bluuebunny/crossref_metadata_2025_split huggingface dataset:
Providing reproductive health services for women who inject drugs: a pilot program
Authors: Owens Lauren , Gilmore Kelly , Terplan Mishka , Prager Sarah , Micks Elizabeth 
Published: July 2020

Abstract
Background
Needle syringe programs (NSPs), a proven harm reduction strategy for people who inject drugs, frequently offer limited healthcare services for their clients. Women who inject drugs face multiple barriers to accessing reproductive health care in traditional settings: personal histories of trauma, judgmental treatment from providers, and competing demands on their time. Our aim was to implement patient-centered reproductive healthcare services at a Seattle NSP.

Methods
We interviewed clients and staff of an NSP in Seattle and staff of other community-based organizations serving women who inject drugs, then used the Consolidated Framework for Implementation Research to code transcripts deductively. Based on our qualitative work, we implemented reproductive health care at the NSP program 1 day per week. We evaluated the implementation by surveying staff and clients and auditing charts over a 9-month period.

Results
Clients and staff (N = 15 for clients, N = 13 for staff) noted a high unmet need for trauma-informed, accessible reproductive health care. We successfully implemented reproductive health care services including short- and long-acting contraception, sexually transmitted disease testing, and cervical cancer screening. Survey data was limited but demonstrated client satisfaction with services.

Conclusions
Integrating reproductive health care into an NSP’s clinical services is feasible and can be a source of low-barrier preventive care for women unable to seek gynecologic care elsewhere.
BDNF reverses aging-related microglial activation
Authors: Wu Shih-Ying , Pan Bo-Syong , Tsai Sheng-Feng , Chiang Yi-Ting , Huang Bu-Miin , Mo Fan-E , Kuo Yu-Min 
Published: July 2020

AbstractBackgroundExcessive microglial activation is implicated in the pathogenesis of various age-related neurodegenerative diseases. In addition to neurons, brain-derived neurotrophic factor (BDNF) and its receptor TrkB are also expressed in microglia. However, the direct effect of BDNF on age-related microglial activation has rarely been investigated.MethodsWe began to address this question by examining the effect of age on microglial activation and the BDNF-TrkB pathway in mice. By using pharmacological and genetic approaches, the roles of BDNF and downstream signaling pathways in microglial activation and related neurotoxicity were examined in microglial cell line and primary microglial cells.ResultsWe showed that microglial activation was evident in the brains of aged mice. The levels of BDNF and TrkB in microglia decreased with age and negatively correlated with their activation statuses in mice during aging. Interestingly, aging-related microglial activation could be reversed by chronic, subcutaneous perfusion of BDNF. Peripheral lipopolysaccharide (LPS) injection-induced microglial activation could be reduced by local supplement of BDNF, while shTrkB induced local microglial activation in naïve mice. In cultured microglial cell line and primary microglial cells, BDNF inhibited LPS-induced microglial activation, including morphological changes, activations of p38, JNK, and NF-кB, and productions of proinflammatory cytokines. These effects were blocked by shTrkB. BDNF induced activations of ErK and CREB which then competed with LPS-induced activation of NF-кB for binding to a common coactivator, CREB-binding protein.ConclusionsDecreasing BDNF-TrkB signaling during aging favors microglial activation, while upregulation BDNF signaling inhibits microglial activation via the TrkB-Erk-CREB pathway.
Nonoperative treatment versus volar locking plate fixation for elderly patients with distal radial fracture: a systematic review and meta-analysis
Authors: Li Qiang , Ke Chao , Han Shuang , Xu Xin , Cong Yu-Xuan , Shang Kun , Liang Ji-Dong , Zhang Bin-Fei 
Published: July 2020

Abstract
Background
This systematic review and meta-analysis assessed the role of nonoperative treatment and volar locking plate (VLP) fixation in elderly patients with distal radial fracture.

Methods
The systematic literature review identified randomized controlled trials (RCTs) and observational studies using VLP and nonoperative treatment for distal radial fractures in the elderly. Two investigators independently extracted data and evaluated the quality of the studies. A meta-analysis was performed using RevMan version 5.3.

Results
The five RCTs and six observational studies included 585 and 604 patients in the VLP and nonoperation groups, respectively. The quality of these 11 studies was moderate. Compared to nonoperation treatment, VLP did not improve the disabilities of the arm, shoulder and hand (DASH) score (weighted mean difference [WMD] = −1.67; 95% confidence interval [CI], −3.58–−0.24; P = 0.09), decrease complications (odds ratio = 1.05; 95% CI, 0.51–2.19; P = 0.89), or improve range of motion in flexion, extension, pronation, supination, and radial deviation. The VLP group had better grip strength (WMD = 10.52; 95% CI, 6.19–14.86; P < 0.0001) and radiographic assessment than the nonoperation group.

Conclusions
Although insufficient, the study evidence shows that VLP does not improve DASH scores, complications, or range of motion, but it might provide better grip strength and radiographic assessment than nonoperation treatment.
Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy
Authors: Cortes Jorge E. , Heidel Florian H. , Fiedler Walter , Smith B. Douglas , Robak Tadeusz , Montesinos Pau , Candoni Anna , Leber Brian , Sekeres Mikkael A. , Pollyea Daniel A. , Ferdinand Roxanne , Ma Weidong Wendy , O’Brien Thomas , O’Connell Ashleigh , Chan Geoffrey , Heuser Michael 
Published: July 2020

Abstract
Background
The phase 2 BRIGHT AML 1003 trial evaluated efficacy and safety of glasdegib + low-dose cytarabine (LDAC) in patients with acute myeloid leukemia ineligible for intensive chemotherapy. The multicenter, open-label study randomized patients to receive glasdegib + LDAC (n = 78) or LDAC alone (n = 38). The rate of complete remission (CR) was 19.2% in the glasdegib + LDAC arm versus 2.6% in the LDAC arm (P = 0.015).

Methods
This post hoc analysis determines whether the clinical benefits of glasdegib are restricted to patients who achieve CR, or if they extend to those who do not achieve CR.

Results
In patients who did not achieve CR, the addition of glasdegib to LDAC improved overall survival (OS) versus LDAC alone (hazard ratio = 0.63 [95% confidence interval, 0.41–0.98]; P = 0.0182; median OS, 5.0 vs 4.1 months). Additionally, more patients receiving glasdegib + LDAC achieved durable recovery of absolute neutrophil count (≥ 1000/μl, 45.6% vs 35.5%), hemoglobin (≥ 9 g/dl, 54.4% vs 38.7%), and platelets (≥ 100,000/μl, 29.8% vs 9.7%). Transfusion independence was achieved by 15.0% and 2.9% of patients receiving glasdegib + LDAC and LDAC alone, respectively.

Conclusions
Collectively, these data suggest that there are clinical benefits with glasdegib in the absence of CR.

Trial registration
ClinicalTrials.gov NCT01546038 (March 7, 2012)
Beyond thrombosis: the impact of tissue factor signaling in cancer
Authors: Unruh Dusten , Horbinski Craig 
Published: July 2020

AbstractTissue factor (TF) is the primary initiator of the coagulation cascade, though its effects extend well beyond hemostasis. When TF binds to Factor VII, the resulting TF:FVIIa complex can proteolytically cleave transmembrane G protein-coupled protease-activated receptors (PARs). In addition to activating PARs, TF:FVIIa complex can also activate receptor tyrosine kinases (RTKs) and integrins. These signaling pathways are utilized by tumors to increase cell proliferation, angiogenesis, metastasis, and cancer stem-like cell maintenance. Herein, we review in detail the regulation of TF expression, mechanisms of TF signaling, their pathological consequences, and how it is being targeted in experimental cancer therapeutics.
A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward
Authors: Wang Bo , Van Oekelen Oliver , Mouhieddine Tarek H. , Del Valle Diane Marie , Richter Joshua , Cho Hearn Jay , Richard Shambavi , Chari Ajai , Gnjatic Sacha , Merad Miriam , Jagannath Sundar , Parekh Samir , Madduri Deepu 
Published: July 2020

Abstract
Background
The COVID-19 pandemic, caused by SARS-CoV-2 virus, has resulted in over 100,000 deaths in the USA. Our institution has treated over 2000 COVID-19 patients during the pandemic in New York City. The pandemic directly impacted cancer patients and the organization of cancer care. Mount Sinai Hospital has a large and diverse multiple myeloma (MM) population. Herein, we report the characteristics of COVID-19 infection and serological response in MM patients in a large tertiary care institution in New York.

Methods
We performed a retrospective study on a cohort of 58 patients with a plasma-cell disorder (54 MM, 4 smoldering MM) who developed COVID-19 between March 1, 2020, and April 30, 2020. We report epidemiological, clinical, and laboratory characteristics including the persistence of viral detection by polymerase chain reaction (PCR) and anti-SARS-CoV-2 antibody testing, treatments initiated, and outcomes.

Results
Of the 58 patients diagnosed with COVID-19, 36 were hospitalized and 22 were managed at home. The median age was 67 years; 52% of patients were male and 63% were non-White. Hypertension (64%), hyperlipidemia (62%), obesity (37%), diabetes mellitus (28%), chronic kidney disease (24%), and lung disease (21%) were the most common comorbidities. In the total cohort, 14 patients (24%) died. Older age (> 70 years), male sex, cardiovascular risk, and patients not in complete remission (CR) or stringent CR were significantly (p < 0.05) associated with hospitalization. Among hospitalized patients, laboratory findings demonstrated elevation of traditional inflammatory markers (CRP, ferritin, D-dimer) and a significant (p < 0.05) association between elevated inflammatory markers, severe hypogammaglobulinemia, non-White race, and mortality. Ninety-six percent (22/23) of patients developed antibodies to SARS-CoV-2 at a median of 32 days after initial diagnosis. The median time to PCR negativity was 43 (range 19–68) days from initial positive PCR.

Conclusions
Drug exposure and MM disease status at the time of contracting COVID-19 had no bearing on mortality. Mounting a severe inflammatory response to SARS-CoV-2 and severe hypogammaglobulinemia was associated with higher mortality. The majority of patients mounted an antibody response to SARS-CoV-2. These findings pave a path to the identification of vulnerable MM patients who need early intervention to improve outcomes in future outbreaks of COVID-19.
A subset of activated fibroblasts is associated with distant relapse in early luminal breast cancer
Authors: Bonneau Claire , Eliès Antoine , Kieffer Yann , Bourachot Brigitte , Ladoire Sylvain , Pelon Floriane , Hequet Delphine , Guinebretière Jean-Marc , Blanchet Christophe , Vincent-Salomon Anne , Rouzier Roman , Mechta-Grigoriou Fatima 
Published: July 2020

AbstractBackgroundEarly luminal breast cancer (BC) represents 70% of newly diagnosed BC cases. Among them, small (under 2 cm) BC without lymph node metastasis (classified as T1N0) have been rarely studied, as their prognosis is generally favorable. Nevertheless, up to 5% of luminal T1N0 BC patients relapse with distant metastases that ultimately prove fatal. The aim of our work was to identify the mechanisms involved in metastatic recurrence in these patients.MethodsOur study addresses the role that autonomous and non-autonomous tumor cell features play with regard to distant recurrence in early luminal BC patients. We created a cohort of T1N0 luminal BC patients (tumors between 0.5–2 cm without lymph node metastasis) with metastatic recurrence (“cases”) and corresponding “controls” (without relapse) matched 1:1 on main prognostic factors: age, grade, and proliferation. We deciphered different characteristics of cancer cells and their tumor micro-environment (TME) by deep analyses using immunohistochemistry. We performed in vitro functional assays and highlighted a new mechanism of cooperation between cancer cells and one particular subset of cancer-associated fibroblasts (CAF).ResultsWe found that specific TME features are indicative of relapse in early luminal BC. Indeed, quantitative histological analyses reveal that “cases” are characterized by significant accumulation of a particular CAF subset (CAF-S1) and decrease in CD4+T lymphocytes, without any other association with immune cells. In multivariate analysis, TME features, in particular CAF-S1 enrichment, remain significantly associated with recurrence, thereby demonstrating their clinical relevance. Finally, by performing functional analyses, we demonstrated that CAF-S1 pro-metastatic activity is mediated by the CDH11/osteoblast cadherin, consistent with bones being a major site of metastases in luminal BC patients.ConclusionsThis study shows that distant recurrence in T1N0 BC is strongly associated with the presence of CAF-S1 fibroblasts. Moreover, we identify CDH11 as a key player in CAF-S1-mediated pro-metastatic activity. This is independent of tumor cells and represents a new prognostic factor. These results could assist clinicians in identifying luminal BC patients with high risk of relapse. Targeted therapies against CAF-S1 using anti-FAP antibody or CDH11-targeting compounds might help in preventing relapse for such patients with activated stroma.
Where is an emotion? Using targeted visceroception as a method of improving emotion regulation in healthy participants to inform suicide prevention initiatives: a randomised controlled trial
Authors: Davey Steven , Bell Elliot , Halberstadt Jamin , Collings Sunny 
Published: July 2020

AbstractBackgroundWilliam James’ 1884 paper “What is an emotion?” has generated much recent interest in affective science regarding somatic contributions to emotion. Studies of interoception (“sensing the physiological condition of the body”) suggest that sensing specific parts of the body contributes to the production of emotion, namely when sensing the viscera (i.e. “visceroception” of the heart, gut or lungs). Improved visceroception has, for instance, been linked to increased emotional intensity, suggesting a role for interoception in emotion regulation that may pertain specifically to visceral bodily locations. Thus, in addition to asking James’ question, “Whatis an emotion?”, we ask, “Whereis an emotion?”. Further, there is an evidence base pointing to the connections between emotion regulation and suicide, and between interoception and suicide. This is a preliminary trial investigating whether targeted interoception/visceroception improves emotion regulation. Ultimately, the overall project aims to inform suicide prevention efforts.MethodsThe trial utilises a pre-test/post-test control group design, with two experimental groups undergoing visceroceptive interventions (focussing on areas pertaining to the gut or heart) and a control group. The interventions will run for 8 weeks. A spatial cueing task will measure reaction times to bodily changes relating to lower abdomen or chest focus. A stop/signal task will measure emotional inhibition, which is hypothesised to obscure awareness of active bodily locations. Visceroceptive ability will be tracked using a heartbeat estimation task, a water load test, and by self-report questionnaire. The sample will consist of healthcare professionals and healthcare students. Despite these being groups that represent a relatively high suicide risk among professional and student groups, all participants will be healthy, given the preliminary nature of this trial.DiscussionTo our knowledge, this will be the first project to address whether emotional feeling presents as a localised bodily phenomenon and whether trained awareness of emotional localisation can improve emotion regulation. It will also be the first to investigate relationships between interoception and emotional inhibition (i.e. whether a sustained interoceptive practice leads to the disinhibition of bodily emotional sensations, which can positively contribute to emotion regulation). These empirical findings on emotion regulation from a healthy sample will be used to inform a desk-based enquiry into the role of embodied emotion in suicide prevention, which may make a significant contribution to a growing evidence base on interoception and suicide.Trial registrationACTRN12619000324112. Registered on 4 March 2019. Universal Trial Number (UTN): U1111-1221-0201.
Large-scale countrywide screening for tick-borne pathogens in field-collected ticks in Latvia during 2017–2019
Authors: Capligina Valentina , Seleznova Maija , Akopjana Sarmite , Freimane Lauma , Lazovska Marija , Krumins Rudolfs , Kivrane Agnija , Namina Agne , Aleinikova Darja , Kimsis Janis , Kazarina Alisa , Igumnova Viktorija , Bormane Antra , Ranka Renate 
Published: July 2020

Abstract
Background
Tick-borne diseases are of substantial concern worldwide in both humans and animals. Several hard tick species are of medical and veterinary interest in Europe, and changes in the range of tick species can affect the spread of zoonotic pathogens. The aim of the present study was to map the current prevalence and distribution pattern of ticks and related tick-borne pathogens in Latvia, a Baltic state in northern Europe.

Methods
Nearly 4600 Ixodes ricinus, I. persulcatus and Dermacentor reticulatus tick samples were collected in all regions of Latvia during 2017–2019 and were screened by molecular methods to reveal the prevalence and distribution pattern of a wide spectrum of tick-borne pathogens.

Results
New localities of D. reticulatus occurrence were found in western and central Latvia, including the Riga region, indicating that the northern border of D. reticulatus in Europe has moved farther to the north. Among the analyzed ticks, 33.42% carried at least one tick-borne pathogen, and 5.55% of tick samples were positive for two or three pathogens. A higher overall prevalence of tick-borne pathogens was observed in I. ricinus (34.92%) and I. persulcatus (31.65%) than in D. reticulatus (24.2%). The molecular analysis revealed the presence of tick-borne encephalitis virus, Babesia spp., Borrelia spp., Anaplasma phagocytophilum and Rickettsia spp. Overall, 15 and 7 tick-borne pathogen species were detected in Ixodes spp. and D. reticulatus ticks, respectively. This is the first report of Borrelia miyamotoi in Latvian field-collected ticks.

Conclusions
This large-scale countrywide study provides a snapshot of the current distribution patterns of Ixodes and Dermacentor ticks in Latvia and gives us a reliable overview of tick-borne pathogens in Latvian field-collected ticks.
NAFLD as a continuum: from obesity to metabolic syndrome and diabetes
Authors: Godoy-Matos Amélio F. , Silva Júnior Wellington S. , Valerio Cynthia M. 
Published: July 2020

Abstract
Background
The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly. It is nowadays recognized as the most frequent liver disease, affecting a quarter of global population and regularly coexisting with metabolic disorders such as type 2 diabetes, hypertension, obesity, and cardiovascular disease. In a more simplistic view, NAFLD could be defined as an increase in liver fat content, in the absence of secondary cause of steatosis. In fact, the clinical onset of the disease is a much more complex process, closely related to insulin resistance, limited expandability and dysfunctionality of adipose tissue. A fatty liver is a main driver for a new recognized liver-pancreatic α-cell axis and increased glucagon, contributing to diabetes pathophysiology.

Main text
This review will focus on the clinical and pathophysiological connections between NAFLD, insulin resistance and type 2 diabetes. We reviewed non-invasive methods and several scoring systems for estimative of steatosis and fibrosis, proposing a multistep process for NAFLD evaluation. We will also discuss treatment options with a more comprehensive view, focusing on the current available therapies for obesity and/or type 2 diabetes that impact each stage of NAFLD.

Conclusion
The proper understanding of NAFLD spectrum—as a continuum from obesity to metabolic syndrome and diabetes—may contribute to the early identification and for establishment of targeted treatment.
Human adult and adolescent biodistribution and dosimetry of the synaptic vesicle glycoprotein 2A radioligand 11C-UCB-J
Authors: Bini Jason , Holden Daniel , Fontaine Kathryn , Mulnix Tim , Lu Yihuan , Matuskey David , Ropchan Jim , Nabulsi Nabeel , Huang Yiyun , Carson Richard E. 
Published: July 2020

Abstract
The ability to quantify synaptic density in vivo in human adults and adolescents is of vital importance to understanding neuropsychiatric disorders. Here, we performed whole-body scans to determine organ radiation dosimetry of 11C-UCB-J in humans.

Methods
Dynamic whole-body PET scans were performed in four healthy adults after injection of 11C-UCB-J. Regions of interest (ROIs) were drawn manually for the brain, heart, stomach, kidneys, liver, pancreas, spleen, gallbladder, lungs, urinary bladder, and intestines. ROIs were applied to dynamic images to generate time-activity curves (TACs). Decay correction was removed from TACs, and the area under the curve (AUC) for each ROI was calculated. AUCs were then normalized by injected activity and organ volumes to produce radioligand residence times for each organ. These times were then used as input into the OLINDA/EXM 1.0 software to determine the total radiation dose in each organ and the effective dose for these OLINDA models: 55-kg female, 70-kg male, and 15-year-old adolescent.

Results
Visual evaluation detected high uptake in the liver, brain, gallbladder, gastrointestinal tract, and urinary bladder. The dose-limiting organ was the urinary bladder for adult males (0.0224 mSv/MBq) and liver for adult females (0.0248 mSv/MBq) with single-study dose limits of 2239 MBq and 2017 MBq 11C-UCB-J, respectively. For adolescents, the large intestine was the dose-limiting organ (0.0266 mSv/MBq) with a single-study dose limit of 188 MBq.

Conclusions
11C-UCB-J dosimetry in adults is consistent with those for many carbon-11-labeled ligands. Overall, 11C-UCB-J can be used safely in adolescents, as in adults, to measure synaptic density in various neuropsychiatric and other relevant disorders.
Anchor-free object detection with mask attention
Authors: Yang He , Fan Beibei , Guo Lingling 
Published: July 2020

AbstractThe anchor-free method based on key point detection has made great progress. However, the anchor-free method is too dependent on using a convolutional network to generate a rough heatmap. This is difficult to detect for objects with a large size variation and dense and overlapping objects. To solve this problem, first, we propose a mask attention mechanism for object detection methods and make full use of the advantages of the attention mechanism to improve the accuracy of network detection heatmap generation. Then, we designed an optimized fire model to reduce the size of the model. The fire model is an extension of grouped convolution. The fire model allows each group of convolutional network features to learn the same feature through purposeful grouping. In this paper, the mask attention mechanism uses object segmentation images to guide the generation of corner heatmaps. Our approach achieved an accuracy of 91.84% and a recall of 89.83% in the Tencent-100 K dataset. Compared with the popular object detection methods, the proposed method has advantages in model size and accuracy.