bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pyrotinib in combination with letrozole for hormone receptor-positive, human epidermal growth factor receptor 2-positive metastatic breast cancer (PLEHERM): a multicenter, single-arm, phase II trial
Authors: Hu Zhe-Yu , Yan Min , Xiong Huihua , Ran Li , Zhong Jincai , Luo Ting , Sun Tao , Xie Ning , Liu Liping , Yang Xiaohong , Xiao Huawu , Li Jing , Liu Binliang , Ouyang Quchang 
Published: June 2023

Abstract
Background
Human epidermal growth factor receptor 2 (HER2) targeted therapy combined with endocrine therapy has been recommended as an alternative treatment strategy for patients with hormone receptor (HR)-positive, HER2-positive metastatic breast cancer (MBC). This study aimed to evaluate the role of pyrotinib, an oral pan-HER irreversible tyrosine kinase inhibitor, in combination with letrozole for patients with HR-positive, HER2-positive MBC.

Methods
In this multi-center, phase II trial, HR-positive and HER2-positive MBC patients who were not previously treated for metastasis disease were enrolled. Patients received daily oral pyrotinib 400 mg and letrozole 2.5 mg until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the clinical benefit rate (CBR) assessed by an investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1.

Results
From November 2019 to December 2021, 53 patients were enrolled and received pyrotinib plus letrozole. As of August 2022, the median follow-up duration was 11.6 months (95% confidence interval [CI], 8.7–14.0 months). The CBR was 71.7% (95% CI, 57.7–83.2%), and the objective response rate was 64.2% (95% CI, 49.8–76.9%). The median progression-free survival was 13.7 months (95% CI, 10.7–18.7 months). The most common treatment-related adverse event of grade 3 or higher was diarrhea (18.9%). No treatment-related deaths were reported, and one patient experienced treatment discontinuation due to adverse event.

Conclusions
Our preliminary results suggested that pyrotinib plus letrozole is feasible for the first-line treatment of patients with HR-positive and HER2-positive MBC, with manageable toxicities.

Trial registration
ClinicalTrials.gov, NCT04407988.
Clinical and genetic analysis of a case of late onset carbamoyl phosphate synthase I deficiency caused by CPS1 mutation and literature review
Authors: Wang Shangyu , Chen Jinglin , Zhu Xiaoqi , Huang Tingting , Xu Haifeng , Ying Guohuan , Qian Hao , Lin Wenxin , Tung Yiehen , Khan Kaleem Ullah , Guo Hu , Zheng Guo , Lu Haiying , Zhang Gang 
Published: June 2023

Abstract
Background
Carbamoyl phosphate synthetase I defect (CPS1D) is a rare disease with clinical case reports mainly in early neonates or adults, with few reports of first onset in late neonatal to childhood. We studied the clinical and genotypic characteristics of children with childhood onset CPS1D caused by two loci mutations (one of these is a rarely reported non-frame shift mutation) in the CPS1.

Case presentation
We present a rare case of adolescent-onset CPS1D that had been misdiagnosed due to atypical clinical features, and further investigations revealed severe hyperammonemia (287µmol/L; reference range 11.2 ~ 48.2umol/L). MRI of the brain showed diffuse white matter lesions. Blood genetic metabolic screening showed elevated blood alanine (757.06umol/L; reference range 148.8 ~ 739.74umol/L) and decreased blood citrulline (4.26umol/L; reference range 5.45 ~ 36.77umol/L). Urine metabolic screening showed normal whey acids and uracil. Whole-exome sequencing revealed compound heterozygous mutations in the CPS1, a missense mutation (c.1145 C > T) and an unreported de novo non-frame shift mutation (c.4080_c.4091delAGGCATCCTGAT), respectively, which provided a clinical diagnosis.

Conclusion
A comprehensive description of the clinical and genetic features of this patient, who has a rare age of onset and a relatively atypical clinical presentation, will facilitate the early diagnosis and management of this type of late onset CPS1D and reduce misdiagnosis, thus helping to reduce mortality and improve prognosis. It also provides a preliminary understanding of the relationship between genotype and phenotype, based on a summary of previous studies, which reminds us that it may help to explore the pathogenesis of the disease and contribute to genetic counselling and prenatal diagnosis.
Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing
Authors: Balke-Want Hyatt , Keerthi Vimal , Gkitsas Nikolaos , Mancini Andrew G. , Kurgan Gavin L. , Fowler Carley , Xu Peng , Liu Xikun , Asano Kyle , Patel Sunny , Fisher Christopher J. , Brown Annie K. , Tunuguntla Ramya H. , Patel Shabnum , Sotillo Elena , Mackall Crystal L. , Feldman Steven A. 
Published: June 2023

Abstract
Background
Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma cell malignancies and could disrupt the therapeutic landscape of solid tumors. However, access to CAR-T cells is not adequate to meet clinical needs, in part due to high cost and long lead times for manufacturing clinical grade virus. Non-viral site directed CAR integration can be accomplished using CRISPR/Cas9 and double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) via homology-directed repair (HDR), however yields with this approach have been limiting for clinical application (dsDNA) or access to large yields sufficient to meet the manufacturing demands outside early phase clinical trials is limited (ssDNA).

Methods
We applied homology-independent targeted insertion (HITI) or HDR using CRISPR/Cas9 and nanoplasmid DNA to insert an anti-GD2 CAR into the T cell receptor alpha constant (TRAC) locus and compared both targeted insertion strategies in our system. Next, we optimized post-HITI CRISPR EnrichMENT (CEMENT) to seamlessly integrate it into a 14-day process and compared our knock-in with viral transduced anti-GD2 CAR-T cells. Finally, we explored the off-target genomic toxicity of our genomic engineering approach.

Results
Here, we show that site directed CAR integration utilizing nanoplasmid DNA delivered via HITI provides high cell yields and highly functional cells. CEMENT enriched CAR T cells to approximately 80% purity, resulting in therapeutically relevant dose ranges of 5.5 × 108–3.6 × 109 CAR + T cells. CRISPR knock-in CAR-T cells were functionally comparable with viral transduced anti-GD2 CAR-T cells and did not show any evidence of off-target genomic toxicity.

Conclusions
Our work provides a novel platform to perform guided CAR insertion into primary human T-cells using nanoplasmid DNA and holds the potential to increase access to CAR-T cell therapies.
Assessment of data demand for informed-decisions among health facility and department heads in public health facilities of Amhara Region, northwest Ethiopia
Authors: Chanyalew Moges Asressie , Yitayal Mezgebu , Atnafu Asmamaw , Tilahun Binyam 
Published: June 2023

Abstract
Background
Evidence-based decision-making is a foundation of health information systems; however, routine health information is not mostly utilized by decision makers in the Amhara region. Therefore, this study aimed to explore the facility and department heads' perceptions towards the demand for and use of routine health information for decision making.

Methods
A phenomenological qualitative study was done in eight districts of the Amhara region from June 10/2019 to July 30/2019. We obtained written informed consent and recruited 22 key informants purposively. The research team prepared a codebook, assigned codes to ideas, identified salient patterns, grouped similar ideas, and developed themes from the data. Thus, data were analyzed thematically using OpenCode software.

Results
The study revealed that health workers collected many data, but little was demanded and utilized to inform decisions. The majority of respondents perceived that data were collected merely for reporting. Lack of skills in data management, analysis, interpretation, and use were the technical attributes. Individual attributes included low staff motivation, carelessness, and lack of value for data. Poor access to data, low support for Health Information System, limited space for archiving, and inadequate finance were related to organizational attributes. The contextual (social-political) factors also influenced the use of eHealth applications for improved data demand and use among health care providers.

Conclusion
In this study, health workers collect routine health data merely for reporting, and they did not demand and use it mostly to inform decisions and solve problems. Technical, individual, organizational, and contextual attributes were contributors to low demand and use of routine health data. Thus, we recommend building the technical capacity of health workers, introducing motivation mechanisms and ensuring accountability systems for better data use.
Disturbance of neuron–microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice
Authors: Xu Jingyi , Yang Chunshu , Zeng Siyuan , Wang Xuejiao , Yang Pingting , Qin Ling 
Published: June 2023

Abstract
Objectives
Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron–microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron–microglia crosstalk and is involved in the pathogenic process of NPSLE.

Methods
Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect.

Results
The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice.

Conclusion
GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron–microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE.
Care pathways and factors associated with interhospital transfer to neurotrauma centers for patients with isolated moderate-to-severe traumatic brain injury: a population-based study from the Norwegian trauma registry
Authors: Cuevas-Østrem Mathias , Thorsen Kjetil , Wisborg Torben , Røise Olav , Helseth Eirik , Jeppesen Elisabeth 
Published: June 2023

Abstract
Background
Systems ensuring continuity of care through the treatment chain improve outcomes for traumatic brain injury (TBI) patients. Non-neurosurgical acute care trauma hospitals are central in providing care continuity in current trauma systems, however, their role in TBI management is understudied. This study aimed to investigate characteristics and care pathways and identify factors associated with interhospital transfer to neurotrauma centers for patients with isolated moderate-to-severe TBI primarily admitted to acute care trauma hospitals.

Methods
A population-based cohort study from the national Norwegian Trauma Registry (2015–2020) of adult patients (≥ 16 years) with isolated moderate-to-severe TBI (Abbreviated Injury Scale [AIS] Head ≥ 3, AIS Body < 3 and maximum 1 AIS Body = 2). Patient characteristics and care pathways were compared across transfer status strata. A generalized additive model was developed using purposeful selection to identify factors associated with transfer and how they affected transfer probability.

Results
The study included 1735 patients admitted to acute care trauma hospitals, of whom 692 (40%) were transferred to neurotrauma centers. Transferred patients were younger (median 60 vs. 72 years, P < 0.001), more severely injured (median New Injury Severity Score [NISS]: 29 vs. 17, P < 0.001), and had lower admission Glasgow Coma Scale (GCS) scores (≤ 13: 55% vs. 27, P < 0.001). Increased transfer probability was significantly associated with reduced GCS scores, comorbidity in patients < 77 years, and increasing NISSs until the effect was inverted at higher scores. Decreased transfer probability was significantly associated with increasing age and comorbidity, and distance between the acute care trauma hospital and the nearest neurotrauma center, except for extreme NISSs.

Conclusions
Acute care trauma hospitals managed a substantial burden of isolated moderate-to-severe TBI patients primarily and definitively, highlighting the importance of high-quality neurotrauma care in non-neurosurgical hospitals. The transfer probability declined with increasing age and comorbidity, suggesting that older patients were carefully selected for transfer to specialized care.
Photoaging and theory-based intervention to improve sun protection behaviors in students in Zahedan: study protocol for a randomized controlled trial
Authors: Okati-Aliabad Hassan , Hosseini Esmat Sadat , Sharifabad Mohammad Ali Morowati , Mohammadi Mahdi , Ardakani Mohamad Ebrahimzadeh , Talebrouhi Amir Hossein 
Published: June 2023

Abstract
Background
Excessive exposure to solar ultraviolet (UV) radiation can cause skin cancer. Implementing new technologies and computational algorithms can potentially change the outlook for cancer prevention and facilitate early detection of melanoma, thereby reducing mortality. Mobile technology as a potential provider of health services in delivering health information and conducting interventions, especially in skin fields, where a significant part of diagnosis is based on visual examination, can be important. Evidence showed that constructs of protection motivation theory (PMT) were good predictors of practicing sun protection behaviors in students. This study will investigate whether mobile applications improve safe and healthy behaviors and affect students' reduced UV exposure.

Method/design
This randomized controlled trial will be conducted on 320 students on 06/04/2022 in Zahedan. We created mobile applications (Sunshine and Skin Health and WhatsApp apps). Sunshine and Skin Health app allows users to see their changed faces in three stages of adolescence, middle age, and old age based on sun protection behavior. The WhatsApp app has 27 health messages based on PMT theory, eight educational files, and a skin cancer clip that will be sent through WhatsApp during a week. Randomization will be performed using a 1:1 (control: intervention) ratio. The primary endpoint is the group difference in sun-protective behaviors and PMT constructs immediately after the intervention. The secondary endpoint is the group difference in sun-protective behaviors and PMT constructs at a 3-month follow-up. The data will be analyzed in SPSS.22, and the significance level will be considered at 0.05.

Discussion
The present study examines the effectiveness of mobile applications in improving sun-protective behaviors. If this intervention enhances sun protection behaviors, it can prevent students’ skin damage.

Trial registration
Iranian Registry of Clinical Trials IRCT20200924048825N1. Prospectively registered on 8 February 2021.
The safety of SGLT-2 inhibitors in diabetic patients submitted to elective percutaneous coronary intervention regarding kidney function: SAFE-PCI pilot study
Authors: Feitosa Mateus Paiva Marques , Lima Eduardo Gomes , Abizaid Alexandre Antônio Cunha , Mehran Roxana , Lopes Neuza Helena Moreira , de Assis Fischer Ramos Thiago , Hideo-Kajita Alexandre , Filho Roberto Kalil , Junior Carlos Vicente Serrano 
Published: June 2023

Abstract
Background
Percutaneous coronary intervention (PCI) is one of the most performed well-succeeded therapeutic procedures worldwide, reducing symptoms and improving quality of life. Neutrophil Gelatinase-associated Lipocalin (NGAL) is a biomarker of acute kidney injury (AKI) produced early after an ischemic renal insult. Osmotic diuresis and the vasoconstriction of the afferent arteriole promoted by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) generate a concern regarding the possibility of dehydration and consequent AKI. There is no consensus on the maintenance or discontinuation of SGTL2i in patients who will undergo PCI. This study aimed to evaluate the safety of empagliflozin in diabetic patients submitted to elective PCI regarding kidney function.

Methods
SAFE-PCI trial is a prospective, open-label, randomized (1:1), single-center pilot study and a follow-up of 30 days. The SGLT2i empagliflozin 25 mg daily was initiated at least 15 days before PCI in the intervention group and maintained until the end of the follow-up period. Serum NGAL was collected 6 h after PCI and creatinine before PCI, 24 h, and 48 h after the procedure. As per protocol, both groups received optimal medical treatment and standard protocol of nephroprotection.

Results
A total of 42 patients were randomized (22 patients in the iSGLT-2 group and 20 patients in the control group). There was no difference between-group baseline data. The primary outcome (NGAL and creatinine values post PCI) did not differ in both groups: the mean NGAL value was 199 ng/dL in the empagliflozin group and 150 ng/dL in the control group (p = 0.249). Although there was an initial increase in creatinine in the SGLT-2i group compared to the control group between baseline creatinine and pre-PCI and 24 h post-PCI creatinine, no difference was detected in creatinine 48 h post-PCI (p = 0.065). The incidence of CI-AKI, determined by KDIGO criteria, in the iSGLT2-group was 13.6% and 10.0% in the control group without statistical difference.

Conclusion
The present study showed that the use of empagliflozin is safe regarding kidney function during elective PCI in patients with T2D when compared with no use of SGLT2i.
Trial registration Our clinical study is registered on ClinicalTrials.gov with the following number: NCT05037695.
Comparison of RNA-Seq analysis data between tracheal mite-infested and uninfested Japanese honey bees (Apis cerana japonica)
Authors: Suzuki Akihiko , Kamakura Masaki , Shiramata Takuya , Nakaoka Shinji , Sakamoto Yoshiko 
Published: June 2023

Abstract
Objective
The purpose of this data set is to investigate differences in RNA-Seq transcriptome profiles between Acarapis woodi-infested and uninfested Japanese honey bees (Apis cerana japonica). The data set is strengthened by data collected from different body parts (head, thorax, and abdomen). The data set will support future studies of molecular biological changes in mite-infested honey bees.

Data description
We collected 5 mite-infested and 5 uninfested A. cerana japonica workers from each of 3 different colonies (designated as A, B, and C). Workers were dissected into 3 body sites (i.e., heads, thoraces, and abdomen), and 5 of each body site were pooled together for RNA extraction, generating a total of 18 RNA-Seq samples (2 infection status × 3 colonies × 3 body sites). FASTQ data files of each sample that were generated by a DNBSEQ-G400 sequencer with the 2 × 100 bp paired-end sequencing protocol are available in the DDBJ Sequence Read Archive under accession number DRA015087 (RUN: DRR415616–DRR415633, BioProject: PRJDB14726, BioSample: SAMD00554139–SAMD00554156, Experiment: DRX401183–DRX401200). The data set is a fine-scale analysis of gene expression in the mite-infested A. cerana japonica workers because 18 RNA-Seq samples are separated by 3 body sites.
GABAergic neurons differentiated from BDNF- and Dlx2-modified neural stem cells restore disrupted neural circuits in brainstem stroke
Authors: Tang Xiangyue , Wu Li , Zhu Juehua , Xu Mindong , Li Shaojun , Zeng Guanfeng , Zhu Shuanggen , Jiang Yongjun 
Published: June 2023

Abstract
Background
Brainstem stroke causes severe and persistent neurological impairment. Due to the limited spontaneous recovery and regeneration of the disrupted neural circuits, transplantation of exogenous neural stem cells (NSCs) was an alternative, while there were limitations for primitive NSCs.

Methods
We established a mouse model of brainstem stroke by injecting endothelin in the right pons. Brain-derived neurotrophic factor (BDNF)- and distal-less homeobox 2 (Dlx2)-modified NSCs were transplanted to treat brainstem stroke. Transsynaptic viral tracking, immunostaining, magnetic resonance imaging, behavioral testing, and whole-cell patch clamp recordings were applied to probe the pathophysiology and therapeutic prospects of BDNF- and Dlx2-modified NSCs.

Results
GABAergic neurons were predominantly lost after the brainstem stroke. No endogenous NSCs were generated in situ or migrated from the neurogenesis niches within the brainstem infarct region. Co-overexpressions of BDNF and Dlx2 not only promoted the survival of NSCs, but also boosted the differentiation of NSCs into GABAergic neurons. Results from transsynaptic virus tracking, immunostaining, and evidence from whole-cell patch clamping revealed the morphological and functional integration of the grafted BDNF- and Dlx2-modified NSCs-derived neurons with the host neural circuits. Neurological function was improved by transplantation of BDNF- and Dlx2-modified NSCs in brainstem stroke.

Conclusions
These findings demonstrated that BDNF- and Dlx2-modified NSCs differentiated into GABAergic neurons, integrated into and reconstituted the host neural networks, and alleviated the ischemic injury. It thus provided a potential therapeutic strategy for brainstem stroke.
VTGAN: hybrid generative adversarial networks for cloud workload prediction
Authors: Maiyza Aya I. , Korany Noha O. , Banawan Karim , Hassan Hanan A. , Sheta Walaa M. 
Published: June 2023

AbstractEfficient resource management approaches have become a fundamental challenge for distributed systems, especially dynamic environment systems such as cloud computing data centers. These approaches aim at load-balancing or minimizing power consumption. Due to the highly dynamic nature of cloud workloads, traditional time series and machine learning models fail to achieve accurate predictions. In this paper, we propose novel hybrid VTGAN models. Our proposed models not only aim at predicting future workloads but also predicting the workload trend (i.e., the upward or downward direction of the workload). Trend classification could be less complex during the decision-making process in resource management approaches. Also, we study the effect of changing the sliding window size and the number of prediction steps. In addition, we investigate the impact of enhancing the features used for training using the technical indicators, Fourier transforms, and wavelet transforms. We validate our models using a real cloud workload dataset. Our results show that VTGAN models outperform traditional deep learning and hybrid models, such as LSTM/GRU and CNN-LSTM/GRU, concerning cloud workload prediction and trend classification. Our proposed model records an upward prediction accuracy ranging from $$95.4\%$$

95.4
%

to $$96.6\%$$

96.6
%

.