bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability in Opioid Prescription Following Primary Single-Level Lumbar Microdiscectomy
Authors: Le Hai , Phan Eileen , Agatstein Lauren , Barber Joshua , Klineberg Eric , Roberto Rolando , Javidan Yashar
Published: August 2020

Study Design:

Retrospective case series.

Objectives:

To evaluate the variability in opioid prescription following primary single-level lumbar microdiscectomy.

Methods:

We retrospectively reviewed consecutive patients who underwent primary single-level lumbar microdiscectomy. Only opioid-naïve patients ≥18 years old were included. Patients who had revision microdiscectomy, multilevel decompression, and/or any complication requiring prolonged hospital stay (>2 days) were excluded. The primary outcomes were the maximum daily dosage of opioids prescribed in morphine milligram equivalents (MME) and the number of pills prescribed (equivalent to 5 mg hydrocodone).

Results:

Between 2014 and 2019, 169 patients (90 men, 79 women) met inclusion criteria, with a mean age of 46.9 years. Surgery resulted in a statistically significant improvement in VAS (Visual Analogue Scale) score (6.4 to 2.5, P < .01). At discharge, 8 patients (4.7%) did not receive any opioid prescription. Of the remaining 161 patients, 1 patient (0.01%) received hydromorphone, 30 (18.6%) Percocet, 43 (26.7%) oxycodone, and 87 Norco (54.0%). The length of opioid prescription was 6.7 days. The maximum daily dosage of opioids prescribed was 70.4 MME (SD 32.1). The total number of pills prescribed was 89.4 (SD 54.7). Twenty-five patients (15.5%) received a refill prescription. Multivariate analysis demonstrated the operating service, prescriber, and hospital admission were statistically significant predictors of maximum daily MME. The prescriber and hospital admission were statistically significant predictors of total number of pills prescribed.

Conclusions:

We found significant variability in opioid prescription following primary single-level lumbar microdiscectomy. For standard spinal procedures like lumbar microdiscectomy, opioid-prescribing guidelines should be established to standardize postoperative pain management.
The 100 Most Cited Articles on Lumbar Spinal Stenosis: A Bibliometric Analysis
Authors: Yin Mengchen , Xu Chongqing , Mo Wen
Published: August 2020

Study Design:

Bibliometric analysis.

Objective:

With the increasing literature of spine surgery, some pioneering research studies have had a significant impact on the field of lumbar spinal stenosis (LSS). The objective of the authors was to identify and analyze the most frequently cited 100 articles in this field.

Methods:

Web of Science was searched to identify 100 top-cited articles related to LSS from 2000 to 2019. Articles on the final list were filtered based on their titles and abstracts. The following information were recorded and analyzed with bibliometric method: article title, first author, year of publication, journal of publication, total number of citations, country, institution, and study topic.

Results:

The citation count for final articles on the list ranged from 71 to 2162, with a mean number of 207.7. The journal Spine contributed the maximum number of articles (37), followed by European Spine Journal (9) and Pain Physician (8). There were collectively 80 first authors contributing to articles on the final list. Twelve authors were represented multiple times in the top 100 articles. The most prolific years were 2008 and 2009, each had 11 articles published. With regard to country and region of origin, most articles were from the United States (58). The most cited article was published in Spine in 2000 by Fairbank and Pynsent, who discussed the role of the Oswestry Disability Index as an evaluation standard in spinal disorders, including LSS.

Conclusion:

The current study analyzed the 100 most cited articles on LSS. It no doubt developed a useful resource with detailed information for many, particularly orthopedic and neurosurgery physicians who want to assimilate research focus and advance of LSS within a relatively short period. Researchers may benefit from emphasis on citation count while citing and evaluating articles and realize the deficiencies when high-level articles appear.
Flipped Lessons and the Secondary-Level Performance-Based Music Classroom: A Review of Literature and Suggestions for Practice
Authors: Weiger Erich A.
Published: August 2020

The purpose of this literature review was to synthesize relevant research concerning the blended learning and flipped lesson models, and their potential role in performance-based music classrooms. I provide theoretical backgrounds of these models and introduce Puentedura’s Substitution Augmentation Modification Redefinition model as a possible framework for implementation. Overall effectiveness and challenges of the blended learning and flipped lesson models are discussed. Finally, research and experience-based suggestions for practice are provided to help music educators implement these learning models in their classrooms.
Highly sensitive and specific diagnosis of COVID-19 by reverse transcription multiple cross-displacement amplification-labelled nanoparticles biosensor
Authors: Li Shijun , Jiang Weijia , Huang Junfei , Liu Ying , Ren Lijuan , Zhuang Li , Zheng Qinni , Wang Ming , Yang Rui , Zeng Yi , Wang Yi
Published: August 2020

Background

The ongoing outbreak of the novel human coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (also known as 2019-nCoV) has become a global health concern. Rapid and easy-to-use diagnostic techniques are urgently needed to diagnose SARS-CoV-2 infection.

Methods

We devised a reverse transcription multiple cross-displacement amplification (RT-MCDA) coupled with a nanoparticle-based biosensor assay (RT-MCDA-BS) for rapid, sensitive and specific diagnosis of coronavirus disease 2019 (COVID-19). Two primer sets were designed to target the open reading frame 1a/b and nucleoprotein gene of SARS-CoV-2. A total of 183 clinical samples, including 65 patients with COVID-19 infection and 118 patients with other pathogen infections were used to testify the assay's feasibility. Diagnosis results were reported visually using the biosensor.

Findings

The assay designed was performed using a simple instrument which could maintain the reaction in a constant temperature at 64°C for only 35 min. The total COVID-19 RT-MCDA-BS test procedure could be finished within 1 h. The COVID-19 RT-MCDA-BS could detect down to five copies of target sequences. Among 65 clinical samples from the COVID-19 patients, 22 (33.8%) positive results were obtained from faeces, nasal, pharyngeal and anal swabsviaCOVID-19 RT-MCDA-BS assay, while real-time reverse transcription-PCR assay only detected 20 (30.7%) positive results in these samples. No positive results were obtained from clinical samples with non-COVID-19 infections.

Interpretation

COVID-19 RT-MCDA-BS was a rapid, reliable, low-cost and easy-to-use assay, which could provide an attractive laboratory tool to diagnose COVID-19 in multiple clinical specimens, especially for field, clinic laboratories and primary care facilities in resource-poor settings.
Rationale and protocol of the StayFitLonger study: a multicentre trial to measure efficacy and adherence of a home-based computerised multidomain intervention in healthy older adults
Authors: Belleville S. , Cuesta M. , Bieler-Aeschlimann M. , Giacomino K. , Widmer A. , Mittaz Hager A. G. , Perez-Marcos D. , Cardin S. , Boller B. , Bier N. , Aubertin-Leheudre M. , Bherer L. , Berryman N. , Agrigoroaei S. , Demonet J. F.
Published: August 2020

Background

In older adults, multidomain training that includes physical and cognitive activities has been associated with improvement of physical and cognitive health. The goal of the multisite StayFitLonger study is to assess a home-based computerised training programme, which combines physical exercises, stimulating cognitive activities and virtual coaching.

Methods

One hundred twenty-eight cognitively healthy older adults will be recruited from the community in Switzerland, Canada and Belgium. The study will comprise (1) a 26-week double-blind randomized controlled efficacy trial and (2) a 22-week pragmatic adherence sub-study. In the efficacy trial, participants will be randomly assigned to an experimental or an active control intervention. In the experimental intervention, participants will use the StayFitLonger programme, which is computerised on a tablet and provides content that combines physical activities with a focus on strength and balance, as well as divided attention, problem solving and memory training. Outcomes will be measured before and after 26 weeks of training. The primary efficacy outcome will be performance on the “Timed-Up & Go” test. Secondary outcomes will include measures of frailty, cognition, mood, fear of falling, quality of life, and activities of daily living. Age, sex, education, baseline cognition, expectation, and adherence will be used as moderators of efficacy. Following the 26-week efficacy trial, all participants will use the experimental programme meaning that participants in the control group will ‘cross over’ to receive the StayFitLonger programme for 22 weeks. Adherence will be measured in both groups based on dose, volume and frequency of use. In addition, participants’ perception of the programme and its functionalities will be characterised through usability, acceptability and user experience.

Discussion

This study will determine the efficacy, adherence and participants’ perception of a home-based multidomain intervention programme and its functionalities. This will allow for further development and possible commercialization of a scientifically validated training programme.

Trial registration

ClinicalTrials.gov,NCT04237519Registered on January 22, 2020 - Retrospectively registered.
Urine neutrophil gelatinase-associated lipocalin and urine output as predictors of the successful discontinuation of continuous renal replacement therapy in critically ill patients with acute kidney injury
Authors: Thomsen Josefine , Sprogøe Ulrik , Toft Palle
Published: August 2020

Background

Continuous renal replacement therapy (CCRT) is a frequently used modality for the support of intensive care patients with acute kidney injury (AKI). Nevertheless, there are no objective criteria for the discontinuation of CRRT. The purpose of this study was to investigate whether urine neutrophil gelatinase-associated lipocalin (uNGAL) alone or in combination with urine output could be used as a diagnostic test for renal function recovery in ICU patients on CRRT.

Methods

This was a single-centre prospective observational study including patients with acute kidney failure needing CRRT. Sixty-nine patients were enrolled, and 54 completed the study. Of the 54 patients, 22 recovered renal function (REC), defined as dialysis independency at 72 h from discontinuation, while 32 patients did not (NREC). Urine NGAL was measured at 0, 6, 12, and 24 h after CRRT discontinuation. The cumulated urine output was measured for 24 h prior to discontinuation and at 6, 12, and 24 h after discontinuation. Missing uNGAL values were calculated by interpolation. The Youden’s index was used to calculate cut-off values in order to define uNGAL and urine output single variable and 2-variable diagnostic tests with the optimum prediction of successful CRRT discontinuation.

Results

Baseline characteristics at CRRT initiation were similar between groups. Compared to the NREC group, the REC group had significantly higher urine output (p < 0.0001) and lower uNGAL (p < 0.001) at all time points, except for uNGAL at 24 h (p < 0.24). The best uNGAL predictor for successful CRRT discontinuation was uNGAL at 6 h after discontinuation (predictive value 80%). The best single predictor was cumulated urine output 24 h before discontinuation (predictive value 85%). The combinations of uNGAL at 6 h (cut-off 1650 μg/L) with cumulated urine output 24 h prior to discontinuation (cut-off 210 ml) proved to be the superior tests (using either “or” or “and”), with predictive values of 93% (successful CRRT discontinuation) and 92% (dialysis dependency).

Conclusions

With a predictive value of 93%, the combination of uNGAL at 6 h after and the cumulated urine output 24 h prior to CRRT cessation proved to be the best diagnostic test for successful CRRT discontinuation in ICU patients.

Clinical trial registration

N/A
A machine learning approach to optimizing cell-free DNA sequencing panels: with an application to prostate cancer
Authors: Cario Clinton L. , Chen Emmalyn , Leong Lancelote , Emami Nima C. , Lopez Karen , Tenggara Imelda , Simko Jeffry P. , Friedlander Terence W. , Li Patricia S. , Paris Pamela L. , Carroll Peter R. , Witte John S.
Published: August 2020

Background

Cell-free DNA’s (cfDNA) use as a biomarker in cancer is challenging due to genetic heterogeneity of malignancies and rarity of tumor-derived molecules. Here we describe and demonstrate a novel machine-learning guided panel design strategy for improving the detection of tumor variants in cfDNA. Using this approach, we first generated a model to classify and score candidate variants for inclusion on a prostate cancer targeted sequencing panel. We then used this panel to screen tumor variants from prostate cancer patients with localized disease in both in silico and hybrid capture settings.

Methods

Whole Genome Sequence (WGS) data from 550 prostate tumors was analyzed to build a targeted sequencing panel of single point and small (< 200 bp) indel mutations, which was subsequently screened in silico against prostate tumor sequences from 5 patients to assess performance against commonly used alternative panel designs. The panel’s ability to detect tumor-derived cfDNA variants was then assessed using prospectively collected cfDNA and tumor foci from a test set 18 prostate cancer patients with localized disease undergoing radical proctectomy.

Results

The panel generated from this approach identified as top candidates mutations in known driver genes (e.g. HRAS) and prostate cancer related transcription factor binding sites (e.g. MYC, AR). It outperformed two commonly used designs in detecting somatic mutations found in the cfDNA of 5 prostate cancer patients when analyzed in an in silico setting. Additionally, hybrid capture and 2500X sequencing of cfDNA molecules using the panel resulted in detection of tumor variants in all 18 patients of a test set, where 15 of the 18 patients had detected variants found in multiple foci.

Conclusion

Machine learning-prioritized targeted sequencing panels may prove useful for broad and sensitive variant detection in the cfDNA of heterogeneous diseases. This strategy has implications for disease detection and monitoring when applied to the cfDNA isolated from prostate cancer patients.
Hole diameter ratio for prediction of anatomical outcomes in stage III or IV idiopathic macular holes
Authors: Qi Yue , Yu Yanping , You Qisheng , Wang Zengyi , Wang Jing , Liu Wu
Published: August 2020

Background

To determine whether preoperative hole diameter ratio (HDR) is a predictive factor for postoperative anatomical outcome for stage III or IV idiopathic macular holes (IMHs).

Methods

One-hundred and one eyes with stage III or IV IMH were included in this retrospective case series study. All cases were treated with vitrectomy combined with internal limiting membrane (ILM) peeling and room air tamponade. The macular hole (MH) minimum and maximum diameter was measured on preoperative optical coherence tomography (OCT) images. The HDR was defined as the minimum to maximum diameter ratio.

Results

Eighty-one eyes (80.2%) got a Type I closure after surgery (group A). Postoperative unclosed MHs were found in 20 eyes (19.8%) (group B). The preoperative minimal diameter (703.6 ± 116.1 μm vs. 597.6 ± 120.1 μm, P < 0.01) and HDR (0.6 ± 0.1 vs. 0.5 ± 0.1, P = 0.01) were both significantly smaller in postoperative closed eyes. The closure rate of IMHs with HDR < 0.6 was significantly higher than those with HDR ≥ 0.6 (90.2% vs. 65.0%P = 0.002) .

Conclusions

Preoperative HDR < 0.6 is predictive for a good postoperative anatomical outcome in stage III or IV IMHs.
Cost-effectiveness of guideline-based stepped and collaborative care versus treatment as usual for patients with depression – a cluster-randomized trial
Authors: Brettschneider Christian , Heddaeus Daniela , Steinmann Maya , Härter Martin , Watzke Birgit , König Hans-Helmut
Published: August 2020

Background

Depression is associated with major patient burden. Its treatment requires complex and collaborative approaches. A stepped care model based on the German National Clinical Practice Guideline “Unipolar Depression” has been shown to be effective. In this study we assess the cost-effectiveness of this guideline based stepped care model versus treatment as usual in depression.

Methods

This prospective cluster-randomized controlled trial included 737 depressive adult patients. Primary care practices were randomized to an intervention (IG) or a control group (CG). The intervention consisted of a four-level stepped care model. The CG received treatment as usual. A cost-utility analysis from the societal perspective with a time horizon of 12 months was performed. We used quality-adjusted life years (QALY) based on the EQ-5D-3L as effect measure. Resource utilization was assessed by patient questionnaires. Missing values were imputed by ‘multiple imputation using chained equations’ based on predictive mean matching. We calculated adjusted group differences in costs and effects as well as incremental cost-effectiveness ratios. To describe the statistical and decision uncertainty cost-effectiveness acceptability curves were constructed based on net-benefit regressions with bootstrapped standard errors (1000 replications). The complete sample and subgroups based on depression severity were considered.

Results

We found no statically significant differences in costs and effects between IG and CG. The incremental total societal costs (+€5016; 95%-CI: [−€259;€10,290) and effects (+ 0.008 QALY; 95%-CI: [− 0.030; 0.046]) were higher in the IG in comparison to the CG. Significantly higher costs were found in the IG for outpatient physician services and psychiatrist services in comparison to the CG. Significantly higher total costs and productivity losses in the IG in comparison to the CG were found in the group with severe depression. Incremental cost-effectiveness ratios for the IG in comparison to the CG were unfavourable (complete sample: €627.000/QALY gained; mild depression: dominated; moderately severe depression: €645.154/QALY gained; severe depression: €2082,714/QALY gained) and the probability of cost-effectiveness of the intervention was low, except for the group with moderate depression (ICER: dominance; 70% for willingness-to-pay threshold of €50,000/QALY gained).

Conclusions

We found no evidence for cost-effectiveness of the intervention in comparison to treatment as usual.

Trial registration

NCT, NCT01731717. Registered 22 November 2012 - Retrospectively registered.
A qualitative investigation of lived experiences of long-term health condition management with people who are food insecure
Authors: Douglas Flora , MacIver Emma , Yuill Chris
Published: August 2020

Background

As more people are living with one or more chronic health conditions, supporting patients to become activated, self-managers of their conditions has become a key health policy focus both in the UK and internationally. There is also growing evidence in the UK that those with long term health conditions have an increased risk of being food insecure. While international evidence indicates that food insecurity adversely affects individual’s health condition management capability, little is known about how those so affected manage their condition(s) in this context. An investigation of lived experience of health condition management was undertaken with food insecure people living in north east Scotland. The study aimed to explore the challenges facing food insecure people in terms of, i. their self-care condition management practices, and ii. disclosing and discussing the experience of managing their condition with a health care professional, and iii. Notions of the support they might wish to receive from them.

Methods

Twenty in-depth interviews were conducted with individuals attending a food bank and food pantry in north east Scotland. Interview audio recordings were fully transcribed and thematically analysed.

Results

Individuals reporting multiple physical and mental health conditions, took part in the study. Four main themes were identified i.e.: 1. food practices, trade-offs and compromises, that relate to economic constraints and lack of choice; 2. illness experiences and food as they relate to physical and mental ill-health; 3. (in) visibility of participants’ economic vulnerability within health care consultations; and 4. perceptions and expectations of the health care system.

Conclusions

This study, the first of its kind in the UK, indicated that participants’ health condition management aspirations were undermined by the experience of food insecurity, and that their health care consultations in were, on the whole, devoid of discussions of those challenges. As such, the study indicated practical and ethical implications for health care policy, practice and research associated with the risk of intervention-generated health inequalities that were suggested by this study. Better understanding is needed about the impact of household food insecurity on existing ill health, wellbeing and health care use across the UK.
Efficacy of HIV interventions among factory workers in low- and middle-income countries: a systematic review
Authors: Chen Dahui , Luo Ganfeng , Meng Xiaojun , Wang Zixin , Cao Bolin , Yuan Tanwei , Xie Yu , Hu Tian , Chen Yaqi , Ke Wujian , Wang Zhenyu , Sun Caijun , Deng Kai , Cai Yong , Zhang Kechun , Zou Huachun
Published: August 2020

Background

Factory workers in low- and middle-income countries (LMICs) are vulnerable to HIV transmission. Interventions are needed to prevent HIV in this population. We systematically reviewed published literature on the efficacy of various HIV interventions in reducing stigma, risk behaviors and HIV transmission among factory workers.

Methods

A systematic review was performed using predefined inclusion and exclusion criteria. Four databases (PubMed, PsycINFO, Scopus and EMBASE) were searched for relevant publications between January 1, 1990 and December 31, 2018. Two independent reviewers assessed the methodological quality of studies.

Results

Thirteen articles were included, with 2 randomized controlled trials and 11 cohort studies. Five interventions and their combinations were summarized. Educational intervention increased condom use and reduced the use of recreational drugs and alcohol before sex. Community intervention that proactively provide HIV counselling and testing (HCT) services could increase the detection rate of HIV and other sexually transmitted diseases (STDs). Lottery intervention increased HCT uptake and decreased HIV public stigma. Education combined with community intervention reduced the proportion of workers with casual sex and enhanced HIV knowledge. Peer education combined with community intervention increased the proportion of workers who were willing to take their partners to HCT. Policy intervention combined with peer education enhanced HIV knowledge, perceived condom accessibility and condom use with regular partners.

Conclusions

Various interventions improved HIV knowledge, decreased HIV stigma and reduced HIV-related risk behaviors among factory workers in LMICs. The combination of multiple interventions tended to achieve better efficacy than a single intervention. Persistent combination interventions are essential to address HIV in this population.
Small cell carcinoma of the bladder with coexisting prostate adenocarcinoma: two cases report and literature review
Authors: Liu Yanxia , Xu Hongming , Wu Bin , Liu Shuguang , Luo Qiang
Published: August 2020

Background

Primary small cell carcinoma of the bladder (SCCB) is a rare disease of the genitourinary tract and reported limitedly. SCCB is very aggressive and always mixed with other histologic components, but coexistence of SCCB and prostate adenocarcinoma is extremely rare.

Cases presentation

Two aged males (72 and 58 years) were included in this study. Both of them presented with gross hematuria as initial symptom. Magnetic resonance imaging (MRI) demonstrated protruding lesions in the urinary bladder. Pathological examination after radical cystectomy and prostatectomy showed the concurrence of SCCB and prostate adenocarcinoma. One patient died of liver and lung metastasis 8 months after surgery, and the other patient was still alive after 19 months of follow-up.

Conclusion

In this paper, we reported two unusual cases of coexistence of SCCB and prostate adenocarcinoma, and reviewed relative literatures with respect to the epidemiology, clinical features, pathologic features, diagnosis, treatment and prognosis of SCCB.
Predictors of intra-hospital mortality in patients with diabetic foot ulcers in Nigeria: data from the MEDFUN study
Authors: Adeleye Olufunmilayo O. , Ugwu Ejiofor T. , Gezawa Ibrahim D. , Okpe Innocent , Ezeani Ignatius , Enamino Marcelina
Published: August 2020

Background

Diabetic foot ulcers (DFU) are associated with high morbidity and mortality globally. Mortality in patients hospitalized for DFU in Nigeria is unacceptably high. This study was undertaken to determine factors that predict mortality in patients hospitalized for DFU in Nigeria.

Methods

The current study was part of Multi-centre Evaluation of Diabetic Foot Ulcer in Nigeria (MEDFUN), an observational study conducted in six tertiary healthcare institutions across the 6 geopolitical zones of Nigeria. Consecutive type 1 or 2 diabetic patients hospitalized for DFU who consented to participate were recruited and subjected to relevant clinical, biochemical, and radiological assessments and multidisciplinary care until discharge or death. Data for type 1 diabetes mellitus (DM) patients were expunged from current mortality analysis due to their small number.

Results

Three hundred and twenty-three type 2 DM subjects with mean age and mean duration of DM of 57.2 ± 11.4 years and 8.7 ± 5.8 years respectively participated in this study. The median duration of ulcers was 39 days with a range of 28 to 54 days and the majority (79.9%) presented with advanced ulcers of at least Wagner grade 3. Mortality of 21.4% was recorded in the study, with the highest mortality observed among subjects with Wagner grade 5.

Variables significantly associated with mortality with their respective p values were DM duration more than 120 months (p 0.005), ulcer duration > 1 month (p 0.020), ulcer severity of Wagner grade 3 and above (p 0.001), peripheral arterial disease (p 0.005), proteinuria (p < 0.001), positive blood cultures (p < 0.001), low HDL (p < 0.001), shock at presentation (p < 0.001), cardiac failure (p 0.027), and renal impairment (p < 0.001). On Multivariate regression analysis, presence of bacteraemia (OR 5.053; 95% CI 2.572–9.428) and renal impairment (OR 2.838; 95% CI 1.349–5.971) were significantly predictive of mortality independent of other variables.

Conclusions

This study showed high intra-hospital mortality among patients with DFU, with the majority of deaths occurring among those with advanced ulcers, bacteraemia, cardiac failure, and renal impairment. Prompt attention to these factors might help improve survival from DFU in Nigeria.
Anti-inflammatory effect of Ganluyin, a Chinese classic prescription, in chronic pharyngitis rat model
Authors: Chen Ye-Hui , Luo Rong , Lei Shan-Shan , Li Bing , Zhou Fu-Chen , Wang Hui-Ying , Chen Xue , He Xinglishang , Wang Yu-Zhi , Zhan Liang-Hui , Lu Ting-Ting , Su Jie , Yu Qiao-Xian , Li Bo , Lv Gui-Yuan , Chen Su-Hong
Published: August 2020

Background

Ganluyin (GLY) is a famous classical prescription with a long history of use as a treatment for inflammatory conditions such as chronic pharyngitis (CP) in many parts of China. However, it has not been developed as a modern pharmaceutic and its anti-inflammatory mechanisms remain unclear. The aim of this study was to assess the anti-inflammatory efficacy of GLY and potential mechanisms in a rat model of CP.

Methods

The chemical profile of GLY was analyzed by HPLC-UV. We used a mouse model of ear edema and a rat model of paw edema. Specifically, xylene was used to induce edema on the surface of one ear in mice, and carrageenan was injected subcutaneously into the right hind paws of rats to induce paw edema. The paw thickness, ear weight, and ear perfusion were measured and recorded. The CP model in rats was induced by irritating the throat with 5% ammonia and was used to evaluate the therapeutic efficacy of GLY. Levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and prostaglandin E2 (PGE2) were measured by ELISA in serum, and protein expression of cyclooxygenase-2 (COX-2) and nuclear factor kappa-B p65 (NF-κB p65) in the throat were detected by immunohistochemistry and Western blot to evaluate the anti-inflammatory mechanism of GLY. Hematological assays were also conducted.

Results

There were four flavonoids identified in GLY: naringin, neohesperidin, baicalin, and wogonoside. The oral administration of GLY showed a significant inhibitory effect on xylene-induced ear swelling and ear blood flow in mice and significantly ameliorated rat right hind paw edema at doses of 6.2 and 12.4 g/kg. Mechanistic studies found that the anti-inflammatory activity of GLY was related to the inhibition of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, and PGE2 and that GLY reduced the expression of COX-2 and NF-κB p65 proteins in the throat, attenuated throat injury, and reduced inflammatory exudates. Hematological analysis showed that treatment with GLY prevented increases in white blood cell (WBC), neutrophil (NEUT), lymphocyte (LYMPH) and monocyte (MONO) levels.

Conclusions

These studies indicated that GLY has beneficial anti-inflammatory effects on CP and that it acts through reducing pro-inflammatory factors such as IL-1β, IL-6, TNF-α, and PGE2, as well as decreasing WBC, NEUT, LYMPH and MONO levels and decreasing the expression of COX-2 and NF-κB p65 proteins. These findings may lay the groundwork for further studies of GLY as a suitable candidate for the treatment of inflammatory diseases such as CP.
The sudden transition to synchronized online learning during the COVID-19 pandemic in Saudi Arabia: a qualitative study exploring medical students’ perspectives
Authors: Khalil Rehana , Mansour Ali E. , Fadda Walaa A. , Almisnid Khaled , Aldamegh Mohammed , Al-Nafeesah Abdullah , Alkhalifah Azzam , Al-Wutayd Osama
Published: August 2020

Background

The closure of educational activities in the Kingdom of Saudi Arabia due to the ongoing COVID-19 pandemic resulted in an unplanned shift from traditional learning to a setup that exclusively involves digital teaching and learning. Within this context, the present study aimed to explore undergraduate medical students’ perceptions regarding the effectiveness of synchronized online learning at Unaizah College of Medicine and Medical Sciences, Qassim University, Saudi Arabia.

Methods

A qualitative study was conducted using virtual focus group discussions synchronously with the help of a discussion guide consisting of seven open-ended questions. Overall, 60 medical students were recruited using a maximum variation sampling technique; these students then participated in eight focus group discussions. All interviews were recorded, transcribed verbatim, and analyzed for thematic contents using the standard (Mayring, Kiger. M. E. and Braun.V) content analysis framework.

Results

A thematic content analysis yielded four core themes: (1) educational impact, (2) time management, (3) challenges encountered, and (4) preferences for the future. The online modality was well-received, and all participants agreed that online sessions were time saving and that their performance was improved due to enhanced utility of time; however, they indicated that they encountered some challenges, including methodological, content perception, technical, and behavioral challenges during sessions and online exams. Most of the preclinical students preferred online learning for the upcoming academic years.

Conclusion

Synchronized online classes were well-accepted by the medical students. This represents significant and promising potential for the future of medical education. The principles of the online learning model and learning outcomes should be rigorously and regularly evaluated to monitor its effectiveness.
PASCAL: a pseudo cascade learning framework for breast cancer treatment entity normalization in Chinese clinical text
Authors: An Yang , Wang Jianlin , Zhang Liang , Zhao Hanyu , Gao Zhan , Huang Haitao , Du Zhenguang , Jiao Zengtao , Yan Jun , Wei Xiaopeng , Jin Bo
Published: August 2020

Backgrounds

Knowledge discovery from breast cancer treatment records has promoted downstream clinical studies such as careflow mining and therapy analysis. However, the clinical treatment text from electronic health data might be recorded by different doctors under their hospital guidelines, making the final data rich in author- and domain-specific idiosyncrasies. Therefore, breast cancer treatment entity normalization becomes an essential task for the above downstream clinical studies. The latest studies have demonstrated the superiority of deep learning methods in named entity normalization tasks. Fundamentally, most existing approaches adopt pipeline implementations that treat it as an independent process after named entity recognition, which can propagate errors to later tasks. In addition, despite its importance in clinical and translational research, few studies directly deal with the normalization task in Chinese clinical text due to the complexity of composition forms.

Methods

To address these issues, we propose PASCAL, an end-to-end and accurate framework for breast cancer treatment entity normalization (TEN). PASCAL leverages a gated convolutional neural network to obtain a representation vector that can capture contextual features and long-term dependencies. Additionally, it treats treatment entity recognition (TER) as an auxiliary task that can provide meaningful information to the primary TEN task and as a particular regularization to further optimize the shared parameters. Finally, by concatenating the context-aware vector and probabilistic distribution vector from TEN, we utilize the conditional random field layer (CRF) to model the normalization sequence and predict the TEN sequential results.

Results

To evaluate the effectiveness of the proposed framework, we employ the three latest sequential models as baselines and build the model in single- and multitask on a real-world database. Experimental results show that our method achieves better accuracy and efficiency than state-of-the-art approaches.

Conclusions

The effectiveness and efficiency of the presented pseudo cascade learning framework were validated for breast cancer treatment normalization in clinical text. We believe the predominant performance lies in its ability to extract valuable information from unstructured text data, which will significantly contribute to downstream tasks, such as treatment recommendations, breast cancer staging and careflow mining.
A renewed call for transdisciplinary action on NCDs
Authors: Toebes Brigit , Hesselman Marlies , Mierau Jochen O. , van Dijk Jitse P.
Published: August 2020

Notwithstanding COVID-19, non-communicable diseases (NCDs) will be the leading cause of death in every region in the world by 2030. This contribution, which forms an introduction to our collection of articles in this journal, identifies elements for a transdisciplinary research agenda between law, public health, health economics and international relations aimed at designing concrete interventions to curb the NCD pandemic, both globally and domestically.
Excess diacylglycerol at the endoplasmic reticulum disrupts endomembrane homeostasis and autophagy
Authors: Li Dan , Yang Shu-Gao , He Cheng-Wen , Zhang Zheng-Tan , Liang Yongheng , Li Hui , Zhu Jing , Su Xiong , Gong Qingqiu , Xie Zhiping
Published: August 2020

Background

When stressed, eukaryotic cells produce triacylglycerol (TAG) to store nutrients and mobilize autophagy to combat internal damage. We and others previously reported that in yeast, elimination of TAG synthesizing enzymes inhibits autophagy under nitrogen starvation, yet the underlying mechanism has remained elusive.

Results

Here, we show that disruption of TAG synthesis led to diacylglycerol (DAG) accumulation and its relocation from the vacuolar membrane to the endoplasmic reticulum (ER). We further show that, beyond autophagy, ER-accumulated DAG caused severe defects in the endomembrane system, including disturbing the balance of ER-Golgi protein trafficking, manifesting in bulging of ER and loss of the Golgi apparatus. Genetic or chemical manipulations that increase consumption or decrease supply of DAG reversed these defects. In contrast, increased amounts of precursors of glycerolipid synthesis, including phosphatidic acid and free fatty acids, did not replicate the effects of excess DAG. We also provide evidence that the observed endomembrane defects do not rely on Golgi-produced DAG, Pkc1 signaling, or the unfolded protein response.

Conclusions

This work identifies DAG as the critical lipid molecule responsible for autophagy inhibition under condition of defective TAG synthesis and demonstrates the disruption of ER and Golgi function by excess DAG as the potential cause of the autophagy defect.
A novel role of Krüppel-like factor 8 as an apoptosis repressor in hepatocellular carcinoma
Authors: Wang Ming-Da , Xing Hao , Li Chao , Liang Lei , Wu Han , Xu Xin-Fei , Sun Li-Yang , Wu Meng-Chao , Shen Feng , Yang Tian
Published: August 2020

Background

Krüppel-like factor 8 (KLF8), a cancer-promoting factor that regulates critical gene transcription and cellular cancer-related events, has been implicated in tumor development and progression. However, the functional role of KLF8 in the pathogenesis of hepatocellular carcinoma (HCC) remains largely unknown.

Methods

The gene expression patterns and genome-wide regulatory profiles of HCC cells after KLF8 knockout were analyzed by using RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) of histone H3 lysine 27 acetylation (H3K27ac) combined with bioinformatics analysis. Transcription factor-binding motifs that recognized by KLF8 were evaluated by motif analysis. For the predicted target genes, transcriptional changes were examined by ChIP, and loss of function experiments were conducted by siRNA transfection.

Results

KLF8 functioned as a transcription repressor in HCC and mainly regulated apoptotic-related genes directly. A total of 1,816 differentially expressed genes after KLF8 knockout were identified and significantly corresponded to global changes in H3K27ac status. Furthermore, two predicted target genes, high-mobility group AT-hook 2 (HMGA2) and matrix metalloproteinase 7 (MMP7), were identified as important participants in KLF8-mediated anti-apoptotic effect in HCC. Knockout of KLF8 enhanced cell apoptosis process and caused increase in the associated H3K27ac, whereas suppression HMGA2 or MMP7 attenuated these biological effects.

Conclusions

Our work suggests a novel role and mechanism for KLF8 in the regulation of cell apoptosis in HCC and facilitates the discovery of potential therapeutic targets for HCC treatment.
Hexokinase inhibition using D-Mannoheptulose enhances oncolytic newcastle disease virus-mediated killing of breast cancer cells
Authors: Al-Ziaydi Ahmed Ghdhban , Al-Shammari Ahmed Majeed , Hamzah Mohammed I. , kadhim Haider Sabah , Jabir Majid Sakhi
Published: August 2020

Background

Most cancer cells exhibit increased glycolysis and use this metabolic pathway cell growth and proliferation. Targeting cancer cells’ metabolism is a promising strategy in inhibiting cancer cell progression. We used D-Mannoheptulose, a specific hexokinase inhibitor, to inhibit glycolysis to enhance the Newcastle disease virus anti-tumor effect.

Methods

Human breast cancer cells were treated by NDV and/or hexokinase inhibitor. The study included cell viability, apoptosis, and study levels of hexokinase enzyme, pyruvate, ATP, and acidity. The combination index was measured to determine the synergism of NDV and hexokinase inhibitor.

Results

The results showed synergistic cytotoxicity against breast cancer cells by combination therapy but no cytotoxic effect against normal cells. The effect was accompanied by apoptotic cell death and hexokinase downregulation and inhibition to glycolysis products, pyruvate, ATP, and acidity.

Conclusions

The combination treatment showed safe significant tumor cell proliferation inhibition compared to monotherapies suggesting a novel strategy for anti-breast cancer therapy through glycolysis inhibition by hexokinase downregulation.
Identification of potential biomarkers and candidate small molecule drugs in glioblastoma
Authors: Lu Wei-cheng , Xie Hui , Yuan Ce , Li Jin-jiang , Li Zhao-yang , Wu An-hua
Published: August 2020

Background and aims

Glioblastoma (GBM) is a common and aggressive primary brain tumor, and the prognosis for GBM patients remains poor. This study aimed to identify the key genes associated with the development of GBM and provide new diagnostic and therapies for GBM.

Methods

Three microarray datasets (GSE111260, GSE103227, and GSE104267) were selected from Gene Expression Omnibus (GEO) database for integrated analysis. The differential expressed genes (DEGs) between GBM and normal tissues were identified. Then, prognosis-related DEGs were screened by survival analysis, followed by functional enrichment analysis. The protein–protein interaction (PPI) network was constructed to explore the hub genes associated with GBM. The mRNA and protein expression levels of hub genes were respectively validated in silico using The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. Subsequently, the small molecule drugs of GBM were predicted by using Connectivity Map (CMAP) database.

Results

A total of 78 prognosis-related DEGs were identified, of which10 hub genes with higher degree were obtained by PPI analysis. The mRNA expression and protein expression levels of CETN2, MKI67, ARL13B, and SETDB1 were overexpressed in GBM tissues, while the expression levels of CALN1, ELAVL3, ADCY3, SYN2, SLC12A5, and SOD1 were down-regulated in GBM tissues. Additionally, these genes were significantly associated with the prognosis of GBM. We eventually predicted the 10 most vital small molecule drugs, which potentially imitate or reverse GBM carcinogenic status. Cycloserine and 11-deoxy-16,16-dimethylprostaglandin E2 might be considered as potential therapeutic drugs of GBM.

Conclusions

Our study provided 10 key genes for diagnosis, prognosis, and therapy for GBM. These findings might contribute to a better comprehension of molecular mechanisms of GBM development, and provide new perspective for further GBM research. However, specific regulatory mechanism of these genes needed further elaboration.
Combined extracts of Moringa oleifera, Murraya koeingii leaves, and Curcuma longa rhizome increases energy expenditure and controls obesity in high-fat diet-fed rats
Authors: Kundimi Sreenath , Kavungala Krishna Chaitanya , Sinha Swaraj , Tayi Venkata Narasimha Rao , Kundurthi Nagendra Rao , Golakoti Trimurtulu , Davis Barbara , Sengupta Krishanu
Published: August 2020

Background

LI85008F is a proprietary combination of leaf extracts of Moringa oleifera, Murraya koeingii, and extract of Curcuma longa rhizome. This herbal extract combination is an effective weight loss supplement for overweight and obese subjects. The present study aimed to investigate the thermogenic potential of the LI85008F in high-fat diet (HFD)-induced obese Sprague Dawley rats.

Methods

Seven rats received a regular diet (RD), and twenty-one rats received a high-fat diet (HFD) for 56 days. On day 28, the HFD-fed rats were randomized into three groups (n = 7). Starting from day 29 through day 56, one HFD-fed group received daily oral gavage of 0.5% Carboxymethylcellulose Sodium (CMC) alone (HFD), and the remaining two groups received 100 and 250 mg/kg LI85008F (LI85008F-100 and LI85008F-250, respectively).

Body weight, fat mass, fat cell size, liver weight, liver triglyceride were measured. The energy metabolism parameters were measured using indirect calorimetry. In serum, the metabolic and endocrine markers were analyzed. The adipogenic and thermoregulatory proteins expression in the white adipose tissue (WAT) were analyzed using an immunoblot assay.

Results

Supplementation with both doses of LI85008F significantly increased resting energy expenditure (REE) in the obese rats. The LI85008F-250 rats showed significant up-regulation of uncoupling protein-1 (UCP-1) expression, as compared with the HFD rats. LI85008F significantly reduced body weight gain, fat mass, fat cell size, liver weight, and hepatic triglycerides. Serum triglyceride, total cholesterol, glucose, leptin, and fat cell markers were significantly reduced in LI85008F-supplemented rats compared to the HFD rats.

Conclusion

The present data suggest that LI85008F reduces body fat mass and controls body weight gain via increasing energy metabolism in combination with reduced lipogenesis in diet-fed obese rats.
Hookah use patterns, social influence and associated other substance use among a sample of New York City public university students
Authors: El Shahawy Omar , Park Su Hyun , Rogers Erin S. , Shearston Jenni A. , Thompson Azure B. , Cooper Spring C. , Freudenberg Nicholas , Ball Samuel A. , Abrams David , Shelley Donna , Sherman Scott E.
Published: August 2020

Background

Most hookah use studies have not included racial and ethnic minorities which limits our understanding of its use among these growing populations. This study aimed to investigate the individual characteristics of hookah use patterns and associated risk behaviors among an ethnically diverse sample of college students.

Methods

A cross-sectional survey of 2460 students (aged 18–25) was conducted in 2015, and data was analyzed in 2017. Descriptive statistics were used to present the sociodemographic characteristics, hookah use-related behavior, and binge drinking and marijuana use according to the current hookah use group, including never, exclusive, dual/poly hookah use. Multivariate logistic regression was conducted to examine how hookah related behavior and other risk behaviors varied by sociodemographics and hookah use patterns.

Results

Among current hookah users (n = 312), 70% were exclusive hookah users and 30% were dual/poly hookah users. There were no statistically significant differences in sociodemographic characteristics except for race/ethnicity (p < 0.05). Almost half (44%) of the exclusive hookah users reported having at least five friends who also used hookah, compared to 30% in the dual/poly use group. Exclusive users were less likely to report past year binge drinking (17%) and past year marijuana use (25%) compared to those in the dual/poly use group (44 and 48% respectively);p < 0.001.

Conclusions

The socialization aspects of hookah smoking seem to be associated with its use patterns. Our study calls for multicomponent interventions designed to target poly tobacco use as well as other substance use that appears to be relatively common among hookah users.