Miracle-dz/UniFAR-FTUs huggingface dataset:
Inorganic Polyphosphate Accumulation in Escherichia coli Is Regulated by DksA but Not by (p)ppGpp

Production of polyP in bacteria is required for virulence and stress response, but little is known about how bacteria regulate polyP levels in response to changes in their environments. Understanding this regulation is important for understanding how pathogenic microbes resist killing by disinfectants, antibiotics, and the immune system. In this work, I have clarified the connections between polyP regulation and the stringent response to starvation stress in Escherichia coli and demonstrated an important and previously unknown role for the transcription factor DksA in controlling polyP levels. ABSTRACT Production of inorganic polyphosphate (polyP) by bacteria is triggered by a variety of different stress conditions. polyP is required for stress survival and virulence in diverse pathogenic microbes. Previous studies have hypothesized a model for regulation of polyP synthesis in which production of the stringent-response second messenger (p)ppGpp directly stimulates polyP accumulation. In this work, I have now shown that this model is incorrect, and (p)ppGpp is not required for polyP synthesis in Escherichia coli. However, stringent mutations of RNA polymerase that frequently arise spontaneously in strains defective in (p)ppGpp synthesis and null mutations of the stringent-response-associated transcription factor DksA both strongly inhibit polyP accumulation. The loss of polyP synthesis in a mutant lacking DksA was reversed by deletion of the transcription elongation factor GreA, suggesting that competition between these proteins for binding to the secondary channel of RNA polymerase plays an important role in controlling polyP activation. These results provide new insights into the poorly understood regulation of polyP synthesis in bacteria and indicate that the relationship between polyP and the stringent response is more complex than previously suspected. IMPORTANCE Production of polyP in bacteria is required for virulence and stress response, but little is known about how bacteria regulate polyP levels in response to changes in their environments. Understanding this regulation is important for understanding how pathogenic microbes resist killing by disinfectants, antibiotics, and the immune system. In this work, I have clarified the connections between polyP regulation and the stringent response to starvation stress in Escherichia coli and demonstrated an important and previously unknown role for the transcription factor DksA in controlling polyP levels.
Risk factors for post‐pancreaticoduodenectomy delayed gastric emptying in the absence of pancreatic fistula or intra‐abdominal infection

Delayed gastric emptying (DGE) occurs commonly following pancreaticoduodenectomy (PD), but the rate of DGE in the absence of other intra‐abdominal complications is poorly understood. The objectives of this study were to define the incidence of DGE and identify risk factors for DGE in patients without pancreatic fistula or other intra‐abdominal infections.
At the Beginning of the End and in the Middle of the Beginning: Structure and Maintenance of Telomeric DNA Repeats and Interstitial Telomeric Sequences

Tandem DNA repeats derived from the ancestral (TTAGGG)n run were first detected at chromosome ends of the majority of living organisms, hence the name telomeric DNA repeats. Subsequently, it has become clear that telomeric motifs are also present within chromosomes, and they were suitably called interstitial telomeric sequences (ITSs). It is well known that telomeric DNA repeats play a key role in chromosome stability, preventing end-to-end fusions and precluding the recurrent DNA loss during replication. Recent data suggest that ITSs are also important genomic elements as they confer its karyotype plasticity. In fact, ITSs appeared to be among the most unstable microsatellite sequences as they are highly length polymorphic and can trigger chromosomal fragility and gross chromosomal rearrangements. Importantly, mechanisms responsible for their instability appear to be similar to the mechanisms that maintain the length of genuine telomeres. This review compares the mechanisms of maintenance and dynamic properties of telomeric repeats and ITSs and discusses the implications of these dynamics on genome stability.
Circular RNA ARHGAP26 is over-expressed and its downregulation inhibits cell proliferation and promotes cell apoptosis in gastric cancer cells

Background/Aims: This study aimed to explore the effect of circular RNA ARHGAP26 (circ-ARHGAP26) on cell proliferation and apoptosis in gastric cancer (GC) cell lines. Materials and Methods: Human GC cell lines including HGC-27, AGS, SGC-7901, BGC-823, NCI-N87 and human normal gastric mucosal cells GSE-1 were cultured. The circ-ARHGAP26 expression was determined by quantitative polymerase chain reaction assay. Blank inhibitor and circ-ARHGAP26 inhibitor plasmids were transfected into HGC-27 or AGS cells as NC (-) and circ-ARHGAP26(-) groups. Counting Kit-8 (CCK-8) and Annexin V (AV)/propidium iodide (PI) were conducted to evaluate cell proliferation and cell apoptosis, respectively. Western blot was performed to determine the expressions of apoptotic markers (C-Caspase3 and Bcl-2). Results: The circ-ARHGAP26 expression was elevated in HGC-27 (P < 0.001), AGS (P < 0.001), SGC-7901 (P < 0.01), BGC-823 (P < 0.05) and NCI-N87 (P < 0.05) GC cell lines compared to GSE-1 cells. In HGC-27 cells, CCK8 assay revealed that cell proliferation was decreased at 48 h (P < 0.05) and 72 h (P < 0.01), while AV/PI assay disclosed that cell apoptosis rate was increased at 72 h in circ-ARHGAP26 (-) group compared to NC (-) group (P < 0.01). Western blot assay also illuminated that apoptotic marker C-Caspase 3 was raised, while anti-apoptotic marker Bcl-2 was reduced at 72 h in circ-ARHGAP26 (-) group compared to NC (-) group. In addition, further validation in AGS cells also exhibited that cells proliferation was repressed, while apoptosis was enhanced in circ-ARHGAP26 (-) group compared to NC (-) group. Conclusion: The circ-ARHGAP26 is over-expressed and its downregulation inhibits cell proliferation and promotes cells apoptosis in GC cells.
Outcome Impact of Coronary Revascularization Strategy Reclassification With Fractional Flow Reserve at Time of Diagnostic Angiography: Insights From a Large French Multicenter Fractional Flow Reserve Registry

Background— There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography. Methods and Results— The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank, P=0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model, P=0.75). Reclassification safety was preserved in high-risk patients. Conclusion— This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.
Effect of High-dose Vitamin C Combined With Anti-cancer Treatment on Breast Cancer Cells

Background/Aim: The anti-cancer effect of high doses of intravenous vitamin C (high-dose vitamin C) remains controversial despite growing evidence that high-dose vitamin C exerts anti-tumorigenic activity by increasing the amount of reactive oxygen species in cancer cells without meaningful toxicities. Therefore, this study attempted to demonstrate the in vitro anti-cancer activity of high-dose vitamin C in combination with conventional treatment in breast cancer. Materials and Methods: The pro-apoptotic effects of high-dose vitamin C (1.25 to 20 mM) with or without anti-cancer agents (eribulin mesylate, tamoxifen, fulvestrant, or trastuzumab) were estimated using an MTT assay to measure the cell viability of a variety of breast cancer cell lines (MCF7, SK-BR3, and MDA-MB-231), as well as normal breast epithelial cells (MCF10A). Results: High-dose vitamin C (≥10 mM) significantly decreased cell viability of all breast cancer cell lines, particularly of MCF-7 cells. The catalase activities of MCF7 and MDA-MD-231 cells were also lower than those of MCF10A cells. Moreover, cell viability of both MCF7 and MDA-MD-231 cells was decreased further when combining high-dose vitamin C and eribulin mesylate, and this was also true for MCF-7 cells when combining high-dose vitamin C with tamoxifen or fulvestrant and for SK-BR3 cells when combining high-dose vitamin C with trastuzumab in comparison with chemotherapy or endocrine therapy alone. Conclusion: Combining high-dose vitamin C with conventional anti-cancer drugs can have therapeutic advantages against breast cancer cells.
Direct and indirect predictors of burden among Bedouin caregivers of family members with terminal cancer in Israel

Abstract Objective: The diverse demands of cancer care, which require time, psychological, physical, and material resources, often lead to caregiver burden. Studies with caregivers from ethnic minority groups suggest that they have unique beliefs and may experience different perceptions of role demands and caregiving. The aim of this study was to identify direct and indirect predictors of burden among Bedouin caregivers of family members with terminal cancer in Israel. Methods: A total of 101 Bedouin family caregivers of terminal cancer patients participated in this study. Participants were recruited from the oncology department of the largest medical center in southern Israel. The questionnaire battery included the Arabic version of the Zarit Burden Interview and other reliable measures validated for cancer caregiving. We performed path analyses on data allowing us to identify hypothesized, and un-hypothesized predictors of burden in this understudied population. Results: Most caregivers were adult children, followed by spouses, siblings and other family members. In our model, caregiver burden was directly predicted by depressive symptoms and (absence of) social support. Burden was indirectly predicted by quality of life (via depressive symptoms), optimism (via social support), emotional exhaustion (via quality of life and depressive symptoms) and mortality communication (via emotional exhaustion, quality of life and depressive symptoms). Conclusion: Social support and depression are the most important factors among all studied measures. Culturally-tailored intervention programs are required to foster community care and mitigate burden for Bedouin and other ethnic minority groups in Israel.
Vaccination perspectives among adolescents and their desired role in the decision-making process

ABSTRACT Background: To assess the knowledge and attitudes of middle school students toward vaccination, we measured their understanding of vaccine safety and effectiveness, expectations for communication with heath care providers, and their desired role in the vaccination decision-making process. Methods: A cross-sectional, self-administered survey was conducted among seventh and eighth grade students in a middle school in Upstate New York. Bivariate analyses were conducted to identify differences in perspective by gender, grade, and attitudes toward vaccination. Results: Of 346 students attending class, 336 (97.1%) participated. The majority of respondents were White (71.3%) and 11 to 13 years of age (78.2%). Boys were significantly more likely than girls to perceive vaccines to be very safe (48.4% vs 30.2%, p < 0.01) and very effective (49.7% vs 29.0%, p < 0.01). Approximately one-third of adolescents reported having a say in the decision to be vaccinated and a quarter of students expressed a desire for specific information about vaccines. Conclusions: This study found that young adolescents in a nonurban area of Upstate New York were generally marginalized in the vaccine decision-making process yet third of them indicated an interest in how vaccines work and a desire to participate in healthcare decisions. Interventions to improve vaccine uptake among adolescents should capitalize on this desire to understand vaccine safety, effectiveness and mechanism of action.
Autologous Chondrocyte Implantation for Bipolar Chondral Lesions in the Patellofemoral Compartment: Clinical Outcomes at a Mean 9 Years’ Follow-up

Background: Treating bipolar chondral lesions in the patellofemoral (PF) compartment is a challenging problem. There are few reports available on the treatment of bipolar chondral lesions in the PF compartment. Purpose: To evaluate the clinical outcomes and graft survivorship after autologous chondrocyte implantation (ACI) for the treatment of bipolar chondral lesions in the PF compartment. Study Design: Case series; Level of evidence, 4. Methods: The authors evaluated 58 patients who had ACI by a single surgeon for the treatment of symptomatic bipolar chondral lesions in the PF compartment between November 1995 and June 2014. All 58 patients (60 knees; mean age, 36.6 years) were included with a minimum 2-year follow-up. The mean ± SD sizes of the patellar and trochlear lesions were 5.6 ± 2.7 cm2 and 4.2 ± 2.8 cm2, respectively. Forty-two patients had osteotomy, as they had PF lateral maltracking, patellar instability, or tibiofemoral malalignment. Patients were evaluated with the modified Cincinnati Knee Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, visual analog scale, the 36-Item Short Form Health Survey, and a patient satisfaction survey. Radiographs were evaluated with the Iwano classification. Results: Overall, the survival rates were 83% and 79% at 5 and 10 years, respectively. Of the 49 (82%) knees with retained grafts, all functional scores significantly improved postoperatively with a very high satisfaction rate (88%) at a mean 8.8 ± 4.2 years after ACI (range, 2-16 years). At the most recent follow-up, 28 of 49 successful knees were radiographically assessed (mean, 4.9 years; range, 2-17 years), with no increase of the Iwano classification in 26 knees. Outcomes for 11 patients were considered failures at a mean 2.9 years. Forty-two knees (70%) required a mean 1.0 subsequent surgical procedure. The primary reasons for chondroplasty were hypertrophy of the ACI graft (17; periosteum in 14, collagen membrane in 3), delamination of the ACI graft (5; periosteum in 4, collagen membrane in 1), and new chondral lesions (3). The best survival rates were observed among patients who underwent ACI with concomitant tibial tubercle osteotomy (TTO) as the first procedure without previous failed TTO and/or marrow stimulation technique (91% at 5 and 10 years), while the worst survival rates were observed among patients who had previous marrow stimulation (43% at 5 and 10 years). Conclusion: Results demonstrated that ACI with concomitant osteotomy, when it is necessary for the treatment of bipolar/kissing lesions in the PF compartments, gives significant improvement in pain and function, with good survival rates at 5 and 10 years (83% and 79%, respectively). The high patient satisfaction rate is encouraging, and a high survival rate can be expected when ACI with a concomitant TTO is performed at the initial surgery for this difficult condition.
Indiscernible Benefit of Double-Unit Umbilical Cord Blood Transplantation in Children: A Single-Center Experience from Hong Kong

Double-unit umbilical cord blood (DU-UCB) may extend the use of UCB transplantation and improve clinical outcomes. Data in the literature show that single-unit dominance happened in a vast majority of recipients, and the mechanism is unknown. We examined the clinical relevance and engraftment kinetics of DU-UCB transplant in 65 consecutive children who underwent unrelated single-unit (n = 25) and double-unit (n = 40) UCB transplantation for various hematological malignancies (n = 45) and nonmalignant disorders (n = 20). Our result showed no discernible benefit to children receiving double-unit transplant over those receiving single-unit transplant when the total nucleated cell (TNC) doses are ≥2.5 × 107/kg, in terms of the hastening of the engraftment of neutrophils and platelets, reduction of nonengraftment, disease recurrence, early mortality, and graft-versus-host disease, despite significantly higher numbers of TNCs in double units. Further analyses demonstrated that the phenomena were not associated with underlying disease, duration of UCB storage, postthaw viability, HLA disparity, ABO incompatibility, gender, or doses of TNCs, CD34+ cells, CD3+ cells, or colony-forming units. Engrafting units in DU-UCB transplants were notably associated with higher CD34+ cell dose. Chimerism studies demonstrated that single-unit dominance started before neutrophil engraftment in DU-UCB transplants. Data from the study suggested no advantage of infusing double-unit UCB, if an adequately dosed single-unit UCB is available. Successful prediction of the dominant graft would optimize algorithms of UCB selection and maximize the long-term engraftment of chosen units.
Dyadic coping, marital adjustment and quality of life in couples during pregnancy: an actor–partner approach

ABSTRACT Objective: This study aimed to examine the impact of dyadic coping on the quality of life of couples during pregnancy and to explore the potential mediating role of marital adjustment on this association. Background: According to the systemic transactional model, pregnancy can be characterised as a situation of dyadic stress because it affects both members of the couple. However, the impact of dyadic coping on couples’ quality of life during pregnancy is unexplored. Also, the potential mediating role of marital adjustment on this association remains understudied. Methods: Participants were 320 pregnant women and their partners (N = 640) who completed the Dyadic Coping Inventory, the Dyadic Adjustment Scale and the World Health Organisation Quality of Life instrument. Data were analysed using the actor–partner interdependence mediation model. Results: Results showed that there was an intrapersonal indirect effect of dyadic coping on quality of life through marital adjustment. Moreover, an interpersonal indirect effect was found with fathers’ dyadic coping being associated with mothers’ quality of life through mothers’ marital adjustment. Conclusions: These findings highlight the importance of assessing dyadic coping strategies of couples during pregnancy and targeting them in the psychological support offered to couples as a way of improving their marital adjustment, and consequently, their quality of life.
Complications following cranioplasty: incidence and predictors in 348 cases.

OBJECT The factors that contribute to periprocedural complications following cranioplasty, including patient-specific and surgery-specific factors, need to be thoroughly assessed. The aim of this study was to evaluate risk factors that predispose patients to an increased risk of cranioplasty complications and death. METHODS The authors conducted a retrospective review of all patients at their institution who underwent cranioplasty following craniectomy for stroke, subarachnoid hemorrhage, epidural hematoma, subdural hematoma, and trauma between January 2000 and December 2011. The following predictors were tested: age, sex, race, diabetic status, hypertensive status, tobacco use, reason for craniectomy, urgency status of the craniectomy, graft material, and location of cranioplasty. The cranioplasty complications included reoperation for hematoma, hydrocephalus postcranioplasty, postcranioplasty seizures, and cranioplasty graft infection. A multivariate logistic regression analysis was performed. Confidence intervals were calculated as the 95% CI. RESULTS Three hundred forty-eight patients were included in the study. The overall complication rate was 31.32% (109 of 348). The mortality rate was 3.16%. Predictors of overall complications in multivariate analysis were hypertension (OR 1.92, CI 1.22-3.02), increasing age (OR 1.02, CI 1.00-1.04), and hemorrhagic stroke (OR 3.84, CI 1.93-7.63). Predictors of mortality in multivariate analysis were diabetes mellitus (OR 7.56, CI 1.56-36.58), seizures (OR 7.25, CI 1.238-42.79), bifrontal cranioplasty (OR 5.40, CI 1.20-24.27), and repeated surgery for hematoma evacuation (OR 13.00, CI 1.51-112.02). Multivariate analysis was also applied to identify the variables that affect the development of seizures, the need for reoperation for hematoma evacuation, the development of hydrocephalus, and the development of infections. CONCLUSIONS The authors' goal was to provide the neurosurgeon with predictors of morbidity and mortality that could be incorporated in the clinical decision-making algorithm. Control of a patient's risk factors and early recognition of complications may help practitioners avoid the exhaustive list of complications.
Inhibition of α5 GABAA receptors has preventive but not therapeutic effects on isoflurane-induced memory impairment in aged rats

The α5 subunit-containing gamma-amino butyric acid type A receptors (α5 GABAARs) are a distinct subpopulation that are specifically distributed in the mammalian hippocampus and also mediate tonic inhibitory currents in hippocampal neurons. These tonic currents can be enhanced by low-dose isoflurane, which is associated with learning and memory impairment. Inverse agonists of α5 GABAARs, such as L-655,708, are able to reverse the short-term memory deficit caused by low-dose isoflurane in young animals. However, whether these negative allosteric modulators have the same effects on aged rats remains unclear. In the present study, we mainly investigated the effects of L-655,708 on low-dose (1.3%) isoflurane-induced learning and memory impairment in elderly rats. Young (3-month-old) and aged (24-month-old) Wistar rats were randomly assigned to receive L-655,708 0.5 hour before or 23.5 hours after 1.3% isoflurane anesthesia. The Morris Water Maze tests demonstrated that L-655,708 injected before or after anesthesia could reverse the memory deficit in young rats. But in aged rats, application of L-655,708 only before anesthesia showed similar effects. Reverse transcription-polymerase chain reaction showed that low-dose isoflurane decreased the mRNA expression of α5 GABAARs in aging hippocampal neurons but increased that in young animals. These findings indicate that L-655,708 prevented but could not reverse 1.3% isoflurane-induced spatial learning and memory impairment in aged Wistar rats. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Academy of Military Medical Science of China (approval No. NBCDSER-IACUC-2015128) in December 2015.