bluuebunny/crossref_metadata_2025_split huggingface dataset:
Percutaneous autologous impaction bone graft for advanced femoral head osteonecrosis: a retrospective observational study of unsatisfactory short-term outcomes
Authors: Kuroda Yutaka , Nankaku Manabu , Okuzu Yaichiro , Kawai Toshiyuki , Goto Koji , Matsuda Shuichi 
Published: February 2021

Abstract
Background
Half of osteonecrosis of the femoral head (ONFH) patients suffer femoral head collapse at initial diagnosis, and more than half are bilaterally affected. This study developed a percutaneous autologous impaction bone graft (IBG) technique as a modification of core decompression (CD). We also summarized the short-term results and treatment efficacy of percutaneous autologous IBG in advanced ONFH.

Methods
Twenty patients (12 males, 8 females) with nontraumatic, postcollapse ONFH except one case underwent CD (10-mm core diameter) and reverse IBG. Radiological changes of the ONFH stage and type were analyzed. Survival analysis using Kaplan–Meier estimates was performed with conversion to total hip arthroplasty (THA) as the endpoint. In addition, the Harris hip score (HHS) and University of California, Los Angeles (UCLA) activity rating scale were evaluated.

Results
Percutaneous autologous IBG was performed successfully, with an average operation time of < 1 h and small blood loss, and 7 patients (35%) needed conversion to THA at an average of 17 months postoperatively. We observed radiological progressive change in 60% of the patients during a mean observation period of 3 years. The mean clinical scores, except data recorded, after THA significantly improved (before vs. after 3 years: UCLA activity score, 3.7 vs. 5.2 [P = 0.014]; HHS, 57.6 vs. 76.5 points [P = 0.005]). In addition, 6 patients showed radiological progression but no clinical deterioration.

Conclusions
Percutaneous autologous IBG was technically simple and minimally invasive, but short-term results were unsatisfactory for advanced ONFH. Indications for this procedure should be carefully examined to improve it in order to enable bone formation.
The International Collaborative Gaucher Group GRAF (Gaucher Risk Assessment for Fracture) score: a composite risk score for assessing adult fracture risk in imiglucerase-treated Gaucher disease type 1 patients
Authors: Deegan Patrick , Khan Aneal , Camelo José Simon , Batista Julie L. , Weinreb Neal 
Published: February 2021

Abstract
Background
Fractures in Gaucher disease type 1 (GD1) patients cause significant morbidity. Fracture risk may be decreased by enzyme replacement therapy (ERT) but not eliminated. When considering initiation of treatment, it is useful to know to what extent fixed patient-specific factors determine risk for future fractures beyond standard risk factors that change with time and treatment, such as decreased bone mineral density. We developed a tool called the GRAF score (Gaucher Risk Assessment for Fracture) that applies 5 widely available characteristics (sex, age at treatment initiation [ATI], time interval between diagnosis and treatment initiation, splenectomy status, history of pre-treatment bone crisis) and provides a practical method to assess future fracture risk when imiglucerase ERT is initiated.

Methods
Inclusion criteria: GD1 patients in the International Collaborative Gaucher Group Gaucher Registry as of September 2019 initially treated with alglucerase/imiglucerase; known splenectomy status; at least one skeletal assessment on treatment (3216 of 6422 patients). Data were analyzed by ATI group (< 18, ≥ 18 to < 50, or ≥ 50 years of age) using Cox proportional hazards regression with all 5 risk factors included in the multivariable model. A composite risk score was calculated by summing the contribution of each parameter weighted by the strength of its association (regression coefficient) with fracture risk.

Results
Patients were followed from the date of treatment initiation (or age 18 years for patients if treatment started earlier) to the date of first adult fracture (n = 288 first fracture endpoints), death, or end of follow-up. The GRAF score for each ATI group was associated with a 2.7-fold increased risk of adult fracture for each one-point increase (p < 0.02 for < 18 ATI, p < 0.0001 for ≥ 18 to < 50 ATI and ≥ 50 ATI).

Conclusions
The GRAF score is a tool to be used with bone density and other modifiable, non-GD-specific risk factors (e.g. smoking, alcohol intake, frailty) to inform physicians and previously untreated GD1 patients about risk for a future fracture after starting imiglucerase regardless of whether there is an eventual switch to an alternative ERT or to substrate reduction therapy. GRAF can also help predict the extent that fracture risk increases if initiation of treatment is further delayed.
Moving fluid biomarkers for Alzheimer’s disease from research tools to routine clinical diagnostics
Authors: Zetterberg Henrik , Blennow Kaj 
Published: February 2021

AbstractFour fluid-based biomarkers have been developed into diagnostic tests for Alzheimer’s disease (AD) pathology: the ratio of 42 to 40 amino acid-long amyloid β, a marker of plaque pathology; total-tau and phosphorylated tau, markers of AD-related changes in tau metabolism and secretion; and neurofilament light, a marker of neurodegeneration. When measured in cerebrospinal fluid, these biomarkers can be used in clinical practice to support a diagnosis of mild cognitive impairment or dementia due to AD. Recently, technological breakthroughs have made it possible to measure them in standard blood samples as well. Here, we give an updated account of the current state of the fluid-based AD biomarker research field. We discuss how the new blood tests may be used in research and clinical practice, and what role they may play in relation to more established diagnostic tests, such as CSF biomarkers and amyloid and tau positron emission tomography, to facilitate the effective implementation of future disease-modifying therapies.
Chinese hamster ovary cell line DXB-11: chromosomal instability and karyotype heterogeneity
Authors: Turilova Victoria I. , Goryachaya Tatyana S. , Yakovleva Tatiana K. 
Published: February 2021

Abstract
Background
Chinese hamster ovary cell lines, also known as CHO cells, represent a large family of related, yet quite different, cell lines which are metabolic mutants derived from the original cell line, CHO-ori. Dihydrofolate reductase-deficient DXB-11 cell line, one of the first CHO derivatives, serves as the host cell line for the production of therapeutic proteins. It is generally assumed that DXB-11 is identical to DUKX or CHO-DUK cell lines, but, to our knowledge, DXB-11 karyotype has not been described yet.

Results
Using differential staining approaches (G-, C-banding and Ag-staining), we presented DXB-11 karyotype and revealed that karyotypes of DXB-11 and CHO-DUK cells have a number of differences. Although the number of chromosomes is equal—20 in each cell line—DXB-11 has normal chromosomes of the 1st and 5th pairs as well as an intact chromosome 8. Besides, in DXB-11 line, chromosome der(Z9) includes the material of chromosomes X and 6, whereas in CHO-DUK it results from the translocation of chromosomes 1 and 6. Ag-positive nucleolar organizer regions were revealed in the long arms of chromosome del(4)(q11q12) and both chromosome 5 homologues, as well as in the short arms of chromosomes 8 and add(8)(q11). Only 19 from 112 (16.96%) DXB-11 cells display identical chromosome complement accepted as the main structural variant of karyotype. The karyotype heterogeneity of all the rest of cells (93, 83.04%) occurs due to clonal and nonclonal additional structural rearrangements of chromosomes. Estimation of the frequency of chromosome involvement in these rearrangements allowed us to reveal that chromosomes 9, der(X)t(X;3;4), del(2)(p21p23), del(2)(q11q22) /Z2, der(4) /Z7, add(6)(p11) /Z8 are the most stable, whereas mar2, probably der(10), is the most unstable chromosome. A comparative analysis of our own and literary data on CHO karyotypes allowed to designate conservative chromosomes, both normal and rearranged, that remain unchanged in different CHO cell lines, as well as variable chromosomes that determine the individuality of karyotypes of CHO derivatives.

Conclusion
DXB-11and CHO-DUK cell lines differ in karyotypes. The revealed differential instability of DXB-11 chromosomes is likely not incidental and results in karyotype heterogeneity of cell population.
Performance of model-based multifactor dimensionality reduction methods for epistasis detection by controlling population structure
Authors: Abegaz Fentaw , Van Lishout François , Mahachie John Jestinah M. , Chiachoompu Kridsadakorn , Bhardwaj Archana , Duroux Diane , Gusareva Elena S. , Wei Zhi , Hakonarson Hakon , Van Steen Kristel 
Published: February 2021

AbstractBackgroundIn genome-wide association studies the extent and impact of confounding due to population structure have been well recognized. Inadequate handling of such confounding is likely to lead to spurious associations, hampering replication, and the identification of causal variants. Several strategies have been developed for protecting associations against confounding, the most popular one is based on Principal Component Analysis. In contrast, the extent and impact of confounding due to population structure in gene-gene interaction association epistasis studies are much less investigated and understood. In particular, the role of nonlinear genetic population substructure in epistasis detection is largely under-investigated, especially outside a regression framework.MethodsTo identify causal variants in synergy, to improve interpretability and replicability of epistasis results, we introduce three strategies based on a model-based multifactor dimensionality reduction approach for structured populations, namely MBMDR-PC, MBMDR-PG, and MBMDR-GC.ResultsSimulation results comparing the performance of various approaches show that in the presence of population structure MBMDR-PC and MBMDR-PG consistently better control type I error rate at the nominal level than MBMDR-GC. Moreover, our proposed three methods of population structure correction outperform MDR-SP in terms of statistical power.ConclusionWe demonstrate through extensive simulation studies the effect of various degrees of genetic population structure and relatedness on epistasis detection and propose appropriate remedial measures based on linear and nonlinear sample genetic similarity.
Proteomic insights into synaptic signaling in the brain: the past, present and future
Authors: Xu Yalan , Song Xiuyue , Wang Dong , Wang Yin , Li Peifeng , Li Jing 
Published: February 2021

AbstractChemical synapses in the brain connect neurons to form neural circuits, providing the structural and functional bases for neural communication. Disrupted synaptic signaling is closely related to a variety of neurological and psychiatric disorders. In the past two decades, proteomics has blossomed as a versatile tool in biological and biomedical research, rendering a wealth of information toward decoding the molecular machinery of life. There is enormous interest in employing proteomic approaches for the study of synapses, and substantial progress has been made. Here, we review the findings of proteomic studies of chemical synapses in the brain, with special attention paid to the key players in synaptic signaling, i.e., the synaptic protein complexes and their post-translational modifications. Looking toward the future, we discuss the technological advances in proteomics such as data-independent acquisition mass spectrometry (DIA-MS), cross-linking in combination with mass spectrometry (CXMS), and proximity proteomics, along with their potential to untangle the mystery of how the brain functions at the molecular level. Last but not least, we introduce the newly developed synaptomic methods. These methods and their successful applications marked the beginnings of the synaptomics era.
Long-range GABAergic projections from the nucleus of the solitary tract
Authors: Shi Mei-Yu , Ding Lu-Feng , Guo Yu-Hong , Cheng Yu-Xiao , Bi Guo-Qiang , Lau Pak-Ming 
Published: February 2021

AbstractThe nucleus of the solitary tract (NTS) plays a crucial role in integrating peripheral information regarding visceral functions. Glutamate decarboxylase 2 (GAD2) inhibitory neurons are abundant in the NTS, and are known to form local and short-range projections within the NTS and nearby hindbrain areas. Here we performed whole-brain mapping of outputs from GAD2 neurons in the NTS using cell-type specific viral labeling together with ultrahigh-speed 3D imaging at 1-μm resolution. In addition to well-known targets of NTS GAD2 neurons including the principle sensory nucleus of the trigeminal (PSV), spinal nucleus of the trigeminal (SPV), and other short-range targets within the hindbrain, the high sensitivity of our system helps reveal previously unknown long-range projections that target forebrain regions, including the bed nuclei of the stria terminalis (BST) involved in stress and fear responses, and the paraventricular hypothalamic nucleus (PVH) involved in energy balance and stress-related neuroendocrine responses. The long-range projections were further verified by retrograde labeling of NTS GAD2 neurons with cholera toxin B (CTB) injections in the BST and PVH, and by Cre-dependent retrograde tracing with rAAV2-retro injections in the two regions of GAD2-Cre mice. Finally, we performed complete morphological reconstruction of several sparsely labeled neurons projecting to the forebrain and midbrain. These results provide new insights about how NTS might participate in physiological and emotional modulation.
The IL33 receptor ST2 contributes to mechanical hypersensitivity in mice with neuropathic pain
Authors: Huang Junting , Gadotti Vinicius M. , Zhang Zizhen , Zamponi Gerald W. 
Published: February 2021

AbstractPathogen infection triggers pain via activation of the innate immune system. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) are the main components of innate immunity and have been implicated in pain signaling. We previously revealed that the TLR2-NLRP3-IL33 pathway mediates inflammatory pain responses during hyperactivity of innate immunity. However, their roles in neuropathic pain had remained unclear. Here we report that although knockout of TLR2 or NLRP3 does not affect spared nerve injury (SNI)-induced neuropathic pain, intrathecal inhibition of IL33/ST2 signaling with ST2 neutralizing antibodies reverses mechanical thresholds in SNI mice compared to PBS vehicle treated animals. This effect indicates a universal role of IL33 in both inflammatory and neuropathic pain states, and that targeting the IL33/ST2 axis could be a potential therapeutic approach for pain treatment.
Re‐amputation in patients with diabetes‐related minor amputations who underwent physical therapy during their hospitalization
Authors: Imaoka Shinsuke , Sato Koji , Furukawa Masahide , Okita Minoru , Higashi Toshio 
Published: February 2021

AbstractBackgroundDiabetes‐related foot lesions are a major cause of non‐traumatic lower limb amputations and are associated with a high re‐amputation rate. Lesions can cause hindrance in activities of daily living, reduce physical function, and lower a patient's quality of life. Physical therapy is necessary to prevent these limitations. Thus far, there has been limited investigation into the re‐amputation rate in patients who have undergone physical therapy. This study aimed to elucidate modifiable risk factors for re‐amputation in patients with minor amputations who were treated with physical therapy during their hospitalization.MethodsThis was a retrospective cohort study of 245 consecutive hospitalized patients who presented to our Wound Care Center between January 2015 and February 2018 and received physical therapy after a minor amputation. Participants were identified from admission records to surgical and physical therapy units stored in the electronic medical records. We examined re‐amputations that occurred in the ipsilateral lower extremity during the 1‐year post‐discharge outpatient period. The maximum follow‐up period was set at 1 year. We used Cox proportional hazards analysis to examine factors affecting the risk of re‐amputation.ResultsOf the 129 patients enrolled, 42 patients (32.5%) underwent re‐amputations during an average observation period of 6.2 months (range, 2.1 to 10.9 months). The factors associated with re‐amputation were a requirement for hemodialysis, ankle dorsiflexion angle, and the Functional Independence Measure (FIM) ambulation score.ConclusionsIn diabetes patients with minor amputations, a requirement for hemodialysis, ankle dorsiflexion angle, and the FIM ambulation score were shown to be modifiable risk factors for re‐amputation. This emphasizes that maintaining vascular endothelial function through lower limb muscle exercises for hemodialysis, improving ankle mobility, and relieving plantar pressure during walking are necessary to reduce the risk of re‐amputation. Patients with these risk factors should be encouraged to participate in physical therapy.
Challenges and opportunities for ovarian cancer management in the epidemic of Covid-19: lessons learned from Wuhan, China
Authors: Chen Zhilan , Zhang Chun , Yin Jiu , Xin Xin , Li Hemei , Wang Yapei , Tsang Benjamin K. , Zhang Qinghua 
Published: February 2021

AbstractChina and the rest of the world are experiencing an outbreak of the 2019 novel coronavirus disease (COVID-19). Patients with cancer are more susceptible to viral infection and are more likely to develop severe complications, as compared to healthy individuals. The growing spread of COVID-19 presents challenges for the clinical care of patients with gynecological malignancies. Ovarian debulking surgery combined with the frequent need for chemotherapy is most likely why ovarian cancer was rated as the gynecologic cancer most affected by COVID-19. Therefore, ovarian cancer presents a particular challenging task. Concerning the ovarian cancer studies with confirmed COVID-19 reported from large-scale general hospitals in Wuhan, we hold that the treatment plan was adjusted appropriately and an individualized remedy was implemented. The recommendations discussed here were developed mainly based on the experience from Wuhan. We advise that the management strategy for ovarian cancer patients should be adjusted in the light of the local epidemic situation and formulated according to the pathological type, tumor stage and the current treatment phase. Online medical service is an effective and convenient communication platform during the pandemic.
Hyperglycaemic hyperosmolar state in an obese prepubertal girl with type 2 diabetes: case report and critical approach to diagnosis and therapy
Authors: Mohn Angelika , Polidori Nella , Castorani Valeria , Comegna Laura , Giannini Cosimo , Chiarelli Francesco , Blasetti Annalisa 
Published: February 2021

Abstract
Introduction
Isolated Hyperosmolar Hyperglycaemic Syndrome (HHS) is a life-threatening condition characterized by elevated serum glucose concentrations and hyperosmolality without significant ketosis. It is often described in obese adults with unknown Type 2 Diabetes (T2D), rarely in youth. In childhood the most common cause of metabolic glucose related derangement is Diabetic Ketoacidosis (DKA) in Type 1 Diabetes (T1D). Interestingly, both components can be combined with each other, thus the prevalent condition needs to be recognised implying a different therapeutic approach.

Case presentation
In this case, we report a prepubertal Caucasian obese girl admitted for two episodes of combined HHS/DKA in order to elucidate her clinical course taking into account the current pediatric recommendations based on adult guidelines for HHS.

Conclusions
The treatment of HHS and even more of HHS/DKA in youth is still controversial as no specific guidelines for children are available especially during the prepubertal age. The description of our case might be helpful and offer relevant points for future consensus.
Prevalence of post-intensive care syndrome among Japanese intensive care unit patients: a prospective, multicenter, observational J-PICS study
Authors: Kawakami Daisuke , Fujitani Shigeki , Morimoto Takeshi , Dote Hisashi , Takita Mumon , Takaba Akihiro , Hino Masaaki , Nakamura Michitaka , Irie Hiromasa , Adachi Tomohiro , Shibata Mami , Kataoka Jun , Korenaga Akira , Yamashita Tomoya , Okazaki Tomoya , Okumura Masatoshi , Tsunemitsu Takefumi 
Published: February 2021

Abstract
Background
Many studies have compared quality of life of post-intensive care syndrome (PICS) patients with age-matched population-based controls. Many studies on PICS used the 36-item Short Form (SF-36) health survey questionnaire version 2, but lack the data for SF-36 values before and after intensive care unit (ICU) admission. Thus, clinically important changes in the parameters of SF-36 are unknown. Therefore, we determined the frequency of co-occurrence of PICS impairments at 6 months after ICU admission. We also evaluated the changes in SF-36 subscales and interpreted the patients’ subjective significance of impairment.

Methods
A prospective, multicenter, observational cohort study was conducted in 16 ICUs across 14 hospitals in Japan. Adult ICU patients expected to receive mechanical ventilation for > 48 h were enrolled, and their 6-month outcome was assessed using the questionnaires. PICS definition was based on the physical status, indicated by the change in SF-36 physical component score (PCS) ≥ 10 points; mental status, indicated by the change in SF-36 mental component score (MCS) ≥ 10 points; and cognitive function, indicated by the worsening of Short-Memory Questionnaire (SMQ) score and SMQ score at 6 months < 40. Multivariate logistic regression model was used to identify the factors associated with PICS occurrence. The patients’ subjective significance of physical and mental symptoms was assessed using the 7-scale Global Assessment Rating to evaluate minimal clinically important difference (MCID).

Results
Among 192 patients, 48 (25%) died at 6 months. Among the survivors at 6 months, 96 patients responded to the questionnaire; ≥ 1 PICS impairment occurred in 61 (63.5%) patients, and ≥ 2 occurred in 17 (17.8%) patients. Physical, mental, and cognitive impairments occurred in 32.3%, 14.6% and 37.5% patients, respectively. Population with only mandatory education was associated with PICS occurrence (odds ratio: 4.0, 95% CI 1.1–18.8, P = 0.029). The MCID of PCS and MCS scores was 6.5 and 8.0, respectively.

Conclusions
Among the survivors who received mechanical ventilation, 64% had PICS at 6 months; co-occurrence of PICS impairments occurred in 20%. PICS was associated with population with only mandatory education. Future studies elucidating the MCID of SF-36 scores among ICU patients and standardizing the PICS definition are required.
Trial registration UMIN000034072.