bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive bioinformatic analysis of the expression and prognostic significance of TSC22D domain family genes in adult acute myeloid leukemia
Authors: Xu XiaoQiang , Sun Rui , Li YuanZhang , Wang JiaXi , Zhang Meng , Xiong Xia , Xie DanNi , Jin Xin , Zhao MingFeng 
Published: May 2023

Abstract
Background
TSC22D domain family genes, including TSC22D1-4, play a principal role in cancer progression. However, their expression profiles and prognostic significance in adult acute myeloid leukemia (AML) remain unknown.

Methods
The online databases, including HPA, CCLE, EMBL-EBI, GEPIA2, BloodSpot, GENT2, UCSCXenaShiny, GSCALite, cBioportal, and GenomicScape, utilized the data of TCGA and GEO to investigate gene expression, mutation, copy number variation (CNV), and prognostic significance of the TSC22D domain family in adult AML. Computational analysis of resistance (CARE) was used to explore the effect of TSC22D3 expression on drug response. Functional enrichment analysis of TSC22D3 was performed in the TRRUST Version 2 database. The STRING, Pathway Commons, and AnimalTFDB3.0 databases were used to investigate the protein–protein interaction (PPI) network of TSC22D3. Harmonizome was used to predict target genes and kinases regulated by TSC22D3. The StarBase v2.0 and CancermiRNome databases were used to predict miRNAs regulated by TSC22D3. UCSCXenaShiny was used to investigate the correlation between TSC22D3 expression and immune infiltration.

Results
Compared with normal adult hematopoietic stem cells (HSCs), the expression of TSC22D3 and TSC22D4 in adult AML tissues was markedly up-regulated, whereas TSC22D1 expression was markedly down-regulated. The expression of TSC22D1 and TSC22D3 was significantly increased in adult AML tissues compared to normal adult tissues. High TSC22D3 expression was significantly associated with poor overall survival (OS) and event-free survival (EFS) in adult AML patients. Univariate and multivariate Cox analysis showed that overexpression of TSC22D3 was independently associated with adverse OS of adult AML patients. High TSC22D3 expression had a adverse impact on OS and EFS of adult AML patients in the chemotherapy group. TSC22D3 expression correlated with drug resistance to BCL2 inhibitors. Functional enrichment analysis indicated that TSC22D3 might promote AML progression. MIR143-3p sponging TSC22D3 might have anti-leukemia effect in adult AML.

Conclusions
A significant increase in TSC22D3 expression was observed in adult AML tissues compared to normal adult HSCs and tissues. The prognosis of adult AML patients with high TSC22D3 expression was unfavorable, which could severe as a new prognostic biomarker and potential target for adult AML.
The inhibitory receptors PD1, Tim3, and A2aR are highly expressed during mesoCAR T cell manufacturing in advanced human epithelial ovarian cancer
Authors: Akbari Behnia , Soltantoyeh Tahereh , Shahosseini Zahra , Yarandi Fariba , Hadjati Jamshid , Mirzaei Hamid Reza 
Published: May 2023

Abstract
Background
Chemotherapy and surgery have been the mainstays of epithelial ovarian cancer (EOC) treatment so far. Cellular immunotherapies such as CAR T cell therapy have recently given hope of a cure for solid tumors like EOC. However, extrinsic factors associated with the CAR T cell manufacturing process and/or intrinsic dysregulation of patient-derived T cells, which could be associated with cancer itself, cancer stage, and treatment regimen, may hamper the efficacy of CAR T cell therapy and promote their exhaustion or dysfunction.

Methods
To investigate the association of these factors with CAR T cell exhaustion, the frequency of T and CAR T cells expressing three immune inhibitory receptors (i.e., TIM3, PD1, A2aR) generated from T cells of EOC patients and healthy controls was measured during each stage of CAR T cell production.

Results
Our findings revealed that primary T cells from EOC patients show significantly elevated expression of immune inhibitory receptors, and this increase was more prominent in patients undergoing chemotherapy and those with advanced cancer. In addition, the CAR T cell manufacturing process itself was found to upregulate the expression of these inhibitory receptors and more importantly increase the population of exhausted mesoCAR T cells.

Conclusions
Our observations suggest that intrinsic characteristics of patient-derived T cells and extrinsic factors in CAR T cell production protocols should be considered and properly counteracted during CAR T cell manufacturing process. In addition, mitigating the signaling of immune inhibitory receptors through pharmacological/genetic perturbation during CAR T cell manufacturing might profoundly improve CAR T cells function and their antitumor activity in EOC and other solid tumors.
A novel incision technique of a totally implanted venous access port in the upper arm for patients with breast cancer
Authors: Song Xue , Chen Shengying , Dai Yan , Sun Yang , Lin Xiaojie , He Jiafa , Xu Rui 
Published: May 2023

Abstract
Background
A totally implanted venous access port (TIVAP) in the upper arm is a safe and cost-effective vascular access device and is widely used in breast cancer patients. Traditional tunnelling technique increases the operation time and has an unsatisfied cosmetic effect, so we explored the feasibility, cosmetic effect and complications of an upper arm port with a novel incision in this retrospective study.

Methods
We reviewed 489 cases of totally implantable venous access port implantation in the upper arm with two types of incisions in our centre from 1 January 2018 to 30 January 2022. The patients were divided into two different incision groups including the puncture site incision group (n = 282) and the conventional tunnelling group (n = 207). The comparison of the results was collected between the two groups, and contributing factors were analyzed for major complications.

Results
A total of 489 patients were successfully implanted with arm ports using the puncture site incision technique (n = 282, 57.7%) and conventional tunnelling technique (n = 207, 42.3%). The average operation time of the two types of incisions was 36.5 ± 15 min in the puncture site incision group and 55 ± 18.1 min in the tunnel needle group (P < 0.05). In terms of complications, 33 catheter-related complications occurred (6.4%), including 9 cases of infection, 15 cases of catheter-related thrombosis and 7 cases of skin exposure. Fourteen patients in the puncture site incision group developed complications compared with 17 in the traditional incision group. There were no significant differences between the two groups in terms of overall complication events (5.0% and 8.2%, P = 0.145) while the same result was found in each complication event. Weight, total cholesterol and diabetes were found to be associated with device-related infections in the univariate Cox proportional hazard regression models. Diabetes was found to be associated with device-related infections in multivariate analysis while hypertension was associated with thrombosis.

Conclusions
The puncture site incision method is a novel technique with a better cosmetic appearance and less operation time than the traditional tunnelling technique, providing a comparable overall rate of complications. It offers a preferable choice for clinicians when dealing with different situations of patients. It is worthy of being used and promoted for patients requiring the totally implanted venous access port in the upper arm.
Cerebellar connectome alterations and associated genetic signatures in multiple sclerosis and neuromyelitis optica spectrum disorder
Authors: Yang Yuping , Li Junle , Li Ting , Li Zhen , Zhuo Zhizheng , Han Xuemei , Duan Yunyun , Cao Guanmei , Zheng Fenglian , Tian Decai , Wang Xinli , Zhang Xinghu , Li Kuncheng , Zhou Fuqing , Huang Muhua , Li Yuxin , Li Haiqing , Li Yongmei , Zeng Chun , Zhang Ningnannan , Sun Jie , Yu Chunshui , Shi Fudong , Asgher Umer , Muhlert Nils , Liu Yaou , Wang Jinhui 
Published: May 2023

Abstract
Background
The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown.

Methods
Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles.

Results
Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases.

Conclusions
We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases.
Suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cell gene delivery vehicles in recurrent glioblastoma multiforme: a first-in-human, dose-escalation, phase I clinical trial
Authors: Oraee-Yazdani Saeed , Tavanaei Roozbeh , Rostami Fatemeh , Hajarizadeh Atieh , Mehrabadi Marzieh , Akhlaghpasand Mohammadhosein , Tamaddon Mona , Khannejad Samin , Yazdani Kaveh Oraii , Zali Alireza 
Published: May 2023

Abstract
Background
Glioblastoma multiforme (GBM) is associated with remarkably poor prognosis, and its treatment is challenging. This investigation aimed to evaluate the safety of suicide gene therapy using allogeneic adipose tissue-derived mesenchymal stem cells (ADSCs) carrying herpes simplex virus-thymidine kinase (HSV-TK) gene for the first time in patients with recurrent GBM.

Methods
This study was a first-in-human, open-label, single-arm, phase I clinical trial with a classic 3 + 3 dose escalation design. Patients who did not undergo surgery for their recurrence were included and received this gene therapy protocol. Patients received the intratumoral stereotactic injection of ADSCs according to the assigned dose followed by prodrug administration for 14 days. The first dosing cohort (n = 3) received 2.5 × 105 ADSCs; the second dosing cohort (n = 3) received 5 × 105 ADSCs; the third dosing cohort (n = 6) received 10 × 105 ADSCs. The primary outcome measure was the safety profile of the intervention.

Results
A total of 12 patients with recurrent GBM were recruited. The median follow-up was 16 (IQR, 14-18.5) months. This gene therapy protocol was safe and well tolerated. During the study period, eleven (91.7%) patients showed tumor progression, and nine (75.0%) died. The median overall survival (OS) was 16.0 months (95% CI 14.3–17.7) and the median progression-free survival (PFS) was 11.0 months (95% CI 8.3–13.7). A total of 8 and 4 patients showed partial response and stable disease, respectively. Moreover, significant changes were observed in volumetric analysis, peripheral blood cell counts, and cytokine profile.

Conclusions
The present clinical trial, for the first time, showed that suicide gene therapy using allogeneic ADSCs carrying the HSV-TK gene is safe in patients with recurrent GBM. Future phase II/III clinical trials with multiple arms are warranted to validate our findings and further investigate the efficacy of this protocol compared with standard therapy alone.
Trial registration: Iranian Registry of Clinical Trials (IRCT), IRCT20200502047277N2. Registered 8 October 2020, https://www.irct.ir/.
Stressor control and regional inflammatory responses in the brain: regulation by the basolateral amygdala
Authors: Adkins Austin M. , Colby Emily M. , Kim Woong-Ki , Wellman Laurie L. , Sanford Larry D. 
Published: May 2023

AbstractIncreasing evidence has connected the development of certain neuropsychiatric disorders, as well as neurodegenerative diseases, to stress-induced dysregulation of the immune system. We have shown that escapable (ES) and inescapable (IS) footshock stress, and memories associated with ES or IS, can differentially alter inflammatory-related gene expression in brain in a region dependent manner. We have also demonstrated that the basolateral amygdala (BLA) regulates stress- and fear memory-induced alterations in sleep, and that differential sleep and immune responses in the brain to ES and IS appear to be integrated during fear conditioning and then reproduced by fear memory recall. In this study, we investigated the role of BLA in influencing regional inflammatory responses within the hippocampus (HPC) and medial prefrontal cortex (mPFC) by optogenetically stimulating or inhibiting BLA in male C57BL/6 mice during footshock stress in our yoked shuttlebox paradigm based on ES and IS. Then, mice were immediately euthanized and RNA extracted from brain regions of interest and loaded into NanoString® Mouse Neuroinflammation Panels for compilation of gene expression profiles. Results showed differential regional effects in gene expression and activated pathways involved in inflammatory-related signaling following ES and IS, and these differences were altered depending on amygdalar excitation or inhibition. These findings demonstrate that the stress-induced immune response, or “parainflammation”, is affected by stressor controllability and that BLA influences regional parainflammation to ES or IS in HPC and mPFC. The study illustrates how stress-induced parainflammation can be regulated at the neurocircuit level and suggests that this approach can be useful for uncovering circuit and immune interactions in mediating differential stress outcomes.
“Evaluation of ROS1 expression and rearrangements in a large cohort of early-stage lung cancer”
Authors: Dyrbekk Anne Pernille Harlem , Warsame Abdirashid Ali , Suhrke Pål , Ludahl Marianne Odnakk , Moe Joakim Oliu , Eide Inger Johanne Zwicky , Lund-Iversen Marius , Brustugun Odd Terje 
Published: May 2023

Abstract
Background
ROS1 fusion is an infrequent, but attractive target for therapy in patients with metastatic non- small-cell lung cancer. In studies on mainly late-stage disease, the prevalence of ROS1 fusions is about 1–3%. In early-stage lung cancer ROS1 might also provide a fruitful target for neoadjuvant or adjuvant therapy. In the present study, we investigated the prevalence of ROS1 fusion in a Norwegian cohort of early-stage lung cancer. We also explored whether positive ROS1 immunohistochemical (IHC) stain was associated with certain mutations, clinical characteristics and outcomes.

Methods
The study was performed using biobank material from 921 lung cancer patients including 542 patients with adenocarcinoma surgically resected during 2006–2018. Initially, we screened the samples with two different IHC clones (D4D6 and SP384) targeting ROS1. All samples that showed more than weak or focal staining, as well as a subgroup of negative samples, were analyzed with ROS1 fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) with a comprehensive NGS DNA and RNA panel. Positive ROS1-fusion was defined as those samples positive in at least two of the three methods (IHC, FISH, NGS).

Results
Fifty cases were IHC positive. Of these, three samples were both NGS and FISH-positive and considered positive for ROS1 fusion. Two more samples were FISH positive only, and whilst IHC and NGS were negative. These were also negative with Reverse Transcription quantitative real time Polymerase Chain Reaction (RT-qPCR). The prevalence of ROS1 fusion in adenocarcinomas was 0.6%. All cases with ROS1 fusion had TP53 mutations. IHC-positivity was associated with adenocarcinoma. Among SP384-IHC positive cases we also found an association with never smoking status. There was no association between positive IHC and overall survival, time to relapse, age, stage, sex or pack-year of smoking.

Conclusions
ROS1 seems to be less frequent in early-stage disease than in advanced stages. IHC is a sensitive, but less specific method and the results need to be confirmed with another method like FISH or NGS.
The impact of variable illumination on vegetation indices and evaluation of illumination correction methods on chlorophyll content estimation using UAV imagery
Authors: Wang Yuxiang , Yang Zengling , Kootstra Gert , Khan Haris Ahmad 
Published: May 2023

AbstractBackgroundThe advancements in unmanned aerial vehicle (UAV) technology have recently emerged as an effective, cost-efficient, and versatile solution for monitoring crop growth with high spatial and temporal precision. This monitoring is usually achieved through the computation of vegetation indices (VIs) from agricultural lands. The VIs are based on the incoming radiance to the camera, which is affected when there is a change in the scene illumination. Such a change will cause a change in the VIs and subsequent measures, e.g., the VI-based chlorophyll-content estimation. In an ideal situation, the results from VIs should be free from the impact of scene illumination and should reflect the true state of the crop’s condition. In this paper, we evaluate the performance of various VIs computed on images taken under sunny, overcast and partially cloudy days. To improve the invariance to the scene illumination, we furthermore evaluated the use of the empirical line method (ELM), which calibrates the drone images using reference panels, and the multi-scale Retinex algorithm, which performs an online calibration based on color constancy. For the assessment, we used the VIs to predict leaf chlorophyll content, which we then compared to field measurements.ResultsThe results show that the ELM worked well when the imaging conditions during the flight were stable but its performance degraded under variable illumination on a partially cloudy day. For leaf chlorophyll content estimation, The$$r^2$$r2of the multivariant linear model built by VIs were 0.6 and 0.56 for sunny and overcast illumination conditions, respectively. The performance of the ELM-corrected model maintained stability and increased repeatability compared to non-corrected data. The Retinex algorithm effectively dealt with the variable illumination, outperforming the other methods in the estimation of chlorophyll content. The$$r^2$$r2of the multivariable linear model based on illumination-corrected consistent VIs was 0.61 under the variable illumination condition.ConclusionsOur work indicated the significance of illumination correction in improving the performance of VIs and VI-based estimation of chlorophyll content, particularly in the presence of fluctuating illumination conditions.
Iodine-supported implants in prevention and treatment of surgical site infections for compromised hosts: a prospective study
Authors: Shirai Toshiharu , Tsuchiya Hiroyuki , Terauchi Ryu , Tsuchida Shinji , Shimomura Seiji , Kajino Yoshitomo , Takahashi Kenji 
Published: May 2023

Abstract
Background
Surgical site infection (SSI) is a common complication following orthopedic implantation. We developed an iodine coating for titanium implants to reduce implant-related infections and conducted a prospective clinical study to evaluate the efficacy and potential drawbacks of iodine-supported implants.

Patients and methods
Between July 2008 and July 2017, 653 patients (377 male and 27 female patients; mean age, 48.6) with postoperative infection or a compromised status were treated using iodine-loaded titanium implants. The mean follow-up period was 41.7 months. In 477 patients, iodine-supported implants were used to prevent infection and in 176 patients, to treat active infection (one-stage surgery, 89 patients; two-stage surgery, 87 patients). In the limbs and pelvis, the primary diagnoses included the following: 161 tumors, 92 deformities/shortening, 47 pseudarthrosis, 42 fractures, 32 infected TKA, 25 osteoarthritis, 21 pyogenic arthritis, 20 infected THA, and 6 osteomyelitis. In the spinal cases, there were 136 cases of tumors, 36 cases of pyogenic spondylitis, and 35 cases of degeneration. Five modes of implant failure were identified and classified as follows: soft tissue failure (type 1), aseptic loosening (type 2), structural failure (type 3), infection (type 4), and tumor progression (type 5).

Results
The overall failure rate in our series was 26.3% (172/653). There were 101 mechanical failures, including 22 type 1, 20 type 2, and 59 type 3 failures. Non-mechanical causes accounted for 71 failures, including 45 type 4 and 26 type 5 failures. The overall incidence of infections was 6.8%. The mean time to the onset of infection after implantation was 9.1 months. The overall infection rate was 3.7% in the prevention cases and 15.3% in the treatment cases. There was no difference between one-stage replacement (14.6%) and two-stage replacement (16.0%). There were 11 cases of treatment for SSI of spine surgery, and the re-infection rate was 0% using iodine-coated instruments.

Conclusions
The five modes of failure of the iodine-supported implant were satisfactory compared with previous reports. In particular, because the infection rate of iodine-coated implants used for compromised hosts is low compared with other methods, postoperative infection is more easily controlled. It can be considered highly effective for spinal infections that require one-stage revision surgery.
Level of evidence IV.
Trial registration Prospective, Observation study.