Question:
You will be shown the title of a chemistry paper, together with sections excerpted from the body of the paper. The paper sections may include HTML tags like `<p>` and `</p>`; please ignore these. Your task is to write an abstract for the paper. Your response should include the abstract and no other text.

Title:
Impact of local composition on the energetics of E-centres in Si1−xGex alloys

Paper sections:

correlation functions of the random substitutional alloys. Their atomistic nature ensures that there is a distribution of distinct local environments that also exist in real random alloys. For the Si 1−x Ge x alloys considered the Si or Ge atoms can be surrounded by various Si n Ge 4−n coordination shells (n ranging from 0 to 4). This forms a distribution of local environments, which in turn influence the formation and energetics of dopant-defect interactions such as the E-centre 29 . The efficacy of the SQS technique to model random alloys has been demonstrated previously in numerous systems including group IV alloys 5,20,28 , oxides 21,30 , and III-V alloys 22,31 .

The E-centre in Si or Ge is a substitutional donor atom (for example P, As, Sb) bound with a nearest neighbor vacancy. The structure and energetics of E-centres in Si or Ge have been extensively investigated using both experimental and theoretical techniques [32][33][34][35][36] . Here as a criterion for the formation of the E-centre we consider the binding energies. A defect pair such as the PV is bound if the energy difference between the pair and the isolated defects (i.e. P and V being at distances long enough that they do not associate) is negative. The more negative the binding enenrgies the more likely it would be for the PV pair to form.

Modelling E-Centres. Figure 1 is a schematic representation of the SQS cells for the Si 1−x Ge x compositions considered. These have been reported in previous work 29 , however, they have not been employed to systematically investigate the defect processes in Si 1−x Ge x alloys. Here to study the binding of the phosphorous substitutional-vacancy defect (PV pairs ot E-centres) we have calculated the energies of all the different nearest neighbour PV combinations in the seven Si 1−x Ge x alloys considered. To limit defect-image errors typically introduced in computational modelling small supercells we have constructed supercells consisting of two SQS cells each (i.e. 64 atomic sites). Therefore, the total number of PV defects considered were 896, whereas more than 1350 DFT calculations were performed to predict the binding energies. The present approach allows the thorough study of defects for a range of compositions and importantly local environment (i.e. Si-rich or Ge-rich). It is an aim of this investigation to derive trends on the impact of composition and environment around the defect on the energetics of E-centres.

Figure 2 considers the effect of the nearest neighbour host atoms to the P substitutional atom. For Si 1−x Ge x cells with up to 62.5% Si content we calculate that there are also positive PV binding energies. This implies that PV pairs in Si 1−x Ge x (x ≤ 0.625) may not form in some areas of the random alloy. This is not the case for Si 1−x Ge x (x > 0.625) were the PV binding ebergy is always negative (refer to Fig. 2). This is not of course implying that it would be equaly likely for the PV to form at any sites in Si 1−x Ge x (x > 0.625). The more negative PV pairs will be more likely to form and more stable against dissociation.

Figure 3 examines the impact of the first nearest neighbour host atoms to the lattice vacancy. The trend observed is that the E-centre will have a more negative binding energy if it forms in the vicinity of Ge atoms, irresppective of the Si 1−x Ge x random alloy composition. The physical basis of this can be traced to the lattice relaxation of the Ge host atoms (which are larger than Si atoms) in the vacant space.

Figure 4 attempts to sum up the impact of nearest neighbours arounf the E-centre. This is to gain an understanding of whether the E-centres in Si 1−x Ge x prefer to form in Si-rich or Ge-rich regions of the alloy. What can be deduced from Fig. 4 is that E-centres form in the vicinity of one or more Ge atoms, irrespective of the alloy composition. For all the alloys considered Ge is strongly represented in the nearest neighbours around the minimum energy PV. The most energetically favourable PV defects and their nearest neighbour atoms are schematically represented (refer to Fig. 5) for every alloy considered here. The present findings are consistent with previous experimental and theoretical work where it was shown that vacancies preferentially form in the vicinity of Ge atoms 5,25,37 .

Figure 6 summarizes the binding energies with respect to alloy composition. The fitted line indicates that binding energies are not linear as a function of alloy composition (i.e. Vegard's law is invalid in this case). The SiGe ) as a function of composition can be described via the following relation: Where θ is called the bowing parameter and is calculated to be −2.0 eV. Although the trend is very similar, this bowing parameter is considerably higher as compared to the one calculated in previous work 5 . This is due to the more substantial SQS cells (32 atom SQS as compared to 16 atom SQS in ref. 5 ) and the more Si 1−x Ge x compositions used here that allow far more E-centre configurations to be considered.   The non-linear dependence of the binding enenrgies with respect to composition is consistent with previous work 5 , however, the present study is far more detailed given more compositions were explored, larger SQS cells and more E-centres with richer nearest neighbour environments. What is the nature of this deviation from linearity and is it determined in other defect processes in Si 1−x Ge x alloys? The Ge content dependence of the most strongly bound PV defects is in agreement with previous experimental studies for donor atom (As and Sb) diffusion in Si 1−x Ge x alloys 2,38 . In particular these experimental investigations established that the activation enthalpies of diffusion of As and Sb are not linearly dependent as a function of the Ge content of Si 1−x Ge x alloy. More recently, Kube et al 3,6 . determined the self-diffusion of Si and Ge in Si 1−x Ge x over a wide range of Ge concentration (x=0.0, 0.05, 0.25, 0.45 and 0.70) and temperatures (963 K-1543 K). These investigations 3,6 showed a non-linear dependence of the activation enthalpy of self-diffusion with Ge concentration with a bowing that is consistent with the present study. Thereafter, Saltas et al 11 . analysed the experimental results within the cBΩ thermodynamic model. In this study, Saltas et al 11 . used the thermoelastic properties (bulk modulus, mean atomic volume and thermal expansion coefficient) of Si and Ge to study the composition and temperature dependence of self-diffusion in Si 1−x Ge x . The resulting deviations from Vegard's law were attributed to the diversification of the bulk properties of Si and Ge 11 . This is anticipated to be the reason for the bowing in the binding energies of the PV defects with respect to composition calculated in the present study, however, further thermodynamic analysis will need to be performed in future work.

Apart from relaxation and thermodynamic issues the electronic properties of the defects including charge transfer can impact the properties of Si 1−x Ge x . To consider this we have performed spin polarized DFT calculations. These calculations enabled us to calculate the amount of charges on the P and its nearest neighbor atoms and plot charge densities localized on the P atoms in each configurations. The relaxed configurations of P interacting vacancies in Si 1−x Ge x are shown in Fig. 7. In each configurations, there is a substantial interaction between www.nature.com/scientificreports www.nature.com/scientificreports/ P and Si (or Ge) is observed. This is reflected in the negative Bader charge on P and positive Bader charge on Si (or Ge) (refer to Fig. 8). The amount of charge on P in each configuration is ~−3.00. In each configurations, the P forms three-coordination with adjacent Si (or Ge) atoms and they donate ~1.00 e each to P to form stable P 3− states. This is further evidenced by the charge density around the P atoms in each configurations (refer to Fig. 8). The Si-P bond distance is calculated to be ~2.30 Å while the Ge-P bond distance is ~2.40 Å. This is due to the larger atomic radius of Ge than that of Si.

summary. In the present study, electronic structure calculations were used to investigate the defect process of the E-centre in Si 1−x Ge x for a range of compositions. It is shown that the binding energies of the E-centres are strongly dependent upon the composition of the alloy, but also on the local environment around the defect. In particular, the more bound E-centres have at least one Ge atom as a nearest neighbour, whereas the dependence of the binding energy of the E-centres with respect to alloy composition is non-linear. It is shown that the more substantial 32 atom SQS can better describe the defect processes in Si 1−x Ge x as compared to 16 atom SQS cells considered previously. The present study is a paradigm of the employment of the SQS method in conjunction with systematic DFT calculations to describe non-linear energetics in random semiconductor alloys. This approach can be extended to other technologically important systems such as random alloys for materials for photovoltaics and solid oxide fuel cells.

Methods. The binding nature of phosphorous with vacancy defects in Si 1−x Ge x was examined by using the plane wave DFT code CASTEP 39,40 . The correlation and the exchange interactions are described using the

Answer: the energetics of the defect chemistry and processes in semiconducting alloys is both technologically and theoretically significant. This is because defects in semiconductors are critical to tune their electronic properties. these processes are less well understood in random semiconductor alloys such as silicon germanium as compared to elementary semiconductors (for example silicon). to model the random silicon germanium alloy we have employed density functional theory calculations in conjunction with the special quasirandom structures model for different compositions. Here we show that, the energetics of substitutional phosphorous-vacancy pairs (E-centres) in si 1−x Ge x alloys vary greatly with respect to the local Ge concentration and the composition of the alloy. the most energetically favourable E-centres have a Ge atom as a nearest neighbour, whereas the dependence of the binding energy of the E-centres with respect to alloy composition is non-linear.The substitution of the silicon native oxide with high-k dielectrics has enabled the replacement of silicon (Si) with materials such as germanium (Ge) or silicon germanium (Si 1−x Ge x ), which have better materials properties (e.g. higher mobilities) 1-10 . Si 1−x Ge x is a random alloy in the sense that two atom species can occupy one lattice site. This in turn can lead to Si-rich and Ge-rich regions that can impact the energetics of point defects. This has been previously demonstrated in Si 1−x Ge x alloys where there is a compositional dependence of self-diffusion (refer to 3,6,11 and references therein) but also oxides where local compositional variation impacts diffusion 12,13 . Recently, Saltas et al 11 . studied self-diffusion in Si 1−x Ge x alloys as a function of temperature and Ge concentration within the cBΩ thermodynamic model [14][15][16][17] . In this study considerable deviations from linearity of the activation energies with respect to compositions were observed 11 . This non-linear behaviour was attributed to the diverse behaviour of the bulk properties of Si and Ge and is consistent with the experimental data.The theoretical investigation of random alloys using advanced techniques such as density functional theory (DFT) is not trivial as it requires a very extensive number of calculations in large supercells. To reduce the supercell size and the number of calculations methods such as the special quasirandom structures (SQS) have been previously proposed 18 and implemented in technologically important random alloys (more details are given in what follows) [19][20][21][22][23] . Considering group IV random alloys previous work has investigated the defect processes in Si 1−x Ge x , Sn 1−x Ge x and Si 1−x−y Ge x Sn y alloys [24][25][26][27][28] .The main aim of the present study is to use extended SQS cells in conjunction with systematic DFT calculations to investigate the energetics of substitutional phosphorous-vacancy pairs (E-centres) in Si 1−x Ge x alloys (x = 0.125, 0.25, 0.375, 0.5, 0.625, 0.75, 0.875). Particular emphasis will be placed on the effect of the composition of the alloy as well as the nearest neighbor environment to the defect. Results and Discussionsi 1−x Ge x structure and E-centres. Typical DFT calculations involve the construction of a supercell with periodic boundary conditions and as such they are immediately applicable for perfectly ordered structures. The situation is not straightforward, however, for disordered random alloys. Brute force methods (i.e. construct a very large supercell and randomly inserting the host atoms) is practically unfeasible for DFT as it necessitates very large supercells to reproduce the statistics of random alloys. Conversely, the SQS approach efficiently mimics the statistics of random alloys using small supercells and therefore it is a method that is compatible with DFT particularly when numerous defect calculations are required [18][19][20][21][22][23] . The qualitative difference of the SQS is that they are designed small-unit-cell periodic structures that mimic the most relevant near neighbour pair and multisite


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
the ganoderma strains listed in table 1 were obtained from the korean collection for type culture ( ktct , jeongeup , korea ) , the american type culture collection ( atcc , rockville , md , usa ) , the korean agricultural culture collection ( kacc , suwon , korea ) , the mushroom division of the rural development administration ( eumseong , korea ) , the centraalbureau voor schimmelcultures ( cbs , utrecht , netherlands ) , incheon university ( incheon , korea ) , and konkuk university ( seoul , korea ) .
ganoderma species were cultured on potato dextrose broth ( difco , detroit , mi , usa ) and incubated at 30 for 2 wk .
cultured mycelia , filtered through 2 layers of miracloth ( calbiochem , la jolla , ca , usa ) , were ground in liquid nitrogen , and genomic dna was extracted using the cetyltrimethylammonium bromide method .
pcrs were performed using a premixed polymerase kit ( taq premix ; tnt research , anyang , korea ) in a 20 l reaction mixture containing 1 l of dna .
amplification of the its region was carried out using a thermal cycler ( takara , tokyo , japan ) at the following conditions : 5 min at 94 for initial denaturation , followed by 30 cycles of 30 sec at 94 for denaturation , 30 sec at 56 for primer annealing , and 1 min at 72 for extension , and 10 min at 72 for a final extension .
pcr products were detected by electrophoresis on 1.2% agarose gels in 0.5 tris - acetate ethylenediaminetetraacetic acid buffer .
pcr products were ligated into the pgem - t easy vector ( promega , madison , wi , usa ) according to the manufacturer 's instructions .
ligation products were transformed into the escherichia coli dh5 competent cell ( rbc , taiwan ) by heat shock .
plasmid dnas were extracted using the dna hybrid - qtm plasmid mini dna isolation kit ( geneall , seoul , korea ) .
recombinant clones were identified , and the presence of inserts was confirmed by ecori restriction enzyme digestion and sequencing ( using the sp6 and t7 promoters ; genotech , daejeon , korea ) .
nucleotide sequences were deposited in the national center for biotechnology information genbank database ( table 1 ) .
the sequences of the its rdna were aligned for phylogenetic analysis using the program bioedit ( http://www.mbio.ncsu.edu/bioedit/bioedit.html ) .
the phylogenetic trees were constructed by using the mega5 program   and the neighbor - joining method .
confidence levels for individual branches of the resulting tree were assessed using the bootstrap test   in which 1,000 replicate trees were generated from resampled data .
the size of basidiospores from the korean cultivated yeongji strains was determined using a fluorescence microscope ( axio observer a1 ; carl zeiss , jena , germany ) and a 5% koh solution as a mounting medium .
the size of each spore was calculated , and the mean value was used in the description .
the ganoderma strains listed in table 1 were obtained from the korean collection for type culture ( ktct , jeongeup , korea ) , the american type culture collection ( atcc , rockville , md , usa ) , the korean agricultural culture collection ( kacc , suwon , korea ) , the mushroom division of the rural development administration ( eumseong , korea ) , the centraalbureau voor schimmelcultures ( cbs , utrecht , netherlands ) , incheon university ( incheon , korea ) , and konkuk university ( seoul , korea ) .
ganoderma species were cultured on potato dextrose broth ( difco , detroit , mi , usa ) and incubated at 30 for 2 wk .
cultured mycelia , filtered through 2 layers of miracloth ( calbiochem , la jolla , ca , usa ) , were ground in liquid nitrogen , and genomic dna was extracted using the cetyltrimethylammonium bromide method .
pcrs were performed using a premixed polymerase kit ( taq premix ; tnt research , anyang , korea ) in a 20 l reaction mixture containing 1 l of dna .
amplification of the its region was carried out using a thermal cycler ( takara , tokyo , japan ) at the following conditions : 5 min at 94 for initial denaturation , followed by 30 cycles of 30 sec at 94 for denaturation , 30 sec at 56 for primer annealing , and 1 min at 72 for extension , and 10 min at 72 for a final extension .
pcr products were detected by electrophoresis on 1.2% agarose gels in 0.5 tris - acetate ethylenediaminetetraacetic acid buffer .
pcr products were ligated into the pgem - t easy vector ( promega , madison , wi , usa ) according to the manufacturer 's instructions .
ligation products were transformed into the escherichia coli dh5 competent cell ( rbc , taiwan ) by heat shock .
plasmid dnas were extracted using the dna hybrid - qtm plasmid mini dna isolation kit ( geneall , seoul , korea ) .
recombinant clones were identified , and the presence of inserts was confirmed by ecori restriction enzyme digestion and sequencing ( using the sp6 and t7 promoters ; genotech , daejeon , korea ) .
nucleotide sequences were deposited in the national center for biotechnology information genbank database ( table 1 ) .
the sequences of the its rdna were aligned for phylogenetic analysis using the program bioedit ( http://www.mbio.ncsu.edu/bioedit/bioedit.html ) .
the phylogenetic trees were constructed by using the mega5 program   and the neighbor - joining method .
confidence levels for individual branches of the resulting tree were assessed using the bootstrap test   in which 1,000 replicate trees were generated from resampled data .
the size of basidiospores from the korean cultivated yeongji strains was determined using a fluorescence microscope ( axio observer a1 ; carl zeiss , jena , germany ) and a 5% koh solution as a mounting medium .
the size of each spore was calculated , and the mean value was used in the description .
the phylogenetic analysis of ganoderma species in this study was generally consistent with the findings reported by the group from china .
the 62 ganoderma strains were divided into 7 groups , a to g ( fig .
in addition , ganoderma lucidum were largely divided into two groups ( groups a and g ) .
group a included all the korean g. lucidum strains , as well as the g. lucidum strains from bangladesh and japan , and chinese g. sichuanense and g. lingzhi .
g. meredithae ( usa and unknown sources ) in group b was closely related to g. lucidum in group a as evidenced by a high bootstrap value of 98% .
g. multipileum ( china and taiwan ) was grouped within group c and g. tropicum ( china and taiwan ) within group d , with 96% and 99% bootstrap support , respectively .
group e includes three strains of g. resinaceum from the czech republic and uk ( two strains ) , and was supported by very high bootstrap values of 99% .
strains of g. weberianum ( australia , china , and philippines ) and two other chinese g. sichuanense strains ( cui 7691 and hmas 86597 ; holotype ) were grouped within group f with 99% bootstrap support . groups e and f were closely related with bootstrap values of 96% .
it is worth noting that other g. lucidum strains from europe ( france , finland , italy , sweden , and uk ) and canada could be clustered into group g with g. tsugae strains from north america ( canada and usa ) , supported by a very high bootstrap value of 99% .
the findings of the current study are consistent with those of park et al .   who reported that g. lucidum strains from europe and north america could be clustered into one group together with g. tsugae based on both analyses of the its rdna gene and partial -tubulin gene sequences .
interestingly , korean g. lucidum strains could be clustered into a group together with g. sichuanense and g. lingzhi strains from china .
reported that g. lucidum is incorrectly recorded in china , as well as in other countries , and suggested that the name ' g. lucidum ' as used for the chinese species should be corrected as g. sichuanense .
however , they did not obtain sequences from type specimens of g. sichuanense ( the holotype ; hmas 42798 ) .
reported that korean g. lucidum ( asi-7004 ) could be clustered into one group together with chinese g. lucidum and g. lingzhi based on the its2 sequences and rna secondary structures .
furthermore , cao et al .   reported that g. sichuanense ( included the holotype ; hmas 42798 ) was distantly phylogenetically related to g. lingzhi ( included the holotype ; wu 1006 - 38 ) , but it was closely related to g. resinaceum . with regard to the morphological characteristics , it has been reported that chinese g. lucidum ( g. lingzhi ) has a yellow pore surface , european g. lucidum has a white pore surface , and korean g. lucidum has pale brownish thread - like tissues in the middle of the context .
cao et al .   found that the morphological characteristics of ' g. lucidum ' from east asia were consistent with those of g. lingzhi .
thus , they concluded that g. sichuanense was a distinct species since they display obvious morphological differences from g. lingzhi and suggested that the name ' g. lucidum ' should be corrected as g. lingzhi not g. sichuanense .
it is commonly called " yeongji " in korea , " lingzhi " in china , and " reishi " or " mannentake " in japan .
however , the ganoderma species from various countries including africa , oceania , america , asia ( china , korea , and japan ) , and europe   have been incorrectly reported as g. lucidum .
in addition , moncalvo et al .   classified g. lucidum collections from different regions ( asia and europe ) into different species based on its and partial nuclear large subunit ribosomal dna sequences .
this is similar to the results of our its nucleotide sequence analysis of g. lucidum .
likewise , hong and jung   reported that the g. lucidum from korea and japan were monophyletic , and were distinguished from the g. lucidum from europe and north america based on sequence analysis of mitochondrial small - subunit ribosomal dna .
as described above , the taxonomy of g. lucidum has been reported by many researchers .
nevertheless , the name g. lucidum has been misapplied to various species around the world .
the results of this study also reveal that korean g. lucidum was clustered into one group together with chinese g. sichuanense and chinese g. lingzhi ( both formerly g. lucidum ) , and it was clearly separated from g. lucidum from europe and north america .
in addition , g. sichuanense were divided into two groups ( groups a and f ) .
g. sichuanense strains ( cui 7691 and hmas 86597 ; holotype ) , including the holotype , could be clustered into group f together with g. weberianum , and it was closely related to g. resinaceum .
cao et al .   also reported that the size of basidiospores of g. lingzhi [ ( 9.85  0.85 )  ( 6.4  0.6 ) m ] differs from that of g. sichuanense [ ( 8.3  0.9 )  ( 5.8  0.8 ) m ] .
interestingly , the average size of the basidiospores from the korean cultivated yeongji strains [ ( 10.65  0.65 )  ( 6.6  0.6 ) m for asi-7004 , ( 10  1 )  ( 6.4  0.3 ) m for asi-7071 ] were similar to that of g. lingzhi ( fig .
the comparison of the its rdna sequences and the estimation of the basidiospores size presented in this study confirm previous findings and contribute additional evidence that suggests the naming korean cultivated yeongji strains of ' g. lucidum ' should be renamed as g. lingzhi .

Answer:
ganoderma lucidum has a long history of use as a traditional medicine in asian countries .
 however , the taxonomy of ganoderma species remains controversial , since they were initially classified on the basis of their morphological characteristics .
 recently , it was proposed that g. lucidum from china be renamed as g. sichuanense or g. lingzhi . in the present study ,
 phylogenetic analysis using the internal transcribed spacer region rdna sequences of the ganoderma species indicated that all strains of the korean ' g. lucidum ' clustered into one group together with g. sichuanense and g. lingzhi from china .
 however , strains from europe and north american , which were regarded as true g. lucidum , were positioned in a clearly different group . in addition , the average size of the basidiospores from the korean cultivated yeongji strains was similar to that of g. lingzhi . based on these results ,
 we propose that the korean cultivated yeongji strains of ' g. lucidum ' should be renamed as g. lingzhi .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
they may be seen in midline or para - axial location , from the brain to the sacral area .
they display a particular tendency to locate in the sacrococcygeal and pre - sacral regions . reported incidence of tumors at these sites
the oropharyngeal cavity is exceedingly rare for teratomas , 2% of all teratomas , present as large masses protruding from the oropharyngeal area .
though oropharyngeal teratomas have a benign histopathology , they are potentially lethal as they may cause airway obstruction and respiratory compromise .
so , principles of management in such patients comprise of the immediate postpartum establishment of a secure airway , if needed via tracheostomy and complete surgical resection of the mass .
a 1980 g female infant born to 22-year - old mother after 38 weeks gestation presented with a growth in oral cavity associated with respiratory distress .
the mother had undergone ultrasonography examination during pregnancy , but the report of the same was unavailable . on examination ,
cleft palate was present and a palatal tumor of size 4 cm  3 cm was found in the cleft area [ figure 1 ] .
it was hampering feeding . computed tomography scan  showed mass lesion in the palatal region ( attached to the palate , more on the right side ) .
no intracranial extension [ figure 2 ] . computed tomography scan image after due preparation , the patient was operated , and the mass was excised in toto [ figure 3 ] .
histopathologic examination  revealed a teratoma composed of mature glial tissue , choroid plexus , glands lined by respiratory type , columnar mucin secreting , and melanin pigment bearing epithelium .
pools of myxoid matrix bearing physaliferous cells are present ( notochord  like / chondroid areas ) [ figures 4 and 5 ] .
microscopic picture 1 microscopic picture 2 following excision , patient recovered faster and gained weight .
now , the patient is under routine follow - up , and palatoplasty has been done .
teratomas are the tumors which contain tissues derived from all three germ layers . these contain tissues foreign to the anatomical site of origin .
most of the teratomas in the pediatric age group are benign , but reports of malignant teratoma do exist .
basic histological classifications which are widely used ( arnold 's system ) are :
 dermoid tumors : these are composed of ectoderm plus mesoderm .
this is the most common form of teratomateratoids : these are poorly differentiated tumors and contain all three germ layersteratomas : these also contain tissue from all three germ layers .
they are histologically more identifiableepignathus : these are tumors which contain fully developed organs and appendages .
the large cervical and nasopharyngeal teratomas which obstruct fetal swallowing of amniotic fluid may contribute to polyhydramnios .
this is the most common form of teratoma teratoids : these are poorly differentiated tumors and contain all three germ layers teratomas : these also contain tissue from all three germ layers .
they are histologically more identifiable epignathus : these are tumors which contain fully developed organs and appendages . the large cervical and nasopharyngeal teratomas which obstruct fetal swallowing of amniotic fluid may contribute to polyhydramnios .
other imaging technique such as magnetic resonance imaging , is useful in finding out the anatomical relationship of these tumors .
clinical differential diagnoses of oropharyngeal teratoma are cystic hygroma , lymphangioma , duplications and neuroblastoma .
moreover , the histopathological differential diagnosis includes hamartoma , dermoid cyst , and a heterotopic gastrointestinal cyst . with growth , oral teratomas
that is why , the respiratory distress may be less . the neonates with oral teratomas
the basic principle of management of oropharyngeal teratomas is the establishment and maintenance of a secure airway .
if an oropharyngeal teratoma is diagnosed antenatally , elective delivery or lower segment cesarean section is carried out .
if orotracheal / nasotracheal intubation is failed / or difficult , tracheostomy must be done .
surgical goal is to remove the complete mass in toto , as a residual tumor may cause recurrence .
associated cleft palate can be repaired when the child grows up , that is , at the age of 1 years . during follow - up , afp should be monitored . in our case , all the afp levels were within normal range .
early diagnosis , the establishment of the good airway , complete excision of tumor and timely follow - up should increase the survival of newborns with oral teratomas .

Answer:
for congenital teratomas , oropharyngeal cavity is one of the rarest sites ( 2% of all teratomas ) .
 they are rarely picked up by prenatal ultrasonography .
 postnatally , newborns present with respiratory distress and at this point role of pediatricians is very crucial in establishing secure airway after which they need to be carefully evaluated and surgically managed .
 we present a female neonate with palatal teratoma which was treated successfully with surgery .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
urea cycle disorders ( ucd ) are among the most common inborn errors of metabolism of the liver .
citrullinemia can be classified into three types : neonatal / infantile ( types i and iii ) and the adult form ( type ii ) .
more than 20 patients with citrullinemia have undergone liver transplantation , with favorable therapeutic results . however , the number of cases with auxiliary partial orthotopic liver transplantation ( apolt ) is limited .
apolt was initially performed in patients with acute liver failure and non - cirrhotic metabolic liver disease to compensate for enzyme deficiencies without complete removal of the native liver and for small - for - size living donor grafts [ 3 - 5 ] .
our patient was a 27-year - old man who was diagnosed with adult - onset type ii citrullinemia ( ctln2 ) at age 24 .
the patient had been treated with a low protein diet and oral administration of lactulose .
recently , the patient has had more frequent alterations of his mental status with irritability and altered consciousness .
even though oral administration of l - arginine , kanamycin and intravenous hyperalimentation with branched chain amino acids was started , his plasma levels of ammonia and citrulline were highly elevated , up to 844 g / dl ( normal range , 19 to 87 g / dl ) and 682 mol / l ( normal range , 12 to 55 mol / l ) , respectively . despite the conservative medical treatment including alternative pathway medication ,
intermittent continuous renal replacement therapy and hemodialysis , his condition failed to improve . therefore , living donor liver transplantation was planned using a right lobe graft from his 25-year - old sister .
however , the estimated volume of the donor 's right lobe was 800 ml compared to 180 ml of the left and in addition there was a type iii portal vein anomaly .
we eventually decided to perform an apolt using the extended left lobe of the liver from the donor .
the actual graft volume was 200 g and the graft - to - recipient weight ratio ( grwr ) was only 0.33% .
the patient 's extended left lobe ( including caudate lobe ) was resected and the extended left lobe graft ( including middle and left hepatic vein ) was transplanted orthotopically .
the left and middle hepatic vein trunk of the extended left lobe graft was anastomosed to the left and middle hepatic vein trunk of the recipient in end - to - end fashion with interposition venoplasty using the recipient 's greater saphenous vein as a patch . the left portal vein of the graft was anastomosed to that of the recipient in end - to - end fashion . considering that the graft was too small ,
the recipient 's right portal vein was narrowed by surgical clipping , instead of total diversion , for prevention of the development of portal venous hypertension .
the left hepatic artery of the graft was anastomosed to that of the recipients in end - to - end fashion .
intraoperative doppler ultrasonography demonstrated that portal and arterial blood flow were well maintained in both the native liver and the graft .
on postoperative day 7 , abdominal computed tomography demonstrated orthotopically transplanted small left lobe graft with well - enhanced pattern ( fig .
the post - operative course was uneventful and the patient was discharged without any problems .
the plasma concentrations of ammonia were at the upper limits of normal , so only a low protein diet ( 50 g / day ) was supplied without any specific medication . on post - operative day 33 ,
the patient reported a sudden severe visual disturbance and the plasma levels of ammonia were noted to have increased up to 209 g / dl .
the estimated computed tomography volume of the graft was decreased to 190 ml and a left portal vein stenosis was suspected .
immediate coil embolization of 8th segmental branch of right anterior portal vein and self - expandable stent placement for left portal vein was performed in order to increase the portal flow to the graft ( fig .
stent insertion day 7 , the calculated computed tomography volume of the graft was increased to 250 ml ( fig .
apolt was initially introduced as a temporary or permanent support for patients with fulminant hepatic failure .
apolt can provide an adequate hepatic mass to correct underlying enzyme deficiencies in adult patients with ucd .
this procedure can be carried out to overcome the limitations of graft volume in living donor liver transplantation . in korea ,
therefore , living donor liver transplantation is the only treatment option for patients with metabolic liver disease such as ucd . in this case , the graft weight of 200 g and the grwr of 0.33% are the smallest graft and lowest margin ever reported to meet the minimum requirements for the demands of adequate metabolic function in adults .
because the remaining native liver function , except for the metabolism of ammonia , is normal , the differential diagnosis including portal steal phenomenon and rejection as well as other problems associated with the vascular system is difficult .
thus the plasma ammonia level is a valuable follow up marker and should be closely monitored in such patients .
in addition , careful monitoring of the portal flow to the graft is important for the detection of delayed graft dysfunction .
selective portal vein embolization is a useful method for the increase of portal flow to the graft . in conclusion
, apolt can be a life saving procedure and an effective treatment for patients with adult - onset type ii citrullinemia , especially when a deceased donor graft is not available or when candidate donors have insufficient graft volume .
however , further confirmation is needed with additional patients and long - term follow - up .
how much volume of graft can be transplanted successfully is questionable in cases of inborn error of metabolism , such as ucd .

Answer:
adult - onset type ii citrullinemia ( ctln2 ) is a disorder caused by an inborn error of metabolism affecting the liver .
 ctln2 is an autosomal recessive disorder characterized by recurrent encephalopathy with hyperammonemia due to highly elevated plasma levels of citrulline and ammonia , caused by a deficiency of argininosuccinate synthetase in the liver .
 a small number of patients have undergone liver transplantation with favorable results . in korea , the limitations of the deceased donor pool have made living donor liver transplantation a common alternative treatment option .
 we report the case of a patient with type ii citrullinemia who was treated successfully with auxiliary partial orthotopic liver transplantation ( apolt ) from a living donor .
 this is the first description of an apolt for a patient with adult onset type ii citrullinemia in korea .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
sialolithiasis is the most common disease of salivary glands caused by the obstruction of a salivary gland or its excretory duct by a calculus .
it may occur at any age but there is a peak incidence in fourth , fifth , and sixth decades .
majority of salivary calculi ( 8095% ) occur in the submandibular gland , whereas only 520% are found in the parotid gland .
sialoliths located in the duct are usually elongated , while those situated in the gland or hilus tend to be round or oval .
the size of the salivary calculi may vary from < 1 mm to a few cms in largest diameter .
most of the calculi ( 88% ) are < 10 mm in size , whereas only 7.6% are larger than 15 mm .
they consist of mainly calcium phosphate with smaller amounts of carbonates in the form of hydroxyapatite , with smaller amounts of magnesium , potassium , and ammonia .
a 45-year - old male reported to the outpatient department of vspm 's dcrc , nagpur , with the chief complaint of pain and swelling in the floor of mouth on the left side since 1 month .
detailed history revealed that it has started as a small swelling which used to increase before meals 1 month back .
intraoral examination revealed a well - defined elongated swelling of approximately 2.5 cm  1 cm in size in the floor of the mouth in relation to lower left incisors to first molar region .
overlying mucosa was inflamed and the swelling was hard in consistency and tender on palpation [ figure 1 ] .
radiographic evaluation included cross - sectional mandibular occlusal view which revealed a large well - defined elongated homogenous radio - opacity in the floor of the mouth on the left side in relation to lower left canine to first molar region .
it was approximately 2.5 cm  1.5 cm in size [ figure 2 ] . swelling in the floor of mouth on the left side mandibular occlusal radiograph showing submandibular salivary duct calculus on the basis of clinical and radiological findings
, a diagnosis of left submandibular duct sialolith was made . as it was a large sialolith , we elected to remove the sialolith surgically under local anesthesia [ figure 3 ] .
the sialolith removed measured 25 mm ( i.e. 2.5 cm ) in length [ figure 4 ] .
removal of the sialolith from wharton 's duct the removed sialolith measured 2.5 cm  1.5 cm in its largest dimension
the sialolith was in the wharton 's duct and the patient had pain before and during meals . for stone formation
it is likely that intermittent stasis produces a change in the mucoid element of saliva , which forms a gel .
this gel produces the framework for deposition of salts and organic substances creating a stone .
traditional theories suggest that the formation occurs in two phases : a central core and a layered periphery .
the central core is formed by the precipitation of salts , which are bound by certain organic substances .
another theory has proposed that an unknown metabolic phenomenon can increase the saliva bicarbonate content , which alters calcium phosphate solubility and leads to precipitation of calcium and phosphate ions . a retrograde theory for sialolithiasis has also been proposed .
aliments , substances , or bacteria within the oral cavity might migrate into the salivary ducts and become the nidus for further calcification .
salivary stagnation , increased alkalinity of saliva , infection or inflammation of the salivary duct or gland , and physical trauma to salivary duct or gland may predispose to calculus formation .
submandibular sialolithiasis is more common as its saliva is ( i ) more alkaline , ( ii ) has an increased concentration of calcium and phosphate , and ( iii ) has a higher mucous content than saliva of the parotid and sublingual glands .
in addition , the submandibular duct is longer and the gland has an antigravity flow .
sialolithiasis typically causes pain and swelling of the involved salivary gland by obstructing the food - related surge of salivary secretion .
calculi may cause stasis of saliva , leading to bacterial ascent into the parenchyma of the gland and therefore infection , pain , and swelling of the gland at meal time .
bimanual palpation of the floor of the mouth , in a posterior to anterior direction , reveals a palpable stone in a large number of cases of submandibular calculi formation and a uniformly firm and hard gland suggests a hypofunctional or nonfunctional gland .
other traditional diagnostic methods include sialography , ultrasound , computed tomography , and scintigraphy for sialoliths .
as the lesions were observed clearly in occlusal radiographs , no further investigations were performed for diagnosis .
the treatment objective for giant sialoliths , as for the standard - sized stones , is restoration of normal salivary secretion .
there are three ways in which we can treat patients with salivary stones : removal through the oral cavity , interventional sialoendoscopy , and resection of the gland .
our choice depends on the site , size , shape , number , and quality of the stones .
the giant sialolith should be removed in a minimally invasive manner , via a transoral sialolithotomy , to avoid the morbidity associated with sialadenectomy . whenever the stone can be palpated intraorally , it is best to remove it through an intraoral approach . for giant sialoliths , transoralsialolithotomy with sialodochoplasty or sialadenectomy
submandibular gland removal is indicated if ( 1 ) the gland has been damaged by recurrent infection and fibrosis , ( 2 ) there is a stone of substantial mass within the gland itself that is not surgically accessible intraorally , ( 3 ) there are small stones present in the vertical portion of wharton 's duct from the comma area to the hilum , ( 4 ) the size of an intraglandular stone reaches 12 mm or more as the success of lithotripsy may be < 20% in such cases .
there are various methods available for the management of salivary stones , depending on the gland affected and stone location .
transoral sialolithotomy remains mainstay of the treatment for giant sialolith in the duct of submandibular gland .
also , patients should be followed up regularly as recurrence has been reported in the literature .

Answer:
salivary gland calculi account for the most common disease of the salivary glands .
 most of the salivary calculi are small in size .
 some calculi that reach several centimeters are reported as megaliths or giant calculi in the literature .
 they may occur in any of the salivary gland ducts but are most common in wharton 's duct and in the submandibular gland .
 this report presents clinical and radiographical sign of an unusually large sialolith .
 a patient came with pain in the floor of mouth .
 there was a swelling on floor of mouth on the left side .
 radiographical examination revealed large irregular radio - opaque mass superimposed on left lateral incisor to molar areas .
 this case report describes a patient presenting with an unusually large submandibular gland duct sialolith , the subsequent patient management , the etiology , diagnosis , and its treatment .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
these include the
 intrinsic flexor pollicis brevis , flexor pollicis longus , lumbricalis , flexor brevis , and
 flexor longus muscles1 .
toe - gripping
 strength is measured in the sitting position with the trunk vertical , the hip and knee
 joints at 90 , and the ankle joint in the neutral position1,2,3 .
low toe - gripping strength is a risk factor of falls for the
 elderly , and several studies have reported that toe - gripping strength is lower in subjects
 with a history of falls than in those with no history of falls1,2,3,4 .
furthermore , toe - gripping
 strength can be increased by training5 ,
 which can decrease the risk of falls1 .

souma et al.6 studied the % iemg of
 several crural muscles ( the soleus muscle , medial head of the gastrocnemius muscle , and
 tibialis anterior ) during toe - gripping in 3 different ankle joint positions10 of plantar
 flexion and 0 and 10 of dorsiflexion  and reported that the crural muscles help the ankle
 joint by co - contracting during toe - gripping . in another study ,
nakae et al.7 calculated the % iemg of the same muscles
 during toe - gripping with subjects seated on the edge of a seat or standing , and reported
 that the % iemg of the medial gastrocnemius muscle was significantly lower when subjects were
 seated than when they were standing .
however , as both studies focused on the activity of the
 crural muscles , the activity of the femoral muscles during toe - gripping remains unclear .
we
 believe it is important to elucidate the contribution of femoral muscles to toe - gripping
 strength . in the present study , we investigated femoral muscle activity during toe - gripping to
 examine the role of the femoral muscles in toe - gripping strength .
their
 average ( mean  sd ) age , height , and body weight were 20.6  1.0  years , 159.4  6.3  cm , and
 51.8  5.8  kg , respectively .
this study was approved by the ethics committee for human
 research of tohoku fukushi university , and written informed consent was received from all of
 the subjects after the purpose of the study had been explained to them .
toe - gripping strength of the dominant toe and emg activity of the ipsilateral thigh were
 synchronously recorded to assess the activity of the rectus femoris and biceps femoris
 muscles .
toe - gripping strength was measured using a toe - gripping dynamometer ( t.k.k.3360 ;
 takei co , ltd , niigata , japan ) . as described by uritani8
, the subjects were instructed to sit with their trunk in the
 vertical position , hip and knee joints at 90 , and ankle joints in the neutral position .
after a sufficient
 number of training trials and adequate rest , toe - gripping strength was measured twice and
 the maximal force was used in the analysis . for all subjects ,
the right toe was dominant
 ( defined as the toe used to kick a ball ) . to measure the maximum voluntary contraction ( mvc ) activity of the rectus femoris muscles ,
 as described by kai9 ,
each subject was
 instructed to sit on a chair with the hip and knee joints at 90 , and to exert maximal
 isometric force of knee extension while resisting an opposing force applied by the examiner .

the emg was recorded for 3 seconds while each subject exerted maximal force of knee
 extension . to measure the mvc of the biceps femoris muscle ,
each subject was instructed to
 generate maximal isometric force of knee flexion while resisting an opposing force applied
 by the examiner .
the emg was recorded for 3 seconds while each subject exerted maximal force
 of knee flexion .
after confirmation of adequate skin preparation ( skin resistance of less
 than 5 k ) , three bipolar lead electrodes ( de-2.1 , delsys , inc . , boston , usa ) were attached
 to the skin over the rectus femoris and the long head of the biceps femoris , as described by
 peroto10 . for measurement of the rectus

femoris muscle , the electrode was attached at the midpoint between the superior edge of the
 patella and the anterior superior iliac spine . for measurement of the long head of the
 biceps femoris ,
the electrode was attached at the midpoint between the head of the fibula
 and ischial tuberosity .
the emg signal was collected using ml846 power lab 4/26 ( sample : 1,000  hz ; ad instruments
 co. , ltd . ) and transferred to a personal computer .
the bandwidth was 20500  hz . the emg
 signal segment selected and integrated ( integrated electromyogram : iemg ) for analysis was
 the middle 1  s of the entire 3-s duration of continuous maximal toe - gripping strength .
the iemg was analyzed using lab chart pro v7.3.5 ( ad instruments co. , ltd . ) and normalized
 to the iemg of each muscle s mvc .
repeated mann - whitney u tests were used to compare the % iemg of the
 rectus and biceps femoris muscles .
relationships between the % iemg of the rectus and biceps
 femoris muscles were statistically analyzed using spearman s correlation coefficient .
the average ( mean  sd ) toe - gripping strength was 20.9  3.6  kg .
the average ( mean  sd )
 % iemg values of the rectus and biceps femoris muscles were 7.0%  6.2% and 25.6%  15.9% ,
 respectively .
the % iemg of the biceps femoris was significantly higher than that of the
 rectus femoris ( p < 0.01 , table 1table 1.comparison of the % iemg values of the rectus femoris and biceps femoris muscles
 during toe - gripping actionrectus femorisbiceps femorismedian ( range :  min  max)median ( range :  min  max)%iemg4.8 * ( 1.521.1)27.2 ( 3.068.1)mann - whitney u test * : p < 0.05 ) .
mann - whitney u test * : p < 0.05 using spearman s correlation coefficient analysis , a significant positive correlation was
 found between the % iemg of the rectus femoris and that of the biceps femoris ( r = 0.548 , p

in the present study , we found that the % iemg of the biceps femoris was significantly
 higher than that of the rectus femoris .
moreover , a significant positive correlation was
 found between the % iemg of these two muscles .
these results suggest that femoral muscles
 co - contract during toe - gripping action , and thus possibly contribute to knee joint
 stability .
we found that toe - gripping action stimulates femoral muscle activity and that the % iemg of
 the biceps femoris was significantly higher than that of the rectus femoris .
sato et
 al.11 reported that during
 toe - gripping , the tibialis anterior and soleus muscles are activated first , followed by the
 gradual activation of the medial head of the gastrocnemius muscle .
the biceps femoris
 initiates knee flexion , and the medial head of the gastrocnemius is a synergist for knee
 flexion .
additionally , active tension of the biceps femoris decreases during toe - gripping in
 knee flexion .
this may be because the length of the biceps femoris is shorter during active
 tension than during resting tension .
we think that the activation of the biceps femoris
 during toe - gripping was caused by increasing motor unit recruitment and synchronization of
 the impulse to compensate for decreasing activity of the biceps femoris . in the present study
, we found a significant positive correlation between the % iemg of the
 rectus femoris and that of the biceps femoris .
this suggests that the % iemg of the rectus
 femoris increases with increases in the % iemg of the biceps femoris .
toe - gripping strength was measured using a closed kinetic chain movement , and therefore ,
 the likelihood of movement in the directions of flexion or extension of the knee joint is
 less . however , because the gastrocnemius also acts on knee joint flexion during exertion of
 toe - gripping strength , the knee joint is readily displaced in the direction of flexion . to
 prevent this
, it is thought that the knee joint is immobilized by contraction of the rectus
 femoris , that is , we think the rectus femoris during exertion of toe - gripping strength acts
 in order to control the action of knee joint flexion by the gastrocnemius .
first , we were unable to avoid the common problems that
 negatively affect surface emg recording , such as skin resistance , artifacts , and the effects
 of proximal muscles .
second , as only healthy young women participated in this study , it is
 difficult to extend our findings to the general population . in future studies
, we need to
 consider this aspect , and involve healthy young men and individuals of different age
 groups .

Answer:
[ purpose ] in the present study , we investigated femoral muscle activity during
 toe - gripping , and the role of the femoral muscles in toe - gripping strength .
 [ subjects ]
 fourteen healthy young women were selected .
 [ methods ] we measured the maximum voluntary
 contraction of the rectus femoris and long head of the biceps femoris muscles .
 we then
 calculated the percent integrated emg ( % iemg ) during the toe - gripping action .
 [ results ] we
 found that the % iemg of the biceps femoris was significantly higher than that of the
 rectus femoris .
 moreover , a significant positive correlation was found between the % iemg
 of the rectus femoris and that of the biceps femoris .
 [ conclusion ] these results suggest
 that femoral muscles co - contract during the toe - gripping action , and thus possibly
 contribute to knee joint stability .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
confident peptide identification through tandem mass spectrometry ( ms ) is one of the most important components in ms - based proteomics .
for this reason , a great amount of effort has been invested to develop automated data analysis tools to identify peptides through tandem ms ( ms ) spectra . among available
because each search method uses a different algorithm and proceeds from a different view of what spectrum components contain the most critical information for identification , the search results for one spectrum from various search engines may differ significantly .
however , it is also well - recognized that such difference may be turned into positive use : it would be useful to find complementary engines and combine the results in an effective way to enhance peptide identification.(1 ) combining search results from different methods , if feasible , definitely bears the possibility to improve the peptide identification confidence via reducing noise and utilizing complementary strengths .
the difficulty in combining results from different search methods largely comes from the lack of a common statistical standard.(2 ) the importance of having a community standard has been stressed , and efforts in reaching such community standard have been invested . using iterative expectation - maximization ( em ) , keller et al .
( 3 ) proposed a statistical model to estimate the probability , determined through a global analysis of ms spectra from an experiment , for a given spectrum to have correct peptide identification . in principle , results from different search methods may go through the same analysis and thus compared . however , if after the statistical analysis two different methods report different confident identifications for the same spectrum , one ends up needing to invent an ad hoc rule to decide which identification should be kept .
furthermore , to use the em approach , one needs to assume or guess , without theoretical / statistical foundation , the forms of the score distributions for true positives and false positives .
this , unfortunately , must weaken the validity of any statistical significance assignment obtained from such type of analyses . in our recent work,(4 ) it was shown possible to calibrate the statistics ( e - value ) of various search methods to reach a universal standard that is in agreement with the fundamental definition of e - value . for a given query spectrum and quality score cutoff s , e - value
is defined as the expected number of hits , in a random database , with quality score being the same as or larger than the cutoff .
a realistic e - value assignment thus provides the user with the number of false positives to anticipate when setting a quality score threshold .
most importantly , this peptide - centric statistical calibration allows one to combine search results even if the top hits from various methods disagree . another possible approach
to establish common statistical standard is through equating the false discovery rate ( fdr ) ( 5 ) of various methods considered .
this approach , however , does not provide statistical significance for each peptide hit and thus is not directly applicable to peptide - centric combination of different search results . to be explicit
, one may refer from fdr the e - value of a peptide hit with score identical to the first false positive , but any peptide hits with score better than the first false positive can not have their e - value assigned .
furthermore , for peptides with scores falling in the range [ sk+1 ,  sk ] , where sk represents the kth best score of false positives , one can not distinguish them statistically well except by using some ad hoc interpolations .
there also exist other issues concerning misleading inference using fdr , but this is not the focus of the current paper and we refer the readers to a few relevant literatures . in this paper , in addition to providing a universal protocol to combine search results , we also carry out the performance assessment for all possible combinations , among seven database search methods , of two and three search methods using the receiver operating characteristic ( roc ) curves .
the database search methods employed in our analysis are sequest(8 ) ( v27 rev12 ) , probid(9 ) ( v1.0 ) , inspect(10 ) ( v20060505 ) , mascot(11 ) ( v2.1 ) , x !
tandem(12 ) ( v2007.07.01.2 ) , omssa(13 ) ( v2.0 ) and raid_dbs.(14 ) to better illustrate the main points of this paper , we have relegated to the supporting information a large number of roc curves that convey similar information of that exhibited in the plots of the main text .
since the centroid mode seems to be the dominant mode in ms database searches today , we present in the main text only results from centroid mode data and results from profile mode data are shown in the . throughout the paper ,
we use dalton ( da ) as the unit for molecular weight . in the following ,
we will then describe briefly in   the implementation , followed by our main results : best combinations within search methods tested .
in this section , we will start with the definitions of p - value and e - value , which will be frequently used for the rest of this paper .
we then describe the mathematical underpinnings of how to combine the p - values of different database search methods to result in a final e - value .
we should note that the mathematical formulation employed here was first introduced by fisher,(15 ) and its extensions and applications to other research areas also exist . to the proteomics community
let us define the p - value and e - value in the context of peptide identification in database searches .
for a given spectrum  and a score cutoff sc , one may ask what is the probability for a qualified ( with molecular weight in the allowed range ) random peptide to reach a score larger than or equal to sc .
this probability p(sc ) , a function of sc , is called the p - value . for spectrum
 , if a database contains n qualified , unrelated random peptides , one will expect to have e(sc ) = np(sc ) number of random peptides to have quality score larger than or equal to sc .
this expectation value e(sc ) is by definition the e - value associated with score cutoff sc .
if one further assumes that the occurrence of a high - scoring random hit is a rare event and thus can be modeled by a poisson process with expected number of occurrence e(sc ) , one may then define another p - value , which is called the database p - value , via

 the database p - value pdb(sc ) represents the probability of seeing at least one hit in a given random database with quality score larger than or equal to sc .
note that , at the level of pdb , one may compare the statistics from different search methods using different sizes of random databases .
because of the differences in the choices of optimal search parameters , it is likely that different search methods , for the same query spectrum , may search over different number of qualified peptides , that is , having different effective database sizes
. therefore , combining the database p - values is the natural choice if one were to merge results from different search methods .
suppose that one wishes to combine the search results from l different search methods , each peptide candidate will have in principle l different p - values reported by the l search methods .
the formula in eq 6 of the next subsection provides us the final combined p - value pcomb from the list .
once pcomb is obtained , we may invert the formula in eq 1 to get a combined e - value ecomb via

 having outlined how to obtain the final quantity of interest , ecomb , we now turn to the mathematical underpinnings of how to combine a list of , ideally independent , p - values reported by different database search methods .
consider an event labeled by a list of l independent quantities s1 ,   s2 , ... ,  sl . each quantity si may have an associated p - value pi depending on the statistics of the variable si .
an important issue to address is how one should combine all the pi values to obtain an overall p - value . in the context of combining search results of different methods to assign statistical significance to a certain candidate peptide
pl ) uniformly distributed in the interval ( 0 ,  1 ) ] , what is the probability of finding their product to be smaller than a certain threshold . to put it in a more concrete framework , one may consider a unit hypercube whose interior points having coordinates ( x1 ,  x2 , ... ,  xl ) with 0  xi  1 for all 1
i  l. one then asks what is the volume bounded by the hypersurfaces xi  0 and ( i=1lxi )   with  = i=1lpi .
we may express this volume f( ) mathematically as an integral :

 where (x ) is a step function with (x > 0 ) = 1 and (x < 0 ) = 0 .
let f( )  f()/ , we have

 with (x ) being the dirac delta function that takes zero value everywhere except when x = 0 where its value approaches infinity .
for the ease of computation , we make the following changes of variables :   e and xi  e. after this change , all the new variables t and ui are in the range ( 0, ) .
equation 4 now becomes ( with  = e understood )

 where the identity (e  e ) = e(t  c ) is used . using the integral expression of the delta function
,

 we may rewrite eq 4 as ( with  = e understood )

 where the last equality results from choosing the integration path to enclose the lower half of the complex k plane .
we may now go back to f( ) by integrating f( ) .

 with
= i=1lpi while combining the lp - values p1 ,  p2 , ... ,  pl . as specific examples , when l = 2 , we have f(p1p2 ) = p1p2[1  ln ( p1p2 ) ] , and when l = 3 , we have f(p1p2p3 ) = p1p2p3[1  ln(p1p2p3 ) +  ln(p1p2p3 ) ]
. we will provide in the   more examples to elucidate the consequence of the formula provided in eq 6 .

Answer:
confident peptide identification is one of the most important components in mass - spectrometry - based proteomics .
 we propose a method to properly combine the results from different database search methods to enhance the accuracy of peptide identifications .
 the database search methods included in our analysis are sequest ( v27 rev12 ) , probid ( v1.0 ) , inspect ( v20060505 ) , mascot ( v2.1 ) , x ! tandem ( v2007.07.01.2 ) , omssa ( v2.0 ) and raid_dbs . using two data sets , one collected in profile mode and one collected in centroid mode , we tested the search performance of all 21 combinations of two search methods as well as all 35 possible combinations of three search methods .
 the results obtained from our study suggest that properly combining search methods does improve retrieval accuracy .
 in addition to performance results , we also describe the theoretical framework which in principle allows one to combine many independent scoring methods including de novo sequencing and spectral library searches . the correlations among different methods are also investigated in terms of common true positives , common false positives , and a global analysis .
 we find that the average correlation strength , between any pairwise combination of the seven methods studied , is usually smaller than the associated standard error .
 this indicates only weak correlation may be present among different methods and validates our approach in combining the search results .
 the usefulness of our approach is further confirmed by showing that the average cumulative number of false positive peptides agrees reasonably well with the combined e - value .
 the data related to this study are freely available upon request .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
we included 3,615 french men and women , aged 3065 years , with baseline fasting glycemia ( fg )
< 6.1 mmol / l , who participated in the 9-year follow - up d.e.s.i.r .
participants provided written informed consent , and the protocol was approved by the ethics committee of bictre hospital , kremlin - bictre , france .
incident hyperglycemia was identified by an fg 6.1 mmol / l or treatment for diabetes , and incident diabetes was identified by an fg 7.0 mmol / l or treatment of diabetes during at least one of the three follow - up examinations ( years 3 , 6 , and 9 ) .
smoking , dietary habits , degree of physical activity , and alcohol consumption were assessed using a self - administered questionnaire .
mean daily intake of water , wine , beer or cider , and sweet beverages was categorized in the questionnaire into six mutually exclusive levels : none , < 0.5 , 0.5 to 1 , 1 to 1.5 , 1.5 to 2.0 , and > 2 l. in the present analyses , the levels were grouped into three classes : < 0.5 , 0.5 to 1 , and > 1 l. other clinical and biological measurements are presented in the supplementary methods .
results are presented as means ( sd ) or median ( 25th75th percentiles ) for quantitative variables and as percentages for qualitative variables .
baseline means and percentages were compared between the three w - intake classes using anova or  tests .
logistic regression models were used to determine odds ratios ( ors ) and 95% cis corresponding to the comparison of incident hyperglycemia in middle and high classes of w - intake in comparison with the lowest class .
adjustment variables were either known risk factors for type 2 diabetes or factors associated ( p < 0.10 ) with hyperglycemia and w - intake in our population .
we included 3,615 french men and women , aged 3065 years , with baseline fasting glycemia ( fg )
< 6.1 mmol / l , who participated in the 9-year follow - up d.e.s.i.r .
participants provided written informed consent , and the protocol was approved by the ethics committee of bictre hospital , kremlin - bictre , france .
incident hyperglycemia was identified by an fg 6.1 mmol / l or treatment for diabetes , and incident diabetes was identified by an fg 7.0 mmol / l or treatment of diabetes during at least one of the three follow - up examinations ( years 3 , 6 , and 9 ) .
smoking , dietary habits , degree of physical activity , and alcohol consumption were assessed using a self - administered questionnaire .
mean daily intake of water , wine , beer or cider , and sweet beverages was categorized in the questionnaire into six mutually exclusive levels : none , < 0.5 , 0.5 to 1 , 1 to 1.5 , 1.5 to 2.0 , and > 2 l. in the present analyses , the levels were grouped into three classes : < 0.5 , 0.5 to 1 , and > 1 l. other clinical and biological measurements are presented in the supplementary methods .
results are presented as means ( sd ) or median ( 25th75th percentiles ) for quantitative variables and as percentages for qualitative variables .
baseline means and percentages were compared between the three w - intake classes using anova or  tests .
logistic regression models were used to determine odds ratios ( ors ) and 95% cis corresponding to the comparison of incident hyperglycemia in middle and high classes of w - intake in comparison with the lowest class .
adjustment variables were either known risk factors for type 2 diabetes or factors associated ( p < 0.10 ) with hyperglycemia and w - intake in our population .
baseline characteristics of the 3,615 normoglycemic participants are presented according to their class of w - intake ( table 1 ) . among them , during follow - up , 565 subjects became hyperglycemic and 202 developed diabetes .
the daily w - intake was negatively associated with the risk of new - onset hyperglycemia , even after adjustment for multiple metabolic risk factors .
compared with daily w - intake of < 0.5 l , ors were 0.64 ( 95% ci 0.490.83 ) and 0.73 ( 0.550.97 ) for classes of 0.51.0 l and > 1.0 l , respectively ( p = 0.003 ) .
after further adjustments for intake of other beverages , the ors were slightly attenuated : 0.68 ( 0.520.89 ) and 0.79 ( 0.591.05 ) for classes of 0.51.0 l and > 1.0 l , respectively ( p = 0.016 ) ( table 1 ) .
with the two upper classes combined , the or was 0.72 ( 0.560.92 ) ( supplementary fig .
1 ) . there was no interaction with several important characteristics , including those related to self - reported alcohol or tobacco consumption ( supplementary table 1 ) .
baseline characteristics of the study population and risk for new - onset hyperglycemia during follow - up , by classes of mean daily w - intake data are means ( sd ) or medians ( 25th75th percentiles ) for continuous variables and percentages of patients for categorical variables .
thzd , thiazidic diuretics ; furo , furosemide ; homa - ir , homeostatic model assessment index of insulin resistance ; homa - b , homeostatic model assessment index of insulin secretion
. hypertension was defined as systolic or diastolic blood pressure > 140 or 90 , respectively , or treated with antihypertensive drugs .
ors ( 95% cis ) for the association between daily w - intake at baseline and the risk of incident hyperglycemia ( fasting plasma glucose 6.1 mmol / l or treatment for diabetes ) are presented according to two statistical models ; variables for adjustment were either known risk factors for type 2 diabetes or factors associated ( p < 0.10 ) with hyperglycemia and w - intake in our population .
model 1 : adjusted for age , sex , bmi , baseline fg , physical activity , smoking status , triglycerides , homa - ir , and total cholesterol .
model 2 : further adjusted on self - reported intake of other fluids ( i.e. , volumes of beer or cider , sweet drinks , and wine consumed per day ) .
the c - reactive protein was available for only 181 , 466 , and 333 subjects in the three classes of w - intake , respectively . * * hdl cholesterol and ldl cholesterol were not available for 28 and 26 subjects , respectively . the same trend , although nonsignificant , was observed for the association with new - onset diabetes : compared with participants with a daily w - intake < 0.5 l , ors for those drinking 0.51.0
l and > 1.0 l water per day were 0.68 ( 95% ci 0.411.15 ) and 0.75 ( 0.431.32 ) , respectively , p = 0.36 .
risk for hyperglycemia was negatively and independently related with self - reported w - intake in normoglycemic middle - aged individuals from the french general population
however , the association was moderately attenuated when important metabolic risk factors and potential confounders were introduced as covariables in the analysis , including intake of other classes of beverages with known adverse long - term effects ( sweet and alcohol - containing drinks ) .
our data support the novel idea that vasopressin , besides its role in urine concentration , is also an important actor in glucose homeostasis ( 1 ) .
the negative association of w - intake and risk for hyperglycemia was relevant among many subsets of participants , and those reporting a low w - intake ( < 0.5 l ) had a higher risk for hyperglycemia ( for example , participants in the high physical activity group ) ( supplementary table 1 ) . this indicates that identification of individuals with a w - intake of < 0.5 l may be widely relevant to target preventive interventions regarding the metabolic risk .
diabetes incidence was low and statistical power was thus limited ; 24-h urine volume was not measured , but the urinary density was inversely associated with self - reported w - intake , arguing for the validity of the questionnaire ( table 1 ) . in addition , we can not exclude residual confounding : healthier behaviors correlating with higher water drinking could account for the observed association .
finally , only volunteers were included and the results may not be extrapolated to the general population . knowing the rise of vasopressin in diabetes , its effect on glycemia , gluconeogenesis , and glucagon release , it is surprising that no attention had been given to vasopressin as a possible risk factor for hyperglycemia and diabetes until a recent report of an association between copeptin and the incidence of diabetes ( 1,4,5,14 ) .
our study extends this observation , drawing attention to a low w - intake as a possible new risk factor for impaired glycemia .
it suggests that an increase in w - intake , an easy and costless intervention , could prevent or delay the onset of hyperglycemia and subsequent diabetes .
hopefully , our study will serve as a benchmark to design appropriate clinical trials testing the efficacy of this intervention in people who report drinking < 0.5 l of water per day , as did almost 20% of the participants in this cohort .

Answer:
objectivewater intake alters vasopressin secretion .
 recent findings reveal an independent association between plasma copeptin , a surrogate for vasopressin , and risk of diabetes.research design and methodsparticipants were 3,615 middle - aged men and women , with normal baseline fasting glycemia ( fg ) , who were recruited in a 9-year follow - up study .
 odds ratios ( ors ) and 95% cis for the incidence of hyperglycemia ( fg 6.1
 mmol / l or treatment for diabetes ) were calculated according to daily water intake classes based on a self - administered questionnaire.resultsduring follow - up , there were 565 incident cases of hyperglycemia . after adjustment for confounding factors , ors ( 95% cis ) for hyperglycemia associated with classes of water intake ( < 0.5 l , n = 677 ; 0.5 to < 1.0
 l , n = 1,754 ; and > 1.0 l , n = 1,184 ) were 1.00 , 0.68 ( 0.520.89 ) , and 0.79 ( 0.591.05 ) , respectively ( p = 0.016).conclusionsself - reported water intake was inversely and independently associated with the risk of developing hyperglycemia .


Question:
You will be presented with the full text of a biomedical research paper. Please write an abstract for this paper. Your response should include the abstract and no additional text.

Paper text:
nowadays cardiac surgeons must face the problem of severely impaired left ventricle function almost on a daily basis .
heart transplantation , due to the limited donor pool , can be offered only to a small number of patients suffering from cardiac failure [ 1 , 2 ] . furthermore , the idea of long - term mechanical support as a destination therapy is still evolving .
hence , efforts to optimize the results of routine cardiac surgery have to be undertaken . in a properly selected group of patients coronary surgery alone or combined with mitral surgery can improve both quality of life and long - term survival .
with borderline ventricular function prior to surgery this may result in failed weaning from cardiopulmonary bypass .
in isolated coronary surgery beating heart strategy , either on or off pump seems to be a safer option .
its use however is hardly possible when mitral valve repair or replacement needs to be done .
intra - aortic balloon pump ( iabp ) is a gold standard here , but some patients may require more sophisticated mechanical assistance [ 3 , 4 ] .
the idea of short - term , perioperative mechanical support , preferably with a low anticoagulation regime , looks very convenient in this respect .
impella microaxial pumps ( abiomed europe gmbh , aachen , germany ) seem to meet these criteria .
they use the idea of pulling the blood from the left ventricle into the aorta , which is accomplished by means of a rotating impeller positioned in the aorta with the tip of the device and inlet area positioned in the left ventricle .
this results in reduction of both left ventricle end diastolic volume ( lvedv ) and left ventricle end diastolic pressure ( lvedp ) . the systemic pressure and flow are increased .
the less stretched left ventricle , with better subendocardial perfusion , has more time to recover . on the other hand ,
the impella pump can be applied either by cardiologists ( impella 2.5/impella cp ) in a cath lab setting or by cardiac surgeons ( impella 5.0/impella ld ) in an operating theatre with either peripheral vascular or central direct access . offering flow up to 5 l / min ,
the anticoagulation management requires only heparin infusion to keep activated clotting time ( act ) not shorter than 160 s. thanks to the automated controller with an intuitive , user friendly interface , operating the device can be easily mastered by doctors and nursing staff .
a 64-year - old woman suffering from ischemic dilated cardiomyopathy associated with mitral insufficiency was referred for combined treatment consisting of resynchronisation therapy followed by simultaneous coronary and mitral surgery .
initial echocardiography revealed impaired global contractility ( ejection fraction [ ef ] 10 - 15% ) , dilated left ventricle ( left ventricle end diastolic diameter [ lvedd ] 7.8 cm ) , significant ventricular asynchrony ( 50 ms ) and moderate mitral regurgitation ( vena contracta [ vc ] 6 mm ) due to both restriction of the posterior leaflet and dilation of the mitral annulus ( 5.5 cm ) .
there were no significant abnormalities regarding the right ventricle , pulmonary valve and tricuspid valve .
clinically the patient presented with end stage cardiac failure including resting dyspnea ( nyha iv ) .
the patient underwent uneventful implantation of an icd crd ( maximo ii ) , which resulted in improved exercise tolerance .
this was consistent with post - procedure echocardiography showing no significant ventricular asynchrony ( 4 ms ) , slightly improved contractility ( ef 20% ) and unchanged moderate mitral regurgitation ( vc 6 mm ) .
therefore the patient was referred for combined cardiac surgery including mitral repair and coronary grafting .
because of poor lv function and the complexity of the procedure , it was decided to apply short - term mechanical support during and after surgery .
the impella ld microaxial pump was chosen due to the simplicity of implantation and the low anticoagulation regime . also , the impella ld does not require a hybrid theater with fluoroscopic guidance .
antegrade cold blood cardioplegic solution was administered through the aortic root . the posterior descending artery ( pda ) and left anterior descending artery ( lad ) were grafted with the long saphenous vein and left internal thoracic artery respectively .
the left atrium was entered in a routine manner after dissecting sondergaard 's plane . on inspection the echocardiographic findings were confirmed .
the only surgical issue was severe atherosclerosis of the ascending aorta affecting both anastomosis of the vein graft and implantation of the impella device . before the implantation
a 10 mm dacron graft was anastomosed to the ascending aorta using a side biting clamp ( fig .
the impella catheter was inserted through the graft and then , under transesophageal echocardiographic ( tee ) guidance , was forwarded through the ascending aorta and the aortic valve into the left ventricle ( figs . 2 and 3 ) . immediately after confirming the position the impeller rotation was initialized .
meticulous attention was paid to maintain proper left ventricle volume preloading in order to avoid pump malfunction . after securing hemostasis
the chest was closed , letting the driveline out above the suprasternal notch and through the upper end of the sternotomy wound .
the patient was transferred to intensive treatment unit ( itu ) in a stable condition .
there she was kept sedated and ventilated electively . therapeutic activated clotting time ( act )
the position of the pump was checked daily and in case of any suspicion of malfunction .
adequate flow was maintained most of the time , with one episode of stopping of the machine , which was easily managed with fluid infusion .
the inotropic support was reduced gradually without affecting hemodynamic stability . on the 2 postoperative day
the further postoperative course was mainly uneventful , although prolonged mechanical ventilation was required ( 8 days ) .
the first follow - up visit two months after discharge confirmed good exercise tolerance and satisfactory echocardiographic findings ( trace mitral regurgitation , lvedd 7.6 cm , ef 25% ) .
impella device inserted through the tubing graft anastomosed to the ascending aorta impella device in the ascending aorta , approaching the aortic valve impella device finally positioned in the left ventricle doppler scan showing the flow from the left atrium to the left ventricle ( blue ) and within the device from the left ventricle to the aorta ( red )
patients with impaired left ventricle function require a particular surgical strategy . obviously , it is crucial to perform a routine procedure such as coronary grafting or valve surgery with meticulous surgical technique and good timing .
therefore , these patients should be operated on by senior surgeons . however , even in experienced hands , such cases may prove quite tricky .
sometimes , even perfect coronary anastomoses and the shortest ischemic time can not prevent failed weaning from cardiopulmonary bypass . the possibility of perioperative mechanical support , exceeding the intra - aortic balloon pump , is quite tempting .
one option is extracorporeal membrane oxygenation ( ecmo ) , which can support the circulation for up to a few weeks .
this requires , however , both arterial and venous cannulation , an aggressive anticoagulation regime and specially trained perfusionists and nursing staff .
extracorporeal membrane oxygenation is also associated with a long list of potential complications including infection , bleeding , thromboembolic events , hemolysis and finally multiorgan failure ( mof ) .
there is no doubt that ecmo is a well - established and recognized life - saving procedure ; however , the question may be raised whether some patients could benefit from an easier technology used in a planned manner .
, there is quite a wide range of indications for their use , two in cardiology : as a rescue treatment in cardiogenic shock caused mainly by acute coronary syndrome   and , electively , as a support in high - risk percutaneous interventions including pci and vt ablation [ 7 , 8 ] . because of endovascular insertion and therefore limited device size ( 12 fr )
the generated flow can not be higher than 2.5 l / min , which usually is enough in the above situations .
impella pumps may be applied in post - cardiotomy shock when an intra - aortic balloon is not enough to succeed in weaning from cardiopulmonary bypass .
cardiac surgeons may also use them more electively as a perioperative support in patients with significantly impaired left ventricular function .
the surgical insertion can be performed either peripherally ( impella 5.0 ) or directly through the ascending aorta ( impella ld ) . in peripheral access
the femoral or axillary artery is exposed , then the device is inserted using a tubing graft and forwarded to the left ventricle under fluoroscopic guidance .
the hybrid theatre setting is required , but on the other hand it is possible to perform less invasive , thoracoscopic surgery . in direct access , after sternotomy , the implantation is quite easy under tee guidance .
whatever the access , the surgical technique allows one to insert a bigger device ( 21 fr ) , which is able to generate flow up to 5 l / min ( ! ) .
that means that after the procedure , which is slightly more complex than insertion of an iabp , and having a device which is almost as easy to operate as an iabp , we achieve an effect that is very close to the benefit of left ventricular assist device ( lvad ) .
the aforementioned problem of left ventricle venting is solved by definition , with impella being an intraventricular device .
it should not stay in for longer than 5 days , which is more than enough to rethink and rearrange a new strategy .
( impella , ecmo , lvad , recovery or transplant ) . when it is applied electively , as in our case , the chances are very high that only the first stage will be necessary .
this being the case , the impella pump can be deservedly regarded as a  short bridge to recovery  .

Answer:
cardiac surgeons have to face the problem of impaired left ventricle function in patients undergoing routine valve or coronary procedures .
 the intra - aortic balloon pump is not always effective in preventing cardiac failure .
 the idea of using a microaxial rotating pump as a short - term perioperative support seems to be a convenient solution .
 the case of a patient with dilated cardiomyopathy undergoing combined mitral and coronary surgery with elective use of the impella ld pump is presented .
 various options of applying the impella device are discussed , especially as a bridge to transplant or bridge to recovery .