bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiplex Tissue Imaging Harmonization: A Multicenter Experience from CIMAC-CIDC Immuno-Oncology Biomarkers Network
Authors: Akturk Guray , Parra Edwin R. , Gjini Evisa , Lako Ana , Lee J. Jack , Neuberg Donna , Zhang Jiexin , Yao Shen , Laface Ilaria , Rogic Anita , Chen Pei-Hsuan , Sanchez-Espiridion Beatriz , Valle Diane M. Del , Moravec Radim , Kinders Robert , Hudgens Courtney , Wu Catherine , Wistuba Ignacio I. , Thurin Magdalena , Hewitt Stephen M. , Rodig Scott , Gnjatic Sacha , Tetzlaff Michael T. 
Published: July 2021

Abstract

Purpose:
The Cancer Immune Monitoring and Analysis Centers – Cancer Immunologic Data Commons (CIMAC-CIDC) network supported by the NCI Cancer Moonshot initiative was established to provide correlative analyses for clinical trials in cancer immunotherapy, using state-of-the-art technology. Fundamental to this initiative is implementation of multiplex IHC assays to define the composition and distribution of immune infiltrates within tumors in the context of their potential role as biomarkers. A critical unanswered question involves the relative fidelity of such assays to reliably quantify tumor-associated immune cells across different platforms.

Experimental Design:
Three CIMAC sites compared across their laboratories: (i) image analysis algorithms, (ii) image acquisition platforms, (iii) multiplex staining protocols. Two distinct high-dimensional approaches were employed: multiplexed IHC consecutive staining on single slide (MICSSS) and multiplexed immunofluorescence (mIF). To eliminate variables potentially impacting assay performance, we completed a multistep harmonization process, first comparing assay performance using independent protocols followed by the integration of laboratory-specific protocols and finally, validating this harmonized approach in an independent set of tissues.

Results:
Data generated at the final validation step showed an intersite Spearman correlation coefficient (r) of ≥0.85 for each marker within and across tissue types, with an overall low average coefficient of variation ≤0.1.

Conclusions:
Our results support interchangeability of protocols and platforms to deliver robust, and comparable data using similar tissue specimens and confirm that CIMAC-CIDC analyses may therefore be used with confidence for statistical associations with clinical outcomes largely independent of site, antibody selection, protocol, and platform across different sites.
Anti-CD19 CAR T Cells That Secrete a Biparatopic Anti-CLEC12A Bridging Protein Have Potent Activity Against Highly Aggressive Acute Myeloid Leukemia In Vitro and In Vivo
Authors: Rennert Paul D. , Dufort Fay J. , Su Lihe , Sanford Tom , Birt Alyssa , Wu Lan , Lobb Roy R. , Ambrose Christine 
Published: July 2021

Abstract
Refractory acute myeloid leukemia (AML) remains an incurable malignancy despite the clinical use of novel targeted therapies, new antibody-based therapies, and cellular therapeutics. Here, we describe the preclinical development of a novel cell therapy that targets the antigen CLEC12A with a biparatopic bridging protein. Bridging proteins are designed as “CAR-T cell engagers,” with a CAR-targeted protein fused to antigen binding domains derived from antibodies. Here, we created a CD19-anti-CLEC12A bridging protein that binds to CAR19 T cells and to the antigen CLEC12A. Biparatopic targeting increases the potency of bridging protein-mediated cytotoxicity by CAR19 T cells. Using CAR19 T cells that secrete the bridging protein we demonstrate potent activity against aggressive leukemic cell lines in vivo. This CAR-engager platform is facile and modular, as illustrated by activity of a dual-antigen bridging protein targeting CLEC12A and CD33, designed to counter tumor heterogeneity and antigen escape, and created without the need for extensive CAR T-cell genetic engineering. CAR19 T cells provide an optimal cell therapy platform with well-understood inherent persistence and fitness characteristics.
An Analysis of the Rug-Washing Ceremony in Mashhad-e Ardehāl, Kāshān
Authors: Sadat Bidgoli Sayyed Mahmood , Melvin-Koushki Matthew 
Published: July 2021

Abstract
The Iranian religious ceremony of rug-washing (qāli-shuyān), commemorating the martyrdom of Emāmzāda Soltān-ʿAli b. Mohammad Bāqer (d. 734/116), is held every year in the second week of autumn in Mashhad-e Ardehāl, a village of Kāshān, Esfahān Province. This ceremony is unique amongst Twelver Shiʿis for its observance in accordance with the solar calendar rather than the lunar. The objective of the present article is to analyze this ceremony and explain its features. The necessary data for this research have been collected from fieldwork on the historical geography of the region and related historical documents. In the analysis of this ceremony, attention is paid to its time, place, and mode of performance. This study suggests that the rug-washing ceremony is at least partly descended from an ancient Mithraic ritual, to which some Zoroastrian features were added in the pre-Islamic period, such as the limiting of its performance to priests; during the Islamic era, ritual Shiʿi elements were further added thereto. As currently performed, this ceremony, exclusive to Ardehāl and dating to the Qajar and possibly Safavid periods, thus bears certain similarities to rituals performed at Karbalāʾ.
The relationship between guilt feelings, conflicts with staff and satisfaction with care in relatives of nursing home residents with dementia: A longitudinal analysis
Authors: Gallego-Alberto Laura , Smaling Hanneke JA , Francke Anneke L , van de Brug Tim , van der Steen Jenny T , Joling Karlijn J 
Published: July 2021

Introduction Family caregivers often experience guilt after nursing home placement. The aim of the present study was to describe family caregivers’ guilt over time and assess the impact of conflicts with staff and satisfaction with care on guilt. Method Data of 222 family caregivers at three assessments during one-year follow-up were used. In addition to caregivers’ guilt and the variables conflicts with staff and satisfaction with the care, potential confounders were measured: sociodemographic data, clinical characteristics of the person with dementia, and caregiver burden. Linear mixed model analyses were performed to examine the longitudinal relationships between variables. Results Guilt remained stable over time. Unadjusted models showed that conflicts with staff were positively associated with guilt ( β = 0.11; p < 0.001; 95% CI: 0.06 to 0.16) and satisfaction with care showed a negative association with guilt ( β = −0.10; p< 0.05; 95% CI: −0.18 to −0.01). After adjusting for the confounders, only the positive association of guilt with conflicts with staff was similar as in the unadjusted analysis ( β = 0.11; p < 0.001; 95% CI: 0.05 to 0.16), whereas satisfaction with care was not significantly associated with guilt in the adjusted analyses ( β = −0.07; p = 0.10; 95% CI: −0.16 to 0.01). Discussion More conflicts with staff are associated with stronger guilt feelings. Guilt feelings are experienced by caregivers even after the admission of the person with dementia, and they remain stable over time. Further studies should focus on how to address guilt in family caregivers of people with dementia living in nursing homes.
Validity and Reliability of a New Radiological Method to Estimate Medial Column Internal Rotation in Hallux Valgus Using Foot Weight-Bearing X-Ray
Authors: Wagner Pablo , Lescure Nicole , Siddiqui Noman , Fink Jessica , Wagner Emilio 
Published: July 2021

Background Medial column internal rotation in hallux valgus (HV) can be measured using weight-bearing computed tomography (WBCT). Anteroposterior weight-bearing foot radiographs’ (WBXR) ability to estimate medial column internal rotation in HV was evaluated comparing these measurements with those obtained from WBCT. Methods Three observers evaluated WBCT and WBXR of 33 HV feet twice. Medial column internal rotation was measured with WBCT and classified into 3 levels according to WBXR findings. Intra- and interobserver reliability were obtained for WBXR and WBCT, in addition to WBXR-WBCT correlation. Results WBXR and WBCT intraobserver agreement was substantial and near perfect, respectively (κ 0.79 and 0.84). Their interobserver agreement was excellent (intraclass correlation 0.85 and 0.9, respectively). The WBXR-WBCT correlation was substantial (κ 0.68). WBXR diagnostic accuracy to predict the WBCT results was 85%. Conclusions The proposed method for medial column internal rotation measurement using WBXR is reliable and has a substantial agreement with WBCT measurements. Levels of Evidence Level III
Preoperative PROMIS Physical Function Scores Predict Postoperative Outcomes Following Total Ankle Replacement
Authors: Conti Matthew S. , Caolo Kristin C. , Cororaton Agnes D. , Deland Jonathan T. , Demetracopoulos Constantine A. , Ellis Scott J. 
Published: July 2021

Background: Despite good evidence that supports significant improvements in pain and physical function following a total ankle replacement (TAR) for end-stage ankle arthritis, there is a subset of patients who do not significantly benefit from surgery. The purpose of this study was to perform a preliminary analysis to determine if preoperative Patient-Reported Outcome Measurement Information System (PROMIS) scores could be used to predict which patients were at risk of not meaningfully improving following a TAR. Methods: Prospectively collected preoperative and ≥2-year postoperative PROMIS physical function, pain interference, pain intensity, and depression scores for 111 feet in 105 patients were included in the study. Significant postoperative improvement was defined using minimal clinically important differences (MCIDs). Logistic regression models and area under the curve (AUC) analyses were used to determine whether preoperative PROMIS scores were predictive of postoperative outcomes. Results: Receiver operating characteristic curves found statistically significant AUCs for the PROMIS physical function (AUC = 0.728, P = .004), pain intensity (AUC = 0.720, P = .018), and depression (AUC = 0.761, P < .001) domains. The preoperative PROMIS pain interference domain did not achieve a statistically significant AUC. Conclusion: Preoperative PROMIS physical function and pain intensity t scores may be used to predict postoperative improvement in patients following a fixed-bearing TAR; however, preoperative PROMIS pain interference scores were not good predictors. The results of this study may be used to guide research regarding patient-reported outcomes following TAR. Level of Evidence: Level III, retrospective comparative series.
Functional capacity and dual-task cost in the institutionalized older adults, both affected and unaffected by mild cognitive impairment
Authors: Zak Marek , Krupnik Szymon , Brola Waldemar , Rebak Dorota , Sikorski Tomasz , Dutheil Frederic , Andrychowski Jaroslaw , Courteix Daniel 
Published: July 2021

Abstract
Background
Mild cognitive impairment (MCI) affects 10–20% of the individuals over the age of 65; this proportion being higher in the institutional care facilities than within a general population.

Aim
To assess whether dual-task cost in the individuals affected by MCI depends exclusively on gait, or possibly some other functional capacity components might also come into play, as compared to the healthy controls also remaining in the institutional care.

Methods
The study was conducted in five nursing facilities, involving 88 subjects in total, i.e. 44 subjects affected by MCI (mean age of 83.8 years; 34 women (77.3%) and 10 men (22.7%), and 44 healthy controls (mean age 81.67 years; 38 women (84.4%) and 7 men (15.6%). Cognitive functions were assessed through Mini–Mental State Examination (MMSE), while gait by Timed Up and Go Test (TUGT). Gait speed was calculated by the 10 Meter Walk Test, and the fear of falling with the Falls Efficacy Scale International. Dual tasks were assessed by TUGTMAN (Timed Up and Go Test Manual) and TUGCOG (Timed Up and Go Test Cognitive). Dual Task Cost (DTC) of TUGTMAN and TUGTCOG was established. Statistical analyses were completed with STATISTICA Package v. 10.

Results
Individuals affected by MCI differed significantly from the unaffected ones with regard to their gait test results, when assigned a single-task activity, and dual-task activities, as well as in the gait speed. Dual Task Cost Manual (DTCMAN) in the MCI group was significantly higher, as compared to the subjects unaffected by MCI.
Around 25% of the variance of DTCMAN result regarding the MCI group was accounted for by gait performance in the single-task conditions (TUGT). In the case of Dual Task Cost Cognitive (DTCCOG), this value equalled to approx. 10%. A 1% change in DTCMAN corresponded to approx. 0.5 s change in TUGT, whereas a 1% change in DTCCOG entailed approx. 0.35 s change in TUGT walking time.

Conclusion
Individual functional capacity affected the dual-task performance, especially the motor-motor tasks. Dual-task cost in the subjects affected by MCI was significantly reduced, being more dependent on the gait speed in the motor-motor tasks, which entailed visual memory, than in the motor-cognitive tasks.
Downregulation of NKG2DLs by TGF-β in human lung cancer cells
Authors: Lee Young Shin , Choi Hojung , Cho Hae-Ryung , Son Woo-Chang , Park You-Soo , Kang Chi-Dug , Bae Jaeho 
Published: July 2021

AbstractBackgroundTransforming growth factor beta (TGF-β) is a typical immuno-inhibitory cytokine and highly secreted by lung cancer cells. It was supposed that its immunosuppressive effects to NK cell might be related with the altered expression of activating and inhibitory molecules in lung cancer cells. In this study, we examined the expression of NKG2DLs, PD-L1 and PD-L2 in lung cancer cells after treatment of TGF-β and a TGF-β inhibitor, Galunisertib (LY2157299).ResultsTGF-β reduced the level of surface proteins of five NKG2DLs without altered transcription levels in lung cancer cells. Galunisertib reversed the effect of TGF-β on the expression of NKG2DLs. Since MMP inhibitors, MMPi III and MMP2 inhibitor I, restored the reduced expression of NKG2DLs after treatment of TGF-β, it was thought that TGF-β induced the expression of MMP2 which facilitated the shedding of the NKG2DLs in cancer cells. However, the expression of PD-L1, L2 were not changed by treatment with TGF-β or Galunisertib.ConclusionsTherefore, inhibition of TGF-β might reverse the immunosuppressive status on immune cells and restore NK cell mediated anticancer immune responses by upregulation of NKG2DLs in cancer cells.
Discrete terminal ileal ulcers in patients diagnosed with ulcerative colitis: clinical significance and natural course
Authors: Lim Hyo-Jin , Do Kim Hyun , Soh Jae Seung , Kim Sung-Yeun , Jung Ye-Ji , Lim Hyun , Kang Ho Suk , Kim Jong Hyeok 
Published: July 2021

Abstract
Background
Terminal ileal (TI) ulcers are occasionally detected in asymptomatic individuals and mostly resolve without any treatment. In patients with ulcerative colitis (UC), TI ulcers are infrequently observed without evidence of backwash ileitis. However, the clinical significance and natural course of the lesions are unclear. The aim of our study was to evaluate the frequency and clinical implications of TI ulcers in patients with UC.

Methods
We retrospectively reviewed 397 patients with UC via successful TI intubation during colonoscopy. We compared the clinical characteristics of patients manifesting TI ulcers with those who did not. The natural course of TI lesions was also investigated during the follow-up periods.

Results
Forty-one patients (10.3%) showed TI ulcers without evidence of inflammation in the right colon. The patients with and without TI ulcers were not different in terms of baseline characteristics, disease activity and extent at the time of the UC diagnosis, proximal extension, Mayo endoscopic score at the last endoscopic examination, medication history, UC-related hospitalization, and relapse during follow-up periods. Of the 30 patients who underwent follow-up colonoscopy in patients with TI ulcers, 23 (76.7%) showed resolution of TI ulcer. In addition, patients with remaining TI ulcers did not differ in disease activity and biopsy results compared with those with resolving TI ulcers.

Conclusions
Discrete TI ulcers are more common in patients with UC, compared with the healthy cohort. No significant clinical impact on disease extension and severity is found.
Cultural malpractices during labor/delivery and associated factors among women who had at least one history of delivery in selected Zones of Amhara region, North West Ethiopia: community based cross-sectional study
Authors: Melesse Misganaw Fikrie , Bitewa Yibelu Bazezew , Dessie Kumneger Nigussie , Wondim Demeke Binalf , Bereka Tefera Marie 
Published: July 2021

Abstract
Background
Every day, at least 810 women die worldwide from the complications of pregnancy and childbirth, 86% of which occurring in Southern Asia and Sub-Saharan Africa. One of the contributing factors for these problems is cultural malpractices during pregnancy and childbirth. The actual incidence of cultural malpractices in developing countries accounts for about 5–15% of maternal deaths. Thus, understanding the link between cultural affairs and maternal health is critical to saving the lives of women and their babies. Therefore, this research was aimed to assess cultural malpractices during labor and delivery and associated factors among women who had at least one history of delivery in selected Zones of the Amhara region, North West Ethiopia.

Method
Community based cross-sectional study was conducted on women who had at least one delivery history in Awi, West, and East Gojjam Zones from January 1 to May 30, 2020. The multistage cluster sampling technique was used to select 845 study participants. Data was collected through a pre-tested and structured interview questionnaire, entered and cleaned using EPI info version 7.2, and exported to SPSS version 23 for analysis. Bivariable and multivariable logistic regression was employed to assess the association of the variables and a P-value less than 0.05 was declared as statistically significant.

Result
Out of 845 women 162(19.2%) practiced nutritional taboo, 77(9.1%) women practiced abdominal massage and 273(32.3%) delivered their babies at home. Educational status of the respondents being un able to read and write (AOR = 14.35,95% CI: 3.12,65.96), husband's educational status (AOR = 3.80,95% CI: 1.24,11.64), residence (AOR = 2.93,95% CI: 1.41: 6.06), ethnicity (AOR = 2.20,95% CI:1.32, 3.67), pregnancy complications (AOR = 1.61,95% CI:1.02, 2.53), gravidity (AOR = 3.54,95% CI:1.38,9.08) and antenatal care follow up (AOR = 2.24, 95% CI:1.18,4.25) had statistically significant association with cultural malpractices during labor and delivery.

Conclusion
This study showed that cultural malpractices during childbirth were high in Awi, West, and East Gojjam Zones relative to the country's maternal health service utilization plan. Working on antenatal care follow-up and women and husband education in a culturally acceptable manner may reduce cultural malpractices during labor and delivery.
Corona virus disease 2019-associated Stevens-Johnson syndrome: a case report
Authors: Shahraki Toktam , Hassanpour Kiana , Arabi Amir , Ansari Iman , Sadoughi Mohammad-Mehdi 
Published: July 2021

Abstract
Background
To report Stevens-Johnson syndrome (SJS) in a patient with acute pneumonia secondary to SARS-CoV-2 infection.

Case presentation
A 45-years-old woman with a diagnosis of acute pneumonia secondary to SARS-CoV-2 infection who had received azithromycin and naproxen. Three days after starting the medication, she appeared ill and developed ocular discomfort, photophobia, dysuria, and macular rashes on the trunk and the extremities. On ophthalmological examination, a total epithelial defect was seen in both eyes. According to the examination, Stevens-Johnson syndrome was diagnosed and the patient was admitted to receive systemic and ocular support and medical care. The patient’s condition improved during the 3 weeks and recovered from both COVID-19 and SJS life-threatening complications but ocular complications, including the destruction of the meibomian glands, irregularity of the eyelid margin, and corneal scarring remained for the patient.

Conclusions
Although, it is not clear whether the cause of Stevens-Johnson syndrome in COVID-19 patients is the virus itself or whether the use of medication, but patients with COVID-19, especially patients receiving medication, should be screened for symptoms of Stevens-Johnson syndrome.
A qualitative study to investigate Swiss hospital personnel’s perceived importance of and experiences with patient’s mental–somatic multimorbidities
Authors: Aebi Nicola Julia , Caviezel Seraina , Schaefert Rainer , Meinlschmidt Gunther , Schwenkglenks Matthias , Fink Günther , Riedo Lara , Leyhe Thomas , Wyss Kaspar ,   SomPsyNet Consortium
Published: July 2021

Abstract
Background
Mental–somatic multimorbidity in general hospital settings is associated with long hospital stays, frequent rehospitalization, and a deterioration of disease course, thus, highlighting the need for treating hospital patients more holistically. However, there are several challenges to overcome to address mental health conditions in these settings. This study investigated hospital personnel’s perceived importance of and experiences with mental–somatic multimorbidities of patients in hospital settings in Basel, Switzerland, with special consideration of the differences between physicians and nurses.

Methods
Eighteen semi-structured interviews were conducted with nurses (n = 10) and physicians (n = 8) in different hospitals located in Basel, Switzerland. An inductive approach of the framework analysis was used to develop the themes.

Results
Four themes emerged from the data analysis: 1) the relevance of mental–somatic multimorbidity within general hospitals, 2) health professionals managing their emotions towards mental health, 3) knowledge and competencies in treating patients with mental–somatic multimorbidity, and 4) interprofessional collaboration for handling mental–somatic multimorbidity in hospital settings.The mental–somatic multimorbidities in general hospital patients was found to be relevant among all hospital professionals, although the priority of mental health was higher for nurses than for physicians. This might have resulted from different working environments or in efficient interprofessional collaboration in general hospitals. Physicians and nurses both highlighted the difficulties of dealing with stigma, a lack of knowledge of mental disorders, the emphasis place on treating somatic disorders, and competing priorities and work availability, which all hindered the adequate handling of mental–somatic multimorbidity in general hospitals.

Conclusion
To support health professionals to integrate mental health into their work, proper environments within general hospitals are needed, such as private rooms in which to communicate with patients. In addition, changes in curriculums and continuing training are needed to improve the understanding of mental–somatic multimorbidities and reduce negative stereotypes. Similarly, interprofessional collaboration between health professionals needs to be strengthened to adequately identify and treat mentally multimorbid patients. A stronger focus should be placed on physicians to improve their competencies in considering patient mental health in their daily somatic treatment care.