bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vulvar cancer during pregnancy and/or breastfeeding: a report of five cases from a single center study at the University Hospital of Düsseldorf
Authors: Winarno Andreas Suhartoyo , Fehm Tanja Natascha , Hampl Monika 
Published: March 2022

Abstract
Background
The incidence of vulvar cancer (VC) in pregnancy is unknown due to its rarity; between 1955 and 2014 only 36 case reports were reported worldwide. Underreporting may also be a contributing factor to the unknown incidence of VC in pregnancy. The aim of this study was to analyze the diagnosis, treatment and outcome of vulvar cancer cases diagnosed during pregnancy and/or breastfeeding.

Case presentation
Patient 1 was diagnosed at 18 weeks’ gestation (WG) with Grade 2 VC (pT1a, pN0, 0/4 sentinel lymph nodes biopsy (SLNB) involved) and was treated by having the tumor resected (R0). She is currently recurrence-free at 4 years post-diagnosis.
Patient 2 was diagnosed at 7 WG with Grade 2 VC (pT1b, pN1a, 1/17 SLNB, R0) and was treated during the first trimester and during the second trimester with SLNB. She is currently recurrence-free at 5 years post-diagnosis.
Patient 3 was diagnosed at 30 WG with Grade 2 VC (pT1b, pN0, 0/5 SLNB, R0). She subsequently experienced a number of local recurrences postpartum that were managed by resection and is currently recurrence-free at 3 years post-diagnosis.
Patient 4 was diagnosed a VL later, at 14 months during breastfeeding, that was diagnosed as Grade 3 VC (pT1b, pN1a, 1/14 SLNB, R0). The patient is currently recurrence-free at 9 years post-diagnosis.
Patient 5 was not diagnosed during pregnancy, but was diagnosed with G3 VC (pT2, pN2c, 2/17 SLNB, R0) 8 months postpartum. The patient due to the extent of tumor involvement and lymph node metastasis, underwent chemoradiation therapy post-surgery. Despite adjuvant therapy, the patient progressed and developed bone metastases. Analysis of the tumour tissue revealed increased expression of PD-L1 (programmed cell death protein 1) indicating that the patient may have benefited from treatment with nivolumab to block the PD-L1 interaction; unfortunately the patient passed away at 24 months post-diagnosis before immunotherapy treatment could commence.

Conclusion
Surgical resection and simultaneous SLNB in VC cases are considered safe during pregnancy, with comparable outcomes to non-pregnant women. Prompt diagnostic workup and treatment should never be delayed during pregnancy as delayed diagnosis could lead to tumour progression with fatal consequences.
Assessment of transparency and selective reporting of interventional trials studying colorectal cancer
Authors: Pellat Anna , Boutron Isabelle , Ravaud Philippe 
Published: March 2022

Abstract
Background
Colorectal cancer (CRC) is currently one of the most frequently diagnosed cancers. Our aim was to evaluate transparency and selective reporting in interventional trials studying CRC.

Methods
First, we assessed indicators of transparency with completeness of reporting, according to the CONSORT statement, and data sharing. We evaluated a selection of reporting items for a sample of randomized controlled trials (RCTs) studying CRC with published full-text articles between 2021–03-22 and 2018–03-22. Selected items were issued from the previously published CONSORT based peer-review tool (COBPeer tool). Then, we evaluated selective reporting through retrospective registration and primary outcome(s) switching between registration and publication. Finally, we determined if primary outcome(s) switching favored significant outcomes.

Results
We evaluated 101 RCTs with published full-text articles between 2021–03-22 and 2018–03-22. Five trials (5%) reported all selected CONSORT items completely. Seventy-four (73%), 53 (52%) and 13 (13%) trials reported the primary outcome(s), the allocation concealment process and harms completely. Twenty-five (25%) trials were willing to share data. In our sample, 49 (49%) trials were retrospectively registered and 23 (23%) trials had primary outcome(s) switching. The influence of primary outcome(s) switching could be evaluated in 16 (16/23 = 70%) trials, with 6 (6/16 = 38%) trials showing a discrepancy that favored statistically significant results.

Conclusions
Our results highlight a lack of transparency as well as frequent selective reporting in interventional trials studying CRC.
Decomposing urban-rural differences in multimorbidity among older adults in India: a study based on LASI data
Authors: Chauhan Shekhar , Srivastava Shobhit , Kumar Pradeep , Patel Ratna 
Published: March 2022

Abstract
Background
Multimorbidity is defined as the co-occurrence of two or more than two diseases in the same person. With rising longevity, multimorbidity has become a prominent concern among the older population. Evidence from both developed and developing countries shows that older people are at much higher risk of multimorbidity; however, urban-rural differential remained scarce. Therefore, this study examines urban-rural differential in multimorbidity among older adults by decomposing the risk factors of multimorbidity and identifying the covariates that contributed to the change in multimorbidity.

Methods
The study utilized information from 31,464 older adults (rural-20,725 and urban-10,739) aged 60 years and above from the recent release cross-sectional data of the Longitudinal Ageing Study in India (LASI). Descriptive, bivariate, and multivariate decomposition analysis techniques were used.

Results
Overall, significant urban-rural differences were found in the prevalence of multimorbidity among older adults (difference: 16.3; p < 0.001). The multivariate decomposition analysis revealed that about 51% of the overall differences (urban-rural) in the prevalence of multimorbidity among older adults was due to compositional characteristics (endowments). In contrast, the remaining 49% was due to the difference in the effect of characteristics (Coefficient). Moreover, obese/overweight and high-risk waist circumference were found to narrow the difference in the prevalence of multimorbidity among older adults between urban and rural areas by 8% and 9.1%, respectively. Work status and education were found to reduce the urban-rural gap in the prevalence of multimorbidity among older adults by 8% and 6%, respectively.

Conclusions
There is a need to substantially increase the public sector investment in healthcare to address the multimorbidity among older adults, more so in urban areas, without compromising the needs of older adults in rural areas.
Incarcerated workers: overlooked as essential workers
Authors: Segule Marjorie Naila , LeMasters Katherine , Peterson Meghan , Behne Michael Forrest , Brinkley-Rubinstein Lauren 
Published: March 2022

Abstract
Objective
To use the example of COVID-19 vaccine prioritization for incarcerated workers to call attention to the need to prioritize incarcerated workers’ health.

Methods
From November to December 2020, we searched publicly available information (e.g. Department Of Corrections websites and press releases) for 53 US prison systems, including all states, Immigration and Customs Enforcement, the Federal Bureau of Prisons, and Puerto Rico. Coders reviewed if states had prison labor policies, if states had COVID-19 specific prison labor policies, the location of work, industries both pre- and during the COVID-19 pandemic, the scope of work, and hourly wage. Findings were compared to the Centers for Disease Control and Prevention’s occupational vaccine prioritization recommendations.

Results
Every facility has incarcerated individuals working in some capacity with some resuming prison labor operations to pre-pandemic levels. All but one prison system has off-site work locations for their incarcerated population and many incarcerated workers have resumed their off-site work release assignments. Additionally, every state has incarcerated workers whose job assignments are considered frontline essential workers (e.g. firefighters). In at least five states, incarcerated workers are participating in frontline health roles that put them at higher risk of acquiring COVID-19. Yet, no state followed the Centers for Disease Control and Prevention recommended vaccination plan for its incarcerated population given their incarcerated workers’ essential worker status.

Conclusion
The Centers for Disease Control and Prevention recommended that incarcerated people be prioritized for vaccination primarily due to the risk present in congregate style prison and jail facilities. Furthermore, our review found that many incarcerated people perform labor that should be considered “essential”, which provides another reason why they should have been among the first in line for COVID-19 vaccine allocation. These findings also highlight the need for incarcerated workers’ health to be prioritized beyond COVID-19.
Are all domains created equal? An exploration of stakeholder views on the concept of physical literacy
Authors: Belton Sarahjane , Connolly Sinead , Peers Cameron , Goss Hannah , Murphy Marie , Murtagh Elaine , Kavanagh Jennifer , Corr Méabh , Ferguson Kyle , O’Brien Wesley 
Published: March 2022

Abstract
Background
Developing physical literacy at population levels provides a transformative appeal for those working in sport, health, education, recreation and physical activity settings. Interdisciplinary approaches to development of policy in this area is recommended. The purpose of this study was to gather empirical data from key stakeholders working with young people in areas related to physical literacy across the Republic of Ireland and Northern Ireland, to capture their current understanding and awareness of the physical literacy to help inform the development of the first all-island consensus statement for physical literacy.

Methods
A total of 1,241 participants (52% male), from a range of stakeholder groups (health, physical activity, sport, recreation and education) completed a researcher developed physical literacy questionnaire. A one-way MANOVA was carried out to investigate differences across stakeholder grouping in terms of perceived importance of three domains of physical literacy. Overlap of independent confidence intervals was analysed to determine importance of the physical literacy domains within stakeholder grouping.

Results
A majority (63%) of respondents indicated they were aware of an existing definition of physical literacy, but this varied by stakeholder group (e.g. 86% for higher education, versus 47% of coaches). Participants working in higher education (69%), or working as physical education specialists (67%), were more likely to rate themselves as experts or near experts in physical literacy, while coaches, education generalists, and decision makers were more likely rate themselves as having no expertise (9%, 12% and 12% respectively). Non-specialist teachers and physical education teachers rated the importance of all domains of physical literacy significantly higher than decision makers, and significantly higher than coaches in the cognitive and affective domains. All stakeholders significantly rated the importance of the physical/psychomotor domain of physical literacy higher than the affective or cognitive domains of physical literacy.

Conclusions
Differences observed across stakeholder groups underline the importance of developing a shared vision for physical literacy, and the need to clarify and gain consensus on a definition of the term and its domains. Engaging and understanding the voice of stakeholders is critical in ensuring the relevance, ownership of and commitment to physical literacy statement operationalisation.
An enhanced recovery after surgery pathway: LOS reduction, rapid discharge and minimal complications after anterior cervical spine surgery
Authors: Leng Xue , Zhang Yaqing , Wang Guanzhong , Liu Libangxi , Fu Jiawei , Yang Minghui , Chen Yu , Yuan Jiawei , Li Changqing , Zhou Yue , Feng Chencheng , Huang Bo 
Published: March 2022

Abstract
Background
Enhance recovery after surgery (ERAS) is a new and promising paradigm for spine surgery. The purpose of this study is to investigate the effectiveness and safety of a multimodal and evidence-based ERAS pathway to the patients undergoing anterior cervical discectomy and fusion (ACDF).

Methods
The patients treated with the ACDF-ERAS pathway were compared with a historical cohort of patients who underwent ACDF before ERAS pathway implementation. Primary outcome was length of stay (LOS). Secondary outcomes included cost, MacNab grading, complication rates and 90-day readmission and reoperation. And perioperative factors and postoperative complications were reviewed.

Results
The ERAS protocol was composed of 21 components. More patients undergoing multi-level surgery (n ≥ 3) were included in the ERAS group. The ERAS group showed a shorter LOS and a lower cost than the conventional group. The postoperative satisfaction of patients in ERAS group was better than that in conventional group. In addition, the rate of overall complications was significantly higher in the conventional group than that in the ERAS group. There were no significant differences in operative time, postoperative drainage, or 90-day readmission and reoperation.

Conclusions
The ACDF-tailored ERAS pathway can reduce LOS, cost and postoperative complications, and improve patient satisfaction without increasing 90-day readmission and reoperation.
The impact of organisational characteristics of staff and facility on infectious disease outbreaks in care homes: a systematic review
Authors: Liljas A. E. M. , Morath L. P. , Burström B. , Schön P. , Agerholm J. 
Published: March 2022

Abstract
Background
Infectious disease outbreaks are common in care homes, often with substantial impact on the rates of infection and mortality of the residents, who primarily are older people vulnerable to infections. There is growing evidence that organisational characteristics of staff and facility might play a role in infectious disease outbreaks however such evidence have not previously been systematically reviewed. Therefore, this systematic review aims to examine the impact of facility and staff characteristics on the risk of infectious disease outbreaks in care homes.

Methods
Five databases (MEDLINE, EMBASE, ProQuest, Web of Science, CINAHL) were searched. Studies considered for inclusion were of any design reporting on an outbreak of any infectious disease in one or more care homes providing care for primarily older people with original data on: facility size, facility location (urban/rural), facility design, use of temporary hired staff, staff compartmentalizing, residence of staff, and/or nursing aides hours per resident. Retrieved studies were screened, assessed for quality using CASP, and analysed employing a narrative synthesis.

Results
Sixteen studies (8 cohort studies, 6 cross-sectional studies, 2 case-control) were included from the search which generated 10,424 unique records. COVID-19 was the most commonly reported cause of outbreak (n = 11). The other studies focused on influenza, respiratory and gastrointestinal outbreaks. Most studies reported on the impact of facility size (n = 11) followed by facility design (n = 4), use of temporary hired staff (n = 3), facility location (n = 2), staff compartmentalizing (n = 2), nurse aides hours (n = 2) and residence of staff (n = 1). Findings suggest that urban location and larger facility size may be associated with greater risks of an infectious disease outbreak. Additionally, the risk of a larger outbreak seems lower in larger facilities. Whilst staff compartmentalizing may be associated with lower risk of an outbreak, staff residing in highly infected areas may be associated with greater risk of outbreak. The influence of facility design, use of temporary staff, and nurse aides hours remains unclear.

Conclusions
This systematic review suggests that larger facilities have greater risks of infectious disease outbreaks, yet the risk of a larger outbreak seems lower in larger facilities. Due to lack of robust findings the impact of facility and staff characteristics on infectious disease outbreaks remain largely unknown.

Prospero
CRD42020213585.
Combining faecal immunochemical testing with blood test results for colorectal cancer risk stratification: a consecutive cohort of 16,604 patients presenting to primary care
Authors: Withrow Diana R. , Shine Brian , Oke Jason , Tamm Andres , James Tim , Morris Eva , Davies Jim , Harris Steve , East James E. , Nicholson Brian D. 
Published: March 2022

AbstractBackgroundFaecal immunochemical tests (FITs) are used to triage primary care patients with symptoms that could be caused by colorectal cancer for referral to colonoscopy. The aim of this study was to determine whether combining FIT with routine blood test results could improve the performance of FIT in the primary care setting.MethodsResults of all consecutive FITs requested by primary care providers between March 2017 and December 2020 were retrieved from the Oxford University Hospitals NHS Foundation Trust. Demographic factors (age, sex), reason for referral, and results of blood tests within 90 days were also retrieved. Patients were followed up for incident colorectal cancer in linked hospital records. The sensitivity, specificity, positive and negative predictive values of FIT alone, FIT paired with blood test results, and several multivariable FIT models, were compared.ResultsOne hundred thirty-nine colorectal cancers were diagnosed (0.8%). Sensitivity and specificity of FIT alone at a threshold of 10 μg Hb/g were 92.1 and 91.5% respectively. Compared to FIT alone, blood test results did not improve the performance of FIT. Pairing blood test results with FIT increased specificity but decreased sensitivity. Multivariable models including blood tests performed similarly to FIT alone.ConclusionsFIT is a highly sensitive tool for identifying higher risk individuals presenting to primary care with lower risk symptoms. Combining blood test results with FIT does not appear to lead to better discrimination for colorectal cancer than using FIT alone.
Evaluation of factors influencing expression and extraction of recombinant bacteriophage endolysins in Escherichia coli
Authors: Balaban Cecilia Lucía , Suárez Cristian Alejandro , Boncompain Carina Andrea , Peressutti-Bacci Natalia , Ceccarelli Eduardo Augusto , Morbidoni Héctor Ricardo 
Published: March 2022

Abstract
Background
Endolysins are peptidoglycan hydrolases with promising use as environment-friendly antibacterials mainly when used topically. However, in general, endolysin expression is hampered by its low solubility. Thus, a critical point in endolysin industrial production is optimizing their expression, including improvement of solubility and recovery from cell extracts.

Results
We report the expression of two endolysins encoded in the genome of phages infecting Staphylococcus aureus. Expression was optimized through changes in the concentration of the inducer and growth temperature during the expression. Usually, only 30–40% of the total endolysin was recovered in the soluble fraction. Co-expression of molecular chaperones (DnaK, GroEL) or N-term fusion tags endowed with increased solubility (DsbC, Trx, Sumo) failed to improve that yield substantially. Inclusion of osmolytes (NaCl, CaCl2, mannitol, glycine betaine, glycerol and trehalose) or tensioactives (Triton X-100, Tween 20, Nonidet P-40, CHAPS, N-lauroylsarcosine) in the cell disruption system (in the absence of any molecular chaperone) gave meager improvements excepted by N-lauroylsarcosine which increased recovery to 54% of the total endolysin content.

Conclusion
This is the first attempt to systematically analyze methods for increasing yields of recombinant endolysins. We herein show that neither solubility tags nor molecular chaperones co-expression are effective to that end, while induction temperature, (His)6-tag location and lysis buffer additives (e.g.N-lauroylsarcosine), are sensible strategies to obtain higher levels of soluble S. aureus endolysins.
Establishment and validation of a novel invasion-related gene signature for predicting the prognosis of ovarian cancer
Authors: Liang Leilei , Li Jian , Yu Jing , Liu Jing , Xiu Lin , Zeng Jia , Wang Tiantian , Li Ning , Wu Lingying 
Published: March 2022

Abstract
Background
Ovarian cancer (OC) is an invasive gynaecologic cancer with a high cancer-related death rate. The purpose of this study was to establish an invasion-related multigene signature to predict the prognostic risk of OC.

Methods
We extracted 97 invasion-related genes from The Cancer Genome Atlas (TCGA) database. Then, the ConsensusClusterPlus and limma packages were used to calculate differentially expressed genes (DEGs). To calculate the immune scores of the molecular subtypes, we used ESTIMATE to evaluate the stromal score, immune score and ESTIMATE score. MCP-counter and the GSVA package ssgsea were used to evaluate the types of infiltrating immune cells. Survival and nomogram analyses were performed to explore the prognostic value of the signature. Finally, qPCR, immunohistochemistry staining and functional assays were used to evaluate the expression and biological abilities of the signature genes in OC.

Results
Based on the consistent clustering of invasion-related genes, cases in the OC datasets were divided into two subtypes. A significant difference was observed in prognosis between the two subtypes. Most genes were highly expressed in the C1 group. Based on the C1 group genes, we constructed an invasion-related 6-gene prognostic risk model. Furthermore, to verify the signature, we used the TCGA-test and GSE32062 and GSE17260 chip datasets for testing and finally obtained a good risk prediction effect in those datasets. Moreover, the results of the qPCR and immunohistochemistry staining assays revealed that KIF26B, VSIG4 and COL6A6 were upregulated and that FOXJ1, MXRA5 and CXCL9 were downregulated in OC tissues. The functional study showed that the expression of KIF26B, VSIG4, COL6A6, FOXJ1, MXRA5 and CXCL9 can regulate the migration and invasion abilities of OC cells.

Conclusion
We developed a 6-gene prognostic stratification system (FOXJ1, MXRA5, KIF26B, VSIG4, CXCL9 and COL6A6) that is independent of clinical features. These results suggest that the signature could potentially be used to evaluate the prognostic risk of OC patients.
Engineered extracellular vesicles: potentials in cancer combination therapy
Authors: Chen Jiangbin , Tan Qi , Yang Zimo , Jin Yang 
Published: March 2022

AbstractExtracellular vesicles (EVs) are a group of secretory vesicles with cell-derived membrane and contents. Due to the cargo delivery capability, EVs can be designed as drug delivery platforms for cancer therapy. Biocompatibility and immune compatibility endow EVs with unique advantages compared with other nanocarriers. With the development of this field, multiple ingenious modification methods have been developed to obtain engineered EVs with desired performance. Application of engineered EVs in cancer therapy has gradually shifted from monotherapy to combinational therapy to fight against heterogeneous cancer cells and complex tumor microenvironment. In addition, the strong plasticity and load capacity of engineered EV make it potential to achieve various combinations of cancer treatment methods. In this review, we summarize the existing schemes of cancer combination therapy realized by engineered EVs, highlight the mechanisms and representative examples of these schemes and provide guidance for the future application of engineered EVs to design more effective cancer combination treatment plans.
Graphical Abstract