bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the impact of exposure to adverse socioeconomic conditions on chronic stress from a complexity science perspective
Authors: Crielaard Loes , Nicolaou Mary , Sawyer Alexia , Quax Rick , Stronks Karien 
Published: October 2021

Abstract
Background
Chronic stress increases chronic disease risk and may underlie the association between exposure to adverse socioeconomic conditions and adverse health outcomes. The relationship between exposure to such conditions and chronic stress is complex due to feedback loops between stressor exposure and psychological processes, encompassing different temporal (acute stress response to repeated exposure over the life course) and spatial (biological/psychological/social) scales. We examined the mechanisms underlying the relationship between exposure to adverse socioeconomic conditions and chronic stress from a complexity science perspective, focusing on amplifying feedback loops across different scales.

Methods
We developed a causal loop diagram (CLD) to interpret available evidence from this perspective. The CLD was drafted by an interdisciplinary group of researchers. Evidence from literature was used to confirm/contest the variables and causal links included in the conceptual framework and refine their conceptualisation. Our findings were evaluated by eight independent researchers.

Results
Adverse socioeconomic conditions imply an accumulation of stressors and increase the likelihood of exposure to uncontrollable childhood and life course stressors. Repetition of such stressors may activate mechanisms that can affect coping resources and coping strategies and stimulate appraisal of subsequent stressors as uncontrollable. We identified five feedback loops describing these mechanisms: (1) progressive deterioration of access to coping resources because of repeated insolvability of stressors; (2) perception of stressors as uncontrollable due to learned helplessness; (3) tax on cognitive bandwidth caused by stress; (4) stimulation of problem avoidance to provide relief from the stress response and free up cognitive bandwidth; and (5) susceptibility to appraising stimuli as stressors against a background of stress.

Conclusions
Taking a complexity science perspective reveals that exposure to adverse socioeconomic conditions implies recurrent stressor exposure which impacts chronic stress via amplifying feedback loops that together could be conceptualised as one vicious cycle. This means that in order for individual-level psychological interventions to be effective, the context of exposure to adverse socioeconomic conditions also needs to be addressed.
New epiretinal implant with integrated sensor chips for optical capturing shows a good biocompatibility profile in vitro and in vivo
Authors: Schaffrath Kim , Lohmann Tibor , Seifert Jan , Ingensiep Claudia , Raffelberg Pascal , Waschkowski Florian , Viga Reinhard , Kokozinski Rainer , Mokwa Wilfried , Johnen Sandra , Walter Peter 
Published: October 2021

Abstract
Background
Retinal degenerative diseases, e.g., retinitis pigmentosa, cause a severe decline of the visual function up to blindness. Treatment still remains difficult; however, implantation of retinal prostheses can help restoring vision. In this study, the biocompatibility and surgical feasibility of a newly developed epiretinal stimulator (OPTO-EPIRET) was investigated. The previously developed implant was extended by an integrated circuit-based optical capturing, which will enable the immediate conversion of the visual field into stimulation patterns to stimulate retinal ganglion cells.

Results
The biocompatibility of the OPTO-EPIRET was investigated in vitro using the two different cell lines L-929 and R28. Direct and indirect contact were analyzed in terms of cell proliferation, cell viability, and gene expression. The surgical feasibility was initially tested by implanting the OPTO-EPIRET in cadaveric rabbit eyes. Afterwards, inactive devices were implanted in six rabbits for feasibility and biocompatibility testings in vivo. In follow-up controls (1–12 weeks post-surgery), the eyes were examined using fundoscopy and optical coherence tomography. After finalization, histological examination was performed to analyze the retinal structure. Regarding the in vitro biocompatibility, no significant influence on cell viability was detected (L929: < 1.3% dead cells; R-28: < 0.8% dead cells). The surgery, which comprised phacoemulsification, vitrectomy, and implantation of the OPTO-EPIRET through a 9–10 mm corneal incision, was successfully established. The implant was fixated with a retinal tack. Vitreal hemorrhage or retinal tearing occurred as main adverse effects. Transitional corneal edema caused difficulties in post-surgical imaging.

Conclusions
The OPTO-EPIRET stimulator showed a good biocompatibility profile in vitro. Furthermore, the implantation surgery was shown to be feasible. However, further design optimization steps are necessary to avoid intra- and postoperative complications. Overall, the OPTO-EPIRET will allow for a wide visual field and good visual acuity due to a high density of electrodes in the central retina.
Intrinsic nucleus-targeted ultra-small metal–organic framework for the type I sonodynamic treatment of orthotopic pancreatic carcinoma
Authors: Zhang Tao , Sun Yu , Cao Jing , Luo Jiali , Wang Jing , Jiang Zhenqi , Huang Pintong 
Published: October 2021

Abstract
Background
Sonodynamic therapy (SDT) strategies exhibit a high tissue penetration depth and can achieve therapeutic efficacy by facilitating the intertumoral release of reactive oxygen species (ROS) with a short lifespan and limited diffusion capabilities. The majority of SDT systems developed to date are of the highly O2-dependent type II variety, limiting their therapeutic utility in pancreatic cancer and other hypoxic solid tumor types.

Results
Herein, a nucleus-targeted ultra-small Ti-tetrakis(4-carboxyphenyl)porphyrin (TCPP) metal–organic framework (MOF) platform was synthesized and shown to be an effective mediator of SDT. This MOF was capable of generating large quantities of ROS in an oxygen-independent manner in response to low-intensity ultrasound (US) irradiation (0.5 W cm−2), thereby facilitating both type I and type II SDT. This approach thus holds great promise for the treatment of highly hypoxic orthotopic pancreatic carcinoma solid tumors. This Ti-TCPP MOF was able to induce in vitro cellular apoptosis by directly destroying DNA and inducing S phase cell cycle arrest following US irradiation. The prolonged circulation, high intratumoral accumulation, and nucleus-targeting attributes of these MOF preparations significantly also served to significantly inhibit orthotopic pancreatic tumor growth and prolong the survival of tumor-bearing mice following Ti-TCPP + US treatment. Moreover, this Ti-TCPP MOF was almost completely cleared from mice within 7 days of treatment, and no apparent treatment-associated toxicity was observed.

Conclusion
The nucleus-targeted ultra-small Ti-TCPP MOF developed herein represents an effective approach to the enhanced SDT treatment of tumors in response to low-intensity US irradiation.

Graphic abstract
Hepatitis C reinfection in former and active injecting drug users in Belgium
Authors: Busschots Dana , Bielen Rob , Koc Özgür M. , Heyens Leen , Verrando Rita , de Galocsy Chantal , Van Steenkiste Christophe , Nevens Frederik , Midgard Håvard , Dalgard Olav , Robaeys Geert 
Published: October 2021

AbstractBackgroundThere is currently no systematic screening for hepatitis C (HCV) reinfection in people who inject drugs (PWID) after treatment in Belgium. However, in a recent meta-analysis, the overall HCV reinfection rate was 5.9/100 person-years (PY) among PWID. Accordingly, this study was undertaken to investigate the reinfection rate in former and active PWID who achieved the end of treatment response after direct-acting antiviral (DAA) treatment in Belgium.MethodsThis observational cross-sectional study recruited individuals with a history of injecting drug use who had achieved the end of treatment response to any DAA treatment between 2015 and 2020. Participants were offered a post-treatment HCV RNA test.ResultsEighty-five potential participants were eligible to participate and contacted, of whom 60 participants were enrolled in the study with a median age of 51.0 (IQR 44.3–56.0) years; it was reported that 23.3% continued to inject drugs intravenously after DAA treatment. Liver cirrhosis was present in 12.9%. The majority had genotype 1a (51.7%) or genotype 3 (15.0%) infection. We detected no reinfections in this study population. The total time patients were followed up for reinfection in the study was 78.5 PY (median 1.0 years IQR 0.4–2.0).ConclusionReinfection after successful treatment with DAA initially appears to be very low in Belgian PWID. Therefore, efforts should be made to screen individuals with persistent risk behaviors for reinfection systematically. In addition, a national HCV registry should be established to accurately define the burden of HCV infection and reinfection in Belgium and support the elimination of viral hepatitis C in Europe.Trial registrationclinicaltrials.gov NCT04251572, Registered 5 Feb 2020–Retrospectively registered,https://clinicaltrials.gov/ct2/show/NCT04251572.
Evaluation of GnRH antagonist pretreatment before ovarian stimulation in a GnRH antagonist protocol in normal ovulatory women undergoing IVF/ICSI: a randomized controlled trial
Authors: Zhang Yisheng , Liu Liling , Qin Jie , Huang Hongyi , Xue Lintao , Wang Shikai , Tan Weihong 
Published: October 2021

Abstract
Background
Synchronization of follicles is key to improving ovulation stimulation with the gonadotropin-releasing hormone (GnRH) antagonist protocol. GnRH antagonist administration in the early follicular phase can quickly decrease gonadotrophin (Gn) levels and achieve downregulation before stimulation, which may improves synchronization. A previous small randomized controlled study (RCT) showed that pretreatment with a GnRH antagonist for 3 days before stimulation may increase oocyte retrieval but cannot increase the pregnancy rate. This study investigated whether the GnRH antagonist pretreatment protocol in ovulatory women can increase the synchronization of follicles and pregnancy outcomes compared with the conventional GnRH antagonist protocol.

Methods
This RCT included 136 normal ovulatory women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). Both groups were treated with recombinant follicle-stimulating hormone (r-FSH) and a flexible GnRH antagonist protocol. The women were randomized into two equal groups with or without GnRH antagonist administration from day 2 of the menstrual cycle for 3 days before stimulation. Our primary outcome was the number of retrieved oocytes. Secondary outcomes included the pregnancy rate and live birth rate.

Results
Both groups had similar baseline characteristics. The number of retrieved oocytes in the study group was comparable to that in the control group (9.5 [8.0–13.0] vs. 11.0 [7.0–14.8], P = 0.469). There was no significant difference in the follicle size. The fertilization rate, number of good-quality embryos, implantation rate, pregnancy rate, ongoing pregnancy rate, live birth rate per embryonic transfer cycle, and miscarriage rate were similar between the two groups.

Conclusion
This large RCT analysed GnRH antagonist pretreatment with the GnRH antagonist protocol applied to normal ovulatory women undergoing IVF/ICSI. The number of retrieved oocytes and pregnancy outcomes did not significantly vary.

Trial registration
Chinese Clinical Trial Registry, ChiCTR1800019730. Registered 26 November 2018.
Community health workers at the dawn of a new era: 2. Planning, coordination, and partnerships
Authors: Afzal Muhammad Mahmood , Pariyo George W. , Lassi Zohra S. , Perry Henry B. 
Published: October 2021

AbstractBackgroundCommunity health workers (CHWs) play a critical role in grassroots healthcare and are essential for achieving the health-related Sustainable Development Goals. While there is a critical shortage of essential health workers in low- and middle-income countries, WHO and international partners have reached a consensus on the need to expand and strengthen CHW programmes as a key element in achieving Universal Health Coverage (UHC). The COVID-19 pandemic has further revealed that emerging health challenges require quick local responses such as those utilizing CHWs. This is the second paper of our 11-paper supplement, “Community health workers at the dawn of a new era”. Our objective here is to highlight questions, challenges, and strategies for stakeholders to consider while planning the introduction, expansion, or strengthening of a large-scale CHW programme and the complex array of coordination and partnerships that need to be considered.MethodsThe authors draw on the outcomes of discussions during key consultations with various government leaders and experts from across policy, implementation, research, and development organizations in which the authors have engaged in the past decade. These include global consultations on CHWs and global forums on human resources for health (HRH) conferences between 2010 and 2014 (Montreux, Bangkok, Recife, Washington DC). They also build on the authors’ direct involvement with the Global Health Workforce Alliance.ResultsWeak health systems, poor planning, lack of coordination, and failed partnerships have produced lacklustre CHW programmes in countries. This paper highlights the three issues that are generally agreed as being critical to the long-term effectiveness of national CHW programmes—planning, coordination, and partnerships. Mechanisms are available in many countries such as the UHC2030 (formerly International Health Partnership), country coordinating mechanisms (CCMs), and those focusing on the health workforce such as the national Human Resources for Health Observatory and the Country Coordination and Facilitation (CCF) initiatives introduced by the Global Health Workforce Alliance.ConclusionIt is imperative to integrate CHW initiatives into formal health systems. Multidimensional interventions and multisectoral partnerships are required to holistically address the challenges at national and local levels, thereby ensuring synergy among the actions of partners and stakeholders. In order to establish robust and institutionalized processes, coordination is required to provide a workable platform and conducive environment, engaging all partners and stakeholders to yield tangible results.
FAM83A promotes proliferation and metastasis via Wnt/β-catenin signaling in head neck squamous cell carcinoma
Authors: Ji Huan , Song Haiyang , Wang Zeyu , Jiao Pengfei , Xu Jiani , Li Xuan , Du Hongming , Wu Heming , Zhong Yi 
Published: October 2021

AbstractThis research aimed to investigate the expression and function of FAM83A in the proliferation and metastasis in head and neck squamous cell carcinoma (HNSCC). FAM83A mRNA and protein expressions in HNSCC were detected in primary HNSCC samples and cell lines. The associations between FAM83A expression and clinicopathologic variables were evaluated through tissue microarrays. Besides, FAM83A knockdown and overexpression cell lines were constructed to assess cell growth and metastasis in vitro and the relationship between FAM83A and epithelial-mesenchymal transition (EMT). Furthermore, two models of xenograft tumors in nude mice were used to assess the tumorigenicity and metastasis ability of FAM83A in vivo. In the present study, overexpression of FAM83A in HNSCC samples was significantly associated with tumor size, lymph node status and clinical tumor stages. Mechanically, FAM83A could promote HNSCC cell growth and metastasis by inducing EMT via activating Wnt/β-catenin signaling pathway. Rescue experiment demonstrated the inhibition of β-catenin could counteract the function of FAM83A. Also, the FAM83A knockdown could suppress tumor growth and distant metastasis in the xenograft animal models of HNSCC. In conclusion, this study identifies FAM83A as an oncogene of HNSCC. This study provides new insights into the molecular pathways that contribute to EMT in HNSCC. We revealed a previously unknown FAM83A-Wnt–β-catenin signaling axis involved in the EMT of HNSCC. There may be a potential bi-directional signaling loop between FAM83A and Wnt/β-catenin signaling pathway in HNSCC.
Source-tracking of the Chinese Chikungunya viruses suggests that Indian subcontinent and Southeast Asia act as major hubs for the recent global spread of Chikungunya virus
Authors: Qiu Shaofu , Guo Jinpeng , Li Peihan , Li Peng , Du Xinying , Hao Rongzhang , Yang Chaojie , Wang Qi , Liu Hongbo , Zhang Haoran , Tian Sai , Shi Hua , Wen Liang , An Daizhi , Yang Xiaocui , An Xiaoyuan , Wang Ligui , Wang Changjun , Song Hongbin 
Published: October 2021

Abstract
Background
Chikungunya fever, caused by the Chikungunya virus (CHIKV), has become a major global health concern, causing unexpected large outbreaks in Africa, Asia, Europe, and the Americas. CHIKV is not indigenous to China, and its origin in the country is poorly understood. In particular, there is limited understanding of the recent global spread of CHIKV in the context of the CHIKV epidemic.

Methods
Here we investigated a novel Chikungunya patient who came from Myanmar to China in August, 2019. Direct genome sequencing was performed via combined MinION sequencing and BGISEQ-500 sequencing. A complete CHIKV genome dataset, including 727 CHIKV genomes retrieved from GenBank and the genome sequenced in this study, was constructed. An updated and comprehensive phylogenetic analysis was conducted to understand the virus’s origin, evolution, transmission routes and genetic adaptation.

Results
All globally distributed CHIKV genomes were divided into West Africa, East/Central/South African and Asian genotypes. The genome sequenced in this study was located in the Indian Ocean lineage, and was closely related to a strain isolated from an Australian patient who returned from Bangladesh in 2017. A comprehensive phylogenetic analysis showed that the Chinese strains mainly originated from the Indian subcontinent and Southeast Asia. Further analyses indicated that the Indian subcontinent and Southeast Asia may act as major hubs for the recent global spread of CHIKV, leading to multiple outbreaks and epidemics. Moreover, we identified 179 distinct sites, including some undescribed sites in the structural and non-structural proteins, which exhibited apparent genetic variations associated with different CHIKV lineages.

Conclusions
Here we report a novel CHIKV isolate from a chikungunya patient who came from Myanmar to China in 2019, and summarize the source and evolution of Chinese CHIKV strains. Our present findings provide a better understanding of the recent global evolution of CHIKV, highlighting the urgent need for strengthened surveillance against viral diversity.
Introduction of day case hip and knee replacement programme at an inpatient ward is safe and may expedite shortening of hospital stays of traditional arthroplasties
Authors: Lovasz Gyorgy , Aros Attila , Toth Ferenc , Va Faye John , La Malfa Marco 
Published: October 2021

Abstract
Purpose
We investigated the safety of primary hip and knee replacements with same day discharge (SDD) and their effect on length of stay (LOS) of traditional inpatient arthroplasties at our elective orthopaedic ward.

Methods
200 patients underwent elective, unilateral primary day case total hip (THA, n = 94), total knee (TKA, n = 60) and unicondylar knee replacements (UKA, n = 46). SDD rates, reasons for failure to discharge, readmission, complication and satisfaction rates were recorded at 6-week follow up. Changes in LOS of inpatient arthroplasties (n = 6518) and rate of patients discharged with only one night stay treated at the same ward were tracked from 1 year prior to introduction of day case arthroplasty (DCA) program to the end of observation period.

Results
166 patients (83%) had SDD while 34 (17%) needed overnight stay. Main reasons for failure to discharge were lack of confidence (4%) fainting due to single vasovagal episode (3.5%), urine retention (3%) and late resolution of spinal anaesthesia (3%). 5 patients (3%) had readmission within 6 weeks, including 1 (0.6%) with a partial and treated pulmonary embolism. 163 patients were satisfied with SDD (98%). After launching the DCA program, average LOS of inpatients was reduced from 2.3 days to 1.8 days and rate of discharge with only 1-night stay increased from 12% to around 60%.

Conclusion
Introduction of routine SDD hip and knee arthroplasty programme at an elective orthopaedic centre is safe and also may confer wider benefits leading to shorter inpatient hospital stays.
A filled chocolates technique to seal negative-pressure wound therapy around external fixation devices: a randomized controlled trial
Authors: Fan Wei , Hou Fushan , Xi Kun , Hao Chen , Lu Xiangdong , Zhao Bin 
Published: October 2021

Abstract
Background
In complex injuries, external fixation device represents a challenge to maintain negative-pressure wound therapy (NPWT). In this trial, we compared a combination of bone wax and colostomy paste versus bone wax alone to seal NPWT around external fixation devices.

Methods
Debridement surgeries of limbs with open fracture and large soft tissue defect need NPWT to be applied around the external fixation devices were randomized into two groups. The seal between external fixation devices and the drape was established using either bone wax first and then reinforced with colostomy paste or bone wax alone. The primary outcome was seal failure within 3 days of debridement. Secondary outcomes included the number of seal failure per debridement surgery and the time spent in repairing the seal within 3 days.

Results
A total of 56 debridement surgeries were enrolled: 28 to the bone wax/colostomy paste group versus 28 to the bone wax control group. One patient in the control group died 1 day after the first debridement surgery. One patient in the bone wax/colostomy paste group was transferred to other hospitals within 3 days. The final analysis included 27 debridement surgeries in the bone wax/colostomy paste group and 27 debridement surgeries in the control group. The rate of seal failure (defined by loss of negative pressure at anytime within 3 days) was 81.5% (22/27) in the control group versus 11.1% (3/27) in the bone wax/colostomy paste group (p < 0.001; χ2 test). The bone wax/colostomy paste group also had significantly lower number of seal failures per debridement (median of 0 vs. 2; p = 0.004), and shorter time spent in repairing the seal (median of 0 vs. 18 min; p < 0.001).

Conclusions
Using bone wax followed by colostomy paste to seal NPWT around external fixation devices reduces seal failure.