bluuebunny/crossref_metadata_2025 huggingface dataset:
Yoga Practice Among Veterans With and Without Chronic Pain
Authors: Donaldson Melvin T. , Neumark-Sztainer Dianne , Gaugler Joseph E. , Groessl Erik J. , Kehle-Forbes Shannon M. , Polusny Melissa A. , Krebs Erin E.
Published: August 2020

Objectives:

The primary aim of this study was to examine differences in yoga practice between persons with and without chronic pain. Secondarily, we describe use of the Essential Properties of Yoga Questionnaire, Short Form (EPYQ-SF) for self-report.

Design:

Participants were members of an existing cohort of veterans who completed a 2015–2016 survey focused on pain and nonpharmacological health practices. Cohort members who reported yoga in the past year [n=174 (9.4%) of 1850] were eligible for the present study, which used multiple-contact mixed-mode survey methodology to collect data on yoga practices. The EPYQ-SF was used to assess properties and context of yoga practice. Practice patterns were compared for participants with and without chronic pain. To explore potential reasons for reported yoga practice patterns, focused semistructured interviews were conducted with a subset of participants.

Results:

Of 174 participants contacted, 141 (82%) returned the yoga questionnaire and 110 (78% of respondents) were still practicing yoga. Among yoga practitioners, 41 (37%) had chronic pain. Practitioners with chronic pain reported gentler (2.8 vs. 3.1, 5-point scale) and less active (2.9 vs. 3.3) yoga practice than those without. Those with chronic pain attended yoga studios less frequently and reported shorter yoga practices than those without. Most yoga practice was self-directed and at home.

Conclusions:

Differences in yoga practice of persons with and without chronic pain have implications for implementation of yoga interventions for chronic pain. Future interventions should focus on alternative individual delivery formats or addressing barriers to group practice among people with chronic pain.
Provider Perspectives of Battlefield Acupuncture
Authors: Giannitrapani Karleen F. , Ackland Princess E. , Holliday Jesse , Zeliadt Steve , Olson Juli , Kligler Benjamin , Taylor Stephanie L.
Published: August 2020

Objectives:

Nonpharmacological options to treat pain are in demand, in part to address the opioid crisis. One such option is acupuncture. Battlefield acupuncture (BFA) is an auricular needling protocol currently used to treat pain in the Veterans Health Administration. We aimed to identify the advantages and disadvantages of BFA from providers’ perspectives.

Methods:

We rely on an inductive qualitative approach to explore provider perceptions through thematic analysis of semistructured interviews with 43 BFA providers across the nation.

Results:

We identified the following themes. Disadvantages included: (1) clinical guidelines are insufficient; (2) patients often request multiple BFA visits from providers; (3) BFA can be uncomfortable; (4) BFA may not be an effective treatment option unless it can be provided “on demand”; and (5) BFA can promote euphoria, which can have deleterious consequences for patient self-care. Perceived advantages included: (1) BFA can simultaneously effectively control pain while reducing opioid use; (2) BFA may alleviate the pain that has been unsuccessfully treated by conventional methods; (3) BFA gives providers a treatment option to offer patients with substance use disorder; (4) BFA helps build a trusting patient-provider relationship; (5) BFA can create the opportunity for hope.

Conclusions:

Providers perceive BFA to have many benefits, both clinical and relational, including ways in which it may have utility in addressing the current opioid crisis. BFA is easy to deliver and has potential clinical and relational utility. Efforts to better understand effectiveness are warranted.
Sleep Duration and Health Care Expenditures in the United States
Authors: Jasani Foram S. , Seixas Azizi A. , Madondo Kumbirai , Li Yan , Jean-Louis Girardin , Pagán José A.
Published: August 2020

Objective:

To estimate the average incremental health care expenditures associated with habitual long and short duration of sleep as compared with healthy/average sleep duration.

Data Source:

Medical Expenditure Panel Survey data (2012; N=6476) linked to the 2010–2011 National Health Interview Survey.

Study Design:

Annual differences in health care expenditures are estimated for habitual long and short duration sleepers as compared with average duration sleepers using 2-part logit generalized linear regression models.

Principal Findings:

Habitual short duration sleepers reported an additional $1400 in total unadjusted health care expenditures compared to people with average sleep duration (P<0.01). After adjusting for demographics, socioeconomic factors, and health behavior factors, this difference remained significant with an additional $1278 in total health care expenditures over average duration sleepers (P<0.05). Long duration sleepers reported even higher, $2994 additional health care expenditures over average duration sleepers. This difference in health care expenditures remained significantly high ($1500, P<0.01) in the adjusted model. Expenditure differences are more pronounced for inpatient hospitalization, office expenses, prescription expenses, and home health care expenditures.

Conclusions:

Habitual short and long sleep duration is associated with higher health care expenditures, which is consistent with the association between unhealthy sleep duration and poorer health outcomes.
Participating in Complementary and Integrative Health Approaches Is Associated With Veterans’ Patient-reported Outcomes Over Time
Authors: Elwy A. Rani , Taylor Stephanie L. , Zhao Shibei , McGowan Michael , Plumb Dorothy N. , Westleigh Wendy , Gaj Lauren , Yan Grace W. , Bokhour Barbara G.
Published: August 2020

Background:

Veterans Affairs is dedicated to providing a Whole Health approach to care, including offering complementary and integrative health (CIH) approaches to Veterans.

Objective:

The objective of this study was to examine the association of CIH participation with Veterans’ patient-reported outcomes over time.

Research Design:

A survey of patient-reported outcomes at 5 timepoints: baseline, 2, 4, 6, and 12 months.

Subjects:

Veterans participating in any type of CIH approach at 2 Veterans Affairs medical centers.

Measures:

Mixed hierarchical models with repeated variables were used to test the hypothesis that participating in any CIH approach would be associated with Veterans’ overall physical/mental health [Patient-Reported Outcomes Measurement Information System 28 (PROMIS 28)], pain intensity, perceived stress (Perceived Stress Scale-4), and engagement in their care (Patient Activation Measure-13), controlling for age, male sex, site, participation in other CIH approaches, and surveys completed.

Results:

We received 401 surveys from 119 Veterans (72% male, age range: 29–85 y) across all timepoints. Yoga participation was related to decreases in perceived stress (P<0.001), while tai chi participation was associated with improvements in overall PROMIS 28 physical and mental health functioning (P<0.02). Specific types of CIH were associated with significant improvements in PROMIS 28 subscales: meditation participation with physical functioning at 2, 6, and 12 months; tai chi participation with anxiety at 2 and 6 months, and ability to participate in social role activities at 2 months. No CIH approach was associated with Veterans’ pain or engagement in their care.

Conclusion:

As specific CIH approaches are associated with improvements in patient-reported outcomes, clinicians, Veterans, and family members may use this information in discussions of nonpharmacological options to address health and well-being.
The Association Between Hospital Characteristics and Emergency Medical Treatment and Labor Act Citation Events
Authors: Terp Sophie , Seabury Seth A. , Axeen Sarah , Pines Jesse M. , Lam Chun Nok , Arientyl Vanessa , Menchine Michael
Published: August 2020

Objectives:

The Emergency Medical Treatment and Labor Act (EMTALA) is a federal law enacted in 1986 prohibiting patient dumping (refusing or transferring patients with emergency medical conditions without appropriate stabilization), and discrimination based upon ability to pay. We evaluate hospital-level features associated with citation for EMTALA violation.

Materials and Methods:

A retrospective analysis of observational data on EMTALA enforcement (2005–2013). Regression analysis evaluates the association between facility-level features and odds of EMTALA citation by hospital-year.

Results:

Among 4916 EMTALA-obligated hospitals there were 1925 EMTALA citation events at 1413 facilities between 2005 and 2013, with 4.3% of hospitals cited per year. In adjusted analyses, increased odds of EMTALA citations were found at hospitals that were: for-profit [odds ratio (OR): 1.61; 95% confidence interval (CI): 1.32–1.96], in metropolitan areas (OR: 1.32; 95% CI: 1.11–1.57); that admitted a higher proportion of Medicaid patients (OR: 1.01; 95% CI: 1.0–1.01); and were in the top quartiles of hospital size (OR: 1.48; 95% CI: 1.10–1.99) and emergency department (ED) volume (OR: 1.56; 95% CI: 1.14–2.12). Predicted probability of repeat EMTALA citation in the year following initial citation was 17% among for-profit and 11% among other hospital types. Among citation events for patients presenting to the same hospital’s ED, there were 1.30 EMTALA citation events per million ED visits, with 1.04 at private not-for-profit, 1.47 at government-owned, and 2.46 at for-profit hospitals.

Conclusions:

For-profit ownership is associated with increased odds of EMTALA citations after adjusting for other characteristics. Efforts to improve EMTALA might be considered to protect access to emergency care for vulnerable populations, particularly at large, urban, for-profit hospitals admitting high proportions of Medicaid patients.
National Health Care Expenditures Associated With Disability
Authors: Khavjou Olga A. , Anderson Wayne L. , Honeycutt Amanda A. , Bates Laurel G. , Razzaghi Hilda , Hollis NaTasha D. , Grosse Scott D.
Published: August 2020

Background:

In 2003, national disability–associated health care expenditures (DAHE) were $398 billion. Updated estimates will improve our understanding of current DAHE.

Objective:

The objective of this study was to estimate national DAHE for the US adult population and analyze spending by insurance and service categories and to assess changes in spending over the past decade.

Research Design:

Data from the 2013–2015 Medical Expenditure Panel Survey were used to estimate DAHE for noninstitutionalized adults. These estimates were reconciled with National Health Expenditure Accounts (NHEA) data and adjusted to 2017 medical prices. Expenditures for institutionalized adults were added from NHEA data.

Measures:

National DAHE in total, by insurance and service categories, and percentage of total expenditures associated with disability.

Results:

DAHE in 2015 were $868 billion (at 2017 prices), representing 36% of total national health care spending (up from 27% in 2003). DAHE per person with disability increased from $13,395 in 2003 to $17,431 in 2015, whereas nondisability per-person spending remained constant (about $6700). Public insurers paid 69% of DAHE. Medicare paid the largest portion ($324.7 billion), and Medicaid DAHE were $277.2 billion. More than half (54%) of all Medicare expenditures and 72% of all Medicaid expenditures were associated with disability.

Conclusions:

The share of health care expenditures associated with disability has increased substantially over the past decade. The high proportion of DAHE paid by public insurers reinforces the importance of public programs designed to improve health care for people with disabilities and emphasizes the need for evaluating programs and health services available to this vulnerable population.
A Brief Report on an 8-Week Course of Mindfulness-based Care for Chronic Pain in the Treatment of Veterans With Back Pain
Authors: Eaton Erica , Swearingen Hannah R. , Zand Vakili Amin , Jones Stephanie R. , Greenberg Benjamin D.
Published: August 2020

Background:

Chronic pain and associated symptoms are debilitating for veterans. Medical costs of treatments are high and current treatment options, most notably with opioid medications, have been associated with significant risk. Mindfulness-based interventions appear promising for chronic pain, but require additional testing in veteran care settings.

Objective:

This project was designed to test the feasibility of engaging and retaining veterans with chronic lower back pain in a new mindfulness protocol tailored for veterans, mindfulness-based care for chronic pain (MBCP). Clinical outcomes were also assessed.

Design:

An open pilot trial of an 8-week MBCP course that included meditation, gentle yoga, and psychoeducation.

Subjects:

Twenty-two veterans (mean age=49.77; 18% women) were recruited from a VA Medical Center in the Northeastern US. After screening for inclusion/exclusion criteria, 20 were eligible at baseline.

Measures:

Veterans were assessed at baseline and postintervention for functional impairment, pain intensity and bothersomeness, depression, and mindfulness.

Results:

The average number of sessions completed was 5; only 4 (20%) attended all sessions. Eleven of the 20 participants (55%) attended 5 or more sessions and had complete preintervention and postintervention visits. Five of the 11 had a clinically meaningful decrease in pain intensity and in depressive symptoms, while 6 of 11 had a meaningful decrease in pain bothersomeness and functional impairment.

Conclusions:

It was challenging to enroll and retain participants in this study, even with our intervention designed for veterans. We discuss possible adaptations and refinements in MBCP for veterans with chronic pain to enhance feasibility and improve upon these interventions.
Role of the Immune System and the Circadian Rhythm in the Pathogenesis of Chronic Pancreatitis
Authors: Kessler Asa , Weksler-Zangen Sarah , Ilan Yaron
Published: August 2020

Pancreatitis, in both acute and chronic forms, poses a major therapeutic challenge and is associated with great morbidity and several complications. The nature of pancreatic injury in chronic pancreatitis (CP) and the wide range of causative processes that lead to CP have made effective therapy a true unmet need. Multiple physiological, genetic, environmental, and behavioral factors contribute to the development of CP. As a result, several fields of research are aimed at identifying and addressing the factors that contribute to pancreatic injury. In this article, we review the current understanding of the pathogenesis and natural history of CP. We focus on the autonomous nervous system, immune system, and role of a chronobiological therapeutic approach to alleviate symptoms and prevent or reverse pancreatic injury associated with CP. We aim to demonstrate that individualizing chronopharmacological treatments for CP is a promising direction for future treatment using immune, nervous, and circadian systems.
Outcomes of Febrile Neutropenia in Children With Cancer Managed on an Outpatient Basis: A Report From Tertiary Care Hospital From a Resource-limited Setting
Authors: Meena Jagdish P. , Gupta Aditya K. , Seth Rachna
Published: August 2020

In low-risk febrile neutropenia (FN) patients, outpatient management is now an accepted treatment, but there is a scarcity of data on high-risk patients. The aim of our study was to describe the outcome of FN treated primarily in an outpatient setting on the basis of the severity of illness at presentation, irrespective of the intensity of chemotherapy, and absolute neutrophil count. In this prospective study, not severely ill (NSI) patients were treated with empiric antibiotics at the daycare center (outpatient) and were admitted subsequently if there was persistent fever or any complication arose. Severely ill (SI) children were admitted to the hospital upfront. A total of 118 FN episodes among children with cancer on chemotherapy 18 years of age and younger were studied. Among NSI patients managed as outpatients (n=103), 89 patients (86%) recovered with outpatient treatment, and 14 patients required hospitalization after the median duration of 5 days (interquartile range: 4 to 6 d) of antibiotic therapy. The main indication for hospital admission in the SI group was hypotension (n=5), and in the NSI group, it was persistent fever (n=11). Overall, 5% of patients (6/118) died, and 2 of these were in the NSI group. The results of this study suggest that carefully selected NSI patients could be successfully treated at outpatient management in resource-poor settings and subsequent admission if warranted.
WNT-activated Pediatric Medulloblastoma Associated With Metastasis to the Suprasellar Region and Hypopituitarism
Authors: Ahmad Naveed , Eltawel Mohamed , Kashgari Amna , Alassiri Ali H.
Published: August 2020

We report on a rare association of WNT-activated medulloblastoma with metastasis to the suprasellar region. Medulloblastoma is the commonest brain tumor in children, and the most common pattern of metastatic disease is that of leptomeningeal involvement and spinal metastasis. Historically, medulloblastoma patients were categorized into different risk groups on the basis of age, histology, size of residium after surgery, and metastatic status, but the discovery of at least 4 molecular subgroups has changed the way these tumors are now treated. We report a 6-year-old patient who had a rare association of WNT-activated medulloblastoma with suprasellar metastasis and went on to develop hypopituitarism during the course of treatment. He remains alive 1 year after completing treatment.
Bone Mineral Metabolism During Chemotherapy in Childhood Acute Lymphoblastic Leukemia
Authors: Maddheshiya Sonal , Singh Surya K. , Kumar Ishan , Aggarwal Priyanka , Gupta Vineeta
Published: August 2020

Objective:

The aim of this study was to evaluate levels of vitamin D, bone mineral density (BMD), and radiograph features at diagnosis and after 6 months of chemotherapy in patients with acute lymphoblastic leukemia (ALL). Vitamin D levels were also correlated with BMD and radiograph features.

Materials and Methods:

25-Hydroxy vitamin D [25(OH)D] levels, BMD, and radiograph features were assessed in 50 newly diagnosed patients of ALL in the age group of 2 to 14 years. A total of 30 age-matched and sex-matched children were recruited as controls. Vitamin D deficiency was defined as 25(OH)D <10 ng/mL, Vitamin D insufficiency as 10 to 29 ng/mL, and Vitamin D sufficiency as ≥30 ng/mL. Enzyme immunoassay (EIA) was used for the quantitative measurement of 25(OH)D levels in plasma and a LUNAR DPX NT bone densitometer was used for the assessment of BMD.

Results:

The mean age of the patients was 6.3 years, with a male:female ratio of 1.38:1. The mean 25(OH)D levels were 31.90±16.90 ng/mL in patients at diagnosis against 41.63±20.50 ng/mL in controls (P=0.02). Levels were 18.50±11.10 ng/mL postchemotherapy (P=0.00). Female sex was a risk factor for deficient 25(OH)D levels. There was a significant decrease in BMD postchemotherapy in the age groups of 5 to 10 and above 10 years at the femoral neck. Osteopenic changes were observed in more number of patients after 6 months of chemotherapy. There was a significant correlation between vitamin D levels, BMD, and osteopenic changes.

Conclusions:

Vitamin D deficiency was common among ALL patients, which worsened after chemotherapy. This had a significant correlation with BMD and osteopenic changes in radiograph.
NUP98-NSD1 Driven MDS/MPN in Childhood Masquerading as JMML
Authors: Behnert Astrid , Lee Alex G. , Young Elizabeth P. , Breese Marcus R. , Leung Stanley G. , Behroozfard Inge , Maruffi Maria , Sweet-Cordero E. Alejandro , Dvorak Christopher C. , Chu Julia , Stieglitz Elliot
Published: August 2020

Overlapping myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are clonal hematopoietic disorders with features of myelodysplasia and myeloproliferation. The only well-characterized MDS/MPN in children is juvenile myelomonocytic leukemia, an aggressive disorder of infants and toddlers. The biochemical hallmark of this disease is hyperactivation of the Ras/MAPK signaling pathway caused by mutations in Ras pathway genes in more than 90% of patients. Translocations involving receptor tyrosine kinases have been identified in rare cases. Here, we report a 2-year-old patient who presented with MDS/MPN driven by a cytogenetically cryptic NUP98-NSD1 fusion, a translocation thought to exclusively occur in patients with acute myeloid leukemia.
Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients
Authors: Citera Gustavo , Mysler Eduardo , Madariaga Hugo , Cardiel Mario H. , Castañeda Oswaldo , Fischer Aryeh , Richette Pascal , Chartrand Sandra , Park Jin Kyun , Strengholt Sander , Rivas Jose L. , Thorat Amit V. , Girard Tanya , Kwok Kenneth , Wang Lisy , Ponce de Leon Dario
Published: August 2020

Background/Objective

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Interstitial lung disease (ILD) is an extra-articular manifestation of RA. We investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD.

Methods

This post hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 2 phase (P)1, 10 P2, 6 P3, 1 P3b/4, and 2 long-term extension studies. Interstitial lung disease events were adjudicated as “probable” (supportive clinical evidence) or “possible” (no supportive clinical evidence) compatible adverse events. Incidence rates (patients with events per 100 patient-years) were calculated for ILD events.

Results

Of 7061 patients (patient-years of exposure = 23,393.7), 42 (0.6%) had an ILD event; median time to ILD event was 1144 days. Incidence rates for ILD with both tofacitinib doses were 0.18 per 100 patient-years. Incidence rates generally remained stable over time. There were 17 of 42 serious adverse events (40.5%) of ILD; for all ILD events (serious and nonserious), 35 of 42 events (83.3%) were mild to moderate in severity. A multivariable Cox regression analysis identified age 65 years or older (hazard ratio 2.43 [95% confidence interval, 1.13–5.21]), current smokers (2.89 [1.33–6.26]), and Disease Activity Score in 28 joints–erythrocyte sedimentation rate score (1.30 [1.04–1.61]) as significant risk factors for ILD events.

Conclusions

Across P1/2/3/4/long-term extension studies, incidence rates for ILD events were 0.18 following tofacitinib treatment, and ILD events were associated with known risk factors for ILD in RA.
Validity of the Mini-Mental State Examination-2 in Diagnosing Mild Cognitive Impairment and Dementia in Patients Visiting an Outpatient Clinic in the Netherlands
Authors: Sleutjes Daan K.L. , Harmsen Iris J. , van Bergen Floor S. , Oosterman Joukje M. , Dautzenberg Paul L.J. , Kessels Roy P.C.
Published: August 2020

This study examined the utility of the recently published MMSE-2:SV in detecting cognitive impairment. We used receiver operating characteristics to test the discriminative power of the MMSE-2:SV for distinguishing between older adults without mild cognitive impairment (MCI) or dementia (n=67) and patients with MCI (n=76) or dementia (n=79). The results show that the MMSE-2:SV had excellent discriminative ability in distinguishing older controls from patients with dementia, with cut-off scores of 26 and 27 (max=30) yielding appropriate sensitivity (0.810 and 0.924, respectively) and specificity (0.940 and 0.806). Discriminative power was close to good in distinguishing between older controls and patients with MCI. Here, however, no optimal cut-off point could be determined. Even though this study shows good sensitivity and adequate specificity for the MMSE-2:SV in discriminating individuals without MCI or dementia from those with dementia, its validity is limited for identifying patients with MCI.
Plasma prolidase levels are high in schizophrenia but not in first-episode psychosis
Authors: Bolu Abdullah , Uzun Özcan , Burak Aydin Mikail , Ertuğrul Sebla , Öznur Taner , Çetinkaya Serdar , Erdem Onur , Nahit Özmenler Kamil
Published: August 2020

An increasing number of studies have focussed on the neurobiology of schizophrenia (SCH), contributing to a better understanding of this disorder. Prolidase is a metalloprotease found in various tissues, which has been associated with the concentrations of proline, a neurotransmitter, in the brain. There is evidence to suggest that elevated proline levels play a role in SCH. The aim of the present study was to compare plasma proline levels in patients with drug-naive first-episode psychosis (FEP) and in those with SCH. Patients diagnosed with FEP (n = 26) and SCH (n = 26) were recruited for this study, in addition to healthy control volunteers (n = 26). Plasma prolidase levels were found to be elevated in the SCH group compared to drug-naive FEP and healthy control groups. This finding indicates that prolidase levels are higher in SCH patients, while levels in patients with drug-naive FEP are similar to those of healthy control. Follow-up studies are needed to provide a better understanding of prolidase in the etiopathogenesis of SCH.
An increase in p62/NBR1 levels in melioidosis patients of Sri Lanka exhibit a characteristic of potential host biomarker
Authors: Saikh Kamal U. , Ranji Cyra M. , Ulrich Robert G. , Corea Enoka , De Silva Aruna Dharshan , Natesan Mohan
Published: August 2020

Introduction. Melioidosis, caused by

Burkholderia pseudomallei

, in endemic areas, poses a challenge for treating the diseased populations without accurate diagnosis, and the disease-specific biomarkers linked with the infection have yet to be reported. Due to the invasive nature of the causative agent,

Burkholderia pseudomallei

, host innate effector mechanisms, including autophagy are known to be activated, resulting in differential expression of cellular proteins and immune markers. Identification of a disease-specific biomarker associated with

B. pseudomallei

infection will be helpful to facilitate rapid confirmation of melioidosis, which would enable early treatment and therapeutic success.

Aim. We aimed to assess the levels of a host autophagy component, p62/NBR1, which function as a cargo-receptor in the process of autophagy activation leading to the degradation of ubiquitin-coated intracellular bacteria in which p62/NBR1 itself is degraded in the clearance of the pathogen. We further probed the extent of intracellular p62/NBR1 degradation and assessed its potential as a melioidosis biomarker.

Methodology. We analysed peripheral blood mononuclear cell (PBMC) lysates using an ELISA-based assay for detecting cytosolic autophagy-related proteins p62/NBR1. We measured p62/NBR1 levels in diseased (confirmed

B. pseudomallei

infection) and non -diseased populations and utilized receiver operating characteristic (ROC) curve and max Youden index analysis for evaluating potential disease biomarker characteristics.

Results. Our results revealed a three to fivefold increase in p62/NBR1 levels confirmed melioidosis cases compared to uninfected healthy donors. Comparable to p62/NBR1, levels of cytosolic LC3-I levels also increased, whereas the levels of degraded membrane bound form LC3-II was low, suggesting autophagy deficiency. Proinflammatory serum cytokine response, particularly IL-6, was consistently higher alongside

B. pseudomallei

infection in comparison to healthy controls.

Conclusions. ROC curve and max Youden index analysis suggest that increased p62/NBR1 levels in diseased populations display characteristics of a potential disease biomarker in melioidosis and illustrates that an elevated p62/NBR1 level, in conjunction with

B. pseudomallei

infection associated with autophagy deficiency.
Covid19data.website
Authors: Malouche Dhafer
Published: August 2020

Covid19data.website Project is a website that contains more than 250 Dashboards about the COVID-19 Toll areas affected by the virus. You can follow-up every day using this website the number of COVID-19 cases, deaths, active cases, the shares by 1 Million population, the mortality rate, the active rate in every country, continent, and territory and all States in the United States. Unlike the other websites, you can also follow-up an estimation of the reproduction number in the previous sixteen days. These statistics tell you how many secondary infections are likely to occur in a specific area.

Furthermore, I provide a classification algorithm of the countries and the affected areas. It’s based on the observation during the previous 14 days of six criteria. A global score is then computed, allowing to evaluate the COVID-19 safeness toll of each area.
Cell-Cell Adhesion During Nephron Development Is Driven by Wnt/PCP Formin Daam1
Authors: Krneta-Stankic Vanja , Corkins Mark , Paulucci-Holthauzen Adriana , Kloc Malgorzata , Gladden Andrew , Miller Rachel
Published: August 2020

E-cadherin junctions facilitate the assembly and disassembly of cell-cell contacts that drive development and homeostasis of epithelial tissues. The stability of E-cadherin-based junctions highly depends on their attachment to the actin cytoskeleton, but little is known about how the assembly of junctional actin filaments is regulated. Formins are a conserved group of proteins responsible for the formation and elongation of filamentous actin (F-actin). In this study, usingXenopusembryonic kidney and Madin-Darby canine kidney (MDCK) cells, we investigate the role of the Wnt/ planar cell polarity (PCP) formin protein Daam1 (Dishevelled-associated activator of morphogenesis 1) in regulating E-cadherin based intercellular adhesion. Using live imaging we show that Daam1 localizes to newly formed cell-cell contacts in the developing nephron. Furthermore, analyses of junctional F-actin upon Daam1 depletion indicate a decrease in microfilament localization and their slowed turnover. We also show that Daam1 is necessary for efficient and timely localization of junctional E-cadherin, which is mediated by Daam1’s formin homology domain 2 (FH2). Finally, we establish that Daam1 signaling is essential for promoting organized movement of renal cells. This study demonstrates that Daam1 formin junctional activity is critical for epithelial tissue organization.
Comparing Lifeact and Phalloidin for Super-resolution Imaging of Actin in Fixed Cells
Authors: Mazloom-Farsibaf Hanieh , Farzam Farzin , Fazel Mohamadreza , Wester Michael J. , Meddens Marjolein B. M. , Lidke Keith A.
Published: August 2020

Visualizing actin filaments in fixed cells is of great interest for a variety of topics in cell biology such as cell division, cell movement, and cell signaling. We investigated the possibility of replacing phalloidin, the standard reagent for super-resolution imaging of F-actin in fixed cells, with the actin binding peptide ‘lifeact’. We compared the labels for use in single molecule based super-resolution microscopy, where AlexaFluor 647 labeled phalloidin was used in a (d)STORM modality and Atto 655 labeled lifeact was used in a single molecule imaging, reversible binding modality. We found that imaging with lifeact had a comparable resolution in reconstructed images and provided several advantages over phalloidin including lower costs, the ability to image multiple regions of interest on a coverslip without degradation, simplified sequential super-resolution imaging, and more continuous labeling of thin filaments.
Integrated environmental and genomic analysis reveals the drivers of local adaptation in African indigenous chickens
Authors: Gheyas Almas A. , Trujillo Adriana Vallejo , Kebede Adebabay , Lozano-Jaramillo Maria , Dessie Tadelle , Smith Jacqueline , Hanotte Olivier
Published: August 2020

Elucidating the genetic basis of environmental adaptation in indigenous livestock populations has important implications for sustainable breeding improvement. It requires a detailed untangling of relevant environmental pressures and fine resolution detection of genomic signatures of selection associated with these environmental parameters. Here, we uniquely employed an integrative approach, combining Ecological Niche Modelling (ENM) with (i) genome-wide analyses of positive signatures of selection (SSA) and (ii) genotype-environment association (GEA) analyses to unravel the environmental adaptation of Ethiopian indigenous chickens. We first examined 34 agro-ecological and climatic variables and identified six main environmental selection drivers (one temperature - strongly correlated to elevation, three precipitation, and two soil/land variables). We then performed genomic analyses using high-density SNP data from whole-genome sequencing of 245 Ethiopian chickens from 25 different populations. Environmental genomic association analyses (SSA and GEA) identify a few strongly supported selected genomic regions, often with clusters of candidate genes, related to altitude-induced stresses (hypoxia, thrombosis, and cold temperatures), water scarcity, and the challenges of scavenging feeding behaviour. These analyses support a predominantly oligogenic control of environmental adaptation and possible regulation by one or few genetic elements only. Our study shows that the pre-identification of the key environmental drivers of adaptation, followed by a detailed genomic investigation of the associated genetic mechanisms provides a powerful new approach for elucidating the effect of natural selection in domestic animals. These results represent new landmarks to inform sustainable poultry breeding improvement.
A small molecule screen identified N-Acetyl-L-cysteine for promotingex vivogrowth of single circulating tumor cells
Authors: Teng Teng , Kamal Mohamed , Iriondo Oihana , Amzaleg Yonatan , Luo Chunqiao , Thomas Amal , Lee Grace , Nguyen John D. , Smith Andrew , Sposto Richard , Yu Min
Published: August 2020

Circulating tumor cells (CTCs) can be isolated via a minimally invasive blood draw and are considered a “liquid biopsy” of their originating solid tumors. CTCs contain a small subset of metastatic precursors that can form metastases in secondary organs, and provide a resource to identify mechanisms underlying metastasis-initiating properties. Despite technological advancements that allow for highly sensitive approaches of detection and isolation, CTCs are very rare and often present as single cells, posing an extreme challenge forex vivoexpansion after isolation. Here, using previously established patient-derived CTC lines, we performed a small molecule drug screening to identify compounds that can improveex vivoculture efficiency for single CTCs. We found that N-acetylcysteine (NAC) and other antioxidants can promoteex vivoexpansion of single CTCs, by reducing oxidative and other stress particularly at the initial stage of single cell expansion. RNA-seq analysis of growing clones and non-growing clones confirmed the effect by NAC, but also indicate that NAC-induced decrease in oxidative stress is insufficient for promoting proliferation of a subset of cells with heterogeneous quiescent and senescent features. Despite the challenge in expanding all CTCs, NAC treatment lead to establishment of single CTC clones that have similar tumorigenic features, which will facilitate future functional analyses.
Photocatalytic plant LPOR forms helical lattices that shape membranes for chlorophyll synthesis
Authors: Nguyen Henry C. , Melo Arthur A. , Kruk Jerzy , Frost Adam , Gabruk Michal
Published: August 2020

Chlorophyll (Chl) biosynthesis, crucial to life on Earth, is tightly regulated because its precursors are phototoxic1. In flowering plants, the enzyme Light-dependent Protochlorophyllide OxidoReductase (LPOR) captures photons to catalyze the penultimate reaction: the reduction of a double-bond within protochlorophyllide (Pchlide) to generate chlorophyllide (Chlide)2,3. In darkness, LPOR oligomerizes to facilitate photon energy transfer and catalysis4,5. However, the complete 3D structure of LPOR, the higher-order architecture of LPOR oligomers, and the implications of these self-assembled states for catalysis, including how LPOR positions Pchlide and the cofactor NADPH, remain unknown. Here we report the atomic structure of LPOR assemblies by electron cryo-microscopy (cryoEM). LPOR polymerizes with its substrates into helical filaments around constricted lipid bilayer tubes. Portions of LPOR and Pchlide insert into the outer membrane leaflet, targeting the product, Chlide, to the membrane for the final reaction site of chlorophyll biosynthesis. In addition to its crucial photocatalytic role, we show that in darkness LPOR filaments directly shape membranes into high-curvature tubules with the spectral properties of the prolammelar body, whose light-triggered disassembly provides lipids for thylakoid assembly. Our structure of the catalytic site, moreover, challenges previously proposed reaction mechanisms6. Together, our results reveal a new and unexpected synergy between photosynthetic membrane biogenesis and chlorophyll synthesis in plants orchestrated by LPOR.
Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons
Authors: Hahn Ines , Voelzmann Andre , Parkin Jill , Fuelle Judith , Slater Paula G , Lowery Laura A , Sanchez-Soriano Natalia , Prokop Andreas
Published: August 2020

The formation and maintenance of microtubules requires their polymerisation, but little is known about how this polymerisation is regulated in cells. Focussing on the essential microtubule bundles in axons ofDrosophilaandXenopusneurons, we show that the plus-end scaffold Eb1, the polymerase XMAP215/Msps and the lattice-binder Tau co-operate interdependently to promote microtubule polymerisation and bundle organisation during axon development and maintenance. Eb1 and XMAP215/Msps promote each other’s localisation at polymerising microtubule plus-ends. Tau outcompetes Eb1-binding along microtubule lattices, thus preventing depletion of Eb1 tip pools. The three factors genetically interact and show shared mutant phenotypes: reductions in axon growth, comet size, comet number and comet velocity, as well as prominent deterioration of parallel microtubule bundles into disorganised curled conformations. This microtubule curling is caused by Eb1 plus-end depletion which impairs spectraplakin-mediated guidance of extending microtubules into parallel bundles. Our demonstration that Eb1, XMAP215/Msps and Tau co-operate during the regulation of microtubule polymerisation and bundle organisation, offers new conceptual explanations for developmental and degenerative axon pathologies and how to treat them.

Summary statement

Eb1, XMAP215 and tau co-operate interdependently in axons to promote the polymerisation of microtubules and their organisation into the parallel bundles required for axonal transport.
N6-methyladenine DNA demethylase ALKBH1 regulates mammalian axon regeneration
Authors: Li Qiao , Qian Cheng , Feng Harry , Lin Tyger , Huang Ying , Zhou Feng-Quan
Published: August 2020

Recent studies have shown that DNA N6-methyladenine (N6-mA) modification is emerging to be a novel and important epigenetic regulator of mammalian gene transcription. Several studies demonstrated DNA N6-mA in human or rodents was regulated by methyltransferase N6AMT1 and demethylase ALKBH1. Moreover, studies in mouse brain or human glioblastoma cells showed that reduced level of N6-mA or higher level of ALKBH1 was correlated with up regulated levels of genes associated with neuronal development. We thus investigated the functional roles of ALKBH1 in sensory axon regeneration. Our results showed that ALKBH1 regulated the level of N6-mA in sensory neurons, and upon peripheral nerve injury ALKBH1 was up regulated in mouse sensory neurons. Functionally, knocking down ALKBH1 in sensory neurons resulted in reduced axon regenerationin vitroandin vivo, which could be rescued by simultaneously knocking down N6AMT1. Moreover, knocking down ALKBH1 led to decreased levels of many neurodevelopment regulatory genes, including neuritin that is well known to enhance axon growth and regeneration. Our study not only revealed a novel physiological function of DNA N6-mA, but also identified a new epigenetic mechanism regulating mammalian axon regeneration.

Significance Statement

The study demonstrated that DNA N6-methyladenine (N6-mA) modification played important roles in regulation of sensory axon regeneration, likely through controlling the expression of neurodevelopmental associated genes. The results will add new evidence about the physiological function of DNA N6-mA and its regulatory demethylase ALKBH1 in neurons.
Variational Inference Using Approximate Likelihood Under the Coalescent With Recombination
Authors: Liu Xinhao , Ogilvie Huw A. , Nakhleh Luay
Published: August 2020

Coalescent methods are proven and powerful tools for population genetics, phylogenetics, epidemiology, and other fields. A promising avenue for the analysis of large genomic alignments, which are increasingly common, are coalescent hidden Markov model (coalHMM) methods, but these methods have lacked general usability and flexibility. We introduce a novel method for automatically learning a coalHMM and inferring the posterior distributions of evolutionary parameters using black-box variational inference, with the transition rates between local genealogies derived empirically by simulation. This derivation enables our method to work directly with three or four taxa and through a divide-and-conquer approach with more taxa. Using a simulated data set resembling a human-chimp-gorilla scenario, we show that our method has comparable or better accuracy to previous coalHMM methods. Both species divergence times and population sizes were accurately inferred. The method also infers local genealogies and we report on their accuracy. Furthermore, we illustrate how to scale the method to larger data sets through a divide-and-conquer approach. This accuracy means our method is useful now, and by deriving transition rates by simulation it is flexible enough to enable future implementations of all kinds of population models.
Neural decoding of gait phase information during motor imagery and improvement of the decoding accuracy by concurrent action observation
Authors: Yokoyama Hikaru , Kaneko Naotsugu , Watanabe Katsumi , Nakazawa Kimitaka
Published: August 2020

Brain decoding of motor imagery (MI) is crucial for the control of neuroprosthesis, and it provides insights into the underlying neural mechanisms. Walking consists of stance and swing phases, which are associated with different biomechanical and neural control features. However, previous studies on the decoding of the MI of walking focused on the classification of more simple information (e.g., walk and rest). Here, we investigated the feasibility of electroencephalogram (EEG) decoding of the two gait phases during the MI of walking and whether the combined use of MI and action observation (AO) would improve decoding accuracy. We demonstrated that the stance and swing phases could be decoded from EEGs during AO or MI alone. Additionally, the combined use of MI and AO improved decoding accuracy. The decoding models indicated that the improved decoding accuracy following the combined use of MI and AO was facilitated by the additional information resulting from the concurrent cortical activations by multiple regions associated with MI and AO. This study is the first to show that decoding the stance versus swing phases during MI is feasible. The current findings provide fundamental knowledge for neuroprosthetic design and gait rehabilitation, and they expand our understanding of the neural activity underlying AO, MI, and AO+MI of walking.

Significance Statement

Brain decoding of detailed gait-related information during motor imagery (MI) is important for brain-computer interfaces (BCIs) for gait rehabilitation. However, previous knowledge on decoding the motor imagery of gait is limited to simple information (e.g., the classification of “walking” and “rest”). Here, we demonstrated the feasibility of EEG decoding of the two gait phases during MI. We also demonstrated that the combined use of MI and action observation (AO) improves decoding accuracy, which is facilitated by the concurrent and synergistic involvement of the cortical activations by multiple regions for MI and AO. These findings extend the current understanding of neural activity and the combined effects of AO and MI and provide a basis for developing effective techniques for walking rehabilitation.
Non-ionotropic NMDA receptor signaling gates bidirectional structural plasticity of dendritic spines
Authors: Stein Ivar S. , Park Deborah K. , Claiborne Nicole , Zito Karen
Published: August 2020

Experience-dependent refinement of neuronal connections is critically important for brain development and learning. Here we show that ion flow-independent NMDAR signaling is required for the long-term dendritic spine growth that is a vital component of brain circuit plasticity. We found that inhibition of p38 MAPK, shown to be downstream of non-ionotropic NMDAR signaling in LTD and spine shrinkage, blocked LTP-induced spine growth but not LTP. We hypothesized that non-ionotropic NMDAR signaling drives the cytoskeletal changes that support bidirectional spine structural plasticity. Indeed, we found that key signaling components downstream of non-ionotropic NMDAR function in LTD-induced spine shrinkage also are necessary for LTP-induced spine growth. Furthermore, NMDAR conformational signaling with coincident Ca2+influx is sufficient to drive CaMKII-dependent long-term spine growth, even when Ca2+is artificially driven through voltage-gated Ca2+channels. Our results support a model in which non-ionotropic NMDAR signaling gates the bidirectional spine structural changes vital for brain plasticity.
Coordination of pupil and saccade responses by the superior colliculus
Authors: Wang Chin-An , Munoz Douglas P.
Published: August 2020

The appearance of a salient stimulus evokes saccadic eye movements and pupil dilation as part of the orienting response. Although the role of the superior colliculus (SC) in saccade and pupil dilation has been established separately, whether and how these responses are coordinated remains unknown. The SC also receives global luminance signals from the retina, but whether global luminance modulates saccade and pupil responses coordinated by the SC remains unknown. Here, we used microstimulation to causally determine how the SC coordinates saccade and pupil responses, and whether global luminance modulates these responses by varying stimulation frequency and global luminance in male monkeys. Stimulation frequency modulated saccade and pupil responses, with trial-by-trial correlations between the two responses. Global luminance only modulated pupil, but not, saccade responses. Our results demonstrate an integrated role of the SC on coordinating saccade and pupil responses, characterizing luminance independent modulation in the SC, together elucidating the differentiated pathways underlying this behavior.
New examples of non-cooperative octahedral tilting in a double perovskite: phase transitions in K3GaF6
Authors: King Graham
Published: August 2020

The crystal structures of three polymorphs of K3GaF6 and the transition temperatures between these phases are reported for the first time. Synchrotron powder diffraction data clearly show that at 300 K α-K3GaF6 crystallizes in space group I41/a with lattice parameters of a = 19.1124 (3) Å, c = 34.4165 (6) Å, and Z = 80. The structure is based on the double perovskite but with two fifths of the GaF6 octahedra rotated by ∼45°. This phase remains stable until ∼460 K, above which it undergoes a transition to I4/m with lattice parameters of a = 13.6088 (4) Å, c = 8.6764 (3) Å, and Z = 10 at 485 K. β-K3GaF6 has a similar structure but with only one fifth of the GaF6 rotated by ∼45°. Above ∼510 K, the cubic Fm
3
m δ-K3GaF6 structure is stabilized, with a lattice parameter of a = 8.6649 (1) Å at 550 K. The F atoms have highly anisotropic displacement parameters which suggest dynamic octahedral tilting is occurring. This work expands the fairly small group of double perovskite compounds which display non-cooperative patterns of octahedral tilting.