donepezil monotherapy or combined therapy with β-blocker may be an alternative pharmacotherapy post-RMI.
Explainable deep drug–target representations for binding affinity prediction
Authors: Monteiro Nelson R. C. , Simões Carlos J. V. , Ávila Henrique V. , Abbasi Maryam , Oliveira José L. , Arrais Joel P.
Published: June 2022

Background

Several computational advances have been achieved in the drug discovery field, promoting the identification of novel drug–target interactions and new leads. However, most of these methodologies have been overlooking the importance of providing explanations to the decision-making process of deep learning architectures. In this research study, we explore the reliability of convolutional neural networks (CNNs) at identifying relevant regions for binding, specifically binding sites and motifs, and the significance of the deep representations extracted by providing explanations to the model’s decisions based on the identification of the input regions that contributed the most to the prediction. We make use of an end-to-end deep learning architecture to predict binding affinity, where CNNs are exploited in their capacity to automatically identify and extract discriminating deep representations from 1D sequential and structural data.

Results

The results demonstrate the effectiveness of the deep representations extracted from CNNs in the prediction of drug–target interactions. CNNs were found to identify and extract features from regions relevant for the interaction, where the weight associated with these spots was in the range of those with the highest positive influence given by the CNNs in the prediction. The end-to-end deep learning model achieved the highest performance both in the prediction of the binding affinity and on the ability to correctly distinguish the interaction strength rank order when compared to baseline approaches.

Conclusions

This research study validates the potential applicability of an end-to-end deep learning architecture in the context of drug discovery beyond the confined space of proteins and ligands with determined 3D structure. Furthermore, it shows the reliability of the deep representations extracted from the CNNs by providing explainability to the decision-making process.
A hierarchical spike-and-slab model for pan-cancer survival using pan-omic data
Authors: Samorodnitsky Sarah , Hoadley Katherine A. , Lock Eric F.
Published: June 2022

Background

Pan-omics, pan-cancer analysis has advanced our understanding of the molecular heterogeneity of cancer. However, such analyses have been limited in their ability to use information from multiple sources of data (e.g., omics platforms) and multiple sample sets (e.g., cancer types) to predict clinical outcomes. We address the issue of prediction across multiple high-dimensional sources of data and sample sets by using molecular patterns identified by BIDIFAC+, a method for integrative dimension reduction of bidimensionally-linked matrices, in a Bayesian hierarchical model. Our model performs variable selection through spike-and-slab priors that borrow information across clustered data. We use this model to predict overall patient survival from the Cancer Genome Atlas with data from 29 cancer types and 4 omics sources and use simulations to characterize the performance of the hierarchical spike-and-slab prior.

Results

We found that molecular patterns shared across all or most cancers were largely not predictive of survival. However, our model selected patterns unique to subsets of cancers that differentiate clinical tumor subtypes with markedly different survival outcomes. Some of these subtypes were previously established, such as subtypes of uterine corpus endometrial carcinoma, while others may be novel, such as subtypes within a set of kidney carcinomas. Through simulations, we found that the hierarchical spike-and-slab prior performs best in terms of variable selection accuracy and predictive power when borrowing information is advantageous, but also offers competitive performance when it is not.

Conclusions

We address the issue of prediction across multiple sources of data by using results from BIDIFAC+ in a Bayesian hierarchical model for overall patient survival. By incorporating spike-and-slab priors that borrow information across cancers, we identified molecular patterns that distinguish clinical tumor subtypes within a single cancer and within a group of cancers. We also corroborate the flexibility and performance of using spike-and-slab priors as a Bayesian variable selection approach.
Benchmarking imputation methods for network inference using a novel method of synthetic scRNA-seq data generation
Authors: Lasri Ayoub , Shahrezaei Vahid , Sturrock Marc
Published: June 2022

Background

Single cell RNA-sequencing (scRNA-seq) has very rapidly become the new workhorse of modern biology providing an unprecedented global view on cellular diversity and heterogeneity. In particular, the structure of gene-gene expression correlation contains information on the underlying gene regulatory networks. However, interpretation of scRNA-seq data is challenging due to specific experimental error and biases that are unique to this kind of data including drop-out (or technical zeros).

Methods

To deal with this problem several methods for imputation of zeros for scRNA-seq have been developed. However, it is not clear how these processing steps affect inference of genetic networks from single cell data. Here, we introduce Biomodelling.jl, a tool for generation of synthetic scRNA-seq data using multiscale modelling of stochastic gene regulatory networks in growing and dividing cells.

Results

Our tool produces realistic transcription data with a known ground truth network topology that can be used to benchmark different approaches for gene regulatory network inference. Using this tool we investigate the impact of different imputation methods on the performance of several network inference algorithms.

Conclusions

Biomodelling.jl provides a versatile and useful tool for future development and benchmarking of network inference approaches using scRNA-seq data.
Genetic diversity and connectivity of chemosynthetic cold seep mussels from the U.S. Atlantic margin
Authors: DeLeo Danielle M. , Morrison Cheryl L. , Sei Makiri , Salamone Veronica , Demopoulos Amanda W. J. , Quattrini Andrea M.
Published: June 2022

Background

Deep-sea mussels in the subfamily Bathymodiolinae have unique adaptations to colonize hydrothermal-vent and cold-seep environments throughout the world ocean. These invertebrates function as important ecosystem engineers, creating heterogeneous habitat and promoting biodiversity in the deep sea. Despite their ecological significance, efforts to assess the diversity and connectivity of this group are extremely limited. Here, we present the first genomic-scale diversity assessments of the recently discovered bathymodioline cold-seep communities along the U.S. Atlantic margin, dominated by Gigantidas childressi and Bathymodiolus heckerae.

Results

A Restriction-site Associated DNA Sequencing (RADSeq) approach was used on 177 bathymodiolines to examine genetic diversity and population structure within and between seep sites. Assessments of genetic differentiation using single-nucleotide polymorphism (SNP) data revealed high gene flow among sites, with the shallower and more northern sites serving as source populations for deeper occurring G. childressi. No evidence was found for genetic diversification across depth in G. childressi, likely due to their high dispersal capabilities. Kinship analyses indicated a high degree of relatedness among individuals, and at least 10–20% of local recruits within a particular site. We also discovered candidate adaptive loci in G. childressi and B. heckerae that suggest differences in developmental processes and depth-related and metabolic adaptations to chemosynthetic environments.

Conclusions

These results highlight putative source communities for an important ecosystem engineer in the deep sea that may be considered in future conservation efforts. Our results also provide clues into species-specific adaptations that enable survival and potential speciation within chemosynthetic ecosystems.
Isolation of nematophagous fungi from soil samples collected from three different agro-ecologies of Ethiopia
Authors: Berhanu Maradona , Waktole Hika , Mamo Gezahegne , Terefe Getachew
Published: June 2022

Background

Several species of nematophagous fungi exist in nature that can capture and kill nematodes as natural predators of soil-dwelling worms. These are important in agriculture and animal husbandry as biological control agents. The diversity of nematophagous fungi found from soil had not been studied in Ethiopia.

Objective

This study aimed to isolate Nematophagous Fungi from Soil Samples Collected From three Different Agro-Ecologies of Ethiopia.

Methods

Cross-sectional study was conducted and samples were collected from three different agro-climatic zones of Ethiopia; Debre-Berhan (highland), Bishoftu (mid-altitude), and Awash (lowland). Twenty-seven soil samples were randomly taken from each of the three different agro-ecological climates (9 from each agro-ecological climatic zone). For each study site, samples were collected from the soil of decomposed animal feces/dung, agricultural/farmlands, and forest lands in triplicates.

Results

The present study disclosed that nematophagous fungi were widespread from the study area. A total of 33 species of nematophagous fungi belonging to four genera, Arthrobotryes, Paecilomyces, Monacrosporium, and Harposporium were identified. Arthrobotrys were the most commonly isolated genera followed by Paecilomyces. The six identified species were Arthrobotrys oligospora, Paecilomyces lilacinus, Arthrobotryes dactyloides, Monacosporum eudermatum, Harposporium helicoides, and Monacosporum cionopagum.

Conclusion

This study indicated that Arthrobothryes oligospora was the most common species in Bishoftu and Awash whereas. In Debre-Berhan, Paecilomyces lilacinus was the most prevalent species. Monacosporum cionapagum was not isolated from dung soil and agricultural soil whereas Harposporium helicoides and Arthrobothryes dactyloides were not found from dung and forest soil respectively.
Predictive value of LDL/HDL ratio in coronary atherosclerotic heart disease
Authors: Sun Ting , Chen Mengyun , Shen Huanhuan , PingYin  , Fan Li , Chen Xin , Wu Jun , Xu Zuojun , Zhang Junfeng
Published: June 2022

Background

Dyslipidemia is one of independent risk factors for coronary atherosclerotic heart disease (CAHD). We determined whether the LDL/HDL ratio is better than LDL-C or HDL-C alone in predicting the severity of CAHD.

Methods

We performed a retrospective study of 1351 patients with myocardial ischemia who underwent coronary angiography between January 2018 and December 2019 in Shanghai Ninth People’s Hospital. Spearman correlation analysis, logistic regression model, Cox proportional hazards model and multicollinearity were used to evaluate LDL/HDL ratio for predicting CAHD severity compared to LDL-C or HDL-C alone.

Results

Higher LDL/HDL ratio was seen in CAHD patients than controls (2.94 ± 1.06 vs 2.36 ± 0.78, P < 0.05). LDL/HDL ratio was significantly associated with the severity of coronary vascular stenosis. The area under the ROC curve of LDL-C, HDL-C, LDL/HDL ratio used to predict CAHD are 0.574 (95% CI 0.547–0.600, P < 0.001), 0.625 (95% CI 0.598–0.651, P < 0.001), 0.668 (95% CI 0.639–0.697, P = 0.000), respectively. The cut-off value of LDL/HDL ratio is 2.517, and the sensitivity and specificity are 65% and 61%, respectively. LDL/HDL ratio was related to the prevalence of CAHD and the odds ratio (OR) was 2.39 [95% confidence interval (CI) 1.698–2.593, P = 0.00] in multicollinearity regression model.

Conclusion

LDL/HDL ratio may become a better predictor of CAHD severity, compared to LDL-C or HDL-C.
Severe small intestinal bacterial overgrowth syndrome after jejunal feeding requiring surgical intervention: a case report and review of the literature
Authors: Aboona Majd B. , Wong Tina W. , Del Prado Paul R. , Paley Keith , Goldberg Ross F. , Weimer Samuel , Dave Harikrishna , Hobohm Dan , Smith Adam
Published: June 2022

Background

Small intestinal bacterial overgrowth (SIBO) is a condition of unknown prevalence characterized by an excessive amount of bacteria in the small bowel, typically resulting in vague gastrointestinal symptoms with bloating being most commonly reported. Here we describe a severe case of SIBO leading to small bowel necrosis requiring surgical intervention.

Case presentation

A 55-year-old Hispanic female with gastric outlet obstruction secondary to a newly diagnosed gastric adenocarcinoma, receiving neoadjuvant chemotherapy, developed bloody gastrostomy output and rapidly progressing nausea and abdominal distention 3 days after jejunostomy tube placement and initiation of jejunal enteral nutrition. Imaging revealed diffuse pneumatosis and portal venous gas. Surgical exploration confirmed segmental bowel necrosis requiring resection. Histologic findings were consistent with SIBO.

Conclusions

Presentation of severe SIBO in the setting of intestinal stasis secondary to gastric outlet after initiation of enteral feeds is a rare phenomenon. Early recognition and diagnosis of SIBO is critical in minimizing patient morbidity and mortality.
Molecular evaluation of hepatitis B virus infection and predominant mutations of pre-core, basal core promoter and S regions in an Iranian population with type 2 diabetes mellitus: a case–control study
Authors: Farshadpour Fatemeh , Taherkhani Reza , Saberi Fatemeh
Published: June 2022

Background

This study was designed to evaluate the prevalence, genotypic patterns, and predominant mutations of hepatitis B virus (HBV) infection among diabetic patients.

Methods

Serum samples were obtained from 733 patients with type 2 diabetes mellitus and 782 non-diabetic controls. The presence of HBsAg and HBcAb was determined by ELISA. Nested PCR, targeting S and pre-core regions of the HBV genome, followed by sequencing was carried out to determine HBV genotypes and predominant mutations in the S, basal core promoter (BCP), and pre-core regions of the HBV genome.

Results

Of 733 diabetic patients, 94 cases (12.82%) were positive for HBcAb, 28 cases (3.82%) were positive for HBsAg, and 19 cases (2.59%) had HBV-DNA with genotype D, sub-genotype D1/D3 and subtype ayw2. An occult HBV infection was found in one of the HBV DNA-positive samples, which was positive for HBcAb but negative for HBsAg. P120T/G145R, G1896A/G1899A, and A1762T/G1764T were the most frequent point substitution mutations detected in the S, pre-core, and BCP regions of the HBV genome, respectively. P120T and G145R mutations were associated with low levels or undetectable levels of HBsAg in serum. Therefore, routine tests based on HBsAg detection cannot detect HBsAg-negative infected patients.

Conclusions

Relatively high prevalence of HBV infection was found in diabetic patients, while all of the HBV-infected patients were unaware of their infection. Therefore, screening for HBV infection should be included in the management program of diabetes for timely diagnosis and treatment of infected but asymptomatic patients.
Neuropsychiatric lupus erythematosus with neurogenic pulmonary edema and anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor limbic encephalitis: a case report
Authors: Li Rongqi , Wang Yingai , Wu Xiuhua , Wang Junping , Wei Wei , Li Xin
Published: June 2022

Background

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune inflammatory disease predominantly found in women of child-bearing age. Neurogenic pulmonary edema (NPE) is a recalcitrant complication that occurs after injury to the central nervous system and has an acute onset and rapid progression. Limbic encephalitis is an inflammatory encephalopathy caused by viruses, immune responses, or other factors involving the limbic system. NPE caused by SLE is rare.

Case presentation

Here, we report a case of a 21-year-old woman with SLE who experienced five episodes of generalized tonic–clonic seizure after headache and dyspnea. Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) 2 antibody was tested positive in the serum and cerebrospinal fluid. Electrocardiography (EEG) indicated paroxysmal or sporadic medium amplitude theta activity. In addition, chest computed tomography (CT) showed multiple diffuse consolidations and ground-glass opacities. We finally considered a diagnosis of NPE and AMPAR limbic encephalitis. The patient's symptoms improved obviously after methylprednisolone pulse therapy and antiepileptic treatment.

Conclusions

NPE can be a complication of neuropsychiatric lupus erythematosus (NPSLE). AMPAR2 antibodies may be produced in NPSLE patients, especially in those with high polyclonal IgG antibody titers. More basic and clinical studies are required to confirm these observations and elucidate the pathogenicity of encephalitis-related autoantibodies in SLE patients.
Frequency and duration of extreme hypoxemic and hyperoxemic episodes during manual and automatic oxygen control in preterm infants: a retrospective cohort analysis from randomized studies
Authors: Bachman Thomas E. , Onland Wes , van Kaam Anton H. , Roubik Karel , Hummler Helmut D. , Lal Mithilesh , Lista Gianluca , Fajardo Carlos A.
Published: June 2022

Objective

Neonatal exposure to episodic hypoxemia and hyperoxemia is highly relevant to outcomes. Our goal was to investigate the differences in the frequency and duration of extreme low and high SpO2 episodes between automated and manual inspired oxygen control.

Design

Post-hoc analysis of a cohort from prospective randomized cross-over studies.

Setting

Seven tertiary care neonatal intensive care units.

Patients

Fifty-eight very preterm neonates (32 or less weeks PMA) receiving respiratory support and supplemental oxygen participating in an automated versus manual oxygen control cross-over trial.

Main measures

Extreme hypoxemia was defined as a SpO2 < 80%, extreme hyperoxemia as a SpO2 > 98%. Episode duration was categorized as < 5 seconds, between 5 to < 30 seconds, 30 to < 60 seconds, 60 to < 120 seconds, and 120 seconds or longer.

Results

The infants were of a median postmenstrual age of 29 (28-31) weeks, receiving a median FiO2 of 0.28 (0.25-0.32) with mostly receiving non-invasive respiratory support (83%). While most of the episodes were less than 30 seconds, longer episodes had a marked effect on total time exposure to extremes. The time differences in each of the three longest durations episodes (30, 60, and 120 seconds) were significantly less during automated than during manual control (p < 0.001). Nearly two-third of the reduction of total time spent at the extremes between automated and manual control (3.8 to 2.1% for < 80% SpO2 and 3.0 to 1.6% for > 98% SpO2) was seen in the episodes of at least 60 seconds.

Conclusions

This study shows that the majority of episodes preterm infants spent in SpO2 extremes are of short duration regardless of manual or automated control. However, the infrequent longer episodes not only contribute the most to the total exposure, but also their reduction in frequency to the improvement associated with automated control.