bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of Childhood Maltreatment and Genetic Risks With Incident Heart Failure in Later Life
Authors: Liang Yannis Yan , Ai Sizhi , Weng Foqian , Feng Hongliang , Yang Lulu , He Zhixuan , Xue Huachen , Zhou Mingqing , Shu Xinyue , Chen Yilin , Ma Huan , Guo Lan , Geng Qingshan , Zhang Jihui
Published: October 2022

Background

We aimed to determine the associations of childhood maltreatment with incident heart failure in later life and explore the potentially modifying effects of genetic risk for heart failure on the associations.

Methods and Results

This cohort study included adults free of heart failure at baseline enrolled between 2006 and 2010 in the UK Biobank. Childhood maltreatment was retrospectively assessed with the online Childhood Trauma Screener in 2016. Five types of childhood maltreatment (range, 0–5), including physical abuse, physical neglect, emotional abuse, emotional neglect, and sexual abuse, were combined into a total score. A weighted polygenic risk score for heart failure was constructed. Incident all‐cause heart failure was prospectively ascertained via hospital inpatient and death records, followed up to May 31, 2021. A total of 153 287 adults (mean [SD] age, 55.9 [7.7] years; 43.6% male) were included. Over a median of 12.2 years (interquartile range, 11.5–12.9 years) of follow‐up, 2352 participants had incident heart failure. Childhood maltreatment was associated with a greater risk of incident heart failure in a dose‐response manner. One additional type of childhood maltreatment was associated with a 15% increase in the risk of developing heart failure (hazard ratio [HR], 1.15 [95% CI, 1.07–1.23]). There was no statistically significant interaction between genetic risk and childhood maltreatment (
P
interaction
=0.218). Among participants with high genetic risk, those with 3 to 5 types of childhood maltreatment had a double hazard (HR, 2.00 [95% CI, 1.43–2.80]) of developing heart failure when taking those without any childhood maltreatment as the reference.

Conclusions

Irrespective of genetic risk for heart failure, childhood maltreatment was associated with an increased risk of incident heart failure in a dose‐dependent manner.
Sweet & Sour Power: The Practice and Social Metaphor of
Pickling
Authors: Jenner Frankie ,   Slavs and Tatars Collective
Published: October 2022

The authors explore pickles, processes of fermentation, and its metaphorical significance as a lens through which we can explore our social history. The authors interrogate how their work speaks to the concept of fermentation as a metaphor.
The Vanitas of Sound Art
Authors: Komarov Sergey
Published: October 2022

The author applies the concept of fermentation to sound through the prism of saturation and sonification, and studies the fermentation process as a medium and approach in sound art. He traces this medium in the works of Alexey Grachev, Rumore Bianco, Wouter Van Veldhoven, Sam Conran, and Vasily Bakanov. The article examines the history of the CYLAND Audio Archive and the formula for archiving, cataloging, and exhibiting works of sound art.
Assessing China–Africa Relations under the Forum for China–Africa Cooperation (FOCAC) (2000–2019)
Authors: Omolo Loreen Auma
Published: October 2022

China–Africa relations have been a topic of huge interest in international relations, as well as the subject of wide scepticism and criticism. Drummond and Liu (2013) observe that more than half of sub-Saharan African countries have a trade deficit with China and that China remains a dominant actor in China–Africa relations. However, is this so? Are African states mere spectators in China–Africa relations or do they also have a strategy to gain something from the engagement? This study examines the role that African agency plays in Sino-African relations under the FOCAC framework. It highlights the main features of Sino-African relations and specifically assesses why China is important to African states. It examines FOCAC objectives for Africa, FOCAC conferences, the decisions adopted and their impact on Sino-African relations. The paper offers recommendations that will allow African states to better leverage their relations with China.
Prospects for Negotiation as a Means of Undoing the Gordian Knot of Just Land Reform in South Africa
Authors: Anstey Mark
Published: October 2022

Creative and courageous negotiations between 1990 and 1994 enabled South African leaders to end apartheid and manage the first phase of a transition to a constitutional democracy. Land was a key issue in the struggle for democracy, but after thirty years remains unresolved. The Bill of Rights in the Constitution affords protection for property rights but also commits the government to land reform by way of restitution or redress of the disadvantaged who suffered through dispossession following the 1913 Land Act. The failure of government’s three-track system to deliver on the goals it set for transfer of land from white to black ownership has strengthened demands for radical change. This article explores the prospects of negotiation as a means for resolving obstacles to progress, including the problem of competing notions of justice. New levels of engagement between stakeholders enabling a sense of justness in the process and outcome are required.
Manifestations of Social Exclusion in Qualitative Interview Material
Authors: Repo-Saeed Nora
Published: October 2022

In this article I examine manifestations of social exclusion in qualitative interview material that was gathered in Finland. In the focus are people with a foreign background whose experiences I study with a decolonising approach. Social exclusion manifests itself in diverse ways in the narratives of the interviewees and can be discerned, for example, as related to discriminative and racist attitudes, people’s appearance, colour of the skin, language skills, religion, study skills, work skills, gender, cultural norms, access to education, social class, future perspectives, transactions with the authorities, questions related to the right to stay in the country, or possibilities to obtain citizenship. The experiences of the interviewees embody a need of further examination of colonialist legacy in the Finnish context, a call for more monitoring and control of institutional structures involved in discriminative measures imposed on people with a foreign background, as well as wider societal debate when it comes to stereotypes and bias that can lead to social exclusion.
‮לכל שלטניה‬‎—A New Edition of the Wolfe Golden Amulet in Jewish Palestinian Aramaic
Authors: Morgenstern Matthew
Published: October 2022

The article presents a new edition of the Wolfe Golden Amulet based upon a close examination of new RTI images and its interpretation in light of related Aramaic and Hebrew sources. New readings and translations are presented for many parts of the text.
Taxonomic study of the leafhopper genus Mitjaevia Dworakowska (Hemiptera: Cicadellidae: Typhlocybinae: Erythroneurini) from China, with descriptions of five new species
Authors: LIN SHUANGHU , ZOU HONGFEN , HUANG MIN , ZHANG YALIN
Published: October 2022

The genus Mitjaevia Dworakowska is reviewed with five new species described from China: M. acrodonta, M. bisecta, M. flexuosa, M. quinquedentata and M. tridentata spp. nov.. Detailed morphological descriptions and illustrations of these five new species and a key to all known species (males) from China are provided.
Parametric Subharmonic Instability of Diurnal Internal Tides in the Abyssal South China Sea
Authors: Hu Qianwen , Huang Xiaodong , Xu Qinbo , Zhou Chun , Guan Shoude , Xu Xing , Zhao Wei , Yang Qingxuan , Tian Jiwei
Published: October 2022

Internal waves close to the seafloor of abyssal oceans are the key energy suppliers driving near-bottom mixing and the upwelling branches of meridional overturning circulation, but their spatiotemporal variability and intrinsic mechanisms remain largely unclear. In this study, measurements from 10 long-term moorings were used to investigate the internal wave activities in the abyssal South China Sea, which is an important upwelling zone. Strong near-inertial internal waves (NIWs) with current velocity pulses exceeding 5 cm s−1 were observed to dominate the near-bottom internal wave field at approximately 14°N. These abyssal NIWs were phase-coupled with diurnal internal tides (D1), and both displayed common seasonal variations that were larger in winter and summer, providing evidence of diurnal parametric subharmonic instability (PSI) near its critical latitudes (CLs). Emitted from the bottom, near-inertial kinetic energy rapidly decreased by one order of magnitude from depths of ∼120 to ∼620 m above the bottom. Near rough topographies, the abyssal PSI was shifted poleward to approximately 14.8°N by negative relative vorticities of passing anticyclonic eddies or topographic Rossby waves. Compared with flat topography, PSI near rough topography was significantly promoted by topographic-localized strong D1 with high-mode structures, creating abyssal NIW bursts. Bottom-reaching shipboard conductivity–temperature–depth profiles revealed that the bottom mixed layers became much thicker when approaching CLs, suggesting that abyssal PSI potentially accelerates the ventilation and upwelling of bottom water. The observational results presented here illustrate notable spatiotemporal variations in abyssal NIWs regulated by PSI and call for consideration of PSI to better understand near-bottom mixing and upwelling.
Adapting a Telehealth Network for Emergency COVID-19 Pandemic Response, 2020-2021
Authors: Stephens David , Weiser Thomas , Mera Jorge , Becker Tom , Essex Whitney , Brown Harry , Vinson Eric , Woodbury Megan , Reilley Brigg , Leston Jessica
Published: October 2022

In March 2020, a Tribal telehealth program—the Indian Country Extension for Community Health Outcomes (ECHO)—added emergency COVID-19 to its programming to support the pandemic response. A long-standing relationship with a network of Indian Health Service, Tribal, and urban Indian clinicians supported a rapid launch of the COVID-19 telehealth program. This nationwide service offered primary care clinicians and staff serving American Indian/Alaska Native people access to virtual learning opportunities, expert clinical recommendations, technical assistance, and capacity building. From March 12, 2020, through April 30, 2021, the program provided 85 clinical sessions in 12 months, with an average participation of 120 attendees per clinic (N = 11 710). Attendees could complete a voluntary evaluation form for each session via an online link. A total of 2595 forms were completed. Attendees came from 33 states and 206 unique locations, primarily from the Pacific Northwest (n = 931, 35.9%). Most pharmacists (78.1%), providers (ie, medical doctor, doctor of osteopathy, advanced practice nurse, physician assistant, or clinical nurse midwife; 70.8%), and nurses (59.6%) gave the sessions the highest rating of “very satisfied.” The highest proportion of attendees indicating that they planned a change in practice were pharmacists (68.0%), nurses, (64.1%), and providers (61.3%). Most attendees (93.1%) said that the COVID-19 sessions gave them a sense of social support. Lessons learned were that (1) a telehealth platform can be quickly retasked for emergency response with no further delays, (2) a telehealth network can be scaled up quickly with participation from preexisting relationships, and (3) the platform is flexible and adaptable to the needs of participants. An existing telehealth program can be a key part of timely, relevant, large-scale emergency readiness and response efforts.
An empirical test of measures of housing degrowth: Learning from the limited experience of England and Wales, 1981–2011
Authors: Tunstall Rebecca
Published: October 2022

This article builds on the concept of ‘degrowth’ to create an experimental, measurable definition of ‘housing degrowth’, which can be applied to the 99% of households in mainstream housing. Like ‘degrowth’, housing degrowth runs against housing policy which has assumed that more housing is good. The article explores whether measurement of housing degrowth is possible with existing data, and whether any housing degrowth has occurred in the existing pro-growth housing system in England and Wales. Building on Kallis et al., ‘housing degrowth’ is defined as a reduction of the total resources going into housing production and use, without an increase in inequality or a loss of wellbeing. First, using the total number of rooms as a proxy, over 1981–2011, England and Wales experienced significant increases in embodied CO2 (from housing construction, maintenance and disposal). Only a handful of areas experienced reductions, even in resources per person, and in these, inequality increased, and some had very little space per person for the worst-off, likely to harm wellbeing. Second, estimated data on direct CO2 production by homes in use 2008–18 showed a reduction, which was equitable between income and tenure groups. However, the poorest were hit hardest by rising energy costs, likely to have depressed wellbeing, again failing the degrowth definition. In conclusion, assessing broad trends in housing degrowth is possible, even with imperfect data. Future intentional degrowth appears possible, but will need more political justification, changes to incentives and regulation, and a focus on those worst-off.
Not just a liberal – Social philosophy as antiauthoritarian and utopian social criticism: Richard Rorty’s Achieving Our Country today
Authors: Brunkhorst Hauke
Published: October 2022

Rorty understands pragmatism in philosophy and social science, literature and art, to be intertwined with the political project of changing the world. Achieving Our Country, together with a lecture on the 150th anniversary of the Communist Manifesto, has become Rorty’s political testament. Rorty understands the leftist American project as the incomplete one of all those who fight for a classless society of boundless diversity (1). At the centre of Achieving Our Country is the tragic division between old and new, social and cultural Left (2). Rorty’s patriotism is progressive and cosmopolitan (3). The American project can only be realized if the Left breaks the hegemony of the political Right (4). For that, America must be understood as a utopia that makes itself the avant-garde of global political, economic, social and cultural change (5). This utopia can be realized only by a new kind of unity between leftist centres in the university and leftist organizational power in the rest of society. In this respect, America could become a model for the rest of the world again (6).
Substance P Inhibitor Promotes Tendon Healing in a Collagenase-Induced Rat Model of Tendinopathy
Authors: Ko Kyung Rae , Han Soo-Hong , Choi Sujin , An Hyun-Ju , Kwak Eun-Bee , Jeong Yunhui , Baek Minjung , Lee Jusung , Choi Junwon , Kim Il-Su , Lee Soonchul
Published: October 2022

Background:

The substance P–neurokinin 1 receptor pathway has been proposed as a therapeutic target for tendinopathy. However, there is a lack of evidence regarding its practical applications.

Purpose:

To investigate the therapeutic effects of substance P inhibitor (SPI) on inflamed tenocytes in vitro and in a collagenase-induced rat model of tendinopathy in vivo.

Study Design:

Controlled laboratory study.

Methods:

We analyzed the mRNA levels of inflammatory (cyclooxygenase [COX]-2 and interleukin [IL]-6) and tenogenic (Mohawk and scleraxis [SCX]) markers using reverse transcription quantitative polymerase chain reaction to demonstrate the effects of SPI on lipopolysaccharide-treated (inflamed) tenocytes. A collagenase-induced rat model of tendinopathy was created by injecting 20 µL of collagenase into the Achilles tendon. A behavior test using an incapacitance apparatus was performed to detect changes in postural equilibrium. The tendon specimens were obtained, and their gross findings were examined. The tensile strength was measured, and histopathological evaluation was performed (hematoxylin and eosin, alcian blue, and immunohistochemical staining).

Results:

The mRNA levels of COX-2, IL-6, Mohawk, and SCX differed significantly between inflamed tenocytes and those treated with SPI. SPI improved the weight burden in a rat model of tendinopathy in a behavioral test. The specimens of the SPI group showed a normal tendon-like appearance. In the biomechanical test, the tensile strength of the SPI group was significantly greater than that of the tendinopathy group. In the histopathological evaluation, the degree of collagen matrix breakdown was mild in the SPI group. In alcian blue staining, only small focal depositions of proteoglycans and glycosaminoglycans were observed in the SPI group. The SPI group showed decreased expression of IL-6 and neurokinin 1 receptor.

Conclusion:

This study suggests that SPI has therapeutic effects on tendon healing and restoration in a collagenase-induced rat model of tendinopathy.

Clinical Relevance:

SPI is a promising agent for tendinopathy in humans.
Equine Odontoclastic Tooth Resorption and Hypercementosis
Authors: James Olivia
Published: October 2022

Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is a recently described painful and progressive condition of unknown etiology that occurs in middle-aged and geriatric equines. It predominantly affects the permanent incisor and canine teeth and, less commonly, the premolar and molar dentition. EOTRH was first reported in peer-reviewed literature in 2008, with subsequent publications of case reports, histological studies and retrospective case series. There have been few significant research developments related to this disease. The existing studies have primarily involved single case studies or small sample sizes, without control groups. This review aimed to report current information about EOTRH in terms of clinical, histopathological, diagnostic, radiological, and therapeutic aspects, by searching the available peer-reviewed scientific literature.
The Limited Benefits of Using Virtual Reality 360° Videos to Promote Empathy and Charitable Giving
Authors: Martingano Alison Jane , Konrath Sara , Henritze Evan , Brown Adam D.
Published: October 2022

Charitable organizations have embraced virtual reality (VR); however, scientific evidence supporting its effectiveness for social good often uses poor experimental methodology and finds inconsistent results. We conducted a rigorous randomized control trial testing whether 360° video virtual reality increases empathy and charitable donations. Participants ( N = 155) were randomly assigned to one of four conditions: (a) Classic: 360° footage of child refugees, (b) Boost: the same, but with perspective-taking instructions, (c) Audiobook: a control condition with the same information about child refugees but in text format, or (d) Waiting Room: another control condition with a 360° view of a waiting room. Although the Classic and Boost conditions increased emotional empathy compared to controls, they did not improve cognitive empathy more than the audiobook. Moreover, any empathic gains were mostly extinguished after 10 days. Critically, the Classic and Boost conditions did not influence charitable donations to a relevant charity (UNICEF). Therefore, charitable organizations may wish to tentatively reconsider their investment in 360° videos as, although they appear to make people feel empathic in the moment, these feelings do not appear to translate into tangible action.
Determinants of self-drive attributes supporting destination advocacy: Case of Thai domestic tourists
Authors: Fakfare Pipatpong , Jianvittayakit Laddawan , Wattanacharoensil Walanchalee
Published: October 2022

This case study aims to provide additional insights into the domestic self-drive market segment. The purpose of this research is threefold. First, the study validates the multidimensional attributes of the car-self-drive experience. Second, this study investigates the effects of self-drive attributes on tourist delight and memorable experience as well as their influence on destination advocacy. Finally, by focusing on different age segments, this study examines the priority of self-drive attributes in relation to importance and performance. An online survey (n = 1260) was conducted via convenience and snowball sampling. Findings indicate four destination attributes and two driving attributes that affect tourist delight as well as two destination attributes and one driving attribute that affect tourists’ memorable experience. The results vary on the basis of age segments. The importance–performance map analysis was further conducted to identify the importance–performance levels of the self-drive attributes. This study provides several contributions to the self-drive tourism industry by complementing previous studies, assembling multidimensional attributes and introducing a new outcome variable. The practical implications of this study also benefit tourism and destination authorities in promoting self-drive tourism to different age groups, particularly in Thailand and in the ASEAN region.
Ultrasound-guided versus conventional peribulbar anaesthesia in cataract surgery: A randomised controlled study
Authors: Naguib Nader N , Mohasseb Tariq M , Ezzat Azza M , Hussien Gomaa Z , Khattab Rehab S , Aboul Fetouh Eman S , Dobal Nasser M
Published: October 2022

Background:

Blind ophthalmic anaesthetic techniques may have serious complications.

Aim:

To assess the safety of ultrasound as a guide in ophthalmic blocks.

Methods:

Fifty adult patients undergoing cataract surgery under peribulbar block anaesthesia were randomly assigned to ultrasound-guided and conventional block groups. In the ultrasound-guided block group, a large amount of the standard ultrasound gel was applied to the closed eyelids. The globes were scanned in both sagittal and transverse planes. The patients were asked to look straight ahead with closed eyes without clenching the eyelids. The depth and gain were adjusted before performing the block. The primary outcome was the rate of complications. Secondary outcomes included the volume of injected anaesthetics and surgeon and patients’ satisfaction.

Results:

The local anaesthetic volume used was not significantly different between the two groups (7.08 ± 1.66 and 6.72 ± 1.97ml). The block onset, time and quality were comparable in both groups. No complications were reported, and there were no significant differences regarding surgeons’ or patients’ satisfaction with either procedure.

Conclusion:

The ultrasound-guided local ophthalmic block is as safe as the conventional method. Although its use was not superior to the conventional procedure, direct visualisation with ultrasound may be important to avoid vulnerable structures such as staphylomas.
Stabilizing effect of an elbow orthosis with an adjustable hinge axis after lateral collateral ligament injury: A biomechanical study
Authors: Badre Armin , Axford David T , Kotzer Sara , Johnson James A , King Graham JW
Published: October 2022

Background

Current commercial elbow braces have a straight hinge that does not account for the native carrying angle of the elbow. The objective of this study was to determine the effectiveness of a custom-designed hinged elbow orthosis (HEO) with variable valgus angulations in stabilizing a lateral collateral ligament (LCL) deficient elbow.

Methods

Eight cadaveric upper extremities were mounted in an elbow motion simulator in the abducted varus gravity-loaded position. The specimens were examined before and after simulated LCL injury and then with the addition of the custom-designed HEO with 0°, 10°, and 20° of valgus angulation. Kinematic data were recorded using an electromagnetic tracking system.

Results

The LCL injured state with or without the brace resulted in significant increases in varus angulation of the elbow compared to the intact state in both pronation and supination ( P < 0.05). There were no significant differences in varus-valgus angulation or ulnohumeral rotation between any of the brace angles and the LCL injured state with the forearm pronated and supinated.

Discussion

The custom-designed HEO did not provide any additional stability to the LCL injured elbow. The varus arm position should be avoided during the rehabilitation of an LCL injured elbow even when an HEO is used.
The Effect of Coumestrol on Hub Genes in Lung Squamous Cell Carcinoma Based on Bioinformatic Strategy
Authors: Shan Qingqing , Zhang Yifan , Zhang Xu , Wang Wei , Liang Zongan
Published: October 2022

Purpose There is limited treatment for lung squamous cell carcinoma (LUSC), so there is an urgent need to find new antitumor drugs. Materials and Methods We downloaded datasets from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas databases. We used GEO2R and the “limma” package to screen differentially expressed genes. We used the Cytoscape software to screen out hub genes. We screened herbs that act on hub genes on the Chinese medicine website. We then studied the effect of coumestrol (CM) on the hub genes in the H226 cell line. Results Seven hub genes were screened, namely CCNB2, CENPF, KIF11, MELK, nucleolar and spindle-associated protein 1 (NUSAP1), PBK, and RRM2. We observed that CM had a tumor-inhibiting effect on H226 cells by inhibiting the expression of CCNB2, KIF11, and NUSAP1. Conclusion CM, screened by bioinformatics and network pharmacology, can inhibit H226 cells by downregulating CCNB2, KIF11, and NUSAP1.
Riociguat and the right ventricle in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension
Authors: Benza Raymond L. , Langleben David , Hemnes Anna R. , Vonk Noordegraaf Anton , Rosenkranz Stephan , Thenappan Thenappan , Hassoun Paul M. , Preston Ioana R. , Ghio Stefano , Badagliacca Roberto , Vizza Carmine D. , Lang Irene M. , Meier Christian , Grünig Ekkehard
Published: October 2022

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive diseases that can lead to right heart failure and death. Right ventricular dysfunction, hypertrophy and maladaptive remodelling are consequences of increased right ventricular (RV) afterload in PAH and CTEPH and are indicative of long-term outcomes. Because RV failure is the main cause of morbidity and mortality in PAH and CTEPH, successful treatments should lead to improvements in RV parameters. Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of PAH and inoperable or persistent/recurrent CTEPH after pulmonary endarterectomy. This review examines the current evidence showing the effect of riociguat on the right ventricle, with particular focus on remodelling, function and structural parameters in preclinical models and patients with PAH or CTEPH.
Genomic characterization of Bacillus cereus sensu stricto 3A ES isolated from eye shadow cosmetic products
Authors: Yossa Nadine , Bell Rebecca , Tallent Sandra , Brown Eric , Binet Rachel , Hammack Thomas
Published: October 2022

Background

The Bacillus cereus group, also known as B. cereus sensu lato (s.l.) contains ubiquitous spore-forming bacteria found in the environment including strains from the B. cereus sensu stricto (s.s.) species. They occur naturally in a wide range of raw materials and in consumer products. Characterizing isolates that have survived in consumer products allows us to better understand the mechanisms that permit spores to persist and potentially cause illness. Here we characterize the draft genome sequence of B. cereus s. s. 3A-ES, originally isolated from eye shadow and since investigated in several cosmetic studies and compared it to other top ten published complete genome sequences of B. cereus s.l. members.

Results

The draft genome sequence of B. cereus s.s. 3A ES consisted of an average of 90 contigs comprising approximately 5,335,727 bp and a GC content of 34,988%, and with 5509 predicted coding sequences. Based on the annotation statistics and comparison to other genomes within the same species archived in the Pathosystems Resource Integration Center (PATRIC), this genome “was of good quality. Annotation of B. cereus s.s. 3A ES revealed a variety of subsystem features, virulence factors and antibiotic resistant genes. The phylogenetic analysis of ten B. cereus group members showed B. cereus s.s. 3A-ES to be a closely related homolog of B. cereus s.s. ATCC 14,579, an established reference strain that is not adapted for cosmetic microbiological studies. Survival of 3A-ES in eye shadow could be linked to predicted stress-response genes and strengthened by additional stress-response genes such as VanB-type, VanRB, CAT15/16, BcrA, BcrB, Lsa(B), and recA that are lacking in B. cereus s.s. ATCC 14,579.

Conclusion

Our genomic analysis of B. cereus s.s. 3A-ES revealed genes, which may allow this bacterium to withstand the action of preservatives and inhibitors in cosmetics, as well as virulence factors that could contribute to its pathogenicity. Having a well-characterized strain obtained from eye-shadow may be useful for establishing a reference strain for cosmetics testing.
Lipopolysaccharide downregulates the expression of ZO-1 protein through the Akt pathway
Authors: Zou Peicen , Yang Fan , Ding Yijun , Zhang Di , Liu Ying , Zhang Jinjing , Wu Dan , Wang Yajuan
Published: October 2022

Background

Neonatal bacterial meningitis is a common neonatal disease with high morbidity, and can cause serious sequelae when left untreated. Escherichia coli is the common pathogen, and its endotoxin, lipopolysaccharide (LPS) can damage the endothelial cells, increasing the permeability of the blood-brain barrier (BBB), leading to intracranial inflammation. However, the specific mechanism of bacterial meningitis induced by LPS damaging BBB remains unclear. In this study, the mouse brain microvascular endothelial (bEND.3) cells were used as a research object to investigate whether LPS damage BBB through the PI3K/Akt pathway.

Methods

The bEND.3 cells were stimulated with different concentrations of LPS for 12 h, and the expression of tight junction proteins (ZO-1, claudin-5, occludin) was detected using western blotting. The cells were challenged with the same concentration of LPS (1ug/ml) across different timepoints (0, 2 h, 4 h, 6 h, 12 h, 24 h). Expression of TJ proteins and signal pathway molecules (PI3K, p-PI3K, Akt, p-Akt) were detected. The distribution of ZO-1 in bEND.3 cells were detected by immunofluorescence staining.

Results

A negative correlation is observed between ZO-1 and LPS concentration. Moreover, a reduced expression of ZO-1 was most significant under 1 ug/ml of LPS, and the difference was statistically significant (P < 0.05). Additionally, there is a negative correlation between ZO-1 and LPS stimulation time. Meanwhile, the expression of claudin-5 and occludin did not change significantly with the stimulation of LPS concentration and time. The immunofluorescence assay showed that the amount of ZO-1 on the surface of bEND.3 cells stimulated with LPS was significantly lower than that of the control group. After LPS stimulation, p-Akt protein increased at 2 h and peaked at 4 h. The titer of p-PI3K did not change significantly with time.

Conclusion

LPS can downregulate the expression of ZO-1; however, its effect on claudin-5 and occludin is minimal. Akt signal pathway may be involved in the regulation of ZO-1 expression induced by LPS in bEND.3 cells.
A prospective study on the application of HINTS in distinguishing the localization of acute vestibular syndrome
Authors: Qiu Tao , Dai Xiaoyan , Xu Xiaoya , Zhang Guiqin , Huang Linming , Gong Qingping
Published: October 2022

Background

Acute vestibular syndrome (AVS) is a common clinical syndrome in neurology clinics and emergency department. Canonical standard for AVS diagnosis requires the presence of persistent vertigo for more than 24 h. HINTS (head impulse-nystagmus-test of skew) is an emerging scheme in the diagnosis of AVS. In this prospective study, we evaluated the specificity and sensitivity of HINTS in distinguishing between central and peripheral AVS.

Methods

A cohort of 239 cases with complete clinical record was recruited in the study. All patients completed emergency brain CT examination to exclude hemorrhagic stroke. HINTS examination was conducted to distinguish between central AVS and peripheral AVS, and all patients completed head MRI, BAEP and vestibular function examinations within one week. Patients diagnosed as central AVS were subject to angiography (CTA/MRA/DSA), and patients with peripheral AVS were considered for a 3-month follow-up to correct the initial diagnosis.

Results

Patients with central AVS were associated with an elder age, higher incidences of hypertension, atrial fibrillation, family history of stroke and previous history of stroke. Posterior circulation cerebral infarction, vestibular migraine and cerebellitis were the dominant diseases associated with central AVS. The sensitivities of HIT, GE, and TS in the diagnosis of central AVS were 73.5%, 61.2%, and 26.5%, and the specificities were 97.9%, 92.6%, and 93.2% respectively.

Conclusions

The sensitivity of HINTS for central AVS diagnosis is 89.8% and the specificity is 84.2%. HINTS is an easy-to-operate, low-cost, high-sensitivity and specific examination technique, which is practical in neurology outpatient clinics and emergency departments.
EVI1 expression in early-stage breast cancer patients treated with neoadjuvant chemotherapy
Authors: Leichsenring Jonas , Vladimirova Valentina , Solbach Christine , Karn Thomas , Ataseven Beyhan , Sinn Bruno Valentin , Barinoff Jana , Müller Volkmar , Blohmer Jens-Uwe , Schem Christian , Engels Knut , Marmé Frederik , Fisseler-Eckhoff Annette , Fasching Peter A. , Stickeler Elmar , van Mackelenbergh Marion , Denkert Carsten , Stenzinger Albrecht , Loibl Sibylle , Gröschel Stefan
Published: October 2022

Background

Overexpression of the EVI1 (ecotropic viral integration site 1) oncogene has recently been implicated as a prognostic factor in breast cancer (BC), particularly in triple-negative BC (TNBC). In this study we aimed to investigate frequency and clinical relevance of EVI1 expression in newly diagnosed BC treated with neoadjuvant chemotherapy.

Methods

EVI1 expression was determined by immunohistochemistry using H-score as a cumulative measurement of protein expression in pretherapeutic biopsies of BC patients treated with anthracycline/taxane based neoadjuvant chemotherapy within the GeparTrio trial. EVI1 was analyzed as a continuous variable and dichotomized into low or high based on median expression. Endpoints were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS).

Results

Of the 993 tumors analyzed, 882 had available subtype information: 50.8% were HR + /HER2-, 15% HR + /HER2 + , 9.8% HR-/HER2 + , and 24.5% TNBC. Median EVI1 H-score was 112.16 (range 0.5–291.4). High EVI1 expression was significantly associated with smaller tumor size (p = 0.002) but not with BC subtype. Elevated EVI1 levels were not significantly associated with therapy response and survival in the entire cohort or within BC subtypes. However, TNBC patients with high EVI1 showed a trend towards increased pCR rates compared to low group (37.7% vs 27.5%, p = 0.114; odds ratio 1.60 (95%CI 0.90–2.85, p = 0.110) and numerically better DFS (HR = 0.77 [95%CI 0.48–1.23], log-rank p = 0.271) and OS (HR = 0.76 [95% 0.44–1.31], log-rank p = 0.314) without reaching statistical significance.

Conclusion

EVI1 was not associated with response to neoadjuvant therapy or patient survival in the overall cohort. Further analyses are needed to verify our findings especially in the pathological work-up of early-stage HER2-negative BC patients.

Trial registration

NCT00544765.
Prognosis of lasso-like penalized Cox models with tumor profiling improves prediction over clinical data alone and benefits from bi-dimensional pre-screening
Authors: Jardillier Rémy , Koca Dzenis , Chatelain Florent , Guyon Laurent
Published: October 2022

Background

Prediction of patient survival from tumor molecular ‘-omics’ data is a key step toward personalized medicine. Cox models performed on RNA profiling datasets are popular for clinical outcome predictions. But these models are applied in the context of “high dimension”, as the number p of covariates (gene expressions) greatly exceeds the number n of patients and e of events. Thus, pre-screening together with penalization methods are widely used for dimensional reduction.

Methods

In the present paper, (i) we benchmark the performance of the lasso penalization and three variants (i.e., ridge, elastic net, adaptive elastic net) on 16 cancers from TCGA after pre-screening, (ii) we propose a bi-dimensional pre-screening procedure based on both gene variability and p-values from single variable Cox models to predict survival, and (iii) we compare our results with iterative sure independence screening (ISIS).

Results

First, we show that integration of mRNA-seq data with clinical data improves predictions over clinical data alone. Second, our bi-dimensional pre-screening procedure can only improve, in moderation, the C-index and/or the integrated Brier score, while excluding irrelevant genes for prediction. We demonstrate that the different penalization methods reached comparable prediction performances, with slight differences among datasets. Finally, we provide advice in the case of multi-omics data integration.

Conclusions

Tumor profiles convey more prognostic information than clinical variables such as stage for many cancer subtypes. Lasso and Ridge penalizations perform similarly than Elastic Net penalizations for Cox models in high-dimension. Pre-screening of the top 200 genes in term of single variable Cox model p-values is a practical way to reduce dimension, which may be particularly useful when integrating multi-omics.
Association of levels of metabolites with the safe margin of rectal cancer surgery: a metabolomics study
Authors: Zhang Shaopeng , Pan Guoqiang , Liu Zhifeng , Kong Yuan , Wang Daguang
Published: October 2022

Background

Rectal cancer is one of the most lethal of gastrointestinal malignancies. Metabonomics has gradually developed as a convenient, inexpensive and non-destructive technique for the study of cancers.

Methods

A total of 150 tissue samples from 25 rectal cancer patients were analyzed by liquid chromatography–mass spectrometry (LC–MS), and 6 tissue samples were collected from each patient (group 1: tumor; group 2: 0.5 cm from tumor; group 3:1 cm from tumor; group 4:2 cm from tumor; group 5:3 cm from tumor and group 6:5 cm from tumor). The differential metabolites of tumor tissues and 5 cm from the tumor (normal tissues) were first selected. The differential metabolites between tumor tissues and normal tissues were regrouped by hierarchical clustering analysis, and further selected by discriminant analysis according to the regrouping of clustering results. The potential safe margin of clinical T(cT)1,cT2 stage rectal cancer and cT3,cT4 stage rectal cancer at the metabolomic level was further identified by observing the changes in the level of differential metabolites within the samples from group 1 to group 6.

Results

We found 22 specific metabolites to distinguish tumor tissue and normal tissue. The most significant changes in metabolite levels were observed at 0.5 cm (cT1, cT2) and 2.0 cm (cT3, cT4) from the tumor, while the changes in the tissues afterwards showed a stable trend.

Conclusions

There are differential metabolites between tumor tissues and normal tissues in rectal cancer. Based on our limited sample size, the safe distal incision margin for rectal cancer surgery in metabolites may be 0.5 cm in patients with cT1 and cT2 stage rectal cancer and 2.0 cm in patients with cT3 and cT4 stage rectal cancer.
Association between obese phenotypes and risk of carotid artery plaque among chinese male railway drivers
Authors: Pan Jia , Wang Zihang , Dong Chaohui , Yang Bo , Tang Lei , Jia Peng , Yang Shujuan , Zeng Honglian
Published: October 2022

Background

China has the world’s highest rail transportation network density, and the prevalence of obesity among railway workers in China is more than twice that of adults in the world. Carotid artery plaque (CAP) is a simple and noninvasive predictor of early atherosclerosis, while the association between different obese phenotypes and CAP risk among Chinese male railway drivers is unclear.

Methods

This cross-sectional study was performed among 8,645 Chinese male railway drivers. Obese phenotypes were assessed based on the obesity status (the body mass index ≥ 28 kg/m2 as obesity vs. < 28 kg/m2 as non-obesity) and metabolic status (metabolically healthy vs. metabolically unhealthy). Metabolically unhealthy was defined as the presence of at least one dysfunction, including elevated blood pressure, elevated fasting blood glucose, elevated triglyceride, and reduced high-density-lipoprotein cholesterol. Four obese phenotypes were defined based on the body mass index and metabolic status, i.e., metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), and metabolically unhealthy non-obesity (MUNO). Multivariable logistic regression was employed to estimate the association between different obese phenotypes and the risk of CAP. Subgroup analysis was performed to examine the variation of the association by age, circadian rhythm disorders, and history of smoking and drinking.

Results

The prevalence of CAP among male railway drivers in MHO, MUO, MUNO, and MHNO was 8.75%, 18.67%, 17.82%, and 5.36%, respectively. Compared to those with MHNO, an increased risk for CAP was observed among those with MHO (OR = 2.18, 95% CI: 0.82, 5.10), MUO (OR = 1.78, 95% CI:1.44, 2.21), and MUNO (OR = 2.20, 95% CI: 1.67, 2.89). The subgroup analysis showed that both of the metabolically unhealthy groups (MUNO and MUO) aged < 45 years were prone to a higher risk of CAP (for the MUNO group, OR = 4.27, 95% CI:2.71, 7.10; for the MUO group, OR = 4.00, 95%CI: 2.26, 7.17).

Conclusion

The obese phenotypes are associated with CAP risk in male railway drivers, especially those with metabolically unhealthy conditions aged < 45 years.
Domains of competence in midwifery students: a basis for developing a competence assessment tool for iranian undergraduate midwifery students
Authors: Firoozehchian Firoozeh , Zareiyan Armin , Geranmayeh Mehrnaz , Behboodi Moghadam Zahra
Published: October 2022

Background

Current study was conducted with the aim of explaining domains of clinical competence in undergraduate midwifery students so that it addresses the challenges in midwifery curriculum and improving clinical assessment methods in Iranian undergraduate midwifery students.

Methods

Qualitative approach and conventional content analysis were used in the design of the present study. The research setting included midwifery and nursing schools and hospitals and health centers affiliated to Tehran and Guilan universities of medical sciences in Iran. The target population consisted of undergraduate midwifery students in the fourth to eighth semesters of school, midwives working in hospitals and health centers, midwifery faculty members, and obstetricians. The participants were selected through purposive maximum variation sampling, which continued until data saturation. After in-depth semi-structured interviews, the content of the interviews was analyzed according to the steps proposed by Zhang & Wildemuth.

Results

Twenty-four people participated in this study, including seven midwifery students, seven midwives, nine midwifery and reproductive and sexual health faculty members, and one obstetrician. The participants were aged 20–56 years and their mean age was 39.75 years. Their level of education varied from midwifery student to PhD. The mean work experience of the participants was 13.62 years and the mean duration of the interviews was 48 min. The analysis of the data obtained from the experiences of the participants led to the formation of the four categories of ethical and professional function in midwifery, holistic midwifery care, effective interaction, and personal and professional development, along with ten subcategories.

Conclusion

The findings of the present study showed that clinical competence in midwifery students involves different domains that correspond well overall to the general definitions of clinical competence in different sources. These findings can be used as a basis for the design and psychometric assessment of a clinical competence assessment tool for undergraduate midwifery students.
Care across the gender spectrum: A transgender health curriculum in the Obstetrics and Gynecology clerkship
Authors: Schmidt Christina N. , Stretten Monica , Bindman Jay G. , Pettigrew Gaetan , Lager Jeannette
Published: October 2022

Background

A lack of undergraduate medical curricula on providing healthcare to transgender and gender diverse (TGD) patients has contributed to significant health disparities for TGD communities. To address this gap, we designed and evaluated a novel curriculum to train Obstetrics and Gynecology (OB/GYN) clerkship students in caring for TGD patients.

Methods

Following Kern’s 6-step method for curriculum development, we created a two-part curriculum on TGD healthcare topics – an online module on gender-affirming care, followed by a series of interactive cases on TGD-specific health topics. Undergraduate medical students completing their core OB/GYN clerkships at a university academic medical center (January-December 2021) were invited to complete this curriculum. Participants completed pre/post assessment surveys to assess their experience caring for TGD patients, as well as a scored knowledge assessment before and after completing the curriculum.

Results

Sixty-five students participated in this curricular assessment. Prior to completing the module, 45% agreed that they had received adequate TGD health training. Following module completion, students reported increased comfort in caring for transgender patients (49.2% vs. 81.5%; p < .001) and endorsed an improved fund of knowledge of both healthcare maintenance for TGD patients (61.5% vs. 100%; p < .001) and gender affirming medical therapies (60.0% vs. 96.9%; p < .001). Knowledge scores increased from a mean of 9.65 (1.81) to 12.5 (2.20) out of 15 (p < .001). In post-assessment surveys, 95% of participants agreed that the module was helpful for their learning. Qualitatively, students suggested longitudinal integration of TGD-topics into the pre-clinical curriculum, and expanded opportunities to practice patient counseling.

Conclusion

The findings of this study support the need for student education on TGD health. Integration of interactive, case-based TGD-care curricula into clinical training may increase medical students’ knowledge and comfort in caring for TGD patients. Ongoing efforts to integrate TGD health training into undergraduate medical student curricula are necessary.