bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial miRNA Determines Chemoresistance by Reprogramming Metabolism and Regulating Mitochondrial Transcription
Authors: Fan Song , Tian Tian , Chen Weixiong , Lv Xiaobin , Lei Xinyuan , Zhang Hanqing , Sun Sheng , Cai Lei , Pan Guokai , He Lile , Ou Zhanpeng , Lin Xinyu , Wang Xinhui , Perez Matthew Francis , Tu Zhiming , Ferrone Soldano , Tannous Bakhos A. , Li Jinsong 
Published: January 2019

Abstract

miRNAs that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNAs (mitomiR). mitomiRs have been shown to modulate the translational activity of the mitochondrial genome, yet their role in mitochondrial DNA (mtDNA) transcription remains to be determined. Here we report that the mitomiR-2392 regulates chemoresistance in tongue squamous cell carcinoma (TSCC) cells by reprogramming metabolism via downregulation of oxidative phosphorylation and upregulation of glycolysis. These effects were mediated through partial inhibition of mtDNA transcription by mitomiR-2392 rather than through translational regulation. This repression required specific miRNA–mtDNA base pairing and Argonaute 2. mitomiR-2392 recognized target sequences in the H-strand and partially inhibited polycistronic mtDNA transcription in a cell-specific manner. A retrospective analysis of TSCC patient tumors revealed a significant association of miR-2392 and regulated mitochondrial gene expression with chemosensitivity and overall survival. The clinical relevance of targeted mitochondrial genes was consistently validated by The Cancer Genome Atlas RNA sequencing in multiple types of cancer. Our study revealed for the first time the role of mitomiR in mtDNA transcription and its contribution to the molecular basis of tumor cell metabolism and chemoresistance.

Significance: These findings uncover a novel mechanism by which mitomiRNA regulates mitochondrial transcription and provide rationale for use of mitomiRNA and mtDNA-encoded genes to predict chemosensitivity and patient clinical prognosis.
Immune Checkpoint Inhibitor-induced Reinvigoration of Tumor-infiltrating CD8+ T Cells is Determined by Their Differentiation Status in Glioblastoma
Authors: Park Junsik , Kwon Minsuk , Kim Kyung Hwan , Kim Tae-Shin , Hong Seon-Hui , Kim Chang Gon , Kang Seok-Gu , Moon Ju Hyung , Kim Eui Hyun , Park Su-Hyung , Chang Jong Hee , Shin Eui-Cheol 
Published: January 2019

Abstract

Purpose:
Immune checkpoint inhibitors (ICI) are used for the treatment of various cancers, but clinical trials of anti-programmed cell death protein 1 (PD-1) with patients with recurrent glioblastoma (GBM) have failed to show clinical benefits. In this study, we examined the differentiation status of CD8+ tumor-infiltrating lymphocytes (TIL) from patients with primary GBM and their reinvigoration by ICIs to understand the nature of T-cell exhaustion in GBM.

Experimental Design:
We isolated TILs from 98 patients with newly diagnosed GBM and examined the expression of immune checkpoint receptors and T-cell transcription factors using flow cytometry. TILs were ex vivo stimulated with anti-CD3 in the presence of anti-PD-1 and/or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) and their proliferation assessed.

Results:
CD8+ TILs had significantly increased expression of immune checkpoint receptors, including PD-1 and CTLA-4, compared with peripheral blood CD8+ T cells. Among CD8+ TILs, PD-1+ cells exhibited more terminally differentiated phenotypes (i.e., EomeshiT-betlo) than PD-1− cells. These data were confirmed by analyzing NY-ESO-1157–specific CD8+ TILs. Evaluating the proliferation of CD8+ TILs after ex vivo stimulation with anti-CD3 and anti-PD-1, we found that proliferation inversely correlated with the percentage of EomeshiT-betlo cells among PD-1+CD8+ TILs. When anti-CTLA-4 was used in combination with anti-PD-1, an additional increase in CD8+ TIL proliferation was observed in patients with low percentages of EomeshiT-betlo CD8+ TILs, who responded well to anti-PD-1 in ex vivo assays, but not in patients with high percentages of EomeshiT-betlo CD8+ TILs, who did not respond to anti-PD-1.

Conclusions:
In primary GBM, the differentiation status of CD8+ TILs determines their reinvigoration ability upon ICI treatment.
PVRIG and PVRL2 Are Induced in Cancer and Inhibit CD8+ T-cell Function
Authors: Whelan Sarah , Ophir Eran , Kotturi Maya F. , Levy Ofer , Ganguly Sudipto , Leung Ling , Vaknin Ilan , Kumar Sandeep , Dassa Liat , Hansen Kyle , Bernados David , Murter Benjamin , Soni Abha , Taube Janis M. , Fader Amanda Nickles , Wang Tian-Li , Shih Ie-Ming , White Mark , Pardoll Drew M. , Liang Spencer C. 
Published: January 2019

AbstractAlthough checkpoint inhibitors that block CTLA-4 and PD-1 have improved cancer immunotherapies, targeting additional checkpoint receptors may be required to broaden patient response to immunotherapy. PVRIG is a coinhibitory receptor of the DNAM/TIGIT/CD96 nectin family that binds to PVRL2. We report that antagonism of PVRIG and TIGIT, but not CD96, increased CD8+ T-cell cytokine production and cytotoxic activity. The inhibitory effect of PVRL2 was mediated by PVRIG and not TIGIT, demonstrating that the PVRIG–PVRL2 pathway is a nonredundant signaling node. A combination of PVRIG blockade with TIGIT or PD-1 blockade further increased T-cell activation. In human tumors, PVRIG expression on T cells was increased relative to normal tissue and trended with TIGIT and PD-1 expression. Tumor cells coexpressing PVR and PVRL2 were observed in multiple tumor types, with highest coexpression in endometrial cancers. Tumor cells expressing either PVR or PVRL2 were also present in numbers that varied with the cancer type, with ovarian cancers having the highest percentage of PVR−PVRL2+ tumor cells and colorectal cancers having the highest percentage of PVR+PVRL2− cells. To demonstrate a role of PVRIG and TIGIT on tumor-derived T cells, we examined the effect of PVRIG and TIGIT blockade on human tumor-infiltrating lymphocytes. For some donors, blockade of PVRIG increased T-cell function, an effect enhanced by combination with TIGIT or PD-1 blockade. In summary, we demonstrate that PVRIG and PVRL2 are expressed in human cancers and the PVRIG–PVRL2 and TIGIT–PVR pathways are nonredundant inhibitory signaling pathways.See related article on p. 244
Herpesviridae Seropositivity in Patients with Multiple Sclerosis: First Polish Study
Authors: Czarnowska Agata , Kapica-Topczewska Katarzyna , Zajkowska Olga , Świerzbińska Renata , Chorąży Monika , Tarasiuk Joanna , Zajkowska Joanna , Kochanowicz Jan , Kułakowska Alina 
Published: January 2019

<b><i>Background:</i></b> Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that leads to inflammation, demyelination and neurodegeneration. Viral aetiology has been suspected to be an MS trigger for a long time, and herpesviruses (HSs) are among the potential pathogens involved. <b><i>Objectives:</i></b> The present investigation aims to detect the presence of antibodies against the herpes simplex virus (HSV), varicella-zoster virus, Epstein-Barr virus (EBV), human cytomegalovirus (CMV) and human herpesvirus 6 (HHV6) in the serum of MS patients and control individuals in north-eastern Poland. <b><i>Method:</i></b> Plasma was collected from 141 MS patients and 44 blood donors who served as the control group. These individuals were assessed for the presence of antibodies using an enzyme-linked immunosorbent assay. <b><i>Results:</i></b> The statistical analysis showed a higher probability of EBV (<i>p</i> = 0.037, OR 4.359) and HHV6 (<i>p</i> = 0.020, OR 3.343) antibody presence in patients with MS compared to that in the control group. In the MS patient group, the prevalence of CMV IgG antibodies was significantly higher in females (<i>p</i> = 0.025). Patients who tested positive for anti-EBV IgG were diagnosed 7.9 years earlier than patients who tested negative for anti-EBV IgG (<i>p</i> = 0.048). <b><i>Conclusions:</i></b> The study showed that MS patients in north-eastern Poland were more likely to be seropositive for EBV and HHV6 than healthy individuals. Further work should be undertaken in other regions of Poland and other European countries with particular attention paid to testing seropositivity in all HSs, particularly in the MS patient population, to evaluate the impact of HSs on MS patients in different environments.
A new name for Stenus absconditus Tang &amp; Hu, 2018 (Coleoptera, Staphylinidae)
Authors: HU CHENG-ZHI , TANG LIANG 
Published: January 2019

Stenus absconditus Hu & Tang, 2018 was published in our recent paper, and latter Dr. Alfred Francis Newton kindly informed us that the name was preoccupied by Stenus absconditus Puthz 2017. After confirming the information, we propose a new replacement name for this species.
Association of maternal prenatal acetaminophen use with the risk of attention deficit/hyperactivity disorder in offspring: A meta-analysis
Authors: Gou Xiaoyun , Wang Yan , Tang Ying , Qu Yi , Tang Jun , Shi Jing , Xiao Dongqiong , Mu Dezhi 
Published: January 2019

Background: Acetaminophen is a widely used medication for fever and pain management during pregnancy. However, recent studies have found a possible connection between maternal prenatal acetaminophen use and attention deficit/hyperactivity disorder in children. Objective: We aimed to explore the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring. Data sources: PubMed, Embase, Web of Science and Cochrane Library were searched from their initial publications through November 2018 for studies. Study selection: We included all studies that examined the association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring if the authors reported odds ratios, risk ratios, hazard ratios, regression coefficient, standard error and 95% confidence intervals. Data extraction and synthesis: Two reviewers independently extracted data on the definition of exposure and outcome, exposed, non-exposed and total number of participants in the sample population, adjusted potential confounders and outcome parameters. Study quality was also assessed. Results: Eight cohort studies with a total of 244,940 participants were included. Maternal exposure to acetaminophen during pregnancy increased the risk of attention deficit/hyperactivity disorder in offspring with a pooled adjusted risk ratio of 1.25 (95% confidence interval = [1.17, 1.34]). Children exposed prenatally to acetaminophen in the third trimester seemed to have the greatest risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.26; 95% confidence interval = [1.08, 1.47]). In addition, a longer duration of maternal acetaminophen use during pregnancy was correlated with a higher risk ratio. Children whose mothers used acetaminophen for 28 or more days during gestation had a higher risk of developing attention deficit/hyperactivity disorder (risk ratio: 1.63; 95% confidence interval = [1.23, 2.16]). Conclusion: There is an association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring. The timing and duration of acetaminophen use during pregnancy may have a major effect on the risk of attention deficit/hyperactivity disorder.
Effects of Task-Induced Fatigue in Prolonged Conditional Automated Driving
Authors: Jarosch Oliver , Bellem Hanna , Bengler Klaus 
Published: January 2019

Objective: The aim of this study was to investigate the effects of task-induced fatigue in prolonged conditional automated driving on takeover performance. Background: In conditional automated driving, the driver can engage in non–driving related tasks (NDRTs) and does not have to monitor the system and the driving environment. In the event that the system hits its limits, the human driver must regain control of the car. To ensure safety, adequate driver fallback performance is necessary. Effects of the drivers’ state and the engagement in NDRTs need to be investigated. Method: Seventy-three participants experienced prolonged conditional automated rides and simultaneously had to engage in either an activating quiz or a fatiguing monitoring task (between subjects). After 50 minutes, a takeover situation occurred, and participants had to regain control of the car. Results: Prolonged conditional automated driving and simultaneously engaging in NDRTs affected the driver’s state and the takeover performance of the participants. Takeover performance was impaired when participants had to deal with monotonous NDRTs. Conclusion: An engagement in monotonous monitoring tasks in conditional automated driving affects the driver’s state and takeover performance when it comes to takeover situations. Especially in prolonged automated driving, an adequate driver state seems to be necessary for safety reasons. Application: The results of this study demonstrate that engagement in monotonous NDRTs while driving conditionally automated may negatively affect takeover performance. A monitoring of the driver state and adapted assistance in a takeover situation seems to be a good opportunity to ensure safety.
Changing trend in nutrition and food consumption predisposes school children to overweight and obesity in Ile-Ife, Osun State, Nigeria
Authors: Oyesiji Oyebola V , Otemuyiwa Israel O , Falade Olumuyiwa S , Adewusi Steve RA 
Published: January 2019

Background: The consumption of instant foods like pasta and sweetened soft drinks have virtually replaced the traditional diets among children. This changing trend in food consumption could negatively affect the health status of school-aged children. Aim: The aim of this study is to investigate the effect of consumption of instant foods (pasta) on anthropometric parameters and nutrient intake among children in Ile-Ife, Nigeria. Methods: Participants (126 healthy children, 66 boys and 60 girls, aged 4–12 years) were recruited from nursery and primary schools in Ife Central Local Government, Ile-Ife. The anthropometric measurements were taken and participants were classified based on body mass index (BMI) percentiles. A food frequency questionnaire was administered to evaluate participants’ pasta consumption patterns, while food intakes were obtained through 24-h dietary recall. The samples of food consumed by the children were analyzed for their nutrient contents. Nutrient intake was calculated using the data obtained from 24-h dietary recall and the results were compared with the recommended dietary allowances. Results: The average estimated energy intakes were 6167 kJ and 6095 kJ for male and female participants, respectively. The energy intake per kg body weight increased with increasing frequency of the consumption of pasta. There was a positive correlation ( r = 0.873 and 0.998 at P ≤ 0.05 for male and female participants, respectively) between energy intake and weight. The BMI classification showed that 12% of males and 17% of females were overweight or obese. Conclusion: It can be concluded that the consumption of pasta could predispose children to overweight/obesity.
Ultrasound-guided TriVex™-powered phlebectomy for debulking of peripheral vascular anomalies – A novel treatment technique
Authors: Parsi Kurosh , Kang Mina , Trimboli Anthony 
Published: January 2019

Background Large vascular anomalies on the trunk or limbs are rare and prove challenging to treat. Currently, treatment options include conservative management, embolisation, sclerotherapy or surgical excision. Once the lesion has been embolised, or if it spontaneously involutes, the residual fibrofatty tissue may be painful and require debulking. Surgical debulking may be associated with complicated wound healing, infection, scarring and may not be not feasible for large lesions. Method We present our technique of using TriVex™-powered phlebectomy to debulk vascular anomalies. Our modification involved performing sclero-emobolisation on the target lesion first to mitigate the risk of haematoma formation. We also used ultrasound guidance to increase the precision and eliminate the use of TriVex™ illuminator. Results Excellent symptom relief and cosmetic outcome were achieved in three patients treated using this method. Conclusion We believe the novel technique of ultrasound-guided TriVex™-powered system provides a viable alternative to surgical debulking of large or complex vascular anomalies.
An exploration of members’ experiences of group therapy: an interpretive phenomenological analysis
Authors: O’Beney Rachel , Salm Anne-Marie , Lavender Tony 
Published: January 2019

NHS patients referred for group analytic psychotherapy often have limited capacity to manage their own or others’ emotions and therefore struggle to use analytic group psychotherapy because its unstructured format can feel too anxiety provoking. This research looked into members’ experiences of group analytic therapy, using a qualitative approach, to examine the experiences of group processes for members and their therapists. Phenomenological Interpretive Analysis was used to analyse the interview transcripts and develop over-arching themes. Findings revealed shared themes between members and therapists, describing strong feelings: ‘anger; competition with members and disappointment with therapists’ and ‘fears of emotional damage’. A super-ordinate theme of ‘weathering’ emerged, which connected to members being able to stay and understand these strong feelings and which led to themes of ‘sharing leading to new learning’ and ‘change’. Differences in themes were also found: ‘anger could be destructive’ and ‘feeling attacked’ were identified by members only, whilst therapists identified ‘re-enactment: repair or re-traumatization’. Members emphasized; ‘therapists as parents providing safety’ and ‘support from other members’ as crucial in helping them to stay to ‘weather’ the group process. The theme of ‘weathering’ was important because it related to all themes and provided an explanation for personal change in members. Clinical implications are discussed.
Evaluation of a Clinical Pharmacist-Led Automated Dispensing Cabinet Stewardship Program at a Tertiary Academic Medical Center
Authors: Lupi Kenneth E. , Day Kevin M. , Gilmore James F. , DeGrado Jeremy R. 
Published: January 2019

Background: There is little guidance regarding the best methodology or frequency to optimize automated dispensing cabinets. Clinical pharmacists are in the unique position to make decisions regarding automated dispensing cabinet inventory to best serve their specific patient population. Objective: The purpose of this evaluation was to determine if automated dispensing cabinet optimization by clinical pharmacists would affect the number of dispenses from central pharmacy, number of stockouts, and inventory cost. Methods: A retrospective analysis was completed to evaluate the quantity of medications dispensed from a central pharmacy department over 2 separate 2-month periods, with optimization of automated dispensing cabinets occurring in between. The differences in quantity of medications dispensed and redispensed, as well as the number of stockouts and inventory cost on all automated dispensing cabinets, were compared pre- and postintervention. Results: There were 1132 medication additions, 262 medication removals, and 167 medication par level adjustments. Medications dispensed from central pharmacy were decreased by 12% from the preintervention group to the postintervention group. The number of stockouts per cabinet per day also decreased from 0.75 to 0.61 in the pre- and postintervention groups, respectively. The inventory-at-par cost level was decreased by 15%. Conclusion and Relevance: Automated dispensing cabinet optimization by clinical pharmacists led to increased medication availability on inpatient units and decreased the number of dispenses from central pharmacy. Simple yet meaningful interventions can be taken to improve multiple medication distribution metrics simultaneously.
Comparison of Plantar Pressure Distribution Between Postoperative Hallux Valgus Feet and Healthy Feet
Authors: Tsujinaka Seiya , Shima Hiroaki , Yasuda Toshito , Mori Katsunori , Kizawa Momoko , Togei Kosho , Neo Masashi 
Published: January 2019

Background: Proximal crescentic osteotomy (PCO) in patients with moderate-to-severe hallux valgus (HV) is a well-established and effective procedure for correcting the deformity. However, there are no published studies comparing plantar pressure in postoperative HV feet with healthy feet. This study aimed to compare the plantar pressure distribution in postoperative HV feet with healthy feet. Methods: Twenty-six patients were included in the HV group, and 24 healthy participants were included in the control (C) group. All patients in the HV group underwent unilateral PCO. After undergoing PCO, this group was defined as the OP group. All subjects were women with no significant differences in age, height, weight, and body mass index. There were no significant differences in demographic characteristics between patients in each group. We divided the subjects’ feet into 8 regions and measured the peak pressure (Peak-P), maximum force (Max-F), contact time, contact area, and the force-time integral in each region. Results: All parameters of the great toe were significantly higher in the OP group than in the HV group. All forefoot parameters were not significantly different between the 2 groups. No parameter of the great toe was significantly different between the OP and C groups. However, mean Peak-P and Max-F of the central forefoot were significantly higher in the OP group than in the C group. Conclusion: PCO can improve the plantar pressure of the great toe in patients with moderate-to-severe HV to a level similar to that in healthy subjects. Level of Evidence: Level III, comparative study.
Postoperative Medial Cuneiform Position Correlation With Patient-Reported Outcomes Following Cotton Osteotomy for Reconstruction of the Stage II Adult-Acquired Flatfoot Deformity
Authors: Conti Matthew S. , Garfinkel Jonathan H. , Kunas Grace C. , Deland Jonathan T. , Ellis Scott J. 
Published: January 2019

Background: Residual supination of the midfoot during reconstruction of the stage II adult-acquired flatfoot deformity (AAFD) is often addressed with a medial cuneiform (Cotton) osteotomy after adequate correction of the hindfoot valgus deformity. The purpose of this study was to determine if there was a correlation between postoperative alignment of the medial cuneiform and patient-reported outcomes. Methods: Sixty-three feet in 61 patients with stage II AAFD who underwent a Cotton osteotomy as part of a flatfoot reconstruction were included in the study. Radiographic angles were measured on weightbearing lateral radiographs at a minimum of 40 weeks postoperatively. Pearson’s correlation analysis was used to determine if there was an association between postoperative radiographic angles and Foot and Ankle Outcome Score (FAOS) at a minimum of 24 months postoperatively. Patients were also divided into mild plantarflexion (cuneiform articular angle [CAA] ≥–2 degrees) and moderate plantarflexion (CAA <–2 degrees) groups to evaluate for differences in clinical outcomes. Results: Postoperative CAA was significantly positively correlated with the postoperative FAOS symptoms ( r = .27, P = .03), daily activities ( r = .29, P = .02), sports activities ( r = .26, P = .048), and quality of life ( r = .28, P = .02) subscales. Patients in the mild plantarflexion group had statistically and clinically better outcomes compared with the moderate plantarflexion group in the FAOS symptoms ( P = .04), daily activities ( P = .04), and sports activities ( P = .01) subscales. Conclusions: Our study suggests that the surgeon should avoid excessive plantarflexion of the medial cuneiform and use the Cotton osteotomy judiciously as part of a flatfoot reconstruction for stage II AAFD. Level of Evidence: Level III, comparative series.