bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vertebral fracture due to Actinobacillus pleuropneumoniae osteomyelitis in a weaner
Authors: Giebels Felix , Geissbühler Urs , Oevermann Anna , Grahofer Alexander , Olias Philipp , Kuhnert Peter , Maiolini Arianna , Stein Veronika Maria 
Published: November 2020

Abstract

Background
Osteomyelitis is relatively frequent in young pigs and a few bacterial species have been postulated to be potential causative agents. Although Actinobacillus (A.) pleuropneumoniae has been sporadically described to cause osteomyelitis, typically, actinobacillosis is characterized by respiratory symptoms. Nevertheless, subclinical infections are a challenging problem in pig herds. To the authors’ knowledge, this is the first case description that reports clinical, diagnostic imaging, pathological and histopathological findings of vertebral osteomyelitis in a pig and first describes A. pleuropneumoniae as the causative agent identified by advanced molecular methods.

Case presentation
An eight-week-old female weaner was presented with a non-ambulatory tetraparesis. The neurological signs were consistent with a lesion in the C6-T2 spinal cord segments. Imaging studies revealed a collapse of the seventh cervical vertebral body (C7) with a well demarcated extradural space-occupying mass ventrally within the vertebral canal severely compressing the spinal cord. Post-mortem examination identified an abscess and osteomyelitis of C7 and associated meningitis and neuritis with subsequent pathological fracture of C7 and compression of the spinal cord. In the microbiological analysis, A. pleuropneumoniae was identified using PCR and DNA sequence analysis.

Conclusions
A. pleuropneumoniae can be responsible for chronic vertebral abscess formation with subsequent pathological fracture and spinal cord compression in pigs.
Rational engineering of Kluyveromyces marxianus to create a chassis for the production of aromatic products
Authors: Rajkumar Arun S. , Morrissey John P. 
Published: November 2020

Abstract

Background
The yeast Kluyveromyces marxianus offers unique potential for industrial biotechnology because of useful features like rapid growth, thermotolerance and a wide substrate range. As an emerging alternative platform, K. marxianus requires the development and validation of metabolic engineering strategies to best utilise its metabolism as a basis for bio-based production.

Results
To illustrate the synthetic biology strategies to be followed and showcase its potential, we describe a comprehensive approach to rationally engineer a metabolic pathway in K. marxianus. We use the phenylalanine biosynthetic pathway both as a prototype and because phenylalanine is a precursor for commercially valuable secondary metabolites. First, we modify and overexpress the pathway to be resistant to feedback inhibition so as to overproduce phenylalanine de novo from synthetic minimal medium. Second, we assess native and heterologous means to increase precursor supply to the biosynthetic pathway. Finally, we eliminate branch points and competing reactions in the pathway and rebalance precursors to redirect metabolic flux to a specific product, 2-phenylethanol (2-PE). As a result, we are able to construct robust strains capable of producing over 800 mg L−1 2-PE from minimal medium.

Conclusions
The strains we constructed are a promising platform for the production of aromatic amino acid-based biochemicals, and our results illustrate challenges with attempting to combine individually beneficial modifications in an integrated platform.
Building a sanitary vulnerability map from open source data in Argentina (2010-2018)
Authors: Rosati Germán Federico , Olego Tomás Alberto , Vazquez Brust H. Antonio 
Published: November 2020

Abstract
Background
Designing public health policies to target the needs of specific places requires highly granular data. When geographic health statistics from official sources are absent or lacking in spatial detail, Sanitary Vulnerability metrics derived from Census and other georeferenced public data can be used to identify areas in particular need of attention. With that aim, a Vulnerability Map was developed, identifying areas with a substantial deficit in its population health coverage. As a result a novel methodology for measuring Sanitary Vulnerability is presented, that can potentially be applied to different time periods or geographies.

Methods
Census, official listings of public health facilities and crowdsourced georeferenced data are used. The Vulnerability Index is built using dimensionality reduction techniques such as Autoencoders and Non-parametric PCA.

Main results
The high resolution map shows the geographical distribution of a Sanitary Vulnerability Index, produced using official and crowdsourced open data sources, overcoming the lack of official sources on health indicators at the local level.

Conclusions
The Sanitary Vulnerability Map’s value as a tool for place specific policymaking was validated by using it to predict local health related metrics such as health coverage. Further lines of work contemplate using the Map to study the interaction between Sanitary Vulnerability and the prevalence of different diseases, and also applying its methodology in the context of other public services such as education, security, housing, etc.
Intersectionality and health-related stigma: insights from experiences of people living with stigmatized health conditions in Indonesia
Authors: Rai Sarju Sing , Peters Ruth M. H. , Syurina Elena V. , Irwanto Irwanto , Naniche Denise , Zweekhorst Marjolein B. M. 
Published: November 2020

AbstractBackgroundHealth-related stigma is a complex phenomenon, the experience of which intersects with those of other adversities arising from a diversity of social inequalities and oppressive identities like gender, sexuality, and poverty – a concept called “intersectionality”. Understanding this intersectionality between health-related stigma and other forms of social marginalization can provide a fuller and more comprehensive picture of stigma associated with health conditions. The main objective of this paper is to build upon the concept of intersectionality in health-related stigma by exploring the convergence of experiences of stigma and other adversities across the intersections of health and other forms of social oppressions among people living with stigmatized health conditions in Indonesia.MethodsThis qualitative study interviewed 40 people affected by either of four stigmatizing health conditions (HIV, leprosy, schizophrenia, and diabetes) in Jakarta and West Java, Indonesia between March and June 2018. Data was analyzed thematically using an integrative inductive-deductive framework approach.ResultsThe main intersectional inequalities identified by the participants were gender and socioeconomic status (n = 21), followed by religion (n = 13), age (n = 11), co-morbidity (n = 9), disability (n = 6), and sexuality (n = 4). Based on these inequalities/identities, the participants reported of experiencing oppression because of prevailing social norms, systems, and policies (macro-level), exclusion and discrimination from societal actors (meso-level), and self-shame and stigma (micro-level). While religion and age posed adversities that negatively affected participants in macro and meso levels, they helped mitigate the negative experiences of stigma in micro level by improving self-acceptance and self-confidence.ConclusionThis study uncovered how the experience of health-related stigma intersects with other oppressions originating from the various social inequalities in an individual’s life. The findings highlight the importance of acknowledging and understanding the multi-dimensional aspect of lives of people living with stigmatized health conditions, and warrant integrated multi-level and cross-cutting stigma reduction interventions to address the intersectional oppressions they experience.
Utilization of statins and LDL-cholesterol target attainment in Turkish patients with type 2 diabetes - a nationwide cross-sectional study (TEMD dyslipidemia study)
Authors:   TEMD Study Group, Bayram Fahri , Sonmez Alper , Haymana Cem , Sabuncu Tevfik , Dizdar Oguzhan Sitki , Gurkan Eren , Carlioglu Ayse Kargili , Agbaht Kemal , Ozdemir Didem , Demirci Ibrahim , Barcin Cem , Salman Serpil , Tetiker Tamer , Balci Mustafa Kemal , Kebapci Nur , Ersoy Canan , Yumuk Volkan , Toth Peter P. , Satman Ilhan 
Published: November 2020

Abstract

Background
Attaining acceptable levels of LDL Cholesterol (LDL-C) significantly improves cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (T2DM). The LDL-C target attainment and the characteristics of patients attaining these targets were investigated in this study. Furthermore, the reasons for not choosing statins and the physicians’ attitudes on the treatment of diabetic dyslipidemia were also examined.

Methods
A nationwide, cross-sectional survey was conducted in tertiary centers for diabetes management. Adult patients with T2DM, who were under follow-up for at least a year in outpatient clinics, were consecutively enrolled for the study. LDL-C goals were defined as below 70 mg/dL for patients with macrovascular complications or diabetic nephropathy, and below 100 mg/dL for other patients. Data about lipid-lowering medications were self-reported.

Results
A total of 4504 patients (female: 58.6%) were enrolled for the study. The mean HbA1c and diabetes duration was 7.73 ± 1.74% and 10.9 ± 7.5 years, respectively. The need for statin treatment was 94.9% (n = 4262); however, only 42.4% (n = 1807) of these patients were under treatment, and only 24.8% (n = 448) of these patients achieved LDL-C targets. The main reason for statin discontinuation was negative media coverage (87.5%), while only a minority of patients (12.5%) mentioned side effects. Physicians initiated lipid-lowering therapy in only 20.3% of patients with high LDL-C levels. It was observed that the female gender was a significant independent predictor of not attaining LDL-C goals (OR: 0.70, 95% CI: 0.59–0.83).

Conclusions
Less than 50 % of patients with T2DM who need statins were under treatment, and only a quarter of them attained their LDL-C targets. There exists a significant gap between the guideline recommendations and the real-world evidence in the treatment of dyslipidemia in T2DM.
Intrinsic disorder is an essential characteristic of components in the conserved circadian circuit
Authors: Pelham Jacqueline F. , Dunlap Jay C. , Hurley Jennifer M. 
Published: November 2020

AbstractIntroductionThe circadian circuit, a roughly 24 h molecular feedback loop, or clock, is conserved from bacteria to animals and allows for enhanced organismal survival by facilitating the anticipation of the day/night cycle. With circadian regulation reportedly impacting as high as 80% of protein coding genes in higher eukaryotes, the protein-based circadian clock broadly regulates physiology and behavior. Due to the extensive interconnection between the clock and other cellular systems, chronic disruption of these molecular rhythms leads to a decrease in organismal fitness as well as an increase of disease rates in humans. Importantly, recent research has demonstrated that proteins comprising the circadian clock network display a significant amount of intrinsic disorder.Main bodyIn this work, we focus on the extent of intrinsic disorder in the circadian clock and its potential mechanistic role in circadian timing. We highlight the conservation of disorder by quantifying the extent of computationally-predicted protein disorder in the core clock of the key eukaryotic circadian model organismsDrosophila melanogaster, Neurospora crassa,andMus musculus. We further examine previously published work, as well as feature novel experimental evidence, demonstrating that the core negative arm circadian period drivers FREQUENCY (Neurospora crassa) and PERIOD-2 (PER2) (Mus musculus), possess biochemical characteristics of intrinsically disordered proteins. Finally, we discuss the potential contributions of the inherent biophysical principals of intrinsically disordered proteins that may explain the vital mechanistic roles they play in the clock to drive their broad evolutionary conservation in circadian timekeeping.ConclusionThe pervasive conservation of disorder amongst the clock in the crown eukaryotes suggests that disorder is essential for optimal circadian timing from fungi to animals, providing vital homeostatic cellular maintenance and coordinating organismal physiology across phylogenetic kingdoms.Graphical abstract
Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome
Authors: Norton Dustin L. , Ceppe Agathe , Tune Miriya K. , McCravy Matthew , Devlin Thomas , Drummond M. Bradley , Carson Shannon S. , Vincent Benjamin G. , Hagan Robert S. , Dang Hong , Doerschuk Claire M. , Mock Jason R. 
Published: November 2020

AbstractBackgroundFoxp3+regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4+T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples.MethodsWe prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48–96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4+T cells that were Tregs.ResultsThe BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood.ConclusionTregs are present in the bronchoalveolar space during ARDS. A greater percentage of CD4+cells were Tregs in the BAL of FR than SR. Tregs may play a role in the resolution of ARDS, and enhancing their numbers or functions may be a therapeutic target.
Revisiting the association between skin toxicity and better response in advanced cancer patients treated with immune checkpoint inhibitors
Authors: Gulati Nicholas , Donnelly Douglas , Qian Yingzhi , Moran Una , Johannet Paul , Zhong Judy , Osman Iman 
Published: November 2020

Abstract

Background
Immune checkpoint inhibition (ICI) improves survival outcomes for patients with several types of cancer including metastatic melanoma (MM), but serious immune-related adverse events requiring intervention with immunosuppressive medications occur in a subset of patients. Skin toxicity (ST) has been reported to be associated with better response to ICI. However, understudied factors, such as ST severity and potential survivor bias, may influence the strength of these observed associations.

Methods
To examine the potential confounding impact of such variables, we analyzed advanced cancer patients enrolled prospectively in a clinicopathological database with protocol-driven follow up and treated with ICI. We tested the associations between developing ST, stratified as no (n = 617), mild (n = 191), and severe (n = 63), and progression-free survival (PFS) and overall survival (OS) in univariable and multivariable analyses. We defined severe ST as a skin event that required treatment with systemic corticosteroids. To account for the possibility of longer survival associating with adverse events instead of the reverse, we treated ST as a time-dependent covariate in an adjusted model.

Results
Both mild and severe ST were significantly associated with improved PFS and OS (all P < 0.001). However, when adjusting for the time from treatment initiation to time of skin event, severe ST was not associated with PFS benefit both in univariable and multivariable analyses (P = 0.729 and P = 0.711, respectively). Receiving systemic steroids for ST did not lead to significant differences in PFS or OS compared to patients who did not receive systemic steroids.

Conclusions
Our data reveal the influence of time to event and its severity as covariates in analyzing the relationship between ST and ICI outcomes. These differences in outcomes cannot be solely explained by the use of immunosuppressive medications, and thus highlight the importance of host- and disease-intrinsic factors in determining ICI response and toxicity.
Trial registration: The patient data used in this manuscript come from patients who were prospectively enrolled in two institutional review board-approved databases at NYU Langone Health (institutional review board #10362 and #S16-00122).
Validity and sensitivity of instrumented postural and gait assessment using low-cost devices in Parkinson’s disease
Authors: Álvarez Ignacio , Latorre Jorge , Aguilar Miquel , Pastor Pau , Llorens Roberto 
Published: November 2020

Abstract

Background
Accurate assessment of balance and gait is necessary to monitor the clinical progress of Parkinson’s disease (PD). Conventional clinical scales can be biased and have limited accuracy. Novel interactive devices are potentially useful to detect subtle posture or gait-related impairments.

Methods
Posturographic and single and dual-task gait assessments were performed to 54 individuals with PD and 43 healthy controls with the Wii Balance Board and the Kinect v2 and the, respectively. Individuals with PD were also assessed with the Tinetti Performance Oriented Mobility Assessment, the Functional Gait Assessment and the 10-m Walking Test. The influence of demographic and clinical variables on the performance in the instrumented posturographic and gait tests, the sensitivity of these tests to the clinical condition and phenotypes, and their convergent validity with clinical scales were investigated.

Results
Individuals with PD in H&Y I and I.5 stages showed similar performance to controls. The greatest differences in posture and gait were found between subjects in H&Y II.5 and H&Y I–I.5 stage, as well as controls. Dual-tasking enhanced the differences among all groups in gait parameters. Akinetic/rigid phenotype showed worse postural control and gait than other phenotypes. High significant correlations were found between the limits of stability and most of gait parameters with the clinical scales.

Conclusions
Low-cost devices showed potential to objectively quantify posture and gait in established PD (H&Y ≥ II). Dual-tasking gait evaluation was more sensitive to detect differences among PD stages and compared to controls than free gait. Gait and posture were more impaired in akinetic/rigid PD.
The clinical and radiographic characteristics of avascular necrosis after pediatric femoral neck fracture: a systematic review and retrospective study of 115 patients
Authors: Xin Pengfei , Tu Yonggang , Hong Zhinan , Yang Fan , Pang Fengxiang , Wei Qiushi , He Wei , Li Ziqi 
Published: November 2020

Abstract

Background
Avascular necrosis (AVN) after pediatric femoral neck fracture (PFNF) showed poor prognosis, but its clinical and radiographic characteristics remained unclear.

Methods
A systematic review and a retrospective study were performed to evaluate the clinical and radiographic characteristics of patients with AVN after PFNF.

Results
A total of 686 patients with PFNF and 203 patients with AVN from 21 articles were analyzed. Ratliff’s classification was used in 178 patients, with types I, II, and III AVN accounting for 58.4%, 25.3%, and 16.3%, respectively. Ratliff’s assessment was used in 147 patients, of whom 88.4% had an unsatisfactory prognosis. In retrospective study, 115 patients with a mean age of 13.6 ± 2.0 years were included. The mean interval between AVN and PFNF was 13.7 ± 9.5 months. At the time of diagnosis, 59.1% cases were symptomatic and 65.2% progressed to collapsed stage. Fifty (43.5%), 61 (53.0%), and 4 patients (3.5%) were defined as types I, II, and III , respectively, via Ratliff’s classification. Thirteen (11.3%), 40 (34.8%), and 62 patients (53.9%) showed types A/B, C1, and C2 disease, respectively, via the JIC classification. Multivariate analysis demonstrated a strong relation between collapsed stage and symptomatic cases (OR = 6.25, 95% CI = 2.39–16.36) and JIC classification (OR = 3.41, 95% CI = 1.62–7.17).

Conclusion
AVN after PFNF showed a tendency toward extensive necrotic lesions, presumably resulting in a rapid progression of femoral head collapse. And the symptoms and the JIC classification are other two risk factors of collapse progression.
The effectiveness of ramosetron and ondansetron for preventing postoperative nausea and vomiting after arthroscopic rotator cuff repair: a randomized controlled trial
Authors: Lee Sang-Uk , Lee Hyo-Jin , Kim Yang-Soo 
Published: November 2020

Abstract

Background
Arthroscopic rotator cuff repair is a painful procedure, and treatment of emetic events associated with drugs used in the current multimodal pain management remains challenging. This study aimed to evaluate the effectiveness of ramosetron or ondansetron to relieve postoperative nausea and vomiting (PONV) and pain after arthroscopic rotator cuff repair.

Methods
In total, 122 consecutive patients undergoing arthroscopic rotator cuff repair were randomly allocated into three groups: ramosetron group (n = 39), ondansetron group (n = 43), and control group (n = 40). Then, 0.3 mg of ramosetron or 8 mg of ondansetron was administered intravenously at the end of surgery according to group. All patients received general anesthesia and multimodal pain management protocol including preemptive analgesic medication, fentanyl-based intravenous patient-controlled analgesia, and postoperative analgesic medication. Incidence of emetic events, rescue antiemetic requirements (10 mg of metoclopramide, IV), complete response, pain level, and side effects were recorded in three periods: 0–6, 6–24, and 24–48 h postoperatively. The severity of nausea and pain was evaluated using a visual analog scale.

Results
The ramosetron group tended to have a lower incidence and severity of nausea during the 6- to 24-h postoperative period and fewer rescue antiemetic drug requirements during the 0- to 48-h period than the control group, showing statistical significance. Additionally, the frequency of complete response of the ramosetron and ondansetron groups was significantly higher than that of the control group. No difference was found among the groups in the pain level except during the 0- to 6-h period. The two groups have a higher complete response during the 6- to 24-h period than the control group.

Conclusions
Ramosetron use led to a lower incidence, mild severity of nausea, and reduced use of rescue antiemetic drug after arthroscopic rotator cuff repair during the 6- to 24-h postoperative period than the control.

Level of evidence
Level I, randomized controlled trials, treatment study