bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a bundle of care to reduce incisional surgical site infection after gastrointestinal surgery
Authors: Phelan Liam , Dilworth Mark P , Bhangu Aneel , Limbrick Jack W , King Stratton , Bowley Doug M , Hardy Katie 
Published: December 2019

Background: Surgical site infection (SSI) is associated with morbidity, mortality and increased care costs; many SSIs are considered preventable. The aim of the present study was to test implementation of a pragmatic, evidence-based bundle designed to reduce incisional SSI after emergency laparotomy and elective major lower gastrointestinal surgery. Method: This was a prospective before-and-after study. Data were collected before the intervention and for two separate subsequent time periods. An evidence-based bundle of care (BOC) was implemented; the primary outcome measure was incisional SSI at 30 days. The secondary outcome measure was 30-day unplanned readmissions. The initial post-intervention group, Group 2, assessed a variable number of potential impacting factors; however, due to funding and staffing levels the second post-bundle group, Group 3, focused on the core aspects of the BOC and rates of incisional SSI and readmission. Results: In total, 99 patients were included in the ‘before’ group; and 71 in Group 2 and 92 in Group 3, the post-intervention groups. The incisional SSI rate was 29.3% (29/99) before and 28.2% (20/71) in Group 2 ( P=0.873) and 21.7% (20/92) in Group 3 ( P=0.234) after the intervention. After adjustment for confounders, the care bundle was associated with a non-significant reduction in SSI (Group 2: odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.45–1.93, P=0.0843). However, it was associated with significantly reduced readmissions 18.1% (18/99) before versus 5.6% (4/71) in Group 2 (OR = 0.236, 95% CI = 0.077–0.72, P=0.012) and 8.7% (8/92) in Group 3 (OR = 0.38, 95% CI = 0.16–0.9, P=0.029). Comparing the pre-bundle group to the post-bundle groups, there was an overall significant reduction in readmissions ( P=0.003). This implies a number needed to treat of 8–11 patients to prevent one readmission. Adherence to antibiotic prophylaxis with the Trust guidelines increased from 91% to 99% (1 vs. 2, P=0.047). Conclusion: Introduction of the bundle was associated with a reduction in the observed rate of incisional SSI from 29.3% to 21.7%; significantly fewer patients required unplanned readmission. Use of the bundle was associated with significantly improved compliance with appropriate antimicrobial prophylaxis.
Eribulin mesylate use as third-line therapy in patients with metastatic breast cancer (VESPRY): a prospective, multicentre, observational study
Authors: Adamo Vincenzo , Ricciardi Giuseppina Rosaria Rita , Giuffrida Dario , Scandurra Giuseppa , Russo Antonio , Blasi Livio , Spadaro Pietro , Iacono Carmelo , Soto Parra Hector J. , Savarino Antonino , Ferraú Francesco , Zerilli Filippo , Verderame Francesco , Butera Alfredo , Santangelo Carlo , Franchina Veronica , Caruso Michele 
Published: December 2019

Background: In real-world practice, eribulin mesylate provides significant survival benefit, with a manageable safety profile in heavily pretreated patients with metastatic breast cancer (MBC). Methods: In this prospective, open-label, multicentre, observational study we evaluated the effectiveness and tolerability of eribulin as third-line treatment in a homogeneous population. The primary endpoints were the safety profile and response in metastatic sites; secondary endpoints included the response in different subtypes, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: From 2013 to 2016, 118 women were treated in 21 Sicilian institutions; the median age was 58 years (range 29–79), with 69% of patients under 65. The median cycles of eribulin were 5.5 (range 1–26). The most common adverse event was neutropenia (9.3%, 3 cases of grade 3, 4 of grade 4); only 1 case of QT prolongation was reported. Eribulin was effective in controlling metastatic disease in all sites, and it achieved the highest ORR in brain (16%) and liver (14.9%). Median OS was 31.8 months (95% CI 27.9–34.4) and median PFS 5.5 months (95% CI 4.2–6.6). PFS was 5.2 months (95% CI 2.8–8.4) in patients with triple-negative subtype. Median PFS was longer in patients over 65 years (6.1 months, 95% CI 4.4–8.3). In patients who had visceral metastases PFS was 5.5 months (95% CI 95% 3.5–6.6) and OS 33.9 months (95% CI 29.8–40.8). Conclusions: Eribulin as third-line treatment shows an acceptable safety profile and a substantial antitumour activity in the treatment of MBC, even in elderly patients and in those with visceral disease.
Treat-to-target strategy for knee osteoarthritis. International technical expert panel consensus and good clinical practice statements
Authors: Migliore Alberto , Gigliucci Gianfranco , Alekseeva Liudmila , Avasthi Sachin , Bannuru Raveendhara R , Chevalier Xavier , Conrozier Thierry , Crimaldi Sergio , Damjanov Nemanja , de Campos Gustavo Constantino , Diracoglu Demirhan , Herrero-Beaumont Gabriel , Iolascon Giovanni , Ionescu Ruxandra , Isailovic Natasa , Jerosch Jörg , Lains Jorge , Maheu Emmanuel , Makri Souzi , Martusevich Natalia , Matucci Cerinc Marco , Micu Mihaela , Pavelka Karel , Petrella Robert J , Tarantino Umberto , Raman Raghu 
Published: December 2019

Background: In this work, we aimed to establish a clinical target in the management of knee osteoarthritis (KOA) and to propose good clinical practice (GCP) statements for carrying out a treat-to-target strategy. Methods: A steering committee of seven experts had formulated a provisional set of recommendations that were exposed for discussion and modification to a technical expert panel (TEP) of 25 multidisciplinary experts from Europe, North America, South America and Asia. The level of evidence and strength of each recommendation was discussed. The TEP formulated overarching principles and GCP statements based on the level of agreement for each item with a vote using a 10-point numerical scale. Results: Two overarching principles and 10 GCP statements were formulated by the TEP. These GCP statements suggest: treatment should achieve clinical improvement bringing the patient to the Patient Acceptable Symptom State (PASS); pharmacological and nonpharmacological treatment should begin as early as possible, with an early diagnosis of symptomatic KOA; the patient should be evaluated every 3–6 months; risk factors of KOA progression should be identified and managed with patients at the beginning of the treatment and monitored regularly; treatment should be adapted according to patient phenotype and disease severity; healthy lifestyle must be promoted and monitored. The level of agreement average ranged from 8.7 to 9.6 on scale. Conclusions: The proposed overarching principles and GCP statements have the aim of involving patients, general practitioners and multidisciplinary specialists in sharing a therapeutic treat-to-target strategy for KOA management based on the best evidence and expert opinions.
Return-to-Play and Rehabilitation Protocols following Cartilage Restoration Procedures of the Knee: A Systematic Review
Authors: Hurley Eoghan T. , Davey Martin S. , Jamal M. Shazil , Manjunath Amit K. , Alaia Michael J. , Strauss Eric J. 
Published: December 2019

Objective The purpose of this study is to systematically review the literature and to evaluate the reported rehabilitation protocols, return-to-play guidelines, and subsequent rates of return to play following cartilage restoration procedures in the knee. Design MEDLINE, EMBASE, and the Cochrane Library were searched according to the PRISMA guidelines to find studies on cartilage restoration procedures in the knee, including (1) microfracture (Mfx), (2) osteochondral autograft transfer (AOT), (3) osteochondral allograft implantation (OCA), and (4) autologous chondrocyte implantation (ACI). Studies were included if they reported return-to-play data or rehabilitation protocols. Results Overall, 179 studies fit our inclusion criteria, with 48 on Mfx, 34 on AOT, 54 on OCA, and 51 on ACI. The rate of return to play was reported as high as 88.2% with AOT, and as low as 77.2% following OCA, with rates of return to play at the same/higher level as high as 79.3% with AOT, and as low as 57.3% following ACI. The average reported time of return to play was as low as 4.9 months with AOT, and as high as 11.6 months following ACI. Conclusions The majority of patients are able to return to play following cartilage restoration procedures in the knee, regardless of surgical procedure utilized. However, while the rate of return to play at the same level was similar to the overall rate of return following AOT, there was a large number of patients unable to return to the same level following Mfx, OCA, and ACI. Additionally, there is wide variety in the rehabilitation protocols, and scant literature on return-to-play protocols.
Health-Related Needs and Barriers for Forcibly Displaced Women: A Systematic Review
Authors: Jesuthasan Jenny , Witte Zara , Oertelt-Prigione Sabine 
Published: December 2019

The number of forcibly displaced people has been steadily increasing over the last decades. Women represent a large proportion of this population. Due to gender roles, duties of care, educational and economic imbalances, their experiences during flight and relocation differ from those of men and children. The currently available information about their specific health-related needs and barriers to access is scarce. We sought to explore the specific needs of the female refugee population employing a user-centered perspective. Rather than focusing on provider-designed interventions, we aimed at defining what female refugees want and need and which priorities they define themselves. We searched PubMed, Medline, EMBASE, Cochrane Library, and Scopus to identify publications that explored the unique experiences of female refugees between January 1, 2008 and June 30, 2018. Publications needed to address the health needs of refugees, asylum seekers, or displaced individuals, include at least 50% women in their study and employ a user-centered perspective. A framework of themes was identified and applied to all publications. We identified 1945 publications of which 13 could be included in the present review. Twelve of these publications employed qualitative and/or innovative methodology. We identified 5 broad categories of health-related needs (immediate health care, communication, cultural/spiritual, social, and economic). The identified publications described the need for complex, coordinated approaches. Concerted action providing information and culturally sensitive care, while supporting language acquisition and economic empowerment is essential to improve the health status of female refugees. Transformative interventions need to address multiple axes of unequal access for female refugees to improve their overall health.
Clinical Spectrum and Long-Term Anatomical and Functional Outcomes of Pars Plana Vitrectomy in Retinal Detachments Associated With Choroidal Coloboma
Authors: Kannan Naresh Babu , Sen Sagnik , Kohli Piyush , Ramachandran Obuli , Ramasamy Kim 
Published: December 2019

Purpose: Choroidal coloboma (CC) eyes are associated with a high risk of retinal detachment (RD), which are challenging to repair. Methods: We retrospectively evaluated medical records of 30 patients with CC associated with RD who underwent pars plana vitrectomy at our tertiary care center. Data recorded were age, CC and RD morphology, breaks, resurgeries performed, and final outcome. Results: Patients’ ages ranged from 2 to 49 years. CC was present in 53 of 60 eyes (88%), with 41 of 60 eyes (68.3%) associated with iris coloboma. RD was present in 36 of 53 CC eyes (67.9%), with 10 of 53 (18.9%) having bilateral RD. Thirty-one eyes with RD underwent 23-gauge pars plana vitrectomy. Colobomatous region breaks were detected in 5 of 31 eyes (16.1%), peripheral breaks only in 12 of 31 (38.7%), and both types in 3 of 31 eyes (9.7%). Silicone oil endotamponade was used in 29 of 31 eyes (93.5%) and perfluoropropane (C3F8) in 2 of 31 eyes (6.45%). Median postoperative follow-up duration was 31.5 months. Fourteen of 31 eyes (45.2%) developed redetachment requiring resurgery, with 50% developing within 6 months. Eighteen of 31 eyes (58.1%) maintained retinal attachment at last follow-up without endotamponade, whereas the rest were oil filled. Final visual outcome between macula-involved and macula-spared CC eyes was not significantly different; however, best visual acuity achieved any time during follow-up was significantly better in macula-spared eyes. Conclusions: RD surgery in CC eyes has a risk of frequent redetachments and subnormal gain of vision over the long term, especially in colobomas involving the macula. Endolaser in 360° peripheries in addition to barrage of the margin of the coloboma may be considered to help maintain the attached retina.
Mesoporous Silica Nanoparticle–Based Combination of NQO1 Inhibitor and 5-Fluorouracil for Potent Antitumor Effect Against Head and Neck Squamous Cell Carcinoma (HNSCC)
Authors: Chen Jing , Zhang Shuzhen , Zhang Shuai , Gao Shanjun , Wang Jianbo , Lei Dongchun , Du Pengqiang , Xu Zhiwei , Zhu Cailiang , Sun Hongbin 
Published: December 2019

AbstractHead and neck squamous cell carcinomas (HNSCC) are one of the deadliest forms of cancer, and 90% of its origin is from squamous cells. NAD(P)H:quinone oxidoreductase 1 (NQO1), an enzyme overexpressed in squamous cell carcinoma, plays an important role in proliferation and chemoresistance. The main aims were to study the inhibitory effect of ß-lapachone (ARQ761 in clinical form) in HNSCC and to study the combinational effect of 5-FU and ß-lap in improving the therapeutic efficacy in HNSCC. Lipid bilayer–assembled mesoporous silica nanoparticles loaded with 5-FU/ß-lap were prepared and studied for its physicochemical and biological properties. ß-lap showed a concentration-dependent inhibition of NQO1 enzyme activity in Cal33 cells. Notably, significant inhibitory effect was observed at a dose of 20–50 μg/ml of ß-lap. Combination of 5-FU+ß-lap resulted in lower cell viability; most notably, 5-FU/ß-lap-loaded mesoporous silica nanoparticles (FNQ-MSN) exhibited significantly lower cell viability compared with that of any of the individual drug or physical combinations. ß-lap resulted in a decrease in the protein band of NQO1 compared with control; however, most notable decrease in the NQO1 level was observed in the FNQ-MSN-treated cell group. FNQ-MSN resulted in more than 60% of cell apoptosis (early and late apoptosis) and predominant nuclear fragmentation of cancer cells indicating the superior anticancer effect of a carrier-based combination regimen. Notable decrease in tumor volume was observed with the physical mixture of 5-FU+ß-lap; however, combined treatment of carrier-based 5-FU and ß-lap (FNQ-MSN) significantly delayed the tumor growth and prolonged the survival of tumor-bearing xenograft mice. These findings suggest the potential of NQO1 inhibitor in enhancing the chemotherapeutic potential of 5-FU in the treatment of HNSCC.
Variability of mitochondrial ORFans hints at possible differences in the system of doubly uniparental inheritance of mitochondria among families of freshwater mussels (Bivalvia: Unionida)
Authors: Guerra Davide , Lopes-Lima Manuel , Froufe Elsa , Gan Han Ming , Ondina Paz , Amaro Rafaela , Klunzinger Michael W. , Callil Claudia , Prié Vincent , Bogan Arthur E. , Stewart Donald T. , Breton Sophie 
Published: December 2019

Abstract
Background
Supernumerary ORFan genes (i.e., open reading frames without obvious homology to other genes) are present in the mitochondrial genomes of gonochoric freshwater mussels (Bivalvia: Unionida) showing doubly uniparental inheritance (DUI) of mitochondria. DUI is a system in which distinct female-transmitted and male-transmitted mitotypes coexist in a single species. In families Unionidae and Margaritiferidae, the transition from dioecy to hermaphroditism and the loss of DUI appear to be linked, and this event seems to affect the integrity of the ORFan genes. These observations led to the hypothesis that the ORFans have a role in DUI and/or sex determination. Complete mitochondrial genome sequences are however scarce for most families of freshwater mussels, therefore hindering a clear localization of DUI in the various lineages and a comprehensive understanding of the influence of the ORFans on DUI and sexual systems. Therefore, we sequenced and characterized eleven new mitogenomes from poorly sampled freshwater mussel families to gather information on the evolution and variability of the ORFan genes and their protein products.

Results
We obtained ten complete plus one almost complete mitogenome sequence from ten representative species (gonochoric and hermaphroditic) of families Margaritiferidae, Hyriidae, Mulleriidae, and Iridinidae. ORFan genes are present only in DUI species from Margaritiferidae and Hyriidae, while non-DUI species from Hyriidae, Iridinidae, and Mulleriidae lack them completely, independently of their sexual system. Comparisons among the proteins translated from the newly characterized ORFans and already known ones provide evidence of conserved structures, as well as family-specific features.

Conclusions
The ORFan proteins show a comparable organization of secondary structures among different families of freshwater mussels, which supports a conserved physiological role, but also have distinctive family-specific features. Given this latter observation and the fact that the ORFans can be either highly mutated or completely absent in species that secondarily lost DUI depending on their respective family, we hypothesize that some aspects of the connection among ORFans, sexual systems, and DUI may differ in the various lineages of unionids.
New insights into mammalian sex chromosome structure and evolution using high-quality sequences from bovine X and Y chromosomes
Authors: Liu Ruijie , Low Wai Yee , Tearle Rick , Koren Sergey , Ghurye Jay , Rhie Arang , Phillippy Adam M. , Rosen Benjamin D. , Bickhart Derek M. , Smith Timothy P. L. , Hiendleder Stefan , Williams John L. 
Published: December 2019

Abstract
Background
Mammalian X chromosomes are mainly euchromatic with a similar size and structure among species whereas Y chromosomes are smaller, have undergone substantial evolutionary changes and accumulated male specific genes and genes involved in sex determination. The pseudoautosomal region (PAR) is conserved on the X and Y and pair during meiosis. The structure, evolution and function of mammalian sex chromosomes, particularly the Y chromsome, is still poorly understood because few species have high quality sex chromosome assemblies.

Results
Here we report the first bovine sex chromosome assemblies that include the complete PAR spanning 6.84 Mb and three Y chromosome X-degenerate (X-d) regions. The PAR comprises 31 genes, including genes that are missing from the X chromosome in current cattle, sheep and goat reference genomes. Twenty-nine PAR genes are single-copy genes and two are multi-copy gene families, OBP, which has 3 copies and BDA20, which has 4 copies. The Y chromosome X-d1, 2a and 2b regions contain 11, 2 and 2 gametologs, respectively.

Conclusions
The ruminant PAR comprises 31 genes and is similar to the PAR of pig and dog but extends further than those of human and horse. Differences in the pseudoautosomal boundaries are consistent with evolutionary divergence times. A bovidae-specific expansion of members of the lipocalin gene family in the PAR reported here, may affect immune-modulation and anti-inflammatory responses in ruminants. Comparison of the X-d regions of Y chromosomes across species revealed that five of the X-Y gametologs, which are known to be global regulators of gene activity and candidate sexual dimorphism genes, are conserved.
Combining transcriptomics and metabolomics to reveal the underlying molecular mechanism of ergosterol biosynthesis during the fruiting process of Flammulina velutipes
Authors: Wang Ruihong , Ma Pengda , Li Chen , Xiao Lingang , Liang Zongsuo , Dong Juane 
Published: December 2019

Abstract
Background
Flammulina velutipes has been recognized as a useful basidiomycete with nutritional and medicinal values. Ergosterol, one of the main sterols of F. velutipes is an important precursor of novel anticancer and anti-HIV drugs. Therefore, many studies have focused on the biosynthesis of ergosterol and have attempted to upregulate its content in multiple organisms. Great progress has been made in understanding the regulation of ergosterol biosynthesis in Saccharomyces cerevisiae. However, this molecular mechanism in F. velutipes remains largely uncharacterized.

Results
In this study, nine cDNA libraries, prepared from mycelia, young fruiting bodies and mature fruiting bodies of F. velutipes (three replicate sets for each stage), were sequenced using the Illumina HiSeq™ 4000 platform, resulting in at least 6.63 Gb of clean reads from each library. We studied the changes in genes and metabolites in the ergosterol biosynthesis pathway of F. velutipes during the development of fruiting bodies. A total of 13 genes (6 upregulated and 7 downregulated) were differentially expressed during the development from mycelia to young fruiting bodies (T1), while only 1 gene (1 downregulated) was differentially expressed during the development from young fruiting bodies to mature fruiting bodies (T2). A total of 7 metabolites (3 increased and 4 reduced) were found to have changed in content during T1, and 4 metabolites (4 increased) were found to be different during T2. A conjoint analysis of the genome-wide connection network revealed that the metabolites that were more likely to be regulated were primarily in the post-squalene pathway.

Conclusions
This study provides useful information for understanding the regulation of ergosterol biosynthesis and the regulatory relationship between metabolites and genes in the ergosterol biosynthesis pathway during the development of fruiting bodies in F. velutipes.