bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of trastuzumab emtansine in older patients with HER2-positive advanced breast cancer: a real-world study
Authors: Cil Ibrahim , Kucukarda Ahmet , Atcı Muhammed Mustafa , Secmeler Saban , Paksoy Nail , Ferhatoglu Ferhat , Ak Naziye , Ayhan Murat , Tataroglu Ozyukseler Deniz , Onder Arif Hakan , Avci Okan , Oyman Abdilkerim , Okten Ilker Nihat , Gulturk Ilkay , Akagunduz Baran , Basoglu Tugba , Cakir Emre , Hacibekiroglu Ilhan , Ozcelik Melike , Aydiner Adnan 
Published: August 2021

Introduction: Ado-trastuzumab emtansine (T-DM1) is an antibody–drug conjugate and its survival advantage has been shown in advanced human epidermal growth factor receptor 2 (HER2)–positive breast cancer. However, clinical trials underrepresent patients ⩾65 years of age, leading to a lack of information in this population. We analyzed the real-world outcomes of older women who were treated with T-DM1 therapy. Methods: We performed a multicenter, observational, retrospective analysis of patients aged ⩾65 years treated with T-DM1. A total of 93 patients from 10 cancer centers were involved in the study. Our goal was to determine the survival, response rates, and toxicity profile in T-DM1–treated patients, as well as the factors that influence survival. Results: Median follow-up was 12.2 months. Objective response rate was 29%. Median progression-free survival (PFS) and overall survival (OS) were 8.47 and 15.0 months, respectively. In multivariate analysis, Eastern Cooperative Oncology Group Performance Score 2 was found to be an independent prognostic factor for worse PFS (hazard ratio [HR] 1.81, p = 0.032) and OS (HR 2.33, p = 0.006). Any adverse event (AE) was seen in 92.5% of patients; grade 3 or 4 AEs were seen in 30.1%. Dose reduction or treatment discontinuation rates were 11.8% and 6.5%, respectively. Conclusion: The efficacy of T-DM1 was acceptable and it was generally well-tolerated among older patients with advanced HER2-positive breast cancer.
He Tūhononga Whaiaro: A Kaupapa Māori Approach to Mate Wareware (Dementia) and Cognitive Assessment of Older Māori
Authors: Menzies Oliver , Dudley Margaret , Garrett Nick , Elder Hinemoa , Daniels Piripi , Wilson Denise 
Published: August 2021

Aim: The aim of this study is to investigate Māori (Indigenous peoples of Aotearoa New Zealand) understandings of dementia ( mate wareware) and develop a framework to inform assessment of cognitive impairment. Method: Qualitative, kaupapa Māori (M āori approach) research with 241 older Māori ( kaumātua) involving 17 focus groups across Aotearoa New Zealand (NZ) and eight families ( whānau) from one region. We thematically analyzed transcribed data from audio-recorded interviews. Results: Two overarching themes, namely, connection ( Tūhononga) and self ( Whaiaro), and eight subthemes in particular mind ( hinengaro), spirit ( wairua), body ( tinana), family ( whānau), social connection ( whanaungatanga), identity and role ( tuakiri), place ( wāhi), and ancestors ( tūpuna) emerged. Māori language ( Te Reo Māori) was important for cognitive health. Conclusion: The findings embedded in cultural values improve understanding of dementia ( mate wareware) in Māori. These themes can inform the assessment of older Māori with cognitive impairment. For those without cognitive impairment, the Tūhononga Whaiaro framework suggests factors potentially crucial for healthy aging in Māori.
The CYP3A5 and ABCB1 Gene Polymorphisms in Kidney Transplant Patients and Establishment of Initial Daily Tacrolimus Dosing Formula
Authors: He Yuting , Ma Yixiao , Fu Qian , Liang Jianbo , Yu Xuegao , Huang Hao , Zhong Liangying , Huang Bin 
Published: August 2021

Background Tacrolimus is an immunosuppressive drug used to prevent organ rejections. Many factors could influence blood concentration of tacrolimus. Objective To detect genotypes of cytochrome P450 3A5 ( CYP3A5) and ABCB1 in kidney transplant patients and establish initial daily tacrolimus dosing formula based on genotypes of CYP3A5 and ABCB1 and patients’ clinical parameters. Methods Sequence specific primer polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism were used to detect genotypes of CYP3A5 and ABCB1. The blood cell, procalcitonin, C-reactive protein, height, weight, age, gender and other clinical parameters were recorded. Multiple linear regression analysis and Pearson correlation analysis were used to conduct date analysis. Results 102 cases were enrolled in cohort 1, and there were 10 cases of CYP3A5 *1/*1 (9.8%), 28 cases of CYP3A5 *1/*3 (27.5%), and 64 cases of CYP3A5 *3/*3 (62.7%). The distributions of ABCB1 C3435T genotype were CC 36 (35.3%), CT 52 (51.0%), and TT 14 (13.7%). The distributions of ABCB1 G2677T/A genotype were GG 39 (38.2%), GT 40 (39.2%), and TT 23 (22.5%). The formula was 7.499 + (0.053 × Weight) − (0.029 × Hemoglobin concentration) − (1.045 × CYP3A5 genotype) ( CYP3A5 genotype: *1/*1 type inputs 0, *1/*3 type inputs 1, *3/*3 type inputs 2). The predicted doses from the established formula had a significant correlation ( r = 0.605) with actual clinical doses ( P < 0.05). Conclusion and Relevance Hemoglobin concentration, weight, and CYP3A5 genotype should be considered using tacrolimus. The initial daily tacrolimus dosing formula established can make a good prediction.
Clinical results of Visian implantable collamer lens implantation according to various sizes and implantation angles
Authors: Kim Bu Ki , Chung Young Taek 
Published: August 2021

Purpose: To investigate the clinical outcomes of Visian implantable collamer lens (ICL) implantation according to lens size and implantation angle. Setting: Onnuri Smile Eye Clinic, Seoul, Republic of Korea. Design: Retrospective case series. Methods: This study included 566 eyes of 283 patients treated with ICL implantation. Patients were divided into three groups: horizontally implanted same-sized ICL (group A), horizontally implanted different sized-ICL (group B: large ICL and small ICL) and same sized-ICL implanted with a different implantation angle (group C: horizontal and vertical). Results: At 12-month follow-up, the mean vault was 0.78 ± 17, 0.48 ± 0.13, 0.71 ± 0.18 and 0.44 ± 0.16 mm when large and small sized ICL was used in group B ( p < 0.001), and when ICL was horizontally and vertically implanted in group C ( p = 0.021), respectively. And the mean SE was −0.11 ± 0.30, −0.34 ± 0.42, −0.3 ± 0.56 and −0.64 ± 0.66 dioptres (D), when the large and the small sized ICL was used group B ( p = 0.039), and when the ICL was horizontally and vertically implanted in group C ( p = 0.036), respectively. No significant difference in UDVA, IOP and ECD between both eyes in groups B and C was observed. No statistical difference was found in the vault between both eyes for groups B and C. Conclusions: The vault was significantly higher and the SE was significantly more hyperopic when a larger-sized ICL was used or the ICL was horizontally implanted compared to when the ICL was vertically implanted.
Safety, Feasibility, and Acceptability of a New Virtual Rehabilitation Platform: A Supervised Pilot Study
Authors: Escalante-Gonzalbo Ana María , Ramírez-Graullera Yoás Saimon , Pasantes Herminia , Aguilar-Chalé José Jonathan , Sánchez-Castillo Gloria Ixchel , Escutia-Macedo Ximena Ameyalli , Briseño-Soriano Tania María , Franco-Castro Paulina , Estrada-Rosales Ana Lilia , Vázquez-Abundes Sandra Elizabeth , Andrade-Morales David , Hernández-Franco Jorge , Palafox Lorena 
Published: August 2021

Purpose: Stroke is the leading cause of disability in adults worldwide, with hemiparesis being the most prevalent consequence. The use of video games and movement sensors could contribute to improving patients’ chances of recovery. We performed a supervised pilot study to validate the safety, feasibility, and acceptability of a new virtual rehabilitation platform in patients with chronic post-stroke upper limb hemiparesis. Methods: The participants (n = 9) participated in 40 rehabilitation sessions, twice a week, for a period of 20 weeks. Their experiences with the platform were documented using a Likert-scale survey. Changes in motor function were evaluated using the Chedoke Arm and Hand Activity Inventory (CAHAI) and the Wolf Motor Function Test (WMFT). Results and conclusions: All participants expressed that they enjoyed the experience and felt comfortable using the platform. Preliminary results showed significant motor recovery ( P = .0039) according to the WMFT scores. Patients with significant impairment showed no improvement in upper limb task-oriented motor function after therapy. The new platform is safe and well-accepted by patients. The improvement in motor function observed in some of the participants should be attributed to the therapy since spontaneous functional recovery is not expected in chronic stroke patients.
How well do children in the North East of England function after a mental health crisis during the COVID-19 pandemic: A service evaluation
Authors: Staite Emily , Howey Lynne , Anderson Clare 
Published: August 2021

The COVID-19 pandemic has affected millions of people, and some researchers postulate that a mental health crisis will follow. The immediate effects of the COVID-19 pandemic on children’s mental health are now starting to be published, and results appear to be mixed. There is no research, to the authors’ knowledge, that empirically examines the functioning of young people following intervention from Child and Adolescent Mental Health Services (CAMHS) Crisis Teams in the UK during the COVID-19 pandemic. This service evaluation aims to do this using data from an NHS trust that supports 1.4 million people in the North East of England. We compared functioning, as measured by the Outcome Rating Scale (ORS), before and after treatment for young people discharged from the CAMHS Crisis Team between December 2019 and December 2020. ORS scores were significantly higher at the end of treatment (t(420) = −57.36, p < 0.001) with a large effect size (d = −1.56). Fifty eight percent of patients exhibited significant and reliable change (i.e. functioning improved to a ‘healthy’ level). No patients significantly deteriorated in functioning after accessing the crisis service.
Acceptability and feasibility of the World Health Organization’s Caregiver Skills Training implemented in the Italian National Health System
Authors: Salomone Erica , Ferrante Camilla , Salandin Arianna , Ferrara Federica , Torchio Elisabetta , Foletti Giulia , Ghersi Sabrina ,   CST Italy Team,   WHO CST Team, Pacione Laura , Servili Chiara 
Published: August 2021

The Caregiver Skills Training programme is an evidence-informed group intervention developed by the World Health Organization to counter the treatment gap for neurodevelopmental disorders in children. We examined feasibility and acceptability of Caregiver Skills Training in public child neuropsychiatry services in Italy. Following a formative adaptation process and a pre-pilot implementation, the programme was piloted in six centres. Caregivers of children (2–5 years) with autism spectrum disorder were randomised to either Caregiver Skills Training ( n = 43) or treatment as usual ( n = 43). Professionals’ and caregivers’ experiences in the treatment arm were examined with focus groups and questionnaires. The programme was largely considered acceptable, relevant and feasible. Specific implementation challenges and suggestions for optimising the package are discussed. Lay abstract Across the globe, children with neurodevelopmental disorders, including autism, have limited access to care through public services. To improve access to care the World Health Organization developed a novel, open-access programme: the Caregiver Skills Training programme. The Caregiver Skills Training consists of nine group sessions and three individual home visits, focused on training the caregiver on how to use everyday play and home routines as opportunities for learning and development. We implemented Caregiver Skills Training in public child neuropsychiatry services in Italy and examined with questionnaires and focus groups how feasible it was to deliver the programme in public health settings and how acceptable and relevant it was for caregiver users. We found that the Caregiver Skills Training was largely considered acceptable and relevant for families and feasible to deliver. We discuss potential solutions to address the specific implementation challenges that were identified, such as strategies to improve training of interventionists and overcome barriers to caregiver participation.
Pharmacological Interventions for the Management of Cancer-Related Fatigue Among Cancer Survivors: Systematic Review and Meta-Analysis
Authors: Sun Xuemei , Chen Yancong , Cheung William KW , Wu Irene XY , Xiao Fang , Chung Vincent CH 
Published: August 2021

Objective: Current guidelines have different recommendations on applying pharmacological interventions for managing cancer-related fatigue (CRF) among cancer survivors. This systematic review aims to synthesize clinical evidence on pharmacological interventions for managing CRF. Methods: Five databases were searched for potential randomized controlled trials (RCTs) from their inception until October 2020. RCTs assessing the effect of pharmacological treatments for CRF among cancer survivors were considered eligible. Clinical significance was determined by comparing the estimated effect with that of minimal important difference (MID). The risk of bias of each included RCT was appraised using the Cochrane risk of bias tool for randomized trials 2. Data were synthesized using random-effect pairwise meta-analyses. Results: A total of 15 RCTs (1238 participants) were included. The majority presented some concerns of bias arising from the randomization process and selection of the reported results. Meta-analysis showed that psychostimulant and wakefulness agents had statistically significant while clinically insignificant effects on the treatment of CRF (pooled weighted mean difference [WMD]: 2.8, 95% confidence interval [CI]: 0.2-5.4, I2: 0%, 3 RCTs, MID: 3.0-6.0). Three natural products, including Renshen Yangrong Tang (mean difference [MD]: −16.1, 95% CI: −8.9 to −23.3, MID: −17.3 to −11.4), Tualang honey (MD: 11.2, 95% CI: 7.1-15.3, MID: 3.0-6.0), and Shenmai injection plus Peptisorb (MD: −1.6, 95% CI: −2.1 to −1.1, MID: −1.1 to −0.8) demonstrated statistically and clinically significant effect in reducing CRF. Conclusions: Existing evidence showed promising effects of 3 natural products in reducing CRF among cancer survivors. The results from this study need to be further confirmed with well-designed and adequately powered RCTs that use validated instruments for the measurement of CRF.
The protective mechanism of folic acid on hyperhomocysteinemia-related arterial injury in spontaneously hypertensive rats: Folic acid against arterial inflammation
Authors: Zhang Lihua , Li Zhongliang , Xing Changcheng , Ma Xiaoshan , Xu Rui 
Published: August 2021

Background Hypertension associated with hyperhomocysteinemia (HHcy) is correlated with a high risk of vascular diseases. Studies found that folic acid (FA) supplementation can reduce the risk of cardiovascular and cerebrovascular events. The aim of the present study was to explore the potential mechanisms of FA attenuating HHcy-related arterial injury in spontaneously hypertensive rats (SHRs). Methods 24 SHRs were randomized into the control group, the HHcy group, and the HHcy + FA group (8 per group). The SHRs in the HHcy group and the HHcy + FA group were given DL-Hcy intraperitoneally to mimic hypertension associated with HHcy. The SHRs in the HHcy + FA group were given FA by gavage to mimic an FA-fortified diet. The histopathology and immunohistochemistry of rat aorta and carotid artery were analyzed, and the relative expression levels of immune/inflammation and oxidative stress molecules in arterial tissue were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Results FA significantly reduced the expression levels of nuclear factor-κ-gene binding (NF-κB) p65/Rela and interleukin-6 (IL-6) in rat arterial tissues, as well as the levels of plasma HHcy and serum malondialdehyde (MDA) in hypertension associated with HHcy rats ( p < 0.05). At the same time, FA significantly increased the serum superoxide dismutase (SOD) level in hypertension associated with HHcy rats, and even the SOD level of the HHcy + FA group was higher than that of the control group ( p < 0.05). However, HHcy induced the opposite results of the above indicators in SHRs compared with the control group ( p < 0.05). Conclusions The arterial protection mechanisms of FA are related to reducing the concentration of HHcy to eliminate the tissue toxicity of HHcy, inhibiting NF-κBp65/Rela/IL-6 pathway molecules to regulate inflammatory response, and promoting the potential anti-oxidative stress pathway molecules to reduce oxidative stress level.
Real-world efficacy and safety of nab-paclitaxel plus gemcitabine-cisplatin in patients with advanced biliary tract cancers: a multicenter retrospective analysis
Authors: Cheon Jaekyung , Lee Choong-kun , Sang Yun Beom , Choi Hye Jin , Kim Min Hwan , Ji Jun Ho , Ko Kwang Hyun , Kwon Chang-Il , Kim Dae Jung , Choi Sung Hoon , Kim Chan , Kang Beodeul , Chon Hong Jae 
Published: August 2021

Background: A recent phase II trial reported prolonged survival in patients with advanced biliary tract cancer (BTC) following treatment with nab-paclitaxel plus gemcitabine-cisplatin (Gem/Cis/nab-P). We aimed to evaluate the clinical outcomes of Gem/Cis/nab-P in Asian patients with advanced BTC in a real-world setting. Methods: We reviewed the data of patients who received Gem/Cis/nab-P for the management of advanced BTC between September 2019 and April 2021 at four institutes in Korea. Patients were classified into the Gem/Cis/nab-P and nab-P addition groups depending on the starting point of nab-P administration. Results: A total of 178 patients treated with Gem/Cis/nab-P were included in the study. Of these, 43.8% had intrahepatic cholangiocarcinoma (CCA), 34.8% had extrahepatic CCA, and 21.3% had gall bladder cancer. A total of 117 (65.7%) patients received Gem/Cis/nab-P as the first-line treatment, while 61 (34.3%) were treated with gemcitabine-cisplatin-based chemotherapy followed by nab-P addition. The objective response rate (ORR) and disease control rate in all patients were 42.1% and 84.8%, respectively. The ORR in the Gem/Cis/nab-P group was 47.9%, while that in the nab-P addition group was 31.1%. The median progression-free survival and overall survival were 8.5 months [95% confidence interval (CI), 6.9–10.1] and 14.6 months (95% CI, 10.2–19.0), respectively. In patients who received Gem/Cis/nab-P as initial treatment, the median PFS was 9.4 months (95% CI, 7.9–10.9) and the median OS was not-reached (95% CI, not available). Anemia ( n = 42, 23.6%), neutropenia ( n = 40, 22.5%), and thrombocytopenia ( n = 16, 9.0%) were the most common grade 3–4 toxicities. A total of 20 patients (11.2%) had conversions from unresectable to resectable disease and underwent surgery with curative intent. Conclusion: Gem/Cis/nab-P showed favorable real-life efficacy and safety outcomes in Korean patients with advanced BTC, which was consistent with the phase II trial outcomes.
Return-to-Sport Criteria After Upper Extremity Surgery in Athletes—A Scoping Review, Part 2: Ulnar Collateral Ligament of the Elbow Procedures
Authors: Griffith Rebecca , Bolia Ioanna K. , Fretes Nickolas , Murray Iain R. , Meyer John , Weber Alexander E. , Gamradt Seth C. , Petrigliano Frank A. 
Published: August 2021

Background: There is a lack of consensus to guide patient return to sport (RTS) after elbow ulnar collateral ligament surgery (eUCLS). Purpose: To describe the reported RTS criteria after eUCLS in the athletic population. Study Design: Scoping review; Level of evidence, 4. Methods: This scoping review was performed by adhering to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses–Scoping Review) guidelines. We searched 5 electronic databases (MEDLINE, Scopus, SPORTDiscus, Embase, Google Scholar Advanced) and the gray literature for English-language studies that reported at least 1 RTS criterion in athletes after eUCLS. Data were extracted and summarized as frequencies or arithmetic mean and standard deviation. Results: Included were 14 studies and 1335 athletes with a mean age of 21.4 ± 1.1 years. Time from surgery (range, 6-16 months) was the most common RTS criterion used, and it was reported by all 14 of the included articles. RTS criteria reported less often were pain (3/14; 21%), successful completion of a throwing program (3/14; 21%), muscle strength of the forearm muscles (1/14; 7%), and “normal” range of motion and muscle strength of the elbow and shoulder joints on the operated upper extremity (1/14; 7%). All studies used 1 to 5 of the above RTS criteria. Conclusion: Only 14 studies reported 1 or more RTS criteria after eUCLS in athletes, and time was the most common RTS criterion used. Our results highlight the need for a coordinated effort among surgeons, physical therapists, and athletic trainers in order to establish evidence-based RTS criteria after eUCLS in athletes so athletes can safely to sport and prolong their athletic careers.
Genome-wide identification of the MADS-box transcription factor family in autotetraploid cultivated alfalfa (Medicago sativa L.) and expression analysis under abiotic stress
Authors: Dong Xueming , Deng Hao , Ma Wenxue , Zhou Qiang , Liu Zhipeng 
Published: August 2021

Abstract
Background
Alfalfa, the “queen of forage”, is the most extensively cultivated forage legume in the world. The development and yield of alfalfa are seriously limited by abiotic stress. MADS-box transcription factors are one of the largest gene families and play a pivotal role in plant development and abiotic stress. However, little is known regarding the MADS-box transcription factors in autotetraploid cultivated alfalfa.

Results
In the present study, we identified 120 MsMADS-box genes in the alfalfa genome. Phylogenetic analysis indicated that 75 type-I MsMADS-box genes were classified into the Mα, Mβ, and Mγ subgroups, and 45 type-II MsMADS-box genes were classified into 11 subgroups. The promoter region of MsMADS-box genes containing several hormone and stress related elements. Chromosomal location analysis revealed that 117 MsMADS-box genes were unevenly distributed on 32 chromosomes, and the remaining three genes were located on unmapped scaffolds. A total of nine pairs of segmental duplications and four groups of tandem duplications were found. Expression analysis showed that MsMADS-box genes were differentially expressed in various tissues and under abiotic stresses. qRT-PCR analysis revealed that the expression profiles of eight selected MsMADS-box genes were distinct under various stresses.

Conclusions
In this study, MsMADS-box genes were identified in the cultivated alfalfa genome based on autotetraploid level, and further confirmed by Gene Ontology (GO) analysis, phylogenetic analysis, sequence features and expression analysis. Taken together, these findings will provide clues for further study of MsMADS-box functions and alfalfa molecular breeding.
Our study is the first to systematically identify and characterize the MADS-box transcription factors in autotetraploid cultivated alfalfa (Medicago sativa L.), and eight MsMADS-box genes were significantly involved in response to various stresses.