bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small molecule screen employing patient-derived iPSC hepatocytes identifies LRRK2 as a novel therapeutic target for Alpha1 Antitrypsin Deficiency
Authors: Kent Deniz , Ng Soon Seng , Khoshkenar Payam , Syanda Adam , Li Chao Zheng , Zieger Marina , Hatch Stephanie , Segal Joe , Blackford Samuel , Le Kaixing , Chowdary Vivek , Ismaili Taylor , Danovi Davide , Lewis Patrick , Sahdeo Sunil , Ebner Daniel , Mueller Christian , Rashid S. Tamir 
Published: February 2022

Abstract
Alpha-1 antitrypsin deficiency (A1ATD) is a life-threatening condition caused by inheritance of the SERPINA1-Z genetic variant (PiZ) leading to protein misfolding and liver toxicity. There remain no approved medicines for this disease. Here we report the results of a small molecule screen performed in patient-derived iPSC hepatocytes that identified Leucine-rich repeat kinase-2 (LRRK2), as a potentially new therapeutic target. Genetic deletion of LRRK2 in PiZ mice reduced both intrahepatic misfolded polymers and fibrosis leading us to test a library of commercially available LRRK2 inhibitors across several cell models. One of these molecules, CZC-25146, a candidate with favourable pharmacokinetic properties, reduced polymer load, increased normal AAT secretion and reduced inflammatory cytokines in both cells and the PiZ mouse. Mechanistically, this effect was achieved via inhibition of LRRK2 kinase activity and autophagy induction. These findings support the use of CZC-25146 (and potentially LRRK2 inhibitors more broadly) in hepatic proteinopathy disease research and as potential new therapies.
Implantable niche with local immunosuppression for islet allotransplantation achieves type 1 diabetes reversal.
Authors: Paez-Mayorga Jesus , Campa-Carranza Jocelyn , Capuani Simone , Hernandez Nathanael , Chua Ying , Pons-Faudoa Fernanda , Malgir Gulsah , Alvarez Bella , Niles Jean , Shelton Kathryn , Kezar Sarah , Nehete Pramod , Berman-Weinberg Dora , Li Xian , Ricordi Camillo , Nichols Joan , Gaber Ahmed , Kenyon Norma , Grattoni Alessandro 
Published: February 2022

Abstract
Pancreatic islet transplantation efficacy for type 1 diabetes (T1D) management is limited by hypoxia-related graft attrition and need for systemic immunosuppression. To overcome these challenges, we developed the Neovascularized Implantable Cell Homing and Encapsulation (NICHE) device, which integrates direct vascularization for facile mass transfer and localized immunosuppressant delivery for islet rejection prophylaxis. Here, we investigated NICHE efficacy for allogeneic islet transplantation and long-term diabetes reversal in an immunocompetent rat model. We demonstrated that polyamide is superior to resin for NICHE subQ integration and vascularization. We demonstrated allogeneic islets transplanted within pre-vascularized NICHE were engrafted, revascularized, and reverted diabetes in rats for over 150 days. Notably, we confirmed that localized immunosuppression prevented islet rejection without inducing toxicity or systemic immunosuppression. Moreover, for translatability efforts, we showed NICHE biocompatibility and feasibility of deployment, as well as short-term allogeneic islet engraftment in an MHC-mismatched nonhuman primate model. In sum, the NICHE is a safe and effective platform for islet transplantation and long-term T1D management.
Thyroid dysfunction induced by immune checkpoint inhibitors and tumor progression in neoadjuvant therapy for Non-Small Cell Lung Cancer: a case report and literature review
Authors: Li Xinyi , Wang Xun , Wang Shaodong , Liu Yanguo , Wang Ruilin , Liu Yi , Huang Lin , Feng Yufei , Xie Xiaohui , Shi Luwen 
Published: February 2022

Abstract
BackgroundThe immune checkpoint inhibitors (ICIs) targeting anti-programmed death receptor 1 (PD-1) and its ligand (PD-L1) has shown promising value in resectable (stage I-IIIA) or potentially resectable (stage IIIB) non-small-cell lung cancer (NSCLC). However, the immune-related adverse events (irAEs) and tumor progression in neoadjuvant therapy are of great concern, which might result in surgical delay or failure to undergo resection. In addition, the association between the development of thyroid dysfunction and the cancer outcomes was controversial and highly concerned.Case presentationA 59-year-old male with NSCLC (squamous, IIIA) was received neoadjuvant immunotherapy in combination with chemotherapy before surgery. However, ICIs-related thyroid dysfunction occurred, and the patient experienced transient hyperthyroidism then transformed into hypothyroidism. Moreover, the patient suffered from tumor progression and was unable to undergo resection. He refused immunotherapy and was given chemotherapy for the subsequent treatment.ConclusionsWe presented the case of ICIs-related thyroid dysfunction and failure to undergo resection because of poor efficacy to elucidate clinical features of irAEs and tumor progression in the neoadjuvant immunotherapy, so as to timely and properly monitor the efficacy and safety of neoadjuvant immunotherapy in resectable NSCLC patients in clinical practice. Our case also demonstrated that the development of ICIs-related thyroid dysfunction might not predict the good efficacy of ICIs in NSCLC.
Simple and Improved Plasmonic Sensor Configuration Established on Mim Waveguide for Enhanced Sensing Performance
Authors: Butt Muhammad Ali , Khonina Svetlana Nikolaevna , Kazanskiy Nikolay Lvovich 
Published: February 2022

Abstract
Herein, two simple configurations of Fano resonance-based plasmonic sensors are proposed for temperature and biosensing applications. The device optimization and sensing performance are numerically investigated via two dimensional-finite element method (2D-FEM). The former configuration is quite simple and based on the side coupled circular cavity (SCCC) whereas in the latter the circular cavity is encapsulated in the ring separated by a small gap and is known as ring encapsulated circular cavity (RECC). For temperature sensing applications, polydimethylsiloxane (PDMS) is utilized as a thermal sensing medium in the circular cavity. The numerical analysis has revealed that the temperature sensitivity (S) of SCCC and RECC configuration is ~ -0.58 nm/oC and -0.64 nm/oC, respectively. The figure of merit (FOM) is another important parameter to analyze the sensing performance which is around 8.6 and 1955.2 for SCCC and RECC configuration, respectively. The sensing capabilities of the biosensor designs are investigated by injecting dielectric materials of different refractive indices in the circular cavity ranges between 1.33 and 1.37. The S of the SCCC and RECC sensor configuration is around 1240 nm/RIU and 1350 nm/RIU, respectively with a FOM of 18.74 RIU-1 and 691 RIU-1. The RECC sensor configuration is considered to be straightforward with fewer fabrication complications and offers high sensing performance.
Introgression of the Low Phytic Acid Locus (lpa2) Into Elite Maize (Zea Mays L.) Inbreds Through Marker-Assisted Backcross Breeding (MABB)
Authors: Yathish K.R. , Karjagi Chikkappa Gangadhar , Gangoliya Shivraj Singh , Kumar Arun , Preeti Preeti , Yadav Hemant Kumar , Srivast Shraddha , Kumar Santosh , Swmay HK M , Singh Alla , Phagna Ramesh Kumar , Das Abhijit Kumar , Sekhar Javaji Chandra , Hossain Firoz , Rakshit Sujay , Gadag Ravindra N 
Published: February 2022

Abstract
Phytic acid (PA) is an important antinutritional component in maize that affects the availability of major micro-nutrients like di- and multi-valent mineral cations like iron (Fe) and zinc (Zn). The long-term consumption of maize as a staple food crop leads to micronutrient malnutrition especially iron and zinc deficiency in the human population. In addition, it also acts as a storehouse of a major part of mineral phosphorous (P), approximately 80% of the total P stored as phytate P is not available to mono-gastric animals like humans and poultry birds, and it gets excreted as such leading to one of the major environmental pollution called eutrophication. Of the various low phytic acid (lpa) mutants, lpa2-2 generated through mutagenesis reduces PA by 30%. BML 6 and BML 45, the parents of the popular maize hybrid DHM 121 with high PA were selected to introgress lpa2-2 through marker-assisted backcross breeding (MABB). The percent recurrent parental genome (RPG) in the selected BC2F2 plants ranged from 88.68 - 91.04% and 90.09 - 91.51% in the genetic background of BML 6 and BML 45, respectively. Based on the highest percentage of RPG, best five BC2F2 plants, viz., #3190, #3283, #3230, #3263 and #3292 with RPG 88.68 - 91.04% in the genetic background of BML 6 and #3720, #3776, #3717, #3828 and #3832 with RPG 90.09 - 91.51% in the genetic background of BML 45 were advanced to BC2F3. The newly developed near-isogenic lines (NILs) possessed low phytate content (2.37 mg/g in BML 6 and 2.40 mg/g in BML 45) compared to 3.59 mg/g and 3.16 mg/g in recurrent parents BML 6 and BML 45, respectively thereby reducing the phytate by an average of 34 and 24 per cent, respectively. These newly developed progenies were similar to their recurrent parents for various morphological traits. These inbreds assume great significance in alleviating Fe and Zn deficiencies in worldwide.
Application of anchoring of the projection point on the inner upper edge of the pedicle in minimally invasive posterior cervical foraminotomy (MI-PCF)
Authors: Wang Kai , Zhao Bin , Yuan Jie , Xu Chaojian , Fang Ge , Zhao Zhenjian , Wang Yongfeng 
Published: February 2022

Abstract
Purpose To describe a new modified MI-PCF, and evaluate its feasibility/short-term efficacy.Method Data from 21 patients with cervical spondylotic radiculopathy who were treated with the modified MI-PCF were collected. Patients’ preoperative/postoperative neck and arm pain were evaluated by the VAS, JOA and modified MacNab scores. The postoperative decompression effect was evaluated by CT and MRI. Cervical CT was performed for 3D reconstruction of the patients’ cervical spine. A cross section through the intersection of the inner and upper edges of the pedicle was used to measure the distance between the projection point on the inner upper edge of the C3-7 pedicle and the V point (a)/the midline of the spinous process (b). This distance was also measured in human cadavers(c)/(d).Result The operation was successful in all patients. The mean operative duration was 70.1± 20.0 min, and the mean number of fluoroscopies was 4.0± 0.9 times. The VAS, JOA and modified MacNab scores were all significantly improved. The values of a, b, c, and d for C3-7 were 1.43 ± 0.07 ~ 4.98 ± 0.22 mm, 14.00 ± 0.29 ~ 16.35 ± 0.45 mm, 1.47± 0.08 ~ 5.08 ± 0.25 mm, and 14.04 ± 0.32 ~ 16.36± 0.43 mm, respectively.Conclusion The number of fluoroscopies and the operative duration were reduced by the anchoring of the projection point on the inner upper edge of the pedicle. Overall this study describes a new method for positioning and verification of the V point in MI-PCF.
Unusual features of lattice dynamics in lawsonite related to its phase transitions: a study using broad-band dielectric spectroscopy
Authors: Kadlec Filip , Nuzhnyy Dmitry , Kadlec Christelle , Petzelt Jan , Savinov Maxim , Kamba Stanislav 
Published: February 2022

Abstract
Lattice dynamics of a single crystal of lawsonite were studied over a broad range of frequencies (1 Hz to 20 THz) using impedance, THz time-domain and infrared spectroscopies. Based on polarized spectra of complex permittivity ε̂ measured as a function of temperature between 10 K and 500 K, we analyzed the properties of the two known phase transitions—an antiferrodistortive one near Tc1 = 270 K and a ferroelectric one, occurring at Tc2 = 124 K. The former one is accompanied by a flat maximum in the THz-range permittivity ε̂c near Tc1, which is due to a polar excitation in the E || c spectra reflecting the dynamics of water and hydroxyl groups. The strength of this mode decreases on cooling below Tc1, and the mode vanishes below Tc2 due to hydrogen ordering. At the pseudoproper ferroelectric phase transition, two independent anomalies in permittivity were observed. First, ε̂a exhibits a peak at Tc2 = 124 K due to critical slowing down of a relaxation in the GHz range. Second, infrared and THz spectra revealed an optical phonon softening towards Tc2 which causes a smaller but pronounced maximum in ε̂b. Such anomaly, consisting in a soft mode polarized perpendicularly to the ferroelectric axis, is unusual in ferroelectrics.
Optic Neuropathy after COVID-19 Vaccination: Case Report and Systematic Review
Authors: Haseeb Abid , Elhusseiny Abdelrahman M. , Elnahry Ayman 
Published: February 2022

Abstract
Purpose:

To report a case of anterior ischemic optic neuropathy (AION) following COVID-19 vaccination and provide a systematic review of all published cases of optic neuropathy following COVID-19 vaccination.
Methods:

A systematic literature search was performed using PubMed and Ovid MEDLINE for cases of optic neuropathy following COVID-19 vaccination. Terms used in the search included “COVID-19 vaccination”, “optic neuropathy”, “optic neuritis”, and “ischemic optic neuropathy”. Titles and abstracts were initially screened then full texts of eligible studies were reviewed for data extraction. Only cases published in the English language, peer reviewed, and that included details on optic nerve involvement were included. All study types were eligible for inclusion.
Results:

Including our patient, a total of 10 patients (8 females) were identified as developing optic neuropathy following COVID-19 vaccination. Five patients (50.0%) were diagnosed with AION, while 4 (40.0%) were diagnosed with optic neuritis. One patient was diagnosed with papillitis and neuroretinitis. Three patients (30.0%) had bilateral involvement. Mean age of patients was 48.5±19.7 years. Mean time from vaccination to onset of ophthalmic symptoms was 6.5±6.4 days. Mean presenting visual acuity was logMAR 0.598±0.621 (20/79, Snellen). For the 8 eyes which had both presenting and final follow-up visual acuity, mean presenting vision was logMAR 0.369±0.420 (20/47) and at final follow-up was 0.114±0.261 (20/26; P=0.184).
Conclusion:

COVID-19 vaccination may result in optic neuropathy in the form of optic neuritis and ischemic optic neuropathy. Further studies are needed to determine the incidence, management, and prognosis of optic neuropathies associated with COVID-19 vaccination.
In Vitro Cytotoxic Performance of Pure and Co-Doped CeO2 Nanoparticles on Breast Cancer Cell, Colon Cancer Cell, and Mouse Embryo Fibroblast Cell Lines
Authors: Miri Abdolhossein , Sarani Mina , Barani Mahmood , Varma Rajender S. , Miri Mohammad Javad 
Published: February 2022

Abstract
Today, according to the progression and prevalence of cancer, efforts to discover new compounds to suppress the tumor and associated with less toxicity. Metal oxide nanoparticles have wide applications in biology and biomedicine due to their unique physical and chemical properties. They have great potential in the treatment of cancer, tumor targeting in tissues, targeted drug delivery, bioimaging, gene therapy and other diagnostic and therapeutic areas. So, in this study, a simple, inexpensive, and environmentally friendly method is described for the pure and 1, 4, and 8% cobalt doped cerium oxide nanoparticles (Co-doped CeO2 NPs) using aqueous extract of Biebersteinia multifidi roots, as a recommended compound for the treatment of cancer. The morphology and size of synthesized nanoparticles were determined using PXRD, UV-Vis, FESEM, EDX, and Raman methods wherein cobalt doped cerium oxide were identified as spherical in shape with an average size of 5-10 nm. The toxicity effect of synthesized pure and Co-doped CeO2 NPs on breast cancer cell (MCF7), colon cancer cell (CaCo2), and mouse embryo fibroblast cell (NIH-3T3) lines was examined using MTT assay; cerium oxide nanoparticles were non-toxic against cancer and normal cell lines while Co-doped CeO2 NPs displayed cytotoxic effects on MCF7 and CaCo2 cell lines, except for NIH-3T3 cell line compared to doxorubicin as control. Thus, synthesized Co-doped CeO2 NPs have shown an acceptable inhibitory effect on breast and colon cancer cell lines.
Combined Endoscopic &amp; Radiologic Intervention For Management Of Acute Perforated Peptic Ulcer : A Randomized Controlled Trial
Authors: Negm Said , Mohamed Hatem , Shafiq Ahmed , AbdelKader Taha , Ismail Adel , Yassin Mahmoud , Mousa Bassam , Abozaid Mohamed , Orban Yasser A. , Alawi Mazoun Al , Farag Ahmed 
Published: February 2022

Abstract
Background : Peptic ulcer perforation is a common and life threatening surgical emergency. The traditional , pedical omental patch is performed for the plugging of perforated peptic ulcer was first described by Cellan-Jones in 1929. Although it is attributed to Graham , who described the use of a free graft of the omentum to repair the perforation in 1937. Many endoscopic methods have been used to treat acute perforated peptic ulcer like over the scope clips , standard endoscopic clips , endoscopic sewing and metallic stents. The main idea in endoscopic management of acute perforated peptic ulcer is early decontamination and decrease sepsis by interventional radiologic drainage.Methods:This study included patients who were developed acute perforated peptic ulcer manifestations and were admitted to our hospital between December 2019 to August 2021. Sample size was 100 patients divided into 2 equal groups. Endoscopic group (EG): included 50 patients who were subjected to endoscopic management . Surgical group (SG): included 50 patients who were subjected to surgical management.Results:Hundred patients were randomized into 2 groups: Surgery Group (SG, n=50) and Endoscopy Group (EG, n=50). Median age of patients was 36( range 27:54) and 47( range 41:50) years-old in SG and EG, respectively. Males constituted 72% and 66% in SG and EG, respectively. Median postoperative hospital stay was 1 (range: 1-2) days in EG , while in SG was 7 (range 6-8) days. Postoperative complications in SG patients were 58% in form of fever , pneumonia , leak , abdominal abcess , renal failure , incisional hernia, ( 11%, 5%, 5%, 3%, 2%, 3% , respectively). While postoperative complications in EG patients were 24% in form of fever , pneumonia , leak , abdominal abcess , renal failure , incisional hernia, ( 10%, 0%, 2%, 0%, 0%, 0% , respectively). Conclusion:combined endoscopic & interventional radiology can effectively manage acute perforated peptic ulcer without need for general anesthesia , within short time , in high risk surgical patients with low incidence of morbidity & mortality.This study was retrospectively submitted in clinicaltrials.gov in September 2021 (NCT05051683).
Clinically relevant pulse-treatment generates bortezomib-resistant myeloma cell line that lacks proteasome mutations and is sensitive to Bcl-2 inhibitor venetoclax
Authors: Downey-Kopyscinski Sondra L , Sriniv Sriraja , Kisselev Alexei F 
Published: February 2022

Abstract
Proteasome inhibitors bortezomib and carfilzomib are the backbone of treatments of multiple myeloma, which remains uncurable despite many recent advances. With many patients relapsing despite high initial response rates to proteasome inhibitor-containing regimens, it is critical to understand the process of acquired resistance. In vitro generated resistant cell lines are important tools in this process. The majority of previously developed bortezomib-resistant cell lines bear mutations in the proteasome PSMB5 sites, the prime target of bortezomib and carfilzomib, which are rarely observed in patients. Here we present a novel bortezomib-resistant derivative of KMS-12-BM multiple myeloma cell line, KMS-12-BM-BPR. Unlike previously published bortezomib-resistant cell lines, this sub-line was created using a clinically relevant twice-weekly pulse treatments with bortezomib instead of continuous incubation. It does not contain mutations in proteasome active sites and retains its sensitivity to carfilzomib. Reduced load on proteasome due to decreased protein synthesis appears to be the main cause of resistance. In addition, KMS-12-BM-BPR cells express less Mcl-1 than wild type and are more sensitive to Bcl-2 inhibitor venetoclax. Overall, this study demonstrates the feasibility of creating a proteasome-resistant myeloma cell lines by using clinically relevant pulse treatments and provides a novel model of acquired resistance.
Development and Validation of a HPLC-UV Method for Methadone Hydrochloride Quantification in a New Oral Solution with Preservatives to be Implemented in Physicochemical Stability Studies.
Authors: Álvaro-Alonso Elena Alba , Lorenzo-García Mª Paz , Escobar-Rodríguez Ismael , Aguilar-Ros Antonio 
Published: February 2022

Abstract
Purpose: The Pharmacy Service of the Infanta Leonor University Hospital acquires, compounds, distributes and dispenses more than 3,000 liters of methadone oral solution to Drug Addiction Patients Centers per year. Our purpose is to develop and validate an improved high performance liquid chromatography (HPLC) method to quantify methadone hydrochloride in a new oral solution with methylhydroxybenzoate (methylparaben) and propylhydroxybenzoate (propylparaben) to be implemented in physicochemical stability studies that allow to provide more information and even to increase the beyond-use date.Methods: A HPLC-Agilent® 1,100 equipment, comprising a quaternary pump and an ultraviolet diode-array-detector (DAD) was used. An analytical method development and validation was completed. The curve was constructed from methadone working concentrations of 75%-125% (7.5, 9.0, 10.0, 11.0 and 12.5 mg/mL) to assess the linear relationship between the concentration of the analyte and the obtained areas. Precision and accuracy were calculated. Detection and quantification limit (LD, LQ) were estimated using the EURACHEM method. Forced-degradation studies were also performed.Results: Chromatographic conditions were: flow rate 1.6 mL/min; mobile phase 55% acetonitrile and 45% sodium phosphate 25 mM (pH=10); injection volume was 5 µL. The column was a Waters-XTerraTM RP18, maintained at 40oC. DAD was λ=254 nm. Retention times for methadone, methylparaben and propylparaben were 4.34, 0.70 and 0.88 minutes respectively.The method was linear (y=284.3x-97.8, r=0.997). Instrumental precision was 0.33% for standards (n=10); intra-assay precision 0.53% (n=6) and inter-assay precision 1.95% (n=12). The relative standard deviation percentage for accuracy was 1.28%. The recovery percentage was 101.5 ± 1.5%. LQ and LD were 2.18 mg/mL and 2.0 mg/mL respectively. The most destabilizing conditions were oxidizing and alkaline. The chromatograms confirmed no interference with the methadone signal.Conclusions: The HPLC method has proved to be valid and reproducible for methadone quantification in a new oral solution with methylparaben and propylparaben. This assay is a rapid, simple and reliable technique that can be used in daily analysis and physicochemical stability studies.