bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpretation of convolutional neural networks reveals crucial sequence features involving in transcription during fiber development
Authors: Liu Shang , Cheng Hailiang , Ashraf Javaria , Zhang Youping , Wang Qiaolian , Lv Limin , He Man , Song Guoli , Zuo Dongyun 
Published: March 2022

Abstract
Background
Upland cotton provides the most natural fiber in the world. During fiber development, the quality and yield of fiber were influenced by gene transcription. Revealing sequence features related to transcription has a profound impact on cotton molecular breeding. We applied convolutional neural networks to predict gene expression status based on the sequences of gene transcription start regions. After that, a gradient-based interpretation and an N-adjusted kernel transformation were implemented to extract sequence features contributing to transcription.

Results
Our models had approximate 80% accuracies, and the area under the receiver operating characteristic curve reached over 0.85. Gradient-based interpretation revealed 5' untranslated region contributed to gene transcription. Furthermore, 6 DOF binding motifs and 4 transcription activator binding motifs were obtained by N-adjusted kernel-motif transformation from models in three developmental stages. Apart from 10 general motifs, 3 DOF5.1 genes were also detected. In silico analysis about these motifs’ binding proteins implied their potential functions in fiber formation. Besides, we also found some novel motifs in plants as important sequence features for transcription.

Conclusions
In conclusion, the N-adjusted kernel transformation method could interpret convolutional neural networks and reveal important sequence features related to transcription during fiber development. Potential functions of motifs interpreted from convolutional neural networks could be validated by further wet-lab experiments and applied in cotton molecular breeding.
The efficacy of human epidermal growth factor receptor 2 (HER2) blockade switching mode in refractory patients with HER2-positive metastatic breast cancer: a phase II, multicenter, single-arm study (SYSUCC-005)
Authors: Duan Fangfang , Zhong Muyi , Ma Yuyu , Song Chenge , Zhang Lehong , Lin Ying , Wu Zhiyong , Zhang Yuanqi , Huang Jiajia , Xu Fei , Shi Yanxia , Wang Shusen , Yuan Zhongyu , Xia Wen , Bi Xiwen 
Published: March 2022

Abstract
Background
Despite significant survival improvement in human epidermal growth factor receptor 2 (HER2) blockade for HER2-positive breast cancer, resistance to anti-HER2 remains inevitable. Subsequent anti-HER2 with continuing trastuzumab beyond progression is acceptable with limited efficacy when other anti-HER2 treatment is unavailable. This single-arm, phase II study (SYSUCC-005) aimed to explore the efficacy of switching mode for HER2-positive refractory metastatic breast cancer.

Methods
Patients with HER2-positive metastatic breast cancer rapidly progressing during pre-trastuzumab from six hospitals in China were designed to switch to lapatinib 1,250 mg orally once per day continuously plus capecitabine (1,000 mg/m2 orally twice per day on days 1–14) or vinorelbine (25 mg/m2 intravenously once per day on days 1 and 8) of each 21-day cycle. The primary endpoint was progression-free survival (PFS).

Results
Between January 5, 2015 and May 31, 2020, 159 patients were eligible in this study. The median follow-up was 33.1 months, a median PFS of 8.5 months was achieved. Brain metastases (hazard ratio [HR] = 1.582, 95% confidence interval [CI] 1.019- 2.453, P = 0.041) and ≥ 2 metastatic sites (HR = 1.679, 95% CI 1.151–2.450, P = 0.007) were independent prognostic factors for PFS. The most common grade ≥ 3 adverse events were diarrhea (3.8%) and hand-foot syndrome (9.4%).

Conclusion
The switching mode showed predominant efficacy, which might be a prior therapeutic option over continuing mode in subsequent anti-HER2 therapy for patients with HER2-positive refractory metastatic breast cancer.

Trial registration
This trial was registered on ClinicalTrials.gov (NCT02362958) on 13/02/2015.
Changes of retinal structure and function in patients with internal carotid artery stenosis
Authors: Wu Dong-hui , Wu Lan-ting , Wang Yan-ling , Wang Jia-lin 
Published: March 2022

Abstract
Background
To investigate the structural and functional changes of the retina in patients with different degrees of internal carotid artery (ICA) stenosis.

Methods
This cross-sectional study included patients with varying degrees ICA stenosis. Clinical characteristics of 41 patients were collected after being divided into four groups according to the ICA stenosis indicated by computed tomographic angiography (Group 0: without ICA stenosis, Group 1: ipsilateral slight ICA stenosis, Group 2: ipsilateral moderate ICA stenosis, Group 3: ipsilateral severe ICA stenosis). Retinal vessel caliber (RVC) was measured quantitatively with the Integrative Vessel Analysis software. The retinal sensitivity was examined with the MP-3 microperimeter. The relationships among central retinal artery equivalent (CRAE), central retinal vein equivalent, arteriole to venule ratio (AVR), mean retinal sensitivity (MS) and ICA stenosis degree were analysed.

Results
The CRAE in Group 3 were significantly smaller compared with Group 0, Group 1 and Group 2 (P < 0.001, P < 0.001, P = 0.002). Significant decrease was found between Group 3 with other groups in MS at fovea (P < 0.001, P < 0.001, P = 0.002). Moreover, there was a positive correlation found between MS and CRAE (Beta = 0.60, P < 0.001 at fovea; Beta = 0.64, P < 0.001 at 2 degree; Beta = 0.60, P < 0.001 at 4 degree; Beta = 0.55, P < 0.001 at 8 degree; Beta = 0.53, P < 0.001 at 12 degree).

Conclusions
The present study revealed smaller CRAE and AVR in ipsilateral severe ICA stenosis patients. And the MS decreased in patients with severe ICA stenosis. In addition, MS had a positive correlation with CRAE.
An analysis of views about supported reduction or discontinuation of antipsychotic treatment among people with schizophrenia and other psychotic disorders
Authors: Crellin Nadia E. , Priebe Stefan , Morant Nicola , Lewis Glyn , Freemantle Nick , Johnson Sonia , Horne Rob , Pinfold Vanessa , Kent Lyn , Smith Ruth , Darton Katherine , Cooper Ruth E. , Long Maria , Thompson Jemima , Gruenwald Lisa , Freudenthal Robert , Stansfeld Jacki L. , Moncrieff Joanna 
Published: March 2022

Abstract
Background
Antipsychotic medication can reduce psychotic symptoms and risk of relapse in people with schizophrenia and related disorders, but it is not always effective and adverse effects can be significant. We know little of patients’ views about continuing or discontinuing antipsychotic treatment.

Aims
To explore the views of people with schizophrenia and other psychotic disorders about continuing their antipsychotic medication or attempting to reduce or discontinue this medication with clinical support.

Methods
We collected quantitative and qualitative data by conducting semi-structured interviews in London, UK. Factors predicting a desire to discontinue medication were explored. Content analysis of qualitative data was undertaken.

Results
We interviewed 269 participants. 33% (95% CI, 27 to 39%) were content with taking long-term antipsychotic medication. Others reported they took it reluctantly (19%), accepted it on a temporary basis (24%) or actively disliked it (18%). 31% (95% CI, 25 to 37%) said they would like to try to stop medication with professional support, and 45% (95% CI, 39 to 51%) wanted the opportunity to reduce medication. People who wanted to discontinue had more negative attitudes towards the medication but were otherwise similar to other participants. Wanting to stop or reduce medication was motivated mainly by adverse effects and health concerns. Professional support was identified as potentially helpful to achieve reduction.

Conclusions
This large study reveals that patients are commonly unhappy about the idea of taking antipsychotics on a continuing or life-long basis. Professional support for people who want to try to reduce or stop medication is valued.
BDNF-TrkB signaling-mediated upregulation of Narp is involved in the antidepressant-like effects of (2R,6R)-hydroxynorketamine in a chronic restraint stress mouse model
Authors: Ju Lingsha , Yang Jiaojiao , Zhu Tingting , Liu Panmiao , Yang Jianjun 
Published: March 2022

Abstract
Background
Preclinical studies have indicated that the ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) is a rapid-acting antidepressant drug with limited dissociation properties and low abuse potential. However, its effects and molecular mechanisms remain unclear. In this work, we examined the involvement of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and Narp in the antidepressant-like actions of (2R,6R)-HNK in a chronic restraint stress (CRS) mouse model.

Methods
C57BL/6 male mice were subjected to CRS for 8 h per day for 14 consecutive days. Open field, forced swimming, novelty suppressed feeding, and tail suspension tests were performed after administering (2R,6R)-HNK (10 mg/kg), a combination of (2R,6R)-HNK and NBQX (an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist; 10 mg/kg), or a combination of (2R,6R)-HNK and ANA-12 (a TrkB receptor antagonist; 0.5 mg/kg). The mRNA levels of Bdnf and Narp in the hippocampus were determined by quantitative reverse transcription-PCR (qRT–PCR). Western blotting was used to determine the hippocampal protein levels of GluA1, GluA2, BDNF, Narp, PSD95, and synaptophysin, as well as the p-TrkB/TrkB protein ratio.

Results
(2R,6R)-HNK had rapid antidepressant-like effects in CRS mice. Furthermore, (2R,6R)-HNK significantly ameliorated CRS-induced downregulation of GluA1, GluA2, BDNF, Narp, PSD95, and the p-TrkB/TrkB protein ratio in the hippocampus. The effects of (2R,6R)-HNK were blocked by combinations with NBQX or ANA-12.

Conclusion
BDNF-TrkB signaling-mediated upregulation of Narp in the hippocampus may play a key role in the antidepressant-like effect of (2R,6R)-HNK in the CRS model of depression.
A comparative study on mental health and adaptability between older and younger adults during the COVID-19 circuit breaker in Singapore
Authors: Yu Chou Chuen , Tou Nien Xiang , Low James Alvin 
Published: March 2022

AbstractBackgroundWhile older age is associated with better emotional well-being, it is unclear whether such age advantages remain during a pandemic. This study examined differences in mental health, adaptive behaviours, social support, perceived stress, digital media usage, and perceived change in circumstances between younger and older adults during the circuit breaker period (partial lockdown) in Singapore.MethodsA door-to-door survey was administered to a nationally representative sample of 602 younger (n = 302) and older (n = 300) adults aged 21–89 years from Singapore from 17 October to 27 November 2020. All participants self-reported their depression, anxiety, stress, adaptive behaviours, social support, perceived stress, change in circumstances, and digital media usage during the partial lockdown period.ResultsOlder adults were found to report significantly lower levels of depression, anxiety, and stress as compared to younger adults. Although older adults were less able to perform essential activities during the lockdown, they were more adaptable psycho-socially. Logistic regression analyses revealed that for older age group, adaptability and health status significantly predicted better mental health. Older adults had higher odds of low depression scores [odds ratio (OR) 1.81, 95% confidence intervals (CI) 1.07–3.08], anxiety scores (OR 1.80, 95% CI 1.05–3.08), and stress scores (OR 3.05, 95% CI 1.72–5.41). In addition, adaptability was found to moderate the relationship between age and mental health with detrimental effects of low adaptability stronger for younger adults than older adults.ConclusionsDuring the lockdown period, older adults in Singapore had better mental health, perceived less stress-related concerns and were more adaptable psycho-socially as compared to younger adults. This study’s findings extend current evidence that age-related advantages in emotional well-being persisted in the wake of the COVID-19 pandemic.
The impact of COVID-19 on access to harm reduction, substance use treatment and recovery services in Scotland: a qualitative study
Authors: Schofield Joe , Dumbrell Joshua , Matheson Catriona , Parkes Tessa , Bancroft Angus 
Published: March 2022

AbstractIntroductionPeople who use drugs (PWUD) are considered vulnerable to COVID-19 exposure and the sequelae of infection due to their social circumstances, health conditions, drug purchasing, and substance use. They can depend on access to services that provide harm reduction, substance use treatment, recovery and support, and general healthcare. Social distancing measures and service restrictions posed significant challenges to the health and wellbeing of PWUD.MethodsEthical approvals were secured. PWUD were recruited from voluntary sector homeless and housing, harm reduction, and recovery organisations across central Scotland. Data was collected via semi-structured interviews and analysed using the Framework Method.ResultsTwenty nine PWUD participated and reported mixed experiences of the impacts of COVID-19 lockdown. Several benefitted from policy and practice developments designed to sustain or increase access to harm reduction services. Some PWUD reported improved access to substitute prescribing and/or appreciated being trusted to manage multiple take-home doses. Others noted the loss of regular in-person contact with treatment providers and dispensers. Access to recovery support was challenging for many, especially those unable to access or uncomfortable with online provision who experienced greater isolation. Lack of access to general healthcare services was common, and especially problematic for PWUD with chronic physical and mental health conditions.ConclusionsThis qualitative research describes the impacts of COVID-19 social and service restrictions on PWUD in Scotland. These impacts were anticipated by policy makers and service providers. Effective and acceptable developments were shown to maintain and even increase service provision for PWUD. Developments were geographically dependent and significant challenges remained for many people. The learning generated can inform responses to increase service access and uptake in post-pandemic times.
Factors associated with increased physical activity among patients prescribed physical activity in Swedish routine health care including an offer of counselor support: a 1-year follow-up
Authors: Andersen Pia , Holmberg Sara , Årestedt Kristofer , Lendahls Lena , Nilsen Per 
Published: March 2022

Abstract
Background
The study addresses knowledge gaps in research regarding influences of routine health care delivery of physical activity on prescription (PAP). The aim was to investigate if patient and health care characteristics are associated with increased physical activity 1 year after prescription among patients offered counselor support in addition to health care professionals’ prescription. The study was conducted in primary and secondary care in a Swedish health care region.

Methods
All PAP recipients during 1 year were invited (N = 1503) to participate in this observational prospective study. Data were collected from medical records and questionnaires (baseline and follow-up). Descriptive statistics and multiple logistic regression analysis were used. The outcome variable was increased physical activity after 1 year. Study variables were patient and health care characteristics.

Results
Three hundred and fifty-five patients with complete follow-up data were included. The mean age was 62 years (SD = 14; range, 18–90) and 68% were females. Almost half (47%) had increased physical activity 1 year after PAP. Multiple logistic regression analysis showed that increased physical activity at follow-up was positively associated with lower baseline activity, counselor use, and positive perception of support. Counselor users with low baseline activity had higher odds ratio for increased physical activity at follow-up than non-users (OR = 7.2, 95% CI = 2.2–23.5 vs. OR = 3.2, 95% CI = 1.4–7.5). Positive perception of support was associated with increased physical activity among counselor users but not among non-users.

Conclusions
An increase in physical activity after PAP was related to low baseline activity, positive perception of support, and use of counselor support after PAP. Qualified counseling support linked to PAP seems to be important for achieving increased physical activity among patients with lower baseline activity.
Increase in tibial internal rotation due to weight-bearing is a key feature to diagnose early-stage knee osteoarthritis: a study with upright computed tomography
Authors: Kaneda Kazuya , Harato Kengo , Oki Satoshi , Yamada Yoshitake , Nakamura Masaya , Nagura Takeo , Jinzaki Masahiro 
Published: March 2022

Abstract
Background
The classification of knee osteoarthritis is an essential clinical issue, particularly in terms of diagnosing early knee osteoarthritis. However, the evaluation of three-dimensional limb alignment on two-dimensional radiographs is limited. This study evaluated the three-dimensional changes induced by weight-bearing in the alignments of lower limbs at various stages of knee osteoarthritis.

Methods
Forty five knees of 25 patients (69.9 ± 8.9 years) with knee OA were examined in the study. CT images of the entire leg were obtained in the supine and standing positions using conventional CT and 320-row detector upright CT, respectively. Next, the differences in the three-dimensional alignment of the entire leg in the supine and standing positions were obtained using 3D-3D surface registration technique, and those were compared for each Kellgren–Lawrence grade.

Results
Greater flexion, adduction, and tibial internal rotation were observed in the standing position, as opposed to the supine position. Kellgren–Lawrence grades 1 and 4 showed significant differences in flexion, adduction, and tibial internal rotation between two postures. Grades 2 and 4 showed significant differences in adduction, while grades 1 and 2, and 1 and 3 showed significant differences in tibial internal rotation between standing and supine positions.

Conclusions
Weight-bearing makes greater the three-dimensional deformities in knees with osteoarthritis. Particularly, greater tibial internal rotation was observed in patients with grades 2 and 3 compared to those with grade 1. The greater tibial internal rotation due to weight-bearing is a key pathologic feature to detect early osteoarthritic change in knees undergoing osteoarthritis.
Impact of a new combined preoperative cleft assessment on dental implant success in patients with cleft and palate: a retrospective study
Authors: Savoldelli Charles , Bailleux Sonanda , Chamorey Emmanuel , Vandersteen Clair , Lerhe Barbara , Afota Franck 
Published: March 2022

Abstract
Background
Bone height assessment alone is frequently used to guide rehabilitation choice, without consideration for soft tissues or adjacent teeth. This study aimed to evaluate the impact of different preoperative cleft assessments on implant success and patient satisfaction.

Methods
The study involved a retrospective assessment of records from 40 patients with cleft lip and palate (CLP). The alveolar cleft score (ACS; clinical criteria), interdental alveolar bone height (IABH) score (radiological criteria), patient compliance score (dental hygiene, medical visit observance, and smoking), and a novel combined score (IABH-ACS-Compliance) were assessed from patient records. Patients who required prosthetic tooth rehabilitation in the cleft dental arch space were included. Twenty-six patients (Group 1) were treated with dental implants, and 14 patients (Group 2) selected another prosthetic option (fixed prosthodontics, removal prosthesis), orthodontic space closure, or no rehabilitation. The main outcomes measured were relative implant success (no implant loss involving marginal bone loss ≤ 1.9 mm) for patients treated with dental implant therapy (Group 1) and patient satisfaction for all patients (Groups 1 and 2).

Results
Forty dental implants were placed in the patients in Group 1. Four implants in four patients (Group 1 relative failure, RF) were lost (implant survival rate of 90%) after 36 (± 12.4) months of follow-up. Twenty-two patients who received implants belonged to the relative implant success group (Group 1 RS). The average “IABH-ACS-Compliance” scores were significantly different (p < 0.05): 16.90 ± 2.35 and 12.75 ± 0.43 for the Group 1 RS and RF groups, respectively.

Conclusions
Preoperative cleft parameters have an impact on relative implant success and patient satisfaction. The new cleft assessment combined-score (“IABH-ACS-Compliance”) allows an accurate selection of cleft cases eligible for dental implants, thereby improving postoperative outcomes.
Students’ perception of educational environment based on Dundee Ready Education Environment Measure and the role of peer mentoring: a cross-sectional study
Authors: Behkam Shadab , Tavallaei Amirhossein , Maghbouli Nastaran , Mafinejad Mahboobeh Khabaz , Ali Jemal Haidar 
Published: March 2022

AbstractObjectiveThe curricular reform at Tehran University of Medical Sciences (TUMS), Iran, has been implemented since 2011 when peer mentoring program started. The program is believed to have a crucial role in students’ perception of the educational environment (EE). We aimed to determine how students perceive the educational environment and compared the mentees and non-mentees’ perception of EE.MethodsA cross-sectional descriptive study was conducted among 190 first-year medical students enrolling at Tehran University of Medical Sciences from March to September 2019. A questionnaire was used to collect information on students’ age, gender, marital status, dormitory status, and their mentoring status including satisfaction of mentor-mentee relationship. The study also employed Dundee Ready Education Environment Measure (DREEM). The collected data were then entered and analysed using SPSS version 20. To compare the perception of EE between mentees and non-mentees, we used independent t-test.ResultsThe mean (SD) for total DREEM score for EE was 144.1 (19.3), which signifies a more positive than negative educational environment perception. Nonetheless, the mean scores of total DREEM was not significantly different between students with or without mentors (P =0.390). The overall mean score for student perceptions of learning for mentees was 32.47 (4.5) while for those without a mentor, the score was 31.70 (4.9) (P =0.491). The items concerned with “emphasizing factual learning” and “teacher-based teaching” were rated the least. The item “having an appropriate support system” was scored significantly different between students with or without mentors (P =0.009).ConclusionsSince having an appropriate support system was significantly different between groups, we suggest curriculum designers focus on the above-mentioned issue under caption for improvement during the reform programs.