bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences and similarities in clinical and functional responses among patients receiving tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate: a post hoc analysis of data from ORAL Strategy
Authors: Takeuchi Tsutomu , Fleischmann Roy , Iikuni Noriko , Shi Harry , Soma Koshika , Paulissen Jerome , Hirose Tomohiro , Smolen Josef S. 
Published: August 2021

Abstract
Background
This post hoc analysis assessed clinical and functional responses to tofacitinib monotherapy, tofacitinib + methotrexate (MTX), and adalimumab + MTX, in patients with rheumatoid arthritis enrolled in the ORAL Strategy study, including evaluation of patient-level data using cumulative probability plots.

Methods
In the 12-month, phase IIIb/IV ORAL Strategy study, patients with rheumatoid arthritis and an inadequate response to MTX were randomized to receive tofacitinib 5 mg twice daily (BID), tofacitinib 5 mg BID + MTX, or adalimumab 40 mg every other week + MTX. In this post hoc analysis, cumulative probability plots were generated for mean percent change from baseline (%∆) in the Clinical Disease Activity Index (CDAI; clinical response) and mean change from baseline (∆) in the Health Assessment Questionnaire-Disability Index (HAQ-DI; functional response) at month 12. Median C-reactive protein (CRP) levels by time period were summarized by CDAI remission (≤ 2.8) status at months 6 and 12.

Results
Data for 1146 patients were analyzed. At month 12, cumulative probability plots for %∆CDAI and ∆HAQ-DI were similar across treatments in patients with greater response. At lower levels of response, patients receiving tofacitinib monotherapy did not respond as well as those receiving combination therapies. With tofacitinib + MTX, numerically higher baseline CRP levels and numerically larger post-baseline CRP reductions were seen in patients achieving CDAI remission at months 6 and 12 vs those who did not.

Conclusions
These results suggest that patients with a greater response did well, irrespective of which therapy they received. Patients with lesser response had better outcomes with combination therapies vs tofacitinib monotherapy, suggesting they benefitted from MTX. High pre-treatment CRP levels may be associated with better response to tofacitinib + MTX.

Trial registration
ClinicalTrials.gov, NCT02187055. Registered on 08 July 2014.
Neuroprotection in early stages of Alzheimer’s disease is promoted by transthyretin angiogenic properties
Authors: Gião Tiago , Saavedra Joana , Vieira José Ricardo , Pinto Marta Teixeira , Arsequell Gemma , Cardoso Isabel 
Published: August 2021

AbstractBackgroundWhile still controversial, it has been demonstrated that vascular defects can precede the onset of other AD hallmarks features, making it an important therapeutic target. Given that the protein transthyretin (TTR) has been established as neuroprotective in AD, here we investigated the influence of TTR in the vasculature.MethodsWe evaluated the thickness of the basement membrane and the length of brain microvessels, by immunohistochemistry, in AβPPswe/PS1A246E (AD) transgenic mice and non-transgenic mice (NT) bearing one (TTR+/−) or two (TTR+/+) copies of the TTR gene. The angiogenic potential of TTR was evaluated in vitro using the tube formation assay, and in vivo using the chick chorioallantoic membrane (CAM) assay.ResultsAD transgenic mice with TTR genetic reduction, AD/TTR+/−, exhibited a thicker BM in brain microvessels and decreased vessel length than animals with normal TTR levels, AD/TTR+/+. Further in vivo investigation, using the CAM assay, revealed that TTR is a pro-angiogenic molecule, and the neovessels formed are functional. Also, TTR increased the expression of key angiogenic molecules such as proteins interleukins 6 and 8, angiopoietin 2, and vascular endothelial growth factor, by endothelial cells, in vitro, under tube formation conditions. We showed that while TTR reduction also leads to a thicker BM in NT mice, this effect is more pronounced in AD mice than in NT animals, strengthening the idea that TTR is a neuroprotective protein. We also studied the effect of TTR tetrameric stabilization on BM thickness, showing that AD mice treated with the TTR tetrameric stabilizer iododiflunisal (IDIF) displayed a significant reduction of BM thickness and increased vessel length, when compared to non-treated littermates.ConclusionOur in vivo results demonstrate the involvement of TTR in angiogenesis, particularly as a modulator of vascular alterations occurring in AD. Since TTR is decreased early in AD, its tetrameric stabilization can represent a therapeutic avenue for the early treatment of AD through the maintenance of the vascular structure.
Stressful life events among incarcerated women and men: Association with depression, loneliness, hopelessness, and suicidality
Authors: Moore Kelly E. , Siebert Shania , Brown Garrett , Felton Julia , Johnson Jennifer E. 
Published: August 2021

AbstractBackgroundJustice-involved populations report a higher than average number of pre-incarceration stressful life events. However, few studies have described stressful life events which occur during incarceration, explored gender differences in these events, or evaluated the effect of these events on well-being.MethodThis study draws from a sample of male and female adults incarcerated in 6 prison facilities across two states (n = 160) to identify the number and type of stressful life events they experienced during incarceration, gender differences in stressful events, and the relationship between stressful life events and markers of well-being (i.e., depression, hopelessness, loneliness, suicidality). We also examined whether perceived social support would buffer the relationship between stressful events and well-being outcomes.ResultsParticipants on average reported experiencing 4 stressful life events during their current incarceration, the most common being relocation to another cell and being made fun of/insulted by someone in the prison. There were few gender differences in types of events experienced. Regression analyses showed that stressful life events were associated with more loneliness, as well as suicidality, but only when participants had low perceived social support.ConclusionsStressful life events, and drawing on social support networks to cope with stress, should be addressed in the context of correctional treatments to reduce suicide risk during incarceration.
Circulating dipeptidyl peptidase 3 on intensive care unit admission is a predictor of organ dysfunction and mortality
Authors: Frigyesi Attila , Lengquist Maria , Spångfors Martin , Annborn Martin , Cronberg Tobias , Nielsen Niklas , Levin Helena , Friberg Hans 
Published: August 2021

Abstract
Background
Our aim was to investigate the prognostic potential of circulating dipeptidyl peptidase 3 (cDPP3) to predict mortality and development of organ dysfunction in a mixed intensive care unit (ICU) population, and for this reason, we analysed prospectively collected admission blood samples from adult ICU patients at four Swedish hospitals. Blood samples were stored in a biobank for later batch analysis. The association of cDPP3 levels with 30-day mortality and Sequential Organ Failure Assessment (SOFA) scores on day two was investigated before and after adjustment for the simplified acute physiology score III (SAPS-3), using multivariable (ordinal) logistic regression. The predictive power of cDPP3 was assessed using the area under the receiver operating characteristic curve (AUROC).

Results
Of 1978 included consecutive patients in 1 year (2016), 632 fulfilled the sepsis 3-criteria, 190 were admitted after cardiac arrest, and 157 because of trauma. Admission cDPP3 was independently (of SAPS-3) associated with 30-day mortality with odds ratios of 1.45 (95% confidence interval (CI) 1.28–1.64) in the entire ICU population, 1.30 (95% CI 1.08–1.57) in the sepsis subgroup and 2.28 (95% CI 1.50–3.62) in cardiac arrest. For trauma, there was no clear association. Circulating DPP3 alone was a moderate predictor of 30-day mortality with AUROCs of 0.68, 0.62, and 0.72 in the entire group, the sepsis subgroup, and the cardiac arrest subgroup, respectively. By adding cDPP3 to SAPS-3, AUROC improved for the entire group, the sepsis subgroup, and the cardiac arrest subgroup (p = 0.023).

Conclusion
Circulating DPP3 on admission is a SAPS-3 independent prognostic factor of day-two organ dysfunction and 30-day mortality in a mixed ICU population and needs further evaluation.
Bacterial arthritis of native joints can be successfully managed with needle arthroscopy
Authors: Stornebrink Tobias , Janssen Stein J. , Kievit Arthur J. , Mercer Nathaniel P. , Kennedy John. G. , Stufkens Sjoerd A. S. , Kerkhoffs Gino M. M. J. 
Published: August 2021

AbstractPurposeTo assess the feasibility of needle arthroscopy for management of suspected bacterial arthritis in native joints.MethodsDuring a pilot period, patients presenting with symptoms suggestive of native joint bacterial arthritis were eligible for initial management with needle arthroscopy. Procedures were performed in the operating theatre or at the patient bedside in the emergency department or inpatient ward. As our primary outcome measure, it was assessed whether needle arthroscopic lavage resulted in a clear joint. In addition, the need for conversion to standard arthroscopy or arthrotomy, the need for conversion from local to general anaesthesia, complications and the need for additional surgical intervention at follow-up during admission were recorded.ResultsEleven joints in 10 patients (four males, age range 35 – 77) were managed with needle arthroscopy. Needle arthroscopic lavage resulted in a clear joint in all cases. Conversion to standard arthroscopy or arthrotomy was not needed. Seven procedures were performed at the patient bedside using local anaesthesia. These procedures were well tolerated and conversion to general or spinal anaesthesia was not required. There were no procedure complications. One patient received multiple needle arthroscopic lavages. No further surgical interventions beside the initial needle arthroscopic lavage were required for successful management in other cases.ConclusionsNeedle arthroscopy can be a feasible tool in the initial management of complaints suggestive for native joint bacterial arthritis, providing an effective, quick and well-tolerable intervention in the operating theatre or at the patient bedside, with the potential to relief health systems from need for scarce operating theatre time.
Linkages between market orientation and brand performance with positioning strategies of significant fashion apparels in Pakistan
Authors: Gul Rana Faizan , Liu Dunnan , Jamil Khalid , Baig Sajjad Ahmad , Awan Fazal Hussain , Liu Mingguang 
Published: August 2021

AbstractThe study explores the importance of market orientation strategy to enhance brand performance and the mediating role of positioning strategies. The researcher used questionnaires to collect data from the managers of middle and high fashion apparel manufacturing firms based on the quantitative research approach. The data was collected from 220 managers who were directly involved in the decision-making process. The analysis has revealed a significant impact of market orientation strategy on Pakistan’s fashion brands' performance, with the mediating effect of positioning strategies. The management of firms must give considerable importance to market orientation strategies to enhance overall brand performance. The market orientation strategies’ development is also helpful in building different positioning strategies through which performance gets enhanced. This study contributes valuable literature because it focuses on the fashion apparel industry's context, which is almost most important for everyone in the present era. Firms can focus on tight product quality control, innovative manufacturing processes, trained and experienced personnel, and extensive customer service.
Experimental infectious challenge in pigs leads to elevated fecal calprotectin levels following colitis, but not enteritis
Authors: Barbosa Jéssica A. , Rodrigues Lucas A. , Columbus Daniel A. , Aguirre Juan C. P. , Harding John C. S. , Cantarelli Vinícius S. , Costa Matheus de O. 
Published: August 2021

Abstract
Background
Fecal calprotectin is largely applied as a non-invasive intestinal inflammation biomarker in human medicine. Previous studies in pigs investigated the levels of fecal calprotectin in healthy animals only. Thus, there is a knowledge gap regarding its application during infectious diarrhea. This study investigated the usefulness of fecal calprotectin as a biomarker of intestinal inflammation in Brachyspira hyodysenteriae and Salmonella Typhimurium infected pigs.

Results
Fecal samples from pigs with colitis (n = 18) were collected from animals experimentally inoculated with B. hyodysenteriae (n = 8) or from sham-inoculated controls (n = 3). Fecal samples from pigs with enteritis (n = 14) were collected from animals inoculated with Salmonella enterica serovar Typhimurium (n = 8) or from sham-inoculated controls (n = 4). For both groups, fecal samples were scored as: 0 = normal; 1 = soft, wet cement; 2 = watery feces; 3 = mucoid diarrhea; and 4 = bloody diarrhea. Fecal calprotectin levels were assayed using a sandwich ELISA, a turbidimetric immunoassay and a point-of-care dipstick test. Fecal calprotectin levels were greater in colitis samples scoring 4 versus ≤ 4 using ELISA, and in feces scoring 3 and 4 versus ≤ 1 using immunoturbidimetry (P < 0.05). No differences were found in calprotectin concentration among fecal scores for enteritis samples, regardless of the assay used. All samples were found below detection limits using the dipstick method.

Conclusions
Fecal calprotectin levels are increased following the development of colitis, but do not significantly change due to enteritis. While practical, the use of commercially available human kits present sensitivity limitations. Further studies are needed to validate the field application of calprotectin as a marker of intestinal inflammation.
Primary breast edema on contrast-enhanced digital mammography: a preliminary experience
Authors: Haggag Marwa A. , Hamed Soha T. , Mawas Aya Sedky Abd El Latif 
Published: August 2021

Abstract
Background
Primary breast edema can cause marked increase in skin thickness, breast density and echogenicity due to dense breast tissue filled with fluid and so causes subsequent significant attenuation of both the x-ray and ultrasound beams. The study aim is to assess the value of contrast-enhanced digital mammography (CEDM) in assessment and characterization of the obscured underlying breast lesions in cases of primary breast edema.

Results
Fifty five female participants were evaluated, of median age 51 years old and IQR 21. CEDM shows high sensitivity and specificity in the lesion detection as well as local extension delineation in cases associated with primary breast edema. It was accurate in detection of multifocal/multi-centric disease. CEDM is considered as a good negative test in cases of metastatic axillary lymph nodes to exclude and assess any associated obscured breast lesions, as it is good in delineating breast masses obscured by condensed parenchymal tissue. The calculated sensitivity of DM & CEDM was 87.5%, 95.8%, specificity was 55.5%, 72%, the PPV and NPV were 91, 93.6% and 45%, 77.8%, respectively.

Conclusions
CEDM has an important additional diagnostic value in the assessment, characterization and better delineation of breast lesions in primary edematous breast cases.
De-implementing and sustaining an intervention to eliminate nursing home resident bed and chair alarms: interviews on leadership and staff perspectives
Authors: Hartmann Christine W. , Gillespie Christopher , Sayre George G. , Snow A. Lynn 
Published: August 2021

Abstract
Background
Improving nursing home quality of care relies partly on reducing or stopping ineffective or harmful practices, a process known as de-implementation. We know little about de-implementation in this setting. Relatively recent policy changes reclassified resident position-change (bed and chair) alarms, which monitor resident movement, as restraints. This created an optimal environment in which to study impressions of an alarm de-implementation and sustainment intervention.

Methods
This cross-sectional interview study focused on understanding participants’ experience of a quality improvement program in the Department of Veterans Affairs Community Living Centers (nursing homes). The program’s goal was to improve resident outcomes and staff communication and teamwork through, among other foci, eliminating resident position-change alarms. The Community Living Centers were located in geographically dispersed areas of the continental United States. Interview participants were leadership and staff members from seven Community Living Centers. We conducted in-depth, semi-structured qualitative interviews using a convenience sample and used a thematic analytic approach.

Results
We conducted seventeen interviews. We identified five main themes: Initiating De-implementation (compelling participants with evidence, engaging local leadership, and site-level education and training), Changing Expectations (educating staff and family members), Using Contrasting Approaches (gradual or abrupt elimination of alarms), Witnessing Positive Effects of De-implementation (reduction in resident falls, improved resident sleep, reduction in distressing behaviors, and increased resident engagement), and Staying the Course (sustainment of the initiative).

Conclusions
Findings highlight how participants overcame barriers and successfully eliminated resident position-change alarms and sustained the de-implementation through using convincing evidence for the initiative, local leadership involvement and support, and staff and family member education and engagement. These findings and the resulting three-phase process to support nursing homes' de-implementation efforts expand the de-implementation science knowledge base and provide a promising framework for other nursing home-based de-implementation initiatives.
Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer
Authors: Rose Tracy L. , Harrison Michael R. , Deal Allison M. , Ramalingam Sundhar , Whang Young E. , Brower Blaine , Dunn Mary , Osterman Chelsea K. , Heiling Hillary M. , Bjurlin Marc A. , Smith Angela B. , Nielsen Matthew E. , Tan Hung-Jui , Wallen Eric , Woods Michael E. , George Daniel , Zhang Tian , Drier Anthony , Kim William Y. , Milowsky Matthew I. 
Published: August 2021

PURPOSE To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer. METHODS Patients with clinical T2-4aN0/XM0 muscle-invasive bladder cancer eligible for RC were enrolled. The initial six patients received lead-in pembrolizumab 200 mg once 2 weeks prior to pembrolizumab 200 mg once on day 1, cisplatin 70 mg/m2 once on day 1, and gemcitabine 1,000 mg/m2 once on days 1 and 8 every 21 days for four cycles. This schedule was discontinued for toxicity and subsequent patients received cisplatin 35 mg/m2 once on days 1 and 8 without lead-in pembrolizumab. The primary end point was pathologic downstaging (< pT2N0) with null and alternative hypothesis rates of 35% and 55%, respectively. Secondary end points were toxicity including patient-reported outcomes, complete pathologic response (pT0N0), event-free survival, and overall survival. Association of pathologic downstaging with programmed cell death ligand 1 staining was explored. RESULTS Thirty-nine patients were enrolled between June 2016 and March 2020 (72% cT2, 23% cT3, and 5% cT4a). Patients received a median of four cycles of therapy. All patients underwent RC except one who declined. Twenty-two of 39 patients (56% [95% CI, 40 to 72]) achieved < pT2N0 and 14 of 39 (36% [95% CI, 21 to 53]) achieved pT0N0. Most common adverse events (AEs) of any grade were thrombocytopenia (74%), anemia (69%), neutropenia (67%), and hypomagnesemia (67%). One patient had new-onset type 1 diabetes mellitus with ketoacidosis related to pembrolizumab and no patients required steroids for immune-related AEs. Clinicians consistently under-reported AEs when compared with patients. CONCLUSION Neoadjuvant gemcitabine and cisplatin plus pembrolizumab met its primary end point for improved pathologic downstaging and was generally safe. A global study of perioperative chemotherapy plus pembrolizumab or placebo is ongoing.
Maintained barostatic regulation of heart rate in digesting snakes (Boa constrictor)
Authors: Wang Tobias , Abe Augusto S. , Cruz-Neto Ariovaldo P. , Andrade Denis V. , Taylor Edwin W. 
Published: August 2021

ABSTRACT
When snakes digest large meals, heart rate is accelerated by withdrawal of vagal tone and an increased non-adrenergic-non-cholinergic tone that seems to stem from circulating blood-borne factors exerting positive chronotropic effects. To investigate whether this tonic elevation of heart rate impairs the ability for autonomic regulation of heart during digestion, we characterised heart rate responses to pharmacological manipulation of blood pressure in the snake Boa constrictor through serial injections of sodium nitroprusside and phenylephrine. Both fasting and digesting snakes responded with a robust tachycardia to hypotension induced by sodium nitroprusside, with digesting snakes attaining higher maximal heart rates than fasting snakes. Both fasting and digesting snakes exhibited small reductions of the cardiac chronotropic response to hypertension, induced by injection of phenylephrine. All heart rate changes were abolished by autonomic blockade with the combination of atropine and propranolol. The digesting snakes retained the capacity for compensatory heart rate responses to hypotension, despite their higher resting values, and the upward shift of the barostatic response curve enables snakes to maintain the cardiac limb of barostatic regulation for blood pressure regulation.