bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterodimerization of T cell engaging bispecific antibodies to enhance specificity against pancreatic ductal adenocarcinoma
Authors: Long Alan W , Xu Hong , Santich Brian H , Guo Hongfen , Hoseini Sayed Shahabuddin , de Stanchina Elisa , Cheung Nai-Kong V 
Published: April 2024

Abstract
Background
EGFR and/or HER2 expression in pancreatic cancers is correlated with poor prognoses. We generated homodimeric (EGFRxEGFR or HER2xHER2) and heterodimeric (EGFRxHER2) T cell-engaging bispecific antibodies (T-BsAbs) to direct polyclonal T cells to these antigens on pancreatic tumors.

Methods
EGFR and HER2 T-BsAbs were constructed using the 2 + 2 IgG-[L]-scFv T-BsAbs format bearing two anti-CD3 scFvs attached to the light chains of an IgG to engage T cells while retaining bivalent binding to tumor antigens with both Fab arms. A Fab arm exchange strategy was used to generate EGFRxHER2 heterodimeric T-BsAb carrying one Fab specific for EGFR and one for HER2. EGFR and HER2 T-BsAbs were also heterodimerized with a CD33 control T-BsAb to generate ‘tumor-monovalent’ EGFRxCD33 and HER2xCD33 T-BsAbs. T-BsAb avidity for tumor cells was studied by flow cytometry, cytotoxicity by T-cell mediated 51Chromium release, and in vivo efficacy against cell line-derived xenografts (CDX) or patient-derived xenografts (PDX). Tumor infiltration by T cells transduced with luciferase reporter was quantified by bioluminescence.

Results
The EGFRxEGFR, HER2xHER2, and EGFRxHER2 T-BsAbs demonstrated high avidity and T cell-mediated cytotoxicity against human pancreatic ductal adenocarcinoma (PDAC) cell lines in vitro with EC50s in the picomolar range (0.17pM to 18pM). They were highly efficient in driving human polyclonal T cells into subcutaneous PDAC xenografts and mediated potent T cell-mediated anti-tumor effects. Both EGFRxCD33 and HER2xCD33 tumor-monovalent T-BsAbs displayed substantially reduced avidity by SPR when compared to homodimeric EGFRxEGFR or HER2xHER2 T-BsAbs (∼150-fold and ∼6000-fold respectively), tumor binding by FACS (8.0-fold and 63.6-fold), and T-cell mediated cytotoxicity (7.7-fold and 47.2-fold), while showing no efficacy against CDX or PDX. However, if either EGFR or HER2 was removed from SW1990 by CRISPR-mediated knockout, the in vivo efficacy of heterodimeric EGFRxHER2 T-BsAb was lost.

Conclusion
EGFR and HER2 were useful targets for driving T cell infiltration and tumor ablation. Two arm Fab binding to either one or both targets was critical for robust anti-tumor effect in vivo. By engaging both targets, EGFRxHER2 heterodimeric T-BsAb exhibited potent anti-tumor effects if CDX or PDX were EGFR+HER2+ double-positive with the potential to spare single-positive normal tissue.
AMD1 promotes breast cancer aggressiveness via a spermidine-eIF5A hypusination-TCF4 axis
Authors: Liao Ruocen , Chen Xingyu , Cao Qianhua , Bai Longchang , Ma Chenglong , Dai Zhijun , Dong Chenfang 
Published: April 2024

Abstract
Background
Basal-like breast cancer (BLBC) is the most aggressive subtype of breast cancer due to its aggressive characteristics and lack of effective therapeutics. However, the mechanism underlying its aggressiveness remains largely unclear. S-adenosylmethionine decarboxylase proenzyme (AMD1) overexpression occurs specifically in BLBC. Here, we explored the potential molecular mechanisms and functions of AMD1 promoting the aggressiveness of BLBC.

Methods
The potential effects of AMD1 on breast cancer cells were tested by western blotting, colony formation, cell proliferation assay, migration and invasion assay. The spermidine level was determined by high performance liquid chromatography. The methylation status of CpG sites within the AMD1 promoter was evaluated by bisulfite sequencing PCR. We elucidated the relationship between AMD1 and Sox10 by ChIP assays and quantitative real-time PCR. The effect of AMD1 expression on breast cancer cells was evaluated by in vitro and in vivo tumorigenesis model.

Results
In this study, we showed that AMD1 expression was remarkably elevated in BLBC. AMD1 copy number amplification, hypomethylation of AMD1 promoter and transcription activity of Sox10 contributed to the overexpression of AMD1 in BLBC. AMD1 overexpression enhanced spermidine production, which enhanced eIF5A hypusination, activating translation of TCF4 with multiple conserved Pro-Pro motifs. Our studies showed that AMD1-mediated metabolic system of polyamine in BLBC cells promoted tumor cell proliferation and tumor growth. Clinically, elevated expression of AMD1 was correlated with high grade, metastasis and poor survival, indicating poor prognosis of breast cancer patients.

Conclusion
Our work reveals the critical association of AMD1-mediated spermidine-eIF5A hypusination-TCF4 axis with BLBC aggressiveness, indicating potential prognostic indicators and therapeutic targets for BLBC.
Insights into the action of phylogenetically diverse microbial expansins on the structure of cellulose microfibrils
Authors: Haddad Momeni Majid , Zitting Aleksi , Jäämuru Vilma , Turunen Rosaliina , Penttilä Paavo , Buchko Garry W. , Hiltunen Salla , Maiorova Natalia , Koivula Anu , Sapkota Janak , Marjamaa Kaisa , Master Emma R. 
Published: April 2024

Abstract
Background
Microbial expansins (EXLXs) are non-lytic proteins homologous to plant expansins involved in plant cell wall formation. Due to their non-lytic cell wall loosening properties and potential to disaggregate cellulosic structures, there is considerable interest in exploring the ability of microbial expansins (EXLX) to assist the processing of cellulosic biomass for broader biotechnological applications. Herein, EXLXs with different modular structure and from diverse phylogenetic origin were compared in terms of ability to bind cellulosic, xylosic, and chitinous substrates, to structurally modify cellulosic fibrils, and to boost enzymatic deconstruction of hardwood pulp.

Results
Five heterogeneously produced EXLXs (Clavibacter michiganensis; CmiEXLX2, Dickeya aquatica; DaqEXLX1, Xanthomonas sacchari; XsaEXLX1, Nothophytophthora sp.; NspEXLX1 and Phytophthora cactorum; PcaEXLX1) were shown to bind xylan and hardwood pulp at pH 5.5 and CmiEXLX2 (harboring a family-2 carbohydrate-binding module) also bound well to crystalline cellulose. Small-angle X-ray scattering revealed a 20–25% increase in interfibrillar distance between neighboring cellulose microfibrils following treatment with CmiEXLX2, DaqEXLX1, or NspEXLX1. Correspondingly, combining xylanase with CmiEXLX2 and DaqEXLX1 increased product yield from hardwood pulp by ~ 25%, while supplementing the TrAA9A LPMO from Trichoderma reesei with CmiEXLX2, DaqEXLX1, and NspEXLX1 increased total product yield by over 35%.

Conclusion
This direct comparison of diverse EXLXs revealed consistent impacts on interfibrillar spacing of cellulose microfibers and performance of carbohydrate-active enzymes predicted to act on fiber surfaces. These findings uncover new possibilities to employ EXLXs in the creation of value-added materials from cellulosic biomass.
Surgical management of renal cell carcinoma with subhepatic inferior vena cava tumor thrombus: a case report and review of the literature
Authors: Ademi Bekim , Jaha Luan , Haxhiu Isa , Çuni Xhevdet , Tahiri Afrim , Gashi Jetmir , Koshi Adhurim , Jaha Art 
Published: April 2024

Abstract
Background
Renal cell carcinomas are the most common form of kidney cancer in adults. In addition to metastasizing in lungs, soft tissues, bones, and the liver, it also spreads locally. In 2–10% of patients, it causes a thrombus in the renal or inferior vena cava vein; in 1% of patients thrombus reaches the right atrium. Surgery is the only curative option, particularly for locally advanced disease. Despite the advancements in laparoscopic, robotic and endovascular techniques, for this group of patients, open surgery continues to be among the best options.

Case report
Here we present a case of successful tumor thrombectomy from the infrahepatic inferior vena cava combined with renal vein amputation and nephrectomy. Our patient, a 58 year old Albanian woman presented to the doctors office with flank pain, weight loss, fever, high blood pressure, night sweats, and malaise. After a comprehensive assessment, which included urine analysis, complete blood count, electrolytes, renal and hepatic function tests, as well as ultrasonography and computed tomography, she was diagnosed with left kidney renal cell carcinoma involving the left renal vein and subhepatic inferior vena cava. After obtaining informed consent from the patient we scheduled her for surgery, which went well and without complications. She was discharged one week after to continue treatment with radiotherapy, chemotherapy, and immunotherapy.

Conclusion
Open surgery is a safe and efficient way to treat renal cell carcinoma involving the renal vein and inferior vena cava. It is superior to other therapeutic modalities. When properly done it provides acceptable long time survival and good quality of life to patients.
Stepwise combined cell transplantation using mesenchymal stem cells and induced pluripotent stem cell-derived motor neuron progenitor cells in spinal cord injury
Authors: Kim Jang-Woon , Kim Juryun , Mo Hyunkyung , Han Heeju , Rim Yeri Alice , Ju Ji Hyeon 
Published: April 2024

Abstract
Background
Spinal cord injury (SCI) is an intractable neurological disease in which functions cannot be permanently restored due to nerve damage. Stem cell therapy is a promising strategy for neuroregeneration after SCI. However, experimental evidence of its therapeutic effect in SCI is lacking. This study aimed to investigate the efficacy of transplanted cells using stepwise combined cell therapy with human mesenchymal stem cells (hMSC) and induced pluripotent stem cell (iPSC)-derived motor neuron progenitor cells (iMNP) in a rat model of SCI.

Methods
A contusive SCI model was developed in Sprague-Dawley rats using multicenter animal spinal cord injury study (MASCIS) impactor. Three protocols were designed and conducted as follows: (Subtopic 1) chronic SCI + iMNP, (Subtopic 2) acute SCI + multiple hMSC injections, and (Main topic) chronic SCI + stepwise combined cell therapy using multiple preemptive hMSC and iMNP. Neurite outgrowth was induced by coculturing hMSC and iPSC-derived motor neuron (iMN) on both two-dimensional (2D) and three-dimensional (3D) spheroid platforms during mature iMN differentiation in vitro.

Results
Stepwise combined cell therapy promoted mature motor neuron differentiation and axonal regeneration at the lesional site. In addition, stepwise combined cell therapy improved behavioral recovery and was more effective than single cell therapy alone. In vitro results showed that hMSC and iMN act synergistically and play a critical role in the induction of neurite outgrowth during iMN differentiation and maturation.

Conclusions
Our findings show that stepwise combined cell therapy can induce alterations in the microenvironment for effective cell therapy in SCI. The in vitro results suggest that co-culturing hMSC and iMN can synergistically promote induction of MN neurite outgrowth.

Graphical Abstract
Mesenchymal stem cells promote ovarian reconstruction in mice
Authors: Li Jiazhao , Fan Haonan , Liu Wei , Zhang Jing , Xiao Yue , Peng Yue , Yang Weijie , Liu Wenwen , He Yuanlin , Qin Lianju , Ma Xiang , Li Jing 
Published: April 2024

Abstract
Background
Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem.

Methods
In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay.

Results
Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary.

Conclusions
The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn’t proliferate in the reconstituted ovary, this discovery suggests a potential new and safe method for the application of MSCs in clinical fertility preservation by enhancing the success rate of cryo-thawed ovarian tissues after transplantation.
A first-in-human clinical study of laparoscopic autologous myoblast sheet transplantation to prevent delayed perforation after duodenal endoscopic mucosal dissection
Authors: Kanetaka Kengo , Maruya Yasuhiro , Higashi Miki , Yamaguchi Shun , Matsumoto Ryo , Kobayashi Shinichiro , Hashiguchi Keiichi , Oohashi Fumiya , Matsumura Masaki , Naka Takahiro , Sakai Yusuke , Nakao Kazuhiko , Miyagawa Shigeru , Eguchi Susumu 
Published: April 2024

Abstract
Background
The detection rate of superficial non-ampullary duodenal epithelial tumors (SNADETs) has recently been increasing. Large tumors may contain malignant lesions and early therapeutic intervention is recommended. Endoscopic mucosal dissection (ESD) is considered a feasible treatment modality, however, the anatomical and physiological characteristics of the duodenum create a risk of postoperative perforation after ESD.

Methods
To explore whether myoblast sheet transplantation could prevent delayed perforation after ESD, a first-in-human (FIH) clinical trial of laparoscopic autologous myoblast sheet transplantation after duodenal ESD was launched. Autologous myoblast sheets fabricated from muscle tissue obtained seven weeks before ESD were transplanted laparoscopically onto the serous side of the ESD. The primary endpoints were the onset of peritonitis due to delayed perforation within three days after surgery and all adverse events during the follow-up period.

Results
Three patients with SNADETs ≥ 20 mm in size underwent transplantation of a myoblast sheet onto the serous side of the duodenum after ESD. In case 1, The patient’s postoperative course was uneventful. Endoscopy and abdominal computed tomography revealed no signs of delayed perforation. Despite incomplete mucosal closure in case 2, and multiple micro perforations during ESD in case 3, cell sheet transplantation could prevent the postoperative massive perforation after ESD, and endoscopy on day 49 after transplantation revealed no stenosis.

Conclusions
This clinical trial showed the safety, efficacy, and procedural operability of this novel regenerative medicine approach involving transplanting an autologous myoblast sheet laparoscopically onto the serosa after ESD in cases with a high risk of delayed perforation. This result indicates the potential application of cell sheet medicine in treating various abdominal organs and conditions with minimal invasiveness in the future.

Trial registration
jRCT, jRCT2073210094. Registered November 8 2021,
https://jrct.niph.go.jp/latest-detail/jRCT2073210094.
Physical mechanism for the temporary intensification of wintertime sporadic E layers in 2009
Authors: Andoh Satoshi , Saito Akinori , Shinagawa Hiroyuki 
Published: April 2024

AbstractThis study provides a physical mechanism for the temporary intensification of wintertime sporadic E layers (EsLs) in 2009. It is widely accepted that vertical wind shears control EsL formations. EsL intensity is minimal in winter, partially because of the weakened vertical wind shears. Despite the wintertime minimum EsL intensity, temporary intensifications of EsLs occurred for 10–30 days in some winters, the cause of which remains unclear. In this study, we conducted month-long EsL simulations in 2009 and 2011, the years when both wintertime EsL (WiEsL) intensification and sudden stratospheric warming (SSW) occurred, and when neither did, respectively. The simulations aimed to reveal the physical mechanisms of the WiEsL intensification in 2009. We succeeded in reproducing the occurrence and non-occurrence of temporary WiEsL intensification in 2009 and 2011, respectively, observed by an ionosonde at Kokubunji, Japan, although day-to-day variations in WiEsL intensity were not reproduced well. Evidently, the temporary WiEsL intensification is attributed to vertical ion convergence (VIC) intensification at altitudes of 100–120 km between 4 and 8 local time (LT) and particularly after 15 LT. The VIC intensification is caused primarily by the vertical wind shears of SW2 tides, westward propagating semi-diurnal tides with wavenumber 2. The SW2 intensification is driven by the major SSW in January–February 2009. Additionally, 6–8-day planetary waves can also affect the WiEsL intensification superposed on the SW2 amplification effects.
Graphical Abstract
Myofibroma of the pinna: a case report and review of the literature
Authors: Bhatt Nupur , Pan Lydia , Ben-Dov Tom , Rickert Scott 
Published: April 2024

Abstract
Background
Myofibromas are rare mesenchymal tumors with a predilection for the head, neck, and oral cavity. Primarily affecting infants and young children, these tumors typically manifest as superficial painless nodules. Diagnosis is confirmed through histopathological examination of a biopsy, revealing nodules characterized by spindle cell proliferation. To our knowledge, only two cases of pinna myofibroma have been previously reported in the literature.

Case presentation
Here, we present the case of a three-year-old male who developed a myofibroma of the left auricle following trauma to the area one year earlier. The patient underwent surgical resection without any postoperative complications. The patient later returned with a lesion consistent with hypertrophic scar.

Conclusions
This study aims to provide a comprehensive review of the clinical presentation, histopathologic and immunohistochemical features, and surgical management of this unique case of myofibroma of the pinna.
An optimized CT-dense agent perfusion and micro-CT imaging protocol for chick embryo developmental stages
Authors: Naïja Azza , Mutlu Onur , Khan Talha , Seers Thomas Daniel , Yalcin Huseyin C. 
Published: April 2024

AbstractCompared to classical techniques of morphological analysis, micro-CT (μ-CT) has become an effective approach allowing rapid screening of morphological changes. In the present work, we aimed to provide an optimized micro-CT dense agent perfusion protocol and μ-CT guidelines for different stages of chick embryo cardiogenesis. Our study was conducted over a period of 10 embryonic days (Hamburger-Hamilton HH36) in chick embryo hearts. During the perfusion of the micro-CT dense agent at different developmental stages (HH19, HH24, HH27, HH29, HH31, HH34, HH35, and HH36), we demonstrated that durations and volumes of the injected contrast agent gradually increased with the heart developmental stages contrary to the flow rate that was unchanged during the whole experiment. Analysis of the CT imaging confirmed the efficiency of the optimized parameters of the heart perfusion.
Exercise Training Attenuates the Muscle Mitochondria Genomic Response to Bed Rest
Authors: COTTER JOSHUA A. , PLAZA-FLORIDO ABEL , ADAMS GREGORY R. , HADDAD FADIA , SCOTT JESSICA M. , EVERETT MEGHAN , PLOUTZ-SNYDER LORI , RADOM-AIZIK SHLOMIT 
Published: April 2024

ABSTRACT

Purpose
Exercise training during the National Aeronautics and Space Administration 70-d bed rest study effectively counteracted the decline in aerobic capacity, muscle mass, strength, and endurance. We aimed to characterize the genomic response of the participants’ vastus lateralis on day 64 of bed rest with and without exercise countermeasures.

Methods
Twenty-two healthy young males were randomized into three groups: 1) bed rest only (n = 7), 2) bed rest + aerobic (6 d·wk−1) and resistance training (3 d·wk−1) on standard equipment (n = 7), and 3) bed rest + aerobic and resistance training using a flywheel device (n = 8). The vastus lateralis gene and microRNA microarrays were analyzed using GeneSpring GX 14.9.1 (Agilent Technologies, Palo Alto, CA).

Results
Bed rest significantly altered the expression of 2113 annotated genes in at least one out of the three study groups (fold change (FC) > 1.2; P < 0.05). Interaction analysis revealed that exercise attenuated the bed rest effect of 511 annotated genes (FC = 1.2, P < 0.05). In the bed rest only group, a predominant downregulation of genes was observed, whereas in the two exercise groups, there was a notable attenuation or reversal of this effect, with no significant differences between the two exercise modalities. Enrichment analysis identified functional categories and gene pathways, many of them related to the mitochondria. In addition, bed rest significantly altered the expression of 35 microRNAs (FC > 1.2, P < 0.05) with no difference between the three groups. Twelve are known to regulate some of the mitochondrial-related genes that were altered following bed rest.

Conclusions
Mitochondrial gene expression was a significant component of the molecular response to long-term bed rest. Although exercise attenuated the FC in the downregulation of many genes, it did not completely counteract all the molecular consequences.