Miracle-dz/UniFAR-FTUs huggingface dataset:
Management of primary refractory acute myeloid leukemia in the era of targeted therapies

Abstract Primary refractory acute myeloid leukemia (AML), or primary induction failure, represents a continued challenge in clinical management. This review presents an overview of primary refractory disease and a discussion of risk factors for induction failure, including current evidence regarding the impact of karyotype and molecular mutation status on responsiveness to chemotherapy. We review the evidence for various treatment options for refractory AML including salvage chemotherapy regimens, allogeneic hematopoietic stem cell transplantation, targeted agents, and non-intensive therapies such as hypomethylating agents. A therapeutic approach to this patient population is presented, and several new and emerging therapies are reviewed.
Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly

Mitochondrial reactive oxygen species (ROS) production is a tightly regulated redox signal that transmits information from the organelle to the cell. Other mitochondrial signals, such as ATP, are sensed by enzymes, including the key metabolic sensor and regulator, AMP-activated protein kinase (AMPK). AMPK responds to the cellular ATP/AMP and ATP/ADP ratios by matching mitochondrial ATP production to demand. Previous reports proposed that AMPK activity also responds to ROS, by ROS acting on redox-sensitive cysteine residues (Cys-299/Cys-304) on the AMPK α subunit. This suggests an appealing model in which mitochondria fine-tune AMPK activity by both adenine nucleotide–dependent mechanisms and by redox signals. Here we assessed whether physiological levels of ROS directly alter AMPK activity. To this end we added exogenous hydrogen peroxide (H2O2) to cells and utilized the mitochondria-targeted redox cycler MitoParaquat to generate ROS within mitochondria without disrupting oxidative phosphorylation. Mitochondrial and cytosolic thiol oxidation was assessed by measuring peroxiredoxin dimerization and by redox-sensitive fluorescent proteins. Replacing the putative redox-active cysteine residues on AMPK α1 with alanines did not alter the response of AMPK to H2O2. In parallel with measurements of AMPK activity, we measured the cell ATP/ADP ratio. This allowed us to separate the effects on AMPK activity due to ROS production from those caused by changes in this ratio. We conclude that AMPK activity in response to redox changes is not due to direct action on AMPK itself, but is a secondary consequence of redox effects on other processes, such as mitochondrial ATP production.
The effect of meals on bone turnover - a systematic review with focus on diabetic bone disease

ABSTRACT Introduction: Type 2 diabetes is associated with an increased risk of bone fractures. Bone mineral density (BMD) is increased and bone turnover is low in type 2 diabetes and the increased BMD does not explain the increased fracture risk. However, the low bone turnover may lead to insufficient bone renewal with unrepaired micro-cracks and thus increase fracture risk. Ingestion of food acutely decreases bone resorption markers and the macronutrient composition of meals and meal frequency may influence bone metabolism adversely in subjects with unhealthy eating patterns, e.g., patients with type 2 diabetes. Areas covered: The treatment strategy of bone disease in type 2 diabetics is covered in this review. The current management of diabetic bone disease consists of anti-osteoporotic treatment. However, anti-resorptives may further reduce an already low bone turnover with uncertain effects. Furthermore, the acute and long-term effects of meal ingestion, weight loss alone and in combination with exercise as well as the possible underlying mechanisms are covered in this systematic review. Expert Commentary: Current management of diabetic bone disease is based on principles of anti-osteoporotic treatment in non-diabetic subjects. However, studies are urged to investigate whether anti-resorptives are equally beneficial in type 2 diabetes as in non-diabetic individuals.
Isolated Medial Patellofemoral Ligament Reconstruction with Semitendinosus Tendon Allograft

Background: Medial patellofemoral ligament (MPFL) reconstruction is recommended to surgically stabilize the patella against excessive lateral patellar translation. It is currently the cornerstone of treatment for recurrent lateral patellar instability. The MPFL is often disrupted during acute patellar dislocations but may also be attenuated in the setting of recurrent lateral instability. Numerous techniques have been developed with the primary goal of restoring the static function of the MPFL in resisting lateral translation of the patella during early flexion of the knee. There are now numerous options for the surgical technique, fixation devices, and graft choice, with equal clinical results as long as key surgical principles are maintained1. This article provides a step-by-step description of our preferred technique as well as offering technical pearls and a review of patient outcomes. Description: The MPFL is reconstructed anatomically using a hamstring allograft or autograft with an ideal width of 4 to 5 mm. The graft is secured to the femur with an interference screw at its anatomic insertion point, which can be defined by radiographic or anatomic landmarks, is passed through the soft tissues between the capsule and the medial retinaculum/vastus medialis oblique muscles, and is secured to the superomedial patellar border. Alternatives: Nonoperative treatment of lateral patellar dislocations is associated with recurrent dislocation rates of 35% to 50%; surgical treatment for recurrent dislocations has afforded improved patient outcomes2,3. In general, there are 3 surgical options to restore the function of the MPFL. Historically, acute repair was thought to offer the MFPL a chance to “heal” and resume its function; however, the literature has failed to support this as a reliable option in the setting of lateral patellar instability4. Similarly, delayed tightening or imbrication of the MPFL in the setting of chronic laxity has not demonstrated worthwhile clinical results5. MPFL reconstruction with a graft, as described here, has provided the most consistent outcomes. Rationale: Isolated reconstruction of the MPFL is indicated for patients with a history consistent with recurrent lateral patellar instability and a physical examination demonstrating excessive lateral patellar translation. Patients with high-grade trochlear dysplasia and patella alta may be better treated with concomitant osseous procedures such as trochleoplasty or tibial tubercle osteotomy.
Evaluation of choroidal perfusion changes in obese patients: ocular effects of insulin resistance.

PURPOSE We aimed to evaluate choroidal per-fusion changes in obese patients using optical coherence tomography and dynamic contour tonometry, to determine whether these changes are associated with body mass index, and to assess the ocular effects of insulin resistance. METHODS We retrospectively evaluated the data of 32 obese patients with body mass index >30 kg/m2 and 45 healthy control individuals. Intraocular pressure and ocular pulse amplitude values of the patients were measured using dynamic contour tonometry, and the mean choroidal thickness was measured using enhanced depth imaging optical coherence tomography. Insulin resistance was assessed using the homeostasis model assessment-estimated insulin resistance index. RESULTS The mean choroidal thickness (294.30 ± 60.87 μm) and ocular pulse amplitude (2.10 ± 0.74) were lower, whereas the mean intraocular pressure (16.61 ± 2.35 mmHg) was higher in obese patients than in controls. There was a significant negative correlation between body mass index and ocular pulse amplitude (r=-0.274; p=0.029) and an insignificant negative correlation between mean choroidal thickness, intraocular pressure, and body mass index. There was an insignificant negative correlation between homeostasis model assessment-estimated insulin resistance index, mean choroidal thickness, and intraocular pressure and significant ne-gative correlation between homeostasis model assessment-estimated insulin resistance index and ocular pulse amplitude (r=-0.317; p=0.022). CONCLUSION We found reduced mean choroidal thickness and ocular pulse amplitude and increased mean intraocular pressure in obese patients. These changes indicated a decrease in choroidal perfusion and ocular blood flow. It may be possible to detect ocular blood flow changes in obese patients through noninvasive assessment using the choroid. The negative correlation between insulin resistance and ocular pulse amplitude may be associated with intracellular fat accumulation in obese patients.
A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for Designing Novel Drugs

A combined in silico method was developed to predict potential protein targets that are involved in cardiotoxicity induced by aconitine alkaloids and to study the quantitative structure–toxicity relationship (QSTR) of these compounds. For the prediction research, a Protein-Protein Interaction (PPI) network was built from the extraction of useful information about protein interactions connected with aconitine cardiotoxicity, based on nearly a decade of literature and the STRING database. The software Cytoscape and the PharmMapper server were utilized to screen for essential proteins in the constructed network. The Calcium-Calmodulin-Dependent Protein Kinase II alpha (CAMK2A) and gamma (CAMK2G) were identified as potential targets. To obtain a deeper insight on the relationship between the toxicity and the structure of aconitine alkaloids, the present study utilized QSAR models built in Sybyl software that possess internal robustness and external high predictions. The molecular dynamics simulation carried out here have demonstrated that aconitine alkaloids possess binding stability for the receptor CAMK2G. In conclusion, this comprehensive method will serve as a tool for following a structural modification of the aconitine alkaloids and lead to a better insight into the cardiotoxicity induced by the compounds that have similar structures to its derivatives.
Are we there yet? A Case Study of Industry-University Collaboration on Communicative Competence for Sustainable Employability and Work Readiness

The Industry-University Collaboration is a unique symbiosis and partnership of any graduate program. The importance of such partnership is not looked upon lightly as students are engaged for eight months with respective host companies. Being a continued shadow of the interns, the researcher was able to see a transformation of wide eyed interns upon entry to blossoming and excited semiprofessionals upon the completion of their internship. Were students competent to be employed and work-ready as result of the eight month attachment? Were the interns able to carry themselves as prospective employees if given the opportunity to begin work? What were the communicative competencies expected of the interns when assigned to real projects? Based on the theory of situated learning and legitimate peripheral participation, the Industry-University collaboration is aimed at equipping the students with out of classroom lifelong learning. Have students become more employable and work ready as a result of the said attachment? What are the communicative competencies attached from such collaboration? Interviews excerpts with managers, academic supervisors and students are captured in this case study relating to work readiness and employability of students from HEI.
Addition of Infiltration Between the Popliteal Artery and the Capsule of the Posterior Knee and Adductor Canal Block to Periarticular Injection Enhances Postoperative Pain Control in Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND Periarticular injections (PAIs) are becoming a staple component of multimodal joint pathways. Motor-sparing peripheral nerve blocks, such as the infiltration between the popliteal artery and capsule of the posterior knee (IPACK) and the adductor canal block (ACB), may augment PAI in multimodal analgesic pathways for knee arthroplasty, but supporting literature remains rare. We hypothesized that the addition of ACB and IPACK to PAI would lower pain on ambulation on postoperative day (POD) 1 compared to PAI alone. METHODS This triple-blinded randomized controlled trial included 86 patients undergoing unilateral total knee arthroplasty. Patients either received (1) a PAI (control group, n = 43) or (2) an IPACK with an ACB and modified PAI (intervention group, n = 43). The primary outcome was pain on ambulation on POD 1. Secondary outcomes included numeric rating scale (NRS) pain scores, patient satisfaction, and opioid consumption. RESULTS The intervention group reported significantly lower NRS pain scores on ambulation than the control group on POD 1 (difference in means [95% confidence interval], -3.3 [-4.0 to -2.7]; P < .001). In addition, NRS pain scores on ambulation on POD 0 (-3.5 [-4.3 to -2.7]; P < .001) and POD 2 (-1.0 [-1.9 to -0.1]; P = .033) were significantly lower. Patients in the intervention group were more satisfied, had less opioid consumption (P = .005, postanesthesia care unit, P = .028, POD 0), less intravenous opioids (P < .001), and reduced need for intravenous patient-controlled analgesia (P = .037). CONCLUSIONS The addition of IPACK and ACB to PAI significantly improves analgesia and reduces opioid consumption after total knee arthroplasty compared to PAI alone. This study strongly supports IPACK and ACB use within a multimodal analgesic pathway.
The anatomy of the forelimb in the anteater (Tamandua) and its functional implications

The forelimbs of anteaters play a major role in obtainment of food, defense, and locomotion. The greatly enlarged claws on the manus are used for ripping open insect nests and insect‐infested wood; the claws also serve as the animals' only defensive weapons, since they lack teeth. Specialization of the claws for these functions has also had a substantial effect on the ways in which the forelimb is used for posture and locomotion.
Visual Distraction During Sleep Induction with Propofol in Pediatric Patients – Can Cartoon Watching Influence the Sedative Dose?

Abstract Background In general anesthesia, cartoon watching and playing video games reduce anxiety in children. It is unknown whether watching a video in the intervention room has a similar effect, and therefore is able to reduce sedative doses in children undergoing small medical procedures. Aim of this prospective study was to determine the effect of watching a standardized cartoon immediately before and during sleep induction for deep sedation on consumption of propofol in children. Patients and Methods 50 children aged 2–14 years undergoing deep sedation were randomly assigned to 2 groups: (A) watching or (B) not watching a standardized videoclip during sleep induction with propofol. The achievement of predefined sedation depth was objectified by measuring Comfort Score (aim 10–14) and Bispectral Index (aim 50–60). Results The median sleep induction dose of propofol did not differ in both groups (A: 1.76 (0.62–4.37) mg/kg; B: 1.37 (0.66–5.26) mg/kgKG; p=0.65). Cartoon watching was associated with shorter sleep onset latency (A: 120 (60–480)s; B: 240 (40–600)s; p=0.043). Subgroup analysis reveals this especially for school children and girls. In both groups no complications occurred. Conclusion Children watching a standard cartoon during sleep induction for deep sedation have a shorter sleep onset time but sedative dose is not reduced.
Impact of Ge Preamorphization Implantation on Both the Formation of Ultrathin TiSix and the Specific Contact Resistivity in TiSix/n-Si Contacts

In this paper, the impact of different Ge preamorphization implantation (PAI) conditions on the formation of ultrathin TiSi<sub><italic>x</italic></sub> as well as on the specific contact resistivity (<inline-formula> <tex-math notation="LaTeX">$\rho _{c}$ </tex-math></inline-formula>) in TiSi<sub><italic>x</italic></sub>/n-Si contacts was investigated systematically. Extensive material characterizations, such as cross-sectional transmission electron microscopy, X-ray diffraction, and angle-resolved X-ray photoelectron spectroscopy, as well as electrical characterizations such <inline-formula> <tex-math notation="LaTeX">$\rho _{c}$ </tex-math></inline-formula> values, Schottky barrier height (SBH), and leakage current of p-n junctions, were performed. It is found that Ge PAI indeed promotes Ti silicidation at 550 °C and the resultant <inline-formula> <tex-math notation="LaTeX">${t}_{\text {TiSix}}$ </tex-math></inline-formula> values are strongly dependent on the thickness of amorphous Si (<inline-formula> <tex-math notation="LaTeX">${t}_{\boldsymbol {\alpha -{\mathrm{ Si}}}}$ </tex-math></inline-formula>) created by Ge PAI. The stoichiometry of TiSi<sub><italic>x</italic></sub> films is rather graded than constant from the TiN/Ti side to Si side. Proper Ge PAI is beneficial in reducing the <inline-formula> <tex-math notation="LaTeX">$\rho _{c}$ </tex-math></inline-formula> values in TiSi<sub><italic>x</italic></sub>/n-Si contacts, and this reduction in <inline-formula> <tex-math notation="LaTeX">$\rho _{c}$ </tex-math></inline-formula> cannot attribute to the reduction of SBH. Though proper Ge PAI leads to reduced <inline-formula> <tex-math notation="LaTeX">$\rho _{c}$ </tex-math></inline-formula> values, the leakage current of p-n diodes is increased as a penalty which needs to be compromised in practical applications.
Update on Misrepresentation of Research Publications Among Orthopaedic Surgery Residency Applicants

Background: Our 2 previous studies (1999, 2007) examining misrepresentation of research publications among orthopaedic residency applicants revealed rates of misrepresentation of 18.0% and 20.6%, respectively. As the residency selection process has become more competitive, the number of applicants who list publications has increased. The purpose of this study was to determine current rates of research misrepresentation by orthopaedic surgery applicants. Methods: We reviewed the publication listings and research section of the Common Application Form from the Electronic Residency Application Service (ERAS) for all applicants applying to 1 orthopaedic residency program. The PubMed-MEDLINE database was principally used to search for citations. The PubMed Identifier (PMID) number was used; if no PMID number was listed, a combination of authors or the title of the work was used. If the citations were not found through PubMed, a previously developed algorithm was followed to determine misrepresentation. Misrepresentation was defined as (1) nonauthorship of a published article in which authorship was claimed, (2) claimed authorship of a nonexistent article, or (3) self-promotion to a higher authorship status within a published article. Results: Five hundred and seventy-three applicants applied to our institution for residency in 2016 to 2017: 250 (43.6%) of 573 applicants did not list a publication, whereas 323 (56.4%) of 573 applicants listed ≥1 publication. We found 13 cases of misrepresentation among a total of 1,100 citations (1.18% in 2017 versus 18.0% in 1999 and 20.6% in 2007, p < 0.001). Ten cases of misrepresentation were self-promotion to a higher authorship status. There were 2 cases of claimed authorship of an article that could not be found. Only 1 applicant misrepresented more than once. Conclusions: Based on our findings, orthopaedic surgery residency applicants are accurately representing their publication information. The incorporation of the PMID number on the ERAS application has streamlined the process for finding publications, and has possibly encouraged veracity on residency applications. Faculty involved in the resident selection process should be aware of the significant decline in the rate of misrepresentation by medical students applying for orthopaedic surgery residency versus the rate in our prior studies.
Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women

Sexually transmitted infection (STI) of the upper reproductive tract can result in inflammation and infertility. A biomarker of STI-induced upper tract inflammation would be significant as many women are asymptomatic and delayed treatment increases risk of sequelae. Blood mRNA from 111 women from three cohorts was profiled using microarray. Unsupervised analysis revealed a transcriptional profile that distinguished 9 cases of STI-induced endometritis from 18 with cervical STI or uninfected controls. Using a hybrid feature selection algorithm we identified 21 genes that yielded maximal classification accuracy within our training dataset. Predictive accuracy was evaluated using an independent testing dataset of 5 cases and 10 controls. Sensitivity was evaluated in a separate test set of 12 women with asymptomatic STI-induced endometritis in whom cervical burden was determined by PCR; and specificity in an additional test set of 15 uninfected women with pelvic pain due to unknown cause. Disease module preservation was assessed in 42 women with a clinical diagnosis of pelvic inflammatory disease (PID). We also tested the ability of the biomarker to discriminate STI-induced endometritis from other diseases. The biomarker was 86.7% (13/15) accurate in correctly distinguishing cases from controls in the testing dataset. Sensitivity was 83.3% (5/6) in women with high cervical Chlamydia trachomatis burden and asymptomatic endometritis, but 0% (0/6) in women with low burden. Specificity in patients with non-STI-induced pelvic pain was 86.7% (13/15). Disease modules were preserved in all 8 biomarker predicted cases. The 21-gene biomarker was highly discriminatory for systemic infections, lupus, and appendicitis, but wrongly predicted tuberculosis as STI-induced endometritis in 52.4%. A 21-gene biomarker can identify asymptomatic women with STI-induced endometritis that places them at risk for chronic disease development and discriminate STI-induced endometritis from non-STI pelvic pain and other diseases.
Dönüştürücü Liderlik ile Rekabet Üstünlüğü Performansı Arasındaki İlişkide Etkileşimsel Liderliğin Aracılık Rolü

Donusturucu liderlik ile rekabet ustunlugu performansi arasindaki iliskide etkilesimsel liderligin aracilik rolunu belirlemek amaciyla ele alinan bu calisma, orneklem olarak Kars ve ilcelerinde faaliyette bulunan 3, 4 ve 5 yildizli otel isletmelerinde calisan 258 personeli kapsamaktadir. Kolayda orneklem yonteminin kullanildigi calismada veriler demografik, donusturucu liderlik, rekabet ustunlugu performansi ve etkilesimsel liderligi iceren sorularin yer aldigi anket teknigiyle elde edilmistir. Elde edilen veriler SPSS programi ile analiz edilmistir. Calismada kullanilan olceklerin gecerlilik ve guvenirliliklerini test etmek icin acimlayici faktor analizi yapilmistir. Ulusal ve uluslararasi literaturde degiskenlere yonelik olarak yapilmis calismalar isiginda hipotezler olusturularak korelasyon ve coklu regresyon analizleri ile test edilmistir. Aracilik rolunun tespit edilmesinde Sobel testinden yararlanilmis ve sonuclar bu dogrultuda yorumlanmistir. Analizler neticesinde elde edilen bulgularda donusturucu liderlik ile rekabet ustunlugu performansi arasinda dusuk, alt boyutu olan vizyon-ilham verme ile yuksek bir iliski tespit edilirken, rekabet ustunlugu performansinin saglanmasinda donusturucu ve etkilesimsel liderligin onemli derecede etkili oldugu gorulmustur. Ayrica donusturucu liderlik ile rekabet ustunlugu performansi iliskisinde etkilesimsel liderligin kismi aracilik rolu ustlendigi tespit edilmistir.