Miracle-dz/UniFAR-FTUs huggingface dataset:
Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index

The melanocortin-4 receptor gene ( MC4R ) is involved in central energy homeostasis and body weight regulation. Both endogenous anorexigenic and orexigenic ligands bind to the receptor.1 Under normal conditions, the anorexigenic tone prevails as revealed by the fact that Mc4r knock-out mice2 develop elevated body weight. Mc4r−/− mice show higher food intake but a similar metabolic rate and similar decreased physical activity compared to wild type (WT) mice of the same strain.2–4 In comparison to a standard low fat diet, this deviant regulation of energy homeostasis is even more pronounced upon intake of a moderately fat diet,5 which leads to an even higher body mass. In all studies, the effect on body weight is smaller in heterozygous than in homozygous knockout mice, but the exact degree of dominance is not clear. In heterozygous Mc4r+/− animals, body mass is increased on average by about 7–45% and in homozygous Mc4r−/− by 50–100% compared to WT2–5 with substantial overlap between groups. The mutations might have a sex dependent effect, but the results are contradictory. In one study, the effect in males was only about half of that in females.2 However, two studies did not detect a sex by genotype interaction in this Mc4r−/− strain.4,5 One study in a different knockout line of the same inbred strain found a sex by genotype interaction in the opposite direction, with only a marginal effect in heterozygous females whereas heterozygous males had a body weight intermediate between WT and homozygous knockouts.3 The first mutations in the human MC4R gene were reported in extremely obese probands.6–8 Since then, several other studies investigated the association of different MC4R mutations with obesity. According to a recent overview,9 at least 34 putatively functionally relevant …
Longevity and determinants of protective humoral immunity after pandemic influenza infection.

RATIONALE Antibodies to influenza hemagglutinin are the primary correlate of protection against infection. The strength and persistence of this immune response influences viral evolution and consequently the nature of influenza epidemics. However, the durability and immune determinants of induction of humoral immunity after primary influenza infection remain unclear. OBJECTIVES The spread of a novel H1N1 (A[H1N1]pdm09) virus in 2009 through an unexposed population offered a natural experiment to assess the nature and longevity of humoral immunity after a single primary influenza infection. METHODS We followed A(H1N1)pdm09-seronegative adults through two influenza seasons (2009-2011) as they developed A(H1N1)pdm09 influenza infection or were vaccinated. Antibodies to A(H1N1)pdm09 virus were measured by hemagglutination-inhibition assay in individuals with paired serum samples collected preinfection and postinfection or vaccination to assess durability of humoral immunity. Preexisting A(H1N1)pdm09-specific multicytokine-secreting CD4 and CD8 T cells were quantified by multiparameter flow cytometry to test the hypothesis that higher frequencies of CD4(+) T-cell responses predict stronger antibody induction after infection or vaccination. MEASUREMENTS AND MAIN RESULTS Antibodies induced by natural infection persisted at constant high titer for a minimum of approximately 15 months. Contrary to our initial hypothesis, the fold increase in A(H1N1)pdm09-specific antibody titer after infection was inversely correlated to the frequency of preexisting circulating A(H1N1)pdm09-specific CD4(+)IL-2(+)IFN-γ(-)TNF-α(-) T cells (r = -0.4122; P = 0.03). CONCLUSIONS The longevity of protective humoral immunity after influenza infection has important implications for influenza transmission dynamics and vaccination policy, and identification of its predictive cellular immune correlate could guide vaccine development and evaluation.
Cyclooxygenase isozymes are expressed in human myeloma cells but not involved in anti‐proliferative effect of cyclooxygenase inhibitors

Considering possible tumorigenic activity of cyclooxygenase (COX) isozymes in myeloma, we examined expression levels of COX‐1 and ‐2 in seven human myeloma cell lines (ARH‐77, IM‐9, RPMI‐8226, HPC, HS‐Sultan, TSPC‐1, and U‐266). As analyzed by reverse transcriptase‐polymerase chain reaction (RT‐PCR), all the cell lines constitutively expressed COX‐1, while COX‐2 levels markedly varied among different cell lines. Induction of COX‐2 by phorbol ester was observed in RPMI‐8226 and HPC cells. In contrast, COX‐2 was constitutively expressed in ARH‐77 and IM‐9 cells. Moreover, the high expression level of COX‐2 protein in ARH‐77 cells was verified by Western blotting. Intact cells of ARH‐77 converted 14C‐labeled arachidonic acid to prostaglandin E2, F2α, and D2, and this activity was dose‐dependently inhibited by selective COX‐2 inhibitors (SC‐58125 and NS‐398), a non‐selective COX inhibitor (indomethacin), and relatively high concentrations of a selective COX‐1 inhibitor (SC‐560). These COX inhibitors also suppressed the proliferation of ARH‐77 cells, but significant suppression was seen only at 100 µM, a much higher concentration than those sufficient for the COX inhibition. Moreover, proliferation of the myeloma cells lacking COX‐2 was also suppressed by 100 µM of SC‐58125. These results suggested that the anti‐proliferative effect of the COX inhibitors is independent of the inhibition of COX‐2. © 2005 Wiley‐Liss, Inc.
Growth inhibition of metronidazole-susceptible and metronidazole-resistant strains of Gardnerella vaginalis by Lactobacilli in vitro

Metronidazole resistance was produced in susceptible Gardnerella vaginalis after subculture in the presence of metronidazole. Metronidazole-resistant gardnerellae were less susceptible to growth inhibition by Lactobacillus culture filtrates. A low pH (+/- 4) and lactic acid accounted for 60 to 95% of inhibitory activity, and H2O2 accounted for only 0 to 30%. However, in the presence of myeloperoxidase, H2O2-producing lactobacilli decreased the viability of metronidazole-susceptible gardnerellae 2,000-fold.
Impact of family history of diabetes on β-cell function and insulin resistance among Chinese with normal glucose tolerance.

OBJECTIVE This study investigated the impact of family history of diabetes (FHD) on β-cell function among Chinese with normal glucose tolerance. RESEARCH DESIGN AND METHODS A multistage, stratified, cluster random sampling method was used to select a provincially representative sample from Fujian Province. Eventually, a total of 1,183 subjects were entered into the analysis. Several indexes were used to assess the function of β cells, including homeostasis model assessment (HOMA) of insulin resistance (IR), HOMA of β cells, insulinogenic index (IGI), and disposition index. RESULTS Overweight, increased body mass index, higher low-density lipoprotein cholesterol, and higher total cholesterol (TC) were the dominant features of positive FHD (FHD(+)). The FHD(+) subjects had lower insulin sensitivity (P<0.05). FHD(+) subjects showed higher risk of IR after adjusting for other risk factors (odds ratio 1.523 [1.272-2.009]). However, there was no significant difference in insulin secretion between the two groups. With the use of the multiple linear regression model, waist circumference (WC) and triglycerides (TGs) were found to be independent risk factors of the decline of insulin sensitivity in FHD(+) subjects, and insulin sensitivity declined significantly (P<0.05) with the increase of WC and TGs. In addition, the offspring of fathers with diabetes (PT2D) were much older and had higher TC than those of mothers with diabetes (MT2D). After adjusting for gender of the parents, there was no difference between MT2D and PT2D on insulin sensitivity. CONCLUSIONS Inheritance if diabetes is associated with the decline of insulin sensitivity. In addition, insulin sensitivity declined with increasing WC and TG in FHD(+) subjects.
Role of low‐density lipoprotein receptor in the hepatitis C virus life cycle

Hepatitis C virus (HCV) particles are known to be in complex with lipoproteins. As a result of this interaction, the low‐density lipoprotein (LDL) receptor (LDLR) has been proposed as a potential entry factor for HCV; however, its implication in virus entry remains unclear. Here, we reinvestigated the role of the LDLR in the HCV life cycle by comparing virus entry to the mechanism of lipoprotein uptake. A small interfering RNA targeting the LDLR in Huh‐7 cells reduced HCV infectivity, confirming that this receptor plays a role in the life cycle of HCV generated in cell culture. However, kinetics of internalization were much faster for lipoproteins than for infectious HCV particles. Furthermore, a decrease in HCV RNA replication was observed by blocking the LDLR with a specific antibody, and this was associated with an increase in the ratio of phosphatidylethanolamine to phosphatidylcholine in host cells. Nevertheless, a soluble form of the LDLR inhibited both HCV entry into the hepatocytes and its binding to the LDLR expressed on Chinese hamster ovary cells, suggesting a direct interaction between the HCV particle and the LDLR. Finally, we showed that modification of HCV particles by lipoprotein lipase (LPL) reduces HCV infectivity and increases HCV binding to LDLR. Importantly, LPL treatment also induced an increase in RNA internalization, suggesting that LDLR, at least in some conditions, leads to nonproductive internalization of HCV. Conclusion: The LDLR is not essential for infectious HCV particle entry, whereas the physiological function of this receptor is important for optimal replication of the HCV genome. (HEPATOLOGY 2012)
Not by science alone: why orangutan conservationists must think outside the box

Orangutan survival is threatened by habitat loss and illegal killing. Most wild populations will disappear over the next few decades unless threats are abated. Saving orangutans is ultimately in the hands of the governments and people of Indonesia and Malaysia, which need to ensure that habitats of viable orangutan populations are protected from deforestation and well managed to ensure no hunting takes place. Companies working in orangutan habitat also have to play a much bigger role in habitat management. Although the major problems and the direct actions required to solve them—reducing forest loss and hunting—have been known for decades, orangutan populations continue to decline. Orangutan populations in Sumatra and Borneo have declined by between 2,280 and 5,250 orangutans annually over the past 25 years. As the total current population for the two species is some 60,000 animals in an area of about 90,000 km2, there is not much time left to make conservation efforts truly effective. Our review discusses what has and has not worked in conservation to guide future conservation efforts.
AgNORs in benign, borderline and transitional cell neoplasms of the urinary bladder

Argyrophilic nucleolar organizer regions (AgNORs) were studied in 106 tissue samples from the urinary bladder (6 normal transitional epithelium, 5 cystitis, 12 hyperplastic, 14 dysplastic lesions, 12 carcinoma in situ, 4 transitional cell carcinoma grade 0, 12 grade 1, 15 grade II and 12 grade III) to evaluate their role in differentiating benign, borderline and malignant lesions. The NOR counts presented a rising scale from normal (2.21), inflammatory (3.93 for both cystitis and hyperplasia), dysplastic (4.16), carcinoma in situ (5.08) to malignant lesions (5.28 grade I, 6.59 grade II and 8.37 grade III). It was concluded that AgNORs do not have a diagnostic role in these lesions, but that they can act as a reliable adjunct to existing parameters in the early detection of tumour recurrence and grading of malignant neoplasms.
EGFR Mutation Is Specific for Terminal Respiratory Unit Type Adenocarcinoma

We have previously reported that terminal-respiratory-unit (TRU) type adenocarcinoma is a distinct subset of lung adenocarcinoma in terms of molecular pathway for carcinogenesis and phenotypic profiles. This type of cancer shows TRU features, characterized by distinct cellular morphology and the expression of TTF-1 and surfactant proteins. Recently, two groups published novel mutations of the epidermal growth factor receptor (EGFR) that are closely associated with clinical response to gefitinib. The clinicopathologic features of gefitinib responders overlap with those of TRU-type adenocarcinoma, and the characteristics of TRU are likely to correspond to the bronchioloalveolar features reported as a predictor of gefitinib response. We therefore examined the characteristics of EGFR-mutated pulmonary adenocarcinomas with special reference to TRU-type adenocarcinoma. EGFR mutation was detected in 97 of 195 adenocarcinomas, 91 of 149 TRU-type adenocarcinomas and 6 of 46 tumors of other types. Conversely, 91 of 97 EGFR-mutated adenocarcinomas were categorized as TRU-type adenocarcinomas. This type-specific involvement was confirmed by logistic regression model. In addition, EGFR mutation was detected in some cases of atypical adenomatous hyperplasia, a preinvasive lesion of TRU-type adenocarcinoma. These findings further confirm that TRU-type-adenocarcinoma is a distinct adenocarcinoma subset in which a particular molecular pathway is involved.
Traumatic Facial Nerve Palsy in Newborns: Is It Always Iatrogenic?

We sought to report an updated incidence, risk factors, and outcome of traumatic facial palsy (TFP) in newborn infants born at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. We performed a 12-year retrospective study at KAMC. The records of infants with the diagnosis of TFP during the study period were reviewed and compared with 148 healthy term infants born during the same study period. Among 83,067 infants delivered between January 1994 and December 2005, 29 infants were diagnosed with TFP for an incidence of 0.03%. Forceps delivery and maternal primiparity were the only significant risk factors for TFP. Only 7 (24.1%) of these infants were delivered by cesarean section. The other 22 cases of TFP (75.9%) were delivered without any forceps application. Almost all infants (93%) with TFP had spontaneous recovery within 2 months. Only one child suffered from permanent facial weakness when he was last examined at the age of 12 years. Although forceps delivery was considered the most significant risk factor, currently most of the cases occur spontaneously without forceps application. The majority of infants with TFP will recover spontaneously within the first 2 months of life.
Opposing Actions of Phosphatidylinositol 3‐Kinase and Glycogen Synthase Kinase‐3β in the Regulation of HSF‐1 Activity

Abstract: Elevated temperatures activate the survival promoters Aktand heat shock factor‐1 (HSF‐1), a transcription factor that induces theexpression of heat shock proteins (HSPs), such as HSP‐70. Because neuronalmechanisms controlling these responses are not known, these were investigatedin human neuroblastoma SH‐SY5Y cells. Heat shock (45°C) rapidly activatedAkt, extracellular signal‐regulated kinases 1 and 2 (ERK1/2), and p38, butonly Akt was activated in a phosphatidylinositol 3‐kinase (PI‐3K)‐dependentmanner, as the PI‐3K inhibitors LY294002 and wortmannin blocked Aktactivation, but not ERK1/2 or p38 activation. Akt activation was not blockedby inhibition of p38 or ERK1/2, indicating the independence of these signalingsystems. Heat shock treatment also caused a rapid increase in HSF‐1 DNAbinding activity that was partially dependent on PI‐3K activity, as both thePI‐3K inhibitors attenuated this response. Because Akt inhibits glycogensynthase kinase‐3β (GSK‐3β), an enzyme that facilitates cell death,we tested if GSK‐3β is a negative regulator of HSF‐1 activation.Overexpression of GSK‐3β impaired heat shock‐induced activation of HSF‐1,and also reduced HSP‐70 production, which was partially restored by theGSK‐3β inhibitor lithium. Thus, heat shock‐induced activation of PI‐3Kand the inhibitory effect of GSK‐3β on HSF‐1 activation and HSP‐70expression imply that Akt‐induced inhibition of GSK‐3β contributes to theactivation of HSF‐1.
Acupuncture as an adjunct to exercise based physiotherapy for osteoarthritis of the knee: randomised controlled trial

Objective To investigate the benefit of adding acupuncture to a course of advice and exercise delivered by physiotherapists for pain reduction in patients with osteoarthritis of the knee. Design Multicentre, randomised controlled trial. Setting 37 physiotherapy centres accepting primary care patients referred from general practitioners in the Midlands, United Kingdom. Participants 352 adults aged 50 or more with a clinical diagnosis of knee osteoarthritis. Interventions Advice and exercise (n=116), advice and exercise plus true acupuncture (n=117), and advice and exercise plus non-penetrating acupuncture (n=119). Main outcome measures The primary outcome was change in scores on the Western Ontario and McMaster Universities osteoarthritis index pain subscale at six months. Secondary outcomes included function, pain intensity, and unpleasantness of pain at two weeks, six weeks, six months, and 12 months. Results Follow-up rate at six months was 94%. The mean (SD) baseline pain score was 9.2 (3.8). At six months mean reductions in pain were 2.28 (3.8) for advice and exercise, 2.32 (3.6) for advice and exercise plus true acupuncture, and 2.53 (4.2) for advice and exercise plus non-penetrating acupuncture. Mean differences in change scores between advice and exercise alone and each acupuncture group were 0.08 (95% confidence interval −1.0 to 0.9) for advice and exercise plus true acupuncture and 0.25 (−0.8 to 1.3) for advice and exercise plus non-penetrating acupuncture. Similar non-significant differences were seen at other follow-up points. Compared with advice and exercise alone there were small, statistically significant improvements in pain intensity and unpleasantness at two and six weeks for true acupuncture and at all follow-up points for non-penetrating acupuncture. Conclusion The addition of acupuncture to a course of advice and exercise for osteoarthritis of the knee delivered by physiotherapists provided no additional improvement in pain scores. Small benefits in pain intensity and unpleasantness were observed in both acupuncture groups, making it unlikely that this was due to acupuncture needling effects. Trial registration Current Controlled Trials ISRCTN88597683.
Determination of the Mean Normal Prothrombin Time for Assessment of International Normalized Ratios

Summary To report a Prothrombin Time (PT) as International Normalized Ratio in controlling oral anticoagulant therapy, the Mean Normal PT (MNPT) is required. To correct for methodological differences in performing the PT test, each laboratory should determine its own MNPT for each batch of reagent using fresh blood samples from a large number of normal individuals. This would be a laborious procedure. Two models for simplified assessment of MNPT were investigated by two laboratories in a collaborative study. According to the models, the MNPT of a new batch of reagent is calculated, using the PT of a lyophilized control plasma measured with the new batch and a reference batch, as well as the MNPT of the reference batch obtained with fresh samples. Experimental results were obtained with 19 batches of bovine thromboplastin, 4 lyophilized normal control plasmas and fresh blood samples of 40 normal individuals. The PTs of the 4 lyophilized normal control plasmas were not identical to the MNPT of the fresh normal samples and also different from each other. Therefore, the uncorrected PTs of these control plasmas cannot be used as MNPT. In general, there was good agreement between measured and calculated MNPT, although some control plasmas gave better results than others. There were no significant differences between the results obtained by both calculation models.
Progressive Changes of Columella Length and Nasal Growth after Nasoalveolar Molding in Bilateral Cleft Patients: A 3-Year Follow-Up Study

Background: The purpose of this study was to assess the progressive changes of columella length and nasal growth after presurgical nasoalveolar molding and primary cheiloplasty in bilateral complete cleft lip–cleft palate infants. Methods: Twenty-two consecutive complete bilateral cleft lip–cleft palate infants were included. All of them underwent nasoalveolar molding for columella lengthening and retraction of the premaxilla for 3 to 4.5 months before primary cheiloplasty. Standard 1:1 basilar photographs were taken before and after nasoalveolar molding, 1 week after cheiloplasty, and yearly for 3 years. Nasal height and width were measured directly on the photographs. Results: The results revealed that columella length was significantly lengthened after nasoalveolar molding and was further improved after primary cheiloplasty. The columella decreased in length slightly in the first and second years postoperatively and started to increase in length slightly in the third year postoperatively, whereas the rest of the nose grew significantly in height year by year. This consequently appeared as relapse of columella length. The shortage of the columella length was 1.9 mm. Conclusions: Both presurgical nasoalveolar molding and primary cheiloplasty lengthened the columella in bilateral cleft lip–cleft palate patients. However, there was a relative relapse in columella length because of the differential growth between the columella and the rest of the nose in the first and second years postoperatively.
Microbial spoilage of whole sheep livers

When liver treated with antibiotics to inhibit microbial growth were held at 10 degrees C, the initial high pH (6.4) declined as lactic acid accumulated throughout the storage period of 10 days. The glycogen content also declined, but the glucose concentration in the tissues remained high. When livers were allowed to spoil at 10 degrees C, distinct but variable floras developed within the tissues, in the drip, and on the upper surface. Deep-tissue floras were composed of anaerobic and facultative organisms (Lactobacillus, Enterobacter, Aeromonas); surface floras were generally dominated by strictly aerobic organisms (Pseudomonas, Acinetobacter); drip floras contained variable proportions of organisms of all three types, but the facultatively anaerobic Enterobacter were usually present as a major component. Spoilage occurred after 4 to 6 days with the development of visible discrete colonies on the upper surface without spoilage odors being evident. Changes in tissue and drip composition due to microbial activity could be detected only when spoilage had reached an advanced stage.
Perceived Overqualification and Dimensions of Job Satisfaction: A Longitudinal Analysis

Abstract The present study is an investigation of the effects of perceived overqualification on dimensions of job satisfaction. The data for this study came from a two-wave panel study of members of a midwestern American Postal Workers Union local. Job satisfaction was operationalized with 4 subscales from the Job Descriptive Index (R Smith, L. Kendall, & C. Hulin, 1969). The following three hypotheses were tested: (a) Perceived overqualification will be negatively related to facets of job satisfaction; (b) there is stability in the test-retest correlations of facets of job satisfaction; and (c) the effects of perceived overqualification on facets of job satisfaction will not change from Time 1 to Time 2 because of adaptation. The cross-sectional results supported the hypotheses and suggested that perceived overqualification has a negative effect on job satisfaction. However, the relationships varied by dimension of perceived overqualification and dimension of job satisfaction. Future researchers of overqualification and dimensions of job satisfaction should consider relative deprivation as a source of work-related deprivations.