bluuebunny/crossref_metadata_2025 huggingface dataset:
Institutional outbreak involving multiple clades of IMP-producing Enterobacter cloacae complex sequence type 78 at a cancer center in Tokyo, Japan
Authors: Harada Sohei , Aoki Kotaro , Ohkushi Daisuke , Okamoto Koh , Takehana Kazumi , Akatsuchi Tomomi , Ida Keito , Shoji Daigo , Ishii Yoshikazu , Doi Yohei , Moriya Kyoji , Hayama Brian
Published: March 2021

Background

Information about the clinical and microbiological characteristics of IMP-producingEnterobacteraleshas been limited. Here, we describe an institutional outbreak of IMP-producingEnterobacter cloacaecomplex (ECC) involving multiple clades of ECC sequence type (ST) 78 strains.

Methods

Antimicrobial susceptibility testing, whole-genome sequencing, and conjugation experiments of 18 IMP-producing ECC strains isolated during four-year study period were performed. Species and subspecies were determined by average nucleotide identity analysis and clonal relatedness of the isolates was analyzed with multilocus sequence typing and core-genome single nucleotide polymorphism (SNP) analysis. Relevant clinical information was extracted from medical records.

Results

Fourteen of 18 IMP-producing ECC isolates were determined asEnterobacter hormaecheiST78. Sixteen isolates, including 13 isolates belonging to ST78, carriedblaIMP-1in In316-like class 1 integron and also carried IncHI2 plasmids. Conjugation experiments were successful for 12 isolates carryingblaIMP-1on IncHI2 plasmids and for an isolate carryingblaIMP-11on an IncL/M plasmid. Although isolation of ST78 strains was clustered in a 14-months period suggesting nosocomial transmission, these strains were subdivided into three clades by SNP analysis: clade A (n = 10), clade B (n = 1), clade C (n = 3). A part of clonal relatedness was unexpected by the epidemiological information at the time of isolation of the strains. Most of the IMP-producing ECC strains were susceptible to non-β-lactam antibiotics and had relatively low minimum inhibitory concentrations to carbapenems (≤4 μg/mL). Five of six infections caused by IMP-producing ECC were treated successfully.

Conclusions

Whole-genome sequencing analysis revealed the outbreak was caused by three different clades of ST78 strains, where patients had favorable treatment outcome of the infections compared with that caused byEnterobacteralesproducing other carbapenemases, possibly due to their non-multidrug-resistant phenotype.
Feasibility and adherence to moderate intensity cardiovascular fitness training following stroke: a pilot randomized controlled trial
Authors: Reynolds Hanna , Steinfort Sarah , Tillyard Jane , Ellis Sarah , Hayes Alan , Hanson Erik D. , Wijeratne Tissa , Skinner Elizabeth H.
Published: March 2021

Background

Stroke is a leading cause of disability worldwide and the cardiovascular fitness levels of stroke survivors are diminished to an extent that impairs functioning and activities of daily living performance. While cardiovascular training seems an empirically appropriate intervention, the optimal dosage and intensity of cardiovascular training in stroke survivors remains unclear. The aim was to determine the safety and feasibility of moderate-intensity cardiovascular training following stroke, including measurement of adherence to training.

Methods

A pilot, prospective, patient- and assessor-blinded randomised controlled trial conducted in a tertiary, metropolitan hospital-based community rehabilitation centre. Eligibility criteria included ambulant (> 100 m), 6 weeks-12 months post stroke. Moderate-intensity fitness training or control (low-intensity) exercise was offered biweekly for 12 weeks. Outcome measures included adverse events, peak oxygen uptake (VO2), functional exercise capacity (6-Minute Walk Test, 10-m Walk Test) and health-related quality of life (Short Form-36) and mood (Patient Health Questionnaire, PHQ9).

Results

Feasibility: Seventy-one (50%) of 141 screened participants were eligible (29% did not agree to participate). Twenty participants (10 intervention, 10 control) were recruited. The median (%; IQR) supervised sessions was 19.5 (81%; 12, 20); and 20 (83%; 19, 22) in the intervention and control groups, respectively. Progression of duration and intensity was limited; mean of 10 sessions to achieve target duration (30 min). There were no adverse events. Baseline peak oxygen uptake (VO2) levels were low (15.94 ml/kg/min). Significant improvements in VO2 peak in both groups were observed (p < 0.05). Although there were no significant between-group differences, this feasibility trial was not powered to detect change.

Conclusions

Moderate-intensity fitness training was safe but achievement of target duration and intensity was challenging for stroke survivors. A definitive adequately-powered randomised trial is required. Alternative fitness training protocols may need to be explored.

Trial registration

The trial protocol was prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN 12613000822785) on 25/07/2013.
Letter to the Editor in response to ‘Parental attachment and depressive symptoms in pregnancies complicated by twin-twin transfusion syndrome: a cohort study’
Authors: Rameh Georges , Tohme Pia , Abi-Habib Rudy , Chalouhi Gihad E
Published: March 2021

Twin-twin transfusion syndrome is a highly morbid condition that can affect parental attachment and depression risk. Studies addressing this rare condition are hard to conduct and thus lacking in the literature. In this letter to the editor, we acknowledge the article of Mackie et al. entitled “Parental attachment and depressive symptoms in pregnancies complicated by twin-twin transfusion syndrome: a cohort study” to be of high importance and impact, but would like to discuss the extent of its conclusions, and push towards bigger studies in this field.
Ultrastructural study of closed macular hole- preliminary application of a novel high magnification module combining with OCT
Authors: Qiu Chang-Yu , Shi Yuan-Yuan , Zhao Hong-Wei , Nie Chuang , Dong Ming-Xia , Zhang Huai-Qiang , Zhao Jun , Xu Qian-Qian , Song Fei-Long , Guo Xiao-Hua , Shi Lin , Liu Chang-Ying , Gong Yu-Bo , Luo Ling
Published: March 2021

Background

As a novel high magnification module (HMM) combining with OCT (OCT-HMM) is able to detect the microstructure of retina, we apply it to explore the ultrastructure of the macula after closure of the idiopathic macular hole (IMH) by surgery.

Methods

This is an observational case series study in which patients with full-thickness IMHs who had undergone successful macular closure by vitrectomy and internal limiting membrane peeling and healthy subjects were recruited. After comprehensive ophthalmic examinations, the images of macular area were obtained and collected by professional operators using OCT-HMM. Then images were independently analyzed by 4 masked vitreoretinal specialists.

Results

A total of 24 IMH eyes and 42 healthy eyes were examined. HMM images were obtained in 10 IMH eyes. Among them, 4 eyes whose macula closed completely with recovery of photoreceptor layer presented a dark arc nasal to the fovea, oriented to the optic, and the notch of arc faced temporally. Six eyes in which the macula closed incompletely with photoreceptor cells loss revealed a dark ring with uneven bright spots inside. The other 14 eyes failed to obtain clear images by OCT-HMM. The contra lateral eyes of the patients and the healthy subjects’ eyes succeeded to obtain the HMM images which displayed evenly grey background thickly covered with tiny bright dots that was in similar size and evenly and widely distributed and there no dark arc or ring. OCT B-scan and IR images could be acquired in all of the IMH and healthy eyes.

Conclusion

The preliminary application of HMM has supplied us a brand-new insight into the microstructure of closed IMH. A dark arc sign could be detected with OCT-HMM in the macula which was functionally closed after surgery that was probably the healing mark on a microstructure photoreceptors level. Its existence and shape indicated that the functional closure followed by a retinal displacement mainly horizontally from temporal side to nasal side but not symmetric centripetally.
Virologic response of treatment experienced HIV-infected Ugandan children and adolescents on NNRTI based first-line regimen, previously monitored without viral load
Authors: Kibalama Ssemambo Phionah , Nalubega-Mboowa Mary Gorrethy , Owora Arthur , Serunjogi Robert , Kironde Susan , Nakabuye Sarah , Ssozi Francis , Nannyonga Maria , Musoke Philippa , Barlow-Mosha Linda
Published: March 2021

Background

Many HIV-infected African children gained access to antiretroviral treatment (ART) through expansion of PEPFAR programs since 2004 and introduction of “Test and Treat” WHO guidelines in 2015. As ART access increases and children transition from adolescence to adulthood, treatment failure is inevitable. Viral load (VL) monitoring in Uganda was introduced in 2016 replacing clinical monitoring. However, there’s limited data on the comparative effectiveness of these two strategies among HIV-infected children in resource-limited settings (RLS).

Methods

HIV-infected Ugandan children aged 1–12 years from HIV-care programs with > 1 year of first-line ART using only immunologic and clinical criteria to monitor response to treatment were screened in 2010. Eligible children were stratified by VL ≤ 400 and > 400 copies/ml randomized to clinical and immunological (control) versus clinical, immunological and VL monitoring to determine treatment failure with follow-up at 12, 24, 36, and 48 weeks. Plasma VL was analyzed retrospectively for controls. Mixed-effects logistic regression models were used to compare the prevalence of viral suppression between study arms and identify factors associated with viral suppression.

Results

At baseline all children (n = 142) were on NNRTI based ART (75% Nevirapine, 25% efavirenz). One third of ART-experienced children had detectable VL at baseline despite high CD4%. Median age was 6 years (interquartile range [IQR]: 5–9) and 43% were female. Overall, the odds of viral suppression were not different between study arms: (arm by week interaction, p = 0.63), adjusted odds ratio [aOR]: 1.07; 95%CI: 0.53, 2.17, p = 0.57) and did not change over time (aOR: 0 vs 24 week: 1.15; 95% CI: 0.91, 1.46, p = 0.24 and 0 vs 48 weeks: 1.26; 95%CI: 0.92, 1.74, p = 0.15). Longer duration of a child’s ART exposure was associated with lower odds of viral suppression (aOR: 0.61; 95% CI: 0.42, 0.87, p < .01). Only 13% (9/71) of children with virologic failure were switched to second-line ART, in spite of access to real-time VL.

Conclusion

With increasing ART exposure, viral load monitoring is critical for early detection of treatment failure in RLS. Clinicians need to make timely informed decisions to switch failing children to second-line ART.

Trial registration

ClinicalTrials.gov NCT04489953, 28 Jul 2020. Retrospectively registered. (https://register.clinicaltrials.gov).
Interactive association of maternal education and peer relationship with oppositional defiant disorder: an observational study
Authors: Liu Ming-Chia , Chang Jung Chen , Lee Chau-Shoun
Published: March 2021

Background

The objectives of this research were to gain insights on the interactive effects, by measuring familial and peer-related risk factors in youths with oppositional defiant disorder (ODD).

Methods

Participants were college students recruited nationwide, with age between 18 and 25. Through the consensus of expert meetings, a set of questionnaires were used to evaluate the familial status, participant’s peer group conditions, high-risk environment of illicit substance use, and oppositional symptoms. The logistic regression was performed to see the independent and interactive risk factors for ODD.

Results

A total of 981 subjects were enrolled. Six variables significantly associated with ODD at the multivariate logistic regression, including male, night division, poor academic performance, high risk environment, peer with illicit substance use and high maternal education level. High maternal education exerted independent protective effect on the development of ODD (adjusted odds ratio, aOR = 0.65, 95% CI = 0.44–0.99). Peer with illicit substance use was more likely to associate with ODD in the low maternal education group. The 2-way interactive effect of maternal education and peer with substance use on the development of ODD was OR = 4.96 (2.96, 8.31).

Conclusion

The present study highlights the influence of maternal education level to ODD and its interaction with peer of illicit substance use. Our findings imply that the familial attachment and peer interaction are essential stages for the development of human behavior.

Trial registration

The research protocol was reviewed and approved by the ethical review committee of National Taiwan University Hospital (number 201505057RINC) and registered at clinical trial systems at National Taiwan University. In addition, subjects’ information was anonymous and de-identified prior to any analysis.
Improving cause of death certification in the Philippines: implementation of an electronic verbal autopsy decision support tool (SmartVA auto-analyse) to aid physician diagnoses of out-of-facility deaths
Authors: Joshi Rohina , Hazard R. H. , Mahesh Pasyodun Koralage Buddhika , Mikkelsen L. , Avelino F. , Sarmiento Carmina , Segarra A. , Timbang T. , Sinson F. , Diango Patrick , Riley I. , Chowdhury H. , Asuncion Irma L. , Khanom G. , Lopez Alan D.
Published: March 2021

Background

The majority of deaths in the Philippines occur out-of-facility and require a medical certificate of cause of death by Municipal Health Officers (MHOs) for burial. MHOs lack a standardised certification process for out-of-facility deaths and when no medical records are available, certify a high proportion of ill-defined causes of death. We aimed to develop and introduce SmartVA Auto-Analyse, a verbal autopsy (VA) based electronic decision support tool in order to assist the MHOs in certifying out-of-facility deaths.

Method

We conducted a stakeholder consultation, process mapping and a pre-test to assess feasibility and acceptability of SmartVA Auto-Analyse. MHOs were first asked to conduct an open-ended interview from the family members of the deceased, and if they were not able to arrive at a diagnosis, continue the interview using the standardised SmartVA questionnaire. Auto-Analyse then presented the MHO with the three most likely causes of death. For the pilot, the intervention was scaled-up to 91 municipalities. We performed a mixed-methods evaluation using the cause of death data and group discussions with the MHOs.

Results

Of the 5649 deaths registered, Auto-Analyse was used to certify 4586 (81%). For the remaining 19%, doctors believed they could assign a cause of death based on the availability of medical records and the VA open narrative. When used, physicians used the Auto-Analyse diagnosis in 85% of cases to certify the cause of death. Only 13% of the deaths under the intervention had an undetermined cause of death. Group discussions identified two themes: Auto-Analyse standardized the certification of home deaths and assisted the MHOs to improve the quality of death certification.

Conclusion

Standardized VA combined with physician diagnosis using the SmartVA Auto-Analyse support tool was readily used by MHOs in the Philippines and can improve the quality of death certification of home deaths.
Double-trajectory lumbar screw placement guided by a set of 3D-printed surgical guide templates: a cadaver study
Authors: Zhao Yonghui , Liang Jinlong , Luo Haotian , Xu Yongqing , Lu Sheng
Published: March 2021

Background

To improve the strength of posterior spine fixation in patients with osteoporosis, some scholars have proposed a method of simultaneously inserting traditional pedicle screws and cortical bone trajectory screws into the pedicle. However, due to the difficulty of the operation and few clinical applications, the safety and accuracy of this method are still unclear. The purpose of this study was to investigate the safety and accuracy of double-trajectory lumbar screw placement guided by surgical guide templates.

Methods

Six wet lumbar specimens were selected for computed tomography (CT) scanning, a three-dimensional (3D) model of the lumbar spine was established using computer software, and surgical guide templates for double-trajectory [traditional pedicle trajectory (TPT) and cortical bone trajectory (CBT)] lumbar screw placement at various segments of the lumbar spine were designed and printed using a 3D printer. Screw placement was guided only by the surgical guide template, with no fluoroscopy. Postoperative CT examination was performed to determine whether the screw penetrated the screw path and the location and depth of penetration of the cortex. The preoperative and postoperative sagittal and axial angles of CBT screws or TPT screws were also measured and compared.

Results

Four screws were placed in each vertebral body of six lumbar specimens for a total of 120 screws. Screw grades: 99 screws as grade 0, 15 as grade 1, six as grade 2, and zero as grade 3. Thus, grade 0 accounted for 82.5% of the screws. No significant differences in the preoperative and postoperative angles of the screws were found (P > 0.05).

Conclusions

3D-printed surgical guide templates for double-trajectory screw placement can reduce the difficulty of surgery and the use of intraoperative fluoroscopy. Using such templates is a safe, feasible, and accurate screw placement method.
The technique for less infectious and earlier healing of stoma closure wound: negative pressure wound therapy with instillation and dwelling followed by primary closure
Authors: Yane Yoshinori , Hida Jin-ichi , Makutani Yusuke , Ushijima Hokuto , Yoshioka Yasumasa , Iwamoto Masayoshi , Wada Toshiaki , Daito Koji , Tokoro Tadao , Ueda Kazuki , Kawamura Junichiro
Published: March 2021

Background

Temporary stomas have been widely used to avoid the risk of complications such as anastomotic leakage after colorectal resection. Stoma closure is relatively easy; however, postoperative surgical site infection (SSI) may be a problem. Various methods have been used to reduce the incidence of SSI. We aimed to evaluate a new technique for stoma wound closure.

Methods

We enrolled patients who underwent stoma closure at our hospital between September 2019 and May 2020. We selected patients who lived far from our hospital and had difficulty visiting the hospital regularly and who agreed to undergo this surgical technique. We used negative pressure wound therapy with instillation and dwelling (NPWTi-d) and delayed primary closure for these patients.

Results

Four patients underwent NPWTi-d and delayed primary closure without the occurrence of SSI. The median postoperative hospital stay was 9 days (range: 7–14 days), and the median number of days to confirmation of epithelialization was 11.5 days (range: 10–16 days).

Conclusion

The combined use of NPWTi-d and delayed primary closure for the stoma wound was very effective. This method may be a valuable new technique for wound management after stoma closure.
Tanshinone IIA combined with CsA inhibit myocardial cell apoptosis induced by renal ischemia-reperfusion injury in obese rats
Authors: Tai He , Jiang Xiao-lin , Lan Zhi-ming , Li Yue , Kong Liang , Yao Si-cheng , Song Nan , Lv Mei-jun , Wu Jin , Yang Ping , Xiao Xuan-si , Yang Guan-lin , Kuang Jin-song , Jia Lian-qun
Published: March 2021

Background

Acute myocardial injury (AMI), which is induced by renal ischemia-reperfusion (IR), is a significant cause of acute kidney injury (AKI)-related associated death. Obesity increases the severity and frequency of AMI and AKI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) pretreatment was used to alleviate myocardial cell apoptosis induced by renal IR, and to determine whether TIIA combined with CsA would attenuate myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

Methods

Male rates were fed a high fat diet for 8 weeks to generate obesity. AKI was induced by 30 min of kidney ischemia followed 24 h of reperfusion. Obese rats were given TIIA (10 mg/kg·d) for 2 weeks and CsA (5 mg/kg) 30 min before renal IR. After 24 h of reperfusion, the rats were anaesthetized, the blood were fetched from the abdominal aorta and kidney were fetched from abdominal cavity, then related indicators were examined.

Results

TIIA combined with CsA can alleviate the pathohistological injury and apoptosis induced by renal IR in myocardial cells. TIIA combined with CsA improved cardiac function after renal ischemia (30 min)-reperfusion (24 h) in obese rats. At the same time, TIIA combined with CsA improved mitochondrial function. Abnormal function of mitochondria was supported by decreases in respiration controlling rate (RCR), intracellular adenosine triphosphate (ATP), oxygen consumption rate, and mitochondrial membrane potential (MMP), and increases in mitochondrial reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore (mPTP), mitochondrial DNA damage, and mitochondrial respiratory chain complex enzymes. The injury of mitochondrial dynamic function was assessed by decrease in dynamin-related protein 1 (Drp1), and increases in mitofusin1/2 (Mfn1/2), and mitochondrial biogenesis injury was assessed by decreases in PPARγ coactivator-1-α (PGC-1), nucleo respiratory factor1 (Nrf1), and transcription factor A of mitochondrial (TFam).

Conclusion

We used isolated mitochondria from rat myocardial tissues to demonstrate that myocardial mitochondrial dysfunction occurred along with renal IR to induce myocardial cell apoptosis; obesity aggravated apoptosis. TIIA combined with CsA attenuated myocardial cell apoptosis by modulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.
Prioritising ‘already-scarce’ intensive care unit resources in the midst of COVID-19: a call for regional triage committees in South Africa
Authors: Naidoo Reshania , Naidoo Kantharuben
Published: March 2021

Background

The worsening COVID-19 pandemic in South Africa poses multiple challenges for clinical decision making in the context of already-scarce ICU resources. Data from national government and the last published national audit of ICU resources indicate gross shortages. While the Critical Care Society of Southern Africa (CCSSA) guidelines provide a comprehensive guideline for triage in the face of overwhelmed ICU resources, such decisions present massive ethical and moral dilemmas for triage teams. It is therefore important for the health system to provide clinicians and critical care facilities with as much support and resources as possible in the face of impending pandemic demand. Following a discussion of the ethical considerations and potential challenges in applying the CCSSA guidelines, the authors propose a framework for regional triage committees adapted to the South African context.

Discussion

Beyond the national CCSSA guidelines, the clinician has many additional ethical and clinical considerations. No single ethical approach to decision-making is sufficient, instead one which considers multiple contextual factors is necessary. Scores such as the Clinical Frailty Score and Sequential Organ Failure Assessment are of limited use in patients with COVID-19. Furthermore, the clinician is fully justified in withdrawing ICU care based on medical futility decisions and to reallocate this resource to a patient with a better prognosis. However, these decisions bear heavy emotional and moral burden compounded by the volume of clinical work and a fear of litigation.

Conclusion

We propose the formation of Provincial multi-disciplinary Critical Care Triage Committees to alleviate the emotional, moral and legal burden on individual ICU teams and co-ordinate inter-facility collaboration using an adapted framework. The committee would provide an impartial, broader and ethically-sound viewpoint which has time to consider broader contextual factors such as adjusting rationing criteria according to different levels of pandemic demand and the latest clinical evidence. Their functioning will be strengthened by direct feedback to national level and accountability to a national monitoring committee. The potential applications of these committees are far-reaching and have the potential to enable a more effective COVID-19 health systems response in South Africa.
Cardiorenal and other diabetes related outcomes with SGLT-2 inhibitors compared to GLP-1 receptor agonists in type 2 diabetes: nationwide observational study
Authors: Lugner Moa , Sattar Naveed , Miftaraj Mervete , Ekelund Jan , Franzén Stefan , Svensson Ann-Marie , Eliasson Björn
Published: March 2021

Background

Major prospective randomized clinical safety trials have demonstrated beneficial effects of treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose co-transporter-2 inhibitors (SGLT-2i) in people with type 2 diabetes and elevated cardiovascular risk, and recent clinical treatment guidelines therefore promote early use of these classes of pharmacological agents. In this Swedish nationwide observational study, we compared cardiorenal outcomes and safety of new treatment with GLP-1RA and SGLT-2i in people with type 2 diabetes.

Methods

We linked data from national Swedish databases to capture patient characteristics and outcomes and used propensity-score based matching to account for differences between the two groups. The treatments were compared using Cox regression models.

Results

We identified 9648 participants starting GLP-1RA and 12,097 starting SGLT-2i with median follow-up times 1.7 and 1.1 years, respectively. The proportion of patients with a history of MACE were 15.8%, and 17.0% in patients treated with GLP-1RA and SGLT-2i, respectively. The mean age was 61 years with 7.6 years duration of diabetes. Mean HbA1c were 8.3% (67.6 mmol/mol) and 8.3% (67.2 mmol/mol), and mean BMI 33.3 and 32.5 kg/m2in patients treated with GLP-1RA or SGLT-2i, respectively. The cumulative mortality risk was non-significantly lower in the group treated with SGLT-2i, HR 0.78 (95% CI 0.61–1.01), as were incident heart failure outcomes, but the risks of cardiovascular or renal outcomes did not differ. The risks of stroke and peripheral artery disease were higher in the SGLT-2i group relative to GLP-1RA, with HR 1.44 (95% CI 0.99–2.08) and 1.68 (95% CI 1.04–2.72), respectively.

Conclusions

This observational study suggests that treatment with GLP-1RA and SGLT-2i result in very similar cardiorenal outcomes. In the short term, treatment with GLP-1RA seem to be associated with lower risks of stroke and peripheral artery disease, whereas SGLT-2i seem to be nominally associated with lower risk of heart failure and total mortality.
Silenced lncRNA DDX11-AS1 or up-regulated microRNA-34a-3p inhibits malignant phenotypes of hepatocellular carcinoma cells via suppression of TRAF5
Authors: Ding Gangqiang , Zeng Yanli , Yang Dongqiang , Zhang Can , Mao Chongshan , Xiao Erhui , Kang Yi , Shang Jia
Published: March 2021

Background

Studies have discussed long noncoding RNA DDX11-AS1 (DDX11-AS1)-mediated downstream mechanism in hepatocellular carcinoma (HCC). The goal of this study was to investigate the regulatory mechanism of DDX11-AS1-mediated microRNA-34a-3p (miR-34a-3p)/tumor necrosis factor receptor-associated factor 5 (TRAF5) axis on HCC cells.

Methods

DDX11-AS1, miR-34a-3p and TRAF5 expression levels in HCC were detected. The correlation of DDX11-AS1, miR-34a-3p and TRAF5 in HCC patients was analyzed by Pearson test. HCC cells were transfected with corresponding plasmid/oligonucleotide, and cell proliferation, migration, invasion, apoptosis and tumor formation ability were detected. Bioinformatics software, dual luciferase report experiment and RNA-pull down experiment analysis were applied to verify the targeting relationship between DDX11-AS1, miR-34a-3p and TRAF5.

Results

Elevated DDX11-AS1 and TRAF5 and reduced miR-34a-3p exhibited in HCC. Silenced DDX11-AS1 or up-regulated miR-34a-3p inhibited the proliferation, migration, invasion, promoted apoptosis of HCC cells and repressed the tumor growth in nude mice. In addition, DDX11-AS1 bound to miR-34a-3p to target TRAF5. Silencing TRAF5 or elevating miR-34a-3p expression mitigated up-regulated DDX11-AS1-mediated promotion of tumor growth.

Conclusion

Silenced DDX11-AS1 or up-regulated miR-34a-3p inhibits HCC cell growth via elevation of TRAF5, which could be of great benefit to find early diagnostic markers for HCC patients.
A rodent model of human dose-equivalent progestin-only implantable contraception
Authors: Allaway Heather C. M. , Pierson Roger A. , Invik Jesse , Bloomfield Susan A.
Published: March 2021

Background

Long-acting, reversible contraceptives (LARC; progestin only) are an increasingly common hormonal contraceptive choice in reproductive aged women looking to suppress ovarian function and menstrual cyclicity. The overall objective was to develop and validate a rodent model of implanted etonogestrel (ENG) LARC, at body size equivalent doses to the average dose received by women during each of the first 3 years of ENG subdermal rod LARC use.

Methods

Intact, virgin, female Sprague-Dawley rats (16-wk-old) were randomized to 1 of 4 groups (n = 8/group) of ENG LARC (high-0.30μg/d, medium-0.17μg/d, low-0.09μg/d, placebo-0.00μg/d) via a slow-release pellet implanted subcutaneously. Animals were monitored for 21 days before and 29 days following pellet implantation using vaginal smears, ultrasound biomicroscopy (UBM), saphenous blood draws, food consumption, and body weights. Data were analyzed by chi-square, non-parametric, univariate, and repeated measures 2-way ANOVA.

Results

Prior to pellet implantation there was no difference in time spent in estrus cycle phases among the treatment groups (p > 0.30). Following pellet implantation there was a dose-dependent impact on the time spent in diestrus and estrus (p < 0.05), with the high dose group spending more days in diestrus and fewer days in estrus. Prior to pellet insertion there was not an association between treatment group and estrus cycle classification (p = 0.57) but following pellet implantation there was a dose-dependent association with cycle classification (p < 0.02). Measurements from the UBM (ovarian volume, follicle count, corpora lutea count) indicate an alteration of ovarian function following pellet implantation.

Conclusion

Assessment of estrus cyclicity indicated a dose-response relationship in the shift to a larger number of acyclic rats and longer in duration spent in the diestrus phase. Therefore, each dose in this model mimics some of the changes observed in the ovaries of women using ENG LARC and provides an opportunity for investigating the impacts on non-reproductive tissues in the future.
Systemic and topical administration of spermidine accelerates skin wound healing
Authors: Ito Daisuke , Ito Hiroyasu , Ideta Takayasu , Kanbe Ayumu , Ninomiya Soranobu , Shimizu Masahito
Published: March 2021

Background

The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.

Methods

A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.

Results

Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.

Conclusion

These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.
Using the Lonsdorf model for estimating habitat loss and fragmentation effects on pollination service
Authors: Rahimi Ehsan , Barghjelveh Shahindokht , Dong Pinliang
Published: March 2021

One of the most important issues related to landscape ecology and ecosystem services is finding the pattern of habitat patches that offers the highest pollination in agricultural landscapes. In this regard, two processes of habitat loss and fragmentation strongly affect the relationship between pollination and the pattern of habitat patches. In the present study, we aimed to examine the effects of habitat loss and fragmentation on pollination separately. For this purpose, first, we generated different simulated agricultural landscapes, including two habitats of forest and agriculture. Then, according to the Lonsdorf model, we estimated the potential of the simulated landscapes in providing pollination in different scenarios. Finally, using statistical models, we estimated the effects of habitat loss and fragmentation on pollination at the landscape and farm levels. Our results showed that the effects of habitat loss and fragmentation on pollination were completely different at the landscape and farm levels. At the landscape level, fragmentation negatively affected pollination, but at the farm level, the maximum pollination rate was observed in the landscapes with a high degree of fragmentation. Regarding the habitat loss effects, our results showed that pollination decreased linearly at the landscape level as habitat amount decreased, but at the farm level, it decreased exponentially. The present study considered the level of analysis (i.e., landscape and farm levels) as a critical factor affecting pollination changes caused by fragmentation. We showed that using the Lonsdorf model could lead to confusing results for the landscape ecologists and alert farmers who want to reduce the adverse effects of fragmentation on their products by creating new forest patches. Therefore, agriculturalists and landscape ecologists should consider that the pollination rate at the landscape and farm levels is completely different according to the model and provide contradictory results about the process of habitat loss effects on pollination.
Extended input–output model for urbanization: an empirical test using Chinese data
Authors: Okamoto Nobuhiro
Published: March 2021

Although the input–output model has been widely used for both pure economic analysis and environmental issues, demographic analysis has been relegated to the periphery of the input–output literature. Previous researchers have made significant contributions in developing the economic–demographic modeling from the unemployment perspective, in the context of shrinking regional economies. This study aims to develop an extended input–output model for urbanization, based on the Batey–Madden model by incorporating the “urbanization process”. This process is associated with one of the facets of demographic change and has received little attention in the literature. The effectiveness of the model is theoretically explored and empirically tested using Chinese data, which show rapid progress of urbanization in China. The study proposes a new “urbanization multiplier”, which implies intense population concentration in cities based on an employment multiplier in urban areas and labor allocation possibilities between urban and rural areas. The result from a preliminary application shows that the economic structure can determine the urbanization multiplier, indicating that the extent of employment opportunities promotes urbanization and the size of the population attracts more workers from rural areas. The model provides a fresh aspect of urbanization in the existing literature.
Age and sex-associated variation in the multi-site microbiome of an entire social group of free-ranging rhesus macaques
Authors: Janiak Mareike C. , Montague Michael J. , Villamil Catalina I. , Stock Michala K. , Trujillo Amber E. , DePasquale Allegra N. , Orkin Joseph D. , Bauman Surratt Samuel E. , Gonzalez Olga , Platt Michael L. , Martínez Melween I. , Antón Susan C. , Dominguez-Bello Maria Gloria , Melin Amanda D. , Higham James P.
Published: March 2021

Background

An individual’s microbiome changes over the course of its lifetime, especially during infancy, and again in old age. Confounding factors such as diet and healthcare make it difficult to disentangle the interactions between age, health, and microbial changes in humans. Animal models present an excellent opportunity to study age- and sex-linked variation in the microbiome, but captivity is known to influence animal microbial abundance and composition, while studies of free-ranging animals are typically limited to studies of the fecal microbiome using samples collected non-invasively. Here, we analyze a large dataset of oral, rectal, and genital swabs collected from 105 free-ranging rhesus macaques (Macaca mulatta, aged 1 month-26 years), comprising one entire social group, from the island of Cayo Santiago, Puerto Rico. We sequenced 16S V4 rRNA amplicons for all samples.

Results

Infant gut microbial communities had significantly higher relative abundances ofBifidobacteriumandBacteroidesand lower abundances ofRuminococcus,Fibrobacter, andTreponemacompared to older age groups, consistent with a diet high in milk rather than solid foods. The genital microbiome varied widely between males and females in beta-diversity, taxonomic composition, and predicted functional profiles. Interestingly, only penile, but not vaginal, microbiomes exhibited distinct age-related changes in microbial beta-diversity, taxonomic composition, and predicted functions. Oral microbiome composition was associated with age, and was most distinctive between infants and other age classes.

Conclusions

Across all three body regions, with notable exceptions in the penile microbiome, while infants were distinctly different from other age groups, microbiomes of adults were relatively invariant, even in advanced age. While vaginal microbiomes were exceptionally stable, penile microbiomes were quite variable, especially at the onset of reproductive age. Relative invariance among adults, including elderly individuals, is contrary to findings in humans and mice. We discuss potential explanations for this observation, including that age-related microbiome variation seen in humans may be related to changes in diet and lifestyle.
Patient’s perception of recovery after osteotome-mediated sinus floor elevation with Bio-Oss collagen compared with no grafting material: a randomized single-blinded controlled trial
Authors: Starch-Jensen Thomas , Bruun Niels Henrik
Published: March 2021

Background

Osteotome-mediated sinus floor elevation with or without a grafting material is associated with high implant survival, intrasinus bone gain, and low frequency of complications. However, patient’s perception of recovery and satisfaction with the surgical intervention are rarely reported. The objective of the present randomized controlled trial was to assess patient’s perception of recovery after osteotome-mediated sinus floor elevation with Bio-Oss collagen compared with no grafting material. Forty healthy patients were randomly allocated to Bio-Oss collagen or no grafting material. Oral health-related quality of life was assessed by Oral Health Impact Profile-14 at enrollment. Patient’s perception of recovery was assessed by self-administrated questionnaires and visual analog scale evaluating pain, social and working isolation, physical appearance, duration and quality of life alterations, eating and speaking ability, diet variations, and sleep impairment after 1 week and 1 month, respectively. Descriptive statistics was expressed as mean percentage with standard deviation. Correlation between impaired oral health-related quality of life, age, gender, and recovery were assessed by T test. Level of significance was 0.05.

Results

Osteotome-mediated sinus floor elevation is associated with high patient satisfaction, limited postoperative discomfort, and willingness to undergo similar surgery. Influence on patient’s daily life activities seems to be minimal and limited to the first postoperative days. Most patients managed to return to work and their routine daily activities after 0-2 days. Impaired preoperative oral health-related quality of life, gender, or younger age seems not to predispose for delayed recovery. However, number of days with pain, eating difficulties, and sleep disturbances were significantly increased with Bio-Oss collagen compared with no grafting material (P<0.05).

Conclusion

Patient’s discomfort seems to be minimal and limited to the first postoperative days following osteotome-mediated sinus floor elevation with or without a grafting material. Impaired preoperative oral health-related quality of life, gender, or younger age seems not to predispose for delayed recovery.
Adaptive sample size determination for the development of clinical prediction models
Authors: Christodoulou Evangelia , van Smeden Maarten , Edlinger Michael , Timmerman Dirk , Wanitschek Maria , Steyerberg Ewout W. , Van Calster Ben
Published: March 2021

Background

We suggest an adaptive sample size calculation method for developing clinical prediction models, in which model performance is monitored sequentially as new data comes in.

Methods

We illustrate the approach using data for the diagnosis of ovarian cancer (n= 5914, 33% event fraction) and obstructive coronary artery disease (CAD;n= 4888, 44% event fraction). We used logistic regression to develop a prediction model consisting only of a priori selected predictors and assumed linear relations for continuous predictors. We mimicked prospective patient recruitment by developing the model on 100 randomly selected patients, and we used bootstrapping to internally validate the model. We sequentially added 50 random new patients until we reached a sample size of 3000 and re-estimated model performance at each step. We examined the required sample size for satisfying the following stopping rule: obtaining a calibration slope ≥ 0.9 and optimism in the c-statistic (or AUC) < = 0.02 at two consecutive sample sizes. This procedure was repeated 500 times. We also investigated the impact of alternative modeling strategies: modeling nonlinear relations for continuous predictors and correcting for bias on the model estimates (Firth’s correction).

Results

Better discrimination was achieved in the ovarian cancer data (c-statistic 0.9 with 7 predictors) than in the CAD data (c-statistic 0.7 with 11 predictors). Adequate calibration and limited optimism in discrimination was achieved after a median of 450 patients (interquartile range 450–500) for the ovarian cancer data (22 events per parameter (EPP), 20–24) and 850 patients (750–900) for the CAD data (33 EPP, 30–35). A stricter criterion, requiring AUC optimism < = 0.01, was met with a median of 500 (23 EPP) and 1500 (59 EPP) patients, respectively. These sample sizes were much higher than the well-known 10 EPP rule of thumb and slightly higher than a recently published fixed sample size calculation method by Riley et al. Higher sample sizes were required when nonlinear relationships were modeled, and lower sample sizes when Firth’s correction was used.

Conclusions

Adaptive sample size determination can be a useful supplement to fixed a priori sample size calculations, because it allows to tailor the sample size to the specific prediction modeling context in a dynamic fashion.
Tumor extracellular matrix: lessons from the second-harmonic generation microscopy
Authors: de Andrade Natal Rodrigo , Adur Javier , Cesar Carlos Lenz , Vassallo José
Published: March 2021

Extracellular matrix (ECM) represents more than a mere intercellular cement. It is physiologically active in cell communication, adhesion and proliferation. Collagen is the most abundant protein, making up to 90% of ECM, and 30% of total protein weight in humans. Second-harmonic generation (SHG) microscopy represents an important tool to study collagen organization of ECM in freshly unfixed tissues and paraffin-embedded tissue samples. This manuscript aims to review some of the applications of SHG microscopy in Oncologic Pathology, mainly in the study of ECM of epithelial tumors. It is shown how collagen parameters measured by this technique can aid in the differential diagnosis and in prognostic stratification. There is a tendency to associate higher amount, lower organization and higher linearity of collagen fibers with tumor progression and metastasizing. These represent complex processes, in which matrix remodeling plays a central role, together with cancer cell genetic modifications. Integration of studies on cancer cell biology and ECM are highly advantageous to give us a more complete picture of these processes. As microscopic techniques provide topographic information allied with biologic characteristics of tissue components, they represent important tools for a more complete understanding of cancer progression. In this context, SHG has provided significant insights in human tumor specimens, readily available for Pathologists.
Fish predation on corals promotes the dispersal of coral symbionts
Authors: Grupstra Carsten G. B. , Rabbitt Kristen M. , Howe-Kerr Lauren I. , Correa Adrienne M. S.
Published: March 2021

Background

The microbiomes of foundation (habitat-forming) species such as corals and sponges underpin the biodiversity, productivity, and stability of ecosystems. Consumers shape communities of foundation species through trophic interactions, but the role of consumers in dispersing the microbiomes of such species is rarely examined. For example, stony corals rely on a nutritional symbiosis with single-celled endosymbiotic dinoflagellates (family Symbiodiniaceae) to construct reefs. Most corals acquire Symbiodiniaceae from the environment, but the processes that make Symbiodiniaceae available for uptake are not resolved. Here, we provide the first comprehensive, reef-scale demonstration that predation by diverse coral-eating (corallivorous) fish species promotes the dispersal of Symbiodiniaceae, based on symbiont cell densities and community compositions from the feces of four obligate corallivores, three facultative corallivores, two grazer/detritivores as well as samples of reef sediment and water.

Results

Obligate corallivore feces are environmental hotspots of Symbiodiniaceae cells: live symbiont cell concentrations in such feces are 5–7 orders of magnitude higher than sediment and water environmental reservoirs. Symbiodiniaceae community compositions in the feces of obligate corallivores are similar to those in two locally abundant coral genera (Pocillopora and Porites), but differ from Symbiodiniaceae communities in the feces of facultative corallivores and grazer/detritivores as well as sediment and water. Combining our data on live Symbiodiniaceae cell densities in feces with in situ observations of fish, we estimate that some obligate corallivorous fish species release over 100 million Symbiodiniaceae cells per 100 m2 of reef per day. Released corallivore feces came in direct contact with coral colonies in the fore reef zone following 91% of observed egestion events, providing a potential mechanism for the transfer of live Symbiodiniaceae cells among coral colonies.

Conclusions

Taken together, our findings show that fish predation on corals may support the maintenance of coral cover on reefs in an unexpected way: through the dispersal of beneficial coral symbionts in corallivore feces. Few studies examine the processes that make symbionts available to foundation species, or how environmental reservoirs of such symbionts are replenished. This work sets the stage for parallel studies of consumer-mediated microbiome dispersal and assembly in other sessile, habitat-forming species.