bluuebunny/crossref_metadata_2025_split huggingface dataset:
HDL functionality in type 1 and type 2 diabetes: new insights
Authors: Chapman M. John 
Published: January 2022

Purpose of review
To critically appraise new insights into HDL structure and function in type 1 diabetes (T1DM) and type 2 diabetes (T2DM).

Recent findings
In young T1DM patients with early renal impairment and a high inflammatory score, both HDL antioxidative activity and endothelial vasodilatory function were impaired, revealing a critical link between HDL dysfunction, subclinical vascular damage, systemic inflammation and end organ damage. HDL may inhibit development of T2DM by attenuating endoplasmic reticulum (ER) stress and apoptotic loss of pancreatic β-cells, an effect due in part to ABC transporter-mediated efflux of specific oxysterols with downstream activation of the hedghehog signalling receptor, Smoothened. The apoM-sphingosine-1-phosphate complex is critical to HDL antidiabetic activity, encompassing protection against insulin resistance, promotion of insulin secretion, enhanced β-cell survival and inhibition of hepatic glucose production. Structure-function studies of HDL in hyperglycemic, dyslipidemic T2DM patients revealed both gain and loss of lipidomic and proteomic components. Such changes attenuated both the optimal protective effects of HDL on mitochondrial function and its capacity to inhibit endothelial cell apoptosis. Distinct structural components associated with individual HDL functions.

Summary
Extensive evidence indicates that both the proteome and lipidome of HDL are altered in T1DM and T2DM, with impairment of multiple functions.
Intraoperative monitoring of femoral head perfusion in adult femoral neck fractures
Authors: Donahue Jeffrey , Schrader Timothy , Bruggers Jennifer , Becher Stephen 
Published: January 2022

Abstract

Objectives:
To validate a novel intraoperative method of quantifying femoral head perfusion in adult patients with femoral neck fractures and to determine whether the lack of a perfusion waveform correlates with the development of osteonecrosis, nonunion, or reoperation.

Design:
Prospective cohort.

Setting:
Level 1 trauma center.

Patients/Participants:
Nineteen patients with 20 acute femoral neck fractures treated with hip-preserving surgical fixation. All patients underwent intraoperative quantification of femoral head perfusion.

Intervention:
Intraoperative quantification of femoral head perfusion pressure and waveform utilizing an intracranial pressure monitor.

Main outcome measurements:
Radiographic union, avascular necrosis, revision surgery.

Results:
Nineteen patients (8 male, 11 female, average age 56 ± 21 years) with 20 femoral neck fractures were enrolled. Eight fractures were stable (Garden 1-2/OTA B1.1–1.3) and 12 were unstable (Garden 3-4/OTAB2.1–3.3). A waveform was present in 12 of 20 cases. The average pressures were systolic 36.8 mm Hg, diastolic 30.8 mm Hg, pulse pressure 6.0 mm Hg. A perfusion waveform was significantly associated with advanced age (P = 0.02) and accompanied by trend toward stable fracture patterns. There were 4 deaths during the 1-year follow-up period (20%), and there were 5 conversions to total hip arthroplasty (25%). There was no significant association between revision surgery or death with the absence of a waveform.

Conclusions:
Our study demonstrated the feasibility of a relatively low cost, minimally invasive, technique to quantify femoral head perfusion. In our limited sample, the absence of perfusion did not correlate with our main outcomes; however, the trend toward correlation with increased fracture displacement was as expected. A larger cohort of patients will be needed to detect a significant difference between those with and without a perfusion waveform with regards to our primary outcomes. Further study is needed to delineate the role such data may play in medical decision making at the time of index surgery.

Level of Evidence:
Prognostic Level II.
Iliosacral screw corridors in Japanese subjects: a study using reconstruction CT scans
Authors: Iga Toru 
Published: January 2022

Abstract

Objectives:
To investigate the characteristics of iliosacral (IS) screw corridors of Japanese pelves.

Methods:
Computer tomography images of 42 adult Japanese subjects without any pelvic injury were analyzed at a workstation. Using the manual reconstruction function, the width of a simulated horizontal corridor for an IS screw on the true coronal and true axial planes in the upper (S1), second (S2), and the third (S3) sacral segments was measured. For pelves without an adequate S1 corridor, a cranially tilted corridor was sought. A corridor was defined as “adequate” if its width on both planes was 10 mm or more.

Results:
An adequate horizontal corridor was found in S1 in 17 (40.5%) subjects, in S2 in 29 (69.0%) subjects, and in S3 in no subject. An independent factor affecting the adequacy of the S1 corridor was the adequacy of the S2 corridor (OR: 0.09). Similarly, an independent factor affecting S2 adequacy was S1 adequacy (OR: 0.10). A tilted, 10 mm diameter corridor was found in all 25 subjects who did not have an adequate horizontal corridor in the S1 segment. The angle required to obtain a 10 mm diameter corridor inversely correlated with the diameter of a horizontal corridor on the true coronal plane (R = −0.713, P = .000).

Conclusions:
The characteristics of IS screw corridors in the 42 Japanese subjects were similar to those reported in previous studies conducted in the West. The importance of preoperative planning using reliable techniques, such as three-dimensional reconstruction, should be emphasized.
Level of evidence: Diagnostic Level III. See Instructions for Authors for a complete description of level of evidence.
Image Fusion Improves Interdisciplinary Communication in the Treatment of Head and Neck Cancer
Authors: Thoenissen Philipp , Bucher Andreas , Burck Iris , Sader Robert , Vogl Thomas , Ghanaati Shahram 
Published: January 2022

Introduction:
The diagnosis and therapy of oral squamous cell carcinoma (Osee) in Germany is according to guidelines and relies on interdisciplinary board meetings. Standard examination techniques are computed tomography (CT) and magnet resonance imaging (MRI). These technologies are used as objective tools for serial presentation in an oncologic board meeting. The presentation of multiple series at different time points can be time consuming and might not often depict a patients case clearly for all involved disciplinaries. A conclusive image fusion could improve the communication. Thus, this study aims to introduce a novel idea of image fusion into the field of craniomaxillofacial surgery in order to ease understanding and improve therapy in complex Osee patients’ cases.

Materials and Methods:
Three key data sets of a patient with OSCC at the right tongue have been merged by image fusion of 3 MRi of head and neck with 3 CT thorax and abdomen using Syngo via (Siemens). Fused images were used as at a glance picture for presenting and discussion a patients case. Focus was on presenting a case of a primary manifestation of OSCC with the potential of a local relapse and distant metastases in an interdisciplinary oncol-ogic board meeting.

Results:
Image fusion enabled to visualize the primary tumor, local relapse as well as distant pulmonary metastasis and within the suprarenal gland, which have been occurred in a linear time line of 13 months.

Discussion:
Image fusion of different modalities that is CT and MRi, which were gathered at different time points, presents a new approach within the field of craniomaxillofacial surgery and helped to understand cancer localization and relapse at 1 glance. This new approach will enable a compact data set of patients oncological history as a more decisive tool for all involved disciplinaries.

Conclusions:
Image fusion might have the potential to become a standard approach in order to ease multiple therapists to make therapy decisions in oncologic board meetings on basis of current three-dimensional ready CT imaging and MRI.
Does International Surgical Mission Involvement During Residency Predict Involvement in Practice?
Authors: Sasson Daniel C. , Kearney Aaron M. , Gosain Arun K. 
Published: January 2022

Abstract
Despite efforts to incorporate global health rotations during residency, it is unclear whether this experience affects the likelihood that plastic surgeons will continue such missions during practice. The authors conducted a survey of the American Society of Plastic Surgeons and the American Council of Academic Plastic Surgeons members regarding the impact of international experiences before practice upon future involvement. 138 surveys were analyzed. Ten percent participated in missions before medical school, 13% during medical school, 53% in residency, and 61% in practice. Sixty-seven percent of surgeons in an academic practice continued to engage in international missions, versus 55% in nonacademic practices (P = 0.152). No significant difference in the number of surgeons participating in missions was found between those who had attended their first mission before starting practice instead of those starting in practice (P = 0.163). Surgeons who graduated recently were more likely to have attended a mission during residency (P = 0.015). Fifty-four percent of surgeons reported that a mentor initiated their interest in missions, and 44% reported that their involvement in missions had decreased over the last 5 years, with most citing a financial disincentive. Given that over 2/3 of plastic surgeons from all practice types participate in international missions, it would behoove residency programs to offer formal training in global health to facilitate this interest. Our study is the largest thus far attempting to quantify the downstream effects of surgical mission participation in residency and highlights the need for further inquiry into this matter.
Cardiovascular Burden Is High in Pediatric Lung Transplant Recipients
Authors: Memaran Nima , Onnen Mareike , Müller Carsten , Schwerk Nicolaus , Carlens Julia , Borchert-Mörlins Bianca , Bauer Elena , Blöte Ricarda , Sugianto Rizky I. , Zürn Katharina , Wühl Elke , Warnecke Gregor , Tudorache Igor , Hansen Gesine , Gjertson David W. , Schmidt Bernhard M. W. , Melk Anette 
Published: January 2022

Background.
Cardiovascular morbidity is common in adults after lung transplantation (LTx) but has not been described for pediatric LTx recipients. Early subclinical cardiovascular damage is reflected by increases in pulse wave velocity (PWV; indicating arteriosclerosis), intima–media thickness (IMT; indicating atherosclerosis), and left ventricular mass index (LVMI; indicating left ventricular hypertrophy).

Methods.
We annually assessed 47 pediatric LTx recipients in a prospective longitudinal study (144 observations, mean 3.1 visits/patient, range of 1–4 visits, mean follow-up 2.2 y).

Results.
At inclusion, increased PWV and IMT were detected in 13% and 30%, respectively, and elevated LVMI was detected in 33%. Higher PWV was associated with male sex, longer time since LTx, higher diastolic blood pressure, and lower glomerular filtration rate. Male sex and lower hemoglobin levels were associated with higher IMT, and the presence of diabetes was associated with higher LVMI.

Conclusions.
Pediatric LTx recipients suffer from a high and sustained burden of subclinical cardiovascular damage. In light of improving long-term outcomes, cardiovascular morbidity needs to be addressed. Our analysis identified classical and nonclassical risk factors to be associated with the measures for cardiovascular damage, which could serve as targets for intervention.
Splicing QTL analysis focusing on coding sequences reveals pathogenicity of disease susceptibility loci
Authors: Yamaguchi Kensuke , Ishigaki Kazuyoshi , Suzuki Akari , Tsuchida Yumi , Tsuchiya Haruka , Sumitomo Shuji , Nagafuchi Yasuo , Miya Fuyuki , Tsunoda Tatsuhiko , Hirofumi Shoda , Fujio Keishi , Yamamoto Kazuhiko , Kochi Yuta 
Published: January 2022

AbstractSplicing QTL (sQTL) are one of the major causal mechanisms in GWAS loci, but their role in disease pathogenesis is poorly understood. One reason is the huge complexity of alternative splicing events producing many unknown isoforms. Here, we proposed two novel approaches, namely integration and selection, for this complexity by focusing on protein-structure of isoforms. First, we integrated isoforms with the same coding sequence (CDS) and identified 369-601 integrated-isoform ratio QTLs (i2-rQTLs), which altered protein-structure, in six immune subsets. Second, we selected CDS incomplete isoforms annotated in GENCODE and identified 175-337 isoform-ratio QTL (i-rQTL). By comprehensive long-read capture RNA-seq among these incomplete isoforms, we revealed 29 full-length isoforms with novel CDSs associated with GWAS traits. Furthermore, we have shown that disease-causal sQTL genes can be identified by evaluating their trans-eQTL effects. Our approaches highlight the understudied role of protein-altering sQTLs and are broadly applicable to other tissues and diseases.
Cell culture model system utilizing engineered A549 cells to express high levels of ACE2 and TMPRSS2 for investigating SARS-CoV-2 infection and antivirals
Authors: Chang Ching-Wen , Parsi Krishna Mohan , Somasundaran Mohan , Vanderleeden Emma , Cruz John , Cousineau Alyssa , Liu Ping , Li Qi , Wang Yang , Maehr Rene , Wang Jennifer P. , Finberg Robert W. 
Published: January 2022

AbstractNovel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose an imminent global threat since its initial outbreak in December 2019. A simple in vitro model system using cell lines highly susceptible to SARS-CoV-2 infection are critical to facilitate the study of the virus cycle and to discover effective antivirals against the virus. Human lung alveolar A549 cells are regarded as a useful and valuable model for respiratory virus infection. However, SARS-CoV-2 uses the ACE2 as receptor for viral entry and the TMPRSS2 to prime the Spike protein, both of which are negligibly expressed in A549 cells. Here, we report the generation of a robust human lung epithelial cell-based model by transducing ACE2 and TMPRSS2 into A549 cells and show that the ACE2 enriched A549ACE2/TMPRSS2 cells (ACE2plus) and its single-cell-derived subclone (ACE2plusC3) are highly susceptible to SARS-CoV-2 infection. These engineered ACE2plus showed higher ACE2 and TMPRSS2 mRNA expression levels than currently used Calu3 and commercial A549ACE2/TMPRSS2 cells. ACE2 and TMPRSS2 proteins were also highly and ubiquitously expressed in ACE2plusC3 cells. Additionally, antiviral drugs like Camostat mesylate, EIDD-1931, and Remdesivir strongly inhibited SARS-CoV-2 replication. Notably, multinucleated syncytia, a clinical feature commonly observed in severe COVID-19 patients was induced in ACE2plusC3 cells either by virus infection or by overexpressing the Spike proteins of different variants of SARS-CoV-2. Syncytial process was effectively blocked by the furin protease inhibitor, Decanoyl-RVKR-CMK. Taken together, we have developed a robust human A549 lung epithelial cell-based model that can be applied to probe SARS-CoV-2 replication and to facilitate the discovery of SARS-CoV-2 inhibitors.
RG203KR mutations in SARS-CoV-2 Nucleocapsid: Assessing the impact using Virus-like particle model system
Authors: Raheja Harsha , Das Soma , Banerjee Anindita , Dikshaya P , Deepika C , Mukhopadhyay Debanjan , Ramachandra Subbaraya G , Das Saumitra 
Published: January 2022

AbstractThe emergence and evolution of SARS-CoV-2 is characterized by the occurrence of diverse sets of mutations that affect virus characteristics, including transmissibility and antigenicity. Recent studies have focused mostly on Spike protein mutations; however, SARS-CoV-2 variants of interest (VoI) or concern (VoC) contain significant mutations in the nucleocapsid protein as well. To study the relevance of the mutations at the virion level, recombinant baculovirus expression system based VLPs were generated for the prototype Wuhan sequence along with Spike mutants like D614G, G1124V and the significant RG203KR mutation in Nucleocapsid. All the four structural proteins assembled in a particle wherein the morphology and size of the particle confirmed by TEM closely resembles the native virion. The VLP harbouring RG203KR mutations in nucleocapsid exhibited augmentation of humoral immune responses and enhanced neutralization by the immunized mice sera. Results demonstrate a non-infectious platform to quickly assess the implication of mutations in structural proteins of the emerging variant.
The common H202D variant in GDF-15 does not affect its bioactivity but can significantly interfere with measurement of its circulating levels
Authors: Karusheva Y , Ratcliff M , Melvin A , Mörseburg A , Sattar N , Barker P , Burling K , Backmark A , Roth R , Jermutus L , Guiu-Jurado E , Blüher M , Welsh P , Hyvönen M , O’Rahilly S 
Published: January 2022

AbstractGenetic variants in proteins can interfere with measurement of their circulating concentrations. Given the growing biomedical importance of GDF-15, we wished to establish whether a common histidine to aspartate variant present in position 6 of the mature GDF-15 protein (H202D variant) interfered with its measurement by two commonly used immunoassays. We first examined the detectability of recombinant monomers, homodimers and heterodimers of GDF-15 by assays and/or reagents used in two widely used immunoassays (Roche Elecsys® GDF-15 and the R&D antibody combinations used in their Quantikine® and DuoSet® ELISA’s). The Roche assay detected the H and D containing peptides similarly but the assays based on the R&D reagents consistently underreported concentrations of the D-containing variant peptide. Measurements of plasma concentrations of GDF-15 in genotyped human participants showed that the R&D reagents reported values in heterozygotes were ∼25% lower, and in homozygotes, 50% lower than the Roche assay. We finally studied the activation of the GDF-15 receptor, GFRAL-Ret, in a cell based assay and found that the activities of the HH and DD containing GDF-15 peptide were indistinguishable. These results have implications for the interpretation of genetic epidemiological studies which have used the R&D reagents to measure GDF-15, and for the emerging clinical use of GDF-15 as a diagnostic and prognostic biomarker. We provide correction equations, which may be of utility for the analysis of data generated with the R&D reagents where the genotype of the participants is known.
Construct a variable-length fragment library forde novoprotein structure prediction
Authors: Feng Qiongqiong , Hou Minghua , Liu Jun , Zhao Kailong , Zhang Guijun 
Published: January 2022

AbstractAlthough remarkable achievements, such as AlphaFold2, have been made in end-to-end structure prediction, fragment libraries remain essential forde novoprotein structure prediction, which can help explore and understand the protein-folding mechanism. In this work, we developed a variable-length fragment library (VFlib). In VFlib, a master structure database was first constructed from the Protein Data Bank through sequence clustering. The Hidden Markov Model (HMM) profile of each protein in the master structure database was generated by HHsuite, and the secondary structure of each protein was calculated by DSSP. For the query sequence, the HMM-profile was first constructed. Then, variable-length fragments were retrieved from the master structure database through dynamically variable-length profile-profile comparison. A complete method for chopping the query HMM-profile during this process was proposed to obtain fragments with increased diversity. Finally, secondary structure information was used to further screen the retrieved fragments to generate the final fragment library of specific query sequence. The experimental results obtained with a set of 120 nonredundant proteins showed that the global precision and coverage of the fragment library generated by VFlib were 55.04% and 94.95% at the RMSD cutoff of 1.5 Å, respectively. Compared to the benchmark method of NNMake, the global precision of our fragment library had increased by 62.89% with equivalent coverage. Furthermore, the fragments generated by VFlib and NNMake were used to predict structure models through fragment assembly. Controlled experimental results demonstrated that the average TM-score of VFlib was 16.00% higher than that of NNMake.
Mito-FUNCAT-FACS reveals cellular heterogeneity in mitochondrial translation
Authors: Kimura Yusuke , Saito Hironori , Osaki Tatsuya , Ikegami Yasuhiro , Wakigawa Taisei , Ikeuchi Yoshiho , Iwasaki Shintaro 
Published: January 2022

AbstractMitochondria possess their own genome that encodes components of oxidative phosphorylation (OXPHOS) complexes, and mitochondrial ribosomes within the organelle translate the mRNAs expressed from mitochondrial genome. Given the differential OXPHOS activity observed in diverse cell types, cell growth conditions, and other circumstances, cellular heterogeneity in mitochondrial translation can be expected. Although individual protein products translated in mitochondria have been monitored, the lack of techniques that address the variation in overall mitochondrial protein synthesis in cell populations poses analytic challenges. Here, we adapted mitochondrial-specific fluorescent noncanonical amino acid tagging (FUNCAT) for use with fluorescence-activated cell sorting (FACS) and developed mito-FUNCAT-FACS. The click chemistry-compatible methionine analog L-homopropargylglycine (HPG) enabled the metabolic labeling of newly synthesized proteins. In the presence of cytosolic translation inhibitors, HPG was selectively incorporated into mitochondrial nascent proteins and conjugated to fluorophores via the click reaction (mito-FUNCAT). The application ofin situmito-FUNCAT to flow cytometry allowed us to disentangle changes in net mitochondrial translation activity from those of the organelle mass and detect variations in mitochondrial translation in cancer cells. Our approach provides a useful methodology for examining mitochondrial protein synthesis in individual cells.
Lipoate protein ligase B primarily recognizes the C8-phosphopantetheine arm of its donor substrate, and weakly binds the acyl carrier protein
Authors: Dhembla Chetna , Yadav Usha , Kundu Suman , Sundd Monica 
Published: January 2022

ABSTRACTLipoic acid is a sulfur containing cofactor, indispensable for the function of several metabolic enzymes. In microorganisms, lipoic acid can be salvaged from the surroundings by Lipoate protein ligase A (LplA), an ATP-dependent enzyme. Alternatively, it can be synthesized by the sequential action of Lipoate protein ligase B (LipB) and Lipoyl synthase (LipA), in a two-step reaction. LipB uptakes octanoyl-chain from C8-acyl carrier protein (C8-ACP), a byproduct of the type II fatty acid synthesis pathway, and transfers it to a conserved lysine of the lipoyl domain of a dehydrogenase. The molecular basis of substrate recognition by LipB is still not fully understood. Using E. coli LipB as a prototype, we show that the enzyme mainly recognizes the 4’-phosphopantetheine tethered acyl-chain of its donor substrate, and weakly binds the apo-acyl carrier protein. It can accept octanoate-from its own ACP, noncognate ACPs, as well as C8-CoA. Further, our NMR studies demonstrate the presence of an adenine and phosphate binding site in LipB, akin to LplA. A loop containing 71RGG73 sequence, analogous to the lipoate binding loop of LplA is also conserved. Collectively, our studies highlight commonalities between LipB and LplA in their mechanism of substrate recognition. This knowledge might be of significance in the treatment of mitochondrial fatty acid synthesis related disorders.