bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptide Enhanced Bone Graft Substitute Presents Improved Short-Term Increase in Bone Volume and Construct Stiffness Compared to Iliac Crest Autologous Bone in an Ovine Lumbar Interbody Fusion Model
Authors: Loenen Arjan C. Y. , Connor Jerome , Johnson Scott , Davis Katherine , Hannigan Nolan , Barnes Tristan , Arts Jacobus J. , van Rietbergen Bert
Published: January 2021

Study design:

Preclinical ovine model.

Objective:

To assess the in vivo efficacy and safety of the P-15 L bone graft substitute and compare its performance to autologous iliac crest bone graft (ICBG) for lumbar interbody fusion indications.

Methods:

Thirty skeletally mature sheep underwent lumbar interbody fusion surgery. Half of the sheep received autologous ICBG and the other half the peptide enhanced bone graft substitute (P-15 L). Following termination at 1, 3, and 6 months after surgery, the operated segments were analyzed using micro computed tomography (µCT), histology, and destructive mechanical testing. Additional systemic health monitoring was performed for the P-15 L group.

Results:

One month after surgery, there was only minor evidence of bone remodeling and residual graft material could be clearly observed within the cage. There was active bone remodeling between 1 and 3 months after surgery. At 3 months after surgery significantly denser and stiffer bone was found in the P-15 L group, whereas at 6 months, P-15 L and ICBG gave similar fusion results. The P-15 L bone graft substitute did not have any adverse effects on systemic health.

Conclusions:

The drug device combination P-15 L was demonstrated to be effective and save for lumbar interbody fusion as evidenced by this ovine model. Compared to autologous ICBG, P-15 L seems to expedite bone formation and remodeling but in the longer-term fusion results were similar.
Lumbar Fusion Surgery for Patients With Back Pain and Degenerative Disc Disease: An Observational Study From the Canadian Spine Outcomes and Research Network
Authors: Evaniew Nathan , Swamy Ganesh , Jacobs W. Bradley , Bouchard Jacques , Cho Roger , Manson Neil A. , Rampersaud Y. Raja , Paquet Jerome , Bailey Christopher S. , Johnson Michael , Attabib Najmedden , Fisher Charles G. , McIntosh Greg , Thomas Kenneth C.
Published: January 2021

Study Design:

Uncontrolled retrospective observational study.

Objectives:

Surgery for patients with back pain and degenerative disc disease is controversial, and studies to date have yielded conflicting results. We evaluated the effects of lumbar fusion surgery for patients with this indication in the Canadian Spine Outcomes and Research Network (CSORN).

Methods:

We analyzed data that were prospectively collected from consecutive patients at 11 centers between 2015 and 2019. Our primary outcome was change in patient-reported back pain at 12 months of follow-up, and our secondary outcomes were satisfaction, disability, health-related quality of life, and rates of adverse events.

Results:

Among 84 patients, we observed a statistically significant improvement of back pain at 12 months that exceeded the threshold of Minimum Clinically Important Difference (MCID) (mean change -3.7 points, SD 2.6, p < 0.001, MCID = 1.2; 77% achieved MCID), and 81% reported being “somewhat” or “extremely” satisfied. We also observed improvements of Oswestry Disability Index (-17.3, SD 16.6), Short Form-12 Physical Component Summary (10.3, SD 9.6) and Short Form-12 Mental Component Summary (3.1, SD 8.3); all p < 0.001). The overall rate of adverse events was 19%.

Conclusions:

Among a highly selective group of patients undergoing lumbar fusion surgery for degenerative disc disease, most experienced a clinically significant improvement of back pain as well as significant improvements of disability and health-related quality of life, with high satisfaction at 1 year of follow-up. These findings suggest that surgery for this indication may provide some benefit, and that further research is warranted.
Back Dominant Pain Has Equal Outcomes to Radicular Dominant Pain Following Posterior Lumbar Fusion in Adult Isthmic Spondylolisthesis: A CSORN Study
Authors: Alnaghmoosh Nabeel , Urquhart Jennifer , Raj Ruheksh , Abraham Edward , Jacobs Bradley , Phan Philippe , Johnson Michael , Paquet Jerome , Nataraj Andrew , McIntosh Greg , Fisher Charles G. , Rampersaud Y. Raja , Manson Neil , Hall Hamilton , Rasoulinejad Parham , Bailey Christopher S.
Published: January 2021

Study Design:

Retrospective Cohort Study.

Objectives:

This study aimed to determine how the surgeon-determined and patient-rated location of predominant pain influences patient-rated outcomes at 1-year after posterior lumbar fusion in adult isthmic spondylolisthesis.

Methods:

We retrospectively reviewed consecutive patients prospectively enrolled in the Canadian Spine Outcomes and Research Network national registry between 2009 and 2017 that underwent posterior lumbar fusion for isthmic spondylolisthesis. Using longitudinal mixed-model repeated-measures analysis the change from baseline in patient-reported outcome measures (PROMs) at 1 year after surgery was compared between surgeon-determined groups (back vs. radicular) and between patient-rated pain groups (back, leg, and equal) derived from preoperative pain scores on the numerical rating scale (NRS).

Results:

83/252 (33%) patients had a surgeon-determined chief complaint of back pain, while 103 (41%) patients rated their back pain as the predominant pain location, and 78 (31%) rated their back and leg pain to be equal. At baseline patients in the surgeon-determined radicular group had worse NRS-leg pain than those in the back-pain group but equal NRS-back pain. At baseline patients in the patient-rated equal pain group had similar back pain compared to the patient-rated back pain group and similar leg pain compared to the patient-rated leg pain group. All PROMs improved post-operatively and were not different between the 2 groups at 1 year.

Conclusions:

Our study found no difference in outcome, irrespective of whether a surgeon determines the patient’s primary pain complaint back or radicular dominant, or the patient rates pain in one location greater than another.
The Effectiveness of a Foundation Year 1 Doctor Preparation Course for Final Year Medical Students
Authors: Beedham William , Wanigasooriya Kasun , Layton Georgia R , Taing Chan Ley , Darr Adnan , Mittapalli Devender
Published: January 2021

Background:

Starting work as a junior doctor can be daunting for any medical student. There are numerous aspects of the hidden curriculum which many students fail to acquire during their training.

Objectives:

To evaluate the effectiveness of a novel foundation year one (FY1) doctor preparation course focusing on certain core topics, practical tips and components of the hidden curriculum. The primary objective was to improve the confidence level and knowledge of final year medical students transitioning to FY1 doctors.

Method:

A 2-day, practical course titled ‘Preparation 2 Practice’ delivering hands-on, small-group and lecture-based teaching, covering core medical student undergraduate curriculum topics in medicine and surgery. The course content spanned therapeutics, documentation skills and managing acute clinical tasks encountered by FY1 doctors during an on-call shift. A pre- and post-course survey and knowledge assessment were carried out to assess the effectiveness of the course. The assessment was MCQ-based, derived from topics covered within our course. The 20-question test and a short survey were administered electronically.

Results:

Twenty students from a single UK medical school attended the course. 100% participation was observed in the pre- and post-course test and survey. The median post-course test result was 22 (IQR 20.25-23.75) which was higher than the median pre-course test score of 18.75 (IQR 17-21.75). A Wilcoxon sign rank test revealed a statistically significant difference between the pre- and post-course test results ( P = .0003). The self-reported confidence score of delegates on starting work as a junior doctor was also significantly higher following the course ( P = .004).

Conclusion:

The results show a significant improvement in perceived confidence and knowledge on core curriculum topics amongst final year medical students having attended our FY1 doctor preparation course. We conclude that there is scope for similar supplementary courses as an adjunct to the undergraduate medical curriculum.
Crystalline Maculopathy Secondary to Retinal Tear Without Detachment
Authors: Tsimchi Imanouel M. , Dayani Pouya N. , Boyer David S. , Roe Richard H.
Published: January 2021

Purpose:

Crystalline maculopathy secondary to chronic retinal detachment (RD) has previously been described. This article proposes a novel mechanism to explain crystalline formation in the absence of RD.

Methods:

Two patients, who were referred for routine examination, were found to have a crystalline maculopathy in the setting of an asymptomatic, chronic-appearing, peripheral retinal tear. Fundoscopy and optical coherence tomography were used to assess the crystals and tear. No specimens were obtained.

Results:

We describe 2 cases of a crystalline maculopathy secondary to an asymptomatic peripheral retinal tear. We hypothesized macrophage ingestion of photoreceptor segments emanating from the tear may have contributed to macular crystalline deposition.

Conclusions:

Because crystalline maculopathy can present in the setting of RD, there may be a shared pathogenesis between the 2 conditions.
On the feasibility of IoT-based smart meters for earthquake early warning
Authors: Taale Alireza , Ventura Carlos E , Marti Jose
Published: January 2021

The microelectromechanical systems (MEMS) accelerometer built into a smart meter (SM) has a nominal digital resolution of 16 bits. However, this resolution collapses to 7 bits of information per sample when used in an urban environment. This collapse in resolution limits the sensitivity required to effectively operate the earthquake early warning platform (EEWP). In this study, we evaluate the performance of the MEMS sensor in present SMs with respect to a reference sensor, with a special focus on its poor noise power spectral density (PSD, [Formula: see text]). We also explore the general capacity of the SM in an IoT-based EEWP and provide explicit information regarding the 16-bit digital MEMS accelerometer. Then, we investigate the functionality of the sensor in the context of event detection in the presence of background vibration. When the value of acceleration root mean square (RMS) exceeds 20 mg, the meter’s error decreases to <20%, whereas the peak ground acceleration error decreases to <20% for the peak value greater than ~70 mg. The MEMS sensor is unreliable for motions with a peak acceleration of less than 148 mg or those with an RMS value less than 46 mg. However, we note that SMs exhibit reasonable amplitude and phase coherence for frequencies above 1 Hz with respect to the reference accelerometer. To enhance the sensitivity, averaging 1000 coherent accelerometer observations enhances the digital resolution to 14 bits, which allows the efficient usage of the network bandwidth. Since the accelerometer is used as an anti-tampering mechanism, the SM is similar to a tiltmeter. Therefore, it is necessary to reconfigure SMs for early warning systems. Despite the challenges, the use of SM for an IoT-based EEWP is technically feasible.
An attempt to unify the Brinell, Janka and Monnin hardness of wood on the basis of Meyer law
Authors: Koczan Grzegorz , Karwat Zbigniew , Kozakiewicz Paweł
Published: January 2021

This work concerns basic research on the concept of wood hardness in a sense similar to Brinell or in the modified sense of Monnin. The experimental part of this article is based on research carried out on beech wood with six indenters: three ball indenters of 10, 15 and 30 mm and three cylindrical indenters of 10, 15 and 30 mm. On the basis of measurements for a wide range of loads, relations analogous to Meyer power law of were obtained, with the exponent determined both for balls equal to 5/2 and for cylinders equal to 3/2. These exponents turned out to be exactly the arithmetic mean of exponents for ideally elastic and ideally plastic bodies. On this basis, new hardness formulae were proposed, taking into account Meyer law and the diameters of indenters. Therefore, the proposed two hardness formulae (for the ball and cylinder) are a generalization and development of Meyer hardness law.
Cobalt Phosphide (Co2P) with Notable Electrocatalytic Activity Designed for Sensitive and Selective Enzymeless Bioanalysis of Hydrogen Peroxide
Authors: Yin Donghang , Tang Junyan , Bai Rongbiao , Yin Shuyi , Jiang Mengnan , Kan Zigui , Li Hongmei , Wang Fei , Li Caolong
Published: January 2021

In this work, cobalt phosphide nanoparticles (Co2P NPs) were prepared by simple and mild hydrothermal method without the use of harmful phosphorous source. The morphological structure and surface component of Co2P were characterized by transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy measurements. Considering the excellent electrocatalytic reduction activity and good electrical conductivity of transition-metal phosphide, we fabricated Co2P NPs on indium tin oxide (ITO) substrate (Co2P/ITO) for H2O2 detection. The Co2P/ITO transducer displayed a rapid amperometric response less than 5 s, a broader response range from 0.001 to 10.0 mM and a low detection limit of 0.65 μM. In addition, the non-enzymatic Co2P/ITO sensor showed outstanding selectivity, reproducibility, repeatability and stability, all of which qualified the Co2P/ITO electrode for quite a reliable and promising biosensor for H2O2 sensing.
The association between pulse wave analysis, carotid-femoral pulse wave velocity and peripheral arterial disease in patients with ischemic heart disease
Authors: Piko Nejc , Bevc Sebastjan , Hojs Radovan , Naji Franjo Husam , Ekart Robert
Published: January 2021

Introduction

Functional changes in peripheral arterial disease (PAD) could play a role in higher cardiovascular risk in these patients.

Methods

123 patients who underwent elective coronary angiography were included. Ankle-brachial index (ABI) was measured and arterial stiffness parameters were derived with applanation tonometry.

Results

6 patients (4.9%) had a previously known PAD (Rutherford grade I). Mean ABI was 1.04 ± 0.12, mean subendocardial viability ratio (SEVR) 166.6 ± 32.7% and mean carotid-femoral pulse wave velocity (cfPWV) 10.3 ± 2.4 m/s. Most of the patients (n = 81, 65.9%) had coronary artery disease (CAD). There was no difference in ABI among different degrees of CAD. Patients with zero- and three-vessel CAD had significantly lower values of SEVR, compared to patients with one- and two-vessel CAD (159.5 ± 32.9%/158.1 ± 31.5% vs 181.0 ± 35.2%/166.8 ± 27.8%; p = 0.048). No significant difference was observed in cfPWV values. Spearman's correlation test showed an important correlation between ABI and SEVR (r = 0.196; p = 0.037) and between ABI and cfPWV (r = − 0.320; p ≤ 0.001). Multiple regression analysis confirmed an association between cfPWV and ABI (β = − 0.210; p = 0.003), cfPWV and mean arterial pressure (β = 0.064; p < 0.001), cfPWV and age (β = 0.113; p < 0.001) and between cfPWV and body mass index (BMI (β = − 0.195; p = 0.028), but not with arterial hypertension, dyslipidemia, diabetes mellitus or smoking status. SEVR was not statistically significantly associated with ABI using the same multiple regression model.

Conclusion

Reduced ABI was associated with increased cfPWV, but not with advanced CAD or decreased SEVR.
The new clinical application of bilateral-contralateral cervix clamp in postpartum hemorrhage: a retrospective cohort study
Authors: Zhang Qianwen , Li Tao , Xu Yu , Hu Yayi
Published: January 2021

Background

To assess the efficacy and safety of bilateral-contralateral cervix clamp firstly applied in postpartum hemorrhage caused by uterine tony of lower segment.

Methods

Totally 47 pregnant women with postpartum hemorrhage secondary to lower uterine segment atony in vaginal delivery or after caesarean delivery were included from March 1, 2020 to May 31, 2020. According to patient’s informed consent, 22 women accepted cervical clamp to treat and 25 only used uterotonics in control group.

Then hemostatic efficacy and safety of bilateral-contralateral cervix clamp were assessed by retrospective analysis.

Results

It was found that mean blood loss in clamp group was much less during vaginal delivery (656.2±72.79 g vs 811.8±86.07 g, p = 0.001) or after caesarean delivery (42.8±6.60 g vs 126.3±86.97 g, p = 0.007), and incidence of uterotonic repeated usage (81.8% vs 36, 18.2% vs 64%, p = 0.001) or side effect (18.2% vs 48.0%, p = 0.031) appeared less than control group, but there was no statistical differences on hospital stay (4.1±1.57 days vs 3.8±1.61 days, p = 0.535), hemoglobin (119±4.10 g vs 121.4±4.19 g, p = 0.058), blood transfusion (9.1% vs 12%,p = 0.746), surgical procedures (4.5% vs 4.0%, p = 0.93), also no clamp complications occurred.

Conclusions

The bilateral-contralateral cervix clamp was effective and safe, this new technique could be a complementary treatment for postpartum hemorrhage.
Preliminary clinical outcomes of the double-row anchor suture-bridge technique for the fixation of tibial intercondylar eminence fractures in adults: a 12-months minimal follow-up
Authors: Chu Yupeng , Hu Ting , Chen Mangmang , Jiang Chendi , Wu Zhuqi , Shi Junwu
Published: January 2021

Background

Tibial intercondylar eminence avulsion fractures occur primarily in adolescents and young adults. However, the incidence of such fractures is increasing in adults, concurrent with an increase in sports injuries and traffic accidents. This study describes the fixation-based double-row anchor suture-bridge technique, a novel technique for treating tibial intercondylar eminence fractures in adults; and evaluates its preliminary clinical outcomes.

Methods

A retrospective evaluation of adult patients with tibial intercondylar eminence fractures treated at our institution from June 2016 to June 2018 was conducted. Seven such patients, treated with the anchor suture-bridge technique, were included. All patients were assessed for knee joint range of motion (ROM), Lysholm knee score, International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form score, Tegner activity score pre-surgery, and the healing of the fracture at 3, 6 and 12 months minimal post-surgery follow-up.

Results

Patients were followed for a mean of 12.43 months (range 9-15 months). By the final follow-up, all fractures had fully healed. The mean Lysholm score improved from 27.86 (range, 2 to 54) pre-surgery to 88.14 (range, 81 to 100) 3 months post-surgery (p < 0.05). Similarly, the mean IKDC score improved from 48.86 (range, 43 to 55) to 84.29 (range, 75 to 90) (P < 0.05); and the mean Tegner activity score improved from 1.71 (range, 0 to 4) to 3.29 (range, 2 to 4) (p < 0.05). Furthermore, knee joint ROM, Lysholm scores, IKDC scores, and Tegner activity scores displayed excellent outcomes at the 6 and 12 months minimal follow-up.

Conclusion

The arthroscopic anchor suture-bridge technique is a valid and secure method for achieving effective fixation of tibial intercondylar eminence fractures in adults.
Pulp volume changes after piezocision-assisted tooth movement: a randomized clinical trial
Authors: Hatrom Abdulkarim A. , Howait Mohammed S. , Zawawi Khalid H. , Al-Turki Ghassan A. , Alansari Reem A. , Almehayawi Nouf F. , Alammari Sarah H. , Mohammed Raghda A. , Hassan Ali H.
Published: January 2021

Background

Orthodontic treatment may result in undesirable side effects, such as root resorption and a decrease in the size of the pulp tissue which could be associated with the duration of the orthodontic treatment. Piezocision-assisted tooth movement was introduced as a minimally invasive surgical procedure to shorten orthodontic treatment time. This prospective randomized clinical trial was aimed to compare the pulp volume changes of maxillary anterior teeth after en-masse retraction with or without piezocision-assisted orthodontics.

Methods

Patients who required orthodontic treatment with bilateral maxillary first premolar extractions and en-masse retraction were recruited. Patients were randomly divided into extraction with piezocision, or only extraction, serving as controls. Pulp volume and root length changes of the maxillary six anterior teeth were measured and compared between the two groups using a 3-Dimensional analytical software. Paired and independent sample t-tests were used to compare within and between groups. Bivariate correlation was done between the mean change in pulp volume and its corresponding root length. The significance level was set at α = 0.05.

Results

A total of 23 patients were included, 12 in the piezocision, and 11 in the control group. At the end of the en-masse retraction phase, (mean = 122.74 ± 3.06 days) pulp volume was significantly decreased in all six anterior teeth in both groups (P < 0.01). The decrease in pulp volume was not statistically different between both groups, (P > 0.05). There was a statistically significant but moderate correlation only between the pulp volume change of the right canine and its root length, r = 0.44, P = 0.034.

Conclusions

The effect of piezocision-assisted orthodontic tooth movement on the pulp volume was comparable to the conventional orthodontic treatment. The degree of change in pulp volume does not appear to be related to the amount of root resorption.

Trial registration NCT03180151. Registered December 25, 2016, retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT03180151.
Effects of treatment status and life quality on anxiety in MMT patients
Authors: Cao Penghui , Zhang Zhaohua , Zhong Jun , Xu Shichao , Huang Qiaofang , Fan Ni
Published: January 2021

Background

Anxiety, an important factor that affects the therapeutic effect and preservation rate of methadone maintenance treatment, has a high prevalence among MMT patients. This study aims to investigate the effects of treatment status and life quality on anxiety in MMT patients.

Methods

One hundred and Seventy-seven methadone maintenance treatment users in Guangzhou, China were evaluated. The socio-demographic, duration and MMT-related characteristics were documented. Anxiety level and quality of life were evaluated by Beck Anxiety inventory (BAI) and the Quality of Life-Drug Addiction (QOL-DA) respectively. The correlation between different factors and BAI score was also analyzed.

Results

The BAI total score and the QOL-DA score were 7.1±8.2, 163.5±21.4 respectively. 30.5% of the subjects showed mild to severe anxiety. Treatment interruption and QOL-DA score had strong correlations with the score of BAI, with correlation coefficients of 0.17 and − 0.08 respectively.

Conclusions

Anxiety symptoms were commonly presented in MMT patients. Treatment interruption and quality of life are two major factors affecting anxiety of MMT patients.
The prevalence and correlates of substance use disorders among patients of two different treatment settings in Thailand
Authors: Pengpid Supa , Peltzer Karl
Published: January 2021

Background

Monk healers provide an accessible and popular service in Southeast Asia, but little is known on the substance use status of their clients. This investigation intended to assess and compare the rate and correlates of substance use disorders in two different treatment settings (monk healers = MH and primary health care = PHC) in Thailand.

Methods

In a cross-sectional study, 1024 patients (591 of MH and 613 of PHC) responded to screening measures of the “World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test Lite”, and two common mental disorders (major depression and generalized anxiety disorder) from November 2018 to February 2019. Logistic regression was used to estimate the determinants of any substance use disorder in the MH and PHC setting.

Results

The prevalence of substance use disorder was higher in MH clients than PHC patients: any substance use disorder 11.7% (95% Confidence Interval-CI: 9.3–14.5%) vs 5.4% (95% CI: 3.9–7.5%), tobacco use disorder 7.6% (95% CI: 5.7–9.9%) vs 2.5% (95% CI: 1.5–4.0%), alcohol use disorder 10.0% (95% CI: 8.4–13.6%) vs 4.3% (95% CI: 3.0–6.3%), any drug use disorder 4.2% (95% CI: 2.8–6.1%) vs 0.3% (95% CI: 0.08–1.3%), and any past three months drug use 8.2% (95% CI: 6.2–10.7%) vs 1.5, 95% CI: 0.8–2.8%). In adjusted logistic regression analysis, among MH clients, male sex (Adjusted Odds Ratio-AOR: 9.52, 95% Confidence Interval-CI: 5.06–17.92) was positively, and were married (AOR: 0.32, 95% CI: 0.16–0.61) and high social support (AOR: 0.40, 95% CI: 0.16–0.99) were negatively associated with any substance use disorder. Among PHC patients, male sex (AOR: 7.05, 95% CI: 2.99–16.63) was positively and age (AOR: 0.95, 95% CI: 0.92–0.98) was negatively associated with any substance use disorder.

Conclusion

The proportion of substance use disorders among MH attendees was more than twice that of PHC attenders in Thailand, calling for collaboration in controlling substance use disorders between the two treatment systems.
Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice
Authors: Kim Jinho , Suh Yoo-Hun , Chang Keun-A
Published: January 2021

The number of young adult patients with major depression, one of the most common mental disorders, is gradually increasing in modern society. Stressful experiences in early life are considered one of the risk factors for chronic depressive symptoms, along with an abnormal inflammatory response in later life. Although increased inflammatory activity has been identified in patients with depression, the cause of long-lasting depressive states is still unclear. To identify the effects of cumulative mild stress in brain development periods, we generated a young adult depression mouse model exposed to cumulative mild stress (CPMS; cumulative mild prenatal stress, mild maternal separation, and mild social defeat) to mimic early life adversities. CPMS mice exhibited more long-lasting anxiety and depression-like behaviors than groups exposed to single or double combinations of mild stress in young adult age. Using the molecular works, we found that inflammatory cytokines, especially interleukin (IL)-17, upregulated microglial activation in the hippocampus, amygdala, and prefrontal cortex of CPMS mice. In the brains of CPMS mice, we also identified changes in the T helper (Th)-17 cell population as well as differentiation. Finally, anti-IL-17 treatment rescued anxiety and depression-like behavior in CPMS mice. In conclusion, we found that cumulative mild stress promoted long-lasting depressive symptoms in CPMS mice through the upregulation of IL-17. We suggest that the CPMS model may be useful to study young adult depression and expect that IL-17 may be an important therapeutic target for depression in young adults.
Targeting hypoxic tumor microenvironment in pancreatic cancer
Authors: Tao Jinxin , Yang Gang , Zhou Wenchuan , Qiu Jiangdong , Chen Guangyu , Luo Wenhao , Zhao Fangyu , You Lei , Zheng Lianfang , Zhang Taiping , Zhao Yupei
Published: January 2021

Attributable to its late diagnosis, early metastasis, and poor prognosis, pancreatic cancer remains one of the most lethal diseases worldwide. Unlike other solid tumors, pancreatic cancer harbors ample stromal cells and abundant extracellular matrix but lacks vascularization, resulting in persistent and severe hypoxia within the tumor. Hypoxic microenvironment has extensive effects on biological behaviors or malignant phenotypes of pancreatic cancer, including metabolic reprogramming, cancer stemness, invasion and metastasis, and pathological angiogenesis, which synergistically contribute to development and therapeutic resistance of pancreatic cancer. Through various mechanisms including but not confined to maintenance of redox homeostasis, activation of autophagy, epigenetic regulation, and those induced by hypoxia-inducible factors, intratumoral hypoxia drives the above biological processes in pancreatic cancer. Recognizing the pivotal roles of hypoxia in pancreatic cancer progression and therapies, hypoxia-based antitumoral strategies have been continuously developed over the recent years, some of which have been applied in clinical trials to evaluate their efficacy and safety in combinatory therapies for patients with pancreatic cancer. In this review, we discuss the molecular mechanisms underlying hypoxia-induced aggressive and therapeutically resistant phenotypes in both pancreatic cancerous and stromal cells. Additionally, we focus more on innovative therapies targeting the tumor hypoxic microenvironment itself, which hold great potential to overcome the resistance to chemotherapy and radiotherapy and to enhance antitumor efficacy and reduce toxicity to normal tissues.
Technology‐enabled remote management of diabetes foot disease and potential for reduction in associated health costs: a pilot study
Authors: Main Fiona , Zubala Ania , Gorman Jane , Jones Sandra , Hall Jenny , Macfarlane David , MacRury Sandra
Published: January 2021

Diabetes‐related foot disease, particularly when associated with amputation, affects quality of life and has a significant impact on health care costs. A pilot study using enhanced technology to facilitate remote access and video conferencing from rural locations to the diabetes MDT through a new service pathway confirmed high levels of patient satisfaction with 89% of foot ulcers improved or stable and only two minor amputations. A health economic analysis suggested potential for significant cost savings if this was scaled up regionally. Further evaluation of an integrated pathway, impact on lower limb amputation rates and full health economic assessment is recommended.
Hsa_circ_0123190 acts as a competitive endogenous RNA to regulate APLNR expression by sponging hsa-miR-483-3p in lupus nephritis
Authors: Zhang Chunyi , Gao Congcong , Di Xueqi , Cui Siwan , Liang Wenfang , Sun Wenbo , Yao Menghui , Liu Shengyun , Zheng Zhaohui
Published: January 2021

Background

Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE). Circular RNAs (circRNAs) can act as competitive endogenous RNAs (ceRNAs) to regulate gene transcription, which is involved in mechanism of many diseases. However, the role of circRNA in lupus nephritis has been rarely reported. In this study, we aim to investigate the clinical value of circRNAs and explore the mechanism of circRNA involvement in the pathogenesis of LN.

Methods

Renal tissues from three untreated LN patients and three normal controls (NCs) were used to identify differently expressed circRNAs by next-generation sequencing (NGS). Validated assays were used by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The interactions between circRNA and miRNA, or miRNA and mRNA were further determined by luciferase reporter assay. The extent of renal fibrosis between the two groups was assessed by Masson-trichome staining and immunohistochemistry (IHC) staining.

Results

159 circRNAs were significantly dysregulated in LN patients compared with NCs. The expression of hsa_circ_0123190 was significantly decreased in the renal tissues of patients with LN (P = 0.014). Bio-informatics analysis and luciferase reporter assay illustrated that hsa_circ_0123190 can act as a sponge for hsa-miR-483-3p, which was also validated to interact with APLNR. APLNR mRNA expression was related with chronicity index (CI) of LN (P = 0.033, R2 = 0.452). Moreover, the fibrotic-related protein, transforming growth factor-β1 (TGF-β1), which was regulated by APLNR, was more pronounced in the LN group (P = 0.018).

Conclusion

Hsa_circ_0123190 may function as a ceRNA to regulate APLNR expression by sponging hsa-miR-483-3p in LN.
AlzGPS: a genome-wide positioning systems platform to catalyze multi-omics for Alzheimer’s drug discovery
Authors: Zhou Yadi , Fang Jiansong , Bekris Lynn M. , Kim Young Heon , Pieper Andrew A. , Leverenz James B. , Cummings Jeffrey , Cheng Feixiong
Published: January 2021

Background

Recent DNA/RNA sequencing and other multi-omics technologies have advanced the understanding of the biology and pathophysiology of AD, yet there is still a lack of disease-modifying treatments for AD. A new approach to integration of the genome, transcriptome, proteome, and human interactome in the drug discovery and development process is essential for this endeavor.

Methods

In this study, we developed AlzGPS (Genome-widePositioningSystems platform forAlzheimer’s Drug Discovery,https://alzgps.lerner.ccf.org), a comprehensive systems biology tool to enable searching, visualizing, and analyzing multi-omics, various types of heterogeneous biological networks, and clinical databases for target identification and development of effective prevention and treatment for AD.

Results

Via AlzGPS: (1) we curated more than 100 AD multi-omics data sets capturing DNA, RNA, protein, and small molecule profiles underlying AD pathogenesis (e.g., early vs. late stage and tau or amyloid endophenotype); (2) we constructed endophenotype disease modules by incorporating multi-omics findings and human protein-protein interactome networks; (3) we provided possible treatment information from ~ 3000 FDA approved/investigational drugs for AD using state-of-the-art network proximity analyses; (4) we curated nearly 300 literature references for high-confidence drug candidates; (5) we included information from over 1000 AD clinical trials noting drug’s mechanisms-of-action and primary drug targets, and linking them to our integrated multi-omics view for targets and network analysis results for the drugs; (6) we implemented a highly interactive web interface for database browsing and network visualization.

Conclusions

Network visualization enabled by AlzGPS includes brain-specific neighborhood networks for genes-of-interest, endophenotype disease module networks for omics-of-interest, and mechanism-of-action networks for drugs targeting disease modules. By virtue of combining systems pharmacology and network-based integrative analysis of multi-omics data, AlzGPS offers actionable systems biology tools for accelerating therapeutic development in AD.
Health economic evaluations comparing faecal microbiota transplantation with antibiotics for treatment of recurrent Clostridioides difficile infection: a systematic review
Authors: Hammeken Lianna Hede , Baunwall Simon Mark Dahl , Hvas Christian Lodberg , Ehlers Lars Holger
Published: January 2021

Background

Faecal microbiota transplantation (FMT) is increasingly being used in the treatment of recurrent Clostridioides difficile infection (rCDI). Health economic evaluations may support decision-making regarding the implementation of FMT in clinical practice. Previous reviews have highlighted several methodological concerns in published health economic evaluations examining FMT. However, the impact of these concerns on the conclusions of the studies remains unclear.

Aims

To present an overview and assess the methodological quality of health economic evaluations that compare FMT with antibiotics for treatment of rCDI. Furthermore, we aimed to evaluate the degree to which any methodological concerns would affect conclusions about the cost-effectiveness of FMT.

Methods

We conducted a systematic literature review based on a search in seven medical databases up to 16 July 2020. We included research articles reporting on full health economic evaluations comparing FMT with antibiotic treatment for rCDI. General study characteristics and input estimates for costs, effectiveness and utilities were extracted from the articles. The quality of the studies was assessed by two authors using the Drummonds ten-point checklist.

Results

We identified seven cost-utility analyses. All studies applied decision-analytic modelling and compared various FMT delivery methods with vancomycin, fidaxomicin, metronidazole or a combination of vancomycin and bezlotoxumab. The time horizons used in the analyses varied from 78 days to lifelong, and the perspectives differed between a societal, a healthcare system or a third-party payer perspective. The applied willingness-to-pay threshold ranged from 20,000 to 68,000 Great Britain pound sterling (GBP) per quality-adjusted life-year (QALY). FMT was considered the most cost-effective alternative in all studies. In five of the health economic evaluations, FMT was both more effective and cost saving than antibiotic treatment alternatives. The quality of the articles varied, and we identified several methodological concerns.

Conclusions

Economic evaluations consistently reported that FMT is a cost-effective and potentially cost-saving treatment for rCDI. Based on a comparison with recent evidence within the area, the multiple methodological concerns seem not to change this conclusion. Therefore, implementing FMT for rCDI in clinical practice should be strongly considered.
An evaluation of service user experience, clinical outcomes and service use associated with urgent care services that utilise telephone-based digital triage: a systematic review protocol
Authors: Sexton Vanashree , Dale Jeremy , Atherton Helen
Published: January 2021

Background

Telephone-based digital triage is widely used by services that provide urgent care. This involves a call handler or clinician using a digital triage tool to generate algorithm-based care advice, based on a patient’s symptoms. Advice typically takes the form of signposting within defined levels of urgency to specific services or self-care advice. Despite wide adoption, there is limited evaluation of its impact on service user experience, service use and clinical outcomes; no previous systematic reviews have focussed on services that utilise digital triage, and its impact on these outcome areas within urgent care. This review aims to address this need, particularly now that telephone-based digital triage is well established in healthcare delivery.

Methods

Studies assessing the impact of telephone-based digital triage on service user experience, health care service use and clinical outcomes will be identified through searches conducted in Medline, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science and Scopus. Search terms using words relating to digital triage and urgent care settings (excluding in-hours general practice) will be used. The review will include all original study types including qualitative, quantitative and mixed methods studies; studies published in the last 20 years and studies published in English. Quality assessment of studies will be conducted using the Mixed Methods Appraisal Tool (MMAT); a narrative synthesis approach will be used to analyse and summarise findings.

Discussion

This is the first systematic review to evaluate service user experience, service use and clinical outcomes related to the use of telephone-based digital triage in urgent care settings. It will evaluate evidence from studies of wide-ranging designs. The narrative synthesis approach will enable the integration of findings to provide new insights on service delivery. Models of urgent care continue to evolve rapidly, with the emergence of self-triage tools and national help lines. Findings from this review will be presented in a practical format that can feed into the design of digital triage tools, future service design and healthcare policy.

Systematic review registration

This systematic review is registered on the international database of prospectively registered systematic reviews in health and social care (PROSPERO 2020 CRD42020178500).
On zeros and growth of solutions of complex difference equations
Authors: Chen Min-Feng , Cui Ning
Published: January 2021

Let f be an entire function of finite order, let $n\geq 1$
n
≥
1
, $m\geq 1$
m
≥
1
, $L(z,f)\not \equiv 0$
L
(
z
,
f
)
≢
0
be a linear difference polynomial of f with small meromorphic coefficients, and $P_{d}(z,f)\not \equiv 0$

P
d

(
z
,
f
)
≢
0
be a difference polynomial in f of degree $d\leq n-1$
d
≤
n
−
1
with small meromorphic coefficients. We consider the growth and zeros of $f^{n}(z)L^{m}(z,f)+P_{d}(z,f)$

f
n

(
z
)

L
m

(
z
,
f
)
+

P
d

(
z
,
f
)
. And some counterexamples are given to show that Theorem 3.1 proved by I. Laine (J. Math. Anal. Appl. 469:808–826, 2019) is not valid. In addition, we study meromorphic solutions to the difference equation of type $f^{n}(z)+P_{d}(z,f)=p_{1}e^{\alpha _{1}z}+p_{2}e^{\alpha _{2}z}$

f
n

(
z
)
+

P
d

(
z
,
f
)
=

p
1

e

α
1

z

+

p
2

e

α
2

z

, where $n\geq 2$
n
≥
2
, $P_{d}(z,f)\not \equiv 0$

P
d

(
z
,
f
)
≢
0
is a difference polynomial in f of degree $d\leq n-2$
d
≤
n
−
2
with small mromorphic coefficients, $p_{i}$

p
i

, $\alpha _{i}$

α
i

($i=1,2$
i
=
1
,
2
) are nonzero constants such that $\alpha _{1}\neq \alpha _{2}$

α
1

≠

α
2

. Our results are improvements and complements of Laine 2019, Latreuch 2017, Liu and Mao 2018.
Survey of CAMHS clinicians about their experience of remote consultation: brief report
Authors: Bhardwaj Anupam , Moore Anna , Cardinal Rudolf N. , Bradley Carol , Cross Lauren , Ford Tamsin J.
Published: January 2021

The Covid-19 crisis necessitated rapid adoption of remote consultations across National Health Service (NHS) child and adolescent mental health services (CAMHS). This study aimed to understand practitioners’ experiences of rapid implementation of remote consultations across CAMHS in one NHS trust in the east of England. Data were collected through a brief questionnaire documenting clinicians’ experiences following remote delivery of services. The questionnaire began before ‘lockdown’ and focused on assessment consultations (n = 102) as part of a planned move to virtual assessment. As the roll-out of remote consultations was extended at lockdown, we extended the questionnaire to include all remote clinical contacts (n = 202). Despite high levels of initial concern, clinicians’ reports were positive overall; importantly, however, their experiences varied by team. When restrictions on face-to-face working are lifted, a blended approach of remote and face-to-face service delivery is recommended to optimise access and capacity while retaining effective and safe care.
Psychological distress, self-harm and attempted suicide in UK 17-year olds: prevalence and sociodemographic inequalities
Authors: Patalay Praveetha , Fitzsimons Emla
Published: January 2021

In a large (n = 10 103), nationally representative sample of 17-year-olds 16.1% had experienced high psychological distress in the past 30 days, 24.1% had self-harmed in the previous 12 months and 7.4% had ever attempted suicide. Females, White adolescents, sexual minorities and those from more socioeconomically disadvantaged families had worse mental health outcomes; with the exceptions of no detected differences in attempted suicide by ethnicity and in self-harm by socioeconomic position. Findings include a narrower gender gap in self-harm at age 17 (males 20.1%, females 28.2%) compared with at age 14 (males 8.5%; females 22.8%) and 2–4 times higher prevalence in sexual minority adolescents (39.3% high distress, 55.8% self-harmed, 21.7% attempted suicide compared with 13.4%, 20.5% and 5.8%, respectively, in heterosexual adolescents).
Artificial Intelligence Clinical Evidence Engine for Automatic Identification, Prioritization, and Extraction of Relevant Clinical Oncology Research
Authors: Saiz Fernando Suarez , Sanders Corey , Stevens Rick , Nielsen Robert , Britt Michael , Yuravlivker Leemor , Preininger Anita M. , Jackson Gretchen P.
Published: January 2021

PURPOSE

We developed a system to automate analysis of the clinical oncology scientific literature from bibliographic databases and match articles to specific patient cohorts to answer specific questions regarding the efficacy of a treatment. The approach attempts to replicate a clinician’s mental processes when reviewing published literature in the context of a patient case. We describe the system and evaluate its performance.

METHODS

We developed separate ground truth data sets for each of the tasks described in the paper. The first ground truth was used to measure the natural language processing (NLP) accuracy from approximately 1,300 papers covering approximately 3,100 statements and approximately 25 concepts; performance was evaluated using a standard F1 score. The ground truth for the expert classifier model was generated by dividing papers cited in clinical guidelines into a training set and a test set in an 80:20 ratio, and performance was evaluated for accuracy, sensitivity, and specificity.

RESULTS

The NLP models were able to identify individual attributes with a 0.7-0.9 F1 score, depending on the attribute of interest. The expert classifier machine learning model was able to classify the individual records with a 0.93 accuracy (95% CI, 0.9 to 0.96, P < .0001), and sensitivity and specificity of 0.95 and 0.91, respectively. Using a decision boundary of 0.5 for the positive (expert) label, the classifier demonstrated an F1 score of 0.92.

CONCLUSION

The system identified and extracted evidence from the oncology literature with a high degree of accuracy, sensitivity, and specificity. This tool enables timely access to the most relevant biomedical literature, providing critical support to evidence-based practice in areas of rapidly evolving science.
Characteristics of Advance Care Planning in Patients With Cancer Referred to Palliative Care
Authors: Berkowitz Callie M. , Wolf Steven P. , Troy Jesse , Kamal Arif H.
Published: January 2021

PURPOSE:

Advance care planning (ACP) is a process in which patients share their values, goals, and preferences regarding future medical care. ACP can improve care quality, yet may be challenging to address for patients with cancer. We sought to characterize key components of ACP in patients with cancer as compared with patients with noncancer serious illness referred to palliative care (PC).

METHODS:

We performed a retrospective cross-sectional analysis of initial outpatient PC visits from the Quality Data Collection Tool for PC database from 2015 to 2019. Quality Data Collection Tool is a web-based point-of-care specialty PC registry to track quality metrics.

RESULTS:

We analyzed 1,604 patients with cancer and 1,094 patients without cancer: 44% of patients were female, 87% were White, and 98% were non-Hispanic. The average age was 72.2 years (standard deviation [SD] 15.4). Patients with cancer were on average younger than patients without cancer (66.5 [SD: 13.9] v 80.5 [SD: 13.8]) and had a higher Palliative Performance Scale (PPS) (59.5 [SD: 22.4] v 33.4 [SD: 25.1]). In our unadjusted comparison, patients with cancer were less likely to be DNR/DNI (37% v 53%; P < .0001) and less likely to have an advance directive (53% v 73%; < .0001); rates of healthcare proxy identification were similar (92.8% v 94.5%; P = .10). These differences did not persist when we accounted for age, race, sex, and PPS, with age being the primary explanatory factor.

CONCLUSION:

Despite having serious illness meriting PC referral, many patients with cancer in our study lacked advance directives. This highlights both the important role of oncologists in facilitating ACP and the utility of PC playing a complementary role.
Perioperative Diabetes Insipidus Caused by Anesthetic Medications: A Review of the Literature
Authors: Van Decar Lauren M. , Reynolds Emily G. , Sharpe Emily E. , Harbell Monica W. , Kosiorek Heidi E. , Kraus Molly B.
Published: January 2021

Diabetes insipidus (DI) is an uncommon perioperative complication that can occur secondary to medications or surgical manipulation and can cause significant hypovolemia and electrolyte abnormalities. We reviewed and evaluated the current literature and identified 29 cases of DI related to medications commonly used in anesthesia such as propofol, dexmedetomidine, sevoflurane, ketamine, and opioids. This review summarizes the case reports and frequency of DI with each medication and presents possible pathophysiology. Medication-induced DI should be included in the differential diagnosis when intraoperative polyuria is identified. Early identification, removal of the agent, and treatment of intraoperative DI are critical to minimize complications.