bluuebunny/crossref_metadata_2025_split huggingface dataset:
High prevalence of hepatitis C virus infection and low level of awareness among people who recently started injecting drugs in a cross-sectional study in Germany, 2011–2014: missed opportunities for hepatitis C testing
Authors:   DRUCK Study group, Enkelmann Julia , Gassowski Martyna , Nielsen Stine , Wenz Benjamin , Roß Stefan , Marcus Ulrich , Bremer Viviane , Zimmermann Ruth 
Published: January 2020

Abstract
Background
In Germany, risk of hepatitis C virus (HCV) infection is highest among people who inject drugs (PWID). New injectors (NI) are particularly vulnerable for HCV-acquisition, but little is known about health seeking behaviour and opportunities for intervention in this group. We describe characteristics, HCV prevalence, estimated HCV incidence and awareness of HCV-status among NIs and missed opportunities for hepatitis C testing.

Methods
People who had injected drugs in the last 12 months were recruited into a cross-sectional serobehavioural study using respondent-driven sampling in 8 German cities, 2011–2014. Data on sociodemographic characteristics, previous HCV testing and access to care were collected through questionnaire-based interviews. Capillary blood was tested for HCV. People injecting drugs < 5 years were considered NI.

Results
Of 2059 participants with available information on duration of injection drug use, 232 (11% were NI. Estimated HCV incidence among NI was 19.6 infections/100 person years at risk (95% CI 16–24). Thirty-six percent of NI were HCV-positive (thereof 76% with detectable RNA) and 41% of those HCV-positive were unaware of their HCV-status. Overall, 27% of NI reported never having been HCV-tested. Of NI with available information, more than 80% had attended low-threshold drug services in the last 30 days, 24% were released from prison in the last 12 months and medical care was most commonly accessed in hospitals, opioid substitution therapy (OST)-practices, practices without OST and prison hospitals.

Conclusion
We found high HCV-positivity and low HCV-status awareness among NI, often with missed opportunities for HCV-testing. To increase early diagnosis and facilitate treatment, HCV-testing should be offered in all facilities, where NI can be reached, especially low-threshold drug services and addiction therapy, but also prisons, hospitals and practices without OST.
Stimulant safe supply: a potential opportunity to respond to the overdose epidemic
Authors: Fleming Taylor , Barker Allison , Ivsins Andrew , Vakharia Sheila , McNeil Ryan 
Published: January 2020

Abstract
Background
Occurring against the backdrop of an overdose crisis, stimulant use and stimulant-involved deaths in North America are increasing at an alarming rate. Many of these deaths are being attributed to fentanyl and related analogs, which have been increasingly found within street-level stimulant supplies. Within this, people experiencing socio-economic marginalization are at the greatest risk of overdose and other harms from adulterated stimulants. Current treatments for stimulant use disorder have limited effectiveness, and even less applicability to the lived realities of marginalized stimulant users. Emerging technologies, such as drug checking, are being implemented to support safer stimulant use, but the accessibility and utility of these technologies to stimulant users are framed by experiences of vulnerability that render them largely ineffective.

Stimulant safe supply
Solutions that provide a legal and safe supply of non-adulterated stimulants of known quality, and within a health care framework, are needed to directly address the risk of an increasingly adulterated stimulant supply. Similar innovative opioid-focused interventions are being piloted with medications that have a similar pharmacological effect as their illicit counterparts. While there are currently no approved pharmacotherapies for stimulant use, research has demonstrated a number of stimulant medications that are promising substitutes for cocaine and methamphetamine use. Much like with opioid-focused pharmacotherapies, having a consistent and safe supply of stimulants can lead to improved health outcomes and will drastically reduce overdose risk. However, for a stimulant safe supply intervention to be a success, it must provide the high and performance-enhancing effects that people seek from the illicit market, which requires doses and user agency that trials to date have not provided.

Conclusion
Efforts are needed to investigate the feasibility of pharmacological stimulant-based interventions that address safe supply needs. The promise of similar opioid-focused approaches in addressing both overdose-related risks and experiences related to vulnerability underscores the need to advance safe supply approaches targeted towards people who use stimulants. Given the current overdose crisis and rising stimulant use across North America, the implementation and evaluation of such novel stimulant-focused interventions should be a public health priority.
Health economic evaluation of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma: a systematic review
Authors: Wang Haiyin , Jin Chunlin , Fang Liang , Sun Hui , Cheng Wendi , HU Shanlian 
Published: January 2020

AbstractStereotactic body radiotherapy (SBRT) is a novel noninvasive treatment for hepatocellular carcinoma. SBRT can achieve effective local control, but it requires a relatively high input of resources; this systematic review was performed to assess the cost effectiveness of SBRT in the treatment of hepatocellular carcinoma to provide a basis for government pricing and medical insurance decision-making. The PubMed, EMBASE, Cochrane Library, CNKI, Wanfang and SinoMed databases were searched to collect economic evaluations of SBRT for the treatment of hepatocellular carcinoma from the date of database inception through December 31, 2018. Two reviewers independently screened the studies, extracted the data and performed a descriptive analysis of the basic characteristics, methods of economic evaluation and main results, as well as the quality and heterogeneity of the reports. A total of 5 studies were included. Among them, the level of heterogeneity was relatively acceptable, with a median score of 90%. Four studies were cost-utility analyses (CUAs), and 1 was a cost-effectiveness analysis (CEA). The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was US $114,795 per quality-adjusted life year gained (cost/QALY) in patients with advanced hepatocellular carcinoma. The ICER for proton beam therapy compared to SBRT was US $6465 in patients with inoperable advanced hepatocellular carcinoma. The ICER for SBRT compared to RFA was US $164,660 for patients with unresectable colorectal cancer (CRC) with liver metastases and US $56,301 for patients with early-stage hepatocellular carcinoma. For patients with inoperable localized hepatocellular carcinoma, compared with RFA–SBRT therapy, the ICERs for SBRT–SBRT and SBRT–RFA were US $558,679 and US $2197,000, respectively; RFA–RFA was dominated. In conclusion, there is limited evidence suggesting that SBRT could be cost-effective for highly specific subpopulations of HCC patients, and further economic evaluations based on randomized controlled trials (RCTs) or cohort studies are needed.
Sepsis-associated encephalopathy: a vicious cycle of immunosuppression
Authors: Ren Chao , Yao Ren-qi , Zhang Hui , Feng Yong-wen , Yao Yong-ming 
Published: January 2020

AbstractSepsis-associated encephalopathy (SAE) is commonly complicated by septic conditions, and is responsible for increased mortality and poor outcomes in septic patients. Uncontrolled neuroinflammation and ischemic injury are major contributors to brain dysfunction, which arises from intractable immune malfunction and the collapse of neuroendocrine immune networks, such as the cholinergic anti-inflammatory pathway, hypothalamic-pituitary-adrenal axis, and sympathetic nervous system. Dysfunction in these neuromodulatory mechanisms compromised by SAE jeopardizes systemic immune responses, including those of neutrophils, macrophages/monocytes, dendritic cells, and T lymphocytes, which ultimately results in a vicious cycle between brain injury and a progressively aberrant immune response. Deep insight into the crosstalk between SAE and peripheral immunity is of great importance in extending the knowledge of the pathogenesis and development of sepsis-induced immunosuppression, as well as in exploring its effective remedies.
Comparison of concomitant injuries and patient-reported outcome in patients that have undergone both primary and revision ACL reconstruction—a national registry study
Authors: Svantesson Eleonor , Hamrin Senorski Eric , Kristiansson Frida , Alentorn-Geli Eduard , Westin Olof , Samuelsson Kristian 
Published: January 2020

Abstract
Background
Anterior cruciate ligament (ACL) revision surgery has been associated with inferior outcome compared with primary ACL reconstruction. However, this has rarely been investigated in a consecutive cohort limited to patients that have undergone both primary and revision ACL reconstruction. This study aimed to assess differences in outcome and concomitant injuries between primary and revision ACL reconstruction in such a cohort, and to identify predictors of the patient-reported outcome after ACL revision.

Methods
Patients who had undergone both primary and revision ACL reconstruction were identified in the Swedish National Knee Ligament Registry. Patients aged 13–49 years with hamstring tendon primary ACL reconstruction and data on the Knee Injury and Osteoarthritis Outcome Score (KOOS) on at least one occasion (preoperative or one year postoperatively) at both surgeries were eligible. Concomitant injuries and the KOOS were compared between each patient’s primary and revision ACL reconstruction. Linear regression analyses were performed to determine predictors of the one-year KOOS after ACL revision.

Results
A total of 1014 patients were included. Cartilage injuries increased at ACL revision (p < 0.001), as 23.0% had a cartilage injury at ACL revision that was not present at primary ACL reconstruction. The 1-year KOOS was lower after ACL revision compared with primary ACL reconstruction, with the largest difference in the KOOS sports and recreation (5.2 points, SD 32.2, p = 0.002). A posterolateral corner (PLC) injury at ACL revision was a negative predictor of KOOS, with the largest effect on the sports and recreation subscale (β = − 29.20 [95% CI − 50.71; − 6.69], p = 0.011). The use of allograft for ACL revision was an independent predictor of a poorer KOOS QoL (β = − 12.69 [95% CI − 21.84; − 3.55], p = 0.0066) and KOOS4 (β = − 11.40 [95% CI − 19.24; − 3.57], p = 0.0044).

Conclusion
Patients undergoing ACL revision reported a 1-year outcome that was slightly inferior to the 1-year outcome after their primary ACL reconstruction. An ACL revision was associated with an increase in cartilage injuries. A PLC injury at ACL revision and the use of allograft for ACL revision predicted a clinically relevant poorer KOOS one year after ACL revision.
Huoxue Wentong Formula ameliorates myocardial infarction in rats through inhibiting CaMKII oxidation and phosphorylation
Authors: Liu Tiantian , Wang Qingqing , Yao Kuiwu 
Published: January 2020

Abstract
Background
The Chinese medicine Huoxue Wentong Formula (HXWTF) was used to treat thoracic obstruction and angina pectoris in clinic, which has not been investigated in myocardial ischemia-induced apoptosis and angiogenic function. Here we aimed to investigate the roles of HXWTF in rats with myocardial ischemia-induced apoptosis and angiogenesis disorders, as well as to reveal the potential mechanisms.

Methods
Male SD rats were subjected to coronary artery ligation followed by HXWTF (420, 840 and 1680 mg/kg/day, p.o.) or isosorbide mononitrate (6.3 mg/kg/day, p.o.) treatment for 4 weeks. Electrocardiogram (ECG) and Echocardiography (ECHO) were used to measure cardiac function. Hematoxylin and eosin (H&E) staining and CD34/α-SMA immunohistochemical staining were performed to observe the ischemic heart sections pathological changes and angiogenesis. Then, the effects on cardiomyocyte apoptosis of H9c2 and tube formation of HCMECs were observed, as well as the changes in the levels of total calmodulin dependent protein kinase II (t-CaMKII), phosphorylated CaMKII (p-CaMKII), oxidized CaMKII (ox-CaMKII), CD34, and Bcl-2/Bax ratio were detected.

Results
Rats with coronary artery ligation exhibited abnormal cardiac function, enlarged myocardial space, disorderly arranged myocardial fibers, inflammatory cells infiltrated, and aggravated myocardial cell apoptosis, along with angiogenesis dysfunction. The expressions of CD34, p-CaMKII, and ox-CaMKII were elevated and Bcl-2/Bax ratio was diminished in ischemic hearts and H/SD-treated H9c2 or HCMECs, while HXWTF treatment completely rescued angiogenic dysfunction, inhibited cardiomyocyte apoptosis, and down-regulated cardiac CaMKII oxidation and phosphorylation activities.

Conclusion
Our study demonstrates that HXWTF improves myocardial infarction possibly through inhibiting CaMKII oxidation and phosphorylation levels, facilitating angiogenic function and alleviating cardiomyocyte apoptosis. Thus, therapeutics targeting CaMKII activities may be a promising strategy for rescuing ischemic cardiomyopathy.
VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice
Authors: El Gaamouch Farida , Audrain Mickael , Lin Wei-Jye , Beckmann Noam , Jiang Cheng , Hariharan Siddharth , Heeger Peter S. , Schadt Eric E. , Gandy Sam , Ehrlich Michelle E. , Salton Stephen R. 
Published: January 2020

Abstract
Background
Multiomic studies by several groups in the NIH Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) identified VGF as a major driver of Alzheimer’s disease (AD), also finding that reduced VGF levels correlate with mean amyloid plaque density, Clinical Dementia Rating (CDR) and Braak scores. VGF-derived peptide TLQP-21 activates the complement C3a receptor-1 (C3aR1), predominantly expressed in the brain on microglia. However, it is unclear how mouse or human TLQP-21, which are not identical, modulate microglial function and/or AD progression.

Methods
We performed phagocytic/migration assays and RNA sequencing on BV2 microglial cells and primary microglia isolated from wild-type or C3aR1-null mice following treatment with TLQP-21 or C3a super agonist (C3aSA). Effects of intracerebroventricular TLQP-21 delivery were evaluated in 5xFAD mice, a mouse amyloidosis model of AD. Finally, the human HMC3 microglial cell line was treated with human TLQP-21 to determine whether specific peptide functions are conserved from mouse to human.

Results
We demonstrate that TLQP-21 increases motility and phagocytic capacity in murine BV2 microglial cells, and in primary wild-type but not in C3aR1-null murine microglia, which under basal conditions have impaired phagocytic function compared to wild-type. RNA sequencing of primary microglia revealed overlapping transcriptomic changes induced by treatment with TLQP-21 or C3a super agonist (C3aSA). There were no transcriptomic changes in C3aR1-null or wild-type microglia exposed to the mutant peptide TLQP-R21A, which does not activate C3aR1. Most of the C3aSA- and TLQP-21-induced differentially expressed genes were linked to cell migration and proliferation. Intracerebroventricular TLQP-21 administration for 28 days via implanted osmotic pump resulted in a reduction of amyloid plaques and associated dystrophic neurites and restored expression of subsets of Alzheimer-associated microglial genes. Finally, we found that human TLQP-21 activates human microglia in a fashion similar to activation of murine microglia by mouse TLQP-21.

Conclusions
These data provide molecular and functional evidence suggesting that mouse and human TLQP-21 modulate microglial function, with potential implications for the progression of AD-related neuropathology.
A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer
Authors: Goldstein Lori J. , Perez Raymond P. , Yardley Denise , Han Linda K. , Reuben James M. , Gao Hui , McCanna Susan , Butler Beth , Ruffini Pier Adelchi , Liu Yi , Rosato Roberto R. , Chang Jenny C. 
Published: January 2020

Abstract
Background
Cancer stem cells (CSCs) are purported to be responsible for tumor initiation, treatment resistance, disease recurrence, and metastasis. CXCR1, one of the receptors for CXCL8, was identified on breast cancer (BC) CSCs. Reparixin, an investigational allosteric inhibitor of CXCR1, reduced the CSC content of human BC xenograft in mice.

Methods
In this multicenter, single-arm trial, women with HER-2-negative operable BC received reparixin oral tablets 1000 mg three times daily for 21 days before surgery. Primary objectives evaluated the safety of reparixin and the effects of reparixin on CSC and tumor microenvironment in core biopsies taken at baseline and at treatment completion. Signal of activity was defined as a reduction of ≥ 20% in ALDH+ or CD24−/CD44+ CSC by flow cytometry, with consistent reduction by immunohistochemistry.

Results
Twenty patients were enrolled and completed the study. There were no serious adverse reactions. CSC markers ALDH+ and CD24−/CD44+ measured by flow cytometry decreased by ≥ 20% in 4/17 and 9/17 evaluable patients, respectively. However, these results could not be confirmed by immunofluorescence due to the very low number of CSC.

Conclusions
Reparixin appeared safe and well-tolerated. CSCs were reduced in several patients as measured by flow cytometry, suggesting targeting of CXCR1 on CSC.

Clinical trial registration
Clinicaltrials.gov, NCT01861054. Registered on April 18, 2013.
Evaluation of the Teaching Recovery Techniques community-based intervention for unaccompanied refugee youth experiencing post-traumatic stress symptoms (Swedish UnaccomPanied yOuth Refugee Trial; SUPpORT): study protocol for a randomised controlled trial
Authors: Sarkadi Anna , Warner Georgina , Salari Raziye , Fängström Karin , Durbeej Natalie , Lampa Elin , Baghdasaryan Zaruhi , Osman Fatumo , Gupta Löfving Sandra , Perez Aronsson Anna , Feldman Inna , Sampaio Filipa , Ssegonja Richard , Calam Rachel , Bjärtå Anna , Leiler Anna , Rondung Elisabet , Wasteson Elisabet , Oppedal Brit , Keeshin Brooks 
Published: January 2020

Abstract
Background
In 2015, 162,877 persons sought asylum in Sweden, 35,369 of whom were unaccompanied refugee minors (URMs). Refugee children, especially URMs, have often experienced traumas and are at significant risk of developing mental health problems, such as symptoms of post-traumatic stress disorder (PTSD), depression and anxiety, which can continue years after resettlement. The Swedish UnaccomPanied yOuth Refugee Trial (SUPpORT) aims to evaluate a community-based intervention, called Teaching Recovery Techniques (TRT), for refugee youth experiencing PTSD symptoms.

Methods/design
A randomised controlled trial will be conducted in which participants will be randomly allocated to one of two possible arms: the intervention arm (n = 109) will be offered the TRT programme, and the waitlist-control arm (n = 109) will receive services as usual, followed by the TRT programme around 20 weeks later. Outcome data will be collected at three points: pre-intervention (T1), post-intervention (T2; about 8 weeks after randomisation) and follow-up (T3; about 20 weeks after randomisation).

Discussion
This study will provide knowledge about the effect and efficiency of a group intervention for URMs reporting symptoms of PTSD in Sweden.

Trial registration
ISRCTN, ISRCTN47820795. Prospectively registered on 20 December 2018.
Effect of temperature-control liner materials on long-term outcomes of lower limb prosthesis use: a randomized controlled trial protocol
Authors: Fiedler Goeran , Singh Anita , Zhang Xueyi 
Published: January 2020

AbstractBackgroundIn people living with limb loss, addressing the resulting functional deficit with prostheses increases the risk for secondary conditions such as pressure sores, impaired blood perfusion, and injuries from accidental falls. Any of those occurrences can render the prosthesis temporarily useless, making it challenging for users to engage in many activities of daily life, including work, exercise, and social participation. Many of the described issues originate at the interface between residual limb and prosthetic socket, where the objectives of sufficient weight distribution and suspension are conflicting with the necessity to facilitate heat exchange and limit contact pressure and friction.Recently, prosthesis liners that contain phase-change material have become commercially available, holding the promise that the micro climate at the interface between the residual limb skin and the prosthetic socket can be regulated to reduce the users’ tendency to sweat. Preliminary studies on these liners indicate that the socket temperatures inside the socket stayed lower and rose slower than in conventional liners. However, the clinical relevance of those findings remains unclear.The purpose of this study is to investigate whether longer (6+ months) periods of use of phase-change material based temperature-control liners have clinically meaningful effects.MethodsThe protocol is a double-blind longitudinal cross-over research design. A sample of trans-tibial prosthesis users are wearing their regular gel or silicone liners for six months and phase-change material liners for another six months in a randomized sequence. Their prostheses is equipped with activity monitors to detect days when they could not wear their prosthesis. In six-week intervals, individuals’ activity, physical performance, and overall prosthesis assessment is recorded using standardized methods.DiscussionExpected results will inform prescription and reimbursement practice of phase-change material-based prosthesis liners and will help improve and economize prosthetic fitting for people with limb loss. The design and duration of the protocol, including randomization, blinding, and within-subject comparison, will generate scientific evidence of a comparably high level. Inclusion of a comparably large sample and different climates, e.g. across all four seasons, will make findings applicable to a large number of prosthesis users.Trial registrationClinicaltrials.gov,NCT03428815. Registered on 12 February 2018.