bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the sustainment of population health programmes from a whole-of-system approach
Authors: Crane Melanie , Nathan Nicole , McKay Heather , Lee Karen , Wiggers John , Bauman Adrian 
Published: April 2022

Abstract
Background
Population health prevention programmes are needed to reduce the prevalence of chronic diseases. Nevertheless, sustaining programmes at a population level is challenging. Population health is highly influenced by social, economic and political environments and is vulnerable to these system-level changes. The aim of this research was to examine the factors and mechanisms contributing to the sustainment of population prevention programmes taking a systems thinking approach.

Methods
We conducted a qualitative study through interviews with population health experts working within Australian government and non-government agencies experienced in sustaining public health programs at the local, state or national level (n = 13). We used a deductive thematic approach, grounded in systems thinking to analyse data.

Results
We identified four key barriers affecting program sustainment: 1) short term political and funding cycles; 2) competing interests; 3) silo thinking within health service delivery; and 4) the fit of a program to population needs. To overcome these barriers various approaches have centred on the importance of long-range planning and resourcing, flexible program design and management, leadership and partnerships, evidence generation, and system support structures.

Conclusion
This study provides key insights for overcoming challenges to the sustainment of population health programmes amidst complex system-wide changes.
Pathogenicity comparison between QX-type and Mass-type infectious bronchitis virus to different segments of the oviducts in laying phase
Authors: Zhang Xiaorong , Yan Kun , Zhang Chengcheng , Guo Mengjiao , Chen Shuqin , Liao Kai , Bo Zongyi , Cao Yongzhong , Wu Yantao 
Published: April 2022

Abstract
Background
The QX-type infectious bronchitis virus (IBV) has become the predominant genotype worldwide in recent years and has caused serious economic losses to the chicken industry. The most significant feature of QX IBV is that its infection in the early growing stage can cause abnormal oviduct development, resulting in a high proportion of ‘false layers’ in poultry flocks of laying hens and breeders. However, few studies have evaluated whether infections of QX-type IBV in laying stages can also cause severe pathological changes in the oviduct.

Methods
In this study, 300-day-old specific-pathogen-free chickens were infected either with the QX-type strain QXL or Massachusetts (Mass)-type strain M41 to compare their pathogenicity on different segments of the oviduct.

Results
Both the QXL and M41 strains successfully replicated in all segments of the oviduct; however, the QXL strain was more highly distributed in mucosal layer and caused severe lesions in the lamina propria, including interstitial dilation, inflammatory cell infiltration, and distinct expansion of tubular glands. Moreover, the QXL strain induced high expression of proinflammatory cytokines and cytotoxic molecules in the majority of segments in the oviduct. Further research found that the QXL strain may affected the formation of shell membranes and eggshells by inhibiting the expression of type I collagen and CaBP-D28k.

Conclusions
Our results indicate that the QX-type IBV is more pathogenic than Mass-type IBV to oviduct in laying phase. Collectively, these findings provide detailed information on the pathological changes in different segments of the oviduct in laying phase, which could offer a better understanding about the pathogenicity of IBV.
Safety assessment of graphene oxide and microcystin-LR complex: a toxicological scenario beyond physical mixture
Authors: Ma Ying , Ding Xiaomeng , Liu Qing , Pang Yanting , Cao Yuna , Zhang Ting 
Published: April 2022

Abstract
Background
Nanomaterials have been widely used in electrochemistry, sensors, medicine among others applications, causing its inevitable environmental exposure. A raising question is the “carrier” effect due to unique surface properties of nanomaterials, which may collectively impact the bioavailability, toxicokinetic, distribution and biological effects of classic toxicants. Noteworthy, this aspect of information remains largely unexplored.

Methods
Here, we deliberately selected two entities to mimic this scenario. One is graphene oxide (GO), which is made in ton quantity with huge surface-area that provides hydrophilicity and π–π interaction to certain chemicals of unique structures. The other is Microcystin-LR (MCLR), a representative double-bond rich liver-toxic endotoxin widely distributed in aquatic-system. Firstly, the adsorption of GO and MCLR after meeting under environmental conditions was explored, and then we focused on the toxicological effect and related mechanism of GO-MCLR complex on human skin cutin forming cells (HaCaT cells) and normal liver cells (L02 cells).

Results
Abiotically, our study demonstrated that GO could effectively adsorb MCLR through hydrogen bonding and π–π interaction, the oxidation degree of GO-MCLR decreased significantly and surface defect level raised. Compared to GO or MCLR, GO-MCLR was found to induce more remarkable apoptosis and ferroptosis in both HaCaT and L02 cells. The underlying mechanism was that GO-MCLR induced stronger intracellular reactive oxygen species (ROS) and mtROS generation, followed by Fe2+ accumulation, mitochondrial dysfunction and cytoskeletal damage.

Conclusions
These results suggest that the GO-MCLR complex formed by GO adsorption of MCLR may exhibit more toxic effects than the single material, which demonstrates the necessity for assessing nano-toxicant complexity. Our discovery may serve as a new toxicological paradigm in which nanomaterial mediated surface adsorption effects could impact the degree of cytotoxicity and toxicological mechanisms of classic toxins.

Graphical Abstract
Foot Function Index for Arabic-speaking patients (FFI-Ar): translation, cross-cultural adaptation and validation study
Authors: Khan Shershah , Faulkner Suzanne , Algarni Fahad S. , Almalki Abdulaziz , Almansour Ahmed , Altowaijri Abdulrahman M. 
Published: April 2022

Abstract
Background
Foot Function Index (FFI) is a valid and reliable outcome measure, which is widely used to measure the foot and ankle functional level and disorders. Until now, no validated Arabic version of the FFI is available. This study was conducted at a tertiary care hospital in Riyadh, Saudi Arabia. The purpose of this project was to translate and adapt the FFI into Arabic and to evaluate its psychometric properties of validity and reliability.

Methods
The study consisted of two phases. The first phase was the translation and cultural adaptation of the FFI to Arabic. The next phase involved, testing the psychometric properties of the Arabic version of the FFI on a sample of 50 consecutive participants which included internal consistency, test–retest reliability, floor and ceiling effects and construct validity.

Results
The mean age of the study participants was 38 ± 12.94 years. Both the genders were evenly enrolled with 50% of the participants as male and 50% as female. Majority of them complained of plantar fasciopathy (32%) followed by pes planus (22%) and ankle sprain (18%). The scores of FFI-Ar were normally distributed, confirmed by a significant Shapiro–Wilk test. The mean value of FFI-Ar total score was 47.73 ± 19.85. There were no floor or ceiling effects seen in any of the subscales and total score. The internal consistency was good with the Cronbach’s alpha value of 0.882, 0.936 and 0.850 for the pain, disability and activity limitation subscales, respectively. The reproducibility of the FFI-Ar was analysed by intra-class correlation coefficient which revealed good to excellent test–retest reliability. A significant correlation was found between FFI-Ar and SF-36 and numeric rating scale (NRS) confirming its construct validity.

Conclusion
The FFI-Arabic version showed good validity and reliability in patients with foot and ankle problems. This tool can be used in usual practice and research for analysing foot and ankle disorders in Arabic-speaking people.
Posterior pilon fracture treated by opening the fibula fracture gap
Authors: Jiang Zhuang , Zhang Chen , Qin Jia-Jun , Wang Guo-Dong , Wang Hua-Song 
Published: April 2022

Abstract
Background
Posterior pilon fracture is a relatively common clinical fracture involving the posterior articular surface of the distal tibia. Currently, this form of fracture is receiving increasing attention. The surgical approach and technique for the treatment of posterior pilon fractures are still controversial. The purpose of this retrospective study was to compare the clinical and imaging outcomes of pilon fractures after treatment with the open fibula fracture line (OFFL) surgical technique versus the traditional posterolateral approach (TPL).

Methods
A retrospective analysis of patients with posterior pilon fractures treated using the open fibula fracture line technique and the traditional posterolateral approach between January 2015 and March 2020. Thirty-one cases were included in the open fibula fracture line technique group and twenty-eight cases were included in the traditional posterolateral approach group. We used the Burwell-Charnley scale to assess the effectiveness of surgical repositioning. The clinical outcomes were evaluated using American Orthopaedic Foot & Ankle Society ankle-hind foot score (AOFAS) and visual analog score (VAS).

Results
The overall anatomic reduction rate was slightly better in the open fibula fracture line group than in the conventional posterolateral group (81% vs. 71%, p = 0.406), but there was no statistically significant difference between the two groups. There were no statistically significant differences between the two groups in terms of fracture healing time and time to full weight bearing (p > 0.05). At the final follow-up, the AOFAS functional score of the open fibula fracture line group was statistically superior to that of the conventional posterolateral group (p < 0.05). However, there was no statistical difference between the two groups in VAS pain scores at rest, during activity, and under weight bearing (p > 0.05).

Conclusion
The trans-fibular fracture approach provides a better surgical option for specific types of posterior pilon fractures with a high rate of anatomic repositioning and a good near-term outcome.
Trial registration: Retrospective registration.
What is the optimal surgical treatment for Neer type IIB (IIC) distal clavicle fractures? A systematic review and meta-analysis
Authors: Panagopoulos Andreas , Solou Konstantina , Tatani Irini , Triantafyllopoulos Ioannis K. , Lakoumentas John , Kouzelis Antonis , Athanasiou Vasileios , Kokkalis Zinon T. 
Published: April 2022

Abstract
Background
The purpose of the present study was to systematically review the current treatment strategies for the treatment of Neer type IIB distal clavicle fractures in terms of functional outcome and complication rates and to examine the most appropriate surgical method by comparing all the available surgical techniques and implants.

Methods
We performed a systematic review of the existing literature (2000–2021) in accordance with the PRISMA statement. We searched PubMed, Scopus, Web of Science, Research Gate and Google Scholar using the general terms ‘distal AND clavicle AND fracture’ to capture as many reports as possible. The MINORS tool was used to assess the risk of bias of the nonrandomized studies. We categorized the reported surgical techniques into four main types: open or arthroscopic coracoclavicular (CC) stabilization, locking plate fixation with or without CC augmentation, hook plate fixation and acromioclavicular joint (ACJ) transfixation. We reported findings for two main outcomes: clinical results and complication rates categorized into major and minor.

Results
Our database search yielded a total of 630 records; 34 studies were appropriate for qualitative analysis. There were 790 patients, with a mean age of 40.1 years, a female percentage of 37% and a mean follow-up period of 29.3 months. In total, 132 patients received a hook plate, 252 received a locking plate, 368 received CC stabilization and 41 received transacromial transfixation. All studies were retrospective and had fair MINORS scores. Locking plate, CC stabilization and ACJ transfixation showed similar clinical results but were much better than hook plate fixation; CC augmentation did not significantly improve the outcome of locking plate fixation. The rate of major complications was similar among groups; hook plate and AC joint transfixation had the worst rates of minor complications. Open CC techniques were slightly better than arthroscopic techniques.

Conclusions
The present systematic review for the optimal fixation method for Neer type IIB fractures of the distal clavicle showed similar major complication rates among techniques; the hook plate technique demonstrated inferior clinical results to other techniques. Open CC stabilization and locking plate fixation without CC augmentation seem to be the best available treatment options.
Challenges in diagnosis and management of acute hepatic porphyrias: from an uncommon pediatric onset to innovative treatments and perspectives
Authors: Marcacci Matteo , Ricci Andrea , Cuoghi Chiara , Marchini Stefano , Pietrangelo Antonello , Ventura Paolo 
Published: April 2022

AbstractAcute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks, characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion, hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney disease. Most symptomatic patients have only a few attacks in their lifetime; nevertheless, some experience frequent attacks that result in ongoing symptoms and a significant negative impact on their quality of life (QoL). Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, $$\delta$$
δ
-aminolaevulinic acid and porphyrins using a single random (spot) sample. However, diagnosis is frequently missed or delayed, often for years, because the clinical symptoms of AHP are non-specific and mimic other more common disorders. Delayed diagnosis is of concern as some commonly used medications can trigger or exacerbate acute attacks, and untreated attacks can become severe, potentially leading to permanent neurological damage or fatality. Other attack triggers include hormonal fluctuations in women, stress, alcohol and low-calorie diets, which should be avoided in patients where possible. For the management of attacks, intravenous hemin is approved, whereas new therapeutic approaches are currently being investigated as a baseline therapy for prevention of attacks and improvement of QoL. Among these, a novel siRNA-based agent, givosiran, has shown very promising results in a recently concluded Phase III trial and has been approved for the management of AHPs. Here, we propose a challenging case study-with a very unusual pediatric onset of variegate porphyria-as a starting point to summarize the main clinical aspects (namely, clinical manifestations, diagnostic challenges, and therapeutic management) of AHPs, with a focus on the latest therapeutic innovations.
The role of tumor-infiltrating lymphocytes in cholangiocarcinoma
Authors: Liu Dong , Heij Lara Rosaline , Czigany Zoltan , Dahl Edgar , Lang Sven Arke , Ulmer Tom Florian , Luedde Tom , Neumann Ulf Peter , Bednarsch Jan 
Published: April 2022

AbstractCholangiocarcinoma (CCA) is the second most common primary liver cancer and associated with a dismal prognosis due to the lack of an efficient systemic therapy. In contrast to other cancers, new immunotherapies have demonstrated unsatisfactory results in clinical trials, underlining the importance of a deeper understanding of the special tumor microenvironment of CCA and the role of immune cells interacting with the tumor. Tumor-infiltrating lymphocytes (TILs) are an important component of the adaptive immune system and the foundation of current immunotherapy. Therefore, the aim of this systemic review is to summarize the current literature focusing on the proportions and distribution, molecular pathogenesis, prognostic significance of TILs and their role in immunotherapy for CCA patients.In CCA, CD8+ and CD4+ T lymphocytes represent the majority of TILs and are mostly sequestered around the cancer cells. CD20+ B lymphocytes and Natural Killer (NK) cells are less frequent. In contrast, Foxp3+ cells (regulatory T cells, Tregs) are observed to infiltrate into the tumor. In the immune microenvironment of CCA, cancer cells and stromal cells such as TAMs, TANs, MSDCs and CAFs inhibit the immune protection function of TILs by secreting factors like IL-10 and TGF-β. With respect to molecular pathogenesis, the Wnt/-catenin, TGF-signaling routes, aPKC-i/P-Sp1/Snail Signaling, B7-H1/PD-1Pathway and Fas/FasL signaling pathways are connected to the malignant potential and contributed to tumor immune evasion by increasing TIL apoptosis. Distinct subtypes of TILs show different prognostic implications for the long-term outcome in CCA. Although there are occasionally conflicting results, CD8+ and CD4+ T cells, and CD20+ B cells are positively correlated with the oncological prognosis of CCA, while a high number of Tregs is very likely associated with worse overall survival. TILs also play a major role in immunotherapy for CCA.In summary, the presence of TILs may represent an important marker for the prognosis and a potential target for novel therapy, but more clinical and translationaldata is needed to fully unravel the importance of TILs in the treatment of CCA.
Amniotic fluid embolism rescued by venoarterial extracorporeal membrane oxygenation
Authors: Aissi James Sarah , Klein Thomas , Lebreton Guillaume , Nizard Jacky , Chommeloux Juliette , Bréchot Nicolas , Pineton de Chambrun Marc , Hékimian Guillaume , Luyt Charles-Edouard , Levy Bruno , Kimmoun Antoine , Combes Alain , Schmidt Matthieu 
Published: April 2022

Abstract
Background
Amniotic fluid embolism (AFE) is a rare but often catastrophic complication of pregnancy that leads to cardiopulmonary dysfunction and severe disseminated intravascular coagulopathy (DIC). Although few case reports have reported successful use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) with AFE, concerns can be raised about the increased bleeding risks with that device.

Methods
This study included patients with AFE rescued by VA-ECMO hospitalized in two high ECMO volume centers between August 2008 and February 2021. Clinical characteristics, critical care management, in-intensive care unit (ICU) complications, and hospital outcomes were collected. ICU survivors were assessed for health-related quality of life (HRQL) in May 2021.

Results
During that 13-year study period, VA-ECMO was initiated in 54 parturient women in two high ECMO volume centers. Among that population, 10 patients with AFE [median (range) age 33 (24–40), SAPS II at 69 (56–81)] who fulfilled our diagnosis criteria were treated with VA-ECMO. Pregnancy evolved for 36 (30–41) weeks. Seven patients had a cardiac arrest before ECMO and two were cannulated under cardiopulmonary resuscitation. Pre-ECMO hemodynamic was severely impaired with an inotrope score at 370 (55–1530) μg/kg/min, a severe left ventricular ejection fraction measured at 14 (0–40)%, and lactate at 12 (2–30) mmol/L. 70% of these patients were alive at hospital discharge despite an extreme pre-ECMO severity and massive blood product transfusion. However, HRQL was lower than age-matched controls and still profoundly impaired in the role-physical, bodily pain, and general health components after a median of 44 months follow-up.

Conclusion
In this rare per-delivery complication, our results support the use of VA-ECMO despite intense DIC and ongoing bleeding. Future studies should focus on customized, patient-centered, rehabilitation programs that could lead to improved HRQL in this population.
Evaluation of the effect of targeted Mass Drug Administration and Reactive Case Detection on malaria transmission and elimination in Eastern Hararghe zone, Oromia, Ethiopia: a cluster randomized control trial
Authors: Abdelmenan Semira , Teka Hiwot , Hwang Jimee , Girma Samuel , Chibsa Sheleme , Tongren Eric , Murphy Matthew , Haile Mebrahatom , Dillu Dereje , Kassim Jawar , Behaksra Sinknesh , Tadesse Fitsum G. , Yukich Joshua , Berhane Yemane , Worku Alemayehu , Keating Joseph , Zewde Ayele , Gadisa Endalamaw 
Published: April 2022

Abstract
Background
Reactive and proactive case detection measures are widely implemented by national malaria elimination programs globally. Ethiopia decided to include Reactive Case Detection (RCD) and targeted Mass Drug Administration (tMDA) approaches as part of their elimination strategy along with rigorous evaluation. The purpose of this study is to compare the impact of RCD and tMDA on malaria elimination over the 2-year study period, by looking at the annual parasite incidence before and after the intervention.

Methods
The study will be conducted in the East Hararghe zone of Ethiopia. Malaria transmission in the area is low to moderate. This study will deploy a community-based, three-arm, cluster-randomized control trial implemented over 2 years. Forty-eight clusters (16 clusters per arm) will be selected based on the annual number of confirmed malaria cases seen in the cluster. All clusters will receive the current standard of care in terms of malaria elimination interventions provided by the national malaria control program. In addition, following the identification of malaria parasite infection, individuals who reside within a 100-m radius of the index case will receive a diagnosis for malaria and treatment if positive in the RCD arm or presumptive treatment in the tMDA arm. The primary effectiveness endpoint will be measured at baseline and endline for each intervention arm and compared to the control arm using a difference in difference approach.

Discussion
This randomized controlled trial will provide evidence of the impact of the proposed intervention approaches for malaria elimination.

Trial registration
ClinicalTrials.gov NCT04241705. Registration date: January 27, 2020.