bluuebunny/crossref_metadata_2025_split huggingface dataset:
Double-Level Osteotomy in Severe Varus Malalignment to Optimize Knee Joint Restoration
Authors: Harrer Jörg , Schenke Max , Lutter Christoph , Dickschas Jörg , Feucht Matthias , Tischer Thomas 
Published: December 2021

Background: Lower extremity alignment-correcting procedures for unicompartmental osteoarthritis are experiencing a rapid rise. Medial open-wedge high tibial osteotomy (MOW-HTO) thereby represents the most common technique among osteotomies but is limited in cases of severe malalignment. Some cases make a double-level osteotomy necessary. Indications: If planning of malalignment correction using a MOW-HTO results in a mechanical medial proximal tibial angle (mMPTA) of more than 93° (causing an oblique joint line), double-level osteotomy is indicated to avoid nonphysiological knee kinematics. Technique Description: After clinical examination and detailed analysis of malalignment (full-weight-bearing long-leg radiograph: hip-knee-angle [HKA], mMPTA, mechanical lateral distal femoral angle [mLDFA], joint line convergence angle [JLCA]), as well as individualized planning of the correction, the surgical procedure starts with an arthroscopy to evaluate the cartilage conditions and eventually treat intraarticular pathologies. Then, the femoral supracondylar correction is performed (closed wedge, biplanar osteotomy [ to increase bony healing]) according to the presurgical planning by resecting the osteotomy wedge with the measured length. K-wires are placed to check the correction. An angle-stable plate is used for osteosynthesis. The wedge taken out will be used as bone stock for the MOW-HTO afterward. The biplanar open-wedge tibial osteotomy is then performed subsequently using a medial tibial approach and an angle-stable plate. Opening of the osteotomy is then performed and double checked with intraoperative fluoroscopy using an alignment rod. Postoperative partial weight bearing for 6 weeks is recommended. Results: In recent literature, only few publications report on results of double-level osteotomies. Babis et al reports that it is a valuable procedure for patients with large varus deformity. Nakayama et al noted a significant improvement in patient-registered clinical outcomes in early postoperative evaluation of 20 patients. Schröter et al reports on 37 knees and findings include good clinical results, despite progressive osteoarthritis. Discussion/Conclusion: In cases of severe malalignment, adequate axis correction may require a double-level osteotomy. Exact preoperative planning is essential. Results reported in recent publications are promising. By splitting 1 large correction into 2 smaller ones, complications like hinge fracture and delayed bone healing are lowered.
Demonstration of a Flexible Graphene-Based Biosensor for Sensitive and Rapid Detection of Ovarian Cancer Cells
Authors: Han Ling , Wan Qi , Zheng Ai , Guo Yunchuan , Chen Yali 
Published: December 2021

AbstractIt is significant to develop an efficient early detection and prediction method for ovarian cancer via a facile and low-cost approach. To address such issues, herein, we develop a novel circulating tumor cell (CTC) detection method to sensitively detect ovarian cancer by using a flexible graphene-based biosensor on polyethylene terephthalate (PET) substrate. The results show that the graphene-based flexible biosensor demonstrates sensitive and rapid detection for ovarian cancer cells: it delivers obvious different responses for cell culture medium and cancer solution, different cancer cells and cancer cell solution with different concentrations; it demonstrates high sensitivity for detecting several tens of ovarian cancer cells per ml; moreover, the flexible graphene biosensor is very suitable for rapid and sensitive detection of ovarian cancer cells within 5 s. This work provides a low-cost and facile graphene biosensor fabrication strategy to sensitively and rapidly detect / identify CTC ovarian cancer cells.
Graphical Abstract
Co-option of the same ancestral gene family gave rise to mammalian and reptilian toxins
Authors: Barua Agneesh , Koludarov Ivan , Mikheyev Alexander S. 
Published: December 2021

Abstract
Background
Evolution can occur with surprising predictability when organisms face similar ecological challenges. For most traits, it is difficult to ascertain whether this occurs due to constraints imposed by the number of possible phenotypic solutions or because of parallel responses by shared genetic and regulatory architecture. Exceptionally, oral venoms are a tractable model of trait evolution, being largely composed of proteinaceous toxins that have evolved in many tetrapods, ranging from reptiles to mammals. Given the diversity of venomous lineages, they are believed to have evolved convergently, even though biochemically similar toxins occur in all taxa.

Results
Here, we investigate whether ancestral genes harbouring similar biochemical activity may have primed venom evolution, focusing on the origins of kallikrein-like serine proteases that form the core of most vertebrate oral venoms. Using syntenic relationships between genes flanking known toxins, we traced the origin of kallikreins to a single locus containing one or more nearby paralogous kallikrein-like clusters. Additionally, phylogenetic analysis of vertebrate serine proteases revealed that kallikrein-like toxins in mammals and reptiles are genetically distinct from non-toxin ones.

Conclusions
Given the shared regulatory and genetic machinery, these findings suggest that tetrapod venoms evolved by co-option of proteins that were likely already present in saliva. We term such genes ‘toxipotent’—in the case of salivary kallikreins they already had potent vasodilatory activity that was weaponized by venomous lineages. Furthermore, the ubiquitous distribution of kallikreins across vertebrates suggests that the evolution of envenomation may be more common than previously recognized, blurring the line between venomous and non-venomous animals.
Enhanced production of γ-amino acid 3-amino-4-hydroxybenzoic acid by recombinant Corynebacterium glutamicum under oxygen limitation
Authors: Kawaguchi Hideo , Hasunuma Tomohisa , Ohnishi Yasuo , Sazuka Takashi , Kondo Akihiko , Ogino Chiaki 
Published: December 2021

Abstract
Background
Bio-based aromatic compounds are of great interest to the industry, as commercial production of aromatic compounds depends exclusively on the unsustainable use of fossil resources or extraction from plant resources. γ-amino acid 3-amino-4-hydroxybenzoic acid (3,4-AHBA) serves as a precursor for thermostable bioplastics.

Results
Under aerobic conditions, a recombinant Corynebacterium glutamicum strain KT01 expressing griH and griI genes derived from Streptomyces griseus produced 3,4-AHBA with large amounts of amino acids as by-products. The specific productivity of 3,4-AHBA increased with decreasing levels of dissolved oxygen (DO) and was eightfold higher under oxygen limitation (DO = 0 ppm) than under aerobic conditions (DO ≥ 2.6 ppm). Metabolic profiles during 3,4-AHBA production were compared at three different DO levels (0, 2.6, and 5.3 ppm) using the DO-stat method. Results of the metabolome analysis revealed metabolic shifts in both the central metabolic pathway and amino acid metabolism at a DO of < 33% saturated oxygen. Based on this metabolome analysis, metabolic pathways were rationally designed for oxygen limitation. An ldh deletion mutant, with the loss of lactate dehydrogenase, exhibited 3.7-fold higher specific productivity of 3,4-AHBA at DO = 0 ppm as compared to the parent strain KT01 and produced 5.6 g/L 3,4-AHBA in a glucose fed-batch culture.

Conclusions
Our results revealed changes in the metabolic state in response to DO concentration and provided insights into oxygen supply during fermentation and the rational design of metabolic pathways for improved production of related amino acids and their derivatives.

Graphical Abstract
The development of clinical guidelines in China: insights from a national survey
Authors: Song Yang , Li Jing , Chen Yaolong , Guo Ruixia , Alonso-Coello Pablo , Zhang Yuan 
Published: December 2021

AbstractBackgroundPrevious research suggests that the quality of clinical guidelines (CGs) in China is suboptimal. However, little is known about the methodology that CGs follow. We conducted a national survey of methods used by Chinese CG developers for CG development, adaptation, and updating.MethodsWe used a previously piloted questionnaire based on methodologies of CG development, adaptation, and updating, which was distributed during September–November 2020 to 114 organizations identified from published Chinese CGs (searched 2017–2020), recommended by Chinese CG developers, and recommended by clinical discipline experts.ResultsWe collected 48 completed questionnaires (42.1% response). Most organizations developed CGs based on scientific evidence (89.6%), existing CGs (75%), or expert experience and opinion (64.6%). Only a few organizations had a specific CG development division (6.3%), a CG monitoring plan (on clinicians 33.3%; on patients 18.8%), funding (33.3%), or a conflict-of-interest (COI) management policy (23.4%). Thirty (62.5%) organizations reported using a CG development methodology handbook, from international organizations (14/30, 46.7%), methodology or evaluation resources (3/30, 10.0%), expert experience and opinion (3/30, 10.0%), or in-house handbooks (3/30, 10.0%). One organization followed a published adaptation methodology. Thirty-eight organizations (88.4%) reported de novo CG development: 21 (55.3%) formed a CG working group, and 29 (76.3%) evaluated the quality of evidence (21 [72.4%] using a methodological tool). Nineteen organizations (52.8%) reported CG adaptation: three (31.6%) had an adaptation working group, and 12 (63.2%) evaluated the quality of source CGs (2 (16.7%) using the AGREE II instrument). Thirty-three organizations (68.8%) updated their CGs, seven (17.5%) using a formal updating process.ConclusionsOur study describes how CGs are developed in a middle-income country like China. To ensure better healthcare, there is still an important need for improvement in the development, adaptation, and updating of CG in China.
Identification and development of a novel 5-gene diagnostic model based on immune infiltration analysis of osteoarthritis
Authors: Han YaGuang , Wu Jun , Gong ZhenYu , Zhou YiQin , Li HaoBo , Wang Bo , Qian QiRong 
Published: December 2021

Abstract
Background
Osteoarthritis (OA), which is due to the progressive loss and degeneration of articular cartilage, is the leading cause of disability worldwide. Therefore, it is of great significance to explore OA biomarkers for the prevention, diagnosis, and treatment of OA.

Methods and materials
The GSE129147, GSE57218, GSE51588, GSE117999, and GSE98918 datasets with normal and OA samples were downloaded from the Gene Expression Omnibus (GEO) database. The GSE117999 and GSE98918 datasets were integrated, and immune infiltration was evaluated. The differentially expressed genes (DEGs) were analyzed using the limma package in R, and weighted gene co-expression network analysis (WGCNA) was used to explore the co-expression genes and co-expression modules. The co-expression module genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and hub genes were identified by the degree, MNC, closeness, and MCC algorithms. The hub genes were used to construct a diagnostic model based on support vector machines.

Results
The Immune Score in the OA samples was significantly higher than in the normal samples, and a total of 2313 DEGs were identified. Through WGCNA, we found that the yellow module was significantly positively correlated with the OA samples and Immune Score and negatively correlated with the normal samples. The 142 DEGs of the yellow module were related to biological processes such as regulation of inflammatory response, positive regulation of inflammatory response, blood vessel morphogenesis, endothelial cell migration, and humoral immune response. The intersections of the genes obtained by the 4 algorithms resulted in 5 final hub genes, and the diagnostic model constructed with these 5 genes showed good performance in the training and validation cohorts.

Conclusions
The 5-gene diagnostic model can be used to diagnose OA and guide clinical decision-making.
RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis
Authors: Wu Yuming , Zhang Yujing , Xie Bing , Abdelgawad Amro , Chen Xiaoyan , Han Mengqi , Shang You , Yuan Shiying , Zhang Jiancheng 
Published: December 2021

AbstractBackgroundAtrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is to assess the effect of ANP on bacterial lipopolysaccharide (LPS)-induced endotoxemia-derived neuroinflammation and cognitive impairment.MethodsLPS (5 mg/kg) was given intraperitoneally to mice. Recombinant human ANP (rhANP) (1.0 mg/kg) was injected intravenously 24 h before and/or 10 min after LPS injection. Subdiaphragmatic vagotomy (SDV) was performed 14 days before LPS injection or 28 days before fecal microbiota transplantation (FMT). ANA-12 (0.5 mg/kg) was administrated intraperitoneally 30 min prior to rhANP treatment.ResultsLPS (5.0 mg/kg) induced remarkable splenomegaly and an increase in the plasma cytokines at 24 h after LPS injection. There were positive correlations between spleen weight and plasma cytokines levels. LPS also led to increased protein levels of ionized calcium-binding adaptor molecule (iba)-1, cytokines and inducible nitric oxide synthase (iNOS) in the hippocampus. LPS impaired the natural and learned behavior, as demonstrated by an increase in the latency to eat the food in the buried food test and a decrease in the number of entries and duration in the novel arm in the Y maze test. Combined prophylactic and therapeutic treatment with rhANP reversed LPS-induced splenomegaly, hippocampal and peripheral inflammation as well as cognitive impairment. However, rhANP could not further enhance the protective effects of SDV on hippocampal and peripheral inflammation. We further found that PGF mice transplanted with fecal bacteria from rhANP-treated endotoxemia mice alleviated the decreased protein levels of hippocampal polyclonal phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotrophic factor (BDNF) and cognitive impairment, which was abolished by SDV. Moreover, TrkB/BDNF signaling inhibitor ANA-12 abolished the improving effects of rhANP on LPS-induced cognitive impairment.ConclusionsOur results suggest that rhANP could mitigate LPS-induced hippocampal inflammation and cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota–brain axis.
Corporate political activity of baby food companies in Thailand
Authors: Cetthakrikul Nisachol , Baker Phillip , Banwell Cathy , Kelly Matthew , Smith Julie 
Published: December 2021

Abstract
Background
Recent studies show corporate political activity (CPA) can have detrimental impacts on health policy processes. The Control of Marketing Promotion of Infant and Young Child Food Act B.E. 2560 (the Act) was implemented in Thailand in 2017, but there have been no studies documenting CPA during its policy processes. Furthermore, the effects of CPA on the Act and how non-industry stakeholders dealt with the CPA have not been explored. This study aimed to analyze the CPA of baby food companies in Thailand, its effects on the Act, and how policymakers have responded to CPA around the Act.

Methods
This qualitative study applied an established framework developed by Mialon and colleagues to collect and systematically analyze publicly available information from seven baby food companies with the highest percentage market share in Thailand. In-depth interviews were also used to explore how people involved in the policy process of the Act experienced the CPA of baby food companies, the consequent effects on the Act, and how they responded to the CPA.

Results
During development of the Act, baby food companies used two main strategies, ‘information and messaging’ and ‘constituency building’. We found the companies met policymakers, and they employed evidence or provided information that was favorable to companies. Also, they established relationships with policymakers, health organizations, communities and media. The effects of CPA were that the scope of products controlled by the Act was reduced, and CPA led relevant people to misunderstand and have concerns about the Act. Officials and others countered the influence of CPA by raising awareness and building understanding among involved people, as well as avoiding contact with companies informally.

Conclusions
CPA consists of a variety of practices that resulted in a weakened Act in Thailand. Government officials and other non-industry stakeholders employed strategies to counteract this influence. This study suggests the Department of Health, and other relevant government agencies, would benefit from establishing safeguards and protections against CPA. Efforts to raise awareness about the harms of CPA within and outside of government and establish a systematic monitoring system, including avoid conflict of interest in policy process would improve policymaking and implementation of the Act.
Transportal versus all-inside techniques of anterior cruciate ligament reconstruction: a systematic review
Authors: Bhimani Rohan , Shahriarirad Reza , Ranjbar Keivan , Erfani Amirhossein , Ashkani-Esfahani Soheil 
Published: December 2021

Abstract
Background
Transportal (TP) and all-inside techniques (AIT) are the most commonly used anterior cruciate ligament (ACL) reconstruction procedures in current clinical practice. However, there is an ongoing debate over which procedure is superior. Therefore, the purpose of this systematic review was to evaluate and compare the clinical outcomes and complications of these two techniques to propose recommendations for future application. Our primary hypothesis was that AIT is a superior ACLR technique compared to TP.

Methods
A systematic literature review, using PRISMA guidelines, was conducted using PubMed, Medline, Google Scholar, and EMBASE, up to February 2021 to identify studies focusing on AIT and TP techniques of ACL reconstruction. We excluded animal experiments, cadaveric studies, retrospective studies, case reports, technical notes, and studies without quantitative data. Patients’ characteristics, surgical technical features, along with postoperative follow-up and complications were extracted and reported accordingly. Methodological quality of the included studies was assessed using the Modified Coleman Methodology Score (MCMS).

Results
A total of 44 studies were selected for this review, of which four were comparative studies. A total of 923 patients underwent AIT and 1678 patients underwent the TP technique for ACLR. A single semitendinosus graft was commonly used in the AIT compard to combined semitendinosus and gracilis graft in the TP group. The postoperative increase in International Knee Documentation Committee (IKDC), Lysholm, KT-1000, and Short Form-12 (physical and mental) scores were similar in the AIT group and the TP group. Contrastingly, the VAS pain score was significantly lower in the AIT group compared to the TP group. Furthermore, the pooled complication rates from all studies were similar between the two groups (AIT: 54 patients, 8.26% vs. PT: 55 patients, 6.62%). However, the four studies that prospectively compared AIT and TP techniques showed lesser complications in the AIT group than the TP group.

Conclusion
Since the future trend in orthopedic surgery is toward less invasive and patients’ satisfaction with good outcomes, AIT is a good alternative method considering preserving bony tissue and gracilis tendon with less post-operative pain, along with more knee flexor strength and equal outcomes compared to conventional ACL reconstruction surgery.
Level of Evidence II.
Growth in achondroplasia including stature, weight, weight-for-height and head circumference from CLARITY: achondroplasia natural history study—a multi-center retrospective cohort study of achondroplasia in the US
Authors: Hoover-Fong Julie E. , Schulze Kerry J. , Alade Adekemi Y. , Bober Michael B. , Gough Ethan , Hashmi S. Shahrukh , Hecht Jacqueline T. , Legare Janet M. , Little Mary Ellen , Modaff Peggy , Pauli Richard M. , Rodriguez-Buritica David F. , Serna Maria E. , Smid Cory , Liu Chengxin , McGready John 
Published: December 2021

AbstractBackgroundAchondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments from birth through 18 years for clinical use and research for achondroplasia patients.MethodsAll available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population.ResultsOver 37,000 length/height, weight and head circumference measures from 1374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves.ConclusionAchondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth.