bluuebunny/crossref_metadata_2025 huggingface dataset:
Membrane remodeling due to mixture of multiple types of curvature proteins
Authors: Kumar Gaurav , Srivastava Anand
Published: October 2021

We present an extension of the Monte Carlo based mesoscopic membrane model, where the membrane is represented as a dynamically triangulated surface and the proteins are modeled as anisotropic inclusions formulated as in-plane nematic field variables adhering to the deformable elastic sheet. In the extended model, we have augmented the Hamiltonian to study membrane deformation due to a mixture of multiple types of curvature generating proteins. This feature opens the door for understanding how multiple kinds of curvature-generating proteins may be working in a coordinated manner to induce desired membrane morphologies. For example, among other things, we study membrane deformations and tubulation due to a mixture of positive and negative curvature proteins as mimics of various proteins from BAR domain family. We also study the effect membrane anisotropy, which manifest as membrane localization and differential binding affinity of a given curvature protein, leading to insights into the tightly regulated cargo sorting and transport processes. Our simulation results show different morphology of deformed vesicles that depend on the curvatures and number of the participating proteins as well as on the protein-protein and membrane-proteins interactions.

Significance

Membrane remodeling requires highly orchestrated interactions between several types of lipids and curvature proteins. Experimentally probing the membrane deformation intermediates is non-trivial. For example, it is not known exactly how two or more different kinds of BAR domain proteins work in concert to induce and stabilize certain membrane curvatures. In this work, we use mesoscopic continuum modeling and explore the factors that induce and stabilize a range of membrane deformation due to a mixture of positive and negative curvature proteins.
Identification and validation of a non-genetically encoded vulnerability to XPO1 inhibition in malignant rhabdoid tumors – expanding patient-driven discovery beyond the N-of-1
Authors: Marks Lianna J. , Diolaiti Daniel , Mundi Prabhjot , Gaviria Ervin S. , Rainey Allison R. , Yamashiro Darrell J. , Fazlollahi Ladan , Hosoi Hajime , Katsumi Yoshiki , Kuwahara Yasumichi , Dela Cruz Filemon S. , Califano Andrea , Kung Andrew L.
Published: October 2021

Malignant rhabdoid tumors (MRTs) are rare, aggressive pediatric solid tumors, characterized by a 22q11 deletion that inactivates the SMARCB1 gene. Outcomes remain poor despite multimodality treatment. MRTs are among the most genomically stable cancers and lack therapeutically targetable genetic mutations. We utilized metaVIPER, an extension of the Virtual Inference of Protein-activity by Enriched Regulon (VIPER) algorithm, to computationally infer activated druggable proteins in the tumor of an eight month old patient and then expanded the analysis to TCGA and TARGET cohorts.In vitrostudies were performed on a panel of MRT and atypical teratoid/rhabdoid tumor cell lines. Two patient-derived xenograft (PDX) mouse models of MRT were used forin vivoefficacy studies. MetaVIPER analysis from the patient’s tumor identified significantly high inferred activity of nuclear export protein Exportin-1 (XPO1). Expanded metaVIPER analysis of TCGA and TARGET cohorts revealed consistent elevations in XPO1 inferred activity in MRTs compared to other cancer types. All MRT cell lines demonstrated baseline activation of XPO1. MRT cell lines demonstratedin vitrosensitivity to the XPO1 inhibitor, selinexor which led to cell cycle arrest and induction of apoptosis. Targeted inhibition of XPO1 in patient-derived xenograft models of MRT using selinexor resulted in abrogation of tumor growth. Selinexor demonstrates efficacy in preclinical models of MRT. These results support investigation of selinexor in a phase II study in children with MRT and illustrate the importance of an N-of-1 approach in driving discovery beyond the single patient.

Statement of Translational Relevance

We describe the patient-driven discovery of XPO1 activation as a non-genetically encoded vulnerability in MRTs. The application of metaVIPER analysis to tumors lacking actionable oncogenic alterations represents a novel approach for identifying potential therapeutic targets and biomarkers of response. Our preclinical validation of selinexor confirms XPO1 inhibition as a promising therapeutic strategy for the treatment of MRT.
Mechanistic Model of Telomere Length Homeostasis in Yeast
Authors: Singh Ghanendra , Sriram K.
Published: October 2021

Cells maintain homeostatic telomere length, and this homeostatic disruption leads to various types of diseases. Presently, it is not clear how telomeres achieve homeostasis. One of the prevailing hypotheses is a protein-counting model with a built-in sensor mechanism that counts proteins that directly regulate the telomeric length. However, it does not explain telomere length regulation at the mechanistic level. Here, we present a mathematical model based on the underlying molecular mechanisms of length regulation needed to establish telomere length homeostasis in yeast. We perform both deterministic and stochastic simulations to validate the models with the experimental data of Teixeira et al., rate-balance plot, and phase plane analysis to understand the nature of dynamics exhibited by the models. For global analysis, we constructed bifurcation diagrams. The model explains the role of negative and positive feedback loops and a delay between telomerase and telomere-bound proteins, leading to oscillations in telomere length. We map these in-silico results to Teixeira’s proposition of telomeres making a transition between extendible and non-extendible states.
Dual medial prefrontal cortex and hippocampus projecting neurons in the paraventricular nucleus of the thalamus
Authors: Viena Tatiana D. , Rasch Gabriela E. , Allen Timothy A.
Published: October 2021

The paraventricular nucleus (PVT) of the midline thalamus is a critical higher-order cortico-thalamo-cortical integration site that plays a critical role in various behaviors including reward seeking, cue saliency, and emotional memory. Anatomical studies have shown that PVT projects to both medial prefrontal cortex (mPFC) and hippocampus (HC). However, dual mPFC-HC projecting neurons which could serve a role in synchronizing mPFC and HC activity during PVT-dependent behaviors, have not been explored. Here we used a dual retrograde adenoassociated virus (AAV) tracing approach to characterize the location and proportion of different projection populations that send collaterals to mPFC and/or ventral hippocampus (vHC). Additionally, we examined the distribution of calcium binding proteins calretinin (CR) and calbindin (CB) with respect to these projection populations PVT. We found that PVT contains separate populations of cells that project to mPFC, vHC, and those that innervate both regions. Interestingly, dual mPFC-HC projecting cells expressed neither CR or CB. Topographically, mPFC- and vHC-projecting CB+ and CR+ cells clustered around dual projecting neurons in PVT. These results are consistent with the features of dual mPFC-vHC projecting cells in the nucleus reuniens (RE) and suggestive of a functional mPFC-PVT-vHC system that may support mPFC-vHC interactions in PVT-dependent behaviors.
BioKIT: a versatile toolkit for processing and analyzing diverse types of sequence data
Authors: Steenwyk Jacob L. , Buida Thomas J. , Gonçalves Carla , Goltz Dayna C. , Morales Grace , Mead Matthew E. , LaBella Abigail L. , Chavez Christina M. , Schmitz Jonathan E. , Hadjifrangiskou Maria , Li Yuanning , Rokas Antonis
Published: October 2021

Bioinformatic analysis—such as genome assembly quality assessment, alignment summary statistics, relative synonymous codon usage, paired-end aware quality trimming and filtering of sequencing reads, file format conversion, and processing and analysis—is integrated into diverse disciplines in the biological sciences. Several command-line pieces of software have been developed to conduct some of these individual analyses; however, the lack of a unified toolkit that conducts all these analyses can be a barrier in workflows. To address this obstacle, we introduce BioKIT, a versatile toolkit for the UNIX shell environment with 40 functions, several of which were community-sourced, that conduct routine and novel processing and analysis of genome assemblies, multiple sequence alignments, coding sequences, sequencing data, and more. To demonstrate the utility of BioKIT, we assessed the quality and characteristics of 901 eukaryotic genome assemblies, calculated alignment summary statistics for 10 phylogenomic data matrices, determined relative synonymous codon usage across 171 fungal genomes including those that use alternative genetic codes, and demonstrate that a novel metric, gene-wise relative synonymous codon usage, can accurately estimate gene-wise codon optimization. BioKIT will be helpful in facilitating and streamlining sequence analysis workflows. BioKIT is freely available under the MIT license from GitHub (https://github.com/JLSteenwyk/BioKIT), PyPi (https://pypi.org/project/jlsteenwykbiokit/), and the Anaconda Cloud (https://anaconda.org/jlsteenwyk/jlsteenwyk-biokit). Documentation, user tutorials, and instructions for requesting new features are available online (https://jlsteenwyk.com/BioKIT).
Cross-sectoral process modelling for smart city development
Authors: Dessai Asmita , Javidroozi Vahid
Published: October 2021

Purpose

Integration of city systems is needed to provide flexibility, agility and access to real-time information for the creation and delivery of efficient services in a smart and sustainable city. Consequently, City Process Modelling (CPMo) becomes an essential element of connecting various city sectors. However, to date, there has been limited research on the requirements of an ideal CPMo approach and the usefulness of available Business Process Modelling (BPMo) approaches. This research develops a framework for CPMo to guide smart city developers when modelling city processes.

Design/methodology/approach

Data from literature analysis was gathered to derive capabilities of existing BPMo techniques. Then, semi-structured interviews were conducted to thematically and qualitatively explore the requirements, challenges and success factors of CPMo.

Findings

The interview findings offered 17 requirements to be addressed by a CPMo approach, along with several challenges and success factors to be considered when implementing CPMo approaches. Then, the paper presents the results of mapping these requirements against 12 existing BPMo capabilities, identified from the literature, concluding that a significant number of requirements (which are mainly related to inputs and visualisation) have been left unfulfilled by existing BPMo approaches. Hence, developing an innovative CPMo approach is necessary to address the components of unfulfilled requirements.

Originality/value

The innovative framework presented in this paper justifies the CPMo requirements, which are unexplored in existing SCD frameworks. Moreover, it will act as a guide for smart city developers, to model cross-sectoral city processes, helping them progress their SCD road map and make their cities smart.
Social and economic empowerment of women through financial inclusion: empirical evidence from India
Authors: Pal Mukesh , Gupta Hemant , Joshi Yogesh C.
Published: October 2021

Purpose

Women empowerment becomes an important policy discussion in development economics and modernization theory. The empowerment of women can lead to an increase in the quality viz-a-viz the capacity of human resources accessible for economic development. The purpose of this study is to evidence the impact of social and economic dimensions on women empowerment through financial inclusion in rural India.

Design/methodology/approach

To reveal the research objective, the study has utilized a primary survey of women respondents from the Gujarat state of India by a simple random sampling method and applied a logistic regression approach to identify the relationship between the need of a bank account (determinant of financial inclusion) as a dependent variable and social and economic dimensions of women empowerment such as earning status, participation in financial decision-making, recipient of social welfare schemes and perception towards the safety of saving as independent variables.

Findings

The results of this study show that earning status, participation in financial decision-making at household level and recipient of social welfare schemes by women have a significant impact on women empowerment through financial inclusion; however, safety of their savings is observed as an insignificant variable, yet the odd value is very high (2.437) in the present study.

Originality/value

The present study is the first of its kind to examine the social and economic status of women and its impact on their requirement of a formal bank account for the overall empowerment of women in rural India.
Student learning outcomes and online engagement in time of crisis: the role of e-learning system usability and teacher behavior
Authors: Dahleez Khalid Abed , El-Saleh Ayman A. , Al Alawi Abrar Mohammed , Abdel Fattah Fadi Abdel Muniem
Published: October 2021

Purpose

This research explores the effect of e-learning Moodle-based system usability on students' learning outcomes with the possible intervening role of teacher's behavior and online engagement.

Design/methodology/approach

In this research, the authors followed a quantitative methodology and a deductive research approach. Data were collected from 433 students at different study levels and academic specializations in higher education institutions (HEIs) in Oman. The data have been analyzed using partial least squares structural equation modeling via Smart-PLS.

Findings

The findings of this research show that e-learning system usability affects students' learning outcomes. Moreover, the relationship between these two variables is mediated by teacher behavior and students' online engagement.

Originality/value

This study is important as it adds to the understanding of the role of e-learning system usability in predicting student outcomes. From practical perspectives, especially during the spread of the COVID-19 pandemic, this study also helps practitioners at private HEIs use e-learning systems more efficiently and effectively to improve students' engagement and learning outcomes.
Does flexible work arrangements decrease or increase turnover intention? A comparison between the social exchange theory and border theory
Authors: Tsen Mung Khie , Gu Manli , Tan Chee Meng , Goh See Kwong
Published: October 2021

Purpose

More companies embrace flexible work arrangements (FWA) as one of their employee retention strategies, yet its effectiveness is not consistent. Generally, past researchers use the social exchange theory to explain how FWA lowers turnover intention, while the rest adopts the border theory to justify why FWA can be ineffective. Here, the authors compare the competing theories for the first time to differentiate the theoretical reasoning of three forms of FWA (flex time, flex leave and homeworking). Two mediators (organisational commitment and work−family conflicts) are chosen to represent the mechanism of each theory.

Design/methodology/approach

The authors employ the latest wave of the International Social Survey Program (ISSP) Work Orientation Module from 2015. Based on nationally representative data from 35 nations and 17,604 participants, the authors employed simple mediation and parallel double-mediation models via bootstrapping procedures to investigate the theoretical reasoning behind each FWA.

Findings

The results indicate that organisational commitment and work−family conflicts as significant mediators in all models, supporting both theories. The authors first tested each mediator in separated models. In models concerning the social exchange theory, all FWA lead to increased organisational commitment before lowering turnover intention, implying the beneficial outcomes of FWA. However, findings also support the border theory's perspective where flex time and homeworking increase turnover intention through heightened work−family conflicts. The parallel double-mediation further suggests that all three FWA forms have their unique theoretical framework, impacting turnover intention differently.

Originality/value

Both the social exchange theory and border theory are well-developed theories but grounded on different theoretical reasoning. This is the first paper that compares both theoretical perspectives in the context of FWA. It offers a new perspective in explaining the inconclusive effectiveness of FWA and provides future researchers a more integrated interpretation and prediction of FWA's impact on turnover intention.
To buy or not to buy, that is the question: understanding the determinants of the urge to buy impulsively on Instagram Commerce
Authors: Herzallah Doaa , Muñoz Leiva Francisco , Liébana-Cabanillas Francisco
Published: October 2021

Purpose

Throughout 2020, especially under the lockdown measures, there was a significant surge in e-commerce and social commerce (s-commerce), with numerous people all over the world adopting and using commerce platforms on social media and other websites to buy desired products and services quickly and easily. Instagram Commerce is a new, cutting-edge social commerce platform. This research aims to explore the positive influence of the measures adopted during summer 2020 on Spanish s-commerce users' urge to buy impulsively.

Design/methodology/approach

Drawing on the stimulus–organism–response (S–O–R) theoretical framework, this study postulates and tests a model to help understand the behaviour of Spanish users towards social commerce, specifically Instagram Commerce. To accomplish this purpose, an SEM analysis is performed using a sample of 251 respondents.

Findings

Generally speaking, the findings obtained in the present study serve to expand and enhance the scientific literature on one of the latest determinants affecting social networks and online commerce.

Originality/value

This research is innovative due to the research background study that is carried out to analyse the urge to buy impulsively.
Diatomaceous earth aggregates based composite masonry blocks for bushfire resistance
Authors: Ariyaratne Indunil Erandi , Ariyanayagam Anthony , Mahendran Mahen
Published: October 2021

Purpose

This paper presents the details of a research study on developing composite masonry blocks using two types of mixes, conventional and lightweight mix, to enhance their fire/bushfire resistance and residual compressive strength.

Design/methodology/approach

Composite masonry blocks (390 × 190 × 90 mm) were fabricated using conventional cement–sand mix as the outer layer and lightweight cement–sand–diatomite mix as the inner layer. Material properties were determined, and all the mixes were proportioned by the absolute volume method. After 28 days of curing, density tests, compression tests before and after fire exposure and fire resistance tests of the developed blocks were conducted, and the results were compared with those of conventional cement–sand and cement–sand–diatomite blocks.

Findings

Developed composite blocks satisfy density and compressive strength requirements for loadbearing lightweight solid masonry units. Fire resistance of the composite block is –/120/120, and no cracks appeared on the ambient side surface of the block after 3 h of fire exposure. Residual strength of the composite block is higher compared to cement–sand and cement–sand–diatomite blocks and satisfies the loadbearing solid masonry unit strength requirements.

Practical implications

Composite block developed in this research can be suggested as a suitable loadbearing lightweight solid masonry block for several applications in buildings in bushfire prone areas.

Originality/value

Limited studies are available for composite masonry blocks in relation to their fire resistance and residual strength.
After-hours work-related technology use and individuals' deviance: the role of interruption overload, psychological transition and task closure
Authors: Khalid Junaid , Weng Qingxiong Derek , Luqman Adeel , Rasheed Muhammad Imran , Hina Maryam
Published: October 2021

Purpose

The information and communication technologies have made it progressively practical for employees to remain associated with work, even when they are not in the workplace. However, prior studies have provided very little understanding of the implications for the deviant behavior aspect. The current study aims to investigate the association between after-hours work-related technology usage and interpersonal, organizational and nonwork deviance through psychological transition, interruption overload and task closure. The authors draw upon the theory of conservation of resource (COR) to examine the research model.

Design/methodology/approach

The primary data for the study has been collected in two waves from the sample of 318 employees who were working in diverse organizations in the Anhui province of the People's Republic of China for empirical testing of the authors’ research model.

Findings

This study's findings have revealed the positive association of after-hour work-related technology use with individuals' deviance in its entire three forms through psychological transition and interruption overload and have negative associations with all forms of deviance through task closure.

Originality/value

The significant contribution of this study is in the literature on technology use and employee outcomes, by identifying the consequences of technology use in both work (interpersonal deviance and organizational deviance) and outside work domain (nonwork deviance) and exploring the underlying mechanisms for these relationships in detail. To the best of the authors’ knowledge, this study is the first of its kind that investigates a relationship between after-hours technology use and all three kinds of deviance while exploring both the positive and negative perspectives in one study.
An acute change? Does treatment within a therapeutic community for personality disorders affect local acute service use
Authors: Pirjamali Vafa , Ivanova Daniela , Howe Andrew John
Published: October 2021

Purpose

The intensive 18-month treatment in the personality disorder (PD) therapeutic community (TC) is felt to offer improvement in many aspects of patients’ lives. This study aims to understand if the use of acute services was also affected via a service evaluation project.

Design/methodology/approach

The authors collected data from electronic records on the use of local services in the two years before, during and the two years after treatment in the TC. Specifically, the authors counted inpatient bed days, Emergency department (ED) presentations and days under home treatment team and liaison psychiatry; the authors used ANOVA to analyse the data.

Findings

The study included 25 adult service users, 17 female and 8 male, with an average age of 40. Whilst there were reductions in the use of inpatient beds and ED presentations, on analysis, these were not found statistically significant. The small size of the study is a limitation and may limit the generalisability of the findings. The study concludes there may be reductions in acute psychiatric service use during and after treatment in the TC. The findings were not statistically significant; the authors suggest larger multi-centre studies may be able to demonstrate statistical significance.

Originality/value

PD patients have a relatively high use of acute psychiatric services compared to other patient groups. The authors are not aware of any similar studies in the published literature.
Structural factors governing starch digestion and glycemic responses and how they can be modified by enzymatic approaches: A review and a guide
Authors: Korompokis Konstantinos , Verbeke Kristin , Delcour Jan A.
Published: October 2021

Starch is the most abundant glycemic carbohydrate in the human diet. Consumption of starch‐rich food products that elicit high glycemic responses has been linked to the occurrence of noncommunicable diseases such as cardiovascular disease and diabetes mellitus type II. Understanding the structural features that govern starch digestibility is a prerequisite for developing strategies to mitigate any negative health implications it may have. Here, we review the aspects of the fine molecular structure that in native, gelatinized, and gelled/retrograded starch directly impact its digestibility and thus human health. We next provide an informed guidance for lowering its digestibility by using specific enzymes tailoring its molecular and three‐dimensional supramolecular structure. We finally discuss in vivo studies of the glycemic responses to enzymatically modified starches and relevant food applications. Overall, structure–digestibility relationships provide opportunities for targeted modification of starch during food production and improving the nutritional profile of starchy foods.
A single change in the aptamer of the Lactiplantibacillus plantarum rib operon riboswitch severely impairs its regulatory activity and leads to a vitamin B2‐ overproducing phenotype
Authors: Ripa Inés , Ruiz‐Masó José Ángel , De Simone Nicola , Russo Pasquale , Spano Giuseppe , del Solar Gloria
Published: October 2021

Manufacturing of probiotics and functional foods using lactic acid bacteria (LAB) that overproduce vitamin B2 has gained growing interest due to ariboflavinosis problems affecting populations of both developing and affluent countries. Two isogenic Lactiplantibacillus plantarum strains, namely a riboflavin‐producing parental strain (UFG9) and a roseoflavin‐resistant strain (B2) that carries a mutation in the FMN‐aptamer of the potential rib operon riboswitch, were analysed for production and intra‐ and extracellular accumulation of flavins, as well as for regulation of the rib operon expression. Strain B2 accumulated in the medium one of the highest levels of riboflavin+FMN ever reported for LAB, exceeding by ~ 25 times those accumulated by UFG9. Inside the cells, concentration of FAD was similar in both strains, while that of riboflavin+FMN was ~ 8‐fold higher in B2. Mutation B2 could decrease the stability of the aptamer’s regulatory P1 helix even in the presence of the effector, thus promoting the antiterminator structure of the riboswitch ON state. Although the B2‐mutant riboswitch showed an impaired regulatory activity, it retained partial functionality being still sensitive to the effector. The extraordinary capacity of strain B2 to produce riboflavin, together with its metabolic versatility and probiotic properties, can be exploited for manufacturing multifunctional foods.
Differential impact of prescriptive norms in the intergenerational transmission of environmental concern in a non‐Western context: Evidence from the Philippines
Authors: Aruta John Jamir Benzon R.
Published: October 2021

Despite the global nature of environmental problems and the known cultural differences in parenting practises, there is a dearth of studies that have examined the intergenerational transmission of environmental concern in non‐Western contexts. This study investigated the interplay of prescriptive norms and interdependent self‐construal in the transmission of environmental concern among 449 parent–adolescent dyads in the Philippines. The results demonstrated that the transmission of environmental concern from parents to their adolescent children was strong across the different levels of prescriptive norms, but the transmission was more pronounced among adolescents with high levels of interdependent self‐construal. The findings also showed that intergenerational transmission of environmental concern weakens at the moderate level of prescriptive norms, and even diminishes at high levels of prescriptive norms among adolescents with moderate and low interdependent self‐construal, respectively. Implications for research, parenting, education, and national campaigns and policies for environmental sustainability are discussed.
Less invasive and equivalent short‐term outcomes with simultaneous en bloc robot‐assisted radical cystectomy and laparoscopic nephroureterectomy: Comparison with conventional open radical cystectomy and nephroureterectomy
Authors: Kamei Jun , Fujisaki Akira , Saito Kimitoshi , Sugihara Toru , Ando Satoshi , Miyagawa Tomoaki , Takayama Tatsuya , Fujimura Tetsuya
Published: October 2021

Introduction

To clarify the safety and efficacy of en bloc simultaneous robot‐assisted radical cystectomy (RARC) and laparoscopic nephroureterectomy (LNU) for synchronous muscle‐invasive bladder carcinoma and upper tract urothelial carcinoma (UTUC) or UTUC of a solitary kidney, we evaluated the perioperative and short‐term outcomes of this surgical procedure compared with those of simultaneous open radical cystectomy and nephroureterectomy.

Methods

We prospectively enrolled consecutive patients receiving en bloc simultaneous RARC and LNU between December 2018 and March 2020 at two institutes. Patients’ characteristics, surgical, perioperative, and pathological outcomes and recurrence rate within 6 months were compared with a historical control receiving simultaneous open radical cystectomy and nephroureterectomy.

Results

Ten patients receiving simultaneous RARC and LNU and 17 receiving simultaneous open radical cystectomy and nephroureterectomy were included in the study. Simultaneous RARC and LNU significantly reduced bleeding volume and blood transfusion (P < .0001, P < .0001, respectively) and significantly prolonged operating time (P = .035). RARC and LNU significantly shortened hospitalization after operation (P = .003) and showed reduced tendency of postoperative complications within 30 days but not significantly (P = .25). Pathological characteristics and recurrence within 6 months were not significantly different between the two groups.

Conclusion

Our results suggested that en bloc simultaneous RARC and LNU were safer surgical procedures with equivalent short‐term oncological outcomes compared to conventional open procedures. It can be a standard minimally invasive surgical method in countries where robot‐assisted radical nephroureterectomy is inaccessible.
Risks and benefits of pediatric inguinal hernia repair: Conventional open repair vs laparoscopic percutaneous extraperitoneal closure
Authors: Kurobe Masashi , Sugihara Tetsuro , Harada Atsushi , Kaji Sayuri , Uchida Goki , Kanamori Daisuke , Baba Yuji , Hiramatsu Tomomasa , Ohashi Shinsuke , Otsuka Masahiko
Published: October 2021

Introduction

Considerable debate exists regarding the benefits of laparoscopic percutaneous extraperitoneal closure (LPEC) over conventional open repair (OR). We assessed the outcomes and feasibility of LPEC compared to OR for pediatric inguinal hernia (IH).

Methods

We retrospectively analyzed 570 children who underwent LPEC or OR. Parents decided the operative method after obtaining informed consent. Patient characteristics, operative time, complications and contralateral metachronous IH (CMIH) were compared between the groups.

Results

A total of 329 children underwent LPEC and 241 underwent OR. There was no significant difference in the incidence of recurrence or testicular ascent between the LPEC and OR groups (0.3% vs 0.4%, P = 0.825, 0.3% vs 0.8%, P = 0.391, respectively). No testicular atrophy was recognized in either group. One patient with postoperative chronic inguinal pain was recognized in each group. There was no surgical site infection (SSI) in the OR group; however, the LPEC group more frequently demonstrated umbilical port site (UPS)‐related complications, such as incisional hernia, minor deformity, granuloma formation, cellulitis and superficial SSI. Ten (4.1%) developed CMIH in OR; in contrast, no case of CMIH was experienced after LPEC (P < 0.001).

Conclusion

In conclusion, both LPEC and OR are feasible in the management of pediatric IH, because of their high success rates and low risk of complications. LPEC could be the superior procedure with respect to the prevention of CMIH. However, to maximize the merits of LPEC over OR, it is important to reduce UPS‐related complications in LPEC. A longer follow‐up is needed to assess male fertility in patients who receive LPEC.
Mechanistic insights into the pathogenesis of microtubule‐targeting agent‐induced peripheral neuropathy from pharmacogenetic and functional studies
Authors: Chua Katherina C. , El‐Haj Nura , Priotti Josefina , Kroetz Deanna L.
Published: October 2021

Chemotherapy‐induced peripheral neuropathy (CIPN) is a common dose‐limiting toxicity that affects 30%–40% of patients undergoing cancer treatment. Although multiple mechanisms of chemotherapy‐induced neurotoxicity have been described in preclinical models, these have not been translated into widely effective strategies for the prevention or treatment of CIPN. Predictive biomarkers to inform therapeutic approaches are also lacking. Recent studies have examined genetic risk factors associated with CIPN susceptibility. This review provides an overview of the clinical and pathologic features of CIPN and summarizes efforts to identify target pathways through genetic and functional studies. Structurally and mechanistically diverse chemotherapeutics are associated with CIPN; however, the current review is focused on microtubule‐targeting agents since these are the focus of most pharmacogenetic association and functional studies of CIPN. Genome‐wide pharmacogenetic association studies are useful tools to identify not only causative genes and genetic variants but also genetic networks implicated in drug response or toxicity and have been increasingly applied to investigations of CIPN. Induced pluripotent stem cell‐derived models of human sensory neurons are especially useful to understand the mechanistic significance of genomic findings. Combined genetic and functional genomic efforts to understand CIPN hold great promise for developing therapeutic approaches for its prevention and treatment.
A defense of conscientious objection: Why health is integral to the permissibility of medical refusals
Authors: Kulesa Ryan
Published: October 2021

Schuklenk, Smalling, and Savulescu put forth four conditions that delineate when conscientious objection is impermissible. Roughly, they argue for the following claim: if some practice is legal, standard, expected of a profession, and in the patient's interest, then medical professionals cannot refuse to perform the practice. In this essay, I argue that these conditions are not jointly sufficient to deny medical professionals the ability to refuse to perform procedures that detract from a patient's health. They are insufficient to bar medical refusals to perform certain practices because, even when these conditions are met, non‐health conducive practices would not be open to refusal by the physician. I provide an example of a non‐health conducive practice female genital mutilation, which meets all of the proposed conditions but, intuitively, should be open to medical refusals. As a result, I conclude that the proposed conditions are insufficient to determine when conscientious objection is impermissible. I then offer an amendment to their position by suggesting that a practice, in addition to the other four conditions, must also be health conducive in order to remove the medical professional's ability to refuse to perform the practice.
The clinical landscape of chronic graft‐versus‐host disease management in 2021
Authors: Holtzman Noa G. , Pavletic Steven Z.
Published: October 2021

Chronic graft‐versus‐host disease (cGVHD) is an important systemic complication of allogeneic haematopoietic stem cell transplantation with heterogeneous, multi‐organ involvement that can lead to increased morbidity and mortality. Despite significant advances in understanding the complex pathophysiology driving the disease, curative treatment options remain suboptimal. The past decade, however, has seen much growth in collaborative research efforts and standardization of criteria for clinical trials that have led to discovery of several new second‐line therapies in cGVHD. The key to successful cGVHD control and management includes a comprehensive and sustained multidisciplinary effort with emphasis on ancillary and supportive care for these patients. The focus of this review is to summarize the new developments in systemic, organ‐specific, and topical treatments in the management of cGVHD that emerged since the 2014 NIH consensus conference.
Extraction, chemical modification, and antioxidant activities of Daucus carota polysaccharide
Authors: Qi Kang , Xia Guangda , Huang Gangliang , Huang Hualiang
Published: October 2021

The Daucus carota polysaccharides were extracted by hot water extraction and alcohol precipitation, and the phosphorylated and carboxymethylated derivatives were prepared. Their structures were characterized by FT‐IR, NMR, and SEM. The antioxidant activities of Daucus carota polysaccharide were enhanced by phosphorylation. However, carboxymethylated Daucus carota polysaccharide was not as good as unmodified one.
Transrectal natural orifice specimen extraction in left hemicolectomy for tumours around the splenic flexure: Old wine in new bottles
Authors: Jong Bor‐Kang , Cheng Ching‐Chung , Hsu Yu‐Jen , Chern Yih‐Jong , Tsai Wen‐Sy , Hung Hsin‐Yuan , Liao Chun‐Kai , Yeh Chien‐Yu , Hsieh Pao‐Shiu , You Jeng‐Fu
Published: October 2021

Aim

Laparoscopic anterior resection with natural orifice specimen extraction (NOSE) has favourable short‐term outcomes. However, NOSE is rarely adopted for left hemicolectomy procedures. This study aimed to review the feasibility, safety and short‐term outcomes of transrectal NOSE in patients undergoing laparoscopic left hemicolectomy.

Method

All consecutive patients who underwent laparoscopic left hemicolectomy surgery with transrectal NOSE in a single institution between January 2018 and December 2020 were reviewed. Transrectal NOSE was performed with an enterotomy at the upper rectum. The specimen was brought out via a transanal endoscopic microsurgery scope inserted through the anus. A supplementary video demonstrates this technique. Surgical outcomes, including complications, postoperative short‐term recovery and the level of pain intensity, are presented.

Results

Twenty patients were reviewed. There were no immediate postoperative complications and no wound infections in these patients. The average time to tolerate a soft diet was 3.6 days, and the average postoperative hospital stay was 4.5 days. The average score on the numerical rating scale of postoperative pain was 3.0 on postoperative day 1. The median follow‐up time was 23.5 months.

Conclusion

Laparoscopic left hemicolectomy with transrectal NOSE is a safe and feasible procedure that leads to early postoperative recovery and a short hospital stay.
Prenatal care: Mechanisms and impacts on infant health and health care utilization
Authors: Bersak Tim , Sonchak‐Ardan Lyudmyla
Published: October 2021

We estimate that prenatal care has positive impacts on health measured at birth, shifts the distribution of future health care utilization away from inpatient care, and find that some of these impacts likely come from an informational mechanism. We also find well child visits are used in a complementary fashion with emergency department care in the production of infant health, suggesting that factors beyond barriers to access may drive the demand for emergency care. Finally, we find differential impacts of prenatal care across racial groups with evidence that the information mechanism may be particularly important for black mothers.
Aptamer‐conjugated mesoporous polydopamine for docetaxel targeted delivery and synergistic photothermal therapy of prostate cancer
Authors: Dai Liang , Wei Dapeng , Zhang Jidong , Shen Tianyu , Zhao Yuming , Liang Junqiang , Ma Wangteng , Zhang Limin , Liu Qingli , Zheng Yue
Published: October 2021

Objectives

It is imperative to develop efficient strategies on the treatment of prostate cancer. Here, we constructed multifunctional nanoparticles, namely AS1411@MPDA‐DTX (AMD) for targeted and synergistic chemotherapy/photothermal therapy of prostate cancer.

Materials and Methods

Mesoporous polydopamine (MPDA) nanoparticles were prepared by a one‐pot synthesis method, DTX was loaded through incubation, and AS1411 aptamer was modified onto MPDA by the covalent reaction. The prepared nanoparticles were characterized by ultra‐micro spectrophotometer, Fourier transform infrared spectra, transmission electron microscope, and so on. The targeting ability was detected by selective uptake and cell killing. The mechanism of AMD‐mediated synergistic therapy was detected by Western blot and immunofluorescence.

Results

The prepared nanoparticles can be easily synthesized and possessed excellent water solubility, stability, and controlled drug release ability, preferentially in acidic context. Based on in vitro and in vivo results, the nanoparticles can efficiently target prostate cancer cells, promote DTX internalization, and enhance the antitumor effects of chemo‐photothermal therapy strategies under the NIR laser irradiation.

Conclusions

As a multifunctional nanoplatform, AS1411@MPDA‐DTX could efficiently target prostate cancer cells, promote DTX internalization, and synergistically enhance the antiprostate cancer efficiency by combining with NIR irradiation.
Understanding landowner decisions regarding access to private land for conservation research
Authors: O'Brien Rebecca S. M. , Dayer Ashley A. , Hopkins William A.
Published: October 2021

Private land comprises over half the land mass of the United States—dominating certain ecosystems and hosting large numbers of threatened and endangered species. Understanding privately owned properties is thus critically important to conservation, yet these lands remain understudied by conservation biologists. A key factor in this lack of research is the difficulty of gaining permission to access private lands. However, there has been almost no empirical work to offer guidance for natural scientists on this issue. Using a combination of mail surveys and interviews, we undertook one of the first empirical studies of landowner decisions regarding access to their private property for research, and we identified the primary drivers and deterrents. We found that natural scientists may have more success gaining access if the landowners are interested in learning about the research taking place, if they have previously allowed research on their property, if they have positive attitudes toward conservation, and if they have larger properties. We also found that many landowners allowed research out of a desire to be helpful. Conversely, landowners are less likely to allow research if they are concerned that doing so will restrict free use of their property. Landowner age, education, trust in science, and attitude toward the subject of study were not significant predictors of landowner decisions. By considering our findings when requesting access to properties and engaging with landowners during research, scientists can improve their chances of accessing properties, enhance landowner satisfaction with the experience, and increase the likelihood that landowners will be amenable to future requests to conduct research on their land.
Evolution of electroencephalogram in infants with tuberous sclerosis complex and neurodevelopmental outcome: a prospective cohort study
Authors: De Ridder Jessie , Kotulska Katarzyna , Curatolo Paolo , Jansen Anna C , Aronica Eleonora , Kwiatkowski David J , Jansen Floor E , Jóźwiak Sergiusz , Lagae Lieven ,   the Epistop Consortium
Published: October 2021

Aim

To describe the evolution of electroencephalogram (EEG) characteristics in infants with tuberous sclerosis complex (TSC) and the relationship with neurodevelopmental outcome at 24 months.

Method

Eighty‐three infants were enrolled in the EPISTOP trial and underwent serial EEG follow‐up until the age of 24 months (males n=45, females n=37, median age at enrolment 28d, interquartile range 14–54d). Maturation of the EEG background and epileptiform discharges were compared between the TSC1 and TSC2 variants and between preventive and conventional groups respectively.

Results

Children with TSC2 more frequently had a slower posterior dominant rhythm (PDR) at 24 months (51% vs 11%, p=0.002), a higher number of epileptiform foci (median=8 vs 4, p=0.003), and a lower fraction of EEGs without epileptiform discharges (18% vs 61%, p=0.001) at follow‐up. A slower PDR at 24 months was significantly associated with lower cognitive (median=70 vs 80, p=0.028) and motor developmental quotients (median=70 vs 79, p=0.008). A higher fraction of EEGs without epileptiform discharges was associated with a lower probability of autism spectrum disorder symptoms (odds ratio=0.092, 95% confidence interval=0.009–0.912, p=0.042) and higher cognitive (p=0.004), language (p=0.002), and motor (p=0.001) developmental quotients at 24 months.

Interpretation

TSC2 is associated with more abnormal EEG characteristics compared to TSC1, which are predictive for neurodevelopmental outcome.
Isolated bulbar palsy and dysphagia in children with respiratory symptoms
Authors: Zimmels Stacey , Balfour‐Lynn Ian M , Christodoulou Loucas , Pantazi Mantha , Pavlidou Efterpi , Pitt Matthew , Kinali Maria , Ismayilova Naila
Published: October 2021

Oropharyngeal dysphagia can cause chronic aspiration leading to significant respiratory symptoms. When dysphagia is diagnosed, an underlying cause is sought. We present a case series of 15 children diagnosed aged 6 months to 5 years (mean 2y 5mo; 11 males, four females) over a 6‐year period, who were found to have an isolated bulbar palsy on genioglossus electromyography, with no accompanying neurological or neurodevelopmental disorder. Eight children had dysphagia but a normal EMG. In those with isolated bulbar palsy, management included thickened fluids (n=13), cooled boiled water (n=1), and nasogastric tube feeding (n=1). Follow‐up over 1 to 8 years (mean 5y) showed complete resolution in six children, improvement in four children, and no improvement in five children (including two requiring fluids via a gastrostomy). Eight children no longer had any respiratory symptoms. Isolated bulbar palsy is under‐recognized and has not been reported previously as a cause of significant dysphagia in children.