bluuebunny/crossref_metadata_2025_split huggingface dataset:
PCR Array Technology in Biopsy Samples Identifies Up-Regulated mTOR Pathway Genes as Potential Rejection Biomarkers After Kidney Transplantation
Authors: Legaz Isabel , Bernardo María Victoria , Alfaro Rafael , Martínez-Banaclocha Helios , Galián Jose Antonio , Jimenez-Coll Victor , Boix Francisco , Mrowiec Anna , Salmeron Diego , Botella Carmen , Parrado Antonio , Moya-Quiles María Rosa , Minguela Alfredo , Llorente Santiago , Peña-Moral Jesús de la , Muro Manuel 
Published: February 2021

Background: Antibody-mediated rejection (AMR) is the major cause of kidney transplant rejection. The donor-specific human leukocyte antigen (HLA) antibody (DSA) response to a renal allograft is not fully understood yet. mTOR complex has been described in the accommodation or rejection of transplants and integrates responses from a wide variety of signals. The aim of this study was to analyze the expression of the mTOR pathway genes in a large cohort of kidney transplant patients to determine its possible influence on the transplant outcome.Methods: A total of 269 kidney transplant patients monitored for DSA were studied. The patients were divided into two groups, one with recipients that had transplant rejection (+DSA/+AMR) and a second group of recipients without rejection (+DSA/–AMR and –DSA/–AMR, controls). Total RNA was extracted from kidney biopsies and reverse transcribed to cDNA. Human mTOR-PCR array technology was used to determine the expression of 84 mTOR pathway genes. STRING and REVIGO software were used to simulate gene to gene interaction and to assign a molecular function.Results: The studied groups showed a different expression of the mTOR pathway related genes. Recipients that had transplant rejection showed an over-expressed transcript (≥5-fold) of AKT1S1, DDIT4, EIF4E, HRAS, IGF1, INS, IRS1, PIK3CD, PIK3CG, PRKAG3, PRKCB (&gt;12-fold), PRKCG, RPS6KA2, TELO2, ULK1, and VEGFC, compared with patients that did not have rejection. AKT1S1 transcripts were more expressed in +DSA/–AMR biopsies compared with +DSA/+AMR. The main molecular functions of up-regulated gene products were phosphotransferase activity, insulin-like grown factor receptor and ribonucleoside phosphate binding. The group of patients with transplant rejection also showed an under-expressed transcript (≥5-fold) of VEGFA (&gt;15-fold), RPS6, and RHOA compared with the group without rejection. The molecular function of down-regulated gene products such as protein kinase activity and carbohydrate derivative binding proteins was also analyzed.Conclusions: We have found a higher number of over-expressed mTOR pathway genes than under-expressed ones in biopsies from rejected kidney transplants (+DSA/+AMR) with respect to controls. In addition to this, the molecular function of both types of transcripts (over/under expressed) is different. Therefore, further studies are needed to determine if variations in gene expression profiles can act as predictors of graft loss, and a better understanding of the mechanisms of action of the involved proteins would be necessary.
COVID-19 and Risk of Acute Ischemic Stroke and Acute Lung Injury in Patients With Type II Diabetes Mellitus: The Anti-inflammatory Role of Metformin
Authors: Al-kuraishy Hayder M. , Al-Gareeb Ali I. , Alblihed M. , Cruz-Martins Natália , Batiha Gaber El-Saber 
Published: February 2021

Background: Coronavirus disease 19 (COVID-19) is regarded as an independent risk factor for acute ischemic stroke (AIS) due to the induction of endothelial dysfunction, coagulopathy, cytokine storm, and plaque instability.Method: In this retrospective cohort study, a total of 42 COVID-19 patients with type 2 diabetes mellitus (T2DM) who presented with AIS within 1 week of displaying COVID-19 symptoms were recruited. According to the current anti-DM pharmacotherapy, patients were divided into two groups: a Metformin group of T2DM patients with COVID-19 and AIS on metformin therapy (850 mg, 3 times daily (n = 22), and a Non-metformin group of T2DM patients with COVID-19 and AIS under another anti-DM pharmacotherapy like glibenclamide and pioglitazone (n = 20). Anthropometric, biochemical, and radiological data were evaluated.Results: Ferritin serum level was lower in metformin-treated patients compared to non-metformin treated patients (365.93 ± 17.41 vs. 475.92 ± 22.78 ng/mL, p = 0.0001). CRP, LDH, and D-dimer serum levels were also lowered in metformin-treated patients compared to non-metformin treated patients (p = 0.0001). In addition, lung CT scan scores of COVID-19 patients was 30.62 ± 10.64 for metformin and 36.31 ± 5.03 for non-metformin treated patients.Conclusion: Metformin therapy in T2DM patients was linked to a lower risk of AIS during COVID-19. Further studies are needed to observe the link between AIS in COVID-19 diabetic patients and metformin therapy.
The Emergence of Invasive Streptococcus pneumoniae Serotype 24F in Lebanon: Complete Genome Sequencing Reveals High Virulence and Antimicrobial Resistance Characteristics
Authors: Reslan Lina , Finianos Marc , Bitar Ibrahim , Moumneh Mohamad Bahij , Araj George F. , Zaghlout Alissar , Boutros Celina , Jisr Tamima , Nabulsi Malak , Kara yaccoub Gilbert , Hamze Monzer , Osman Marwan , Bou Raad Elie , Hrabak Jaroslav , Matar Ghassan M. , Dbaibo Ghassan 
Published: February 2021

BackgroundInvasive pneumococcal disease (IPD) remains a global health problem. IPD incidence has significantly decreased by the use of pneumococcal conjugate vaccines (PCV). Nevertheless, non-PCV serotypes remain a matter of concern. Eight Streptococcus pneumoniae serotype 24F isolates, belonging to a non-PCV serotype, were detected through the Lebanese Inter-Hospital Pneumococcal Surveillance Program. The aim of the study is to characterize phenotypic and genomic features of the 24F isolates in Lebanon.MethodsWGS using long reads sequencing (PacBio) was performed to produce complete circular genomes and to determine clonality, antimicrobial resistance and virulence determinants.ResultsThe sequencing results yielded eight closed circular genomes. Three multilocus sequence typing (MLST) types were identified (ST11618, ST14184, ST15253). Both MLST and WGS analyses revealed that these isolates from Lebanon were genetically homogenous belonging to clonal complex CC230 and clustered closely with isolates originating from Canada, United States of America, United Kingdom and Iceland. Their penicillin binding protein profiles correlated with both β-lactam susceptibility patterns and MLST types. Moreover, the isolates harbored the macrolide and tetracycline resistance genes and showed a similar virulence gene profile. To our knowledge, this study represents the first report of complete phenotypic and genomic characterization of the emerging Streptococcus pneumoniae, serotype 24F, in the Middle East and North Africa region.
Cerebral Small Vessel Disease Load Predicts Functional Outcome and Stroke Recurrence After Intracerebral Hemorrhage: A Median Follow-Up of 5 Years
Authors: Xu Mangmang , Li Baojin , Zhong Di , Cheng Yajun , Wu Qian , Zhang Shuting , Zhang Shihong , Wu Bo , Liu Ming 
Published: February 2021

Background: Uncertainty exists over the long-term prognostic significance of cerebral small vessel disease (CSVD) in primary intracerebral hemorrhage (ICH).Methods: We performed a longitudinal analysis of CSVD and clinical outcomes in consecutive patients with primary ICH who had MRI. Baseline CSVD load (including white matter hyperintensities [WMH], cerebral microbleeds [CMBs], lacunes, and enlarged perivascular spaces [EPVS]) was evaluated. The cumulative CSVD score was calculated by combining the presence of each CSVD marker (range 0–4). We followed participants for poor functional outcome [modified Rankin scale [mRS] ≥ 4], stroke recurrence, and time-varying survival during a median follow-up of 4.9 [interquartile range [IQR] 3.1–6.0] years. Parsimonious and fuller multivariable logistic regression analysis and Cox-regression analysis were performed to estimate the association of CSVD markers, individually and collectively, with each outcome.Results: A total of 153 patients were included in the analyses. CMBs ≥ 10 [adjusted OR [adOR] 3.252, 95% CI 1.181–8.956, p = 0.023] and periventricular WMH (PWMH) (adOR 2.053, 95% CI 1.220–3.456, p = 0.007) were significantly associated with poor functional outcome. PWMH (adOR 2.908, 95% CI 1.230–6.878, p = 0.015) and lobar CMB severity (adOR 1.811, 95% CI 1.039–3.157, p = 0.036) were associated with stroke recurrence. The cumulative CSVD score was associated with poor functional outcome (adOR 1.460, 95% CI 1.017–2.096) and stroke recurrence (adOR 2.258, 95% CI 1.080–4.723). Death occurred in 36.1% (13/36) of patients with CMBs ≥ 10 compared with 18.8% (22/117) in those with CMB &lt; 10 (adjusted HR 2.669, 95% CI 1.248–5.707, p = 0.011). In addition, the cumulative CSVD score ≥ 2 was associated with a decreased survival rate (adjusted HR 3.140, 95% CI 1.066–9.250, p = 0.038).Conclusions: Severe PWMH, CMB, or cumulative CSVD burden exert important influences on the long-term outcome of ICH.
The Neurophysiological Impact of Experimentally-Induced Pain on Direct Muscle Spindle Afferent Response: A Scoping Review
Authors: Lima Carla R. , Sahu Pradeep K. , Martins Daniel F. , Reed William R. 
Published: February 2021

Background: Musculoskeletal pain disorders are among the leading causes of years lived with disability worldwide representing a significant burden to society. Studies investigating a “nociceptive-fusimotor” relationship using experimentally-induced pain/noxious stimuli and muscle spindle afferent (MSA) response have been published over several decades. The purpose of this scoping review was to systematically identify and summarize research findings related to the impact of experimentally-induced pain or noxious stimulation on direct MSA discharge/response.Methods: PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane and Embase were searched from database inception to August 2020. Eligible studies were: (a) published in English; (b) clinical or pre-clinical studies; (c) original data studies; (d) included the investigation of MSA response to experimentally-induced pain or noxious stimulation; (e) included quantification of at least one direct physiological measure associated with MSA activity/response. Two-phase screening procedures were conducted by a pair of independent reviewers and data extracted from eligible studies.Results: The literature search resulted in 195 articles of which 23 met inclusion criteria. Six studies (26%) were classified as clinical and 17 (74%) as pre-clinical. Two clinical studies investigated the effects of sacral dermatome pin-pricking on MSA response, while the remaining 4 studies investigated the effects of tonic muscle and/or skin pain induced by injection/infusion of hypertonic saline into the tibialis anterior muscle or subdermal tissues. In pre-clinical studies, muscle pain was induced by injection of noxious substances or the surgical removal of the meniscus at the knee joint.Conclusion: Clinical studies in awake humans reported that experimentally-induced pain did not affect, or else slightly decreased MSA spontaneous discharge and/or response during weak dorsiflexor muscle contraction, thus failing to support an excitatory nociceptive-fusimotor relationship. However, a majority of pre-clinical studies indicated that ipsilateral and contralateral muscle injection of noxious substances altered MSA resting discharge and/or response to stretch predominately through static fusimotor reflex mechanisms. Methodological differences (use of anesthesia, stretch methodology, etc.) may ultimately be responsible for the discrepancies between clinical and pre-clinical findings. Additional investigative efforts are needed to reconcile these discrepancies and to clearly establish or refute the existence of nociceptive-fusimotor relationship in muscular pain.
Repetitive Transcranial Magnetic Stimulation With H-Coil in Alzheimer's Disease: A Double-Blind, Placebo-Controlled Pilot Study
Authors: Leocani Letizia , Dalla Costa Gloria , Coppi Elisabetta , Santangelo Roberto , Pisa Marco , Ferrari Laura , Bernasconi Maria Paola , Falautano Monica , Zangen Abraham , Magnani Giuseppe , Comi Giancarlo 
Published: February 2021

Focal repetitive transcranial magnetic stimulation (rTMS) has been applied to improve cognition in Alzheimer's disease (AD) with conflicting results. We applied rTMS in AD in a pilot placebo-controlled study using the H2-coil. H-coils are suitable for targeting wider neuronal structures compared with standard focal coils, in particular the H2-coil stimulates simultaneously the frontal-parietal-temporal lobes bilaterally. Thirty patients (mean age 70.9 year, SD 8.1; mean MMSE score 16.9, SD 5.5) were randomized to sham or real 10 Hz rTMS stimulation with the H2-coil. Each patient underwent 3 sessions/week for 4 weeks, followed by 4 weeks with maintenance treatment (1 session/week). Primary outcome was improvement of ADAS-cog at 4 and 8 weeks compared with baseline. A trend toward an improved ADAS-cog score over time was observed for patients undergoing real rTMS, with actively treated patients experiencing a mean decrease of −1.01 points at the ADAS-Cog scale score per time point (95% CIs −0.02 to −3.13, p &lt; 0.04). This trend was no longer evident 2 months after the end of treatment. Real rTMS showed no significant effect on MMSE and BDI changes over time. These preliminary findings suggest that rTMS with H-coil is feasible and safe in patients with probable AD and might provide beneficial, even though transient, effects on cognition. This study prompts larger studies in the early stages of AD, combining rTMS and cognitive rehabilitation.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04562506.
Impact of COVID-19 on the Speech and Language Therapy Profession and Their Patients
Authors: Chadd Katie , Moyse Kathryn , Enderby Pam 
Published: February 2021

Introduction: The UK's response to the COVID-19 pandemic presented multiple challenges to healthcare services including the suspension of non-urgent care. The impact on neurorehabilitation professions, including speech and language therapy (SLT), has been substantial.Objectives: To review the changes to SLT services triggered by the COVID-19 pandemic with respect to referral rates, service delivery and outcomes, as well as examining the contribution of SLTs to the neurorehabilitation of COVID-19 patients.Methods: Two surveys were distributed to Royal College of Speech and Language Therapists (RCSLT) members exploring experiences of service provision at 6 weeks and 22 weeks after the pandemic was declared in the UK. Responses to closed-ended questions, including questions regarding referral numbers were analyzed descriptively and compared at the two time-points. A database comprising routine clinical data from SLT services across the UK was used to compare information on patients receiving services prior to and during the pandemic. Data on COVID-19 patients was extracted, and findings are provided descriptively.Results: Referrals to SLT services during the acute COVID-19 period in the UK were substantially less than in the same period in 2019. A number of service changes were common including adopting more flexible approaches to provision (such as tele-therapy) and being unable to provide services to some patients. Database analysis suggests fewer patients have accessed SLT since the pandemic began, including a reduction in neurorehabilitation patients. For those who received SLT, the outcomes did not change. SLTs supported a range of needs of COVID-19 patients. Treatment outcomes for COVID-19 patients with dysphagia were positive.Discussion: The pandemic has affected neurorehabilitation and SLT services broadly: referral patterns are different, usual care has been disrupted and interventions have been modified affecting the impact on patient outcomes both positively and negatively. Some patients with COVID-19 require and benefit from SLT intervention.
No Impact of Stochastic Galvanic Vestibular Stimulation on Arterial Pressure and Heart Rate Variability in the Elderly Population
Authors: Matsugi Akiyoshi , Nagino Koji , Shiozaki Tomoyuki , Okada Yohei , Mori Nobuhiko , Nakamura Junji , Douchi Shinya , Oku Kosuke , Nagano Kiyoshi , Tamaru Yoshiki 
Published: February 2021

ObjectiveNoisy galvanic vestibular stimulation (nGVS) is often used to improve postural stability in disorders, such as neurorehabilitation montage. For the safe use of nGVS, we investigated whether arterial pressure (AP) and heart rate vary during static supine and slow whole-body tilt with random nGVS (0.4 mA, 0.1–640 Hz, gaussian distribution) in a healthy elderly population.MethodsThis study was conducted with a double-blind, sham-controlled, cross-over design. Seventeen healthy older adults were recruited. They were asked to maintain a static supine position on a bed for 10 min, and the bed was tilted up (TU) to 70 degrees within 30 s. After maintaining this position for 3 min, the bed was passively tilted down (TD) within 30 s. Real-nGVS or sham-nGVS was applied from 4 to 15 min. The time course of mean arterial pressure (MAP) and RR interval variability (RRIV) were analyzed to estimate the autonomic nervous activity.ResultnGVS and/or time, including pre-/post-event (nGVS-start, TU, and TD), had no impact on MAP and RRIV-related parameters. Further, there was no evidence supporting the argument that nGVS induces pain, vertigo/dizziness, and uncomfortable feeling.ConclusionnGVS may not affect the AP and RRIV during static position and whole-body tilting or cause pain, vertigo/dizziness, and discomfort in the elderly.
Cognitive Behavioral Approach to Treat Obesity: A Randomized Clinical Trial
Authors: Moraes Amanda dos Santos , Padovani Ricardo da Costa , La Scala Teixeira Cauê Vazquez , Cuesta Maria Gabriela Soria , Gil Silvandro dos Santos , de Paula Bárbara , dos Santos Gilberto Monteiro , Gonçalves Rodrigo Tributino , Dâmaso Ana Raimunda , Oyama Lila Missae , Gomes Ricardo José , Caranti Danielle Arisa 
Published: February 2021

Our aim was to analyze and compare the effects of three different long-term treatments on anthropometric profiles, eating behaviors, anxiety and depression levels, and quality of life of groups of adults with obesity.Methods: The 43 participants in the study were randomly assigned to one of three groups: the education and health group (EH, n = 12), which received lectures on health topics; the physical exercise group (PE, n = 13), which underwent physical training; and the interdisciplinary therapy plus cognitive behavioral therapy (IT + CBT) (n = 18) group, which received physical training, nutritional advice, and physical and psychological therapy.Results: Total quality of life increased significantly in the EH group (△ = 2.00); in the PE group, body weight significantly decreased (△ = −1.42) and the physical domain of quality of life improved (△ = 1.05). However, the most significant changes were seen in the IT + CBT group, in which the anthropometric profile improved; there were an increase in quality of life in all domains (physical, psychological, social, and environmental), an improvement in eating behaviors [Dutch Eating Behavior Questionnaire (DEBQ), total △ = −8.39], and a reduction in depression [Beck Depression Inventory (BDI), △ = −10.13).Conclusion: The IT + CBT program was more effective than the PE and EH programs.Clinical Trial Registration Number:NCT02573688.
MiR-1539 and Its Potential Role as a Novel Biomarker for Colorectal Cancer
Authors: Cui Xueyang , Lv Zhi , Ding Hanxi , Xing Chengzhong , Yuan Yuan 
Published: February 2021

PurposeWe investigated microRNA (miR) 1539 as a potential biomarker for predicting the risk and pathobiological behavior of colorectal cancer (CRC).MethodsOur strategy consisted of analyzing 100 serum samples from 51 CRC patients, 49 healthy controls (HCs), and another 56 CRC tissue and matched normal adjacent to tumor (NAT) samples. The relative expression levels of miR-1539 in exosomes, serum and tissues were detected and compared in the different groups, using reverse transcription-polymerase chain reaction (RT-qPCR). The diagnostic value and potential function of miR-1539 were investigated using clinicopathological data combined with bioinformatics analysis.ResultsMiR-1539 expression was significantly up-regulated in exosomes (p = 0.003) and cancer tissue (p &lt; 0.001) from CRC patients. MiR-1539 expression levels in serum varied according to different tumor sites (right-sided vs. left-sided, p = 0.047; left-side CRC vs. HCs, p = 0.031). In terms of diagnostic efficacy, miR-1539 expression in exosomes may help distinguish CRC cases from HCs with a sensitivity of 92.2%, and miR-1539 expression in serum may improve the specificity to 96.6% for left-sided CRC diagnosis. When combined with clinicopathological data, serum miR-1539 levels were positively associated with vascular endothelial growth factor (VEGF) expression (p = 0.028), whilst levels in CRC tissue were positively associated with increased Ki-67 levels (p = 0.035). Poorer pathologic differentiation was potentially related to an increased tendency of miR-1539 expression in CRC tissue (p = 0.071). Based on our bioinformatics analysis, miR-1539 may have a significant mechanistic influence on CRC genesis and progression.ConclusionsCirculating or tissue based miR-1539 may be used as a novel potential biomarker for CRC screening, and a predictor of poor clinicopathological behavior in tumors.
Treatment, Survival, and Prognosis of Advanced-Stage Natural Killer/T-Cell Lymphoma: An Analysis From the China Lymphoma Collaborative Group
Authors: Liu Weiping , Yang Yong , Qi Shunan , Wang Ying , He Xia , Zhang Liling , Qu Baolin , Qian Liting , Hou Xiaorong , Qiao Xueying , Wang Hua , Li Gaofeng , Zhang Yujing , Zhu Yuan , Cao Jianzhong , Wu Junxin , Wu Tao , Zhu Suyu , Shi Mei , Xu Liming , Su Hang , Lin Ningjing , Zhu Jun , Li Yexiong , Song Yuqin 
Published: February 2021

Patients with advanced-stage natural killer/T-cell lymphoma (NKTCL) usually have a poor prognosis. However, there is limited data of comprehensive analysis on this particular patient population due to the rarity of the disease. The present study aimed to investigate the treatment models, survival outcomes, and prognosis of advanced-stage NKTCL. Data from 336 patients with advanced-stage NKTCL diagnosed between 2006 and 2015 in the China Lymphoma Collaborative Group database were retrospectively analyzed. The median age was 42 years and the male/female ratio was 2.4:1. About 97% of patients had stage IV disease and 77% had &gt;1 extranodal involvement site. All patients received chemotherapy, with the most common option being asparaginase (Asp)-containing regimens (n=146; 43.5%). Among 286 patients with available response data, the overall response rate (ORR) was 57.3% with a complete remission (CR) rate of 35.7%. Asp-containing regimens led to better ORRs (86/132, 65.2% vs. 54/113, 47.8%, P = 0.006) and CR rates (60/132, 45.5% vs. 27/113, 23.9%, P &lt; 0.001) than non-Asp-containing regimens. The expected 5-year progression-free survival (PFS) and overall survival (OS) rates were 22.6 and 32.0%, respectively, for the whole cohort. Compared to non-Asp-containing chemotherapy, Asp-containing chemotherapy improved 5-year PFS (34.2 vs. 17.1%, P &lt; 0.001) and OS (45.3 vs. 27.8%, P &lt; 0.001). A trend toward improvement in OS was observed when gemcitabine was added to Asp-containing chemotherapies. Moreover, those undergoing autologous hematopoietic stem cell transplantation had prolonged survival time. In conclusion, Asp-containing chemotherapy could improve the prognosis of advanced-stage NKTCL, and refinement of treatment models is warranted in the future.