bluuebunny/crossref_metadata_2025_split huggingface dataset:
Irinotecan dose reduction in metastatic colorectal cancer patients with homozygous UGT1A1*28 polymorphism: a single-center case series
Authors: Tsai Hsiang-Lin , Chen Po-Jung , Chen Yen-Cheng , Li Ching-Chun , Chang Tsung-Kun , Su Wei-Chih , Yin Tzu-Chieh , Huang Ching-Wen , Wang Jaw-Yuan 
Published: July 2022

Objective The UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity, which may increase the risk of severe toxicity in patients who receive standard-dose irinotecan, such as severe neutropenia and diarrhea. This real-world study assessed the optimal irinotecan dose in terms of efficacy and toxicity in metastatic colorectal cancer (mCRC) patients homozygous for the UGT1A1*28 polymorphism and receiving FOLFIRI plus bevacizumab or cetuximab as first-line therapy. Methods We analyzed toxicity and treatment outcomes in seven mCRC patients who were homozygous for UGT1A1*28 and received FOLFIRI plus bevacizumab or cetuximab, with an initial irinotecan dose of 120 mg/m2. Results Six of the seven patients tolerated 120 mg/m2 irinotecan without requiring dose reductions in subsequent cycles. The overall response and disease control rates were 43.0% (3/7) and 71.4% (5/7), respectively. The median progression-free survival and overall survival were 11.0 and 33.0 months, respectively. Only one severe adverse event, grade III neutropenia (2.5%), was observed. Conclusions mCRC patients homozygous for the UGT1A1*28 allele can tolerate irinotecan at an initial dose of 120 mg/m2 with favorable oncological outcomes and toxicity profiles. Further prospective studies are warranted to optimize irinotecan-based chemotherapy in these patients.
Experimental assessment of proposed seismic strengthening scheme for adobe structures
Authors: Rafi Muhammad Masood , Khan Muhammad Saad , Rais Adnan , Ahmed Shoaib 
Published: July 2022

A new scheme of seismic strengthening of adobe structures has been proposed in this paper. The scheme involves horizontal and vertical bands of steel wire mesh plastered with cement-sand mortar. The effectiveness of the proposed scheme is assessed by dynamically testing a half-scale model of the adobe structure on a shaking table. The acceleration time history record of the 1995 Kobe earthquake was used to simulate the ground motion for the strengthened model which was increased sequentially in increments of 25% of peak ground acceleration (PGA). Initial (hairline) cracks were observed in the in-plane wall of the model at a PGA of 0.439 g. Although the out-of-plane walls also sustained damages, the in-plane walls were the most damaged parts of the structure. The proposed strengthening method reduced the torsional irregularity of the structure. It also increased strength, ductility and energy dissipation capacities of the walls. The data of observed structural damages and building drift were used to propose four performance levels for the strengthened adobe structures corresponding to the applied PGAs of ground motion.
An Exploratory Study Testing Environmental Wayfinding Aids as an Intervention for Children With Autism
Authors: Irish Julie E. N. 
Published: July 2022

Purpose: This exploratory mixed methods experiment aimed to determine whether the application of wayfinding aids (colored doors, shapes on the floor, and signage) as an intervention could help children with autism spectrum disorder (ASD) find their way to a destination to promote independence. Background: Several individuals with ASD have described the difficulties they experienced finding their way in the environment. This is especially relevant to complex environments like healthcare. Methods: Participants with ASD aged 8–11 ( n = 9) were randomly assigned to control or treatment groups. The test location was an empty school corridor unfamiliar to participants. Each participant was shown the way to a destination using a script pointing out existing cues (control group) or applied wayfinding aids (treatment group). Participants were taken back to the start and then asked to lead the way to the destination. Afterward, they were interviewed about their experience. Data collection included observation, behavioral mapping, and video recording. Results: The variable of wayfinding scripts helped all participants find their way to the destination, but those in the treatment group found their way directly compared to 75% of the control group. Wayfinding aids made the environment more memorable to those in the treatment group. Some children were distracted by environmental stimuli, and some noticed surprising elements that helped them wayfind. Conclusions: Study results suggest that wayfinding instruction could be used as an intervention in environments with and without the application of wayfinding aids. This needs further testing in other environments. Issues included recruitment and random assignment.
Invariant NKT cells dictate antitumor immunity elicited by a bispecific antibody cotargeting CD3 and BCMA
Authors: Casey Mika , Tu Cui , Harrison Simon J. , Nakamura Kyohei 
Published: July 2022

Abstract
CD3-engaging bispecific antibodies (BsAbs) have emerged as powerful therapeutic approaches by their ability to redirect T cells to eliminate tumor cells in a major histocompatibility complex–independent manner. However, how we can potentiate the efficacy of BsAbs remains largely unknown. To address this question, we investigated immunological mechanisms of action of a BsAb cotargeting CD3 and B-cell maturation antigen (BCMA) in syngeneic preclinical myeloma models. Treatment with the CD3/BCMA BsAb stimulated multiple CD3-expressing T-cell subsets and natural killer (NK) cells in the myeloma bone marrow (BM), highlighting its broad immunostimulatory effect. Notably, the BsAb-mediated immunostimulatory and antitumor effects were abrogated in mice lacking invariant NKT (iNKT) cells. Mechanistically, activation of iNKT cells and interleukin-12 production from dendritic cells (DCs) were crucial upstream events for triggering effective antitumor immunity by the BsAb. Myeloma progression was associated with a reduced number of BM iNKT cells. Importantly, the therapeutic efficacy of a single dose of CD3/BCMA BsAb was remarkably augmented by restoring iNKT cell activity, using adoptive transfer of α-galactosylceramide-loaded DCs. Together, these results reveal iNKT cells as critical players in the antitumor activity of CD3 engaging BsAbs and have important translational implications.
Quantitative proteomics analysis to assess protein expression levels in the ovaries of pubescent goats
Authors: Qin Ping , Ye Jing , Gong Xinbao , Yan Xu , Lin Maosen , Lin Tao , Liu Tong , Li Hailing , Wang Xiujuan , Zhu Yanyun , Li Xiaoqian , Liu Ya , Li Yunsheng , Ling Yinghui , Zhang Xiaorong , Fang Fugui 
Published: July 2022

Abstract
Background
Changes in the abundance of ovarian proteins play a key role in the regulation of reproduction. However, to date, no studies have investigated such changes in pubescent goats. Herein we applied isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography–tandem mass spectrometry to analyze the expression levels of ovarian proteins in pre-pubertal (n = 3) and pubertal (n = 3) goats.

Results
Overall, 7,550 proteins were recognized; 301 (176 up- and 125 downregulated) were identified as differentially abundant proteins (DAPs). Five DAPs were randomly selected for expression level validation by Western blotting; the results of Western blotting and iTRAQ analysis were consistent. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that DAPs were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways. Besides, gene ontology functional enrichment analysis revealed that several DAPs enriched in biological processes were associated with cellular process, biological regulation, metabolic process, and response to stimulus. Protein–protein interaction network showed that proteins interacting with CDK1, HSPA1A, and UCK2 were the most abundant.

Conclusions
We identified 301 DAPs, which were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways, suggesting the involvement of these processes in the onset of puberty. Further studies are warranted to more comprehensively explore the function of the identified DAPs and aforementioned signaling pathways to gain novel, deeper insights into the mechanisms underlying the onset of puberty.
Risk factors and mortality for elderly patients with bloodstream infection of carbapenem resistance Klebsiella pneumoniae: a 10-year longitudinal study
Authors: Chen Yili , Chen Yao , Liu Pingjuan , Guo Penghao , Wu Zhongwen , Peng Yaqin , Deng Jiankai , Kong Yannan , Cui Yingpeng , Liao Kang , Huang Bin 
Published: July 2022

Abstract
Background
Bloodstream infection (BSI) caused by carbapenem resistant Klebsiella pneumoniae (CRKP), especially in elderly patients, results in higher morbidity and mortality. The purpose of this study was to assess risk factors associated with CRKP BSI and short-term mortality among elderly patients in China.

Methods
In this retrospective cohort study, we enrolled 252 inpatients aged ≥ 65 years with BSI caused by KP from January 2011 to December 2020 in China. Data regarding demographic, microbiological characteristics, and clinical outcome were collected.

Result
Among the 252 BSI patients, there were 29 patients (11.5%) caused by CRKP and 223 patients (88.5%) by carbapenem-susceptible KP (CSKP). The overall 28-day mortality rate of elderly patients with a KP BSI episode was 10.7% (27/252), of which CRKP BSI patients (14 / 29, 48.3%) were significantly higher than CSKP patients (13 / 223, 5.83%) (P < 0.001). Hypertension (OR: 13.789, [95% CI: 3.883–48.969], P < 0.001), exposure to carbapenems (OR: 8.073, [95% CI: 2.066–31.537], P = 0.003), and ICU stay (OR: 11.180, [95% CI: 2.663–46.933], P = 0.001) were found to be associated with the development of CRKP BSI in elderly patients. A multivariate analysis showed that isolation of CRKP (OR 2.881, 95% CI 1.228–6.756, P = 0.015) and KP isolated in ICU (OR 11.731, 95% CI 4.226–32.563, P < 0.001) were independent risk factors for 28-day mortality of KP BSI.

Conclusion
In elderly patients, hypertension, exposure to carbapenems and ICU stay were associated with the development of CRKP BSI. Active screening of CRKP for the high-risk populations, especially elderly patients, is significant for early detection and successful management of CRKP infection.
Thyroid cancer incidence trend and association with obesity, physical activity in the United States
Authors: Chen Biaoyou , Xie Zhaomin , Duan Xuwei 
Published: July 2022

Abstract
Background
State-level racial/ethnic and age differences and the temporal trend of thyroid cancer (TC) incidence in the USA remain unknown. Our research purposes include: Characterizing state-level temporal variation in TC incidence; examining the disparities of TC incidence by state-level race/ethnicity and age; performing an ecological correlation between TC incidence and obesity/physical activity.

Methods
TC incidence data during 2000–2017 were extracted from the United States cancer statistics. Using joinpoint regression to evaluate TC incidence trends. Annual percent change (APC), average APC (AAPC) and incidence rates were calculated. The obesity prevalence and physical activity level at the state-level were extracted from Behavioral Risk Factor Surveillance System, and the association between state-level AAPC of TC and obesity/physical activity was tested by Pearson correlation coefficient.

Results
We found that the TC incidence had shown an overall downward trend in recent years, but 10 states continued increasing. There were significant differences in state-level race/ethnicity (non-Hispanic Whites as a reference) and age group (45–59 age group as a reference) incidence: Incidence Rate Ratio (IRR) was 0.4–1.2 for non-Hispanic Blacks, 0.7–1.6 for non-Hispanic Asian and Pacific Islanders, 0.4–1.2 for non-Hispanic American Indians/Alaskan Natives, and 0.5–1.3 for Hispanics. High IRR in young people were distributed in northern USA, while in older people were distributed in south. The state-level obesity/physical activity level and AAPC had a weak correlation (r = 0.34, P = 0.016) and inverse weak correlation (r = -0.29, P = 0.037), respectively. The AAPC of states with a consistent increasing trend had an extremely strong correlation with obesity prevalence (r = 0.80, p = 0.006), and an inverse strong correlation with physical activity level (r = -0.65, P = 0.04).

Conclusions
Thyroid cancer incidence in 10 states continued increasing. State-level variation in race/ethnicity and age group incidence were found. Lifestyle and environmental factors may interfere with the incidence trend of TC in the USA.
Efficacy of corticosteroids for hand osteoarthritis - a systematic review and meta-analysis of randomized controlled trials
Authors: Estee Mahnuma Mahfuz , Cicuttini Flavia M. , Page Matthew J. , Butala Anant D. , Wluka Anita E. , Hussain Sultana Monira , Wang Yuanyuan 
Published: July 2022

Abstract
Background
There is some evidence that corticosteroids may have a beneficial effect in hand osteoarthritis. We examined the efficacy of corticosteroids on symptoms and structural outcomes in hand osteoarthritis.

Methods
Ovid MEDLINE, Embase and Cochrane Central Register of Controlled Trials were searched from inception to October 2021 for randomized controlled trials investigating the efficacy of corticosteroids in hand osteoarthritis. Two authors independently screened records, extracted data, and assessed risk of bias using the RoB 2 tool. Standardized mean difference (SMD) or mean difference (MD) was calculated, and random-effects meta-analyses were performed.

Results
Of 13 included trials, 3 examined oral corticosteroids and clinical outcomes in any hand joints, 9 examined intra-articular injection of corticosteroids and clinical outcomes at the first carpometacarpal joint and one in the interphalangeal joints. In meta-analysis, oral corticosteroids reduced pain (SMD -0.53, 95% CI -0.79 to -0.28) and improved stiffness (MD -5.03, 95% CI -9.91 to -0.15; Australian Canadian Osteoarthritis Hand Index stiffness subscale) and function (SMD -0.37, 95% CI -0.63 to -0.12) at 4-6 weeks. However, there was no significant persistent effect on pain and function at 3 months which was 6-8 weeks after study medication was stopped. There was no significant effect of intra-articular corticosteroids on pain or function at 4-6 weeks or over 3-12 months in first carpometacarpal osteoarthritis. Two trials evaluated joint structure at 4-6 weeks: one study showed oral corticosteroids reduced synovial thickening, neither showed an effect on synovitis.

Conclusions
There was low-certainty evidence for a medium effect of oral corticosteroids on pain relief and stiffness improvement and small-to-medium effect on functional improvement at 4-6 weeks, with no significant effect for intra-articular corticosteroids. Corticosteroids had no significant effect on any outcomes over longer term (3-12 months) off treatment. No trials examined the effect of corticosteroids on disease progression. The role of corticosteroids in hand osteoarthritis is limited.
A novel multimodal needs assessment to inform the longitudinal education program for an international interprofessional critical care team
Authors: Li Heyi , Sun Yuqiang , Barwise Amelia , Cui Wenjuan , Dong Yue , Tekin Aysun , Yuan Qingzhong , Qiao Lujun , Gajic Ognjen , Niven Alexander 
Published: July 2022

Abstract
Background
The current global pandemic has caused unprecedented strain on critical care resources, creating an urgency for global critical care education programs. Learning needs assessment is a core element of designing effective, targeted educational interventions. In theory, multimodal methods are preferred to assess both perceived and unperceived learning needs in diverse, interprofessional groups, but a robust design has rarely been reported. Little is known about the best approach to determine the learning needs of international critical care professionals.

Method
We conducted multimodal learning needs assessment in a pilot group of critical care professionals in China using combined quantitative and qualitative methods. The assessments consisted of three phases: 1) Twenty statements describing essential entrustable professional activities (EPAs) were generated by a panel of critical care education experts using a Delphi method. 2) Eleven Chinese critical care professionals participating in a planned education program were asked to rank-order the statements according to their perceived learning priority using Q methodology. By-person factor analysis was used to study the typology of the opinions, and post-ranking focus group interviews were employed to qualitatively explore participants’ reasoning of their rankings. 3) To identify additional unperceived learning needs, daily practice habits were audited using information from medical and nursing records for 3 months.

Results
Factor analysis of the rank-ordered statements revealed three learning need patterns with consensual and divergent opinions. All participants expressed significant interest in further education on organ support and disease management, moderate interest in quality improvement topics, and relatively low interest in communication skills. Interest in learning procedure/resuscitation skills varied. The chart audit revealed suboptimal adherence to several evidence-based practices and under-perceived practice gaps in patient-centered communication, daily assessment of antimicrobial therapy discontinuation, spontaneous breathing trial, and device discontinuation.

Conclusions
We described an effective mixed-methods assessment to determine the learning needs of an international, interprofessional critical care team. The Q survey and focus group interviews prioritized and categorized perceived learning needs. The chart audit identified additional practice gaps that were not identified by the learners. Multimodal methods can be employed in cross-cultural scenarios to customize and better target medical education curricula.
The roles of personal interview and cognitive abilities at admission to medical school in predicting performance of medical students in their internal medicine sub-internship
Authors: Liberty Idit F. , Novack Lena , Hershkovitz Reli , Katz Amos 
Published: July 2022

Abstract
Background
The medical school admission process is complicated, perhaps reflecting unresolved debates concerning the most important skills necessary to become an ideal physician. The Goldman Medical School at Ben-Gurion University in Israel is known for placing great emphasis on the personal attributes of candidates in addition to their academic excellence. To this end, 1-h consecutive interviews are embedded in the admission process. This study aims to determine whether there is an association between candidates’ personal interview ratings and the ratings assigned to these students at the conclusion of their 6th year internal medicine sub-internship.

Methods
Our study sample included 136 students who were admitted to the medical school in 2015, and who completed their 6th year internal medicine sub-internship in 2019–2020. Our data were derived from the admissions information for each candidate and from structured interviews concerning medical competence and personal traits, which were completed by medical personnel who were in contact with these students during their clinical rounds.

Results
Higher interview ratings of candidates during the admission process were associated with a higher probability that students would be evaluated as top-rated internists 6 years later (Odds Ratio (OR) = 9.4, p-value = 0.049), independent of gender (OR for male vs female = 0.2, p-value = 0.025) and age (OR = 1.3 per each year, p-value = 0.115). Although significant, the numeric difference in interview rating was relatively small (median 9.5 and 9.4 for top-rated and not top-rated internists, respectively).

Conclusions
Our study shows that high personal interview ratings assigned to candidates as part of the medical school admission process are predictive of high performance ratings of students after they complete their 6th year internal medicine sub-internships. These findings demonstrate the value and importance of using semi-structured personal interviews in the medical school admission process.
Staff and patient experience of the implementation and delivery of a virtual health care home monitoring service for COVID-19 in Melbourne, Australia
Authors: Jessup R. L. , Awad N. , Beauchamp A. , Bramston C. , Campbell D. , Semciw Al , Tully N. , Fabri A. M. , Hayes J. , Hull S. , Clarke A. C. 
Published: July 2022

AbstractBackgroundProvision of virtual health care (VHC) home monitoring for patients who are experiencing mild to moderate COVID-19 illness is emerging as a central strategy for reducing pressure on acute health systems. Understanding the enablers and challenges in implementation and delivery of these programs is important for future implementation and re-design. The aim of this study was to explore the perspectives of staff involved with the implementation and delivery, and the experience of patients managed by, a VHC monitoring service in Melbourne, Australia during the COVID-19 pandemic.MethodsA descriptive qualitative approach informed by naturalist inquiry was used. Staff interviews were analysed using the Consolidated Framework for Implementation Research (CFIR). Patient experience was captured using a survey and descriptive statistics were used to describe categorical responses while content analysis was used to analyse free text responses as they related to the CFIR. Finally, data from the interviews and patient experience were triangulated to see if patient experience validated data from staff interviews.ResultsAll 15 staff were interviewed, and 271 patients were surveyed (42%). A total of four final overarching themes emerged: service implementation enablers, service delivery benefits for patients, fragmentation of care, and workforce strengths. 19 subthemes aligned with 18 CFIR constructs from staff and patient data.ConclusionRapid implementation was enabled through shared resources, dividing implementation tasks between senior personnel, engaging furloughed healthcare staff in design and delivery, and having a flexible approach that allowed for ongoing improvements. Benefits for patients included early identification of COVID-19 deterioration, as well as provision of accurate and trustworthy information to isolate safely at home. The main challenges were the multiple agencies involved in patient monitoring, which may be addressed in the future by attributing responsibility for monitoring to a single agency.