Miracle-dz/UniFAR-FTUs huggingface dataset:
Patients' perspectives of variants of uncertain significance and strategies for uncertainty management

Variants of uncertain significance (VUS) are a well‐recognized source of uncertainty in genomic medicine. Despite the existence of straightforward clinical management recommendations, patients report feeling anxiety, worry, and uncertainty in response to VUS. We report the first structured analysis of patient perspectives of VUS‐related uncertainty in genome sequencing using Han's taxonomy of genomic uncertainty. We conducted in‐depth semi‐structured interviews with 11 patients to elicit their thoughts regarding implications of the result for themselves and their family members. Patients' primary concern with VUS‐related uncertainty involved personal and practical issues as they directly inform health‐care decisions. Patients demonstrated good understanding of the epistemic nature of VUS uncertainty—that information about such variant is currently unknown. However, between‐provider discordance in explanations of the implication of this uncertainty for patients' diagnosis, prognosis, and therapy was a major contributor to the overall experience of uncertainty. Strategies for uncertainty reduction involved periodically checking back for reclassification and receiving concordant and clear recommendation from providers. Other proactive strategies of uncertainty reduction—such as information seeking and reading the genetic test report—were not helpful. Collectively, these findings offer previously unreported insight into uncertainty management strategies used by patients which have the potential to guide clinical management practices.
Effects of Quercetin Metabolites on Triglyceride Metabolism of 3T3-L1 Preadipocytes and Mature Adipocytes

Quercetin (Q) has rapid metabolism, which may make it worthwhile to focus on the potential activity of its metabolites. Our aim was to evaluate the triglyceride-lowering effects of Q metabolites in mature and pre-adipocytes, and to compare them to those induced by Q. 3T3-L1 mature and pre-adipocytes were treated with 0.1, 1 and 10 µM of Q, tamarixetin (TAM), isorhamnetin (ISO), quercetin-3-O-glucuronide (3G), quercetin-3-O-sulfate (3S), as well as with 3S and quercetin-4-O-sulfate (4S) mixture (3S+4S). Triglyceride (TG) content in both cell types, as well as free fatty acid (FFA) and glycerol in the incubation medium of mature adipocytes were measured spectrophotometrically. Gene expression was assessed by RT-PCR. In mature adipocytes, Q decreased TG at 1 and 10 µM, 3S metabolite at 1 and 10 µM, and 3S+4S mixture at 10 µM. 3S treatment modified the glucose uptake, and TG assembling, but not lipolysis or apoptosis. During differentiation, only 10 µM of ISO reduced TG content, as did Q at physiological doses. In conclusion, 3S metabolite but not ISO, 3G, 4S and TAM metabolites can contribute to the in vivo delipidating effect of Q.
Mitotic regulators TPX2 and Aurora A protect DNA forks during replication stress by counteracting 53BP1 function

53BP1 is a chromatin-associated protein that regulates the DNA damage response. In this study, we identify the TPX2/Aurora A heterodimer, nominally considered a mitotic kinase complex, as a novel binding partner of 53BP1. We find that TPX2/Aurora A plays a previously unrecognized role in DNA damage repair and replication fork stability by counteracting 53BP1 function. Loss of TPX2 or Aurora A compromises DNA end resection, BRCA1 and Rad51 recruitment, and homologous recombination. Furthermore, loss of TPX2 or Aurora A causes deprotection of stalled replication forks upon replication stress induction. This fork protection pathway counteracts MRE11 nuclease activity but functions in parallel to BRCA1. Strikingly, concurrent loss of 53BP1 rescues not only BRCA1/Rad51 recruitment but also the fork instability induced upon TPX2 loss. Our work suggests the presence of a feedback mechanism by which 53BP1 is regulated by a novel binding partner and uncovers a unique role for 53BP1 in replication fork stability.
Alteration in gut microbiota caused by time‐restricted feeding alleviate hepatic ischaemia reperfusion injury in mice

Time‐restricted feeding (TRF), that is, no caloric intake for 14‐16 hours each day leads to favourable nutritional outcomes. This study is the first to investigate TRF through a surgical perspective verifying its efficacy against liver ischaemia reperfusion (I/R) injury. We randomly assigned 100 10‐week‐old wild‐type male C57BL/6 mice into two feeding regimens: TRF and ad libitum access to food. Main outcomes were evaluated at 6, 12 and 24 hours post‐I/R surgery after 12 weeks of intervention. TRF group demonstrated minor liver injury via histological study; lower serum levels of liver enzymes, glucose and lipids; higher concentrations of free fatty acid and β‐hydroxybutyrate; decreased oxidative stress and inflammatory biomarkers; as well as less severe cell apoptosis and proliferation. Further exploration indicated better gut microenvironment and intestinal epithelial tight junction function. TRF employed its positive influence on a wide spectrum of biochemical pathways and ultimately revealed protective effect against hepatic I/R injury possibly through adjusting the gut microbiota. The results referred to a strong indication of adopting better feeding pattern for surgical patients.
Effect of short exposure to radiofrequency electromagnetic fields on saliva biomarkers: a study on the electrohypersensitive individuals

Abstract Context: Some individuals are reporting being sensitive to electromagnetic fields. They report some unspecific symptoms like headeache, sleep disruption, heart palpitations, itching, etc. The lack of scientific objective links between EHS symptoms and EMF exposure renders the diagnosis of EHS more complex. Purpose: Our present work aimed to look for the effect of RF EMF exposure on saliva alpha amylase (AA) and other biological markers such as cortisol and IgA in EHS individuals. Participants and methods: Ten EHS individuals participated in this double-blind provocation study. They were aged between 35 and 63 yr. Experiment consisted of two sessions (sham and real exposure). No external EMF sources were allowed, and the exposure consisted of a series of EMF signals emitted from a generator (Rhode & Schwarz) and a horn antenna (Schwarzbeck BBHA9120b). Consecutive RF signals were applied: GSM 900, GSM 1800, DECT, and Wi-Fi signals for 5 min each. Results: Exposure to 4 consecutive radiofrequency signals did not show any significant modification (p > .05) on the saliva AA, cortisol or immunoglobulin A concentrations in the electrohypersensitive individuals. Conclusions: Our study, under current conditions, do not presently allow us to propose an identification of marker for EHS.
Adverse Childhood Experiences and Adulthood Negotiation in Intimate Partner Violence: The Sequentially Paradoxical Role of Interpersonal Sensitivity Among Female Inmates

The present study examined interpersonal sensitivity and hostility as separate and sequential mediators in the association between adverse childhood experiences (ACE) and the conflict tactic of negotiation (e.g., a strategy utilized to resolve conflict with a romantic partner) among female inmates. Participants were 258 female inmates recruited from three Southern California jails. After statistically controlling for partner-negotiation, results from a sequential mediation model revealed that the association between ACE and negotiation was mediated through three separate pathways. The first single mediational pathway indicated that ACE was positively associated with interpersonal sensitivity, which in turn had a positive association with negotiation. The second single mediational pathway revealed that ACE was positively associated with hostility, which in turn had a negative association with negotiation. Finally, the sequential meditational path revealed that interpersonal sensitivity through hostility mediated the ACE and negotiation relationship. The present results suggest that ACE may result in increased interpersonal sensitivity, which may paradoxically result in both more and less negotiation with romantic partners. That is, ACE through interpersonal sensitivity alone may result in more negotiation, and ACE through interpersonal sensitivity and then hostility may result in less negotiation with romantic partners. We explicate how the psychopathological construct of interpersonal sensitivity may lead to increased and decreased rates of the positively construed conflict tacit of negotiation. In addition, the present findings are discussed in light of the high rates of both revictimization and perpetration of violence among female inmates.
Non-Contact Detection of Vital Signs Using a UWB Radar Sensor

The ultra-wide band (UWB) radar sensor is useful in the field of mission critical sensors and sensor networks due to its short detection time, high penetration, and low energy consumption. To support critical missions such as search and rescue, this paper designs a non-contact detection system based on a UWB radar sensor module to obtain vital signs of human beings. There are noise and clutter due to non-contact detection, and therefore the coherent background noise removal and moving target display filter are applied. Then, the variational mode decomposition (VMD) algorithm is used to extract heartbeat signals and respiratory signals. In addition, the Hilbert transform is applied to heartbeat signals and respiratory signals to obtain the time-frequency information. The electrocardiogram is also employed to compare the results of the UWB radar sensor. We also detect the human target through-the-wall. It turns out that the system can obtain respiratory and heartbeat characteristics simultaneously in one measurement, saving cost with high accuracy.
Use of archival versus newly collected tumor samples for assessing PD-L1 expression and overall survival: an updated analysis of KEYNOTE-010 trial

BACKGROUND In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data. PATIENTS AND METHODS PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis. RESULTS At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS ≥1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]. CONCLUSION Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples. TRIAL REGISTRATION ClinicalTrials.gov: NCT01905657.
Altered expression of long non-coding RNA GAS5 in digestive tumors

Cancer has become one of the most important diseases that affect human health and life. The effects of cancer in the digestive system are particularly prominent. Recently, long non-coding RNA (lncRNA) has attracted the attention of more and more researchers and has become an emerging field of gene research. The lncRNA growth arrest-specific 5 (GAS5) is a novel lncRNA that has attracted the attention of researchers in recent years and plays an important role in the development of tumors, especially in digestive system tumors. GAS5 was first identified in a mouse cDNA library. It was generally considered that it has the role of tumor suppressor genes, but there are still studies that have a certain ability to promote cancer. Furthermore, the 5-bp indel polymorphism (rs145204276) in the GAS5 promoter region also has a carcinogenic effect. The discovery of GAS5 and in-depth study of single nucleotide polymorphism (SNP) mechanism can provide a new way for the prevention and treatment of digestive system tumors.
Meeting the Challenge of Magnetic Coupling in a Triply-Bridged Chromium Dimer: Complementary Broken-Symmetry Density Functional Theory and Multireference Density Matrix Renormalization Group Perspectives

Face-sharing octahedral dinuclear Cr(III) compounds with d3–d3 electronic configurations represent nontrivial examples of electronic complexity, posing particular challenges for theoretical and computational studies. A tris-hydroxy-bridged Cr(III)–Cr(III) system has proven to be a richly rewarding target for studies of magnetism and electron paramagnetic resonance spectroscopy. It was also reported to be a peculiarly difficult system to treat with density functional theory (DFT). In this work the magnetic coupling problem for this dimer is approached with broken-symmetry (BS)-DFT and multireference calculations that utilize the density matrix renormalization group (DMRG) to handle full-valence active spaces. BS-DFT is shown to recover the correct ordering and energy spacing of Heisenberg spin states if used in conjunction with appropriate spin projection procedures, albeit with pronounced functional sensitivity. The contrasting conclusions of previous studies are traced to incorrect inclusion of electronically excited configurations. Analysis of the direct and differential overlap of corresponding orbital pairs from the BS-DFT solution indicates that metal–metal through-space interaction is the dominant contributor to antiferromagnetic coupling. At the DFT level a procedure that utilizes pseudopotential substitution is demonstrated that allows evaluation of the direct exchange vs superexchange contributions. A complementary description is obtained with DMRG-SCF calculations that enable state-averaged CASSCF calculations with both metal and bridge orbitals in the active space. A localized orbital subspace analysis supports the DFT conclusions that in contrast to doubly bridged isoelectronic analogues, antiferromagnetic coupling in the chromium dimer arises primarily from direct metal–metal interaction but is significantly enhanced by ligand-mediated superexchange.
Attachment Styles and Employee Performance: The Mediating Role of Burnout

Abstract Researchers are becoming increasingly interested in how early experiences within the family are relevant to an individual’s behavior at work. Drawing on Bowlby’s attachment theory, the present study addresses this topic by examining the relationship between attachment in adulthood and job performance, and the mediating role of burnout in that relationship. We used data from two samples (201 Dutch employees and 178 Romanian working students) and structural equation modeling to test this mediation model and its possible invariance across both samples. The results showed that in both samples, attachment-related anxiety was positively related to burnout, which was in turn negatively related to job performance. Attachment-related avoidance was not significantly associated with burnout or performance. These results were similar in both samples, thus increasing their validity. The results suggest that childhood and early socialization experiences play a role in shaping the employee’s behavior and well-being at work. The study is one of the few examining attachment styles in relation to burnout and performance.
Analysis of factors responsible for intrauterine fetal death in rural pregnant women at tertiary care centre of Northern India

The prevalence of IUFD has been decreased in developed countries but it still remains very high in underdeveloped and developing countries. Rate of incidence varies in different parts of the world. Annually 2.6 million stillbirths occur worldwide in 2015 with average still birth rate of 18.4 per 1000 births and the developing countries of Asia and sub Saharan Africa together are responsible for two -thirds of the world‘s stillbirth burden. Rate of still births in India ranges from 20 to 66 per thousand births in different states. It is also found that inadequate healthcare, lack of antenatal checkups, illiteracy and socio-cultural factors contribute to the increase rate of stillbirths in India.
The Role of Macrophage Migration Inhibitory Factor in Remote Ischemic Conditioning Induced Hepatoprotection in A Rodent Model of Liver Transplantation.

BACKGROUND Macrophage migration inhibitory factor (MIF) is an important stress-regulating mediator of acute ischemia/reperfusion (I/R) injury and ischemic conditioning. The present study aimed to investigate whether MIF is involved in the effects of remote ischemic conditioning (RIC) in a rat model of orthotopic liver transplantation (OLT). METHODS OLTs were performed in male Lewis rats (245-340 g). Recipients were allocated in a randomized fashion into three experimental groups: remote preconditioning-RIPC, remote postconditioning-RIPOST, control. RIC was applied as 4x5-5 min I/R via clamping of the infrarenal aorta. Animals were followed for 1, 3, 24, 168 h post-reperfusion (n = 6 recipient/group/time point). Graft micro- and macrocirculation and hepatocellular damage were assessed. mRNA expression, serum and tissue protein levels of MIF, as well as additional markers of I/R injury were measured. RESULTS RIC resulted in a prominent downregulation of MIF mRNA, serum and tissue protein. Compared to control, hepatocellular damage was significantly mitigated after RIPC or RIPOST (serum ALT; RIPC, RIPOST vs. Control, p = 0.008, p = 0.030, respectively). Graft circulation was better preserved in the RIC groups. Furthermore, there was a significant positive correlation between serum MIF and transaminase levels (r = 0.330; p = 0.02). RIC showed a significant effect on iNOS and STAT5 mRNA expressions. Supporting findings were obtained from the measurements of tissue CXCL12 mRNA expression and pAkt/Akt, pErk/Erk. CONCLUSION In this sophisticated experimental model of OLT, RIC-induced hepatoprotective effects were associated with a downregulation of MIF at mRNA and protein levels, suggesting the role of MIF as a mediator in RIC induced protection following OLT.
Contemporary Issues in Cancer Rehabilitation

Background: Evidence supports the benefits of exercise for patients with cancer; however, specific guidance for clinical decision making regarding exercise timing, frequency, duration, and intensity is lacking. Efforts are needed to optimize clinical recommendations for exercise in the cancer population. Objectives: To aggregate information regarding the benefit of exercise through a systematic review of existing systematic reviews in the cancer exercise literature. Data Sources: PubMed, CINAHL Plus, Scopus, Web of Science, and EMBASE. Study Eligibility Criteria: Systematic reviews and meta-analyses of the impact of movement-based exercise on the adult cancer population. Methods: Two author teams reviewed 302 abstracts for inclusion with 93 selected for full-text review. A total of 53 studies were analyzed. A Measurement Tool to Assess Systematic Reviews (AMSTAR) was used as a quality measure of the reviews. Information was extracted using the PICO format (ie, participants, intervention, comparison, outcomes). Descriptive findings are reported. Results: Mean AMSTAR score 1⁄4 7.66/11 ( 2.04) suggests moderate quality of the systematic reviews. Exercise is beneficial before, during, and after cancer treatment, across all cancer types, and for a variety of cancer-related impairments. Moderate-tovigorous exercise is the best level of exercise intensity to improve physical function and mitigate cancer-related impairments. Therapeutic exercises are beneficial to manage treatment side effects, may enhance tolerance to cancer treatments, and improve functional outcomes. Supervised exercise yielded superior benefits versus unsupervised. Serious adverse events were not common. Limitations: Movement-based exercise intervention outcomes are reported. No analysis of pooled effects was calculated across reviews due to significant heterogeneity within the systematic reviews. Findings do not consider exercise in advanced cancers or pediatric populations. Conclusions: Exercise promotes significant improvements in clinical, functional, and in some populations, survival outcomes and can be recommended regardless of the type of cancer. Although generally safe, patients should be screened and appropriate precautions taken. Efforts to strengthen uniformity in clinical trial reporting, develop clinical practice guidelines, and integrate exercise and rehabilitation services into the cancer delivery system are needed.
A controlled randomized clinical trial to assess postoperative analgesia after thiopental–isoflurane anaesthesia or total intravenous anaesthesia with alfaxalone in dogs

Alfaxalone, a synthetic neuroactive steroid, has been attributed with properties including sedation, anaesthesia and analgesia. The clinical relevance of any analgesic properties of alfaxalone has not been demonstrated. This study was a prospective, blinded, randomized, negative control clinical trial in 65 healthy dogs presented for ovariohysterectomy. Anaesthesia was induced and maintained, for Group 1 (TIVA) dogs (n = 30) with intravenous alfaxalone alone and for Group 2 dogs (n = 35) with thiopental followed by isoflurane in 100% oxygen inhalation. After ovariohysterectomy, quantitative measures of pain or nociception were recorded at 15 min intervals for 4 hr using three independent scoring systems, a composite measure pain scale (CMPS), von Frey threshold testing and measures of fentanyl rescue analgesia. The mean CMPS scores of Group 2 (THIO/ISO) dogs remained higher than Group 1 (TIVA) dogs from 15 to 135 min post-surgery but this difference was not statistically significant. There were no significant differences between groups in the proportions of dogs requiring rescue fentanyl analgesia, the total fentanyl dose used or the time to first fentanyl dose. The Von Frey threshold testing was found to be unsuitable for measurement of pain in this experimental model. When administered as total intravenous anaesthesia, alfaxalone did not provide analgesia in the postoperative period.