bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Undergoing Outpatient Hand Surgery Lead to Prolonged Opioid Use? A Comparison of Surgical and Nonsurgical Patients
Authors: Wang William L. , Lutsky Kevin F. , McEntee Richard M. , Banner Lauren , Katt Brian M. , Nakashian Michael N. , Sodha Samir C. , Rivlin Michael , Beredjiklian Pedro K.
Published: October 2020

Background:

Orthopedic surgical patients in general have been found to be at higher risk for developing opioid dependence in the postoperative period. However, there is conflicting evidence in the literature whether opioid exposure after hand surgery leads to prolonged use. In the absence of a nonoperative control group, it is not clear whether prolonged opioid use in hand surgical patients is related to undergoing a surgical intervention. The purpose of our study to compare opioid prescription fulfillment patterns in surgical and nonoperative patients in a hand surgery practice.

Methods:

We retrospectively compared 320 patients that underwent elbow, wrist, and hand surgery procedures with 741 nonoperative patients treated by 2 hand surgeons. The Pennsylvania Drug Monitoring Program (PDMP), a mandatory statewide database, was used to evaluate the primary outcomes of filling more than one opioid prescription and filling opioid prescriptions beyond 6 months of the index surgery or clinic visit. Bivariate and multivariable logistic regression analysis was performed using the following variables: surgery, prior benzodiazepine use, and prior opioid use.

Results:

There was no difference in prior opioid use (15.2% vs 16.9%, P = .51) or prior benzodiazepine (10.4% vs 8.4%, P = .33) use between the nonoperative and operative groups. Patients that underwent surgery had a higher incidence of filling more than one opioid prescription (20.9% vs 8.8%, P < .001). However, continued opioid use was not statistically different between nonoperative and operative patients (2.8% vs 5%, P = .08). Bivariate analysis demonstrated that prior opioids (odds ratio [OR] = 12.94, P < .001) and prior benzodiazepines (OR = 1.95, P < .001) were significant independent risk factors for prolonged opioid use. Multivariable analysis demonstrated prior opioid use to be the only independent risk factor for prolonged opioid use (OR = 12.58, P < .001).

Conclusion:

Undergoing outpatient hand surgery do not appear to be an independent risk factor for filling opioid prescriptions beyond 6 months. Significant risk factors for prolonged opioid use include prior use of controlled substances, particularly prior opioid use.
Rosmarinic Acid Prevents Radiation-Induced Pulmonary Fibrosis Through Attenuation of ROS/MYPT1/TGFβ1 Signaling Via miR-19b-3p
Authors: Zhang Tingting , Ma Shanshan , Liu Chang , Hu Kai , Xu Meng , Wang Rensheng
Published: October 2020

The mechanism of pulmonary fibrosis caused by irradiation remains obscure. Since rosmarinic acid (RA) have anti-oxidant and anti-inflammatory properties, we aimed to evaluate the effect of RA on the X-ray-induced lung injury. Male rats received RA (30, 60, or 120 mg/kg) 7 days before 15 Gy of X-ray irradiation. Here, we showed that RA reduced X-ray-induced the expression of inflammatory related factors, and the level of reactive oxygen species. RA down-regulated the phosphorylation of nuclear factor kappa-B (NF-κB). We found that thoracic tumor patients whose lung regions received radiation showed lower level of microRNA-19b-3p (miR-19b-3p). Furthermore, we provided evidence that miR-19b-3p targets myosin phosphatase target subunit 1 (MYPT1), and RA attenuated RhoA/Rock signaling through upregulating miR-19b-3p, leading to the inhibition of fibrosis. In conclusion, RA may be an effective agent to relieve the pulmonary fibrosis caused by radiotherapy of thoracic tumor.
Rigid Flexibility: Seeing the Opportunities in “Failed” Qualitative Research
Authors: CohenMiller Anna S. , Schnackenberg Heidi , Demers Denise
Published: October 2020

This article highlights an experience of “failing” within a qualitative research study. Specifically, the authors speak to the failure of recruiting participants in conducting synchronous video and telephone interviews. Drawing from literature in business and examples from research method texts to demonstrate the cross-disciplinary concerns and insights of failure within one’s work, the authors discuss how failure can be reframed as opportunity through the lens of “rigid flexibility” and the innovative steps they implemented. Providing additional insight into the process of framing and reframing failure in research, the authors integrate poetic inquiry as a tool for reflection to highlight their process and suggested steps for new researchers. The authors argue that researchers can approach studies with the idea that failures in the planning and/or execution can lead to opportunities and new insights.
Direct integrator of block type methods with additional derivative for general third order initial value problems
Authors: Turki Mohammed Yousif , Ismail Fudziah , Senu Norazak , Ibrahim Zarina Bibi
Published: October 2020

This paper presents the construction of the two-point and three-point block methods with additional derivatives for directly solving [Formula: see text]. The proposed block methods are formulated using Hermite Interpolating Polynomial and approximate the solution of the problem at two or three-point concurrently. The block methods obtain the numerical solutions directly without reducing the equation into the first order system of initial value problems (IVPs). The order and zero-stability of the proposed methods are also investigated. Numerical results are presented and comparisons with other existing block methods are made. The performance shows that the proposed methods are very efficient in solving the general third order IVPs.
Asymmetries in Mutual Understanding: People With Low Status, Power, and Self-Esteem Understand Better Than They Are Understood
Authors: Talaifar Sanaz , Buhrmester Michael D. , Ayduk Özlem , Swann William B.
Published: October 2020

All too often, people who develop exceptionally astute insights into others remain mysterious to these others. Evidence for such asymmetric understanding comes from several independent domains. Striking asymmetries occur among those who differ in status and power, such that individuals with low status and power understand more than they are understood. We show that this effect extends to people who merely perceive that they have low status: individuals with low self-esteem. Whereas people with low self-esteem display insight into people with high self-esteem, people with high self-esteem fail to reciprocate. Conceptual analysis suggests that asymmetries in mutual understanding may be reduced by addressing deficits in information and motivation among perceivers. Nevertheless, several interventions have been unsuccessful, indicating that the path to symmetric understanding is a steep and thorny one. Further research is needed to develop strategies for fostering understanding of those who are most misunderstood: people with low self-esteem, low status, and low power.
The mechanical fixation of a cementless conical cup in cortical versus cancellous trapezial bone: an experimental study
Authors: Thillemann Janni K. , Dremstrup Lene , Hansen Torben B. , Stilling Maiken
Published: October 2020

In a pig bone model mimicking the human trapezium, we assessed the cementless fixation of trapezial cups in cancellous and cortical bone. Thirty-two saddle-shaped pig forefoot bones were prepared for cup fixation. Conical Konos cups (Beznoska, Kladno, Czech Republic) size 9 mm or 10 mm diameter were impacted. Cup migration was evaluated with repeated radiostereometry after intervals of cyclic-load tests. Migration increased for every load-interval up to 750 N and was higher with cancellous bone fixation than with cortical bone fixation. In cancellous bone, 9 mm cups migrated more than 10 mm cups. At the highest load (1050 N), the cumulative implant survival was 88% for 10 mm cups with cortical bone fixation and 13% for 9 mm cups with cancellous bone fixation. We conclude that mechanical fixation of conical Konos cups was better in cortical than in cancellous bone. Our results further suggest that the largest possible cup diameter should be used.
Safety and long-term outcomes of early gastric cardiac cancer treated with endoscopic submucosal dissection in 499 Chinese patients
Authors: Cao Shouli , Zou Tianhui , Sun Qi , Liu Tianyun , Fan Ting , Yin Qin , Fan Xiangshan , Jiang Jingwei , Raymond Dekusaah , Wang Yi , Zhang Bin , Lv Ying , Zhang Xiaoqi , Ling Tingsheng , Zhuge Yuzheng , Wang Lei , Zou Xiaoping , Xu Guifang , Huang Qin
Published: October 2020

Aims:

Early gastric cardiac cancer (EGCC) has a low risk of lymph node metastasis with the potential for endoscopic therapy. We aimed to evaluate the short- and long-term outcomes of endoscopic submucosal dissection (ESD)-resected EGCCs in a large cohort of Chinese patients and compare endoscopic and clinicopathologic features between EGCC and early gastric non-cardiac cancer (EGNC).

Methods:

We retrospectively studied 512 EGCCs in 499 consecutive patients and 621 EGNCs in 555 consecutive patients between January 2011 and March 2018 at our center. We investigated clinicopathological characteristics of EGCC tumors, ESD treatment results, adverse events, and postresection patient survival.

Results:

Compared with EGNC patients, EGCC patients were significantly older (average age: 66 years versus 62 years, p < 0.001). The percentage of the gross 0–IIc pattern was higher in EGCCs (46.1%) than in EGNCs (41.5%), while the frequency of the 0–IIa pattern was lower in EGCCs (14.9%) than in EGNCs (22.4%) ( p = 0.001). Compared with EGNCs, EGCCs showed smaller size, deeper invasion, fewer ulcerated or poorly differentiated tumors, but more cases with gastritis cystica profunda. The prevalence of ESD-related complications was higher in EGCCs (6.1%) than in EGNCs (2.3%) ( p = 0.001). In EGCCs, the disease-specific survival rate was significantly higher in patients of the noncurative resection group with surgery (100%), compared with that (93.9%) without surgery ( p < 0.001).

Conclusion:

Clinicopathological characteristics were significantly different between EGCCs and EGNCs. ESD is a safe and effective treatment option with favorable outcomes for patients with EGCC. Additional surgery improved survival in patients with noncurative ESD resection.
Applying opportunistic observations to model current and future suitability of the Kopet Dagh Mountains for a Near Threatened avian scavenger
Authors: Sheykhi Ilanloo Sayyad , Khani Ali , Kafash Anooshe , Valizadegan Negin , Ashrafi Sohrab , Loercher Franziska , Ebrahimi Elham , Yousefi Masoud
Published: October 2020

Many avian species are in danger of extinction due to anthropogenic activities and climate change. Human activities have led to eradication of many natural habitats and climate change has altered species distribution especially in mountainous habitats. In the present study, we used distribution records of a Near Threatened avian scavenger, bearded vulture ( Gypaetus barbatus) that were collected through 9 years of opportunistic observations and modeled its distribution in the Khorasane-Razavi Province in Iran. We also assessed the impacts of future climate change on the distribution of this species. Our results show that most suitable habitats for bearded vulture are in the northern regions of the Khorasan-e-Razavi province. The most important variables affecting the distribution of the bearded vulture were the annual precipitation (37.5% contribution), landcover (22% contribution), and distance to road (16.2% contribution). Our results also showed that around 80% to 91% of the species’ suitable habitats will decrease due to climate change in the future. Suitable habitats of the species that are predicted to remain suitable in the future should be prioritized for conservation. Human activities like road expansion should be avoided in areas with high suitability for this species. This study stresses the need for action to conserve this vulture in the Khorasan-e-Razavi province, and beyond its borders.
Seedlings of the Invasive Strawberry Guava Psidium cattleianum Were More Sensitive to Defoliation Than the Closely Related Malagasy Native Eugenia goviala in a Simulated Herbivory Experiment
Authors: Rakotonoely Harisoa , Ramamonjisoa Noelikanto
Published: October 2020

The success of non-native plants in their recipient environments is often attributed to their relatively lower herbivorous attack (i.e., leaf damage). However, whether non-native plants are inherently more tolerant to leaf damage than native ones remains unclear. We conducted a field experiment to test the effects of clipping (25%, 50%, and 75% leaf area loss) on growth (stem height and production of new leaves) of the natural regenerations of invasive strawberry guava Psidium cattleianum (Myrtaceae) and its closely related native, Eugenia goviala (VU, Myrtaceae,), in a degraded forest in Andasibe, Madagascar. Each clipped individual was paired with a neighboring control (0% defoliation). Survival rates after 105 days were high (>93%) for both species and were not related to clipping levels. Eugenia goviala increased stem growth by 98% at 25% clipping but exhibited no response at higher clipping levels. Clipping tended to reduce stem growth in P. cattleianum but effects were only significant at 75% defoliation (46% reduction in stem growth). Defoliation did not affect the production of new leaves but we detected a tendency for P. cattleianum to produce fewer leaves at higher clipping levels. These results indicate a higher sensitivity to defoliation in the invasive strawberry guava compared to its close native relative E. goviala, which does not support the hypothesis that non-native plant species are more tolerant to leaf damage than native ones. Heavy defoliation can represent a substitute for mechanical control of the strawberry guava. Future studies should focus on identifying suitable native herbivores as part of an integrated control program for this invasive species.
Pharmacokinetics in routine haemophilia clinical practice: rationale and modalities—a practical review
Authors: Hermans Cedric , Dolan Gerry
Published: October 2020

Prophylactic therapy with exogenous clotting factor concentrates in haemophilia A and B aims to achieve levels of circulating FVIII or FIX that are adequate for the prevention or reduction of spontaneous joint bleeding. Historically, a minimum trough level of at least 1% of the normal levels of circulating clotting factor has been targeted using standardised protocols. However, clearance of clotting factor varies between products and patients, and other pharmacokinetic (PK) parameters such as the frequency and magnitude of peaks may be important for ensuring optimal coverage. Thus, it is increasingly recognised that an individualised, PK-based approach to prophylaxis is necessary to achieve optimal protection.

This review focuses on the clinical implications of using PK-guided, individualised prophylaxis in haemophilia to improve patient outcomes and considers practical methods of establishing patients’ PK parameters. The most useful PK parameters will depend on the aim of the specific treatment (e.g. preventing activity-related and traumatic bleeds or addressing subclinical bleeding). In clinical practice, lengthy and frequent post-infusion sampling for PK analysis is costly and a significant burden for patients. However, a Bayesian analysis allows for the estimation of different PK parameters (e.g. half-life, factor concentrations over time, etc.) with only a minimum number of samples (e.g. 4, 24 and 48 h for haemophilia A), by using the patient’s data to adjust a relevant population PK value towards the actual value. Numerous tools are available to aid in the practical use of Bayesian PK-guided dosing in the clinic, including the Web-based Application for the Population Pharmacokinetic Service hosted by McMaster University, Canada. The PK data can be used to determine the appropriate prophylaxis regimen for the individual patient, which can be monitored by assessment of the trough level at each clinic visit.

Collection of PK data and subsequent PK-guided dosing should become standard practice when determining treatment strategies for people with haemophilia.
Worse cardiovascular prognosis after endovascular surgery for intermittent claudication caused by infrainguinal atherosclerotic disease in patients with diabetes
Authors: Dakhel Ardwan , Zarrouk Moncef , Ekelund Jan , Acosta Stefan , Nilsson Peter , Miftaraj Mervete , Eliasson Björn , Svensson Ann-Marie , Gottsäter Anders
Published: October 2020

Background:

Diabetes mellitus (DM) is an established risk factor for intermittent claudication (IC) and other manifestations of atherosclerotic peripheral arterial disease. Indications for surgery in infrainguinal IC are debated, and there are conflicting reports regarding its outcomes in patients with DM. Aims of this study were to compare both short- and long-term effects on total- and cardiovascular (CV) mortality, major adverse cardiovascular events (MACEs), acute myocardial infarction (AMI), stroke, and major amputation following infrainguinal endovascular surgery for IC in patients with and without DM. We also evaluated potential relationships between diabetic control and outcomes in patients with DM.

Methods:

Nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Registry. Propensity score adjusted comparison of total and CV mortality, MACE, AMI, stroke, and major amputation after elective infrainguinal endovascular surgery for IC in 626 patients with and 1112 without DM at 30 postoperative days and after median 5.2 [interquartile range (IQR) 4.2–6.3] years of follow-up for patients with DM, and 5.4 (IQR 4.3–6.5) years for those without.

Results:

In propensity score adjusted Cox regression after 30 postoperative days, there were no differences between groups in morbidity or mortality. At last follow-up, patients with DM showed higher rates of MACE [hazard ratio (HR) 1.26, confidence interval (CI) 1.07–1.48; p < 0.01], AMI (HR 1.48, CI 1.09–2.00; p = 0.01), and major amputation (HR 2.31, CI 1.24–4.32; p < 0.01). Among patients with DM, higher HbA1c was associated with higher total mortality during follow-up (HR 1.01, CI 1.00–1.03; p = 0.045).

Conclusion:

Patients with DM have higher rates of MACE, AMI, and major amputation in propensity score adjusted analysis during 5 years of follow-up after infrainguinal endovascular surgery for IC. Furthermore, HbA1c is associated with total mortality in patients with DM. Prevention and treatment of DM is important to improve cardiovascular and limb outcomes.
Intrinsic functional connectivity alterations of the primary visual cortex in patients with proliferative diabetic retinopathy: a seed-based resting-state fMRI study
Authors: Yu Yao , Lan Dong-Yi , Tang Li-Ying , Su Ting , Li Biao , Jiang Nan , Liang Rong-Bin , Ge Qian-Min , Li Qiu-Yu , Shao Yi
Published: October 2020

Purpose:

In this study, we aimed to investigate the differences in the intrinsic functional connectivity (iFC) of the primary visual cortex (V1), based on resting-state functional magnetic resonance imaging (rs-fMRI), between patients with proliferative diabetic retinopathy (PDR) and healthy controls (HCs).

Methods:

In total, 26 patients (12 males, 14 females) with PDR and 26 HCs (12 males, 14 females), matched for sex, age, and education status, were enrolled in the study. All individuals underwent rs-fMRI scans. We acquired iFC maps and compared the differences between PDR patients and the HCs.

Results:

The PDR group had significantly increased FC between the left V1 and the right middle frontal gyrus (RMFG), and significantly reduced FC between the left V1 and the cuneus/calcarine/precuneus. In addition, the PDR patients had significantly increased FC between the right V1 and the right superior frontal gyrus (RSFG), and significantly reduced FC between the right V1 and the cuneus/calcarine/precuneus. The individual areas under the curve (AUCs) of FC values for the left V1 were as follows: RMFG (0.871, p < 0.001) and the cuneus/calcarine/precuneus (0.914, p < 0.001), while the AUCs of FC values for the right V1 were as follows: RSFG (0.895, p < 0.001) and the cuneus/calcarine/precuneus (0.918, p < 0.001).

Conclusions:

The results demonstrated that, in PDR patients, altered iFC in distinct brain regions, including regions related to visual information processing and cognition. Considering the rise in the diabetes mellitus incidence rate and the consequences of PDR, the results could provide promising clues for exploring the neural mechanisms related to PDR and possible approaches for the early identification of PDR.
Methicillin-resistant Staphylococcus aureus urosepsis: A rare complication of neonatal circumcision
Authors: Khalil Ahmed , Hamid Eiman , Siddiq Khaled , Hassan Manasik
Published: October 2020

The role of circumcision and its benefits has received increased attention across several disciplines in recent years; however, there is increasing concern that some uncommon complications such as severe infections are being related to post-circumcision. We describe the clinical course of a 14-day-old boy who had Methicillin-resistant Staphylococcus aureus urosepsis after circumcision.
Interleukin-6 serum level and -597 A/G gene polymorphism in moderate and severe chronic obstructive pulmonary disease
Authors: Chiș Ana Florica , Cătană Andreea , Sorițău Olga , Chiș Bogdan Augustin , Cutaș Ancuța , Pop Carmen Monica
Published: October 2020

Inflammation is a major pathogenic pathway in pulmonary chronic obstructive disease (COPD). Interleukin-6 (IL-6) mediates the local and systemic immune response. The aim consisted in investigating the relationship between IL-6 serum levels and IL-6 -597A/G gene polymorphism (rs1800797) with COPD. Serum levels of IL-6 were determined using an enzyme-linked immune-sorbent assay, in 120 participants (60 COPD patients and 60 healthy subjects), from Transylvanian region. The IL-6 -597A/G gene polymorphism was investigated by high molecular weight genomic DNA extracted from the peripheral blood leukocytes, and subsequently analyzed by the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Smoking history, the severity of the disease, expressed by the GOLD stages, and arterial blood partial pressure of oxygen (PaO2) levels were also investigated. COPD patients had significantly elevated blood levels of IL-6 when compared to the control group ( p < 0.05). The frequencies of AA, AG, and GG genotypes were 61.6%, 26.6%, and 11.6% in the COPD cases and 70%, 23.3%, and 6.7% in healthy subjects, respectively. There were no statistically significant differences in IL-6 rs1800797 genotypes and allele frequencies between cases and controls ( χ2 = 0.54, OR = 1.29 and χ2 = 0.21, OR = 1.48, respectively). Higher serum levels of IL-6 were found in the GG genotype subgroup in COPD patients. IL 6 levels are higher in COPD patients, where positively correlate with pack-year index, but not with clinical features. Although COPD patients did not have statistically different rs1800797 allele distribution compared to healthy subjects, the GG genotype is associated with higher IL6 serum levels.
Pathologically Proven Intraocular Infiltration With Adult T-Cell Leukemia/Lymphoma: Two New Cases With Either Vitreous Opacity or Aqueous Hypopyon and Literature Review of 16 Cases
Authors: Matsuo Toshihiko , Shimizu Takehiro , Tanaka Takehiro , Yamamoto Akira , Takasuka Hiroki
Published: October 2020

This study reported 2 new patients and 16 historical cases with pathologically proven intraocular infiltration with adult T-cell leukemia and lymphoma (ATLL) to know the timing of intraocular infiltration in the disease course. The first case was a 67-year-old woman who developed bilateral vitreous opacity about half a year after the onset of acute type of ATLL that had been unresponsive to chemotherapy. She underwent vitrectomy combined with cataract surgery in both eyes. She had bilateral optic disc atrophy and localized retinal white infiltrates in both eyes. Cytological examination of vitreous aspirates demonstrated medium-sized cells with aberrant flower-like convoluted nuclei, positive for CD3, and thus indicative of T-cells. The second case was a 38-year-old man who was diagnosed acute type of ATLL at the presentation of acute kidney injury. About half a year after initial chemotherapy and allogeneic hematopoietic stem cell transplantation, he developed aqueous hypopyon in the right eye, concurrent with cutaneous and central nervous system relapse. Aqueous tap disclosed class V abnormal cells. The aqueous “pseudohypopyon” resolved in response to another round of chemotherapy with mogamulizumab. In review of 18 patients, intraocular infiltration with ATLL was diagnosed by vitrectomy in 9, aqueous tap in 3, chorioretinal biopsy in 3, and autopsy in 3. The intraocular infiltration developed concurrently with systemic diagnosis of ATLL in 5 patients, but developed later after chemotherapy in 13. In conclusion, intraocular infiltration with ATLL appears rare, and pathological diagnosis by vitrectomy and aqueous tap would help determine therapeutic plan in relapse after chemotherapy.
Impact of a Hands-on Pre-Clinical Neurosurgery Elective Course on Second-Year Medical Student Interest and Attitudes
Authors: Sansosti Alexandra A , Jacobs Rachel C , Safonova Aleksandra , Jani Ronak H , Schumann Jack , Friedlander Robert M , Lunsford L Dade , McDowell Michael M , Sekula Raymond F
Published: October 2020

Introduction:

Medical student involvement opportunities and educational experiences with surgical residents during medical school have been shown to increase the chance of students deciding to specialize in surgical specialties. This study aims to determine the effect of a neurosurgery elective during the second preclinical year on student interest and opinion of neurosurgery.

Methods:

Thirty-nine students completed opinion-based surveys and factual knowledge quizzes during a neurosurgical elective course over 3 iterations, which included lecture and skills lab instruction. Pre- and post-course surveys used the Likert scale, with a score of 1 corresponding to the most negative opinion and a score of 10 corresponding to the most positive opinion, in order to measure various aspects including interest in neurological surgery, understanding of the field, and perception of female inclusion in the field. Weekly pre- and post-lecture quizzes assessed practical knowledge of neurosurgical topics.

Results:

A higher percentage of students rated neurosurgery highly as a career possibility (⩾8/10 interest level) post-course (58.6%) compared to pre-course (45.7%). Post-course, students reported a significantly increased mean understanding of neurosurgery on the Likert scale compared to pre-course (6.1 ± 1.7 vs 4.4 ± 2.0; P = .001). Knowledge based-content assessment revealed a significant increase in overall correct answers after lectures (meanpre = 3.85, meanpost = 5.05, P = .001). Inclusion of female instructors in the second and third iteration of the course resulted in a significant increase in students’ perception of female inclusion in the field of neurosurgery (7.6 compared to 5.6, P = .01).

Conclusions:

Early exposure to subspecialties may assist in making important career decisions. The implementation of this neurosurgical elective improved medical students’ perception of the field and enhanced knowledge of the lectures and procedures. This study can be used as a framework for implementation of this curriculum at other institutions.
COVID-19 and systemic sclerosis: Rising to the challenge of a pandemic
Authors: Denton Christopher P , Campochiaro Corrado , Bruni Cosimo , Distler Oliver , Iagnocco Annamaria , Matucci Cerinic Marco
Published: October 2020

COVID-19, caused by infection of the novel coronavirus SARS-CoV-2, has caused a pandemic of enormous impact that has challenged healthcare and political system throughout the world. This new health emergency has occurred on top of the usual burden of diseases, including systemic sclerosis, and has led to many unanticipated consequences. An early consequence of the pandemic was postponement of the Sixth Systemic Sclerosis World Congress that was recently completed as a successful virtual congress with more than 1000 delegates. In this article, we summarise the relevance and impact of COVID-19 from the perspective of systemic sclerosis. Shared concepts of pathogenesis are considered, and the relevant literature emerging about COVID-19 and systemic sclerosis summarised. The specific impact of this pandemic on delivery of optimal scleroderma care is considered, together with the broader effect on rheumatic and musculoskeletal diseases and the activities of European League Against Rheumatism. As the World continues to struggle against this new infectious disease, it is notable that expertise and growing understanding of systemic sclerosis has been able to help tackle COVID-19. Moreover, the essential adjustments to deliver clinical care and establishment of new ways of working due to the pandemic have offered potential avenues for future improvement in systemic sclerosis care.
Challenges and opportunities in New Zealand seismic hazard and risk modeling using OpenQuake
Authors: Abbott Elizabeth , Horspool Nick , Gerstenberger Matt , Huso Rand , Van Houtte Chris , McVerry Graeme , Canessa Silvia
Published: October 2020

The corrected 2010 New Zealand National Seismic Hazard Model has been adapted for use in the Global Earthquake Model’s OpenQuake engine through an extensive benchmarking exercise with GNS Science’s legacy Fortran code. Resolution of differences between the legacy code and OpenQuake result in hazard curve output comparisons with discrepancies of less than 3% nationally and remaining discrepancies highlight challenges faced when moving away from in-house legacy code. OpenQuake’s multiple and varied computation options for both hazard and risk and OpenQuake’s consistent, software-friendly output formats allow for exploration and development of innovative approaches to future seismic hazard and risk modeling in New Zealand. The end-to-end seismic hazard-to-risk capabilities already enabled by the inclusion of New Zealand seismic hazard, vulnerability, and building exposure models in OpenQuake have already had significant impact on post-disaster response to the 2016 Kaikōura earthquake.
del(17p) without TP53 mutation confers a poor prognosis in intensively treated newly diagnosed patients with multiple myeloma
Authors: Corre Jill , Perrot Aurore , Caillot Denis , Belhadj Karim , Hulin Cyrille , Leleu Xavier , Mohty Mohamad , Facon Thierry , Buisson Laure , Do Souto Laura , Lannes Romain , Dufrechou Stephanie , Prade Naïs , Orsini-Piocelle Frederique , Voillat Laurent , Jaccard Arnaud , Karlin Lionel , Macro Margaret , Brechignac Sabine , Dib Mamoun , Sanhes Laurence , Fontan Jean , Clement-Filliatre Lauriane , Marolleau Jean-Pierre , Minvielle Stephane , Moreau Philippe , Avet-Loiseau Hervé
Published: October 2020

Despite tremendous improvements in the outcome of patients with multiple myeloma in the past decade, high-risk patients have not benefited from the approval of novel drugs. The most important prognostic factor is the loss of parts of the short arm of chromosome 17, known as deletion 17p (del(17p)). A recent publication (on a small number of patients) suggested that these patients are at very high-risk only if del(17p) is associated with TP53 mutations, the so-called “double-hit” population. To validate this finding, we designed a much larger study on 121 patients presenting del(17p) in > 55% of their plasma cells, and homogeneously treated by an intensive approach. For these 121 patients, we performed deep next generation sequencing targeted on TP53. The outcome was then compared with a large control population (2505 patients lacking del(17p)). Our results confirmed that the “double hit” situation is the worst (median survival = 36 months), but that del(17p) alone also confers a poor outcome compared with the control cohort (median survival = 52.8 months vs 152.2 months, respectively). In conclusion, our study clearly confirms the extremely poor outcome of patients displaying “double hit," but also that del(17p) alone is still a very high-risk feature, confirming its value as a prognostic indicator for poor outcome.
CDKAM: a taxonomic classification tool using discriminative k-mers and approximate matching strategies
Authors: Bui Van-Kien , Wei Chaochun
Published: October 2020

Background

Current taxonomic classification tools use exact string matching algorithms that are effective to tackle the data from the next generation sequencing technology. However, the unique error patterns in the third generation sequencing (TGS) technologies could reduce the accuracy of these programs.

Results

We developed a Classification tool using Discriminative K-mers and Approximate Matching algorithm (CDKAM). This approximate matching method was used for searching k-mers, which included two phases, a quick mapping phase and a dynamic programming phase. Simulated datasets as well as real TGS datasets have been tested to compare the performance of CDKAM with existing methods. We showed that CDKAM performed better in many aspects, especially when classifying TGS data with average length 1000–1500 bases.

Conclusions

CDKAM is an effective program with higher accuracy and lower memory requirement for TGS metagenome sequence classification. It produces a high species-level accuracy.
Cancer prognosis prediction using somatic point mutation and copy number variation data: a comparison of gene-level and pathway-based models
Authors: Zheng Xingyu , Amos Christopher I. , Frost H. Robert
Published: October 2020

Background

Genomic profiling of solid human tumors by projects such as The Cancer Genome Atlas (TCGA) has provided important information regarding the somatic alterations that drive cancer progression and patient survival. Although researchers have successfully leveraged TCGA data to build prognostic models, most efforts have focused on specific cancer types and a targeted set of gene-level predictors. Less is known about the prognostic ability of pathway-level variables in a pan-cancer setting. To address these limitations, we systematically evaluated and compared the prognostic ability of somatic point mutation (SPM) and copy number variation (CNV) data, gene-level and pathway-level models for a diverse set of TCGA cancer types and predictive modeling approaches.

Results

We evaluated gene-level and pathway-level penalized Cox proportional hazards models using SPM and CNV data for 29 different TCGA cohorts. We measured predictive accuracy as the concordance index for predicting survival outcomes. Our comprehensive analysis suggests that the use of pathway-level predictors did not offer superior predictive power relative to gene-level models for all cancer types but had the advantages of robustness and parsimony. We identified a set of cohorts for which somatic alterations could not predict prognosis, and a unique cohort LGG, for which SPM data was more predictive than CNV data and the predictive accuracy is good for all model types. We found that the pathway-level predictors provide superior interpretative value and that there is often a serious collinearity issue for the gene-level models while pathway-level models avoided this issue.

Conclusion

Our comprehensive analysis suggests that when using somatic alterations data for cancer prognosis prediction, pathway-level models are more interpretable, stable and parsimonious compared to gene-level models. Pathway-level models also avoid the issue of collinearity, which can be serious for gene-level somatic alterations. The prognostic power of somatic alterations is highly variable across different cancer types and we have identified a set of cohorts for which somatic alterations could not predict prognosis. In general, CNV data predicts prognosis better than SPM data with the exception of the LGG cohort.
Genomic differences between the new Fusarium oxysporum f. sp. apii (Foa) race 4 on celery, the less virulent Foa races 2 and 3, and the avirulent on celery f. sp. coriandrii
Authors: Henry Peter , Kaur Sukhwinder , Pham Quyen Anh Tran , Barakat Radwan , Brinker Samuel , Haensel Hannah , Daugovish Oleg , Epstein Lynn
Published: October 2020

Background

Members of theF. oxysporiumspecies complex (FOSC) in the f. sp.apii(Foa) are pathogenic on celery and those in f. sp.coriandrii(Foci) are pathogenic on coriander (=cilantro). Fociwas first reported in California in 2005; a new and highly aggressive race 4 ofFoawas observed in 2013 in California. Preliminary evidence indicated thatFoacan also cause disease on coriander, albeit are less virulent thanFoci. Comparative genomics was used to investigate the evolutionary relationships betweenFoarace 4,Foarace 3, and theFoci, which are all in FOSC Clade 2, andFoarace 2, which is in FOSC Clade 3.

Results

A phylogenetic analysis of 2718 single-copy conserved genes and mitochondrial DNA sequence indicated thatFoaraces 3 and 4 and theFociare monophyletic within FOSC Clade 2; these strains also are in a single somatic compatibility group. However, in the accessory genomes, theFociversusFoaraces 3 and 4 differ in multiple contigs. Based on significantly increased expression ofFoarace 4 genesin plantavs. in vitro, we identified 23 putative effectors and 13 possible pathogenicity factors. PCR primers for diagnosis of eitherFoarace 2 or 4 and theFociwere identified. Finally, mixtures of conidia that were pre-stained with different fluorochromes indicated thatFoarace 4 formed conidial anastomosis tubes (CATs) withFoci.Foarace 4 andFoarace 2, which are in different somatic compatibility groups, did not form CATs with each other.

Conclusions

There was no evidence thatFoarace 2 was involved in the recent evolution ofFoarace 4;Foarace 2 and 4 are CAT-incompatible. AlthoughFoaraces 3 and 4 and theFociare closely related, there is no evidence that eitherFocicontributed to the evolution ofFoarace 4, or thatFoarace 4 was the recent recipient of a multi-gene chromosomal segment from another strain. However, horizontal chromosome transfer could account for the major difference in the accessory genomes ofFoarace 4 and theFociand for their differences in host range.
Methylome and transcriptome profiles in three yak tissues revealed that DNA methylation and the transcription factor ZGPAT co-regulate milk production
Authors: Xin Jinwei , Chai Zhixin , Zhang Chengfu , Zhang Qiang , Zhu Yong , Cao Hanwen , Yangji Cidan , Chen Xiaoying , Jiang Hui , Zhong Jincheng , Ji Qiumei
Published: October 2020

Background

Domestic yaks play an indispensable role in sustaining the livelihood of Tibetans and other ethnic groups on the Qinghai-Tibetan Plateau (QTP), by providing milk and meat. They have evolved numerous physiological adaptations to high-altitude environment, including strong blood oxygen transportation capabilities and high metabolism. The roles of DNA methylation and gene expression in milk production and high-altitudes adaptation need further exploration.

Results

We performed genome-wide DNA methylome and transcriptome analyses of breast, lung, and biceps brachii muscle tissues from yaks of different ages. We identified 432,350 differentially methylated regions (DMRs) across the age groups within each tissue. The post-mature breast tissue had considerably more differentially methylated regions (155,957) than that from the three younger age groups. Hypomethylated genes with high expression levels might regulate milk production by influencing protein processing in the endoplasmic reticulum. According to weighted gene correlation network analysis, the “hub” gene ZGPAT was highly expressed in the post-mature breast tissue, indicating that it potentially regulates the transcription of 280 genes that influence protein synthesis, processing, and secretion. The tissue network analysis indicated that high expression of HIF1A regulates energy metabolism in the lung.

Conclusions

This study provides a basis for understanding the epigenetic mechanisms underlying milk production in yaks, and the results offer insight to breeding programs aimed at improving milk production.
Weighted gene coexpression network analysis-based identification of key modules and hub genes associated with drought sensitivity in rice
Authors: Yu Baiyang , Liu Jianbin , Wu Di , Liu Ying , Cen Weijian , Wang Shaokui , Li Rongbai , Luo Jijing
Published: October 2020

Background

Drought stress is an adverse factor with deleterious effects on several aspects of rice growth. However, the mechanism underlying drought resistance in rice remains unclear. To understand the molecular mechanism of the drought response in rice, drought-sensitive CSSL (Chromosome Single-substitution Segment Line) PY6 was used to map QTLs of sensitive phenotypes and to reveal the impact of the QTLs on transcriptional profiling.

Results

The QTL dss-1 was mapped onto the short arm of chromosome 1 of rice. According to transcriptomic analysis, the identified differentially expressed genes (DEGs) exhibited a downregulated pattern and were mainly enriched in photosynthesis-related GO terms, indicating that photosynthesis was greatly inhibited under drought. Further, according to weighted gene coexpression network analysis (WGCNA), specific gene modules (designating a group of genes with a similar expression pattern) were strongly correlated with H2O2 (4 modules) and MDA (3 modules), respectively. Likewise, GO analysis revealed that the photosynthesis-related GO terms were consistently overrepresented in H2O2-correlated modules. Functional annotation of the differentially expressed hub genes (DEHGs) in the H2O2 and MDA-correlated modules revealed cross-talk between abiotic and biotic stress responses for these genes, which were annotated as encoding WRKYs and PR family proteins, were notably differentially expressed between PY6 and PR403.

Conclusions

We speculated that drought-induced photosynthetic inhibition leads to H2O2 and MDA accumulation, which can then trigger the reprogramming of the rice transcriptome, including the hub genes involved in ROS scavenging, to prevent oxidative stress damage. Our results shed light on and provide deep insight into the drought resistance mechanism in rice.
Lesion outline and thermal field distribution of ablative in vitro experiments in myocardia: comparison of radiofrequency and laser ablation
Authors: Li Wei , Liu Jia , Huang Tong-yi , Zhong Xian , Yang Dao-peng , Xie Xiao-hua , Liu Dong-hong , Xie Xiao-yan , Zhuang Bo-wen
Published: October 2020

Objectives

To explore the lesion outline and thermal field distribution of radiofrequency ablation (RFA) and laser ablation (LA) in myocardial ablation in vitro.

Materials and methods

Twenty-four fresh porcine hearts were ablated with RFA or LA in vitro. The radiofrequency electrode or laser fiber and two parallel thermocouple probes were inserted into the myocardium under ultrasound guidance. The output power for RFA was 20 W/s and for LA was 5 W/s, and the total thermal energies were 1200 J, 2400 J, 3600 J, and 4800 J. The range of ablation lesions was measured, and temperature data were recorded simultaneously.

Results

All coagulation zones were ellipsoidal with clear boundaries. The center of LA was carbonized more obviously than that of RFA. With the accumulation of thermal energy and the extended time, all the ablation lesions induced by both RFA and LA were enlarged. By comparing the increase in thermal energy between the two groups, both the short-axis diameter and the volume change showed significant differences between the 1200 J and 3600 J groups and between the 2400 J and 4800 J groups (all P < 0.05). Both the short-axis diameter and the volume of the coagulation necrosis zone formed by LA were always larger than those of RFA at the same accumulated thermal energy. The temperatures of the two thermocouple probes increased with each energy increment. At the same accumulated energy, the temperature of LA was much higher than that of RFA at the same point. The initial temperature increase at 0.5 cm of LA was rapid. The temperature reached 43 °C and the accumulated energy reached 1200 J after approximately 4 min. After that the temperature increased at a slower rate to 70  C. For the RFA at the point of 0.5 cm, the initial temperature increased rapidly to 30 °C with the same accumulated energy of 1200 J after only 1 min. In the range of 4800 J of accumulated thermal energy, only the temperature of LA at the point of 0.5 cm exceeded 60 °C when the energy reached approximately 3000 J.

Conclusions

Both RFA and LA were shown to be reliable methods for myocardial ablation. The lesion outline and thermal field distribution of RFA and LA should be considered when performing thermal ablation in the intramyocardial septum during hypertrophic obstructive cardiomyopathy.
Machine learning techniques for mortality prediction in critical traumatic patients: anatomic and physiologic variables from the RETRAUCI study
Authors: Serviá Luis , Montserrat Neus , Badia Mariona , Llompart-Pou Juan Antonio , Barea-Mendoza Jesús Abelardo , Chico-Fernández Mario , Sánchez-Casado Marcelino , Jiménez José Manuel , Mayor Dolores María , Trujillano Javier
Published: October 2020

Background

Interest in models for calculating the risk of death in traumatic patients admitted to ICUs remains high. These models use variables derived from the deviation of physiological parameters and/or the severity of anatomical lesions with respect to the affected body areas. Our objective is to create different predictive models of the mortality of critically traumatic patients using machine learning techniques.

Methods

We used 9625 records from the RETRAUCI database (National Trauma Registry of 52 Spanish ICUs in the period of 2015–2019). Hospital mortality was 12.6%. Data on demographic variables, affected anatomical areas and physiological repercussions were used. The Weka Platform was used, along with a ten-fold cross-validation for the construction of nine supervised algorithms: logistic regression binary (LR), neural network (NN), sequential minimal optimization (SMO), classification rules (JRip), classification trees (CT), Bayesian networks (BN), adaptive boosting (ADABOOST), bootstrap aggregating (BAGGING) and random forest (RFOREST). The performance of the models was evaluated by accuracy, specificity, precision, recall, F-measure, and AUC.

Results

In all algorithms, the most important factors are those associated with traumatic brain injury (TBI) and organic failures. The LR finds thorax and limb injuries as independent protective factors of mortality. The CT generates 24 decision rules and uses those related to TBI as the first variables (range 2.0–81.6%). The JRip detects the eight rules with the highest risk of mortality (65.0–94.1%). The NN model uses a hidden layer of ten nodes, which requires 200 weights for its interpretation. The BN find the relationships between the different factors that identify different patient profiles. Models with the ensemble methodology (ADABOOST, BAGGING and RandomForest) do not have greater performance. All models obtain high values ​​in accuracy, specificity, and AUC, but obtain lower values ​​in recall. The greatest precision is achieved by the SMO model, and the BN obtains the best recall, F-measure, and AUC.

Conclusion

Machine learning techniques are useful for creating mortality classification models in critically traumatic patients. With clinical interpretation, the algorithms establish different patient profiles according to the relationship between the variables used, determine groups of patients with different evolutions, and alert clinicians to the presence of rules that indicate the greatest severity.