bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mini-Invasive Approach and Minor Amputation in the Management of Diabetic Foot Ulcer: A Retrospective Study of 110 Cases
Authors: Marzano Fabrizio , Ceccarini Paolo , Petruccelli Rosario , di Giacomo Lorenzo , Rinonapoli Giuseppe , Caraffa Auro 
Published: February 2022

Category: Diabetes; Other Introduction/Purpose: The diabetic foot is an increasing issue over the last years. The 25% of diabetic patients have a risk to develop a diabetic foot ulcer (DFU) in their lifetime, among these, the 28% of patients will result in an amputation. The amputation is associated with a high rate of complications. Therefore, percutaneous mini-invasive (PMI) approaches and minor amputations (MA) have a widespread use in the last years. The aim of our work is to evaluate the clinical and functional outcomes of PMI and MA in the treatment of recurrences and unhealed DFU after conservative treatment. Methods: We retrospectively enrolled 110 patients treated in our orthopedic department in Perugia between January 2012 and October 2019. Included were the patients underwent to a PMI or MA treatment after failed conservative treatment for 12 weeks. The PMI technique consist of flexor tenotomy, metatarsal osteotomy and resection arthroplasty sec. Kessler. DFU were classified according to the Texas Foot Ulcer Classification. Exclusion criteria were: patient affected by peripheral vasculopathy disease, previous major amputation, psychiatric disease. The patients were divided in 2 groups. The group A included 57 patients treated with PMI, mean age 62.8 y.o. (range 50-80). The group B included 53 patients treated with MI, mean age 66.2 y.o. (range 53-85). The mean follow up was 18 months (range 4-40 months). Clinical outcomes, complication's rate, functional scores (FFI and VAS- FA) were assessed. The statistical analysis was performed with the t-student test, the significativity value was set p<0.05. Results: In the group A, the patients had a healing's rate in 90,7 % of cases, the ulcer was healed in average in 5.77 weeks ( range 4-8.1). The postoperative complications accounts 35% of cases, including 2 cases of osteomyelitis, 1 acute Charcot foot, 1 case of acute renal insufficiency and pneumonia. Transfer ulcer occurred in 12.96%. Overall a reintervention with a mini-invasive approach was performed in 2 cases. Group B healed in 77% of cases, in a mean time of 9.11 weeks (range 8-13.3), no postoperative complication occurred. In 23% of patients occurred a transfer ulcer after an average time of 30 months, in 1 case a major amputation was mandatory. The mean value at postoperative follow-up was 78 for VAS-FA for group A and 72.2 for group B, the FFIindex was 70% for group A and 68% for group B. Conclusion: The PMI and AM are effective procedures for the treatment of DFU, associated with low complications rate, fast recovery and ulcer's healing process, low rate of recurrences and ulcer transfer. Overall the percutaneous technique show encouraging results, however, these procedures must be addressed to the patient's feature. As prospective, in the future percutaneous treatments might play a role in prevention's strategy.
Targeting macrophages for enhancing CD47 blockade–elicited lymphoma clearance and overcoming tumor-induced immunosuppression
Authors: Cao Xu , Wang Yingyu , Zhang Wencan , Zhong Xiancai , Gunes E. Gulsen , Dang Jessica , Wang Jinhui , Epstein Alan L. , Querfeld Christiane , Sun Zuoming , Rosen Steven T. , Feng Mingye 
Published: February 2022

Abstract
Tumor-associated macrophages (TAMs) are often the most abundant immune cells in the tumor microenvironment (TME). Strategies targeting TAMs to enable tumor cell killing through cellular phagocytosis have emerged as promising cancer immunotherapy. Although several phagocytosis checkpoints have been identified, the desired efficacy has not yet been achieved by blocking such checkpoints in preclinical models or clinical trials. Here, we showed that late-stage non-Hodgkin lymphoma (NHL) was resistant to therapy targeting phagocytosis checkpoint CD47 due to the compromised capacity of TAMs to phagocytose lymphoma cells. Via a high-throughput screening of the US Food and Drug Administration–approved anticancer small molecule compounds, we identified paclitaxel as a potentiator that promoted the clearance of lymphoma by directly evoking phagocytic capability of macrophages, independently of paclitaxel’s chemotherapeutic cytotoxicity toward NHL cells. A combination with paclitaxel dramatically enhanced the anticancer efficacy of CD47-targeted therapy toward late-stage NHL. Analysis of TME by single-cell RNA sequencing identified paclitaxel-induced TAM populations with an upregulation of genes for tyrosine kinase signaling. The activation of Src family tyrosine kinases signaling in macrophages by paclitaxel promoted phagocytosis against NHL cells. In addition, we identified a role of paclitaxel in modifying the TME by preventing the accumulation of a TAM subpopulation that was only present in late-stage lymphoma resistant to CD47-targeted therapy. Our findings identify a novel and effective strategy for NHL treatment by remodeling TME to enable the tumoricidal roles of TAMs. Furthermore, we characterize TAM subgroups that determine the efficiency of lymphoma phagocytosis in the TME and can be potential therapeutic targets to unleash the antitumor activities of macrophages.
Unbiased cell surface proteomics identifies SEMA4A as an effective immunotherapy target for myeloma
Authors: Anderson Georgina S. F. , Ballester-Beltran Jose , Giotopoulos George , Guerrero Jose A. , Surget Sylvanie , Williamson James C. , So Tsz , Bloxham David , Aubareda Anna , Asby Ryan , Walker Ieuan , Jenkinson Lesley , Soilleux Elizabeth J. , Roy James P. , Teodósio Ana , Ficken Catherine , Officer-Jones Leah , Nasser Sara , Skerget Sheri , Keats Jonathan J. , Greaves Peter , Tai Yu-Tzu , Anderson Kenneth C. , MacFarlane Marion , Thaventhiran James E. , Huntly Brian J. P. , Lehner Paul J. , Chapman Michael A. 
Published: February 2022

Abstract
The accessibility of cell surface proteins makes them tractable for targeting by cancer immunotherapy, but identifying suitable targets remains challenging. Here we describe plasma membrane profiling of primary human myeloma cells to identify an unprecedented number of cell surface proteins of a primary cancer. We used a novel approach to prioritize immunotherapy targets and identified a cell surface protein not previously implicated in myeloma, semaphorin-4A (SEMA4A). Using knock-down by short-hairpin RNA and CRISPR/nuclease-dead Cas9 (dCas9), we show that expression of SEMA4A is essential for normal myeloma cell growth in vitro, indicating that myeloma cells cannot downregulate the protein to avoid detection. We further show that SEMA4A would not be identified as a myeloma therapeutic target by standard CRISPR/Cas9 knockout screens because of exon skipping. Finally, we potently and selectively targeted SEMA4A with a novel antibody–drug conjugate in vitro and in vivo.
GRNDaD: big data and sickle cell disease
Authors: Lanzkron Sophie , Manwani Deepa , Desai Payal , Kanter Julie , Little Jane 
Published: February 2022

Abstract
Big data are used in the pursuit of precision medicine in the general population. Applying these tools to patients with sickle cell disease (SCD) is essential for ensuring that they receive the most appropriate customized therapy for their disease. For these tools to be applied, there must be a large number of willing, fully phenotyped participants in collaborative registries. Working collaboratively to respond to unmet clinical needs and the lack of a large multisite registry, SCD providers at multiple sites developed The Globin Regional Data and Discovery (GRNDaD) registry. The specific goals of GRNDaD are to (1) prospectively obtain high-quality curated data on the evolving population affected by SCD; (2) improve adherence to guideline-based care; (3) provide a platform for ongoing quality improvement across sites; (4) allow for real-time investigation of therapies, and collaborate broadly to address research questions using GRNDaD as a shared platform. GRNDaD’s current strength lies in the generous participation of people living with SCD, collaborative investigators, and the opportunity to conduct quality improvement activities across a large number of sites. GRNDaD will serve as the data collection tool for the Health Resources and Services Administration Sickle Cell Treatment Demonstration Program and for the newly established National Alliance for Sickle Cell Centers (https://www.sicklecellcenters.org/). GRNDaD is a robust collaborative registry that providers and researchers will use to identify genetic markers that will help predict outcomes and lead to a better understanding of the natural history of SCD in the modern era of novel therapies.
Genetic analysis of disease resilience of wean-to-finish pigs under a natural disease challenge model using reaction norms
Authors: Cheng Jian , Lim KyuSang , Putz Austin M. , Wolc Anna , Harding John C. S. , Dyck Michael K. , Fortin Frederic , Plastow Graham S. ,   PigGen Canada, Dekkers Jack C. M. 
Published: February 2022

Abstract
Background
Disease resilience is the ability to maintain performance across environments with different disease challenge loads (CL). A reaction norm describes the phenotypes that a genotype can produce across a range of environments and can be implemented using random regression models. The objectives of this study were to: (1) develop measures of CL using growth rate and clinical disease data recorded under a natural polymicrobial disease challenge model; and (2) quantify genetic variation in disease resilience using reaction norm models.

Methods
Different CL were derived from contemporary group effect estimates for average daily gain (ADG) and clinical disease phenotypes, including medical treatment rate (TRT), mortality rate, and subjective health scores. Resulting CL were then used as environmental covariates in reaction norm analyses of ADG and TRT in the challenge nursery and finisher, and compared using model loglikelihoods and estimates of genetic variance associated with CL. Linear and cubic spline reaction norm models were compared based on goodness-of-fit and with multi-variate analyses, for which phenotypes were separated into three traits based on low, medium, or high CL.

Results
Based on model likelihoods and estimates of genetic variance explained by the reaction norm, the best CL for ADG in the nursery was based on early ADG in the finisher, while the CL derived from clinical disease traits across the nursery and finisher was best for ADG in the finisher and for TRT in the nursery and across the nursery and finisher. With increasing CL, estimates of heritability for nursery and finisher ADG initially decreased, then increased, while estimates for TRT generally increased with CL. Genetic correlations for ADG and TRT were low between high versus low CL, but high for close CL. Linear reaction norm models fitted the data significantly better than the standard genetic model without genetic slopes, while the cubic spline model fitted the data significantly better than the linear reaction norm model for most traits. Reaction norm models also fitted the data better than multi-variate models.

Conclusions
Reaction norm models identified genotype-by-environment interactions related to disease CL. Results can be used to select more resilient animals across different levels of CL, high-performance animals at a given CL, or a combination of these.
Comparison of linkage disequilibrium estimated from genotypes versus haplotypes for crossbred populations
Authors: Alemu Setegn Worku , Bijma Piter , Calus Mario P. L. , Liu Huiming , Fernando Rohan L. , Dekkers Jack C. M. 
Published: February 2022

Abstract
Background
Linkage disequilibrium (LD) is commonly measured based on the squared coefficient of correlation $$\left({r}^{2}\right)$$

r

2

between the alleles at two loci that are carried by haplotypes. LD can also be estimated as the $${r}^{2}$$

r

2

between unphased genotype dosage at two loci when the allele frequencies and inbreeding coefficients at both loci are identical for the parental lines. Here, we investigated whether $${r}^{2}$$

r

2

for a crossbred population (F1) can be estimated using genotype data. The parental lines of the crossbred (F1) can be purebred or crossbred.

Methods
We approached this by first showing that inbreeding coefficients for an F1 crossbred population are negative, and typically differ in size between loci. Then, we proved that the expected $${r}^{2}$$

r

2

computed from unphased genotype data is expected to be identical to the $${r}^{2}$$

r

2

computed from haplotype data for an F1 crossbred population, regardless of the inbreeding coefficients at the two loci. Finally, we investigated the bias and precision of the $${r}^{2}$$

r

2

estimated using unphased genotype versus haplotype data in stochastic simulation.

Results
Our findings show that estimates of $${r}^{2}$$

r

2

based on haplotype and unphased genotype data are both unbiased for different combinations of allele frequencies, sample sizes (900, 1800, and 2700), and levels of LD. In general, for any allele frequency combination and $${r}^{2}$$

r

2

value scenarios considered, and for both methods to estimate $${r}^{2}$$

r

2

, the precision of the estimates increased, and the bias of the estimates decreased as sample size increased, indicating that both estimators are consistent. For a given scenario, the $${r}^{2}$$

r

2

estimates using haplotype data were more precise and less biased using haplotype data than using unphased genotype data. As sample size increased, the difference in precision and biasedness between the $${r}^{2}$$

r

2

estimates using haplotype data and unphased genotype data decreased.

Conclusions
Our theoretical derivations showed that estimates of LD between loci based on unphased genotypes and haplotypes in F1 crossbreds have identical expectations. Based on our simulation results, we conclude that the LD for an F1 crossbred population can be accurately estimated from unphased genotype data. The results also apply for other crosses (F2, F3, Fn, BC1, BC2, and BCn), as long as (selected) individuals from the two parental lines mate randomly.
Sudanese emergency departments: a study to identify the barriers to a well-functioning triage
Authors: Ibrahim Bayan E. 
Published: February 2022

Abstract
Background
Triage system is a sorting system that categorizes patients on the basis of the severity of their condition and the availability of the resources in the emergency department. There has been little attention in the public literature to triage systems in Sudan. The aim of this study was to explore the triage system and identify the barriers in its application in hospitals in Sudan.

Methods
A cross-sectional hospital based study was conducted at eight hospitals in Khartoum during December 2020. A multi-stage cluster sampling was applied. Data were obtained by interviewing emergency department staff using a structured questionnaire. The data were analyzed using statistical package for social sciences to find the association between various variables by chi-square test.

Results
Most of the respondents stated that the triage system was deficient. Most of the participants of this study agreed that the role played by the administration in taking legislative decisions is crucial in improving the triage system. Among the factors found to be significant to a well-functioning triage system were, the need for substantial capital expenditure, p-value: 0.026, prudent legislative decisions, p-value: 0.026, adequate training of staff on means of performing efficient triaging, p-value: 0.007 and raising the awareness of the staff on the correct application of triage guidelines, p-value: 0.017.

Conclusion
Currently there is no formal triage system in the State of Khartoum and has yet to be established. Policy making by administrators will play an important role in its implementation. It is suggested that prompt executive orders on improving the current triage system in Khartoum, should be carried out sooner than later, as the ripple effects of a well-functioning triage will decrease the average length of stay, mortality and morbidity rates and will eventually increase the patient’s satisfaction.
Determinants of suboptimal immune recovery among a Chinese Yi ethnicity population with sustained HIV suppression
Authors: Chen Liyu , Liu Chang-Hai , Kang Shuang , Du Lingyao , Ma Fanghua , Li Changmin , Bai Lang , Li Hong , Tang Hong 
Published: February 2022

Abstract
Objectives
Despite sustained viral suppression with effective antiretroviral therapy (ART), HIV-infected patients with suboptimal immune recovery are still at high risk of both non-AIDS-related and AIDS-related events. The aim of this study was to investigate determinants potentially associated with suboptimal CD4 + T cell count recovery during free ART with sustained viral suppression among an HIV-infected Yi ethnicity population in Liangshan Prefecture, an area in China with high HIV prevalence.

Methods
This retrospective study included HIV-infected Yi adults (≥ 18 years and baseline CD4 + T cell count less than 500 cells/μL) for whom ART supported by National Free Antiretroviral Treatment Program was initiated between January 2015 and December 2018 in Zhaojue County, Liangshan Prefecture. Virological suppression (viral load < 50 copies/mL) was achieved within 12 months after ART initiation, and sustained virological suppression was maintained. Multivariate log-binomial regression analysis was used to assess determinants of suboptimal immune recovery.

Results
There were 140 female and 137 male patients in this study, with a mean age of 36.57 ± 7.63 years. Most of the Yi patients were infected through IDU (48.7%) or heterosexual contact (49.8%), and the anti-HCV antibody prevalence was high (43.7%, 121/277). Of the 277 patients with a mean ART duration of 3.77 ± 1.21 years, complete immune recovery occurred in only 32.9%. The baseline CD4 + T cell count in patients with suboptimal and intermediate immune recovery was 248.64 ± 108.10 and 288.59 ± 108.86 cells/μL, respectively, which was much lower than the baseline 320.02 ± 123.65 cells/μL in patients who achieved complete immune recovery (p < 0.001). Multivariable analysis demonstrated that low pre-ART CD4 + cell count and coinfection with HCV were associated with immune recovery of the HIV patients.

Conclusions
Our study suggests that for HIV-infected Yi patients in Liangshan Prefecture, prompt ART initiation after diagnosis of HIV infection should be applied, and curative HCV treatment should be given to patients with HCV/HIV coinfection to improve the immunological effectiveness of ART.
Trial registration None
Sources of information used by women during pregnancy and the perceived quality
Authors: Vogels-Broeke Maaike , Daemers Darie , Budé Luc , de Vries Raymond , Nieuwenhuijze Marianne 
Published: February 2022

Abstract
Background
Access to reliable information is critical to women’s experience and wellbeing during pregnancy and childbirth. In our information-rich society, women are exposed to a wide range of information sources. The primary objective of this study was to explore women’s use of information sources during pregnancy and to examine the perceived usefulness and trustworthiness of these sources.

Method
A quantitative cross-sectional study of Dutch women's experiences with various information sources during pregnancy, including professional (e.g. healthcare system), and informal sources, divided into conventional (e.g. family or peers) and digital sources (e.g. websites or apps). Exploratory backward stepwise multiple regression was performed to identify associations between the perceived quality of information sources and personal characteristics.

Results
A total of 1922 pregnant women were included in this study. The most commonly used information sources were midwives (91.5%), family or friends (79.3%), websites (77.9%), and apps (61%). More than 80% of women found professional information sources trustworthy and useful, while digital sources were perceived as less trustworthy and useful. Personal factors explain only a small part of the variation in the perceived quality of information sources.

Conclusion
Even though digital sources are perceived as less trustworthy and useful than professional and conventional sources, they are among the most commonly used sources of information for pregnant women. To meet the information needs of the contemporary generation of pregnant women it is essential that professionals help in the development of digital information sources.
Positive H. pylori status predicts better prognosis of non-cardiac gastric cancer patients: results from cohort study and meta-analysis
Authors: Jia Zhifang , Zheng Min , Jiang Jing , Cao Donghui , Wu Yanhua , Zhang Yuzheng , Fu Yingli , Cao Xueyuan 
Published: February 2022

Abstract
Background
Previous researches have associated Helicobacter pylori (H. pylori) with a prognosis of gastric cancer (GC), however, without a concert conclusion. This study aimed to study this issue further by a prospective cohort study and a meta-analysis.

Methods
Histologically diagnosed gastric cancer (GC) patients were recruited into the primary prospective cohort study between January 2009 to December 2013. All the patients were followed-up periodically to record information on post-surgery therapy and overall survival status. The pre-surgery status of H. pylori was measured by enzyme-linked immunosorbent assay. A meta-analysis was conducted after retrieving related researches in the databases of PubMed and Embase up to April 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and the survival time of GC patients. I2 statistics and Q test were used to assess the heterogeneity. Sensitivity analyses were performed using Galbraith’s plot, leave-one-out analysis, subgroup analyses and meta-regression to explore the sources of heterogeneity and the stability of the summary results.

Results
A total of 743 GC patients with radical tumorectomy were included prospectively and 516 (69.4%) were positive on H. pylori. H. pylori-positive patients tended to survive longer than -negative ones (HR 0.92, 95%CI: 0.74–1.15), though the tendency was not statistically significant. Cohort studies on the prognosis of GC were retrieved comprehensively by assessing the full-text and 59 published studies, together with the result of our study, were included in the further meta-analysis. The summarized results related the positive status of H. pylori to better overall survival (HR 0.81, 95%CI: 0.72–0.90) and disease-free survival (HR 0.83, 95%CI: 0.67–0.99). Results from subgroup analyses indicated that the pooled magnitude of this association was relatively lower in studies not referring to H. pylori in title and abstract.

Conclusions
In conclusion, gastric cancer patients with H. pylori have a better prognosis than patients of H. pylori negative. More stringent surveillance strategies may be necessary for patients with H. pylori negative at cancer diagnosis.