bluuebunny/crossref_metadata_2025 huggingface dataset:
Autologous Osteochondral Transplantation for Large Osteochondral Lesions of the Talus Is a Viable Option in an Athletic Population
Authors: Nguyen Anthony , Ramasamy Arul , Walsh Melanie , McMenemy Louise , Calder James D.F.
Published: October 2019

Background:

Autologous osteochondral transplantation (AOT) has been shown to be a viable treatment option for large osteochondral lesions of the talus. However, there are limited data regarding the management of large lesions in an athletic population, notably with regard to return to sport. Our investigation focused on assessing both qualitative and quantitative outcomes in the high-demand athlete with large (>150 mm2) lesions.

Hypothesis:

AOT is a viable option in athletes with large osteochondral lesions and can allow them to return to sport at their preinjury level.

Study Design:

Case series; Level of evidence, 4.

Methods:

The study population was limited to professional and amateur athletes (Tegner score, >6) with a talar osteochondral lesion size of 150 mm2 or greater. The surgical intervention was AOT with a donor site from the lateral femoral condyle. Clinical outcomes at a minimum of 24 months included return to sport, visual analog scale (VAS) for pain score, and Foot and Ankle Outcome Score (FAOS). In addition, graft incorporation was evaluated by magnetic resonance imaging (MRI) using MOCART (magnetic resonance observation of cartilage repair tissue) scores at 12 months after surgery.

Results:

A total of 38 athletes, including 11 professional athletes, were assessed. The mean follow-up was 45 months. The mean lesion size was 249 mm2. Thirty-three patients returned to sport at their previous level, 4 returned at a lower level compared with preinjury, and 1 did not return to sport (mean return to play, 8.2 months). The VAS improved from 4.53 preoperatively to 0.63 postoperatively ( P = .002). FAOSs improved significantly in all domains ( P < .001). Two patients developed knee donor site pain, and both had 3 osteochondral plugs harvested. Univariant analysis demonstrated no association between preoperative patient or lesion characteristics and ability to return to sport. However, there was a strong correlation between MOCART scores and ability to return to sport. The area under receiver operating characteristic of the MOCART score and return to play was 0.891 ( P = .005), with a MOCART score of 52.50 representing a sensitivity of 0.85 and specificity of 0.80 in determining ability to return to one’s previous level of activity.

Conclusion:

Our study suggests that AOT is a viable option in the management of large osteochondral talar defects in an athletic population, with favorable return to sport level, patient satisfaction, and FAOS/VAS scores. The ability to return to sport is predicated upon good graft incorporation, and further research is required to optimize this technique. Our data also suggest that patients should be aware of the increased risk of developing knee donor site pain when 3 osteochondral plugs are harvested.
Environmental and geotechnical suitability of recycling waste materials from plasterboard manufacturing
Authors: Imteaz Monzur Alam , Arulrajah Arul , Maghool Farshid
Published: October 2019

This paper presents the geotechnical and environmental suitability of recycling gypsum-based waste material produced from plasterboard manufacturing. Most of the current plasterboard manufacturing industries are dumping these wastes to landfills. Among the major impediments to recycling such waste are environmental concerns around using such recycled material, as well as proper and suitable places to use it. To investigate these, such a waste from an Australian plasterboard manufacturing company was collected and a series of geotechnical properties were tested to evaluate the materials’ suitability for any engineering construction. It was found that the tested gypsum-based plasterboard materials are suitable to use as road subgrade, pipe bedding and pipe backfill material. To ascertain the environmental safety of using such material in regards to manual handling as well as contaminants’ leaching into the surrounding environment, materials were thoroughly tested for more than a hundred different contaminants. Tests were conducted to evaluate both the contaminants’ concentrations in the sample as well as the leaching behaviour of those contaminants. It was found that concentrations of the tested contaminants were either below the individual detection limit or the safe limit defined by the local regulatory authority.
Application of healthcare waste indicators for assessing infectious waste management in Bolivia
Authors: Ferronato Navarro , Ragazzi Marco , Torrez Elias Marisol Secundina , Gorritty Portillo Marcelo Antonio , Guisbert Lizarazu Edith Gabriela , Torretta Vincenzo
Published: October 2019

In the developing world, healthcare waste management is a human health and environmental burden that should be solved for improving sustainability. Solutions should be introduced in the short term, concerning management, planning, financial assistance and expertise. The paper introduces an indicator set for assessing healthcare waste management in developing cities, implemented in La Paz (Bolivia) as a case study. The objective is to suggest an integrated management tool as a first assessment technique to identify the prevailing problems with a healthcare waste management system. Results suggest that, in La Paz, the application of such indicators is useful for evaluating which priorities should be addressed for improving the healthcare waste management system. The tool was applied for introducing a study necessary for the application of new management plans, especially concerning healthcare waste treatment. The method can be replicated in other contexts worldwide, with a focus on the developing world, for comparing cities, management solutions and improvements carried out along the years. The approach is of interest for boosting sustainability and human health, improving the awareness of the actors and policy-makers involved in waste management.
The Armenian Embroidered Bible
Authors: Stone Michael E
Published: October 2019

The pseudepigraphic literature of the ‘Old Testament’ in the Armenian language is an extraordinarily rich corpus. For example, the texts relating to Joseph are eight in number, four otherwise unknown and two translated from Greek. This rich literature comprises a number of genres, including parabiblical narrative, homilies and sermons, erotapokritic texts, scholastic lists, allegory and more. By examining the forms of literature, some preliminary conclusions are drawn as to matrices of origins of different types of works.
Combination treatment of autologous bone marrow stem cell transplantation and hyperbaric oxygen therapy for type 2 diabetes mellitus: A randomized controlled trial
Authors: Estrada Esteban J. , Decima José Luis , Bortman Guillermo , Roberti Javier , Romero Elida Beatriz , Samaja Gustavo , Saavedra Aldo Rodríguez , Martínez Gerardo , Gutiérrez Samuel
Published: October 2019

The objective of this study was to compare standard treatment versus the combination of intrapancreatic autologous stem cell (ASC) infusion and hyperbaric oxygen treatment (HBOT) before and after ASC in the metabolic control of patients with type 2 diabetes mellitus (T2DM). This study was a prospective, randomized controlled trial. The combined intervention consisted of 10 sessions of HBOT before the intrapancreatic infusion of ASC and 10 sessions afterwards. ASCs were infused into the main arterial supply of the pancreas to maximize the presence of the stem cells where the therapeutic effect is most desired. A total of 23 patients were included (control group = 10, intervention group = 13). Age, gender, diabetes duration, number of medications taken, body weight and height, and insulin requirements were recorded at baseline and every three months. Also, body mass index, fasting plasma glucose, C-peptide, and HbA1c, C-peptide/glucose ratio (CPGR) were measured every three months for one year. HbA1c was significantly lower in the intervention group compared with control throughout follow-up. Overall, 77% of patients in the intervention group and 30% of patients in the control group demonstrated a decrease of HbA1c at 180 days (compared with baseline) of at least 1 unit. Glucose levels were significantly lower in the intervention group at all timepoints during follow-up. C-peptide levels were significantly higher in the intervention group during follow-up and at one year: 1.9 ± 1.0 ng/mL versus 0.7 ± 0.4 ng/mL in intervention versus control groups, respectively, p = 0.0021. CPGR was higher in the intervention group at all controls during follow-up. The requirement for insulin was significantly lower in the intervention group at 90, 180, 270, and 365 days. Combined therapy of intrapancreatic ASC infusion and HBOT showed increased metabolic control and reduced insulin requirements in patients with T2DM compared with standard treatment.
“Farewell” to Prognosis in Shared Decision-Making
Authors: Johnson Robert F.
Published: October 2019

Whether because of a cultural pattern or personal preference, palliative care clinicians encounter persons approaching the end of life who wish to limit or forego prognostic information relating to their situation. This scenario has received attention in a recent motion picture as well as a newly available advance directive modification—the Prognosis Declaration form. The ordinary expectation for end-of-life shared decision-making with a capable person is clinician disclosure of the best effort at prognostic assessment. The optimal match between the expressed values, goals, and preferences of the person with available clinician expertise is hopefully achieved. For the clinician, a person’s choice to modify information disclosure and participation in shared decision-making represents a significant challenge of balancing key ethical principles of intervention with tolerance and compassion for these different preferences. Attention to communication strategies that elicit and appropriately reassess individual information and decision-making wishes, flexibility in information disclosure patterns with capable persons and their representatives, and recognition that a respect for autonomy includes the choice to opt out can approach this challenge while providing compassionate and ethical end-of-life care.
Photogrammetric Evaluation of Soft Tissue Profile and Frontal Photographs in Repaired Bilateral Cleft Lip and Palate
Authors: Ajami Shabnam , Babanouri Neda , Afshinpoor Roya
Published: October 2019

Objective:

To evaluate the soft tissue profile and frontal photographs of 8- to 12-year-old patients with repaired complete bilateral cleft lip and palate (BCLP).

Methods:

The profile and frontal photographs obtained from 31 nonsyndromic BCLP children (aged 8-12 years: 14 boys and 17 girls) were analyzed and compared with an age- and sex-matched normal population (18 boys and 32 girls). In each patient, 12 soft tissue angular and proportional parameters on the frontal photograph and 12 angular parameters for the profile photographs were developed and measured. Student t test was used to compare the mean value of the parameters between both sexes.

Results:

In the frontal view, there was a significant difference between the 2 study groups in the facial symmetry angle ( P < .001), lower facial height proportion ( P < .001), upper lip proportion ( P < .001), and interalar width/distance between the inner canthus of the eyes ( P < .001). In the profile view, there was a significant difference between the control group and the patients with cleft lip and palate in terms of nasofrontal angle ( P < .001), nasal angle ( P < .001), angle of the inferior facial third ( P = .032), head position angle ( P < .001), facial convexity angle ( P < .001), total facial convexity angle ( P < .001), and vertical nasal angle ( P < .001).

Conclusion:

In comparison with the normal population, the face of patients with repaired BCLP showed several soft tissue deformities, especially in the nasofrontal region, even after a surgical repair.
Content Validation of Direct Behavior Rating Multi-Item Scales for Assessing Problem Behaviors
Authors: Daniels Brian , Briesch Amy M. , Volpe Robert J. , Owens Julie Sarno
Published: October 2019

Direct Behavior Rating (DBR) is an efficient method for monitoring changes in student behavior in response to intervention. Emerging research on DBR Multi-Item Scales (DBR-MIS) indicates that DBR-MIS has promising characteristics as a progress-monitoring assessment. Specifically, the multiple items within DBR-MIS allow stakeholders to measure specific behaviors at the item level, as well as global constructs at the scale level. In addition, studies have shown that fewer rating occasions are necessary to reach acceptable levels of dependability when using DBR-MIS as opposed to single-item scales (DBR-SIS). The purpose of the study was to develop and validate DBR-MIS problem behavior scales (Disruptive, Oppositional, Interpersonal Conflict, and Conduct Problems) that may be used to evaluate students’ response to social-emotional or behavioral intervention. Within the first phase of development, item content was generated and subjected to evaluation by panels of researchers and school-based consumers. Exploratory factor analysis (EFA) was then used in the second phase to identify items that represented the strongest indicators of each construct. Teachers ( N = 307) in Grades K–3, from 35 school districts across 13 states in the Northeastern, Midwestern, Southern, and Southwestern United States each completed ratings for one randomly selected student ( N = 307). Results of the EFA using a starting pool of nine to 11 items for each DBR-MIS initially indicated one-factor solutions for the Disruptive and Oppositional scales and a two-factor solution for the Interpersonal Conflict scale. Consequently, a new Conduct Problems scale was created from items loading on the second factor. Implications for progress monitoring and future research are discussed.
The Mediating Role of Diabetes Distress and Depressive Symptoms in Type 2 Diabetes Medication Adherence Gender Differences
Authors: Aronson Benjamin D. , Sittner Kelley J. , Walls Melissa L.
Published: October 2019

Background. Medication adherence is negatively related to both diabetes distress (DD) and depressive symptoms (DS). Past research suggests gender differences in adherence, DD, and DS. A gap exists in determining if gender differences in adherence are mediated by DD and DS, or if gender moderates differences in adherence by DD/DS. Aims. This study investigated the relationship between gender, DD, DS, and medication adherence and tested for mediating and moderating effects on medication adherence among American Indian adults with type 2 diabetes. Method. The Maawaji idi-oog mino-ayaawin (Gathering for Health) study was a community-based participatory research collaboration with five American Indian tribes. Participants, randomly recruited from clinic records, shared information during computer-assisted personal interviews. This study includes the 166 participants who reported using medications to treat their diabetes. The relationship between gender, DD, DS, and medication adherence are explored. Possible mediating and moderating effects on medication were tested using regression and path analysis. Results. Females had higher levels of DD and DS and lower levels of medication adherence. Higher levels of DD and DS were both associated with lower medication adherence. No evidence was found that gender moderates the relationship between DD or DS and medication adherence. Instead, DD and DS mediated the relationship between gender and medication adherence. Conclusions. Medication adherence differences in male and female patients may be attributable to DD and DS. The present research highlights both DD and DS as targets for clinicians and researchers alike.
Use of anti-vascular endothelial growth factor drugs for eye disease in Tuscany: Development and test of indicators of treatment intensity
Authors: Virgili Gianni , Tosi Gian Marco , Figus Michele , Rizzo Stanislao , Murro Vittoria , Mucciolo Dario Pasquale , Roberto Giuseppe , Gini Rosa
Published: October 2019

Purpose:

We aimed to develop indicators based on electronic administrative data to compare treatment intensity at a hospital level in Tuscany, Italy.

Methods:

Data from 3 university hospitals (UHs), 11 local hospitals (LHs) and 2 private hospitals were analysed. Patients newly treated with an intravitreal injection were followed up for 365 days. Indicator #1 concerned hospitals with >80% of injections linked to a drug and patients with all injections linked to a drug. Indicator #2 included patients who received ⩾3 injections during the first 90 days, regardless of injection-drug linkage.

Results:

Indicator #1 was computed on four hospitals and included 3210 patients (48.3%). The average number of injections was 3.24 in the largest UH1. Compared to the latter, indicator #1 was significantly lower in UH2 and UH3 (−0.47 and −0.58, respectively; p < 0.001). Indicator #2 was computed on all hospitals and included 2789 patients (41.9%). UH1 delivered about 4.33 injections. Compared to the latter, LH4 delivered +0.62 injections ( p < 0.001) and nine other hospitals delivered between −0.22 and −0.94 injections ( p < 0.05).

Conclusion:

The two indicators proved to have the potential for supporting clinicians and policy makers in promoting the appropriate treatment intensity with intravitreal anti-vascular endothelial growth factor drugs.
Risk of intraocular pressure elevation after topical steroids in children and adults: A systematic review
Authors: Musleh Mohammud G , Bokre Desta , Dahlmann-Noor Annegret H
Published: October 2019

Topical steroids may induce a rise in intraocular pressure. The risk may increase with prolonged use, high frequency of administration, young age, higher ocular penetrance and higher anti-inflammatory potency. We aimed to study this relationship by comparing published rates of intraocular pressure elevation following administration of topical steroids and compared the risk of higher versus lower dosage regimes, high- versus low-potency/penetration steroids and adults versus children. Data sources used were Ovid Embase, Ovid Medline, the Cochrane Central Register of Controlled Trials, Web of Science, Scopus, CINHAL Plus and LILACS. Eligible studies were randomised controlled trials of topical steroids versus any other topical steroid, nonsteroidal anti-inflammatory drugs, placebo or vehicle, or a different mode of administration administered for 7 days or longer that reported intraocular pressure elevation from baseline as >10, 6–15 or >15 mm Hg in adults or children. Risks of bias were reviewed using the GRADE quality approach. Data were extracted into the software package, RevMan, Version 5 (Cochrane Collaboration). In total, 43 studies were included. Meta-analysis was not possible. Topical steroids of lower anti-inflammatory potency, and with reduced intraocular penetration, are associated with reduced incidence of intraocular pressure elevation. A comparison of data in children and adults is limited by the use of different reporting systems. The principal obstacle to meta-analysis is the different reporting systems used to categorise intraocular pressure elevation. We recommend future studies should report intraocular pressure elevation >10 mm Hg from baseline to allow meta-analysis of data.
Meeting in the Middle: Using Lingua Franca in Cross-Language Qualitative Health Research in Papua New Guinea
Authors: Redman-MacLaren Michelle , Mafile’o Tracie , Tommbe Rachael , MacLaren David
Published: October 2019

With words as data, qualitative researchers rely upon language to understand the meaning participants make of the phenomena under study. Cross-language research requires communication about and between linguistic systems, with language a site of power. This article describes the use of the lingua franca of Tok Pisin in a study conducted to explore the implications of male circumcision for human immunodeficiency virus (HIV) prevention for women in Papua New Guinea. Utilizing a transformational grounded theory methodology, researchers conducted an analysis of data from an HIV prevention study. Researchers then facilitated individual interviews and interpretive focus groups to explore preliminary categories identified during the analysis. Most focus groups and interviews were conducted in the local lingua franca Tok Pisin, which is neither the researchers’ nor most participants’ first language. Audio recordings were transcribed and analyzed. Researchers returned to research participants to discuss research findings and recommendations. Following critical reflection by the authors and further discussions with participants, it was evident that using Tok Pisin enriched the research process and findings. Using the lingua franca of Tok Pisin enabled interaction in a language closer to the lived experience of participants, devolved the power of the researcher, and was consistent with decolonizing methodologies. Participants reported the use of Tok Pisin, em i tasim (pilim) bun bilong mipela, “it touches our bones,” and enabled a flow of conversation with the researchers that engendered trust. It is critical researchers address hierarchies of language in order to enable cogeneration of quality research findings.
Study of ultrasonic vibration–assisted thread turning of Inconel 718 superalloy
Authors: He Yu , Zhou Zhongming , Zou Ping , Gao Xiaogang , Ehmann Kornel F
Published: October 2019

With excellent properties, high-temperature superalloys have become the main application materials for aircraft engines, gas turbines, and many other devices. However, superalloys are typically difficult to machine, especially for the thread cutting. In this article, an ultrasonic vibration–assisted turning system is proposed for thread cutting operations in superalloys. A theoretical analysis of ultrasonic vibration–assisted thread cutting is carried out. An ultrasonic vibration–assisted system was integrated into a standard lathe to demonstrate thread turning in Inconel 718 superalloy. The influence of ultrasonic vibration–assisted machining on workpiece surface quality, chip shape, and tool wear was analyzed. The relationship between machining parameters and ultrasonic vibration–assisted processing performance was also explored. By analyzing the motion relationship between tool path and workpiece surface, the reasons for improved workpiece surface quality by ultrasonic vibration–assisted machining were explained.
Risk Factors for Alanine Aminotransferase Elevations in a Prospective Cohort of HIV-Infected Tanzanian Adults Initiating Antiretroviral Therapy
Authors: Mugusi Sabina F. , Sando David , Mugusi Ferdinand M. , Hawkins Claudia , Aboud Said , Fawzi Wafaie W. , Sudfeld Christopher R.
Published: October 2019

Introduction:

Serum alanine aminotransferase (ALT) elevations are common among HIV-infected patients on combination antiretroviral therapy (cART).

Approach:

We conducted a prospective cohort study of 3023 HIV-infected Tanzanian adults initiating cART. We assessed risk factors for mild/moderate ALT elevations >40 IU/L and severe ALT elevations >200 IU/L.

Results:

We found that over a median follow-up of 32.5 months (interquartile range: 19.4-41.5), 44.8% of participants had at least 1 incident ALT elevation >40 IU/L of which 50.1% were persistent elevations. Risk factors for incident ALT elevation >40 IU/L included male sex, CD4 count <100 cells/μL, d4T+3TC+NVP cART, and triglycerides ≥150 mg/dL ( P values <.05). Hepatitis B coinfection and alcohol consumption increased the risk of severe ALT elevations >200 IU/L ( P values: <.05).

Conclusion:

Incident mild and moderate ALT elevations are common among Tanzanians initiating cART, and the clinical and demographic information can identify patients at increased risk.
Isaiah Tishby, Új Kelet (New East), and the Cultural Mediation of Zionism in Transylvania (1920–1930)
Authors: Gondos Andrea
Published: October 2019

This article investigates the spread of Zionism in the Jewish communities of Transylvania devoting special attention to the cultural mediation of the Jewish newspaper, Új Kelet ( New East). Considering representative issues of the Jewish daily, Új Kelet, within 10 years of its inception (from the 1920s), will allow me to describe its key role as the foremost communications outlet for the promotion of Zionist ideas and activities in Transylvania. I will further trace the impact of this newspaper on the life and writings of Isaiah Tishby (1908–1992), one of the preeminent scholars of Kabbalah in the twentieth century, who was exposed to the Jewish daily in his youth and became indelibly transformed by it after its precipitous launch in 1918 on the heels of World War I.
Comparison of Satisfaction With Comorbid Depression Care Models Among Low-Income Patients With Diabetes
Authors: Evanson Olivia , Wu Shinyi
Published: October 2019

Introduction:

Patient satisfaction is a patient-reported outcome with the potential to assess and improve the quality of newer care-management models such as remote patient monitoring using telecommunication technology.

Objective:

To evaluate differences in patient satisfaction among 3 care management groups in a comparative effectiveness trial.

Methods:

This study analyzed a comparative effectiveness trial that tested automated remote assessment technology–facilitated comorbid depression care-management (TC, n = 254) in comparison to team-supported depression care (SC, n = 228) and usual primary care (UC, n = 218) among low-income patients with type 2 diabetes. Relationships between patient satisfaction and care group were evaluated at each 6-month phase up to 18 months using linear regression models that controlled for depression status, diabetes symptoms, patient characteristics, and study group differences.

Results:

While receiving care management, SC and TC patients were significantly more satisfied with depression care than UC patients. No consistently significant associations between patient satisfaction and patient characteristics or disease symptoms were found.

Conclusions:

Patient satisfaction was found to be influenced by elements of care-management, not by patient characteristics or disease symptoms. Results suggest greater patient satisfaction with depression care in a care-management model than UC, whether through clinician team support or automated remote monitoring technology.
Analysis of the cost-effectiveness of treatment strategies for CML with incorporation of treatment discontinuation
Authors: Yamamoto Chihiro , Nakashima Hirotomo , Ikeda Takashi , Kawaguchi Shin-ichiro , Toda Yumiko , Ito Shoko , Mashima Kiyomi , Nagayama Takashi , Umino Kento , Minakata Daisuke , Nakano Hirofumi , Morita Kaoru , Yamasaki Ryoko , Sugimoto Miyuki , Ishihara Yuko , Ashizawa Masahiro , Hatano Kaoru , Sato Kazuya , Oh Iekuni , Fujiwara Shin-ichiro , Ueda Masuzu , Ohmine Ken , Muroi Kazuo , Kanda Yoshinobu
Published: October 2019

Key Points

The cost of TKI for treatment of CML can be substantially saved by treatment discontinuation in patients who achieved DMR. Starting treatment with imatinib is the most cost-effective strategy even after incorporation of treatment discontinuation.
Determinants of ADL and IADL disability in older adults in southeastern Poland
Authors: Ćwirlej-Sozańska Agnieszka , Wiśniowska-Szurlej Agnieszka , Wilmowska-Pietruszyńska Anna , Sozański Bernard
Published: October 2019

Background

The extension of the life span has led to an increase in the number of older people and an increase in the prevalence of disability in people over 60 years of age. The aim of this study was to assess the prevalence of ADL and IADL disability and to analyze its determinants among people aged 60 and older living in southeastern Poland.

Methods

This cross-sectional study was carried out among a randomly selected, representative population of people aged 60 and older living in southeastern Poland. Disability was assessed using the Katz Index of Independence in Basic Activities of Daily Living and Instrumental Activities of Daily Living. Logistic regression models were used to identify the factors related to ADLs and IADLs. For the variables that were included in the above models, their clustered influence on the increase in the odds ratio for the occurrence of an ADL or IADL limitation was also examined.

Results

The research results show that 35.75% of the participants reported at least one problem with IADLs. At least one problem with ADLs was reported by 17.13% of the participants. The most significant modifiable factors influencing the occurrence of disability were the presence of barriers in the participant’s environment, poor relations with relatives, a lack of social contacts, multimorbidity and pain. A multiple increase in the odds ratio of disability was found with the presence of pairs of analyzed factors. The highest odds ratio of at least one ADL limitation was observed for the combination of barriers in the participant’s environment with multimorbidity (OR 74.07). With regard to IADL disability, the highest odds ratio was observed for the combination of pain on the VAS scale ≥3 points with older age (OR 19.47).

Conclusions

The study showed a high prevalence of ADL and IADL disability in older people living in southeastern Poland. It also indicated the extent to which modifiable factors influenced the occurrence of disability and the extent to which the risk of disability increased with the presence of pairs of factors, especially those that included environmental barriers in the participant’s environment.
Probable progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation: a case report and literature review
Authors: Ishii Kazuhiro , Yamamoto Fumiko , Homma Shinsuke , Okada Yoshinori , Nakamichi Kazuo , Saijo Masayuki , Tamaoka Akira
Published: October 2019

Background

Progressive multifocal leukoencephalopathy (PML) is a rapidly developing demyelinating disease in the cerebral white matter and is often caused by JC polyomavirus (JCV). PML after lung transplantation is rare and has a poor prognosis, with no established therapies. Reducing the patient’s immunosuppressant doses, thereby restoring immunity, could be used to treat PML. However, some patients develop immune reconstitution inflammatory syndrome (IRIS) with this treatment, an immune-induced inflammatory response to JCV that results in serious neuronal damage. We herein report a case of a 60-year-old female who suffered from PML 5 years after lung transplantation, had worsened brain lesions thought to be related to PML-IRIS at the time of immunosuppressant reduction, and missed treatment opportunities.

Case presentation

A 60-year-old female developed PML 5 years after lung transplantation. Fluid-attenuated inversion recovery and diffusion-weighted brain magnetic resonance imaging (MRI) revealed multiple high-signal lesions, mainly in the cerebral white matter. Polymerase chain reaction found 0.32 million copies/mL of JCV in the cerebrospinal fluid. Thus, she was given a diagnosis of PML. Mycophenolate mofetil and tacrolimus dosages were reduced, and CD4-positive cell counts and the blood concentration of each immunosuppressant were monitored. Mefloquine was also orally administered at a daily dose of 275 mg for 3 days and was then administered at a dose of 275 mg per week. Although the patient’s CD4-positive cell counts increased and her immune system recovered, her symptoms and brain MRI findings worsened. We suspected PML progression or a transition to PML-IRIS. Steroid pulse therapy to suppress the inflammatory lesions was not possible but was retrospectively indicated. The patient rapidly began to exhibit akinetic mutism and died 4 months after the onset of neurologic symptoms.

Conclusions

When neurologic symptoms and abnormal brain MRI findings are noted during immune recovery, it is often difficult to distinguish between progressed PML and PML-IRIS. However, the pathogenesis of brain lesions usually involves inflammation and immune-reactive mechanisms for JCV. Steroid pulse therapy, which can reduce inflammation, should thus be administered in organ transplantation cases with differential diagnoses including PML-IRIS.
Tumor cell sensitivity to vemurafenib can be predicted from protein expression in a BRAF-V600E basket trial setting
Authors: Carroll Molly J. , Parent Carl R. , Page David , Kreeger Pamela K.
Published: October 2019

Background

Genetics-based basket trials have emerged to test targeted therapeutics across multiple cancer types. However, while vemurafenib is FDA-approved forBRAF-V600E melanomas, the non-melanoma basket trial was unsuccessful, suggesting mutation status is insufficient to predict response. We hypothesized that proteomic data would complement mutation status to identify vemurafenib-sensitive tumors and effective co-treatments forBRAF-V600E tumors with inherent resistance.

Methods

Reverse Phase Proteomic Array (RPPA, MD Anderson Cell Lines Project), RNAseq (Cancer Cell Line Encyclopedia) and vemurafenib sensitivity (Cancer Therapeutic Response Portal) data forBRAF-V600E cancer cell lines were curated. Linear and nonlinear regression models using RPPA protein or RNAseq were evaluated and compared based on their ability to predictBRAF-V600E cell line sensitivity (area under the dose response curve). Accuracies of all models were evaluated using hold-out testing. CausalPath software was used to identify protein-protein interaction networks that could explain differential protein expression in resistant cells. Human examination of features employed by the model, the identified protein interaction networks, and model simulation suggested anti-ErbB co-therapy would counter intrinsic resistance to vemurafenib. To validate this potential co-therapy, cell lines were treated with vemurafenib and dacomitinib (a pan-ErbB inhibitor) and the number of viable cells was measured.

Results

Orthogonal partial least squares (O-PLS) predicted vemurafenib sensitivity with greater accuracy in both melanoma and non-melanomaBRAF-V600E cell lines than other leading machine learning methods, specifically Random Forests, Support Vector Regression (linear and quadratic kernels) and LASSO-penalized regression. Additionally, use of transcriptomic in place of proteomic data weakened model performance. Model analysis revealed that resistant lines had elevated expression and activation of ErbB receptors, suggesting ErbB inhibition could improve vemurafenib response. As predicted, experimental evaluation of vemurafenib plus dacomitinb demonstrated improved efficacy relative to monotherapies.

Conclusions: Combined, our results support that inclusion of proteomics can predict drug response and identify co-therapies in a basket setting.
Short-term treatment with high dose liraglutide improves lipid and lipoprotein profile and changes hormonal mediators of lipid metabolism in obese patients with no overt type 2 diabetes mellitus: a randomized, placebo-controlled, cross-over, double-blind clinical trial
Authors: Peradze Natia , Farr Olivia M. , Perakakis Nikolaos , Lázaro Iolanda , Sala-Vila Aleix , Mantzoros Christos S.
Published: October 2019

Objective

Long-term treatment with up to 1.8 mg liraglutide improves cardiovascular and all-cause mortality in patients with type 2 diabetes at high risk for cardiovascular disease (CVD) and is currently under investigation in subjects without diabetes. Aim of our study was to investigate whether high dose (3 mg) short-term (5 weeks) treatment with liraglutide in obese patients with no overt type 2 diabetes affects metabolites, lipid and lipoprotein profile and components of activin–follistatin axis in cardiovascular beneficial or detrimental way.

Research design and methods

Twenty obese patients participated in a randomized, placebo-controlled, cross-over, double-blind study and were administrated liraglutide 3 mg or placebo for 5 weeks. Metabolites, fatty acids, lipid–lipoprotein profile and concentrations of activins and follistatins (250 parameters) were assessed in serum at start and completion of each treatment.

Results

Concentrations of important cardiovascular markers such as total, free and remnant cholesterol were reduced with liraglutide before and after adjusting for weight loss. Similarly, reductions in number of small and medium size LDL particles and in their total lipid concentration were observed with liraglutide and partially weight-loss related. Tyrosine levels were reduced and behenic acid levels were increased whereas only minor changes were observed in HDL, VLDL and IDL. Concentrations of activin AB and follistatin were significantly reduced in liraglutide-treated group.

Conclusions

Treatment of obese patients without overt type 2 diabetes with high dose of liraglutide for a short period of time induces changes in lipid–lipoprotein and hormonal profile that are suggestive of lower risk of atherosclerosis and CVD.

Trial registration ClinicalTrials.gov Identifier: NCT02944500. Study ID Number 2015P000327. Registered November 2016
Luseogliflozin attenuates neointimal hyperplasia after wire injury in high-fat diet-fed mice via inhibition of perivascular adipose tissue remodeling
Authors: Mori Yusaku , Terasaki Michishige , Hiromura Munenori , Saito Tomomi , Kushima Hideki , Koshibu Masakazu , Osaka Naoya , Ohara Makoto , Fukui Tomoyasu , Ohtaki Hirokazu , Tsutomu Hirano , Yamagishi Sho-ichi
Published: October 2019

Background

Excess fat deposition could induce phenotypic changes of perivascular adipose tissue (PVAT remodeling), which may promote the progression of atherosclerosis via modulation of adipocytokine secretion. However, it remains unclear whether and how suppression of PVAT remodeling could attenuate vascular injury. In this study, we examined the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor, luseogliflozin on PVAT remodeling and neointima formation after wire injury in mice.

Methods

Wilt-type mice fed with low-fat diet (LFD) or high-fat diet (HFD) received oral administration of luseogliflozin (18 mg/kg/day) or vehicle. Mice underwent bilateral femoral artery wire injury followed by unilateral removal of surrounding PVAT. After 25 days, injured femoral arteries and surrounding PVAT were analyzed.

Results

In LFD-fed lean mice, neither luseogliflozin treatment or PVAT removal attenuated the intima-to-media (I/M) ratio of injured arteries. However, in HFD-fed mice, luseogliflozin or PVAT removal reduced the I/M ratio, whereas their combination showed no additive reduction. In PVAT surrounding injured femoral arteries of HFD-fed mice, luseogliflozin treatment decreased the adipocyte sizes. Furthermore, luseogliflozin reduced accumulation of macrophages expressing platelet-derived growth factor-B (PDGF-B) and increasedadiponectingene expression. Gene expression levels ofPdgf-bin PVAT were correlated with the I/M ratio.

Conclusions

Our present study suggests that luseogliflozin could attenuate neointimal hyperplasia after wire injury in HFD-fed mice partly via suppression of macrophage PDGF-B expression in PVAT. Inhibition of PVAT remodeling by luseogliflozin may be a novel therapeutic target for vascular remodeling after angioplasty.
Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis
Authors: Bielecka-Dabrowa Agata , Bytyçi Ibadete , Von Haehling Stephan , Anker Stefan , Jozwiak Jacek , Rysz Jacek , Hernandez Adrian V. , Bajraktari Gani , Mikhalidis Dimitri P. , Banach Maciej
Published: October 2019

Background

The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins’ prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF.

Methods

We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization.

Results

Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72–0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76–0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69–0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68–0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69–0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79–0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77–0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64–0.99, P = 0.04 and HR 0.76 95% CI: 0.61–0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins.

Conclusions

In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.
Correction to: SNHG15 is a bifunctional MYC-regulated noncoding locus encoding a lncRNA that promotes cell proliferation, invasion and drug resistance in colorectal cancer by interacting with AIF
Authors: Saeinasab Morvarid , Bahrami Ahmad Reza , González Jovanna , Marchese Francesco P. , Martinez Dannys , Mowla Seyed Javad , Matin Maryam M. , Huarte Maite
Published: October 2019

In the original publication of this article,[1] the Funding section needs to be revised, and the corrected Funding section appears below.
Correction to: The small molecule WNT/β-catenin inhibitor CWP232291 blocks the growth of castration-resistant prostate cancer by activating the endoplasmic reticulum stress pathway
Authors: Pak Sahyun , Park Sejun , Kim Yunlim , Park Jung-Hyuck , Park Chan-Hee , Lee Kyoung-June , Kim Choung-soo , Ahn Hanjong
Published: October 2019

In the original publication of this article [1], there are mistakes in Fig. 4d. The corrected Fig. 4 should be:
A green and facile synthesis of an industrially important quaternary heterocyclic intermediates for baricitinib
Authors: Cui Xin , Du Junming , Jia Zongqing , Wang Xilong , Jia Haiyong
Published: October 2019

Background

Baricitinib, with a 2-(1-(ethylsulfonyl)azetidin-3-yl)acetonitrile moiety at N-2 position of the pyrazol skeleton, is an oral and selective reversible inhibitor of the JAK1 and JAK2 and displays potent anti-inflammatory activity. Several research-scale synthetic methods have been reported for the preparation of key quaternary heterocyclic intermediates of baricitinib. However, they were all associated with several drawbacks, such as the expensive materials, usage of pollutional reagents, and poor yields.

Results

In this manuscript, we established a green and cost-effective synthesis of 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile and tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate for further scale-up production of baricitinib. This synthetic method employs commercially available and low-cost starting material benzylamine and an industry-oriented reaction of green oxidation reaction in microchannel reactor to yield important quaternary heterocyclic intermediates.

Conclusion

Generally, this procedure is reasonable, green and suitable for industrial production.
Evolving liver inflammation in biochemically normal individuals with anti-mitochondria antibodies
Authors: Baldo Danielle Cristiane , Dellavance Alessandra , Ferraz Maria Lucia Gomes , Andrade Luis Eduardo C.
Published: October 2019

Background

Anti-mitochondria autoantibodies (AMA) occur in > 95% primary biliary cholangitis (PBC) patients. Biochemically normal AMA-positive (BN/AMA+) individuals, occasionally noticed by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed in AMA-specific assays, may represent early stages of PBC. The Enhanced Liver Fibrosis (ELF) score is a surrogate marker for liver fibrosis. This prospective study investigated the ELF score in BN/AMA+ individuals and PBC patients, considering autoantibody avidity and serum levels along the years.

Methods

327 samples from 35 PBC and 59 BN/AMA+ were prospectively obtained in average 3.83 (range 0.50–7.40) years apart. Samples were tested by IIF on rat-kidney (IIF-AMA), western-blot for AMA (WB-AMA), and ELISA for antibodies against pyruvate-dehydrogenase (PDC-E2), gp210, sp100 and CENP-A/B. Anti-PDC-E2 avidity was determined by 6 M urea-elution ELISA. Alkaline phosphatase (ALP), gamma glutamyl transferase (ɣGT) and ELF score were measured by automated methods.

Results

Along the follow-up period BN/AMA+ subjects and PBC patients presented significant increase in serum anti-PDC-E2 (mean 10.45% and 8.86% per year; respectively), anti-PDC-E2 avidity (3.02% and 4.94%/year) and ELF score (3.24% and 2.71%/year). IIF-AMA and ɣGT increased in BN/AMA+ (6.59% and 2.36%) and decreased in PBC (− 4.89%/year and − 3.88%/year). In BN/AMA+ individuals there was positive correlation of ELF with IIF-AMA titer (r = 0.465; p < 0.001) and with anti-PDC-E2 levels (r = 0.239; p < 0.001). Expansion of autoantibody targets along time occurred in 39% BN/AMA+ and 49% PBC patients. The frequency of BN/AMA+ with high probability of having established PBC increased from 7 to 14%.

Conclusions

BN/AMA+ individuals present an orchestrated increase in ELF score and humoral autoimmune response over time, indicating an opportunity for early therapeutic intervention and prevention in autoimmunity.
Identification of novel B cell epitopes in the fiber protein of serotype 8 Fowl adenovirus
Authors: Lu Hao , Shao Hongxia , Chen Hongjun , Zhang Jianjun , Wang Weikang , Li Tuofan , Xie Quan , Qin Aijian , Ye Jianqiang
Published: October 2019

In recent years, hepatitis-hydropericardium syndrome (HHS) and inclusion body hepatitis (IBH) caused by fowl adenovirus (FAdV) infection have resulted in significant economic losses to the poultry industry worldwide. Epidemiological analysis revealed that serotype FAdV-8 is one of the major pathogenic FAdVs currently prevalent in domestic flocks. Although the fiber protein of FAdV plays vital roles in viral infection and pathogenesis, the B cell epitope in the fiber protein is less known. In this study, two monoclonal antibodies (mAbs) specific to fiber protein of FAdV-8, designated as 4D9 and 5F10, were prepared. Although the mAb 4D9 and 5F10 could not neutralize FAdV-8 infection, 4D9 and 5F10 showed good activities of indirect immunofluorescence, western blot and immunoprecipitation. Epitope analysis revealed that mAb 5F10 recognized 187–219aa in the fiber whereas mAb 4D9 recognized 113–149aa in the fiber. Sequence analysis showed that the epitope recognized by mAb 5F10 was conserve across serotypes FAdV-7, 8a and 8b whereas that for mAb 4D9 was only conserve in FAdV-8b. The generation of mAbs specific to fiber of FAdV-8 and the identification of the novel B cell epitopes here lay the foundation for further studying the antigenicity of the fiber and developing specific diagnosis for FAdV-8.