bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse events in deceased hospitalised cancer patients as a measure of quality and safety in end-of-life cancer care
Authors: Haukland Ellinor Christin , von Plessen Christian , Nieder Carsten , Vonen Barthold
Published: June 2020

Background

Anticancer treatment exposes patients to negative consequences such as increased toxicity and decreased quality of life, and there are clear guidelines recommending limiting use of aggressive anticancer treatments for patients near end of life. The aim of this study is to investigate the association between anticancer treatment given during the last 30 days of life and adverse events contributing to death and elucidate how adverse events can be used as a measure of quality and safety in end-of-life cancer care.

Methods

Retrospective cohort study of 247 deceased hospitalised cancer patients at three hospitals in Norway in 2012 and 2013. The Global Trigger Tool method were used to identify adverse events. We used Poisson regression and binary logistic regression to compare adverse events and association with use of anticancer treatment given during the last 30 days of life.

Results

30% of deceased hospitalised cancer patients received some kind of anticancer treatment during the last 30 days of life, mainly systemic anticancer treatment. These patients had 62% more adverse events compared to patients not being treated last 30 days, 39 vs. 24 adverse events per 1000 patient days (p < 0.001, OR 1.62 (1.23–2.15). They also had twice the odds of an adverse event contributing to death compared to patients without such treatment, 33 vs. 18% (p = 0.045, OR 1.85 (1.01–3.36)). Receiving follow up by specialist palliative care reduced the rate of AEs per 1000 patient days in both groups by 29% (p = 0.02, IRR 0.71, CI 95% 0.53–0.96).

Conclusions

Anticancer treatment given during the last 30 days of life is associated with a significantly increased rate of adverse events and related mortality. Patients receiving specialist palliative care had significantly fewer adverse events, supporting recommendations of early integration of palliative care in a patient safety perspective.
Functional oral nanoparticles for delivering silibinin and cryptotanshinone against breast cancer lung metastasis
Authors: Liu Ying , Xie Xingmei , Hou Xuefeng , Shen Junyi , Shi Jiangpei , Chen Haizhen , He Yuanzhi , Wang Zhi , Feng Nianping
Published: May 2020

Background

Breast cancer lung metastasis occurs in more than 60% of all patients with breast cancer, and most of those afflicted by it eventually die of recurrence. The tumor microenvironment plays vital roles in metastasis. Modulating the tumor microenvironment via multiple pathways could efficiently prevent or inhibit lung metastasis. Silibinin and cryptotanshinone are natural plant products that demonstrate anti-metastasis effects and modulate the tumor microenvironment via different pathways. However, they have poor aqueous solubility, membrane permeability, and oral bioavailability. Oral drug administration may help improve the quality of life and compliance of patients with breast cancer, primarily under long-term and/or follow-up therapy. Herein, we developed poly-N-(2-hydroxypropyl) methacrylamide (pHPMA)-coated wheat germ agglutinin-modified lipid-polymer hybrid nanoparticles, co-loaded with silibinin and cryptotanshinone (S/C-pW-LPNs). We assessed their oral bioavailability, and evaluated their anti-metastasis efficacy in a 4T1 breast cancer tumor-bearing nude mouse model.

Results

An in vitro mucus diffusion study revealed that pHPMA enhanced W-LPN mucus penetration. After oral administration, pHPMA enhanced nanoparticle distribution in rat jejunum and substantially augmented oral bioavailability. S/C-W-LPNs markedly increased 4T1 cell toxicity and inhibited cell invasion and migration. Compared to LPNs loaded with either silibinin or cryptotanshinone alone, S/C-pW-LPNs dramatically slowed tumor progression in 4T1 tumor-bearing nude mice. S/C-pW-LPNs presented with the most robust anti-metastasis activity on smooth lung surfaces and mitigated lung metastasis foci. They also downregulated tumor microenvironment biomarkers such as CD31, TGF-β1, and MMP-9 that promote metastasis.

Conclusions

Silibinin- and cryptotanshinone-co-loaded pW-LPNs efficiently penetrate intestinal barriers, thereby enhancing the oral bioavailability of the drug loads. These nanoparticles exhibit favorable anti-metastasis effects in breast cancer-bearing nude mice. Hence, S/C-pW-LPNs are promising oral drug nanocarriers that inhibit breast cancer lung metastasis.
Pattern and risk factors of local recurrence after nephroureterectomy for upper tract urothelial carcinoma
Authors: Li Xiaoying , Cui Ming , Gu Xiaobin , Fang Dong , Li Hongzhen , Qin Shangbin , Yang Kunlin , Zhu Tianzhao , Li Xuesong , Zhou Liqun , Gao Xian-Shu , Wang Dian
Published: May 2020

Purpose

This study aims to identify predictive local recurrence risk factors and site-specific local recurrence pattern of upper tract urothelial carcinoma (UTUC) with different primary tumor locations.

Methods

Three hundred and eighty-nine UTUC patients with radical nephroureterectomy were included in this study. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of local recurrence. We also mapped the position of local recurrence sites stratified by primary tumor locations.

Results

A total of 73 patients (18.7%) developed local recurrence within a median follow-up of 41 months (range, 3-80 months). For patients with local recurrence, the median interval of local recurrence was 9 months. Ureter tumor, multifocality, T stage, G grade, lymph node metastasis (LNM), lymph node dissection (LND), and lymph vascular invasion (LVI) were all significantly associated with increased local recurrence by univariable analyses (P < 0.05). Only multifocality, T3–4, G3, and LNM remained independent predictors of increased local recurrence by multivariable analyses. Adjuvant radiotherapy could reduce the local recurrence (HR = 0.177; 95% CI 0.064-0.493, P = 0.001). Patients with local recurrence had poorer cancer-specific survival (4-year cancer-specific survival rate 36 ± 7.5% vs 88.4 ± 2.2%, P = 0.000). We evaluated local recurrence pattern stratified by tumor locations. Para-aortic lymph node region was the most common recurrence area for all the patients. Left-sided UTUC had more than 70% recurrent lymph nodes in the left para-aortic region (LPA). For right-sided UTUC patients, recurrent para-aortic lymph nodes distributed in the LPA (33.3%), aortocaval (AC) (41.5%), and right paracaval (RPC) (25.2%) regions. Recurrence in the internal and external iliac regions was only found in the distal ureter group (P < 0.05). Renal pelvic fossa recurrence was only found in renal pelvic tumor (22.2%, P = 0.007). The ureter tumor bed recurrence rate was higher for ureter patients (P = 0.001).

Conclusions

Multifocality, T3–4, G3, and LNM are predictors of higher local recurrence rate of UTUC. Adjuvant radiotherapy can reduce local recurrence rate. Local recurrence patterns are different according to primary tumor locations.
Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy
Authors: Hong Fenfen , Gao Yu , Li Yang , Zheng Linfeng , Xu Feng , Li Xianpeng
Published: May 2020

Background

Hepatocellular carcinoma (HCC) is still a major health burden in China considering its high incidence and mortality. Long non-coding RNAs (lncRNAs) were found playing vital roles in tumor progression, suggesting a new way of diagnosis and prognosis prediction, or treatment of HCC. This study was designed to investigate the role of HIF1A-AS1 during the progression of HCC and to explore its related mechanisms.

Methods

The expression of HIF1A-AS1 was detected in 50 paired carcinoma tissues and adjacent normal tissues by quantitative real-time PCR assay. HCC cell apoptosis was induced by nutrient-deficient culture medium and detected by Cell Counting Kit-8 and flow cytometer assays. HIF1A-AS1 inhibition in HCC cells was accomplished by small interfering RNA transfection.

Results

HIF1A-AS1 was overexpressed in HCC tissues and was associated with tumor size, TNM stage, and lymph node metastasis. Compared with the low HIF1A-AS1 group, the high HIF1A-AS1 group had a shorter overall survival and a worse disease-free survival. HIF1A-AS1 expression was significantly higher in HCC cell lines (7721 and Huh7) than that in normal hepatocyte cell line L02 under normal culture condition. However, under nutrient-deficient condition, HIF1A-AS1 expression was significantly increased in both HCC and normal hepatocyte cell lines and was increased with the prolongation of nutrient-free culture. Inhibition of HIF1A-AS1 promoted starvation-induced HCC cell apoptosis. Furthermore, inhibition of HIF1A-AS1 could also reduce starvation-induced HCC cell autophagy. The expression of HIF-1α and phosphorylated mTOR was significantly decreased in HCC cells after HIF1A-AS1 inhibition.

Conclusions

HIF1A-AS1, overexpressed in HCC and associated with HCC prognosis, could regulate starvation-induced HCC cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy, promoting HCC cell progression.
Motivation of emergency medical services volunteers: a study of organized Good Samaritans
Authors: Khalemsky Michael , Schwartz David G. , Herbst Raphael , Jaffe Eli
Published: June 2020

Background

Early professional care in emergencies is beneficial in general and its utility has been proven in many studies, particularly in regard to out-of-hospital cardiopulmonary arrest. A person in distress can expect help from two sources: bystanders, including family members, community members, and complete strangers; and professionals, including emergency medical services, first responders, firefighters, and police officers. Emergency Medical Services try to achieve faster first response times through various approaches. Recent technological and social developments have enabled a new form of Emergency Medical Services volunteering, called Organized Good Samaritans, which represents a new layer between occasional volunteers and time-donation volunteers. Organized Good Samaritans are people with a medical background, particularly off-duty medical professionals who are willing and able to provide first aid in emergencies in their vicinity.

Methods

A qualitative formalization of technology-enabled Organized Good Samaritans is presented. One thousand eight hundred Israeli National Emergency Medical Services volunteers were surveyed using Clary and Snyder’s Volunteer Functions Inventory instrument. Demographics, professional backgrounds, and volunteering functions of Time-Donation Volunteers and Organized Good Samaritans are compared.

Results

Significant differences between Organized Good Samaritans and Time Donation Volunteers were found. Demographically, Organized Good Samaritans are older and the percentage of males is higher. Professionally, the percentage of physicians and nurses among Organized Good Samaritans is higher. Motivation measures find that the motivation of Organized Good Samaritans is higher and the order of importance of the volunteering functions differs.

Conclusion

A clearly identifiable and differently motivated class of emergency services volunteers has emerged. An appropriate information technology infrastructure enables Emergency Medical Services organizations to integrate Organized Good Samaritans into core business processes to shorten response times to emergencies.Organized Good Samaritans provide a volunteering opportunity for highly skilled people unable to be Time-Donation Volunteers. Our findings provide an empirical basis for further research on Organized Good Samaritans integration into Emergency Medical Services operations. Emergency Medical Services administrators can use these findings to establish an Organized Good Samaritans infrastructure and adjust recruitment and retention. This study is limited to one national Emergency Medical Services organization in Israel. Cultural differences can impact results in other countries. Organized Good Samaritans effectiveness should also be studied in terms of response times and medical outcomes.
Tropical dry forest dynamics in the context of climate change: syntheses of drivers, gaps, and management perspectives
Authors: Siyum Zenebe Girmay
Published: May 2020

This review attempts to synthesize the available literature on tropical dry forests and their dynamics in the context of climate change and thereby identifies possible gaps and priority areas for further research and management endeavors. Tropical dry forests (TDFs) occur in dryland environments, which are characterized by prolonged periods of dry months. They experience distinct seasonality and high inter-annual variability in climatic variables, particularly rainfall. Despite the enormous ecological and livelihood importance of TDFs, these forests are highly threatened by global changes. So far, they have received far less attention from research and development interventions as compared to the humid tropical forests. Their significance is still overlooked in many countries’ national policies. Current modeling frameworks show that drought, precipitation, and temperature are highlighted as strong drivers of tree growth and/or mortality in these forests. Well-valued and sustainably managed TDFs have the potential to contribute to climate change adaptation and mitigation, buffer against erosion and desertification, and contribute to economic development, food security, and poverty alleviation. TDFs suffer notable disregard from research and development strategies. Thus, greater awareness and appropriate policies and investments are needed at various levels to counteract the increasing vulnerability of people, forest ecosystems, and species living in these fragile ecosystems. Further research is also needed to generate knowledge on the status and significances of TDFs and their responses in the face of the changing climate so as to bring their sustainable management to the attention of policymakers and managers.
Aggravated pulmonary injury after subarachnoid hemorrhage in PDGF-Bret/ret mice
Authors: Pan Pengyu , Qu Jie , Li Qiang , Li Rongwei , Yang Yang , Zuo Shilun , Liu Xin , Feng Hua , Chen Yujie
Published: June 2020

Background

Recent advances in surgical and neuroprotective strategies could effectively manage the pathophysiological progression of subarachnoid hemorrhage (SAH). However, pulmonary dysfunction frequently occurs in SAH patients with an increased risk of unsatisfactory outcomes. Based on the similar microvascular structures in the blood-air barrier and blood-brain barrier and possible brain-lung crosstalks, we believe that pericytes may be involved in both neurological and pulmonary dysfunction after SAH.

Methods

In our experiments, platelet-derived growth factor B (PDGF-B) retention motif knockout (PDGF-Bret/ret) mice and adeno-associated virus PDGF-B were employed to show the involvement of pericyte deficiency and PDGF-B expression. Neurological score, SAH grade, hematoxylin-eosin staining, and PaO2/FiO2 ratio analysis were performed to evaluate the neurological deficits and pulmonary functions in endovascular perforation SAH models at 24 h after surgery, as well as western blotting and immunofluorescence staining for underlying molecular expressions.

Results

We found that neonatal PDGF-Bret/retmice exhibited pulmonary atelectasis 12 h after birth. Further investigation showed a decrease in PaO2/FiO2and lung-specific surfactant proteins in adult PDGF-Bret/retmice. These dysfunctions were much worse than those in wild-type mice at 24 h after SAH. PDGF-B overexpression alleviated pulmonary dysfunction after SAH.

Conclusions

These results suggested pulmonary dysfunction after SAH and the pivotal role of PDGF-B signaling for the pathophysiological process and future therapeutic targets of pulmonary injury treatment after SAH. Further studies are needed for pathophysiological investigations and translational studies on pulmonary injuries after SAH.
Foundation News
Authors: Burk Katie
Published: June 2020

Experiential learning is a process through which students develop knowledge, skills, and values from direct experiences outside of a traditional academic setting. Experiential learning is also referred to as learning through action, learning by doing, learning through experience, and learning through discovery and exploration.
Multiple joint wavefield inversions: Theory and field data implementations
Authors: Colombo Daniele , Rovetta Diego , Al-Yousuf Taqi , Sandoval Ernesto , Turkoglu Ersan , McNeice Gary
Published: June 2020

Accurate velocity models for the near surface and overburden are needed for seismic processing and reliable depth imaging. Seismic with multiphysics data, well logs, and geology information need to be quantitatively integrated to obtain high-resolution velocity models. We detail our development and application of the joint wavefield inversion software platform, which enables flexible algorithmic schemes for the integration of multiparameter data and constraints. Inversion is performed in cascade or simultaneously using a variety of input data to constrain the velocity field reconstruction at multiple scales. Coupling mechanisms based on structure similarity together with rock-physics relations are optimally combined to boost resolution and enhance accuracy of the inverted velocity models. Ill-posed inversion problems are then solved using extensive geologic and rock-physics regularization instead of relying on smoothness constraints alone. We detail workflows and algorithms to guide the application of multiparameter joint inversion for velocity model building whether the input data are seismic traveltimes, electromagnetics (time/frequency domains), gravity, and/or surface waves. Extensive applications of multiparameter joint inversion are presented for a variety of complex geologic scenarios in which various multiparameter coupling strategies are illustrated. Robust velocity modeling and enhanced seismic imaging in time and depth domains are obtained as a result, proving the importance of multiphysics integration for reliable earth model parameter estimation.
Seismic-while-drilling applications from the first DrillCAM trial with wireless geophones and instrumented top drive
Authors: Bakulin Andrey , Aldawood Ali , Silvestrov Ilya , Hemyari Emad , Poletto Flavio
Published: June 2020

Advanced geophysical sensing while drilling is being driven by trends to automate and optimize drilling and the desire to better characterize complex near surface and overburden in desert environments. We introduce the DrillCAM system, which combines a set of geophysical techniques from seismic while drilling (SWD), drill-string vibration health, estimation of formation properties at the bit, and imaging ahead of and around the bit. We present data acquisition, processing, and initial application results from the first field trial on an onshore well in a desert environment. In this study, we focus on SWD applications. For the first time, wireless geophones installed around a rig were used to acquire continuous data while drilling. We demonstrate the feasibility of such a system to provide flexible acquisition geometries that are easily expandable with increasing bit depth without interference from drilling operations. Using a top-drive sensor as a pilot, we transform the drill-bit noise into meaningful and reliable seismic signals. The data were used to retrieve a check shot while drilling, make kinematic look-ahead predictions, and obtain a vertical seismic profiling corridor stack matching surface seismic. Robust near-offset check-shot signals were received from roller-cone and polycrystalline diamond compact (PDC) bits above 7200 ft after limited preprocessing of challenging single-sensor data with supergrouping. Detecting signals from deeper sections drilled with PDC bits may require more advanced processing by using an entire 2D spread of wireless geophones and downhole pilots. The real-time capabilities of the system make the data available for continuous data processing and interpretation that will facilitate drilling automation and improve real-time decision making.
Extreme gravity: Geologic effects
Authors: Milsom John
Published: June 2020

The maximum positive combined effect on the earth's gravity field of all geologic sources present in a given area, including any isostatic compensation, is limited by the ability of the lithosphere to support load. Bouguer gravity is one possible proxy for this effect. Bouguer maxima close to +350 mGal have been measured on Chichijima Island and Penrhyn Atoll in the Pacific Ocean. These may be the highest values anywhere on the planet. Suggestions of even higher values in the northernmost segment of the Colombian Andes rely on extrapolation of trends established in areas surrounding the Santa Marta Massif and must be treated with caution.
Prior Treatment Time Affects Survival Outcomes in Metastatic Breast Cancer
Authors: Rocque Gabrielle B. , Gilbert Aidan , Williams Courtney P. , Kenzik Kelly M. , Nakhmani Arie , Kandhare Pravinkumar G. , Bhatia Smita , Burkard Mark E. , Azuero Andres
Published: June 2020

PURPOSE

Sequential drug treatments in metastatic breast cancer (MBC) are disparate. Clinical trial data includes limited reporting of treatment context, primarily including the number of prior therapies. This study evaluates the relationship between prior treatment time, prior lines of treatment, and survival using a novel visualization technique coupled with statistical analyses.

PATIENTS AND METHODS

This retrospective cohort study used a nationwide, de-identified electronic health record–derived database to identify women with hormone receptor–positive, human epidermal growth factor receptor 2–negative MBC diagnosed in 2014 who subsequently received paclitaxel. Images were created, with individual patients represented on the y-axis and time, on the x-axis. Specific treatments were represented by colored bars, with Kaplan-Meier curves overlaying the image. Separate images assessed progression-free survival and overall survival (OS). Hazard ratios (HRs) and 95% CIs from Cox proportional hazards models evaluated the association between prior treatment time and OS.

RESULTS

Of 234 patients, median survival from first paclitaxel administration was 20 months (interquartile range, 8-53 months). An inverse relationship was observed between OS after paclitaxel and timing of administration. In adjusted models, each year on treatment prior to paclitaxel was associated with a 16% increased hazard of death after paclitaxel (HR, 1.16; 95% CI, 1.05 to 1.29).

CONCLUSION

OS after a specific treatment is dependent on when a drug is given in the disease context, highlighting the potential for an overall OS benefit to be observed on the basis of treatment timing. Prior time on treatment should be considered as a stratifying factor in randomized trials and a confounding factor when examining survival in observational data.
Clinical impact of COVID-19 on patients with cancer: Data from the COVID-19 and Cancer Consortium (CCC19).
Authors: Warner Jeremy Lyle , Rubinstein Sam , Grivas Petros , Choueiri Toni K. , Kuderer Nicole Maria , Shah Dimpy , Rivera Donna R , Gupta Shilpa , Bilen Mehmet Asim , Halfdanarson Thorvardur Ragnar , Doroshow Deborah Blythe , Wehbe Firas , Shah Sumit , Shyr Yu , Lopes Gilberto , Painter Corrie , Lyman Gary H. , Thompson Michael A. , Peters Solange , Rini Brian I.
Published: June 2020

LBA110

Background: There are limited data on COVID-19 in patients with cancer. We characterize the outcomes of patients with cancer and COVID-19 and identify potential prognostic factors. Methods: The COVID-19 and Cancer Consortium (CCC19) cohort study includes patients with active or prior hematologic or invasive solid malignancies reported across academic and community sites. Results: We included 1,018 cases accrued March-April 2020. Median age was 66 years (range, 18-90). Breast (20%) and prostate (16%) cancers were most prevalent; 43% of patients were on active anti-cancer treatment. At time of data analysis, 106 patients (10.4%) have died and 26% met the composite outcome of death, severe illness requiring hospitalization, and/or mechanical ventilation. In multivariable logistic regression analysis, independent factors associated with increased 30-day mortality were age, male sex, former smoking, ECOG performance status (2 versus 0/1: partially adjusted odds ratio (pAOR) 2.74, 95% CI 1.31-5.7; 3/4 versus 0/1: pAOR 5.34, 95% CI 2.44-11.69), active malignancy (stable/responding, pAOR 1.93, 95% CI 1.06-3.5; progressing, pAOR 3.79, 95% CI 1.78-8.08), and receipt of azithromycin and hydroxychloroquine. Tumor type, race/ethnicity, obesity, number of comorbidities, recent surgery, and type of active cancer therapy were not significant factors for mortality. Conclusions: All-cause 30-day mortality and severe illness in this cohort were significantly higher than previously reported for the general population and were associated with general risk factors as well as those unique to patients with cancer. Cancer type and treatment were not independently associated with increased 30-day mortality. Longer follow-up is needed to better understand the impact of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.
Dose-Response Relationships Between Gonadal Steroids and Bone, Body Composition, and Sexual Function in Aging Men
Authors: Finkelstein Joel S , Lee Hang , Burnett-Bowie Sherri-Ann M , Darakananda Karin , Gentile Emily C , Goldstein David W , Prizand Sarah H , Krivicich Laura M , Taylor Alexander P , Wulczyn Kendra E , Leder Benjamin Z , Yu Elaine W
Published: June 2020

Context

Most labs set the lower limit of normal for testosterone at the 2.5th percentile of values in young or age-matched men, an approach that does not consider the physiologic changes associated with various testosterone concentrations.

Objective

To characterize the dose-response relationships between gonadal steroid concentrations and measures regulated by gonadal steroids in older men.

Design, Participants, and Intervention

177 men aged 60 to 80 were randomly assigned to receive goserelin acetate plus either 0 (placebo), 1.25, 2.5, 5, or 10 grams of a 1% testosterone gel daily for 16 weeks or placebos for both medications (controls).

Primary Outcomes

Changes in serum C-telopeptide (CTX), total body fat by dual energy X-ray absorptiometry, and self-reported sexual desire.

Results

Clear relationships between the testosterone dosage (or the resulting testosterone levels) and a variety of outcome measures were observed. Changes in serum CTX exceeded changes in the controls in men whose testosterone levels were 0 to 99, 100 to 199, 200 to 299, or 300 to 499 ng/dL, whereas increases in total body fat, subcutaneous fat, and thigh fat exceeded controls when testosterone levels were 0 to 99 or 100 to 199 ng/dL. Sexual desire and erectile function were indistinguishable from controls until testosterone levels were <100 ng/dL.

Conclusion

Changes in measures of bone resorption, body fat, and sexual function begin at a variety of testosterone concentrations with many outcome measures remaining stable until testosterone levels are well below the stated normal ranges. In light of this variation, novel approaches for establishing the normal range for testosterone are needed.
Associations of Per- and Polyfluoroalkyl Substances (PFAS) With Glucose Tolerance During Pregnancy in Project Viva
Authors: Preston Emma V , Rifas-Shiman Sheryl L , Hivert Marie-France , Zota Ami R , Sagiv Sharon K , Calafat Antonia M , Oken Emily , James-Todd Tamarra
Published: June 2020

Context

Per- and polyfluoroalkyl substances (PFAS) exposure may alter glucose homeostasis. Research on PFAS exposure and glucose tolerance during pregnancy is limited.

Objective

The objective of this work is to estimate associations between first-trimester plasma PFAS concentrations and glucose tolerance assessed in late second pregnancy trimester.

Design, Setting, Participants, and Main Outcome Measures

Pregnant women (n = 1540) enrolled in Project Viva in 1999 to 2002 provided first-trimester plasma samples analyzed for 8 PFAS. At approximately 28 weeks’ gestation, women completed 1-hour nonfasting, 50-g oral glucose challenge tests (GCTs); if abnormal, women completed subsequent 3-hour oral glucose tolerance tests (OGTTs) to screen for gestational diabetes mellitus (GDM). We assessed both continuous GCT glucose levels and 4 categories of glucose tolerance (normal glycemia [reference], isolated hyperglycemia, impaired glucose tolerance, GDM). We used multinomial logistic regression to estimate associations of PFAS with glucose tolerance categories. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) to assess individual and joint effects of PFAS on continuous GCT glucose levels, respectively. We evaluated effect modification by maternal age and race/ethnicity.

Results

PFAS were not associated with glucose tolerance categories. In BKMR analyses, we observed a positive association between ln-perfluorooctane sulfonate (PFOS) and glucose levels (Δ25th to 75th percentile: 6.2 mg/dL, 95% CI, 1.1-11.3) and an inverse-U shaped association between 2-(N-perfluorooctane sulfonamide) acetate and glucose levels. Individual linear regression results were similar. We found suggestive evidence that associations varied by age and racial/ethnic group.

Conclusion

Certain PFAS may alter glucose homeostasis during pregnancy, but may not be associated with overt GDM.
Heterozygous Deletions in MKRN3 Cause Central Precocious Puberty Without Prader-Willi Syndrome
Authors: Meader Brooke N , Albano Alessandro , Sekizkardes Hilal , Delaney Angela
Published: June 2020

Context

Loss-of-function mutations in the imprinted genes MKRN3 and DLK1 cause central precocious puberty (CPP) but whole gene deletions have not been reported. Larger deletions of the chromosome 15q11-13 imprinted locus, including MKRN3, cause Prader-Willi syndrome (PWS). CPP has been reported in PWS but is not common, and the role of MKRN3 in PWS has not been fully elucidated.

Objective

To identify copy number variants in puberty-related, imprinted genes to determine their role in CPP.

Methods

Probands with idiopathic CPP had chromosomal microarray (CMA) and targeted deletion/duplication testing for MKRN3 and DLK1.

Results

Sixteen female probands without MKRN3 or DLK1 variants identified by Sanger sequencing were studied. Whole gene deletions of MKRN3 were identified in 2 subjects (13%): a complete deletion of MKRN3 in Patient A (pubertal onset at 7 years) and a larger deletion involving MAGEL2, MKRN3, and NDN in Patient B (pubertal onset 5.5 years). Both were paternally inherited. Patient B had no typical features of PWS, other than obesity, which was also present in her unaffected family.

Conclusions

We identified 2 cases of whole gene deletions of MKRN3 causing isolated CPP without PWS. This is the first report of complete deletions of MKRN3 in patients with CPP, emphasizing the importance of including copy number variant analysis for MKRN3 mutation testing when a genetic diagnosis is suspected. We speculate that there is a critical region of the PWS locus beyond MKRN3, MAGEL2, and NDN that is responsible for the PWS phenotype.
Cardiac and Pulmonary Disorders and the Nervous System
Authors: Weathered Natalie R.
Published: June 2020

PURPOSE OF REVIEW

This article reviews the neurologic complications encountered with cardiac and pulmonary disorders, specifically focusing on endocarditis, cardiac arrest, heart failure, hypercapnia, hypoxia, and cystic fibrosis. As neurologic dysfunction is one of the most frequent complications of these diseases and may even be the presenting symptom, it is important to be familiar with these complications to foster early recognition and intervention.

RECENT FINDINGS

Advances have been made in the identification of which patients can safely undergo valvular surgery for treatment of infective endocarditis in the setting of stroke, which, ideally, will minimize the risk of recurrent stroke in these patients. Additionally, technologic advances are improving our ability to use a multimodal approach for prognostication after cardiac arrest.

The neurologic complications from the described disorders range from cerebrovascular complications to encephalitis, cognitive impairment, sleep-disordered breathing, headache, and increased intracranial pressure leading to coma or even death. Given the severity of these symptoms, it is paramount that neurologists be closely involved in the care of patients with neurologic complications from cardiac and pulmonary disorders.
Obstetric and Gynecologic Disorders and the Nervous System
Authors: O’Neal Mary Angela
Published: June 2020

PURPOSE OF REVIEW

This article highlights the multiple intersections between obstetric/gynecologic issues and neurologic disorders.

RECENT FINDINGS

Neurologic issues can arise related to contraceptive medications, infertility treatments, pregnancy, and menopause. This article explores these areas in chronologic order, beginning with women’s neurologic conditions that overlap their reproductive years and those that may occur during pregnancy and continuing through menopause. For each disorder, the epidemiology, pathophysiology, complications, and best sex-based treatment are described. Recent findings and treatments are highlighted.

Obstetric and gynecologic disorders may present with neurologic symptoms, so it is important for neurologists to understand these intersections to deliver the best care for our female patients.
Gastrointestinal Disorders and the Nervous System
Authors: White Halina
Published: June 2020

PURPOSE OF REVIEW

This article describes the neurologic sequelae of various nutritional micronutrient deficiencies, celiac disease, inflammatory bowel disease, and liver disease. Where relevant, appropriate treatments for these conditions are also discussed. The developing field of the microbiome and nervous system interaction is also outlined.

RECENT FINDINGS

Pathology in the gastrointestinal system can affect the nervous system when it causes micronutrient deficiency, when immune responses created by the gastrointestinal system affect the nervous system, when toxins caused by gastrointestinal organ failure harm the nervous system, and when treatments aimed at a gastrointestinal medical condition cause damage to the nervous system as a side effect.

This article addresses familiar concepts and new developments in the treatment and understanding of diseases that affect the gut and nervous system simultaneously.
React or Be Killed
Authors: Santos Andreia Beatriz Silva dos , Nascimento-Mandingo Fábio , Chazkel Amy
Published: June 2020

This conversation places a historian from the Brazilian political organization Reaja ou Será Morto / Reaja ou Será Morta (React or Be Killed) in dialogue with other members of that group to reflect on how the study of history on the one hand and the struggle against racist police brutality and the possibility of creating a world without such violence on the other might inform each other. The interlocutors explore historical continuities in policing Black communities, and in what they have identified as genocidal violence against Black Brazilians, as well as in anti-Black racist notions of public safety that have become imbricated in the way the state functions. With their Pan-Africanist community school, Escola Winnie Mandela, with their militant commitment to autonomy, and in the face of persistent neglect by the state, members of Reaja suggest that theirs is already a world without police.
Foot-and-mouth disease virus induces PERK mediated autophagy to suppress antiviral interferon response
Authors: Ranjitha H. B. , Ammanathan Veena , Guleria Neha , Hosamani Madhusudan , Sreenivasa B. P. , Dhanesh V. V. , Santhoshkumar Rashmi , Sagar B. K. Chandrasekhar , Mishra B. P. , Singh R. K. , Sanyal Aniket , Manjithaya Ravi , Basagoudanavar Suresh H.
Published: June 2020

Foot-and-mouth disease virus (FMDV) is a picornavirus that causes contagious acute infection in cloven-hoofed animals. FMDV replication associated viral protein expression induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR), in turn inducing autophagy to restore cellular homeostasis. We observed that inhibition of BiP, a master regulator of ER stress and UPR, decreased FMDV infection confirming their involvement. Further, we show that the FMDV infection induces UPR mainly through PKR-like ER kinase (PERK)-mediated pathway. Knockdown of PERK and chemical inhibition of PERK activation resulted in decreased expression of FMDV proteins along with the reduction of autophagy marker protein LC3B-II. There are conflicting reports on the role of autophagy in FMDV multiplication. Our study systematically demonstrates that during FMDV infection, PERK mediated UPR stimulated an increased level of endogenous LC3B-II and turnover of SQSTM1, thus confirming the activation of functional autophagy. Modulation of UPR and autophagy by pharmacological and genetic approaches resulted in reduced viral progeny, by enhancing antiviral interferon response. Taken together, this study underscores the prospect of exploring the PERK mediated autophagy as an antiviral target.
Comparison of Likert and PI-RADS version 2 MRI scoring systems for the detection of clinically significant prostate cancer
Authors: Zawaideh Jeries P , Sala Evis , Pantelidou Maria , Shaida Nadeem , Koo Brendan , Caglic Iztok , Warren Anne Y , Carmisciano Luca , Saeb-Parsy Kasra , Gnanapragasam Vincent J , Kastner Christof , Barrett Tristan
Published: June 2020

Objective:

To compare the performance of Likert and Prostate Imaging–Reporting and Data System (PI-RADS) multiparametric (mp) MRI scoring systems for detecting clinically significant prostate cancer (csPCa).

Methods:

199 biopsy-naïve males undergoing prostate mpMRI were prospectively scored with Likert and PI-RADS systems by four experienced radiologists. A binary cut-off (threshold score ≥3) was used to analyze histological results by three groups: negative, insignificant disease (Gleason 3 + 3; iPCa), and csPCa (Gleason ≥3 +4). Lesion-level results and prostate zonal location were also compared.

Results:

129/199 (64.8%) males underwent biopsy, 96 with Likert or PI-RADS score ≥3, and 21 with negative MRI. A further 12 patients were biopsied during follow-up (mean 507 days). Prostate cancer was diagnosed in 87/199 (43.7%) patients, 65 with (33.6%) csPCa. 30/92 (32.6%) patients with negative MRI were biopsied, with an NPV of 83.3% for cancer and 86.7% for csPCa. Likert and PI-RADS score differences were observed in 92 patients (46.2%), but only for 16 patients (8%) at threshold score ≥3. Likert scoring had higher specificity than PI-RADS (0.77 vs 0.66), higher area under the curve (0.92 vs 0.87, p = 0.002) and higher PPV (0.66 vs 0.58); NPV and sensitivity were the same. Likert had more five score results (58%) compared to PI-RADS (36%), but with similar csCPa detection (81.0 and 80.6% respectively). Likert demonstrated lower proportion of false positive in the predominately AFMS-involving lesions.

Conclusion:

Likert and PI-RADS systems both demonstrate high cancer detection rates. Likert scoring had a higher AUC with moderately higher specificity and lower positive call rate and could potentially help to reduce the number of unnecessary biopsies performed.

Advances in knowledge:

This paper illustrates that the Likert scoring system has potential to help urologists reduce the number of prostate biopsies performed.
A case of adrenal infarction in a patient with COVID 19 infection
Authors: Kumar Raekha , Guruparan Thushyanthan , Siddiqi Safa , Sheth Roosey , Jacyna Meron , Naghibi Mani , Vrentzou Eirini
Published: June 2020

This case report highlights an unusual presentation of acute adrenal infarction in a Covid-19 patient who presented with abdominal symptoms and hyponatraemia. We discuss the recent literature reviewing how Covid-19 creates a hypercoaguable state, with acute adrenal infarction as a possible prothrombotic complication.
Highly specific, multiplexed isothermal pathogen detection with fluorescent aptamer readout
Authors: Aufdembrink Lauren M. , Khan Pavana , Gaut Nathaniel J. , Adamala Katarzyna P. , Engelhart Aaron E.
Published: June 2020

Isothermal, cell-free, synthetic biology-based approaches to pathogen detection leverage the power of tools available in biological systems, such as highly active polymerases compatible with lyophilization, without the complexity inherent to live-cell systems, of which nucleic acid sequence based amplification (NASBA) is well known. Despite the reduced complexity associated with cell-free systems, side reactions are a common characteristic of these systems. As a result, these systems often exhibit false positives from reactions lacking an amplicon. Here we show that the inclusion of a DNA duplex lacking a promoter and unassociated with the amplicon fully suppresses false positives, enabling a suite of fluorescent aptamers to be used as NASBA tags (Apta-NASBA). Apta-NASBA has a 1 pM detection limit and can provide multiplexed, multicolor fluorescent readout. Furthermore, Apta-NASBA can be performed using a variety of equipment, for example, a fluorescence microplate reader, a qPCR instrument, or an ultra-low-cost Raspberry Pi-based 3D-printed detection platform using a cell phone camera module, compatible with field detection.
Encontros nas margens: percursos urbanos, corpo e desejo na filmografia de Marcelo Caetano
Authors: Ramalho Fabio Allan Mendes
Published: June 2020

Neste artigo, pretendemos discutir como os locais públicos e as zonas liminares desempenham um papel central nos filmes Bailão (2009), Na sua companhia (2011) e Corpo elétrico (2017), dirigidos por Marcelo Caetano. O que está em jogo nestas obras é a própria possibilidade de experienciar espaços urbanos como lugares de encontro afetivo e desejo erótico. Mediante um investimento em relações e itinerários à margem, traçamos uma tensão e também uma ambivalência recorrente em relação às cidades que os personagens habitam. A forma cinematográfica destaca a cidade como topografia imaginada e, ainda, como um plano de percepção composto por várias modulações entre desconexão e pertencimento, disciplina e prazer, proximidade e exclusão
Eye care in the intensive care unit during the COVID-19 pandemic
Authors: Sansome Stafford G , Lin Pei-Fen
Published: May 2020

Ocular complications in critical care patients are common. There has been a surge in intensive care admissions following the COVID-19 outbreak. The management of COVID-19 exposes patients to a number of specific risk factors for developing ocular complications, which include non-invasive ventilation, mechanical ventilation and prone positioning. Consequently, it is likely that there will be an increase in the number of ocular complications secondary to the management of COVID-19 patients in the intensive care unit setting, and these complications could lead to permanent visual loss and blindness. Increased awareness of eye care in the intensive care unit setting is therefore vital to help prevent visual loss and maintain quality of life for patients recovering from COVID-19.
EXPECTATIVAS ACADÉMICAS DEL ALUMNADO NO TRADICIONAL AL INICIO DE SUS ESTUDIOS UNIVERSITARIOS
Authors: De-Besa-Gutiérrez Manuel Rafael , Gil-Flores Javier
Published: June 2020

INTRODUCCIÓN. La presencia de alumnado no tradicional en la educación superior se ha incrementado en las últimas décadas. Las instituciones universitarias han de ofrecer una respuesta ajustada a las necesidades de este alumnado para facilitar su adaptación. En este sentido, las expectativas académicas previas han sido reconocidas como una variable que contribuye al ajuste de los estudiantes de nuevo ingreso. MÉTODO. En el presente estudio nos planteamos como objetivo conocer las expectativas de inicio de los estudiantes no tradicionales y determinar si estas difieren de las que caracterizan al alumnado tradicional. Además, pretendemos analizar la relación entre expectativas y rendimiento esperado. Para ello, hemos utilizado una muestra de 940 estudiantes de primer año en titulaciones de las cinco áreas de conocimiento que han respondido a un cuestionario de expectativas académicas. El análisis se ha apoyado en estadísticos descriptivos básicos, análisis de la varianza para muestras relacionadas, correlaciones, análisis multivariante de la varianza y prueba t, estimando el tamaño del efecto mediante la d de Cohen. RESULTADOS. Las expectativas del alumnado no tradicional son elevadas, aunque menores en comparación con los estudiantes tradicionales. Las principales diferencias afectan a las expectativas de no defraudar a las personas de su contexto inmediato, aprovechar oportunidades para una interacción social extracurricular y lograr una formación para el empleo. Unas mayores expectativas en el alumnado no tradicional se asocian, aunque débilmente, a esperar mayor rendimiento académico. DISCUSIÓN. Se derivan recomendaciones de cara a la actuación de las instituciones universitarias relacionadas con la empleabilidad y el desarrollo profesional y a la intervención orientadora sobre el alumnado no tradicional de nuevo ingreso, con el fin de atender a sus expectativas y favorecer su adaptación al contexto universitario.
Policy overreaction styles during manufactured crises
Authors: Maor Moshe
Published: June 2020

This article focuses on governments’ attempts to intensify crises for political gain, and identifies a series of unnecessary crisis management responses that follow distinctive policy overreaction styles. It is based on the premise that political executives at times face incentives to shape voters’ perceptions regarding the timing and scope of a crisis, even though no crisis actually exists. Analysing Trump’s response towards the so-called ‘invasion’ by a caravan of asylum seekers, the article identifies three distinctive crisis overreaction policy styles: communicating in absolutes, performing in absolutes, and challenging the rule of law. Each of these overreaction styles includes a specific set of tool preferences; an active means of implementation; and an impositional manner of execution. By highlighting the potential advantages of marrying the concept of crisis to the ideas of policy overreaction and policy style, this article makes an important contribution to our understanding of the politics of crisis management.