Miracle-dz/UniFAR-FTUs huggingface dataset:
The PAT randomized clinical trial.

AIMS A pragmatic, single-centre, double-blind randomized clinical trial was conducted in a NHS teaching hospital to evaluate whether there is a difference in functional knee scores, quality-of-life outcome assessments, and complications at one-year after intervention between total knee arthroplasty (TKA) and patellofemoral arthroplasty (PFA) in patients with severe isolated patellofemoral arthritis. METHODS This parallel, two-arm, superiority trial was powered at 80%, and involved 64 patients with severe isolated patellofemoral arthritis. The primary outcome measure was the functional section of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 12 months. Secondary outcomes were the full 24-item WOMAC, Oxford Knee Score (OKS), American Knee Society Score (AKSS), EuroQol five dimension (EQ-5D) quality-of-life score, the University of California, Los Angeles (UCLA) Physical Activity Rating Scale, and complication rates collected at three, six, and 12 months. For longer-term follow-up, OKS, EQ-5D, and self-reported satisfaction score were collected at 24 and 60 months. RESULTS Among 64 patients who were randomized, five patients did not receive the allocated intervention, three withdrew, and one declined the intervention. There were no statistically significant differences in the patients' WOMAC function score at 12 months (adjusted mean difference, -1.2 (95% confidence interval -9.19 to 6.80); p = 0.765). There were no clinically significant differences in the secondary outcomes. Complication rates were comparable (superficial surgical site infections, four in the PFA group versus five in the TKA group). There were no statistically significant differences in the patients' OKS score at 24 and 60 months or self-reported satisfaction score or pain-free years. CONCLUSION Among patients with severe isolated patellofemoral arthritis, this study found similar functional outcome at 12 months and mid-term in the use of PFA compared with TKA. Cite this article: Bone Joint J 2020;102-B(3):310-318.
A predictive model for personalization of nanotechnology-based phototherapy in cancer treatment

A major challenge in radiation oncology is the prediction and optimization of clinical responses in a personalized manner. Recently, nanotechnology-based cancer treatments are being combined with photodynamic therapy (PDT) and photothermal therapy (PTT). Predictive models based on machine learning techniques can be used to optimize the clinical setup configuration, including such parameters as laser radiation intensity, treatment duration, and nanoparticle features. In this article we demonstrate a methodology that can be used to identify the optimal treatment parameters for PDT and PTT by collecting data from in vitro cytotoxicity assay of PDT/PTT-induced cell death using a single nanocomplex. We construct three machine learning prediction models, employing regression, interpolation, and low- degree analytical function fitting, to predict the laser radiation intensity and duration settings that maximize the treatment efficiency. To examine the accuracy of these prediction models, we construct a dedicated dataset for PDT, PTT, and a combined treatment; this dataset is based on cell death measurements after light radiation treatment and is divided into training and test sets. The preliminary results show that the performance of all three models is sufficient, with death rate errors of 0.09, 0.15, and 0.12 for the regression, interpolation, and analytical function fitting approaches, respectively. Nevertheless, due to its simple form, the analytical function method has an advantage in clinical application and can be used for further analysis of the sensitivity of performance to the treatment parameters. Overall, the results of this study form a baseline for a future personalized prediction model based on machine learning in the domain of combined nanotechnology- and phototherapy-based cancer treatment.
Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER−). We further compared associations with ER+ and ER− subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER− breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER− breast cancer.
The demand-control model and work-related threats and violence: Short- and long-term associations.

BACKGROUND Work-related violence and threats are frequent in human service sectors. Although previous studies have identified several psycho-social work environmental risk factors for work-related violence and threats, the research domain still remains mainly descriptive and non-theoretical in nature. OBJECTIVE Using the Job-Demands-Control model we analysed the relationship between the psycho-social work environment and work-related threats and violence. METHOD Using a two-wave (2011 and 2015) longitudinal study of 2678 participants, we analysed the main and interactive effects of quantitative demands and job control on exposure to work-related violence and threats. RESULTS High work demands and low job-control were associated with elevated risk of work-related threats in 2011 and in 2015. The associations of work demands and job control and work-related violence were mixed. There were not statistically significant interaction effects between high demands and low job control on neither work-related violence nor threats. CONCLUSION In sectors where work-related threats and violence are likely to occur, risk prevention may also require improving the work conditions for employees, more specifically by reducing work-demands and increasing job control for instance by differentiating between important and less important work demands and by implementing self- autonomous work-teams may be a way to increase job control.
Myocardial reperfusion reverses the J-curve association of cardiovascular risk and diastolic blood pressure in patients with left ventricular dysfunction and heart failure after myocardial infarction: insights from the EPHESUS trial.

AIMS The described association of low diastolic blood pressure (DBP) with increased cardiovascular outcomes could be due to reduced coronary perfusion or is simply due to reverse causation. If DBP is physiologically relevant, coronary reperfusion after myocardial infarction (MI) might influence DBP-risk association. METHODS AND RESULTS The relation of achieved DBP with cardiovascular death or cardiovascular hospitalization, cardiovascular death, and all-cause death was explored in 5929 patients after acute myocardial infarction (AMI) with impaired left ventricular function, signs and symptoms of heart failure, or diabetes in the EPHESUS trial according to their reperfusion status. Cox regression models were used to assess the impact of reperfusion status on the association of DBP and systolic blood pressure (SBP) with outcomes in an adjusted fashion. In patients without reperfusion, lower DBP <70 mmHg was associated with increased risk for all-cause death [adjusted hazard ratios (HRs) 1.80, 95% confidence interval (CI) 1.41-2.30; P < 0.001], cardiovascular death (HR 1.70, 95% CI 1.3-3.22; P < 0.001), cardiovascular death or cardiovascular hospitalization (HR 1.54, 95% CI 1.26-1.87; P < 0.001). In patients with reperfusion, the risk increase at low DBP was not observed. At low SBP, risk increased independently of reperfusion. A sensitivity analysis in the subgroup of patients with optimal SBP of 120-130 mmHg showed again risk reduction of reperfusion at low DBP. Adding the treatment allocation to eplerenone or placebo into the models had no effects on the results. CONCLUSION Patients after AMIs with a low DBP had an increased risk, which was sensitive to reperfusion therapy. Low blood pressure after MI identifies in patients with particular higher risk. These data support the hypothesis that low DBP in patients with stenotic coronary lesions is associated with risk, potentially involving coronary perfusion pressure and the recommendations provided by guidelines suggesting lower DBP boundaries for these high-risk patients.
Healthy ageing in the far North: perspectives and prescriptions

ABSTRACT Objectives: This study captured factors integral to healthy ageing in central Alaska. To date, conceptual models fail to meaningfully address how healthy ageing is impacted by location and context, particularly in remote or sparsely populated areas. The way “healthy”, or “successful”, ageing is defined in an extreme environment, and how that contrasts with global definitions of healthy ageing, has yet to be examined. Method: Residents of central Alaska aged 60 and older completed background demographics and several measures of personality and well-being and then engaged in a guided discussion. Results: Themes identified as important to healthy ageing were attitude/perspective, socialisation, sense of community, purpose and staying active, and independence. Challenges endorsed included service gaps, transportation, seasonality, cost of living, and isolation. Discussion: The current data parallels previous investigations of healthy ageing and provides a new understanding of the importance of resilience factors for those living in central Alaska.
Beneficial Effects of Ipragliflozin on the Renal Function and Serum Uric Acid Levels in Japanese Patients with Type 2 Diabetes: A Randomized, 12-week, Open-label, Active-controlled Trial

Objective To examine the add-on effects, compared to the existing antidiabetes treatment, of the sodium-glucose cotransporter 2 inhibitor ipragliflozin on glycemic control and the risk factors of cardiovascular disease (CVD) and chronic kidney disease (CKD) in patients with inadequately controlled type 2 diabetes. Methods This 12-week, randomized, open-label, active-controlled trial included 30 patients with type 2 diabetes who were randomized 1:1 to ipragliflozin and control groups (n=15 each). The ipragliflozin group received 50 mg of ipragliflozin once daily in addition to conventional therapy. The primary outcome was the change in hemoglobin A1c (HbA1c) from the baseline. Secondary outcomes were changes from the baseline in indices of glycemic control, uric acid (UA), renal function, and arterial stiffness. Results The patients' diminished estimated glomerular filtration rate (eGFR) was alleviated in the ipragliflozin group compared to the control group [difference between groups (Δ)=4.6 (95% confidence interval (CI): 1.5-7.7) mL/min/1.73 m2, p=0.006] prior to significant improvements in HbA1c and other parameters, including anthropometric indices and arterial stiffness. Furthermore, ipragliflozin add-on therapy resulted in a greater reduction in serum UA levels than control therapy [Δ=-52.3 (95% CI: -85.5-19.1) μmol/L, p=0.003]. The changes in the eGFR with ipragliflozin treatment were associated with ipragliflozin-mediated changes in the UA, even after adjusting for the age, sex, baseline HbA1c, baseline UA, and baseline eGFR (standardized regression coefficient=-0.535, p=0.010). Conclusion Ipragliflozin add-on therapy was associated with beneficial renal effects in parallel with reducing serum UA levels.
Targeted mutagenesis using CRISPR-Cas9 in the chelicerate herbivore Tetranychus urticae

The use of CRISPR-Cas9 has revolutionized functional genetic work in many organisms, including more and more insect species. However, successful gene editing or genetic transformation has not yet been reported for chelicerates, the second largest group of terrestrial animals. Within this group, some mite and tick species are economically very important for agriculture and human health, and the availability of a gene-editing tool would be a significant advancement for the field. Here, we report on the use of CRISPR-Cas9 to create gene knock-outs in the spider mite Tetranychus urticae. The ovary of virgin adult females was injected with a mix of Cas9 and sgRNAs targeting the phytoene desaturase gene. Natural mutants of this gene have previously shown an easy-to-score albino phenotype. Albino sons of injected virgin females were mated with wild-type females, and two independent transformed lines where created and further characterized. Albinism inherited as a recessive monogenic trait. Sequencing of the complete target-gene of both lines revealed two different lesions at expected locations near the PAM site in the target-gene. Both lines did not genetically complement each other in dedicated crosses, nor when crossed to a reference albino line with a known genetic defect in the same gene. In conclusion, two independent mutagenesis events were induced in the spider mite T. urticae using CRISPR-Cas9, providing an impetus for genetic transformation in chelicerates and paving the way for functional studies using CRISPR-Cas9 in T. urticae.
A Multi-Modality Treatment of Retroperitoneal De-Differentiated Liposarcoma

Patient: Male, 73-year-old Final Diagnosis: Retroperitoneal dedifferentiated liposarcoma Symptoms: Abdominal pain Medication: — Clinical Procedure: Exploratory laparotomy Specialty: Oncology Objective: Rare disease Background: Retroperitoneal sarcomas are rare tumors, only affecting 2 to 5 people per million population and accounting for 0.1% of all malignancies. Liposarcoma is the most common of all retroperitoneal sarcomas, responsible for approximately 20% of all sarcomas in adults. The most important prognostic factors are tumor grade, the presence of positive margins, tumor integrity, and degree of resection. Case Report: Our patient was a 73-year-old man with abdominal pain whose CT scan of the abdomen and pelvis demonstrated a 15×15 cm heterogeneous, left-sided intra-abdominal mass. He underwent resection of the retroperitoneal tumor, left colectomy, and left nephrectomy. Final pathology demonstrated a high-grade, de-differentiated liposarcoma with a rhabdosarcomatous component. The postoperative course was complicated by a small intra-abdominal abscess and abdominal dehiscence. a CT scan after surgery showed a residual tumor of the retroperitoneal posterior margin. Re-exploration to resect the residual tumor and repair the fascial dehiscence were performed. The patient underwent an initial chemotherapy regimen with doxorubicin, then moved to targeted therapy with Palbociclib, and is now on chemotherapy using Eribulin. Conclusions: Achieving complete resection and the grade of the tumor at diagnosis are the 2 most important prognostic factors for patient survival in retroperitoneal liposarcoma, as survival rates are inversely proportional to the grade of the tumor. Even with the best resection attempts, there is always a risk of residual tumor cells within the tumor bed, which contribute to recurrence and need for additional surgical interventions. It is important to approach this disease process with a multidisciplinary team that includes surgical, medical, and radiation oncology to ensure the best survival outcomes. Retroperitoneal sarcoma recurrence and survival are directly related to the ability to achieve negative margins of resection, as well as the grade and size of the primary tumor. Adjuvant therapies that include radiation and immunotherapy may be effective in treating recurrent disease.
Metoclopramide-Induced Acute Dystonia

Objectives Metoclopramide is a commonly used medication in pediatric practice, and dystonia is a common adverse effect of it. The present study aims to evaluate the clinical characteristics of metoclopramide-induced acute dystonic reactions (MIADRs) in pediatric patients admitted to the pediatric emergency unit. Methods Twenty-eight patients were admitted with MIADRs between June 2004 and April 2016; they were enrolled into the study retrospectively. Results The study group was composed of 13 females and 15 males with the mean ± SD age of the females higher than that of the males, 12.3 ± 4.5 and 7.8 ± 4.3 years, respectively. Only 9 (32.1%) of the patients were diagnosed as MIADRs at the time of admission. Seventeen patients (60.7%) received over the recommended daily dose of metoclopramide. Dystonia was focal in most of the patients, with the most affected parts consisting of the neck, eyes, and orolingual regions. In 9 of the patients, the dystonia was episodic in nature. Pharmacological treatment was used for 18 patients. No patients died, and none suffered long-term injury related to MIADRs. Conclusions Metoclopramide administration may be associated with the occurrence of acute dystonic reaction. Metoclopramide-induced acute dystonic reactions may be misdiagnosed, so detailed medical history gathering and a high index of suspicion are warranted. Our data suggest that MIADRs may be dose related and that there may be age- and sex-related differences in the epidemiology of MIADRs.
Foliar micromorphology and its role in identification of the Apocynaceae taxa

In the present study, we evaluate the importance of foliar epidermal micromorphological characteristics of Apocyanaceae for accurate identification and classification. The species were collected from the University of Peshawar's main campus in the spring season to observe its qualitative and quantitative features. The length and width of guard cells, stomatal pore and subsidiary cells, trichomes, and crypts on both sides of the leaf were examined. Many species were observed to be hypostomatic. Plumeria rubra, Raulfia serpentine, Thevetia peruviana, Trachelospermum lucidum, Alstonia scholaris, and Catharanthus roseus demonstrated hypostomatic leaves. Nearly all the investigated species had anisocytic type of stomata only or in combination with other types of stomata on the upper and lower epidermis. Carissa carandas had anomocytic, anisocytic, and cyclocytic type of stomata on the upper epidermis, and the lower epidermis showed variations in stomatal type, such as anomocytic, stephanocytic, brachyparacytic, and hemiparacytic. Nerium oleander had no specific shape of stomata but showed stomatal crypts in which the stomata were enclosed inside many trichomes. The taxonomic key based on stomatal types, epidermal cells, stomatal index value, and statistical analysis, along with the variations in the epidermal cells, shows the link between the selected plants species, which will provide a baseline for future anatomical studies. This study highlights many undocumented micromorphological characteristics. The anatomical characteristics observed in this study will be helpful for taxonomic identification and species delimitation of the family Apocynaceae.
Recharacterizing The Metabolic State of Energy Balance in Thrifty and Spendthrift Phenotypes.

PURPOSE The human thrifty phenotype hypothesis presupposes that lower 24-hour energy expenditure (24EE) during famine preserves body mass and promotes survival. The prevailing view defines thrifty individuals as having a lower 24EE during fasting. However, it is also plausible that the greater decline in 24EE during fasting in thrifty individuals is due to higher 24EE during energy balance conditions (ENBAL). Herein, we provide evidence that this is indeed the case. METHODS In 108 healthy subjects, 24EE was measured in a whole-room indirect calorimeter both during ENBAL and 24h fasting conditions. Subjects were categorized as thrifty or spendthrift based on the median value (-162 kcal/day) of the difference in 24EE (adjusted for body composition) between fasting and ENBAL conditions. Concomitant 24h urinary catecholamines were assessed by liquid chromatography-mass spectrometry. RESULTS Compared to ENBAL, on average 24EE decreased by 172 kcal/day (SD=93, range -470 to 122) during 24h fasting. A greater-than-median decrease in 24EE ("thriftier" phenotype) was due to higher 24EE during ENBAL (+124 kcal/day, p<0.0001) but not to lower 24EE during fasting (p=0.35). Greater fasting-induced increase in epinephrine associated with concomitant lower decrease in 24EE (r=0.27, p=0.006). MAIN CONCLUSION The greater decrease in 24EE during acute fasting (which characterizes the thrifty phenotype) is not due to reduced metabolic rate during fasting but to a relatively higher 24EE during feeding conditions, and this decrease in 24EE during fasting is accompanied by smaller increase in epinephrine. These results recharacterize the prevailing view of the short-term 24EE responses that define the human metabolic phenotypes.
Development and characterization of standard reagents for cell-based prepandemic influenza vaccine products

ABSTRACT Outbreaks of infection by novel avian influenza virus strains in humans cause public health issues worldwide, and the development of vaccines against such novel strains is the most effective method for the prevention of these virus outbreaks. All types of vaccines must be tested for potency before use; thus, quantitative potency assays are needed for influenza vaccines. The single radial immunodiffusion (SRID) assay is considered the gold standard for quantification of influenza virus antigens, and the SRID reference reagents are essential for the determination of vaccine potency. However, it remains debatable whether reference reagents derived from egg-based vaccine platforms can be used to precisely quantify non-egg-derived vaccines; thus, influenza vaccine production using cell-based platforms has attracted increasing attention. To evaluate the utility of reference reagents derived from a cell-based influenza vaccine platform, we prepared cell-based reference reagents from MDCK cell-grown viruses and compared them with egg-derived reference reagents. A primary liquid standard (PLS) was purified from cell-derived candidate influenza vaccine viruses, and hemagglutinin (HA) antigen content was determined by a densitometric method. The produced PLS could be stored at 4°C for more than 10 months. We also established a simple HA protein purification method for goat antiserum preparation, and the performance of the resulting antiserum was compared to that of standard reagents obtained using different production platforms. The results of this study indicate that these reference reagents can be used for both cell-based and egg-based production platforms and that the differences between these two types of platforms are negligible.