bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of HPV E6/E7 mRNA examination using in situ hybridization in diagnosing cervical intraepithelial lesions
Authors: Hui Chang , Bai Huimin , Liu Jun , Lu Xuerong , Wang Shuzhen , Zhang Zhenyu , Jin Mulan , Wang Yue , Liu Yuzhen
Published: February 2021

Background

The consistency of pathologists in the diagnosis of cervical intraepithelial neoplasia (CINs) is not ideal, especially between low- and high-grade squamous intraepithelial lesions (LSIL and HSIL). This study was aimed to explore efficient strategies for the grading of CINs.

Methods

The medical records of patients with high risk human papillomavirus (HR-HPV) infections who had underwent cervical biopsy or conization from April 2018 to April 2019 in Beijing Chao-Yang Hospital were collected and examined. The HR-HPV E6/E7 mRNA in the tissues of patients with CINs was detected using RNAscope chromogenic in situ hybridization (RISH). Immunohistochemistry (IHC) was performed to evaluate the expression of p16INK4a (P16) and Ki67.

Results

HR-HPV E6/E7 mRNA signals were detected in 3/27 (11.1 %) of CIN 1, and in 32/33 (97.0 %) of CIN 2/3. Most of the staining patterns (27/32, 84.4 %) had a full-thickness epithelial layer staining with weak-to-strong nuclear and cytoplasmic dot-like signals in CIN 2/3, and there were also few special staining patterns that were significantly different from the others. A number of indicators were compared between LSIL and HSIL. There were statistically significant differences in E6/E7 mRNA, p16, Ki67 and cytology between the two groups (P < 0.05). According to the logistic regression analysis, merely E6/E7 mRNA positivity was significantly associated with CIN2/3 (OR: 52.53, 95 % CI,P < 0.05). In the detection of CIN 2/3, the sensitivity and specificity of HPV E6/E7 mRNA alone was not significantly inferior to that of its different combinations with Ki67, p16 and cytology (all,P > 0.05).

Conclusions

RISH is efficient in grading of CINs. The HPV E6/E7 mRNA expression might reflect the phase HPV infections, and its positive pattern might predict the development direction of CINs, providing the possibility to realize more accurate treatments for patients.
Traditional knowledge and practice of the Triassic variegated clay from Silesia (Krasiejów), Poland, in human medicine
Authors: Spielvogel Izabela , Spałek Krzysztof , Badora Krzysztof , Proćków Jarosław
Published: February 2021

Background

Krasiejów clay (in German: Krascheow) became famous following the discovery of numerous fossilised bones of Upper Triassic amphibians and reptiles, which have been extracted from clay deposits since the 1980s. These organic remnants remained in Krasiejów clay due to the large amount of slime deposits and the optimal concentration of basal mineral salts.

The main aims of the paper are to determine the historical evolution of the use of clay in Silesia for therapeutic purposes and to provide a summary of the historical uses of Krasiejów clay as a medical treatment, based on the knowledge of the local population.

Methods

The mode of utilisation of Triassic variegated claystone treatment from Krasiejów was surveyed based on oral communication with local people. This information was collected over the last 35 years (1982–2017) by interviewing those who used clay as a traditional remedy, especially the eldest residents. Each resident was interviewed several times regarding the healing properties of Krasiejów clay, including the causes and symptoms of the ailments treated, mode of clay preparation, application methods, and dosage through semistructured interviews.

Results

Clay from Krasiejów was used in medicine after proper preparation. The clay underwent a complicated preparation process before the use in wraps, compresses, poultices, and baths as a skin peeling agent and even as a potion to be drunk. All recorded applications, diseases, and ailments to which it were applied are described here in detail, divided into treatments with warm, and cold clay.

Conclusions

Krasiejów variegated claystone had different benefits depending on the form in which it was used; different diseases were treated with warm and cold clay. According to informants, many of these diseases have been successfully treated, in particular eczema of various origins, purulent ulcers on the skin, and following internal use, digestive ailments. According to informants, in cases where the disease could not be cured, for instance, psoriasis, a significant improvement in the condition of the skin was visible in a short period of time. Clay from Krasiejów should be subjected to more detailed physicochemical analyses to determine its exact chemical composition and healing properties.
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

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

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

Four 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

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

Background

In 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.

Methods

To 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.

Results

Simulation 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.

Conclusion

We 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

Chemical 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

The 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

Pathogen 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.
Correction to: MCL-1 inhibitors, fast-lane development of a new class of anti-cancer agents
Authors: Bolomsky Arnold , Vogler Meike , Köse Murat Cem , Heckman Caroline A. , Ehx Grégory , Ludwig Heinz , Caers Jo
Published: February 2021

An amendment to this paper has been published and can be accessed via the original article.
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

Background

Diabetes‐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.

Methods

This 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.

Results

Of 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.

Conclusions

In 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

China 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

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

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.
Surge effects and survival to hospital discharge in critical care patients with COVID-19 during the early pandemic: a cohort study
Authors: Dale Christopher R. , Starcher Rachael W. , Chang Shu Ching , Robicsek Ari , Parsons Guilford , Goldman Jason D. , Vovan Andre , Hotchkin David , Gluckman Tyler J.
Published: February 2021

Background

The early months of the COVID-19 pandemic were fraught with much uncertainty and some resource constraint. We assessed the change in survival to hospital discharge over time for intensive care unit patients with COVID-19 during the first 3 months of the pandemic and the presence of any surge effects on patient outcomes.

Methods

Retrospective cohort study using electronic medical record data for all patients with laboratory-confirmed COVID-19 admitted to intensive care units from February 25, 2020, to May 15, 2020, at one of 26 hospitals within an integrated delivery system in the Western USA. Patient demographics, comorbidities, and severity of illness were measured along with medical therapies and hospital outcomes over time. Multivariable logistic regression models were constructed to assess temporal changes in survival to hospital discharge during the study period.

Results

Of 620 patients with COVID-19 admitted to the ICU [mean age 63.5 years (SD 15.7) and 69% male], 403 (65%) survived to hospital discharge and 217 (35%) died in the hospital. Survival to hospital discharge increased over time, from 60.0% in the first 2 weeks of the study period to 67.6% in the last 2 weeks. In a multivariable logistic regression analysis, the risk-adjusted odds of survival to hospital discharge increased over time (biweekly change, adjusted odds ratio [aOR] 1.22, 95% CI 1.04–1.40, P = 0.02). Additionally, an a priori-defined explanatory model showed that after adjusting for both hospital occupancy and percent hospital capacity by COVID-19-positive individuals and persons under investigation (PUI), the temporal trend in risk-adjusted patient survival to hospital discharge remained the same (biweekly change, aOR 1.18, 95% CI 1.00–1.38, P = 0.04). The presence of greater rates of COVID-19 positive/PUI as a percentage of hospital capacity was, however, significantly and inversely associated with survival to hospital discharge (aOR 0.95, 95% CI 0.92–0.98, P < 0.01).

Conclusions

During the early COVID-19 pandemic, risk-adjusted survival to hospital discharge increased over time for critical care patients. An association was also seen between a greater COVID-19-positive/PUI percentage of hospital capacity and a lower survival rate to hospital discharge.
FlsnRNA-seq: protoplasting-free full-length single-nucleus RNA profiling in plants
Authors: Long Yanping , Liu Zhijian , Jia Jinbu , Mo Weipeng , Fang Liang , Lu Dongdong , Liu Bo , Zhang Hong , Chen Wei , Zhai Jixian
Published: February 2021

The broad application of single-cell RNA profiling in plants has been hindered by the prerequisite of protoplasting that requires digesting the cell walls from different types of plant tissues. Here, we present a protoplasting-free approach, flsnRNA-seq, for large-scale full-length RNA profiling at a single-nucleus level in plants using isolated nuclei. Combined with 10x Genomics and Nanopore long-read sequencing, we validate the robustness of this approach in Arabidopsis root cells and the developing endosperm. Sequencing results demonstrate that it allows for uncovering alternative splicing and polyadenylation-related RNA isoform information at the single-cell level, which facilitates characterizing cell identities.
In situ measurements of oxidation–reduction potential and hydrogen peroxide concentration as tools for revealing LPMO inactivation during enzymatic saccharification of cellulose
Authors: Kadić Adnan , Várnai Anikó , Eijsink Vincent G. H. , Horn Svein Jarle , Lidén Gunnar
Published: February 2021

Background

Biochemical conversion of lignocellulosic biomass to simple sugars at commercial scale is hampered by the high cost of saccharifying enzymes. Lytic polysaccharide monooxygenases (LPMOs) may hold the key to overcome economic barriers. Recent studies have shown that controlled activation of LPMOs by a continuous H2O2 supply can boost saccharification yields, while overdosing H2O2 may lead to enzyme inactivation and reduce overall sugar yields. While following LPMO action by ex situ analysis of LPMO products confirms enzyme inactivation, currently no preventive measures are available to intervene before complete inactivation.

Results

Here, we carried out enzymatic saccharification of the model cellulose Avicel with an LPMO-containing enzyme preparation (Cellic CTec3) and H2O2 feed at 1 L bioreactor scale and followed the oxidation–reduction potential and H2O2 concentration in situ with corresponding electrode probes. The rate of oxidation of the reductant as well as the estimation of the amount of H2O2 consumed by LPMOs indicate that, in addition to oxidative depolymerization of cellulose, LPMOs consume H2O2 in a futile non-catalytic cycle, and that inactivation of LPMOs happens gradually and starts long before the accumulation of LPMO-generated oxidative products comes to a halt.

Conclusion

Our results indicate that, in this model system, the collapse of the LPMO-catalyzed reaction may be predicted by the rate of oxidation of the reductant, the accumulation of H2O2 in the reactor or, indirectly, by a clear increase in the oxidation–reduction potential. Being able to monitor the state of the LPMO activity in situ may help maximizing the benefit of LPMO action during saccharification. Overcoming enzyme inactivation could allow improving overall saccharification yields beyond the state of the art while lowering LPMO and, potentially, cellulase loads, both of which would have beneficial consequences on process economics.
Lymphatic muscle cells contribute to dysfunction of the synovial lymphatic system in inflammatory arthritis in mice
Authors: Liang Qianqian , Zhang Li , Xu Hao , Li Jinlong , Chen Yan , Schwarz Edward M. , Shi Qi , Wang Yongjun , Xing Lianping
Published: February 2021

Background

Our previous studies reveal that impaired draining function of the synovial lymphatic vessel (LV) contributes to the pathogenesis of inflammatory arthritis, but the cellular and molecular mechanisms involved are not fully understood.

Objective

To investigate the involvement of lymphatic muscle cells (LMCs) in mediating impaired LV function in inflammatory arthritis.

Methods

TNF transgenic (TNF-Tg) arthritic mice were used. The structure and function of the LVs that drained the hind limbs were examined by whole-mount immunofluorescence staining, electron microscopy, and near-infrared lymphatic imaging. Primary LMCs were treated with TNF, and the changes in proliferation, apoptosis, and functional gene expression were assessed. The roles of the herbal drug, Panax notoginseng saponins (PNS), in arthritis and LVs were studied.

Results

TNF-Tg mice developed ankle arthritis with age, which was associated with abnormalities of LVs: (1) dilated capillary LVs with few branch points, (2) mature LVs with reduced LMC coverage and draining function, and (3) degenerative and apoptotic appearance of LMCs. TNF caused LMC apoptosis, reduced expression of muscle functional genes, and promoted the production of nitric oxide (NO) by lymphatic endothelial cells (LECs). PNS attenuated arthritis, restored LMC coverage and draining function of mature LVs, inhibited TNF-mediated NO expression, and reduced LMC apoptosis.

Conclusion

The impaired draining function of LVs in TNF-Tg mice involves LMC apoptosis. TNF promotes LMC death directly and indirectly via NO production by LECs. PNS attenuates arthritis, improves LVs, and prevents TNF-induced LMC apoptosis by inhibiting NO production of LECs. LMCs contribute to the dysfunction of synovial LVs in inflammatory arthritis.
The effect of pelvic pathology on uterine vein diameters
Authors: Amin T. N. , Wong M. , Foo X. , Pointer S.-L. , Goodhart V. , Jurkovic D.
Published: February 2021

Background

Transvaginal ultrasound (TVS) is a sensitive tool for detecting various conditions that contribute to pelvic pain. TVS can be also used to assess blood flow and measure the size of pelvic veins. Pelvic venous congestion (PVC) is characterised by enlargement of the pelvic veins and has been recognised as a cause of chronic pelvic pain. The reference ranges for uterine venous diameter in women with normal pelvic organs have been established, but there is no information regarding the potential effect of pelvic pathology on the uterine venous diameters. The aim of this study was to examine the size of uterine venous plexus in women with evidence of pelvic abnormalities on TVS and to determine whether the reference ranges need to be adjusted in the presence of pelvic pathology.

A prospective, observational study was conducted in our gynaecological outpatient clinic. Morphological characteristics of all pelvic abnormalities detected on TVS and their sizes were recorded. The uterine veins were identified and their diameters were measured in all cases. The primary outcome measure was the uterine venous diameter. Regression analyses were performed to determine factors affecting the uterine venous size in women with pelvic pathology.

Results

A total of 1500 women were included into the study, 1014 (67%) of whom were diagnosed with pelvic abnormalities. Women with pelvic pathology had significantly larger uterine venous diameters than women with normal pelvic organs (p < 0.01). Multivariable analysis showed that pre-menopausal status, high parity, presence of fibroids (p < 0.001) and Black ethnicity were all associated with significantly larger uterine vein diameters. Based on these findings modified reference ranges for uterine venous diameters have been designed which could be used for the diagnosis of PVC in women with uterine fibroids.

Conclusions

Our findings show that of all pelvic pathology detected on TVS, only fibroids are significantly associated with uterine venous enlargement. Factors known to be associated with enlarged veins in women with normal pelvic organs, namely parity and menopausal status, also apply in patients with pelvic pathology. Future studies of uterine venous circulation should take into account the presence and size of uterine fibroids when assessing women for the signs of PVC.
Gut microbiota of patients with different subtypes of gastric cancer and gastrointestinal stromal tumors
Authors: Sarhadi Virinder , Mathew Binu , Kokkola Arto , Karla Tiina , Tikkanen Milja , Rautelin Hilpi , Lahti Leo , Puolakkainen Pauli , Knuutila Sakari
Published: February 2021

Background

Gastric adenocarcinoma is associated withH. pyloriinfection and inflammation that can result in the dysbiosis of gastric microbiota. The association of intestinal microbiota with gastric adenocarcinoma subtypes or with gastric gastrointestinal stromal tumors (GIST) is however not well known. Therefore, we performed 16S rRNA gene sequencing on DNA isolated from stool samples of Finnish patients and controls to study differences in microbiota among different histological subtypes of gastric adenocarcinoma, gastric GIST and healthy controls.

Results

We found that gut microbiota alpha diversity was lowest in diffuse adenocarcinoma patients, followed by intestinal type and GIST patients, although the differences were not significant compared to controls. Beta-diversity analysis however showed significant differences in microbiota composition for all subtypes compared to controls. Significantly higher abundance ofEnterobacteriaceaewas observed in both adenocarcinoma subtypes, whereas lower abundance ofBifidobacteriaceaewas seen only in diffuse adenocarcinoma and ofOscillibacterin intestinal adenocarcinoma. Both GIST and adenocarcinoma patients had higher abundance ofEnterobacteriaceaeand lower abundance ofLactobacillaceaeandOscillibacterwhile lower abundance ofLachnoclostridium, Bifidobacterium, ParabacteroidesandBarnesiellawas seen only in the adenocarcinoma patients.

Conclusions

Our analysis shows association of higherEnterobacteriaceaeabundance with all types of gastric tumors. Therefore it could be potentially useful as a marker of gastric malignancies. Lower gut microbiota diversity might be indicative of poorly differentiated, invasive, advanced or aggressive tumors and could possibly be a prognostic marker for gastric tumors.
Data on gender representation in food and beverage print advertisements found in corner stores from Guatemala and Peru
Authors: Rozas Lucila , Busse Peter , Barnoya Joaquin , Garrón Alejandra
Published: February 2021

Objectives

Data on gender representation in food and beverage advertisements may allow for a better understanding of how the food industry is targeting different audiences based on gender. Nonetheless, scant research on food and beverage print advertising with a gender approach has been conducted. Therefore, we sought to assess the prevalence of gender focus in print advertisements found inside corner stores in two cities: Guatemala City, Guatemala, and Lima, Peru.

Data description

We developed two complementary datasets as part of the study: (1) a dataset of digital photographs of 200 food and beverage print advertisements found in corner stores located near schools (100 ads per country selected according to criteria such as product type, image quality, and uniqueness); (2) a quantitative dataset with data of the content analysis of these photographs. We employed 19 variables to record the general information and gender assessment of the ads. These datasets should allow scholars and public officials to identify gender-specific marketing strategies of the food industry that might impact children’s and adolescents’ nutrition differently.
MicroRNAs overexpressed in Crohn’s disease and their interactions with mechanisms of epigenetic regulation explain novel aspects of Crohn’s disease pathogenesis
Authors: Fernández-Ponce Cecilia , Navarro Quiroz Roberto , Díaz Perez Anderson , Aroca Martinez Gustavo , Cadena Bonfanti Andrés , Acosta Hoyos Antonio , Gómez Escorcia Lorena , Hernández Agudelo Sandra , Orozco Sánchez Christian , Villarreal Camacho José , Atencio Ibarra Linda , Consuegra Machado Jose , Espinoza Garavito Alberto , García-Cózar Francisco , Navarro Quiroz Elkin
Published: February 2021

Background

In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease.

Methods

We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database.

Results

We found 190 miRNAs with great abundance in patients with CD, of which 26 miRNAs regulate the gene expression of enzymes known to catalyze epigenetic modifications involved in essentials pathophysiological processes, such as chromatin architecture reorganization, immune response regulation including CD4+ T cells polarization, integrity of gut mucosa, gut microbiota composition and tumorigenesis.

Conclusion

The integrated analysis of miRNAs with a high relative abundance in patients with CD showed a combined and superimposed gene expression regulation of enzymes associated with relevant epigenetic mechanisms and that could explain, in part, the pathogenesis of CD.
Cognitive trajectories of patients with focal ß-amyloid deposition
Authors: Kim Si Eun , Lee Byungju , Jang Hyemin , Chin Juhee , Khoo Ching Soong , Choe Yeong Sim , Kim Ji Sun , Kang Sung Hoon , Kim Hang-Rai , Hwangbo Song , Jeong Jee Hyang , Yoon Soo Jin , Park Kyung Won , Kim Eun-Joo , Yoon Bora , Jang Jae-Won , Hong Jin Yong , Na Duk L. , Seo Sang Won , Choi Seong Hye , Kim Hee Jin
Published: February 2021

Background

The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition.

Methods

We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer’s disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1–9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group.

Results

Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7–9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1–3 or 4–6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex.

Conclusions

When predicting cognitive decline of patients with focal Aß deposition, the patients’ cognitive level, extent, and location of the focal involvement are important.
ARID1A genomic alterations driving microsatellite instability through somatic MLH1 methylation with response to immunotherapy in metastatic lung adenocarcinoma: a case report
Authors: Durán Mercedes , Faull Iris , Lastra Enrique , Laes Jean-Francois , Rodrigo Ana Belén , Sánchez-Escribano Ricardo
Published: February 2021

Background

Tumor molecular screening allows categorization of molecular alterations to select the best therapeutic strategy. AT-rich interactive domain-containing 1A (ARID1A) gene mutations are present in gastric, endometrial, and clear cell ovarian tumors. Inactivation of this gene impairs mismatch repair (MMR) machinery leading to an increased mutation burden that correlates with microsatellite instability (MSI), associated with tumor-infiltrating lymphocytes and programmed death ligand 1 (PD-L1) expression. This is the first case report in lung adenocarcinoma of ARID1A gene alterations leading to sporadic MSI, through somatic mutL homolog 1 (MLH1) promoter methylation, with an MLH1 gene mutation as the second somatic hit.

Case presentation

A 50-year-old never-smoker Bulgarian woman, with no comorbidities and no family history of cancer, was diagnosed with metastatic lung adenocarcinoma. PD-L1 immunohistochemistry (IHC) of tissue biopsies on right groin adenopathies resulted in 30% positivity. Liquid biopsy test reported actionable alterations in ARID1A gene, rearranged during transfection (RET) gene fusions, epidermal growth factor receptor (EGFR) gene R776H mutation, breast cancer (BRCA) genes 1/2, and cyclin-dependent kinase inhibitor 2A (CDKN2A) gene mutations. The patient was treated with immunotherapy, and showed a treatment response lasting for 19 months until a new metastasis appeared at the right deltoid muscle. Genomic analysis of a sample of this metastasis confirmed PD-L1 positivity of greater than 50% with CD8+ T cells expression and showed MSI with a deleterious c.298C>T (p.R100*) MLH1 gene mutation. Multiplex ligation-dependent probe amplification (MLPA) of this sample unveiled MLH1 gene promoter methylation. The MLH1 gene mutation and the MLH1 gene methylation were not present at the germline setting.

Conclusions

In this particular case, we show that ARID1A gene mutations with sporadic MSI due to somatic MLH1 gene promoter methylation and MLH1 gene mutation could change the prognosis and define the response to immunotherapy in a patient with lung adenocarcinoma. Comprehensive solid and liquid biopsy tests are useful to find out resistance mechanisms to immune checkpoint inhibitors. Our data encourages the development of new therapies against ARID1A mutations and epigenomic methylation when involved in MSI neoplasms.