bluuebunny/crossref_metadata_2025_split huggingface dataset:
STAT3 phosphorylation inhibition for treating inflammation and new bone formation in ankylosing spondylitis
Authors: Jo Sungsin , Won Eun Jeong , Kim Moon-Ju , Lee Yu Jeong , Jin So-Hee , Park Pu-Reum , Song Ho-Chun , Kim Jahae , Choi Yoo-Duk , Kim Ji-Young , Shim Seung Cheol , Choi Sung Hoon , Park Ye-Soo , Kim Tae-Hwan , Kim Tae-Jong 
Published: November 2020

AbstractObjectiveAS is a rheumatic disease characterized by chronic inflammation and bony ankylosis. This study was to evaluate whether a signal transducer and activator of transcription 3 phosphorylation inhibitor (stat3-p Inh) could treat both chronic inflammation and bone formation in AS.MethodsPrimary AS osteoprogenitor cells and spinal entheseal cells were examined for osteogenic differentiation. SF mononuclear cells (SFMCs) and lamina propria mononuclear cells (LPMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analysed using flow cytometry and ELISA. Female SKG mice were treated with stat3-p Inh, IL-17A blocker or vehicle. Inflammation and new bone formation were evaluated using immunohistochemistry, PET and micro-CT.ResultsIn the SKG mouse model, stat3-p Inh significantly suppressed arthritis, enthesitis, spondylitis and ileitis. In experiments culturing SFMCs and LPMCs, the frequencies of IFN-γ-, IL-17A- and TNF-α-producing cells were significantly decreased after stat3-p Inh treatment. When comparing current treatments for AS, stat3-p Inh showed a comparable suppression effect on osteogenesis to Janus kinase inhibitor or IL-17A blocker in AS-osteoprogenitor cells. Stat3-p Inh suppressed differentiation and mineralization of AS-osteoprogenitor cells and entheseal cells toward osteoblasts. Micro-CT analysis of hind paws revealed less new bone formation in stat3-p Inh-treated mice than vehicle-treated mice (P = 0.005). Hind paw and spinal new bone formation were similar between stat3-p Inh- and anti-IL-17A-treated SKG mice (P = 0.874 and P = 0.117, respectively).ConclusionStat-3p inhibition is a promising treatment for both inflammation and new bone formation in AS.
A panel of urinary proteins predicts active lupus nephritis and response to rituximab treatment
Authors: Davies Jennifer C , Carlsson Emil , Midgley Angela , Smith Eve M D , Bruce Ian N , Beresford Michael W , Hedrich Christian M ,   the BILAG-BR and MRC MASTERPLANS Consortia
Published: November 2020

Abstract

Objectives
∼30% of patients with SLE develop LN. Presence and/or severity of LN are currently assessed by renal biopsy, but biomarkers in serum or urine samples may provide an avenue for non-invasive routine testing. We aimed to validate a urinary protein panel for its ability to predict active renal involvement in SLE.

Methods
A total of 197 SLE patients and 48 healthy controls were recruited, and urine samples collected. Seventy-five of the SLE patients had active LN and 104 had no or inactive renal disease. Concentrations of lipocalin-like prostaglandin D synthase (LPGDS), transferrin, alpha-1-acid glycoprotein (AGP-1), ceruloplasmin, monocyte chemoattractant protein 1 (MCP-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were quantified by MILLIPLEX® Assays using the MAGPIX Luminex platform. Binary logistic regression was conducted to examine whether proteins levels associate with active renal involvement and/or response to rituximab treatment.

Results
Urine levels of transferrin (P &lt;0.005), AGP-1 (P &lt;0.0001), MCP-1 (P &lt;0.001) and sVCAM-1 (P &lt;0.005) were significantly higher in SLE patients when compared with healthy controls. Furthermore, levels of transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 (all P &lt;0.0001) were higher in SLE patients with active LN when compared with patients without active LN. A combination of five urine proteins, namely LPGDS, transferrin, ceruloplasmin, MCP-1 and sVCAM-1 was a good predictor of active LN (AUC 0.898). A combined model of LPGDS, transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 predicted response to rituximab treatment at 12 months (AUC 0.818).

Conclusions
Findings support the use of a urinary protein panel to identify active LN and potentially predict response to treatment with rituximab in adult SLE patients. Prospective studies are required to confirm findings.
SECRETARY OF STATE FOR HEALTH v SERVIER LABORATORIES LTD
Authors:   Court of Appeal
Published: November 2020

Abstract
H1 Patents – European patents - Pharmaceuticals – Generic products – Economic torts – Unlawful means – Strike out application – Necessary elements of the tort – Whether the unlawful means relied upon had to interfere with claimant’s liberty to deal with third party against whom the unlawful act relied upon had been committed – Invalid patents – Proceedings for patent infringement – Interim injunctions – Market entry of third party generic product delayed – Prices thereby maintained – Patent later invalidated – Claim struck out at first instance – Appeal to Court of Appeal
Timing, Distribution, and Relationship Between Nonpsychotic and Subthreshold Psychotic Symptoms Prior to Emergence of a First Episode of Psychosis
Authors: Cupo Lani , McIlwaine Sarah V , Daneault Jean-Gabriel , Malla Ashok K , Iyer Srividya N , Joober Ridha , Shah Jai L 
Published: November 2020

AbstractProspective population studies suggest that psychotic syndromes may be an emergent phenomenon—a function of severity and complexity of more common mental health presentations and their nonpsychotic symptoms. Examining the relationship between nonpsychotic and subthreshold psychotic symptoms in individuals who later developed the ultimate outcome of interest, a first episode of psychosis (FEP), could provide valuable data to support or refute this conceptualization of how psychosis develops. We therefore conducted a detailed follow-back study consisting of semistructured interviews with 430 patients and families supplemented by chart reviews in a catchment-based sample of affective and nonaffective FEP. The onset and sequence of 27 pre-onset nonpsychotic (NPS) or subthreshold psychotic (STPS) symptoms was systematically characterized. Differences in proportions were analyzed with z-tests, and correlations were assessed with negative binomial regressions. Both the first psychiatric symptom (86.24% NPS) and the first prodromal symptom (66.51% NPS) were more likely to be NPS than STPS. Patients reporting pre-onset STPS had proportionally more of each NPS than did those without pre-onset STPS. Finally, there was a strong positive correlation between NPS counts (reflecting complexity) and STPS counts (β = 0.34, 95% CI [0.31, 0.38], P &lt; 2 e-16). Prior to a FEP, NPS precede STPS, and greater complexity of NPS is associated with the presence and frequency of STPS. These findings complement recent arguments that the emergence of psychotic illness is better conceptualized as part of a continuum—with implications for understanding pluripotential developmental trajectories and strengthening early intervention paradigms.
The use of traditional medicines among mycetoma patients
Authors: Kunna Ezzan , Yamamoto Taro , Fahal Ahmed 
Published: November 2020

AbstractBackgroundMycetoma patients frequently present with advanced disease, the cause of which is multi-factorial, but the use of traditional medicine modalities has been shown to be an important one. Traditional medicine is an integral part of the Sudanese culture and many mycetoma patients revert to it because it is accessible, cheap and available.MethodsTo confirm this anecdotal observation, the pattern and characteristics of traditional medicine use among a group of mycetoma patients seen at the Mycetoma Research Center in Khartoum, Sudan, were studied.ResultsIn this descriptive, cross-sectional, hospital-based study, 389 mycetoma-confirmed patients were included. All of them had used traditional medicine at some stage of their mycetoma treatment. Among them, 66% had first consulted traditional healers for mycetoma treatment. In this study, 58% had consulted religious healers known as fakis, while the majority (72%) of those who consulted specialist healers had consulted herbalists. The most frequent type of traditional medicine received by patients from religious healers was al-azima (31%) and the most common treatment given by the specialist healers was herbal medicine (46%).ConclusionTraditional medicine can lead to a delay in seeking medical care and serious complications. Collaboration with traditional healers, and training and educating them to refer mycetoma patients to specialised centres is vital to ensure that they receive proper treatment in a timely and efficient manner.
Assessment of adherence to anti-tuberculosis treatment and predictors for non-adherence among the caregivers of children with tuberculosis
Authors: Laghari Madeeha , Talpur Bandeh Ali , Sulaiman Syed Azhar Syed , Khan Amer Hayat , Bhatti Zohra 
Published: November 2020

Abstract

Background
Information on the extent of patient medication adherence and the use of interventions to advance adherence are scarce in clinical practice. This study aimed to assess medication adherence and risk factors for non-adherence among the caregivers of children with tuberculosis (TB).

Methods
This prospective study was conducted among the caregivers of 443 child TB patients registered during the study. Caregivers of children were queried using a structured questionnaire consisting of sociodemographic and socio-economic factors and the role of healthcare workers during the treatment course. Risk factors for non-adherence were estimated using a logistic regression model.

Results
In multivariate analysis, the independent variables that had a statistically significant positive association with non-adherence were male sex (adjusted odds ratio [AOR] 5.870 [95% confidence interval {CI} 1.99 to 17.29]), age ≥45 y (AOR 5.627 [95% CI 1.88 to 16.82]), caregivers with no formal education (AOR 3.905 [95% CI 1.29 to 11.79]), financial barriers (AOR 30.297 [95% CI 6.13 to 149.54]), insufficient counselling by healthcare workers (AOR 5.319 [95% CI 1.62 to 17.42]), insufficient counselling by health professionals (AOR 4.117 [95% CI 1.05 to 16.05]) and unfriendly attitude and poor support from healthcare professionals (AOR 11.150 [95% CI 1.91 to 65.10]).

Conclusions
Treatment adherence in the present study was 86% using the Morisky Green Levine Medication Adherence Scale and 90.7% using the visual analogue scale tool. Predictors of non-adherence need to be a focus and caregivers should be given complete knowledge about the importance of adherence to TB treatment.
Magnetic sphincter augmentation device placement for treatment of gastroesophageal reflux
Authors: Laird Jason 
Published: November 2020

ABSTRACT
Gastroesophageal reflux disease typically is treated with lifestyle modifications and proton pump inhibitors (PPIs). Surgery is effective in treating the symptoms associated with gastroesophageal reflux, but common procedures involve invasive techniques that can leave the patient unable to belch or vomit. Research has raised concerns regarding the long-term use of PPIs, leaving few treatment options for patients with refractory reflux symptoms. The magnetic sphincter augmentation device demonstrates similar efficacy to existing antireflux procedures, avoids complex surgery techniques, and preserves normal physiologic functions at the lower esophageal sphincter. This device is a safe and effective alternative to more invasive procedures for patients whose GERD does not respond to medical management.
Recognizing and treating child overweight and obesity
Authors: Cooper Christen Cupples , Mandel Ellen D. 
Published: November 2020

ABSTRACT
Primary care providers can help prevent and address child overweight and obesity, conditions that can affect children's present and future health as well as their psychologic, emotional, and social well-being. This article describes approaches to preventing, identifying, and addressing overweight and obesity using empathetic, practical, family-focused recommendations and actions.
Percutaneous Fixation of Pediatric Fractures of the Proximal Phalanx Neck: A Novel Technique
Authors: Pientka William F. , Cheng Jonathan 
Published: November 2020

Introduction:
Proximal phalanx neck fractures occur almost exclusively in children. Fractures of the proximal phalanx neck can be difficult to treat nonoperatively given the anatomic location and associated extrinsic forces. A divergent or crossed pin configuration is often utilized for the stabilization of these fractures.

Purpose:
We present a surgical technique with a single Kirschner (K-wire) placed axially along the affected finger, with a hyperextension reduction maneuver, to reduce and fixate proximal phalanx neck fractures in children and adolescents.

Methods:
We performed a retrospective review of all pediatric proximal phalanx neck fractures treated by a single surgeon. Demographic data, as well as clinical and radiographic outcomes were recorded. We then directly compared axial pinning [14 patients; average age 6.63 y (9 mo to 17 y)] with nonoperative treatment [28 patients; average age 8.03 y (9 mo to 16 y)], and open treatment [8 patients; average age 8.13 y (1 to 14 y)].

Results:
Patients who underwent closed reduction and axial pinning had significantly improved final coronal alignment compared with nonoperative treatment. Compared with fractures which required open reduction, closed reduction with axial pinning resulted in significantly shorter surgical duration and time to radiographic healing. The final range of motion showed no difference between intervention types, as all patients regained full range of motion.

Conclusions:
We find this axial pinning technique to be simpler and faster than divergent pin fixation, with no significant differences in time to radiographic healing, time to full activity, final proximal interphalangeal active flexion or extension, loss of reduction, or radiographic parameters.

Level of Evidence:
Level III—Therapeutic.
Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Health-Related Quality of Life in Sepsis
Authors: Grossestreuer Anne V. , Moskowitz Ari , Andersen Lars W. , Holmberg Mathias J. , Konacki Varun , Berg Katherine M. , Chase Maureen , Cocchi Michael N. , Donnino Michael W. 
Published: November 2020

Objectives:
Patients who experience sepsis often have long-term effects that may impact health-related quality of life. This study aimed to investigate whether the combination of ascorbic acid, corticosteroids, and thiamine compared with placebo improves health-related quality of life in patients with septic shock.

Design:
Secondary analysis of the Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis randomized controlled trial (NCT03389555).

Setting:
Thirteen tertiary-care hospitals in the United States.

Patients:
Patients who were enrolled in Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis, survived to 90 days post enrollment and were able to be contacted by telephone.

Interventions:
Patients were randomly assigned to parenteral ascorbic acid (1,500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days or placebo.

Measurements and Main Results:
One hundred seventeen patients (59%) survived to 90 days and were administered the Short Form 36 questionnaire; of these, 72 (62%) completed the Short Form 36 (38 [53%] in the intervention group, 34 [47%] in placebo). Sixty-six (92%) completed all survey questions (36 [95%] in the intervention group, 30 [88%] in placebo). There was no significant difference in overall Short Form 36 score between intervention and placebo group (median score: 39.4 [interquartile range, 31.2–45.4] vs 43.2 [37.0–46.7], respectively, p = 0.18). We found no statistically significant difference between the two groups in any of the other health-related quality of life domains used.

Conclusions:
We found no difference in the health-related quality of life in patients with septic shock treated with a combination of ascorbic acid, corticosteroids, and thiamine compared to placebo.
COVID-19 antibody development fueled by HIV-1 broadly neutralizing antibody research
Authors: Mendoza Pilar , Lorenzi Julio C.C. , Gaebler Christian 
Published: November 2020

Purpose of review
The coronavirus disease 2019 (COVID-19) pandemic has caught the world unprepared, with no prevention or treatment strategies in place. In addition to the efforts to develop an effective vaccine, alternative approaches are essential to control this pandemic, which will most likely require multiple readily available solutions. Among them, monoclonal anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have been isolated by multiple laboratories in record time facilitated by techniques that were first pioneered for HIV-1 antibody discovery. Here, we summarize how lessons learned from anti-HIV-1 antibody discovery have provided fundamental knowledge for the rapid development of anti-SARS-CoV-2 antibodies.

Recent findings
Research laboratories that successfully identified potent broadly neutralizing antibodies against HIV-1 have harnessed their antibody discovery techniques to isolate novel potent anti-SARS-CoV-2 antibodies, which have efficacy in animal models. These antibodies represent promising clinical candidates for treatment or prevention of COVID-19.

Summary
Passive transfer of antibodies is a promising approach when the elicitation of protective immune responses is difficult, as in the case of HIV-1 infection. Antibodies can also play a significant role in post-exposure prophylaxis, in high-risk populations that may not mount robust immune responses after vaccination, and in therapy. We provide a review of the recent approaches used for anti-SARS-CoV-2 antibody discovery and upcoming challenges in the field.
Bisphosphonate use and the risk of atypical fractures
Authors: Bose Debdipta , Gogtay Nithya J. 
Published: November 2020

Summary
Bisphosphonates (BPs) have been in the market for the past 40 years and proven beneficial especially for patients with osteoporosis and prevention of hypercalcemic in malignancy. However, their long-term use raises safety concerns like Atypical femoral fracture and Osteonecrosis of the Jaw whose pathophysiology still remains unclear. Atypical femoral fracture is more commonly seen among BP users with at least six years of therapy and concomitant use of drugs such as glucocorticoids. The most common treatment for atypical femoral fracture is to withdraw the therapy with monitoring of bone resorption markers but the definitive treatment is intramedullary nail fixation where necessary. Hence, physicians must be vigilant to rarer and long-term BP-reported adverse effects and understand the evidence around the use of these drugs including drug free holidays. A structured benefit-risk assessment should be made for every individual patient including communicating the risk of these rare side effects.
POSITION OF IN-THE-BAG POSTERIOR CHAMBER INTRAOCULAR LENSES RELATIVE TO THE LIMBUS
Authors: Vingopoulos Filippos , Nair Archana , See Craig W. , Iyengar Nishanth , Haberman Ilyse , Sperber Laurence , Lazzaro Douglas R. , Singh Rishi , Ho Allen , Gupta Omesh , Sharma Sumit , Modi Yasha 
Published: November 2020

Purpose:
To characterize the true position of in-the-bag intraocular lenses (IOLs) relative to the limbus using ultrasound biomicroscopy and estimate scleral-sutured IOL positioning.

Methods:
This prospective single-center study included 70 eyes of 41 patients with in-the-bag posterior chamber IOLs. Four vertical ultrasound biomicroscopy captures were performed in each eye in the superior, inferior, nasal, and temporal quadrants. Postoperative biometric data were collected. The primary outcome was the vertical distance of the in-the-bag IOL from the sclerocorneal limbus. Secondary outcomes included anterior shift and refractive change of a theoretical scleral-sutured IOL using sclerotomies at 2.5 mm and 3 mm posterior to the limbus.

Results:
A total of 265 ultrasound biomicroscopy images were analyzed, including 64 superior, 69 inferior, 66 nasal, and 66 temporal. The true in-the-bag IOL position measured as distance posterior to the sclerocorneal limbus was 4.23 ± 0.56 mm superiorly, 4.22 ± 0.46 mm inferiorly, 3.95 ± 0.48 mm nasally, and 3.86 ± 0.52 mm temporally. The anterior shift of a theoretical scleral-sutured IOL was 0.60 mm for a 3-mm sclerotomy and 0.93 mm for a 2.5-mm sclerotomy, resulting in a theoretical myopic shift of 0.45 diopter (D) and 0.79 D, respectively, assuming a 15-D IOL. Larger biometric measurements correlated with a more posterior in-the-bag position.

Conclusion:
True in-the-bag IOL position was found to be more posterior than estimates of scleral-sutured IOLs. Additional corrections in scleral-sutured IOL calculations may improve refractive outcomes.
CLINICOPATHOLOGIC CORRELATION OF PRERETINAL TISSUES IN MYOPIC TRACTION MACULOPATHY
Authors: Russell Jonathan F. , Naranjo Andrea , Dubovy Sander R. , Smiddy William E. 
Published: November 2020

Purpose:
To evaluate histopathologic features of preretinal tissues removed from eyes with myopic traction maculopathy (MTM).

Methods:
We retrospectively studied preretinal tissue specimens from eyes with MTM removed during pars plana vitrectomy. A control group of six idiopathic epiretinal membranes was studied for comparison.

Results:
Six MTM specimens were studied histopathologically. Outer retinal schisis-like thickening was present in 100% of preoperative optical coherence tomography images; four of the six eyes had subfoveal neurosensory retinal detachment. Postoperative optical coherence tomography images demonstrated complete resolution of the schisis-like appearance in all eyes; a full-thickness macular hole occurred in two of the six eyes. Histopathologic examination disclosed fibrocellular tissue that was strongly positive for glial fibrillary acidic protein, weak to moderately positive for cytokeratin, and weakly positive for smooth muscle actin and CD68. There were no apparent histopathologic or immunohistochemical differences between preretinal tissues from eyes with MTM and idiopathic epiretinal membranes from control eyes.

Conclusion:
The outer retinal schisis-like thickening, commonly associated with subretinal fluid, that characterizes MTM is associated with preretinal tissues that are histopathologically indistinguishable from idiopathic epiretinal membranes. These findings suggest that anteroposterior traction caused by axial elongation rather than a uniquely abnormal cellular process is the etiologic mechanism of MTM.