Miracle-dz/UniFAR-FTUs huggingface dataset:
Medial Plantar Artery Island Flap for Heel Reconstruction

Coverage of soft tissue defects of the heel has been a challenge to reconstructive surgeons in the past. The medial plantar artery flap has facilitated heel coverage since its development in the 1980s. This was a prospective study in 2 centers assessing the complications and durability of this flap primarily in patients with sensory impairment. All patients but 1 had chronic plantar ulceration due to sensory loss, and 5 patients also had developed squamous cell carcinoma. Fifty-one flaps were carried out in 48 patients. One flap underwent necrosis, and delayed healing was seen in 4 cases. Total flap survival was 98%. Minor revision of the flap or its pedicle was required in 3 cases. With a mean follow-up of 14 months, there were recurrences of ulceration in 7 feet (14%). The relevant literature is reviewed. The medial plantar artery flap is a reliable flap for heel coverage in both our centers and others. It is durable and long lasting even in insensate.
Comparison of responses of cutaneous nociceptive and nonnociceptive brain stem neurons in trigeminal subnucleus caudalis (medullary dorsal horn) and subnucleus oralis to natural and electrical stimulation of tooth pulp.

The activity of 160 single neurons excited by electrical stimulation of the canine tooth pulp was studied in the subnucleus caudalis (medullary dorsal horn) and the subnucleus oralis of the trigeminal (V) spinal tract nucleus in chloralose-anesthetized cats to test the effects of natural as well as electrical stimulation of the tooth pulp. The neurons were functionally classified on the basis of their cutaneous receptive-field properties as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR), or nociceptive specific (NS). The orofacial receptive-field properties and responses evoked by electrical stimulation of the tooth pulp indicated that the oralis and caudalis neurons examined had characteristics typical of those previously documented for oralis LTM neurons and for caudalis LTM, WDR, and NS neurons. Each neuron was also tested with cold and warm stimulation of the canine tooth, and some neurons were also tested for responsiveness to thermal stimulation of the premolar tooth or to mechanical and chemical stimuli delivered to the dentine of the canine tooth. Although all the neurons could be excited by electrical stimulation of the pulp, we found that the only neurons that consistently responded to thermal pulp stimuli were those located in the V subnucleus caudalis. Moreover, only those caudalis neurons that had been functionally classified as nociceptive (4 WDR and 21 NS neurons) showed this responsiveness. Heating of the canine or premolar tooth excited 24 of these 25 nociceptive neurons; cooling activated only 3, and none of the small number of neurons tested with mechanical and chemical stimulation of the dentine was excited. The response of the nociceptive neurons to heating of the tooth contrasted with the responses of the same neurons to pinching and heating of their cutaneous receptive field. (ABSTRACT TRUNCATED AT 400 WORDS)
The 'Do Not Resuscitate' Order: A Profile of Its Changing Use

• The "do not resuscitate" (DNR) order has wide-ranging ethical, legal, and economic implications. We reviewed the course of 244 patients who died during two three-month periods, in 1982 and 1986. We found that 68% of patients who died had a DNR order written, including 94% with malignancy and half of patients with cardiovascular disease. Most orders (61%) were written within three days of death, with 64% written on medical-surgical floors and 34% in critical care units. Even among patients under the age of 60 years, 57% had a DNR order written by the time of death. Ninety-one percent of DNR orders were written by attending physicians, with accompanying explanatory note in 84%. Documentation showed only 14% of patients but 77% of families being consulted. In 1983 a new two-level DNR order system defined two levels of intensity: "all but cardiopulmonary resuscitation" and "comfort measures only. " Equal numbers of patients received each order in the 1986 sample. No patient was transferred to the critical care units after a DNR order had been written. The prevalence of DNR orders written for patients dying of cardiovascular disease increased from 27% to 64% over the four years. We conclude, from study of deaths in this representative community hospital, that an explicit DNR order is now the rule rather than the exception, but decisions are made late and involve family far more than the patient. (Arch Intern Med1988;148:2373-2375)
Disinfection of water using Pt- and Ag-doped TiO2 photocatalysts

In this article we have reported heterogeneous photocatalytic disinfection using pristine and Ag- and Pt-doped nano TiO2 under near-UV light and solar light irradiation. Disinfection experiments were conducted in slurry reactors with Escherichia coli, artificial light and sunlight. The influence of various amounts of Pt and Ag loading (0.5% to 5%) on the E. coli inactivation was examined and results indicated that 5% Pt-TiO2 and 0.5% Ag-TiO2 showed the highest photocatalytic E. coli inactivation. The Pt- and Ag-doped photocatalysts were characterized using XPS and TEM analysis. The influence of experimental parameters such as various photocatalysts, photocatalyst concentration, reactor geometry effect, pH and temperature on the photocatalytic disinfection was studied. The experimental results show that sunlight or near-UV light with TiO2 photocatalyst strongly inactivates E.coli. The Ag-TiO2 photocatalyst was the most efficient photocatalyst tested for bactericidal activity. A plausible mechanism of photocatalysed E. coli inactivation is discussed. In conclusion, the doped nano TiO2 photocatalysts is a potential candidate for E. coli inactivation.
PPTX, a pentraxin domain‐containing protein, interacts with the T1 domain of Kv4

Voltage‐gated K+ (Kv) channels reside as tetramers in the membrane. The events that coordinate folding, trafficking, and tetramerization are mediated by an array of associated proteins and phospholipids whose identification is vital to understanding the dynamic nature of channel expression and activity. An interaction between an A‐type K+ channel, Kv4.2, and a protein containing a pentraxin domain (PPTX) was demonstrated in the cochlea (Duzhyy et al. [ 2005 ] J. Biol. Chem. 280:15165–15172). Here, we present results based on fold recognition and homology modeling that revealed the tetramerization (T1) domain of Kv4.2 as a potential docking site for interacting proteins such as PPTX. By using this model, putative sites were experimentally tested with the yeast two‐hybrid system to assay interactions between PPTX and the T1 domain of Kv4.2 wild type (wt) and mutants (mut). Results showed that amino acid residues 86 and 118 in the T1 domain are essential for interaction, because replacing these negatively charged with neutrally charged amino acids inhibits interactions. Cotransfections of Chinese hamster ovary cells with PPTX and Kv4.2wt further revealed that PPTX increases Kv4.2wt expression in vitro when analyzing total lysates, whereas interactions with Kv4.2mut resulted in a decrease. These studies suggest that portions of the T1 domain can act as docking sites for proteins such as PPTX, further underscoring the significance of this domain. © 2009 Wiley‐Liss, Inc.
Critical Success Factors in New Product Development

New product development (NPD) is essential for outstanding corporate performance, and research about what leads to new product success has been carried out for both goods and services frequently. Despite extensive documentation on how to achieve success, NPD remains a high risk venture. Recent studies showed that the overall rate of success for newly commercialized products has remained stable at less than 60 %, indicating that substantial resources continue to be devoted to new product development efforts that fail in the marketplace. Therefore, In this research, to prevent the unsuccessful resource use that allocate to new product development, critical success factors that affect new product performance are presented. Key Words: New product development (NPD), critical success factors Ozet: Firmalarin performanslarinin artirilmasinda yeni urun gelistirme onemli bir etkiye sahiptir. Bundan dolayi gerek mal gerekse hizmet uretiminde yeni urun gelistirmede etkili olan basari faktorleri siklikla ele alinmaktadir. Bu cabalar sonucu yeni urun gelistirme hakkinda yiginla bilgi bulunmasina ragmen hala yeni urun gelistirme cabalari riskli bir macera olarak gorulmektedir.Yeni ticarilestirilen urunlerin genel basari ortalamasinin % 60’in altinda olmasi, yeni urun gelistirmeye ayrilan kaynaklarin basarisiz kullanildiginin bir gostergesidir. Bundan dolayi bu arastirmada, yeni urun gelistirmeye ayrilan basarisiz kaynak kullanimini engelleyici kritik basari faktorleri ele alinacaktir. Anahtar Kelimeler: Yeni urun gelistirme, kritik basari faktorleri
Preferential association with ClC-3 permits sorting of ClC-4 into endosomal compartments

ClC-4 is an intracellular Cl−/H+ exchanger that is highly expressed in the brain and whose dysfunction has been linked to intellectual disability and epilepsy. Here we studied the subcellular localization of human ClC-4 in heterologous expression systems. ClC-4 is retained in the endoplasmic reticulum (ER) upon overexpression in HEK293T cells. Co-expression with distinct ClC-3 splice variants targets ClC-4 to late endosome/lysosomes (ClC-3a and ClC-3b) or recycling endosome (ClC-3c). When expressed in cultured astrocytes, ClC-4 sorted to endocytic compartments in WT cells but was retained in the ER in Clcn3−/− cells. To understand the virtual absence of ER-localized ClC-4 in WT astrocytes, we performed association studies by high-resolution clear native gel electrophoresis. Although other CLC channels and transporters form stable dimers, ClC-4 was mostly observed as monomer, with ClC-3–ClC-4 heterodimers being more stable than ClC-4 homodimers. We conclude that unique oligomerization properties of ClC-4 permit regulated targeting of ClC-4 to various endosomal compartment systems via expression of different ClC-3 splice variants.
FTIR studies on differential intermolecular association in crystalline and amorphous states of structurally related non-steroidal anti-inflammatory drugs.

Information on molecular interactions critically impacts the physical stability and "stabilization" strategy for the amorphous state of pharmaceuticals. The present study was designed to understand the differences in intermolecular interactions in amorphous and crystalline phases in a series of structurally related compounds--celecoxib (CLB), valdecoxib (VLB), rofecoxib (RFB), and etoricoxib (ETB). FTIR spectra of the compounds in their crystalline and amorphous phase were obtained. Interaction patterns in respective crystalline states were obtained from single crystal data. The intermolecular interaction patterns varied between the crystalline and amorphous phase of CLB, VLB, and ETB, while no variation was observed for RFB. Comparison of four crystalline phases though revealed significantly variations, the interactions were remarkably similar in the amorphous state, possibly as a result of constraints of crystal packing ceasing to exist. Conversion of crystalline state to amorphous state led to weakening of some interactions while others got strengthened. The differences in intermolecular interactions could successfully explain the differences in thermodynamic properties studied previously (Kaushal, A. M. ; Bansal, A. K. Thermodynamic behavior of glassy state of structurally related compounds.
Association of MicroRNA Expression in Hepatocellular Carcinomas with Hepatitis Infection, Cirrhosis, and Patient Survival

Purpose: MicroRNA (miRNA) is a new class of small, noncoding RNA. The purpose of this study was to determine if miRNAs are differentially expressed in hepatocellular carcinoma (HCC). Experimental Design: More than 200 precursor and mature miRNAs were profiled by real-time PCR in 43 and 28 pairs of HCC and adjacent benign liver, respectively, and in normal liver specimens. Results: Several miRNAs including miR-199a, miR-21, and miR-301 were differentially expressed in the tumor compared with adjacent benign liver. A large number of mature and precursor miRNAs were up-regulated in the adjacent benign liver specimens that were both cirrhotic and hepatitis-positive compared with the uninfected, noncirrhotic specimens (P < 0.01). Interestingly, all of the miRNAs in this comparison had increased expression and none were decreased. The expression of 95 randomly selected mRNAs was not significantly altered in the cirrhotic and hepatitis-positive specimens, suggesting a preferential increase in the transcription of miRNA. Comparing the miRNA expression in the HCC tumors with patient's survival time revealed two groups of patients; those with predominantly lower miRNA expression and poor survival and those with predominantly higher miRNA expression and good survival (P < 0.05). A set of 19 miRNAs significantly correlated with disease outcome. A number of biological processes including cell division, mitosis, and G1-S transition were predicted to be targets of the 19 miRNAs in this group. Conclusion: We show that a global increase in the transcription of miRNA genes occurs in cirrhotic and hepatitis-positive livers and that miRNA expression may prognosticate disease outcome in HCC.
Oral combination chemotherapy in conjunction with filgrastim (G‐CSF) in the treatment of AIDS‐related non‐Hodgkin's lymphoma: Evaluation of the role of G‐CSF; Quality‐of‐life analysis and long‐term follow‐up

In 1993 we reported the efficacy and toxicity profile of an oral combination regimen administered to 18 patients with AIDS‐related lymphoma (NHL‐1 study). We observed a 61% response rate; 39% one‐year survival rate; nearly two‐thirds of patients developed ≥ grade 3 leukopenia; and 28% of cycles were associated with febrile neutropenia. These results prompted us to shorten the duration of therapy and to add G‐CSF to ameliorate the myelosuppression. Twenty patients with biopsy‐proven AIDS‐related lymphoma were treated with three 6‐week cycles of oral chemotherapy consisting of lomustine (CCNU) 100 mg/m2 on day 1, cycles no. 1 and 3; etoposide 200 mg/m2 days 1–3; cyclophosphamide and procarbazine both 100 mg/m2 days 22–31; and G‐CSF 5 μg/kg subcutaneously days 5–21 and days 33–42 (NHL‐2 study). The following analyses were undertaken: (1) evaluation of toxicity and efficacy parameters for patients in the current (NHL‐2) study; (2) analysis of the clinical role of G‐CSF by (historical) comparison with the NHL‐1 study of the same regimen without G‐CSF; (3) quality‐of‐life assessments using the Functional Living Index—Cancer (FLIC) and Brief Symptom Inventory (BSI) instruments for all 38 patients (NHL‐1+2); and (4) long‐term follow‐up for all 38 patients. In the current study the overall objective response using ECOG criteria was 70% (95% CI, 50–90%) with 6 CRs (30%) and 8 PRs (40%). The median survival duration was 7.3 months (range: 0.5–51+ months). One patient developed CNS relapse. There were no significant differences with respect to demographics or prognostic factors between the patient populations of the NHL‐1 study and the current study (P > 0.2 for each factor).
Trafficking of the Phosphoprotein PfCRT to the Digestive Vacuolar Membrane in Plasmodium falciparum

The digestive vacuole plays an important role in the pathophysiology of the human malaria parasite Plasmodium falciparum. It is a terminal degradation organelle involved in the proteolysis of the host erythrocyte's haemoglobin; it is the site of action of several antimalarial drugs and its membrane harbours transporters implicated in drug resistance. How the digestive vacuole recruits residential proteins is largely unknown. Here, we have investigated the mechanism underpinning trafficking of the chloroquine resistance transporter, PfCRT, to the digestive vacuolar membrane. Nested deletion analysis and site‐directed mutagenesis identified threonine 416 as a functional residue for sorting PfCRT to its site of residence. Mass spectroscopy demonstrated that threonine 416 can be phosphorylated. Further phosphorylation was detected at serine 411. Our data establish PfCRT as a phosphoprotein and suggest that phosphorylation of threonine 416 is a possible deciding signal for the sorting of PfCRT to the digestive vacuolar membrane.
Role of the Serine-Threonine Kinase PAK-1 in Myxoma Virus Replication

ABSTRACT Subversion or appropriation of cellular signal transduction pathways is a common strategy employed by viruses to promote an environment within infected cells that supports the viral replicative cycle. Using subsets of 3T3 murine fibroblasts previously shown to differ in their ability to support myxoma virus (MV) replication, we investigated the role of host serine-threonine kinases (STKs) as potential mediators of the permissive phenotype. Both permissive and nonpermissive 3T3 cells supported equivalent levels of virion binding, entry, and early virus gene expression, indicating that MV tropism in 3T3 cells was not determined by receptor-mediated entry. In contrast, late virus gene expression and viral DNA replication were selectively compromised in restrictive 3T3 cells. Addition of specific protein kinase inhibitors, many of which shared the ability to influence the activity of the STKs p21-activated kinase 1 (PAK-1) and Raf-1 attenuated MV replication in permissive 3T3 cells. Western blot detection of the phosphorylated forms of PAK-1 (Thr423) and Raf-1 (Ser338) confirmed activation of these kinases in permissive cells after MV infection or gamma interferon treatment, but the activated forms of both kinases were greatly reduced or absent in restrictive 3T3 cells. The biological significance of these activations was demonstrated by using the autoinhibitory domain of PAK-1 (amino acids 83 to 149), expression of which reduced the efficiency of MV infection in permissive 3T3 cells concurrent with a decrease in PAK-1 activation. In comparison, overexpression of a constitutively active PAK-1 (T423E) mutant increased MV replication in restrictive 3T3 cells. These observations suggest that induced signaling via cellular STKs may play important roles in determining the permissiveness of host cells to poxvirus infection.
A systematic review and meta-analysis of immunochemotherapy with rituximab for B-cell non-Hodgkin's lymphoma

Abstract Background. Although some randomized controlled trials had compared the anti-CD20 monoclonal antibody rituximab plus chemotherapy (R-chemo) to chemotherapy alone for B-cell non-Hodgkin's lymphoma, the curative effects of R-chemo were still controversial. A systematic review and meta-analysis was performed to examine the efficacy of using R-chemo compared with the identical chemotherapy alone in the patients with B-cell non-Hodgkin's lymphoma. Material and methods. Medical databases and conference proceedings were searched for randomized controlled trials which compared R-chemo with chemotherapy alone in patients with newly diagnosed or relapsed B-cell non-Hodgkin's lymphoma. Endpoints were overall survival, overall response, disease control, and adverse events. Results. Twelve eligible trials were identified, reporting outcomes of 4 996 patients. Fixed-effects analysis showed overall survival to be superior for R-chemo-treated patients (relative risks [RR], 1.09; 95%confidence interval [CI], 1.06–1.12, p <0.00001). Superiority was also observed for the patients receiving R-chemo with respect to overall response (RR, 1.17; 95%CI, 1.10–1.25, p <0.00001), complete response (RR, 1.52; 95%CI, 1.27–1.82, p <0.00001), and disease control (RR, 1.36; 95%CI, 1.26–1.46, p <0.00001). R-chemo improved overall survival, overall response and disease control in patients with diffuse large B-cell lymphoma (RR, 1.11, 95%CI: 1.06–1.16, p <0.0001; RR, 1.09, 95%CI: 1.01–1.19, p = 0.03 and RR, 2.00, 95%CI: 1.59–2.53, p< 0.00001, respectively) and follicular lymphoma (RR, 1.08, 95%CI: 1.04–1.12, p <0.0001; RR, 1.19, 95%CI: 1.07–1.33, p =0.001 and RR, 2.58, 95%CI: 1.61–4.12, p <0.0001, respectively). Meanwhile, R-chemo improved overall response in patients with mantle cell lymphoma (RR, 1.22, 95%CI: 1.07–1.40, p =0.004). Conclusion. R-chemo is superior to chemotherapy alone in patients with B-cell non-Hodgkin's lymphoma, especially for diffuse large B-cell lymphoma and follicular lymphoma.
Reproducibility study for free‐breathing measurements of pyruvate metabolism using hyperpolarized 13C in the heart

Spatially resolved images of hyperpolarized 13C substrates and their downstream products provide insight into real‐time metabolic processes occurring in vivo. Recently, hyperpolarized 13C pyruvate has been used to characterize in vivo cardiac metabolism in the rat and pig, but accurate and reproducible measurements remain challenging due to the limited period available for imaging as well as physiological motion. In this article, time‐resolved cardiac‐ and respiratory‐gated images of [1‐13C] pyruvate, [1‐13C] lactate, and 13C bicarbonate in the heart are acquired without the need for a breathhold. The robustness of these free‐breathing measurements is demonstrated using the time‐resolved data to produce a normalized metric of pyruvate dehydrogenase and lactate dehydrogenase activity in the heart. The values obtained are reproducible in a controlled metabolic state. In a 60‐min ischemia/reperfusion model, significant differences in hyperpolarized bicarbonate and lactate, normalized using the left ventricular pyruvate signal, were detected between scans performed at baseline and 45 min after reperfusion. The sequence is anticipated to improve quantitative measurements of cardiac metabolism, leading to feasible validation studies using fewer subjects, and potentially improved diagnosis, serial monitoring, and treatment of cardiac disease in patients. Magn Reson Med 69:1063–1071, 2013. © 2012 Wiley Periodicals, Inc.
Level of radiation dose in university hospital non-insured private health screening programs in Korea

Objectives The aim of this study is to evaluate radiation exposure resulting from the comprehensive health examinations of selected university hospital programs and to present basic data for research and management strategies on the health effects of medical radiation exposure. Methods Radiation-based diagnostic studies of the comprehensive health examination programs of ten university hospitals in Seoul, Korea, as introduced in their websites, were analyzed. The medical radiation studies of the programs were reviewed by radiologists. Only the effective doses of the basic studies were included in the analysis. The optional studies of the programs were excluded. Results Among the 190 comprehensive health examination programs, 132 programs (69.5%) included computed tomography studies, with an average of 1.4 scans. The average effective dose of radiation by program was 3.62 mSv for an intensive program for specific diseases; 11.12 mSv for an intensive program for cancer; 18.14 mSv for a premium program; and 24.08 mSv for an overnight program. A higher cost of a programs was linked to a higher effective dose (r=0.812). The effective doses of the examination programs for the same purposes differed by as much as 2.1 times by hospital. Inclusion of positron emission tomography–computed tomography was the most critical factor in determining the level of effective dose. Conclusions It was found that radiation exposure dose from comprehensive health exam programs targeted for an asymptomatic, healthy public reached between 3.6 and 24 times the annual dose limit for the general public. Relevant management policies at the national level should be provided to minimize medical radiation exposure.