bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of fragility surfaces for reinforced concrete buildings under mainshock‐aftershock sequences
Authors: Yu Xiaohui , Zhou Zhou , Du Wenqi , Lu Dagang
Published: September 2021

A single intensity measure (IM) is commonly used to develop fragility curves for structures subjected to mainshock‐aftershock (MS‐AS) scenarios. This study aims to propose a framework to develop MS‐AS fragility surfaces by characterizing the MS‐AS sequences with two IMs. To do this, the well‐known Park & Ang damage index, which increases monotonically with the ground motion duration, is adopted to represent the accumulative structural damage during sequential excitations. The MS‐AS accumulative damage of structures is thus represented by the combination of the initial damage caused by MS and the incremental damage caused by AS. Based on total probability theorem, the process of assessing MS‐AS fragility is consequently divided into two parts, namely the MS fragility assessment and the AS fragility assessment, respectively, where the cases of dynamic instability are considered. The proposed framework is illustrated using a typical four‐story reinforced concrete frame building. The peak ground velocity values of both MS and AS are taken as the representative IMs for the MS‐AS sequences. The fragility results for MS only and MS‐AS sequences are compared to scrutinize the effects of AS on structural damage. It is found that the MS‐AS sequence can cause significantly larger exceedance probabilities of limit states compared to the MS only. The MS‐AS sequence also leads to a reduction of the MS‐AS fragility median conditioned on a given AS intensity. Such reduction increases with the increase of the AS intensity.
Internationalizing the curriculum: The power of agency and authenticity
Authors: Marantz‐Gal Amit , Leask Betty
Published: September 2021

Internationalization is a core activity of universities today, and one in which academic staff play a crucial role. A decade of research into academic staff engagement in internationalization of the curriculum (IoC) has highlighted the importance of in‐depth qualitative case studies in which researchers collect detailed information over a sustained period of time in different institutions, programs, and contexts. This article analyses the results of multiple IoC case studies conducted in universities in Australia and Israel at different times over a 10‐year period. Academic staff in six different discipline areas and four institutions were engaged in IoC. Taken together, the results of these studies provide insight into the process of IoC and key engagement points in it. It is concluded that IoC is best facilitated when the authentic perspectives, experiences, and motivations of faculty are respected and institutions recognize their agency, leadership, and differentiated needs in the process.
Integrated approaches to the assessment of internationalization
Authors: Merrill Martha C. , Kretovics Mark A.
Published: September 2021

Assessment has become an important aspect of almost every academic or extracurricular program within institutions of higher education in the United States. This article defines internationalization and its related activities while discussing educational outcomes and offering a model for developing assessment strategies for said activities. Assessment should not be episodic but rather needs to be systematic and ongoing, as well as comprehensive and integrated.
Research in U.S.‐based strategies for education abroad and international student experiences
Authors: Liebschutz‐Roettger Elizabeth K.
Published: September 2021

International education is a content area with a rich history and yet within the lens of higher education research, is relatively new to the field. While seminal works have historically informed the field, emerging research and scrutiny have led to a better understanding of the overall student experience for international students and education abroad for degree‐seeking students. In addition to learning about incoming and out‐going student experience, research is also focusing more on the abroad experience as it pertains to student identity, self‐efficacy, long‐term outcomes, and the necessity for changing historical trends. For international students, the impact of foreign policies continues to influence their experiences as they navigate their education outside of their home country. But even more than their efforts to get to the United States, developing research highlights that international students have a differentiated experience once they arrive on campus from their domestic counterparts. Emerging and future areas of research are also discussed.
Preparing faculty for internationalization: Opportunities through teaching, research, and service
Authors: Witkowsky Patricia , Gibbes Cerian
Published: September 2021

This article overviews efforts, outcomes, and theoretical foundations that prepare faculty members with the knowledge, experiences, and dispositions necessary to promote internationalization and global learning in higher education. The article addresses inequities in faculty development for internationalization and provides recommendations for both faculty and institutions of higher education to promote faculty learning and development. The article focuses on faculty learning and development as it relates to internationalizing teaching, research, and service. Finally, considerations for institutional support of faculty development around internationalization are presented as well as how faculty development is impacted by a pandemic.
Who is resilient in a time of crisis? The importance of financial and non‐financial resources
Authors: Johnston David W. , Kung Claryn S. J. , Shields Michael A.
Published: September 2021

Enhancing population resilience to adverse events is now a policy priority. Accordingly, there have been calls for more evidence on the determinants of resilience. We answer this call by identifying financial and non‐financial resources associated with psychological resilience during the COVID‐19 pandemic. Using longitudinal survey data, psychological resilience is measured by comparing distress reported pre‐COVID‐19 with distress reported during the outbreak and initial lockdown in April 2020. Methodologically, we compare differences in resilience and resources between people with identical gender, ethnicity, health, parenthood status, education, employment status, and region of residence (all measured pre‐2020). We also provide estimates from within‐household comparisons. Surprisingly, income, savings, and debt levels did not affect the likelihood of psychologically resilient outcomes. Cognitive ability, religiosity, and neighborhood social capital also had no protective effect. In contrast, we find robust evidence that non‐cognitive skills, measured by self‐efficacy, strongly protected against psychological distress. Self‐efficacy also dampened the increase in distress caused by large earnings shocks. These findings support investments in non‐cognitive skills that modify the damage‐function from adverse events.
Transverse cervical artery anterior perforator flap for head and neck oncological reconstruction: Preliminary study
Authors: Wang Liang , Ma Chun‐yue , Shen Yi , Fang Jin , Haugen Thorsen W. , Guo Bing , Sun Jian
Published: September 2021

Background

To describe the indications, technique, and our experience in the application of the transverse cervical artery anterior perforator flap (ap‐TCAF) for reconstruction of head and neck oncological defects.

Methods

From September 2016 to September 2019, 11 patients underwent surgical treatment for head neck squamous cell carcinoma and were subsequently reconstructed with ap‐TCAFs. The clinical details were recorded, and the postoperative appearance and function were analyzed.

Results

The ap‐TCAF was used to reconstruct intraoral defects in eight patients and to repair an oropharyngeal defect in one patient. In two remaining patients, the ap‐TCAF was divided into two to restore defects with both an intraoral and extraoral component. The flap size ranged from 6 × 4 cm to 15 × 9 cm. All flaps healed uneventfully. There was no delayed wound healing or dysfunction at the donor site.

Conclusions

The ap‐TCAF is reliable with characteristics making it useful for head and neck oncological reconstruction, especially in male patients.
Requirement of RORα for maintenance and antitumor immunity of liver‐resident natural killer cells/ILC1s
Authors: Song Jiaxi , Song Hao , Wei Haiming , Sun Rui , Tian Zhigang , Peng Hui
Published: September 2021

Backgroud and Aims

Liver type 1 innate lymphoid cells (ILC1s), also known as liver‐resident natural killer (LrNK) cells, comprise a high proportion of total hepatic ILCs. However, factors regulating their maintenance and function remain unclear.

Approach and Results

In this study, we found high expression of retinoid‐related orphan nuclear receptor alpha (RORα) in LrNK cells/ILC1s. Mice with conditional ablation of retinoid‐related orphan nuclear receptor alpha (Rorα) in LrNK cells/ILC1s and conventional natural killer (cNK) cells had decreased LrNK cells/ILC1s but normal numbers of cNK cells. RORα‐deficient LrNK cells/ILC1s displayed increased apoptosis and significantly altered transcriptional profile. Using a murine model of colorectal cancer liver metastasis, we found that RORα conditional deficiency resulted in more aggressive liver tumor progression and impaired effector molecule expression in LrNK cells/ILC1s. Consequently, treatment with the RORα agonist efficiently limited liver metastases and promoted effector molecule expression of LrNK cells/ILC1s.

Conclusions

This study reveals a role of RORα in LrNK cell/ILC1 maintenance and function, providing insights into the harnessing of LrNK cell/ILC1 activity in the treatment of liver cancer.
Magnetic resonance elastography for prediction of long‐term progression and outcome in chronic liver disease: A retrospective study
Authors: Gidener Tolga , Yin Meng , Dierkhising Ross A. , Allen Alina M. , Ehman Richard L. , Venkatesh Sudhakar K.
Published: September 2021

Background and Aims

Although magnetic resonance elastography (MRE) has been well‐established for detecting and staging liver fibrosis, its prognostic role in determining outcomes of chronic liver disease (CLD) is mostly unknown.

Approach and Results

This retrospective study consisted of 1269 subjects who underwent MRE between 2007 and 2009 and followed up until death or last known clinical encounter or end of study period. Charts were reviewed for cirrhosis development, decompensation, and transplant or death. The cohort was split into baseline noncirrhosis (group 1), compensated cirrhosis (group 2), and decompensated cirrhosis (group 3). Cox‐regression analysis with age, sex, splenomegaly, CLD etiology, Child‐Pugh Score (CPS), Fibrosis‐4 Index (FIB‐4) score, and Model for End‐Stage Liver Disease (MELD)–adjusted HR for every 1‐kPa increase in liver stiffness measurement (LSM) were used to assess the predictive performance of MRE on outcomes. Group 1 (n = 821) had baseline median LSM of 2.8 kPa, and cirrhosis developed in 72 (8.8%) subjects with an overall rate of about 1% cirrhosis/year. Baseline LSM predicted the future cirrhosis with multivariable adjusted HR of 2.38 (p < 0.0001) (concordance, 0.84). In group 2 (n = 277) with baseline median LSM of 5.7 kPa, 83 (30%) subjects developed decompensation. Baseline LSM predicted the future decompensation in cirrhosis with FIB‐4 and MELD‐adjusted HR of 1.22 (p < 0.0001) (concordance, 0.75). In group 3 (n = 171) with median baseline LSM of 6.8 kPa (5.2, 8.4), 113 (66%) subjects had either death or transplant. Baseline LSM predicted the future transplant or death with HR of 1.11 (p = 0.013) (concordance 0.53) but not in CPS and MELD‐adjusted models (p = 0.08).

Conclusion

MRE‐based LSM is independently predictive of development of future cirrhosis and decompensation, and has predictive value in future transplant/death in patients with CLD.
Aging exaggerates acute‐on‐chronic alcohol‐induced liver injury in mice and humans by inhibiting neutrophilic sirtuin 1‐C/EBPα‐miRNA‐223 axis
Authors: Ren Ruixue , He Yong , Ding Dong , Cui Aoyuan , Bao Huarui , Ma Jing , Hou Xin , Li Yu , Feng Dechun , Li Xiaoling , Liangpunsakul Suthat , Gao Bin , Wang Hua
Published: September 2021

Background and Aims

Aging exacerbates liver neutrophil infiltration and alcohol‐associated liver disease (ALD) in mice and humans, but the underlying mechanisms remain obscure. This study aimed to examine the effect of aging and alcohol consumption on neutrophilic Sirtuin 1 (SIRT1) and microRNA‐223 (miR‐223), and their contribution to ALD pathogeneses.

Approach and Results

Young and aged myeloid‐specific Sirt1 knockout mice were subjected to chronic‐plus‐binge ethanol feeding. Blood samples from healthy controls and patients with chronic alcohol drinking who presented with acute intoxication were analyzed. Neutrophilic Sirt1 and miR‐223 expression were down‐regulated in aged mice compared with young mice. Deletion of the Sirt1 gene in myeloid cells including neutrophils exacerbated chronic‐plus‐binge ethanol‐induced liver injury and inflammation and down‐regulated neutrophilic miR‐223 expression. Immunoprecipitation experiments revealed that SIRT1 promoted C/EBPα deacetylation by directly interacting with C/EBPα, a key transcription factor that controls miR‐223 biogenesis, and subsequently elevated miR‐223 expression in neutrophils. Importantly, down‐regulation of SIRT1 and miR‐223 expression was also observed in circulating neutrophils from middle‐aged and elderly subjects compared with those from young individuals. Chronic alcohol users with acute intoxication had a reduction in neutrophilic SIRT1 expression in young and middle‐aged patients, with a greater reduction in the latter group. The neutrophilic SIRT1 expression correlated with neutrophilic miR‐223 and serum alanine transaminase levels in those patients.

Conclusions

Aging increases the susceptibility of alcohol‐induced liver injury in mice and humans through the down‐regulation of the neutrophilic SIRT1‐C/EBPα‐miR‐223 axis, which could be a therapeutic target for the prevention and/or treatment of ALD.
Current and Emerging Tools for Hepatocellular Carcinoma Surveillance
Authors: Adeniji Nia , Dhanasekaran Renumathy
Published: September 2021

Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related mortality worldwide. Early detection of HCC enables patients to avail curative therapies that can improve patient survival. Current international guidelines advocate for the enrollment of patients at high risk for HCC, like those with cirrhosis, in surveillance programs that perform ultrasound every 6 months. In recent years, many studies have further characterized the utility of established screening strategies and have introduced new promising tools for HCC surveillance. In this review, we provide an overview of the most promising new imaging modalities and biomarkers for the detection of HCC. We discuss the role of imaging tools like ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) in the early detection of HCC, and describe recent innovations which can potentially enhance their applicability, including contrast enhanced ultrasound, low‐dose CT scans, and abbreviated MRI. Next, we outline the data supporting the use of three circulating biomarkers (i.e., alpha‐fetoprotein [AFP], AFP lens culinaris agglutinin‐reactive fraction, and des‐gamma‐carboxy prothrombin) in HCC surveillance, and expand on multiple emerging liquid biopsy biomarkers, including methylated cell‐free DNA (cfDNA), cfDNA mutations, extracellular vesicles, and circulating tumor cells. These promising new imaging modalities and biomarkers have the potential to improve early detection, and thus improve survival, in patients with HCC.
Secondary primary malignancies in patients with multiple myeloma: A single institution experience
Authors: Fei Fei , Reddy Vishnu , Rosenblum Frida
Published: September 2021

The purpose of our study is to highlight the demographic characteristics, pathological features, and clinical course of multiple myeloma (MM) patients with secondary primary malignancies (SPM). A retrospective chart review was performed from January 2009 to February 2020. Patients' demographic, pathologic and cytogenetic features, treatment characteristics and clinical outcomes were collected. We identified 871 MM patients including 40 patients who developed SPM. Among the 40 patients with SPM, 17 patients developed hematological SPM and 23 patients developed solid SPM. The median time from diagnosis of MM to the occurrence of hematological SPM was 6.85 versus 3.91 years in solid SPM, with a median overall survival (OS) after diagnosis of SPM of 120 and 880 days, respectively. Interestingly, we observed that there was no significant difference in OS between MM patients with or without SPM. Multivariable analysis showed that age and autologous stem cell transplantation were independent factors associated with patients' clinical outcomes. Our study highlights the importance of understanding the etiology, biology, clinical outcome and management in MM patients with SPM.
The performance impact of gender diversity in the top management team and board of directors: A multiteam systems approach
Authors: Wu Jie , Richard Orlando C. , Triana María del Carmen , Zhang Xinhe
Published: September 2021

Given the mixed evidence that having both women and men in the top management team (TMT) or in the board of directors (BOD) has a significant influence on organizational innovation, we resolve this issue by conceptualizing TMT–BOD gender diversity as part of a multiteam system, that has joint effects which impact organizational innovation. Evidence from the study of both Chinese firms and UK firms confirm our conceptualization by showing an interaction effect between TMT gender diversity and BOD gender diversity such that innovation is greatest when both are high. The positive TMT–BOD gender diversity interaction effect on innovation improves subsequent firm performance particularly in dynamic environments. The findings refine current thinking by going beyond research that tests intra‐team TMT or BOD diversity independently and instead considers inter‐team diversity across both leadership teams within the strategic leadership upper echelons. In sum, findings show that high levels of TMT and BOD gender diversity result in more organizational innovation, which ultimately improves firm performance. We offer implications for women's inclusion in leadership as well as for research on the upper echelons.
Interventions for managing professional isolation among health professionals in low resource environments: A scoping review
Authors: Kutoane Mahlomola , Brysiewicz Petra , Scott Tricia
Published: September 2021

Background

Professional isolation is viewed as a sense of isolation from ones professional peers and this has contributed to compromised quality of health service delivery as well as quality of life for health professionals in low resource environments. Professional isolation is a multidimensional concept which may be either geographic, social, and/or ideological. However, professional isolation in low resource environments remains poorly defined with a limited body of research focusing on health professionals.

Aim

To map and examine available literature on interventions for managing professional isolation among health professionals in low resource environments.

Methods

We conducted a scoping review of the published and grey literature to examine the extent, range and nature of existing research studies relevant to professional isolation in health professionals.

Results

Of the 10 articles retrieved, 70% were conducted in high income countries where the context may be different if applied to other low‐income settings such as in Africa. Only 20% of the studies focused specifically on nurses or the nursing profession and only 10% were conducted on the African continent.

Conclusion

There is insufficient research on the definition and origins of professional isolation among health professionals including the interventions that can be employed. Rural, remote and/or isolated settings significantly predispose health professionals to professional isolation but remain poorly defined. Additional research is recommended to explore and determine the interventions for managing professional isolation among health professionals in low resource environments.
Detection of Victoria lineage influenza B viruses with K162 and N163 deletions in the hemagglutinin gene, South Africa, 2018
Authors: Hellferscee Orienka , Treurnicht Florette , Gaelejwe Lucinda , Moerdyk Alexandra , Reubenson Gary , McMorrow Meredith , Tempia Stefano , McAnerney Johanna , Walaza Sibongile , Wolter Nicole , von Gottberg Anne , Cohen Cheryl
Published: September 2021

Background

A group of Victoria lineage influenza B viruses with a two amino acid deletion in the hemagglutinin (HA) at residues K162 and N163, was detected during the 2016 to 2017 Northern Hemisphere influenza season and continues to spread geographically. We describe the first identification of viruses with these deletions from South Africa in 2018.

Methods

Nasopharyngeal samples were obtained from the syndromic surveillance programs. Real‐time reverse transcription‐polymerase chain reaction was used for virus detection and lineage determination. Influenza genetic characterization was done using next‐generation sequencing on the MiSeq platform. The duration of virus circulation was determined using thresholds calculated using the Moving Epidemic Method; duration was used as an indicator of disease transmissibility and impact.

Results

In 2018, 42% (426/1015) of influenza‐positive specimens were influenza B viruses. Of 426 influenza B‐positive samples, 376 (88%) had the lineage determined of which 75% (283/376) were Victoria lineage. The transmissibility of the 2018 South African influenza season was high for a few weeks, although the severity remained moderate through most of the season. The sequenced 2018 South African Victoria lineage influenza B viruses clustered in sub‐clade V1A.1 with the 162‐163 deletions.

Conclusions

We report the first detection of the 162‐163 deletion variant of influenza B/Victoria viruses from South Africa in 2018, and suggest that this deletion variant replaced the previous circulating influenza B/Victoria viruses. These deletions putatively affect the antigenic properties of the viruses because they border an immune‐dominant region at the tip of the HA. Therefore, close monitoring of these newly emerging viruses is essential.
Lung sound analysis in infants with risk factors for asthma development
Authors: Miyamoto Manabu , Yoshihara Shigemi , Shioya Hiromi , Tadaki Hiromi , Imamura Tomohiko , Enseki Mayumi , Koike Hideki , Furuya Hiroyuki , Mochizuki Hiroyuki
Published: September 2021

Background and objectives

Using a lung sound analysis, the prognosis of asthma was investigated in infants with risk factors for asthma development by a long‐term observation.

Methods

A total of 268 infants were included (median age: 8 months old). The lung sound parameters (the ratio of the third and fourth area to the total area under the curve [A3/AT and B4/AT], and the ratio of power and frequency at 50% and 75% of the highest frequency [RPF50 and RPF75]) were evaluated at the first visit. At 3 years old, using a questionnaire, we examined the relationship between the lung sound parameters and risk factors of asthma development.

Results

Among the 268 infants, 175 infants were in good health and 93 had a history of acute respiratory infection (ARI) within 7 days at the first visit. Among the 3‐ to 12‐month‐old infants with an ARI, the A3/AT, B4/AT values in those with a history of asthma/asthmatic bronchitis, atopic dermatitis, and atopy were smaller than in the infants without such histories. Among the 13‐ to 24‐month‐old infants with an ARI, the A3/AT and B4/AT values in those with a wheezing history were larger than in the infants without such a history.

Conclusions

The characteristics of the lung sounds in infants with risk factors for asthma development were demonstrated over long‐term follow‐up. Lung sound analyses may be useful for assessing the airway condition of infants.
Unsteady MHD oscillatory Casson fluid flow past an inclined vertical porous plate in the presence of chemical reaction with heat absorption and Soret effects
Authors: Kodi Raghunath , Mopuri Obulesu
Published: September 2021

The purpose of this paper is to perform unsteady hydrodynamic flow over an inclined plate embedded in a porous medium with Soret‐aligned magnetic field and chemical reaction. Once momentum, energy, and mass are equal, they can be combined using the diffusion equation to yield the dimensionless momentum/energy/mass model. Computations were performed to analyze the behavior of fluid velocity, temperature and concentration on the inclined vertical plate with the variation of emerging physical parameters like aligned magnetic field, Casson parameter, inclined angle, chemical reaction including soret parameter. The findings derived from skin friction, Nusselt number, and Sherwood number are included in the tables provided for different parameters. The results match with a special case of previously published work. From the present analysis, it is reported that the presence of angle of inclination, aligned magnetic field, and Casson fluid parameters sustains a retarding effect on velocity. The velocity decreases with increasing angle of inclination, aligned magnetic field parameter, and Casson fluid parameter. Comparisons with previously published work performed and the results are found to be in excellent agreement.
The Chemical Bond – an Entrance Door of Chemistry to the Neighboring Sciences and to Philosophy
Authors: Frenking Gernot
Published: September 2021

Human understanding of the nature of chemical bonding as a physical phenomenon based on quantum theory and the limits of human knowledge are discussed and scrutinized.
The clinical importance of polyp size measurement through two‐dimensional saline infusion sonohysterography prior to hysteroscopic resection in predicting premalignant and malignant endometrial lesions
Authors: Akış Serkan , Kıran Gürkan , Göçmen Ahmet
Published: September 2021

Objective

To evaluate the clinical importance of endometrial polyp size measured using saline infusion sonohysterography (SIS) before performing a hysteroscopic resection in predicting premalignant/malignant lesions.

Methods

A retrospective observational study analysis was conducted of 365 patients, who underwent SIS, in a reference hospital. The longest plane of the polyp size was taken as base. Polyps were classified as benign, premalignant, or malignant.

Results

The rates of premalignant and malignant lesions were 7.4% and 0.9%, respectively. The mean polyp size was 17.7 ± 0.5 mm in benign patients and 23.7 ± 1.8 mm in premalignant/malignant individuals (P < 0.001). In the group of polyps that were 0–10, 10–20, 20–30, and >30 mm, premalignancy/malignancy rates were 0.0%, 4.8%, 13.3%, and 18.8%, respectively. The cut‐off value for polyp size to be able to predict lesions was calculated as 22.5 mm (sensitivity: 63%, specificity: 80%) on receiver operating characteristics curve analysis (P = 0.001, area under the curve 0.732). The power of the study was calculated as 90.86%.

Conclusion

During the female reproductive years, endometrial polyps smaller than 10 mm, as measured in SIS, can be followed. However, when the polyp size is 22.5 mm or more, especially in postmenopausal women, treatment should be planned.
A meta‐synthesis of qualitative studies on stress urinary incontinence in women for the development of a Core Outcome Set: A systematic review
Authors: Rada Maria Patricia , Jones Stephanie , Betschart Cornelia , Falconi Gabriele , Haddad Jorge Milhem , Doumouchtsis Stergios K. ,   CHORUS: An International Collaboration for Harmonising Outcomes, Research, and Standards in Urogynaecology and Women’s Health (i‐chorus.org)
Published: September 2021

Objective

Given the high variation of perceptions of women with stress urinary incontinence (SUI), qualitative meta‐synthesis in this field appears warranted. We aimed to synthesize evidence on women's experiences of SUI by analyzing qualitative data.

Methods

A literature search of Medline, Embase, Scopus, PsycInfo, and CINAHL databases was performed by a CHORUS Working Group, from inception to August 2020. Qualitative studies on women's perspectives on SUI were included. Thematic analysis was used as a conceptual approach to analyze the data and develop a set of overarching themes. The quality of studies was assessed based on the Critical Appraisal Skills Program tool.

Results

Seven studies were included. Six themes encompassing women's perspectives on SUI emerged: experiencing SUI, awareness of SUI, treatments for SUI, sexuality, communication, and psychosocial effects. The quality appraisal of the studies showed good coherence.

Conclusion

This study revealed six overarching themes, of which treatment had the highest prevalence. Assessment of women's perceptions of SUI in the context of a qualitative meta‐synthesis may inform policy and practice around this condition, may guide and help set research priorities, and will ideally contribute to the development of a Core Outcome Set for SUI.
Integration of clinical perspective into biomimetic bioreactor design for orthopedics
Authors: Drapal Victoria , Gamble Jordan M. , Robinson Jennifer L. , Tamerler Candan , Arnold Paul M. , Friis Elizabeth A.
Published: September 2021

The challenges to accommodate multiple tissue formation metrics in conventional bioreactors have resulted in an increased interest to explore novel bioreactor designs. Bioreactors allow researchers to isolate variables in controlled environments to quantify cell response. While current bioreactor designs can effectively provide either mechanical, electrical, or chemical stimuli to the controlled environment, these systems lack the ability to combine all these stimuli simultaneously to better recapitulate the physiological environment. Introducing a dynamic and systematic combination of biomimetic stimuli bioreactor systems could tremendously enhance its clinical relevance in research. Thus, cues from different tissue responses should be studied collectively and included in the design of a biomimetic bioreactor platform. This review begins by providing a summary on the progression of bioreactors from simple to complex designs, focusing on the major advances in bioreactor technology and the approaches employed to better simulate in vivo conditions. The current state of bioreactors in terms of their clinical relevance is also analyzed. Finally, this review provides a comprehensive overview of individual biophysical stimuli and their role in establishing a biomimetic microenvironment for tissue engineering. To date, the most advanced bioreactor designs only incorporate one or two stimuli. Thus, the cell response measured is likely unrelated to the actual clinical performance. Integrating clinically relevant stimuli in bioreactor designs to study cell response can further advance the understanding of physical phenomenon naturally occurring in the body. In the future, the clinically informed biomimetic bioreactor could yield more efficiently translatable results for improved patient care.
Clinical significance of kallikrein 5 as a novel prognostic biomarker in gastric adenocarcinoma
Authors: Abuduhadeer Xiaokaiti , Xu Xincai , Aihesan Kamali , Yilihamu Maimaiti , Zhao Yanjun , Zhang Wenbin
Published: September 2021

Backgrounds

Gastric cancer is one of the most common cancers with unsatisfied prognosis. It is challenging to predict gastric cancer prognosis due to its highly heterogeneous nature. Kallikrein 5 (KLK5) belongs to the family of kallikreins, which plays a crucial role in serine proteolysis and exerts diverse physiological functions. The role of KLK5 in human gastric adenocarcinoma (GAC) has not been elucidated. In the present study, we aimed to examine the expression level of KLK5 and dissect whether the KLK5 expression was associated with GAC prognosis.

Patients and methods

Clinicopathological analyses were performed in a retrospective GAC patient cohort (n = 138). The expression of KLK5 was tested by quantitative RT‐PCR and immunohistochemistry staining. The prognostic role of KLK5 in GAC was assessed by univariate and multivariate analyses. The effects of KLK5 on cell proliferation, migration, and invasion were examined through cellular experiments.

Results

The data showed that KLK5 expression was elevated in GAC tissues compared with normal stomach tissues. Protein expression of KLK5 was positively correlated with tumor invasion depth and lymph node metastasis. Patients with higher KLK5 expression had poorer overall survival. KLK5 was identified to be an independent risk factor according to multivariate analysis. Using human GAC cell lines, we found that KLK5 can promote tumor cell migration and invasion.

Conclusions

Our study demonstrated that higher expression of KLK5 was significantly correlated with a poorer prognosis of GAC patients, implying the potential of KLK5 as a novel prognostic biomarker in GAC.
Genetic counseling for congenital heart disease – Practice resource of the National Society of Genetic Counselors
Authors: Ison Hannah E. , Griffin Emily L. , Parrott Ashley , Shikany Amy R. , Meyers Lindsay , Thomas Matthew J. , Syverson Erin , Demo Erin M. , Fitzgerald Kristi K. , Fitzgerald‐Butt Sara , Ziegler Katie L. , Schartman Allison F. , Stone Kristyne M. , Helm Benjamin M.
Published: September 2021

Congenital heart disease (CHD) is an indication which spans multiple specialties across various genetic counseling practices. This practice resource aims to provide guidance on key considerations when approaching counseling for this particular indication while recognizing the rapidly changing landscape of knowledge within this domain. This resource was developed with consensus from a diverse group of certified genetic counselors utilizing literature relevant for CHD genetic counseling practice and is aimed at supporting genetic counselors who encounter this indication in their practice both pre‐ and postnatally.
A case of Wernicke encephalopathy in a dementia caregiver: The need for nutritional evaluation in family caregivers
Authors: Ishida Mayumi , Uchida Nozomu , Itami Kumi , Sato Izumi , Yoshioka Akira , Onishi Hideki
Published: September 2021

A 63‐year‐old woman had started caring for her mother with dementia 6 months previously. A loss of appetite had appeared 2 months prior to her visit. Neurologically, she experienced mild unsteadiness, but she was fully conscious and had no ocular symptoms. MRI examination of her head did not reveal any notable findings. From these symptoms, the possibility of thiamine deficiency was considered, and her unsteadiness disappeared within a few days after an intravenous injection of thiamine. The burden of caring for a dementia patient may affect the nutritional status of the family caregiver.
Efficient synthesis of piperidine derivatives using dendrimer based catalytical pockets
Authors: Vettukattil Unnikrishnan , Govindan Avudaiappan , James Kiran , Anilkumar Ajay , Krishnapillai Sreekumar
Published: September 2021

The synthesis of highly functionalized piperidine derivatives using amine functionalized maltitol‐cored dendritic polymer (MAL‐G0) in acetonitrile as the reaction medium is reported. A variety of piperidine derivatives were synthesized and the reaction gave an excellent yield of 89%–95%. The highly functionalized nature of the catalyst provided large number of active sites which resulted in good yield within a short period of time. Maltitol is a carbohydrate polyol system which was chosen here as the core for the synthesis of the dendritic catalyst; it was an effective approach for the preparation of piperidine like medicinal compounds. Maltitol‐cored dendritic polymer was effectively synthesized and characterized using GPC, TG, UV–Visible, IR, and NMR techniques and also all the synthesized piperidine derivatives were characterized using LCMS, IR, and NMR techniques.
Whole‐Heart 4D Flow MRI for Evaluation of Normal and Regurgitant Valvular Flow: A Quantitative Comparison Between Pseudo‐Spiral Sampling and EPI Readout
Authors: Blanken Carmen P.S. , Gottwald Lukas M. , Westenberg Jos J.M. , Peper Eva S. , Coolen Bram F. , Strijkers Gustav J. , Nederveen Aart J. , Planken R. Nils , van Ooij Pim
Published: September 2021

Background

Pseudo‐spiral Cartesian sampling with compressed sensing reconstruction has facilitated highly accelerated 4D flow magnetic resonance imaging (MRI) in various cardiovascular structures. However, unlike echo planar imaging (EPI)‐accelerated 4D flow MRI, it has not been validated in whole‐heart applications.

Hypothesis

Pseudo‐spiral 4D flow MRI (PROUD [PROspective Undersampling in multiple Dimensions]) is comparable to EPI in robustness of valvular flow measurements and remains comparable as the undersampling factor is increased and scan time reduced.

Study Type

Prospective.

Population

Twelve healthy subjects and eight patients with valvular regurgitation.

Field Strength/Sequence

3.0 T; PROUD and EPI 4D flow sequences, 2D flow and balanced steady‐state free precession sequences.

Assessment

Valvular blood flow was quantified using valve tracking. PROUD‐ and EPI‐based measurements of aortic (AV) and pulmonary (PV) flow volumes and left and right ventricular stroke volumes were tested for agreement with 2D MRI‐based measurements. PROUD reconstructions with undersampling factors (R) of 9, 14, 28, and 56 were tested for intervalve consistency (per valve, compared to the other valves) and preservation of peak velocities and E/A ratios.

Statistical Tests

We used repeated measures ANOVA, Bland‐Altman, Wilcoxon signed rank, and intraclass correlation coefficients. P < 0.05 was considered statistically significant.

Results

PROUD and EPI intervalve consistencies were not significantly different both in healthy subjects (valve‐averaged mean difference [limits of agreement width]: 3.2 ± 0.8 [8.7 ± 1.1] mL/beat for PROUD, 5.5 ± 2.9 [13.7 ± 2.3] mL/beat for EPI, P = 0.07) and in patients with valvular regurgitation (2.3 ± 1.2 [15.3 ± 5.9] mL/beat for PROUD, 0.6 ± 0.6 [19.3 ± 2.9] mL/beat for EPI, P = 0.47). Agreement between EPI and PROUD was higher than between 4D flow (EPI or PROUD) and 2D MRI for forward flow, stroke volumes, and regurgitant volumes. Up to R = 28 in healthy subjects and R = 14 in patients with valvular regurgitation, PROUD intervalve consistency remained comparable to that of EPI. Peak velocities and E/A ratios were preserved up to R = 9.

Conclusion

PROUD is comparable to EPI in terms of intervalve consistency and may be used with higher undersampling factors to shorten scan times further.

Level of Evidence

1

Technical Efficacy Stage

2
Rescheduling‐based congestion management by metaheuristic algorithm: Hybridizing lion and moth search models
Authors: Srivastava Jyoti , Yadav Naresh Kumar
Published: September 2021

Congestion management (CM) is becoming a challenging task in the power system due to the increase in the system complexities in the deregulated environment. The congestion causes grave damage to the power system components if the outages tend to occur more frequently. Hence, in the present power system scenario, CM is a complex task of an independent system operator (ISO). This proposal intends to introduce a novel optimization‐based CM model with advanced soft computing techniques. A new hybrid algorithm is introduced in this paper, which optimizes the generating power of added generators with the bus system. Thereby manages the congestion with minimized rescheduling cost. The proposed optimization algorithm termed Lion Algorithm with Moth‐based Mutation (LA‐MM) hybridizes the concepts of both Lion Algorithm (LA) and Moth Search Algorithm (MS). Subsequently, the experimentation is conducted in two test bus systems like IEEE 14 and 30 bus systems. The performance of the proposed model is compared over other state‐of‐the‐art models concerning cost analysis and convergence analysis, respectively.
Anesthesia in mice activates discrete populations of neurons throughout the brain
Authors: Yatziv Shai‐lee , Yudco Or , Vaso Kristina , Mizrahi Adi , Devor Marshall
Published: September 2021

The brain undergoes rapid, dramatic, and reversible transitioning between states of wakefulness and unconsciousness during natural sleep and in pathological conditions such as hypoxia, hypotension, and concussion. Transitioning can also be induced pharmacologically using general anesthetic agents. The effect is selective. Mobility, sensory perception, memory formation, and awareness are lost while numerous housekeeping functions persist. How is selective transitioning accomplished? Classically a handful of brainstem and diencephalic “arousal nuclei” have been implicated in driving brain‐state transitions on the grounds that their net activity systematically varies with brain state. Here we used transgenic targeted recombination in active populations mice to label neurons active during wakefulness with one reporter and neurons active during pentobarbital‐induced general anesthesia with a second, contrasting reporter. We found ‘wake‐on’ and ‘anesthesia‐on’ neurons in widely distributed regions‐of‐interest, but rarely encountered neurons labeled with both reporters. Nearly all labeled neurons were either wake‐on or anesthesia‐on. Thus, anesthesia‐on neurons are not unique to the few nuclei discovered to date whose activity appears to increase during anesthesia. Rather neuronal populations selectively active during anesthesia are located throughout the brain where they likely play a causative role in transitioning between wakefulness and anesthesia. The widespread neuronal suppression reported in prior comparisons of the awake and anesthetized brain in animal models and noninvasive imaging in humans reflects only net differences. It misses the ubiquitous presence of neurons whose activity increases during anesthesia. The balance in recruitment of anesthesia‐on versus wake‐on neuronal populations throughout the brain may be a key driver of regional and global vigilance states.

[Correction added on September 22, 2021, after first online publication: Due to a typesetting error, the abstract text was cut off. This has been corrected now.]
Overexpression of α‐synuclein inhibits mitochondrial Ca2+ trafficking between the endoplasmic reticulum and mitochondria through MAMs by altering the GRP75–IP3R interaction
Authors: Erustes Adolfo Garcia , D'Eletto Manuela , Guarache Gabriel Cicolin , Ureshino Rodrigo Portes , Bincoletto Claudia , da Silva Pereira Gustavo José , Piacentini Mauro , Smaili Soraya Soubhi
Published: September 2021

Mitochondria‐associated ER membranes (MAMs) are formed by close and specific components in the contact sites between the endoplasmic reticulum (ER) and mitochondria, which participate in several cell functions, including lipid metabolism, autophagy, and Ca2+ signaling. Particularly, the presence of α‐synuclein (α‐syn) in MAMs was previously demonstrated, indicating a physical interaction among some proteins in this region and a potential involvement in cell dysfunctions. MAMs alterations are associated with neurodegenerative diseases such as Parkinson's disease (PD) and contribute to the pathogenesis features. Here, we investigated the effects of α‐syn on MAMs and Ca2+ transfer from the ER to mitochondria in WT‐ and A30P α‐syn‐overexpressing SH‐SY5Y or HEK293 cells. We observed that α‐syn potentiates the mitochondrial membrane potential (Δψm) loss induced by rotenone, increases mitophagy and mitochondrial Ca2+ overload. Additionally, in α‐syn‐overexpressing cells, we found a reduction in ER–mitochondria contact sites through the impairment of the GRP75–IP3R interaction, however, with no alteration in VDAC1–GRP75 interaction. Consequently, after Ca2+ release from the ER, α‐syn‐overexpressing cells demonstrated a reduction in Ca2+ buffering by mitochondria, suggesting a deregulation in MAM activity. Taken together, our data highlight the importance of the α‐syn/MAMs/Ca2+ axis that potentially affects cell functions in PD.
Comparing axon regeneration in male and female mice after peripheral nerve injury
Authors: Jang Eun‐Hae , Bae Yun‐Hee , Yang Eun Mo , Gim Yunho , Suh Hyun‐Jun , Kim Subin , Park Seong‐min , Park Jong Bae , Hur Eun‐Mi
Published: September 2021

Axons in the adult mammalian central nervous system fail to regenerate after injury. By contrast, spontaneous axon regeneration occurs in the peripheral nervous system (PNS) due to a supportive PNS environment and an increase in the intrinsic growth potential induced by injury via cooperative activation of multifaceted biological pathways. This study compared axon regeneration and injury responses in C57BL/6 male and female mice after sciatic nerve crush (SNC) injury. The extent of axon regeneration in vivo was indistinguishable in male and female mice when observed at 3 days after SNC injury, and primary dorsal root ganglion (DRG) neurons from injured, male and female mice extended axons to a similar length. Moreover, the induction of selected regeneration‐associated genes (RAGs), such as Atf3, Sprr1a, Gap43, Sox11, Jun, Gadd45a, and Smad1 were comparable in male and female DRGs when assessed by quantitative real‐time reverse transcription polymerase chain reaction. Furthermore, the RNA‐seq analysis of male and female DRGs revealed that differentially expressed genes (DEGs) in SNC groups compared to sham‐operated groups included many common genes associated with neurite outgrowth. However, we also found that a large number of genes in the DEGs were sex dependent, implicating the involvement of distinct gene regulatory network in the two sexes following peripheral nerve injury. In conclusion, we found that male and female mice mounted a comparable axon regeneration response and many RAGs were commonly induced in response to SNC. However, given that many DEGs were sex‐dependently expressed, future studies are needed to investigate whether they contribute to peripheral axon regeneration, and if so, to what extent.
Decline in executive function in patients with white matter hyperintensities from the static and dynamic perspectives of amplitude of low‐frequency fluctuations
Authors: Cao Shanshan , Zhang Jun , Chen Chen , Wang Xiaojing , Ji Yang , Nie Jiajia , Tian Yanghua , Qiu Bensheng , Wei Qiang , Wang Kai
Published: September 2021

Cognitive impairments are characteristics of patients with white matter hyperintensities (WMHs), and hypoperfusion is currently a relatively recognized mechanism of WMHs. Brain activity is closely coupled to the regulation of local blood flow. This study aimed to investigate the abnormal local brain activity of patients with WMHs from the viewpoint of the static amplitude of low‐frequency fluctuations (sALFF) and dynamic amplitude of low‐frequency fluctuations (dALFF). Seventy‐four patients with WMHs and 35 healthy controls (HCs) were included. Based on the Fazekas scale, patients with WMHs were further divided into a mild WMH group (n = 33, Fazekas score 1–2) and moderate‐severe WMH group (n = 41, Fazekas score 3–6). The sALFF and dALFF values were calculated separately and neuropsychological tests including the Montreal Cognitive Assessment (MoCA), Auditory Verbal Learning Test (AVLT), Trail Making Test (TMT), and Boston Naming Test (BNT) were completed by all participants. Patients with WMHs showed increased sALFF and dALFF values in the bilateral thalamus and decreased performance in the MoCA test, AVLT‐immediate, AVLT‐delay, AVLT‐recognition, TMT‐A, and BNT. The dALFF values in the bilateral thalamus was correlated with the MoCA in HCs. The sALFF values in the bilateral thalamus correlated with TMT‐B in patients with WMHs. Patients with WMHs showed abnormal brain activity and decreased functional stability of the bilateral thalamus, which may be a potential mechanism of decreased executive function.