bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the role of inflammation in keratoconus: A retrospective analysis of 551 eyes
Authors: Nichani Prem A H , Solomon Benjamin , Trinh Tanya , Mimouni Michael , Rootman David , Singal Neera , Chan Clara C
Published: September 2022

Purpose

Keratoconus (KCN), classically defined as a noninflammatory corneal ectasia, was recently associated with chronic inflammation. This study aimed to further evaluate the association between inflammation and KCN severity by assessing patient tear films.

Methods

Retrospective chart review of consecutive patients (July 2016–February 2020) referred to a tertiary KCN centre. Using tomography Kmax values, the worst-eyes of patients with a diagnosis of KCN and tear film test results were included. Eyes were stratified as matrix metalloproteinase-9 (MMP9) positive or negative and analyzed using independent t and Pearson chi-squared tests. A p-value ≤ 0.05 was considered significant.

Results

551 (51.40%) unilateral eyes were included. Mean age was 30.1 years and 70.1% were male. 55.5% of the eyes were MMP9 positive. Mean corrected distance visual acuity was 20/30<συπ>−3 Snellen and Kmax was 60.1 Diopters. MMP9 positive eyes had a higher Kmax (p = 0.048), and were more likely from patients who were male (p < 0.001), had a paediatric history of asthma (p = 0.042), and used glasses (p = 0.041). MMP9 negative eyes more likely corresponded to soft contact lens users (p = 0.012). No other significant differences were found in risk factors, topography, tomography, and tear film osmolarity.

Conclusion

MMP9 positive keratoconic eyes had significantly higher Kmax readings which may correlate with increased disease severity, supporting an association between keratoconus and inflammation. Further research is warranted to evaluate the role of targeted therapy and contact lens use on MMP9 levels in keratoconic eyes and whether disease progression is affected.
Factors Influencing Drug Use Information Received at Primary Healthcare Centre Pharmacies in Ghana
Authors: Ansah Edward Wilson , Menyanu Elias Kweshievi
Published: September 2022

Background:

Health literacy addresses environmental, political, and social factors that determine health. Drug dispensers play a major role in educating patients on drug use to increase effective and efficient drug utilisation, thereby promoting positive healthcare outcomes. From the patients’ perspective, this study examined the communication quality between patients and drug dispensers at primary healthcare centres in the Cape Coast Metropolis of Ghana.

Method:

We conveniently surveyed 269 patients seeking health care at primary healthcare facilities using a researcher-constructed 13-item instrument. In SPSS version 21 software, we analysed the data using percentages, chi-square analysis, and logistic regression.

Results:

Almost half of the participants (n = 132) reported low health literacy, with 81% (n = 218) reporting that drug side effects were not discussed with them at the pharmacies. The findings further indicated that health literacy and educational level predicted general communication quality between participants and drug dispensers; participants with secondary education were about 3 times more likely to report not being told of the side effects of prescribed drugs as compared with those who had completed only basic education.

Conclusions:

There is still a high level of low health literacy among patients seeking healthcare at primary healthcare centres and a very high percentage of patients did not receive any education on side effects of dispensed drugs. Drug use directives from dispensers at primary healthcare facilities can make a difference between any 2 patients.
Does migration fear affect tourism demand? Evidence from instrumental variable cointegration test
Authors: Kocak Emrah , Yucel Ali Gokhan
Published: September 2022

Migration and migration-caused concerns and uncertainties have been rising dramatically in recent years at the global level. However, our knowledge of the impact of migration-related concerns on tourism is limited. To address this gap, we estimate the impact of the US migration fears on tourist arrivals from Western Europe to the US using a tourism demand model. The paper employs a new robust cointegration approach with instrumental variables. Our estimates suggest that tourists from Western Europe have a negative and significant long-term response to the fear of migration in the US. The results show that migration-related concerns are constraints on the development of the tourism industry in the US.
‘It’s not who I want to be!’: Negotiating the ‘illegible’ single woman in US–UK popular culture
Authors: Gilchrist Kate R
Published: September 2022

Drawing on analysis of media representations and interviews with 25 single women, this article argues that the single woman is abjectified in US–UK popular culture through processes of instability and incoherence, which construct her as a threat to heteronormative femininity and recentres the coupled norm. Yet there are moments of contestation within media portrayals, where her ‘illegibility’ allows for a troubling of the gender binary and opens up spaces for working with and against such oppressive structures. Drawing on Butler’s heterosexual matrix, I show that singledom is produced here as a non-normative heterosexual practice, which radically destabilises femininity and heteronormativity. This article examines not only how single femininity is being culturally delegitimised, but also how single women in the United Kingdom experience such delegitimisation. Through complex processes of what José Esteban Muñoz calls ‘(dis)identification’, the women work with, alongside and against representations of normative coupled femininity. They also tactically work with portrayals of the single woman to self-reflexively construct alternative single feminine subjectivities. Yet more troublingly, even in moments of resistance, the single women make painful identifications with their abject positioning.
Stability analysis and design of an unmanned deformable vehicle during coupled reconfiguration motion
Authors: Liu Jun , Yan Zhenkun , Lu Mingming , Zhang Liang , Cui Taowen , Zheng Minyi , Wu Di
Published: September 2022

An unmanned deformable vehicle, which is a new type of robot combining a car and a robot, can drive at high speed with wheels and walk with steps. An unmanned deformable vehicle is prone to tipping instability when reconfigured between the automotive and humanoid states. The following work reported herein addresses these issues. The kinematic model of an unmanned deformed vehicle during the coupled reconfiguration process was established. The zero moment point (ZMP) theory was used as the stability criterion, and based on the requirement for stability during the reconstruction process, a genetic algorithm was used to find the optimal value of the support state foot landing position for the parking and driving coupled reconfiguration, and for the optimal value of the driving acceleration of the deformed vehicle during the driving coupled reconfiguration. On the basis of the optimal foot landing position, the total reconfiguration time threshold, deformed vehicle driving acceleration threshold, and support surface tilt angle threshold were analysed and calculated in accordance with stability requirements during the reconfiguration. Finally, the stability performance of the optimised system was verified through prototype testing.
Intravascular Lithotripsy Assisted Carotid Stent Expansion
Authors: Mehta Veena , Wooster Mathew
Published: September 2022

Purpose:

Carotid stenting has been demonstrated to effectively reduce the risk of stroke in appropriately selected patients. However, application of carotid artery stenting remains limited in the setting of heavily calcified disease.

Case Report:

We present here 3 patients, who were treated with intravascular lithotripsy of the internal and common carotid arteries. All 3 patients recovered uneventfully and have demonstrated excellent stent expansion on surveillance imaging.

Conclusion:

Intravascular lithotripsy is an effective adjunct for enabling stent expansion in heavily calcified lesions and can be employed for the treatment of high-risk carotid lesions that would otherwise be poor endovascular candidates.

Clinical Impact

Carotid artery stenting via transfemoral or transcarotid application remains limited by heavily calcified disease. We present here the off-label use of intravascular lithotripsy as an effective adjunct for enabling stent expansion in heavily calcified lesions. There is potential for intravascular lithotripsy to expand the use of carotid stenting.
Giant Inferior Mesenteric Vein Aneurysm Secondary to Iatrogenic Inferior Mesenteric Arteriovenous Fistula
Authors: Pedersen Vilde , Ohrlander Tomas , Frevert Susanne , Malina Martin
Published: September 2022

Purpose:

Visceral venous aneurysms are rare, especially in the inferior mesenteric vein (IMV). We report a giant IMV aneurysm secondary to an iatrogenic arteriovenous fistula (AVF).

Case Report:

A woman presented with an incidental finding of a 7 cm large IMV aneurysm and an inferior mesenteric arteriovenous shunt. The patient underwent successful endovascular occlusion of the shunt to avoid aneurysm rupture and portal hypertension.

Conclusion:

Embolization is a possible treatment strategy for mesenteric venous aneurysms with an AVF.

Clinical Impact

We describe an unusual mesenteric AV-shunt from a surgical crush injury that caused a giant venous mesenteric aneurysm and offer technical aspects on minimally invasive endovascular treatment.
Anti-metastatic Potential of Natural Triterpenoid Cucurbitacin B Against Cholangiocarcinoma Cells by Targeting Src Protein
Authors: Kaewmeesri Putthaporn , Pocasap Piman , Kukongviriyapan Veerapol , Prawan Auemduan , Kongpetch Sarinya , Senggunprai Laddawan
Published: September 2022

Owing to the crucial role of Src in cancer metastasis, interruption of Src and its signaling has been considered a promising strategy for cancer metastasis treatment. Cucurbitacin B, a dietary triterpenoid, has been shown to possess anti-proliferative and apoptosis-inducing activities in cholangiocarcinoma (CCA) cells via suppressing the activation of FAK which is a main downstream Src effector. We hypothesized that cucurbitacin B might act as a Src suppressant which conferring anti-metastasis effect against CCA cells. To investigate this, the role of Src in regulating metastasis behavior of CCA cells and the effect of cucurbitacin B on Src-mediated metastatic phenotype of these cells were determined. The results showed that activation of Src significantly enhanced the migratory and invasive abilities of CCA cells. Molecular analysis revealed that Src-facilitated metastasis behavior of CCA cells occurred by modifying expression of a wide range of metastasis-related genes in the cells. Consistent with gene expression results, activation of Src significantly induced the protein expression of 2 important metastasis-associated molecules, MMP-9 and VEGF. Cucurbitacin B markedly suppressed activation of Src and its key effector, FAK. As a consequence, the alteration of expression profiles of metastasis-associated genes induced by Src activator in CCA cells was diminished by cucurbitacin B treatment. The compound also down-regulated Src-induced expression of MMP-9 and VEGF proteins in the cells. Moreover, molecular docking analysis revealed that cucurbitacin B could interact with Src kinase domain and possibly restrain the kinase from being activated by hindering the ATP binding. In conclusion, cucurbitacin B exhibited anti-metastatic property in CCA cells via negatively influencing Src and Src-related oncogenic signaling. This compound may therefore be a potential therapeutic drug for further development as an anti-Src agent for treatment of metastatic CCA.
A new promising oncogenic target (p.C382R) for treatment with pemigatinib in patients with cholangiocarcinoma
Authors: Hempel Louisa , Lapa Constantin , Dierks Alexander , Gaumann Andreas , Scheiber Josef , Veloso de Oliveira Julia , Philipp Patrick , Oyarzun Laura Cristina , Wesarg Stefan , Robert Sebastian , Hempel Dirk
Published: September 2022

Point mutations of the fibroblast growth factor receptor (FGFR)2 receptor in intrahepatic cholangiocarcinoma (iCC) are mainly of unknown functional significance compared to FGFR2 fusions. Pemigatinib, a tyrosine kinase inhibitor, is approved for the treatment of cholangiocarcinoma with FGFR2 fusion/rearrangement. Although it is hypothesized that FGFR2 mutations may cause uncontrolled activation of the signaling pathway, the data for targeted therapies for FGFR2 mutations remain unclear. In vitro analyses demonstrated the importance of the p.C382R mutation for ligand-independent constitutive activation of FGFR2 with transforming potential. The following report describes the clinical case of a patient diagnosed with an iCC carrying a FGFR2 p.C382R point mutation which was detected in liquid, as well as in tissue-based biopsies. The patient was treated with pemigatinib, resulting in a sustained complete functional remission in fluorodeoxyglucose-positron emission tomography/computed tomography over 10 months to date. The reported case is the first description of a complete functional remission under the treatment with pemigatinib in a patient with p.C383R mutation.
Influence of Graft Type on Lower Extremity Functional Test Performance and Failure Rate After Anterior Cruciate Ligament Reconstruction
Authors: Roach Megan H. , Aderman Michael J. , Gee Shawn M. , Peck Karen Y. , Roach Sean P. , Goss Donald L. , Posner Matthew A. , Haley Chad A. , Svoboda Steven J. , Cameron Kenneth L.
Published: September 2022

Background:

Both autografts and allografts are used to reconstruct the anterior cruciate ligament (ACL) after injury; however, it is unclear whether graft source affects lower extremity functional test performance or failure rate in an active military population.

Objective:

To compare lower extremity functional test performance and graft failure rates between ACL grafts [allograft, hamstring, bone-patellar tendon-bone (BTB)].

Study Design:

Cross-sectional.

Level of Evidence:

Level 2.

Methods:

Ninety-eight cadets entering a US Service Academy with a history of unilateral ACL reconstruction (ACLR) agreed to participate. Before basic training, participants completed 4 lower extremity functional tests. Active injury surveillance was conducted within the study cohort to identify all subsequent graft failures.

Results:

Cadets with hamstring autografts outperformed the BTB and allograft groups on the Lower Quarter Y-Balance Test-Posteromedial direction and single-leg hop test, respectively. No differences were detected by graft type for the other functional tests. The incidence of subsequent ipsilateral graft failures in patients with autograft was 8.11%. No failures were observed in the allograft group during the follow-up period. After controlling for sex, joint hypermobility, and time since injury and surgery, the risk of graft failure was 9.8 times higher for patients with a hamstring autograft than with a BTB ( P = 0.045).

Conclusion:

After ACLR, graft type appears to influence some single-limb measures of lower extremity function and the risk of subsequent failure. Hamstring autografts demonstrated better functional performance but increased risk of graft failure.

Clinical Relevance:

Surgeons need to weigh the pros and cons of all graft options in relation to the patient’s lifestyle. Regardless of graft type, individuals with an ACLR may require additional rehabilitation to regain neuromuscular control during dynamic single-limb tasks and mitigate graft failure.
The Relationship of Knee-related Quality of Life With Function, Psychological Factors, Strength, Performance, and Postural Stability After ACL Reconstruction: A Cross-Sectional Study
Authors: Tavares Maria Larissa Azevedo , Lima Pedro Olavo de Paula , Albano Thamyla Rocha , Rodrigues Carlos Augusto Silva , Almeida Gabriel Peixoto Leão
Published: September 2022

Background:

Patients after anterior cruciate ligament reconstruction (ACLR) have decreased health-related quality of life (QoL) compared with healthy control participants. Few studies have verified the predictors of QoL using Quality of Life Outcome Measure Questionnaire for Chronic Anterior Cruciate Ligament Deficiency (ACL-QoL), and no study has verified the relationship of psychological factors and knee function with ACL-QoL in patients after ACLR.

Hypothesis:

Knee functional status, muscle strength, performance in hop tests, postural stability, and psychological factors would be the predictors of QoL after ACLR.

Study Design:

Cross-sectional study.

Level of Evidence:

Level 4.

Methods:

A total of 131 participants who had undergone ACLR at least 6 months previously were evaluated. QoL was assessed using ACL-QoL; knee functional status, using International Knee Documentation Committee Subjective Knee (IKDC) and global rating scale (GRS); psychological readiness, using Anterior Cruciate Ligament Return to Sport after Injury Scale (ACL-RSI); kinesiophobia, using Tampa Scale for Kinesiophobia (TSK-17); knee strength, using isokinetic dynamometer; performance, using single-leg hop tests; and postural stability, using Biodex Balance System. Pearson’s linear correlation and stepwise hierarchical multiple linear regression analyses were performed to verify the predictors of QoL.

Results:

ACL-QoL showed a moderate correlation with IKDC ( r = 0.69), GRS ( r = 0.55), ACL-RSI ( r = 0.50), and TSK-17 ( r = -0.49). ACL-QoL presented none to low correlations with the variables of muscle strength, postural stability, and performance in hop tests. The variables related to the knee functional status and psychological factors (IKDC, GRS, ACL-RSI, and TSK-17) were found to be the predictors of QoL ( R2 = 0.56; P = 0.01).

Conclusion:

Knee functional status, psychological readiness, and kinesiophobia were the predictors of knee-related QoL in patients after ACLR.

Clinical Relevance:

These results can assist clinicians in the therapeutic monitoring of the factors that may interfere with QoL in patients after ACLR.
Stenting-assisted embolization of a saccular aneurysm of the azygos anterior cerebral artery associated with fenestration at its beginning
Authors: Yu Jinlu
Published: September 2022

Aneurysms of the azygos anterior cerebral artery (AACA) associated with fenestration are exceptional. We reported such a case. A 61-year-old woman presented with subarachnoid hemorrhage. Computed tomography angiography and digital subtraction angiography showed an aneurysm at the distal end of the AACA with a fenestration at its beginning. Stenting-assisted coiling of the aneurysm was performed. The postoperative recovery was uneventful. Follow-up DSA showed complete coiling of the aneurysm. By this case report and review of the literature, we found that the coexistence of the aneurysm and fenestration on the AACA was exceptional. Endovascular treatment of saccular AACA aneurysms is an appealing option.
Evaluating the integration of eye-tracking and motion capture technologies: Quantifying the accuracy and precision of gaze measures
Authors: Hunt Rhys , Blackmore Tim , Mills Chris , Dicks Matt
Published: September 2022

Integrating mobile eye tracking and optoelectronic motion capture enables point of gaze to be expressed within the laboratory co-ordinate system and presents a method not commonly applied during research examining dynamic behaviors, such as locomotion. This paper examines the quality of gaze data collected through the integration. Based on research suggesting increased viewing distances are associated with reduced data quality; the accuracy and precision of gaze data as participants ( N = 11) viewed floor-based targets at distances of 1–6 m was investigated. A mean accuracy of 2.55 ± 1.12° was identified, however, accuracy and precision measures (relative to targets) were significantly ( p < .05) reduced at greater viewing distances. We then consider if signal processing techniques may improve accuracy and precision, and overcome issues associated with missing data. A 4th-order Butterworth lowpass filter with cut-off frequencies determined via autocorrelation did not significantly improve data quality, however, interpolation via Quintic spline was sufficient to overcome gaps of up to 0.1 s. We conclude the integration of gaze and motion capture presents a viable methodology in the study of human behavior and presents advantages for data collection, treatment, and analysis. We provide considerations for the collection, analysis, and treatment of gaze data that may help inform future methodological decisions.
A randomized controlled trial for evaluating the impact of integrating a computerized clinical decision support system and a socially assistive humanoid robot into grand rounds during pre/post-operative care
Authors: Mlakar Izidor , Smrke Urška , Flis Vojko , Bergauer Andrej , Kobilica Nina , Kampič Tadej , Horvat Samo , Vidovič Damjan , Musil Bojan , Plohl Nejc
Published: September 2022

Although clinical decision support systems (CDSSs) are increasingly emphasized as one of the possible levers for improving care, they are still not widely used due to different barriers, such as doubts about systems’ performance, their complexity and poor design, practitioners’ lack of time to use them, poor computer skills, reluctance to use them in front of patients, and deficient integration into existing workflows. While several studies on CDSS exist, there is a need for additional high-quality studies using large samples and examining the differences between outcomes following a decision based on CDSS support and those following decisions without this kind of information. Even less is known about the effectiveness of a CDSS that is delivered during a grand round routine and with the help of socially assistive humanoid robots (SAHRs). In this study, 200 patients will be randomized into a Control Group (i.e. standard care) and an Intervention Group (i.e. standard care and novel CDSS delivered via a SAHR). Health care quality and Quality of Life measures will be compared between the two groups. Additionally, approximately 22 clinicians, who are also active researchers at the University Clinical Center Maribor, will evaluate the acceptability and clinical usability of the system. The results of the proposed study will provide high-quality evidence on the effectiveness of CDSS systems and SAHR in the grand round routine.
Management Strategy of Intracranial Complications of Sinusitis: Our Experience and Review of the Literature
Authors: Hallak Bassel , Bouayed Salim , Ghika Joseph André , Teiga Pedro S. , Alvarez Vincent
Published: September 2022

Objective

Sinusitis or rhinosinusitis is a very common disease worldwide, and in some cases, it leads to intracranial complications (ICS). These are more common in immunocompromised patients or with underlying comorbidities, but even healthy individuals, can be affected. Nowadays, ICS have become less common thanks to improved antibiotic therapies, radiological diagnostic methods, surgical techniques and skills. Nonetheless, they can still cause significant morbidity and mortality. For this reason, management of these complications requires a multidisciplinary approach to plan and customize treatment options. This paper presents our strategy in the management of a series of intracranial complications induced by acute sinusitis and compares our experience and outcomes with the literature.

Study design

Single institute experience, retrospective analysis of cases series and literature review.

Methods

Adult and child patients who were treated for ICS in the Department of Otorhinolaryngology at Sion Hospital, in Switzerland from 2016 to 2020 were included. Their symptoms, medical history, clinical and radiological findings, treatment, and outcome were documented.

Results

Eight patients (6 males- 2 females) aged from 14 to 88 y.o., were enrolled. None had any previous history of chronic, or recurrent sinusitis. Moreover, very few presented specific rhinological symptoms, but with neurological or other symptoms. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) were used to confirm the diagnosis of all ICS. All types of known intracranial complications were observed in our cohort with a wide range of extension and severity of sinusitis. A multidisciplinary approach with individual treatments was tailored to each patient. Outcomes were favorable in almost all patients with neither recurrence, nor neurological sequels being observed in the follow-up. Only one patient was lost due to fatal complications of advanced lung cancer.

Conclusion

ICS remain a challenging clinical problem due to substantial associated morbidity and mortality. The incidence of these complications is relatively low. Therapeutical management guidelines are lacking. Early detection and multidisciplinary approach are key to successful treatment.
The Effects of Multilevel Orientations on Frontline Deliberate Learning
Authors: Wu Jiajun , Chen Liwei
Published: September 2022

The study proposes a frontline deliberate learning (FDL) process involving knowledge generation, knowledge articulation, and knowledge codification, which enable organizations to capture knowledge embedded in the frontlines. It examines the antecedent effects of three orientations (i.e., performance, learning, and customer orientation) at both the individual dispositional level and strategic business unit (SBU) level on frontline deliberate learning. The proposed model was tested using survey data from multiple respondents from the healthcare industry. The results indicate that knowledge articulation plays a mediating role in the influence of knowledge generation on knowledge codification. Individual performance, learning, and customer orientation primarily affect knowledge generation. However, these three orientations at the unit level have different effects on knowledge articulation and the unit level’s codification.
Feminist digital natures
Authors: Nelson Ingrid L , Hawkins Roberta , Govia Leah
Published: September 2022

This commentary proposes a research agenda for the concept of feminist digital natures (FDN). To demonstrate how we see FDN connecting existing research efforts, we review both the well-established and much-needed work in three overlapping areas of scholarship where we see the potential for productive discussions, new questions, and empirical analysis: feminist digital geographies (FDG), digital natures (DN), and feminist political ecology (FPE). We offer specific and grounded examples of topics and questions that scholars might pursue through an FDN approach. We encourage sustained, collaborative, and critical attention to the uneven consequences and political terrain of understanding natures as increasingly digitally monitored, managed, manipulated, and represented. We can and should think with digital relations, and we might benefit from new creative conversations across our areas of inquiry and action.
Maternal and Newborn Care Practices among the Muslim Slum Dwellers in India: Does the Popular Common Sense Matter?
Authors: Khan Abul Salim , Shahid Mohd.
Published: September 2022

Despite a large number of government health programs, schemes and incentives, India is trailing in achieving global sustainable development goals on ensuring healthy lives and reducing maternal mortality ratio, under-five mortality and neonatal mortality. For improving maternal and child health, one of the possible ways could be making sense of maternal and newborn care practices. These practices are dynamic and interwoven in the socio-cultural milieu. Many of these practices have detrimental effect on the health of mother and newborn. There is need to explore, understand and negotiate with maternal and newborn care practices for locating elements of ‘good sense’ in these practices, which could be helpful in promoting better maternal and child health. It is in this context that an attempt is made to describe the maternal and newborn care practices among the Muslim slum dwellers in Hyderabad, Telangana (India).
Theoretical accuracy for indirect predictions based on SNP effects from single-step GBLUP
Authors: Garcia Andre , Aguilar Ignacio , Legarra Andres , Tsuruta Shogo , Misztal Ignacy , Lourenco Daniela
Published: September 2022

Background

Although single-step GBLUP (ssGBLUP) is an animal model, SNP effects can be backsolved from genomic estimated breeding values (GEBV). Predicted SNP effects allow to compute indirect prediction (IP) per individual as the sum of the SNP effects multiplied by its gene content, which is helpful when the number of genotyped animals is large, for genotyped animals not in the official evaluations, and when interim evaluations are needed. Typically, IP are obtained for new batches of genotyped individuals, all of them young and without phenotypes. Individual (theoretical) accuracies for IP are rarely reported, but they are nevertheless of interest. Our first objective was to present equations to compute individual accuracy of IP, based on prediction error covariance (PEC) of SNP effects, and in turn, are obtained from PEC of GEBV in ssGBLUP. The second objective was to test the algorithm for proven and young (APY) in PEC computations. With large datasets, it is impossible to handle the full PEC matrix, thus the third objective was to examine the minimum number of genotyped animals needed in PEC computations to achieve IP accuracies that are equivalent to GEBV accuracies.

Results

Correlations between GEBV and IP for the validation animals using SNP effects from ssGBLUP evaluations were ≥ 0.99. When all available genotyped animals were used for PEC computations, correlations between GEBV and IP accuracy were ≥ 0.99. In addition, IP accuracies were compatible with GEBV accuracies either with direct inversion of the genomic relationship matrix (G) or using the algorithm for proven and young (APY) to obtain the inverse of G. As the number of genotyped animals included in the PEC computations decreased from around 55,000 to 15,000, correlations were still ≥ 0.96, but IP accuracies were biased downwards.

Conclusions

Theoretical accuracy of indirect prediction can be successfully obtained by computing SNP PEC out of GEBV PEC from ssGBLUP equations using direct or APY G inverse. It is possible to reduce the number of genotyped animals in PEC computations, but accuracies may be underestimated. Further research is needed to approximate SNP PEC from ssGBLUP to limit the computational requirements with many genotyped animals.
LncRNA RPL34-AS1 suppresses the proliferation, migration and invasion of esophageal squamous cell carcinoma via targeting miR-575/ACAA2 axis
Authors: Zhang Hu , Pan Enchun , Zhang Ying , Zhao Chao , Liu Qiwei , Pu Yuepu , Yin Lihong
Published: September 2022

Background

Long noncoding RNAs (lncRNAs) are abnormally expressed in a broad type of cancers and play significant roles that regulate tumor development and metastasis. However, the pathological roles of lncRNAs in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Here we aimed to investigate the role and regulatory mechanism of the novel lncRNA RPL34-AS1 in the development and progression of ESCC.

Methods

The expression level of RPL34-AS1 in ESCC tissues and cell lines was determined by RT-qPCR. Functional experiments in vitro and in vivo were employed to explore the effects of RPL34-AS1 on tumor growth in ESCC cells. Mechanistically, fluorescence in situ hybridization (FISH), bioinformatics analyses, luciferase reporter assay, RNA immunoprecipitation (RIP) assay and western blot assays were used to detect the regulatory relationship between RPL34-AS1, miR-575 and ACAA2.

Results

RPL34-AS1 was significantly down-regulated in ESCC tissues and cells, which was negatively correlated with overall survival in ESCC patients. Functionally, upregulation of RPL34-AS1 dramatically suppressed ESCC cell proliferation, colony formation, invasion and migration in vitro, whereas knockdown of RPL34-AS1 elicited the opposite function. Consistently, overexpression of RPL34-AS1 inhibited tumor growth in vivo. Mechanistically, RPL34-AS1 acted as a competing endogenous RNA (ceRNA) of miR-575 to relieve the repressive effect of miR-575 on its target ACAA2, then suppressed the tumorigenesis of ESCC.

Conclusions

Our results reveal a role for RPL34-AS1 in ESCC tumorigenesis and may provide a strategy for using RPL34-AS1 as a potential biomarker and an effect target for patients with ESCC.
High CENPA expression in papillary renal cell carcinoma tissues is associated with poor prognosis
Authors: Li Junwu , Li Qinke , Yuan Yang , Xie Yiteng , Zhang Yuanfeng , Zhang Ronggui
Published: September 2022

Objective

This work focused on investigating the relation of centromeric protein A (CENPA) gene expression with prognosis of papillary renal cell carcinoma (PRCC).

Methods

We obtained data from PRCC cases in TCGA. Thereafter, CENPA levels between the paired PRCC and matched non-carcinoma samples were analyzed by Wilcoxon rank-sum test, while the relations of clinicopathological characteristics with CENPA level were examined by logistic regression and Wilcoxon rank-sum test. The prognostic value of CENPA was assessed by plotting the receiver operating feature curve (ROC) and calculating the value of area under curve (AUC). In addition, relations between clinicopathological characteristics and PRCC survival were analyzed through Kaplan–Meier (KM) and Cox regression analyses. After dividing the total number of patients into the trial cohort and the validation cohort in a ratio of 7:3, we constructed a nomogram in trial cohort according to multivariate Cox regression results for predicting how CENPA affected patient survival and used the calibration curve to verify its accuracy in both cohorts. We also determined CENPA levels within cancer and matched non-carcinoma samples through immunohistochemistry (IHC). Finally, we utilized functional enrichment for identifying key pathways related to differentially expressed genes (DEGs) between PRCC cases with CENPA up-regulation and down-regulation.

Results

CENPA expression enhanced in PRCC tissues compared with healthy counterparts (P < 0.001). CENPA up-regulation was related to pathological TNM stage and clinical stage (P < 0.05). Meanwhile, the ROC curves indicated that CENPA had a remarkable diagnostic capacity for PRCC, and the expression of CENPA can significantly improve the predictive accuracy of pathological TNM stage and clinical stage for PRCC. As revealed by KM curves, PRCC cases with CENPA up-regulation were associated with poor survival compared with those with CENPA down-regulation (Risk ratio, RR = 3.07, 95% CI: 1.58–5.97, P = 0.001). In the meantime, univariate as well as multivariate analysis showed an independent association of CENPA with overall survival (OS, P < 0.05) and the nomogram demonstrated superior predictive ability in both cohorts. IHC analysis indicated that PRCC cases showed an increased CENPA positive rate compared with controls. As revealed by functional annotations, CENPA was enriched into pathways associated with neuroactive ligand receptor interactions, cytokine receptor interactions, extracellular matrix regulators, extracellular matrix glycoproteins and nuclear matrisome.

Conclusion

CENPA expression increases within PRCC samples, which predicts dismal PRCC survival. CENPA may become a molecular prognostic marker and therapeutic target for PRCC patients.
Oral cleaning habits and the copy number of periodontal bacteria in pregnant women and its correlation with birth outcomes: an epidemiological study in Mibilizi, Rwanda
Authors: Arima Hiroaki , Calliope Akintije Simba , Fukuda Hideki , Nzaramba Theoneste , Mukakarake Marie Goretti , Wada Takayuki , Yorifuji Takashi , Mutesa Leon , Yamamoto Taro
Published: September 2022

Background

Since 1996, many studies have reported that periodontal disease during pregnancy may be a risk factor for preterm birth and low birth weight; however, in Africa, periodontal disease is considered a non-high-priority disease. In addition, there are few dental facilities in rural Rwanda; thus, the oral condition of pregnant women has not been investigated. The objective of this study was to assess the tooth brushing habits of pregnant women in rural Rwanda and evaluate whether periodontal bacteria in the oral cavity of pregnant women are related to birth outcomes or oral cleaning habits.

Methods

A questionnaire survey and saliva collection were conducted for pregnant women in the catchment area population of Mibilizi Hospital located in the western part of Rwanda. Real-time PCR was performed to quantitatively detect total bacteria and 4 species of periodontal bacteria. The relationship of the copy number of each bacterium and birth outcomes or oral cleaning habits was statistically analyzed.

Results

Among the participants, high copy numbers of total bacteria, Tannerella forsythia, and Treponema denticola were correlated with lower birth weight (p = 0.0032, 0.0212, 0.0288, respectively). The sex ratio at birth was higher in women who had high copy numbers of Porphyromonas gingivalis and T. denticola during pregnancy (p = 0.0268, 0.0043). Furthermore, regarding the correlation between oral cleaning habits and the amount of bacteria, the more frequently teeth were brushed, the lower the level of P. gingivalis (p = 0.0061); the more frequently the brush was replaced, the lower the levels of P. gingivalis and T. forsythia (p = 0.0153, 0.0029).

Conclusions

This study suggested that improving tooth brushing habits may reduce the risk of periodontal disease among pregnant women in rural Rwanda. It also indicated that the amount of bacteria is associated with various birth outcomes according to the bacterial species. Both access to dental clinics and the oral cleaning habits of pregnant women should be important considerations in efforts to alleviate reproductive-related outcomes in rural Africa.
Transparency and reporting characteristics of COVID-19 randomized controlled trials
Authors: Kapp Philipp , Esmail Laura , Ghosn Lina , Ravaud Philippe , Boutron Isabelle
Published: September 2022

Background

In the context of the COVID-19 pandemic, randomized controlled trials (RCTs) are essential to support clinical decision-making. We aimed (1) to assess and compare the reporting characteristics of RCTs between preprints and peer-reviewed publications and (2) to assess whether reporting improves after the peer review process for all preprints subsequently published in peer-reviewed journals.

Methods

We searched the Cochrane COVID-19 Study Register and L·OVE COVID-19 platform to identify all reports of RCTs assessing pharmacological treatments of COVID-19, up to May 2021. We extracted indicators of transparency (e.g., trial registration, data sharing intentions) and assessed the completeness of reporting (i.e., some important CONSORT items, conflict of interest, ethical approval) using a standardized data extraction form. We also identified paired reports published in preprint and peer-reviewed publications.

Results

We identified 251 trial reports: 121 (48%) were first published in peer-reviewed journals, and 130 (52%) were first published as preprints. Transparency was poor. About half of trials were prospectively registered (n = 140, 56%); 38% (n = 95) made their full protocols available, and 29% (n = 72) provided access to their statistical analysis plan report. A data sharing statement was reported in 68% (n = 170) of the reports of which 91% stated their willingness to share. Completeness of reporting was low: only 32% (n = 81) of trials completely defined the pre-specified primary outcome measures; 57% (n = 143) reported the process of allocation concealment. Overall, 51% (n = 127) adequately reported the results for the primary outcomes while only 14% (n = 36) of trials adequately described harms. Primary outcome(s) reported in trial registries and published reports were inconsistent in 49% (n = 104) of trials; of them, only 15% (n = 16) disclosed outcome switching in the report. There were no major differences between preprints and peer-reviewed publications. Of the 130 RCTs published as preprints, 78 were subsequently published in a peer-reviewed journal. There was no major improvement after the journal peer review process for most items.

Conclusions

Transparency, completeness, and consistency of reporting of COVID-19 clinical trials were insufficient both in preprints and peer-reviewed publications. A comparison of paired reports published in preprint and peer-reviewed publication did not indicate major improvement.
Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in glioma
Authors: Xiong Ye , Qi Yanhua , Pan Ziwen , Wang Shaobo , Li Boyan , Feng Bowen , Xue Hao , Zhao Rongrong , Li Gang
Published: September 2022

Background

Thymosin family genes (TMSs), biologically important peptides with diverse intracellular and extracellular functions, have been shown to promote the progression of multiple cancers. However, multiomics characterization of TMSs and their role in human cancer prognosis has not been systematically performed.

Methods

We performed a comprehensive analysis of TMSs and thymosin β10 (TMSB10) using multiomics data from more than 10,000 tumor samples of 33 cancer types from The Cancer Genome Atlas (TCGA). We used single-sample gene set enrichment analysis (ssGSEA) and the gene set variation analysis (GSVA) algorithm to investigate the differences in tumor microenvironment (TME) cell infiltration and functional annotation for individual tumor samples, respectively. The role of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration,and immunosuppressive polarization, and the combination drug efficacy were assessed via biological function assays.

Results

We comprehensively assessed genomic mutations, expression dysregulation, prognosis and immunotherapeutic response across 33 human cancer samples and showed that TMSB10 is specifically overexpressed in almost all types of cancer tissues. Further pan-cancer analysis showed that TMSB10 is closely related to the biological function, immune regulation and prognosis of glioma. Similar results were also found in several public glioma cohorts and our Qilu local cohort. Further integration with other biological experiments revealed the key roles of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration and immunosuppressive polarization. We also identified multiple drugs targeting cells with high TMSB10 expression and validated that knockdown of TMSB10 improved the efficacy of selumetinib (a MEK1/2 inhibitor approved by the FDA for the treatment of neurofibromatosis-associated tumors) and anti-PD1 treatment in glioma.

Conclusion

These results indicate that TMSB10 holds promise as a novel prognostic marker and therapeutic target, providing a theoretical basis for the development of more effective and targeted clinical treatment strategies for glioma patients.
MiR-34b/c play a role in early sex differentiation of Amur sturgeon, Acipenser schrenckii
Authors: Zhang Xiujuan , Wu Wenhua , Zhou Jiabin , Li Linmiao , Jiang Haiying , Chen Jinping
Published: September 2022

Background

Sex differentiation can be viewed as a controlled regulatory balance between sex differentiation-related mRNAs and post-transcriptional mechanisms mediated by non-coding RNAs. In mammals, increasing evidence has been reported regarding the importance of gonad-specific microRNAs (miRNAs) in sex differentiation. Although many fishes express a large number of gonadal miRNAs, the effects of these sex-biased miRNAs on sex differentiation in teleost fish remain unknown. Previous studies have shown the exclusive and sexually dimorphic expression of miR-34b/c in the gonads of the Amur sturgeon (Acipenser schrenckii), suggesting its potential role in the sex differentiation process.

Results

Using quantitative real-time PCR (qPCR), we observed that miR-34b/c showed consistent spatiotemporal expression patterns; the expression levels significantly increased during early sex differentiation. Using in situ hybridization, miR-34c was found to be located in the germ cells. In primary germ cells in vitro, the group subjected to overexpression and inhibition of miR-34c showed significantly higher proliferation ability and lower apoptosis, respectively, compared to the corresponding control group. Luciferase reporter assays using the ar-3′UTR-psiCHECK-2 luciferase vector suggested a targeted regulatory interaction between miR-34b/c and the 3′UTR of the androgen receptor (ar) mRNA. Furthermore, miR-34b/c and ar showed negative expression patterns during early sex differentiation. Additionally, a negative feedback regulation pattern was observed between foxl2 expression in the ovaries and amh and sox9 expression in the testes during early sex differentiation.

Conclusions

This study sheds new light on the roles of miR-34b/c in gonad development of Amur sturgeon, and provides the first comprehensive evidence that the gonad-predominant microRNAs may have a major role in sex differentiation in teleost fish.
Traces of JC polyomavirus in papillary thyroid cancer: a comprehensive study in Iran
Authors: Karimi Amir Ali , Tarharoudi Rahil , Kianmehr Zahra , Sakhaee Fatemeh , Jamnani Fatemeh Rahimi , Siadat Seyed Davar , Fateh Abolfazl
Published: September 2022

Background

JC polyomavirus (JCPyV) is known to induce solid tumors such as astrocytomas, glioblastomas, and neuroblastomas in experimental animals, and recent studies have shown that the virus may be correlated with carcinogenesis. This study aimed to evaluate the impact of JCPyV on the progression of papillary thyroid cancer (PTC).

Methods

A total of 1057 samples, including 645 paraffin-embedded PTC biopsy samples (PEBS) and 412 fresh biopsy samples (FBS), and 1057 adjacent non-cancerous samples were evaluated for the presence of JCPyV DNA and RNA.

Results

We observed that 10.8% (114/1057) samples, including 17.5% (72/412) FBS and 6.5% (42/645) PEBS were positive for the JCPyV DNA. Among the JCPyV-positive samples, the mean JCPyV copy number was lower in patients with PEBS (0.3 × 10–4 ± 0.1 × 10–4 copies/cell) compared to FBS (1.8 × 10–1 ± 0.4 × 10–1 copies/cell) and non-PTC normal samples (0.2 × 10–5 ± 0.01 × 10–5 copies/cell), with a statistically significant difference (P < 0.001). The LT-Ag RNA expression was lower in PEBS than in FBS, while no VP1 gene transcript expression was found.

Conclusions

Although our results confirmed the presence of JCPyV in some Iranian patients with PTC, more research is needed to verify these results.