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 protein folding problem , or the protein structure prediction problem , is one of the most interesting problems in biological science .
studies have indicated that proteins biological functions are determined by their dimensional folding structures . because the structure of a protein is strongly correlated with the sequence of amino acid residues , predicting the native conformation of a protein from its given sequence
since the problem is too difficult to be approached with fully realistic potentials , the theoretical community has introduced and examined several highly simplified models .
one of them is the hp model of dill et al . 1 . , 2 . , 3 . where each amino acid is treated as a point particle on a regular ( quadratic or cubic ) lattice , and only two types of amino acids
although the hp model is extremely simple , it still captures the essence of the important components of the protein folding problem ( 4 ) .
the protein folding problem in the hp model has been shown to be np - complete , and hence unlikely to be solvable in polynomial time 5 .
.. for relatively short chains , an exact enumeration of all the conformations is possible . in dealing with longer chains ,
the methods used to find low energy structures of the hp model include genetic algorithm ( ga ; ref . 8 . , 9 .
these algorithms can find optimal or near - optimal energy structures for most benchmark sequences , however , their computation time is rather long . in this paper ,
a branch and bound algorithm is proposed to find the native conformation for the two - dimensional ( 2d ) hp model .
the experimental results have shown that our algorithm is very efficient , which can find optimal or near - optimal conformations in a very short time for a number of sequences with lengths ranging from 20 to 100 monomers .
the monomers are numbered consecutively from 1 to n along the chain , which is folded on the square lattice , and each monomer occupies one site with the center on the lattice point .
note that each monomer should be connected to its chain neighbors and is unable to occupy a site filled by other monomers .
if monomer i is placed on the square lattice , then the coordinates of its location are denoted by ( xi , yi ) .
the hp model is based on the assumption that the hydrophobic interaction is one of the fundamental principles in the protein folding .
an attractive hydrophobic interaction provides for the main driving force for the formation of a hydrophobic core that is screened from the aqueous environment by a shell of polar monomers .
therefore , the energy function of the hp model is defined as:(1)e=-i , j < i-1ij where i = 1 if the i monomer in the chain is hydrophobic , otherwise i = 0 . in other words ,
the energy of a conformation can be obtained by counting the number of adjacent pairs of hydrophobic monomers ( h  h ) that are not consecutively numbered , and multiplying by 1 .
the goal of the protein folding problem is to find the conformation with the minimal energy .
it can be seen that each monomer occupies one lattice site connected to its chain neighbors .
the energy of this conformation is 4 , which is the lowest energy state of the sequence .
in our algorithm , a conformation is built by adding a new monomer at an allowed neighbor site of the last placed monomer on the square lattice . in order to obtain a self - avoiding conformation ,
the monomers are placed consecutively until all the n ( the length of the chain ) monomers are placed , that is , our algorithm is a growth algorithm .
if k  1 ( 1  k  n ) monomers have been placed on the square lattice , the k monomer may have three possible locations : turn 90 right , turn 90 left , or continue ahead .
figure 2 gives a partial conformation where four monomers have been placed on the square lattice .
the next monomer , namely monomer 5 , can be placed at any one of these unoccupied positions , resulting in three different partial conformations accordingly . in this way
as shown in figure 3 , a search tree representation can be used to denote all possible folding conformations , with three descendants at most for each node .
each node in the search tree corresponds to a partial conformation , and a line between two nodes represents a placement choice of a new monomer to the existing partial conformation .
consequently , leaf nodes at the end of the tree correspond to the complete conformation . from figure 3 , it is obvious that the conformational space grows exponentially when the length of the protein chain increases .
as mentioned by unger and moult ( 12 ) , the number of possible ( self - avoiding ) conformations for an l - long sequence on a 2d square lattice is al , where   2.63 and   0.333 .
accordingly , for a protein chain of not too short length , the search space is too huge to find the lowest energy conformation within a reasonable running time . to reduce the computational cost ,
a so - called branch and bound method is introduced in this paper . in this search method , only the promising nodes are kept for further branching and the remaining nodes are pruned off permanently . since a large part of the search tree is pruned off aggressively to obtain a solution , its running time is polynomial in the size of the problems . in our algorithm , we treat h monomers and p monomers differently . for a partial conformation where
k1 monomers have been placed on the square lattice , if the k monomer is p , then all possible branches should be kept .
otherwise , if the k monomer is h , then the benefit of all possible branches of the k monomer will be evaluated and some branches may be pruned .
that is to say , the main part of our algorithm is centered on the evaluation and pruning of the h monomers .
this strategy maintains the diversity of the conformations and eliminates the hopeless partial conformation at the same time .
the details are as follows : we set two variables , uk and zk , as the thresholds to evaluate the benefit of all branches for monomer k. here , uk is defined as the lowest energy of the partial conformation with length k that has ever been generated so far , and zk is the arithmetic average energy of the partial conformation with length k so far . after pseudo - placing monomer k at a possible location , we calculate ek , which is defined as the energy of the current partial conformation with k monomers placed .
it should be pointed out that the term  pseudo - place  means that it is just a test and the placing process can be reverted .
then we compare ek with thresholds uk and zk : if ek  uk , it means that this partial conformation is very promising and this branch should be kept .
if ek > zk , that means the benefit of the partial conformation is below the average , so this conformation is discarded with probability 1 otherwise , if zk  ek > uk , the partial conformation is discarded with probability 2 .
the pseudo - code of this subroutine is presented in figure 4 , including the details of evaluation criterion and the pruning mechanism , which is the main part of our algorithm .
the above process is implemented in a recursive way until all the conformations are either pruned or hit length n. from the conformations hitting length n , we choose one with the lowest energy as the output of the algorithm .
it should be mentioned that the search could be implemented by depth - first or breadth - first , where the two results are identical . in this paper ,
our algorithm is implemented by depth - first . here , emin is the minimal energy of the complete conformations ever built .
note that the first two monomers of a chain can be placed on the square lattice randomly .
the initial values of the two thresholds uk and zk are both 0 . obviously ,
if 1 = 0 and 2 = 0 , the search space will be the complete tree ( no node be pruned ) and it will take a prohibitively long time to search for the lowest energy conformation . if 1 = 1 and 2 = 1 , it takes a very little time to search the entire search space because the thresholds are so high that many promising nodes may be discarded . that is to say , the higher the value of the probabilities , the more difficult a branch is to be kept .
therefore , choosing the value of 1 and 2 is an essential factor affecting the speed and efficiency of this approach . in this paper
the probability 2 is chosen to be less than 1 because a partial conformation with energy below average is more promising than a high energy partial conformation . in this way , ek , the energy of the partial conformation , can be viewed as the energy expectation of the partial conformation after looking one step ahead and zk is expressed as the mean energy of the already generated partial conformations of length k. zk keeps a historical record , which is , to a large extent , conducive to the formulation of promising conformations .
for any partial conformation , it would have more opportunities to procreate if holding higher individual quality ( ek ) , which is in accordance with the law of natural selection .
to test the performance of the branch and bound algorithm , we compared it with the mc , ga , and mixed search ( ms ; ref . 13 ) algorithms by using 10 benchmark sequences for evaluation ( table 1 ) .
table 2 presents the results obtained by the four methods on the 10 different sequences .
as shown in the table , our branch and bound algorithm can find the optimal lowest energy conformations for six sequences .
it is noteworthy that our algorithm can find one native state for the sequence of length 60 , whereas the other three methods failed .
for the two long sequences of length 85 and 100 , respectively , our algorithm can find near - optimal energy conformations .
it should be pointed out that predicting the longest sequence of length 100 is a hard problem , whose native state can only be obtained by a few methods such as the perm algorithm 14 .
, 15 . and the guided simulated annealing method ( 7 ) . we did not compare the speed with other methods directly because the machines were different .
moreover , the running time of the other three methods was presented in terms of  number of steps  while the exact cpu time was used in our test .
all the computations in this study were carried on a 2.4  ghz pc with 512  m memory .
the cpu time for all sequences was less than 10  s except the sequence of length 64 , for which the cpu time was 39.46  s. it can be seen from unger and moult ( 12 ) that the  number of steps  of mc and ga methods increases badly with the increase of sequence lengths , therefore , it is imaginable that the computational speed of mc and ga methods in unger and moult ( 12 ) for practical applications is unacceptable .
the resulting folding conformations for sequences with 24 , 36 , 60 , 85 , and 100 monomers are given in figure 5 , respectively .
for sequences with 24 , 36 , and 60 monomers , the corresponding conformations are all of the lowest energy . for the other two sequences with longer lengths , the corresponding conformations are also of near - optimal energy .
it can be seen that the conformation has a single compact hydrophobic core for all sequences , which is analogous to the real protein structure .
the branch and bound algorithm proposed in this paper is a novel and effective tool for the conformational search in the low - energy regions of the protein folding problem in the 2d hp model .
the experimental results on 10 benchmark sequences demonstrate that our algorithm outperforms other three methods in terms of speed and efficiency .
our algorithm is similar to the  population control  scheme ( 15 ) where individuals would have more opportunities to procreate if holding higher individual quality , and the pruning mechanism reduces considerably the computational burden of search .
we should point out that , the coding of this algorithm is very simple and hence it can be easily implemented by practitioners .

Answer:
a branch and bound algorithm is proposed for the two - dimensional protein folding problem in the hp lattice model . in this algorithm ,
 the benefit of each possible location of hydrophobic monomers is evaluated and only promising nodes are kept for further branching at each level . the proposed algorithm is compared with other well - known methods for 10 benchmark sequences with lengths ranging from 20 to 100 monomers .
 the results indicate that our method is a very efficient and promising tool for the protein folding problem .


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:
bilateral carotid artery occlusion accompanied with basilar tip aneurysm is extremely rare.15 ) it has been suggested that increased blood flow through the vertebrobasilar system , which is the major source of collateral circulation , intensifies the hemodynamic stress on the arterial walls and this may result in the formation of saccular aneurysms.13 ) direct clipping for these aneurysms is difficult and the morbidity is high due to the extensive collateral networks as well as the already compromised cerebral blood flow and high internal blood pressure.2)3)7)14 ) thanks to the development of endovascular techniques , the aneurysms that are difficult to reach by craniotomy can now be treated with excellent results.3)4)6 ) to the best of our knowledge , there have been only seven cases of bilateral carotid artery occlusion with concurrent basilar tip aneurysm not being related to moyamoya disease.5)7)8)11)12)17)18 ) among them , only three cases were treated with coil embolization.7)12)17 ) we report here on a rare case of a ruptured basilar tip aneurysm that was successfully treated with coil embolization in the bilateral cervical internal carotid artery ( ica ) occlusions with abnormal vascular networks from the posterior circulation .
a 43-year old man with a sudden onset of headache , nausea and vomiting visited the emergency room at our institution .
his aunt suffered from moyamoya disease , but he had not undergone diagnostic work - up for familial cerebrovascular diseases because he had not experienced neurological deficits such as ischemic attacks , including dysarthria , dizziness and gait disturbances .
mentally alert , the patient had meningismus , experiencing neck stiffness on admission . a brain computed tomography ( ct )
scan demonstrated diffuse and thick subarachnoid hemorrhage ( sah ) in the bilateral sylvian fissures , the anterior interhemispheric fissure , the basal cistern and the posterior fossa , including the perimesencephalic region ( fig .
subsequent carotid angiography showed complete occlusion of both icas , the so called ' bottle neck appearance ' or ' beak shape , ' at the level of the carotid bulb without appreciable intracranial filling and there were small collaterals from both external carotid arteries through the middle meningeal arteries to the anterior cranial fossa ( fig .
vertebral artery angiography demonstrated that both hemispheres were seen filling in an antegrade fashion from the upper basilar artery and both posterior cerebral arteries through an extensive network of collateral vessels to the ica bifurcations .
a 6  4 mm aneurysm was also observed at the basilar artery bifurcation ( fig .
perfusion ct scans revealed no reduction of cerebral blood flow and normal cerebrovascular reactivity to acetazolamide ( fig .
4 ) . the abdominal ct aortograms did not demonstrate any other extracranial pathological vascular findings , including renal artery stenosis and fibromuscular dysplasia ( figures not shown ) .
two guglielmi electrically detachable platinum coils and two hydrosoft helical coils were successfully deployed into the aneurysm .
we tried to deploy a microplex coil at the lower neck portion of the aneurysm , but failed due to the wide neck of the aneurysm .
the balloon or stent - assisted technique was not used even though there was a relatively large orifice because of the risk of thromboembolism and obstruction of the parent arteries during the procedure .
eventually , only the dome and waist of the aneurysm were packed completely ( fig .
after embolization , we closely monitored the patient 's neurological condition in the intensive care unit .
the first follow - up angiograms 6 months after treatment did not show aneurysm recanalization .
atherosclerosis and aortic inflammation are known to be the most common causes of bilateral carotid artery occlusion without moyamoya disease.17 ) atherosclerosis can occur at the point of ica bifurcation , leading to chronic and progressive arterial stenosis , whereas aortic inflammation is likely to be involved with the aortic arch and its branches , resulting in bilateral carotid artery occlusion .
generally , an occlusion at the beginning part of the ica is likely to be caused by atherosclerosis , while the occlusion of the bilateral common carotid artery is likely aortitis.17 ) according to the study by aburahma and copeland,1 ) all patients with atherosclerotic bilateral ica occlusion had a history of cerebral ischemic attack such as transient ischemic attack ( tia ) , amaurosis fugax , or stroke even though collateral circulation was present , and they all needed surgical interventions such as endarterectomy , carotid - subclavian bypass or medical treatments using warfarin or aspirin .
by contrast , definite cases of moyamoya disease are diagnosed in patients with bilateral stenosis or occlusion that occurs at the terminal portion of the ica together with an abnormal vascular network at the base of the brain , as is shown by cerebral angiography .
thus , moyamoya syndromes that have underlying diseases such as cerebrovascular disease with atherosclerosis , autoimmune disease , meningitis , brain neoplasm , down 's syndrome , neurofibromatosis , head trauma or irradiation to the head , as well as other conditions , should be excluded.9 ) meanwhile , our case showed complete occlusion at the bilateral proximal portion of the internal carotid arteries above the carotid bulbs with abnormal vascular networks from the posterior circulation without basal moyamoya vessels .
the patient did not have any underlying diseases such as cerebral infection , trauma and aortic inflammation that may lead to stenosis or occlusion of the ica .
although he had no past history of tia , he had two risk factors for atherosclerosis which were hypertension and smoking .
no abnormal findings that may imply fibromuscular dysplasia were seen on the vertebral and abdominal angiograms .
these findings are not characteristics of moyamoya disease or moyamoya syndrome , but suggest idiopathic or atherosclerotic bilateral carotid artery occlusion .
the basilar tip aneurysm associated with bilateral carotid artery occlusion or moyamoya disease is well known , life - threatening complication that causes sah . to the best of our knowledge ,
there have been only seven cases of bilateral carotid artery occlusion with concurrent basilar tip aneurysm without moyamoya disease in the literature.5)7)8)11)12)17)18 ) the causes of carotid artery occlusion included aortic inflammation in two cases and atherosclerosis in five cases.5)7)8)11)12)17)18 ) of them , 5 cases had sah.8)11)12)17)18 ) it has been suggested that increased blood flow through the vertebrobasilar system , which is the major source of collateral circulation in bilateral carotid artery occlusion , intensifies the hemodynamic stress on the arterial walls and this may result in the formation of saccular aneurysms.13 ) although the formation of anastomosis from the external carotid artery may alleviate the hemodynamic burden on the posterior circulation , the effect is limited and local blood pressure still rises which leads to the risk of basilar artery aneurysms.17 ) conservative management for these aneurysms can lead to dismal results,11)18 ) therefore quick , aggressive treatments should be considered .
however , direct clipping is difficult and dangerous due to extensive collateral channels,2)14 ) stiffness of the carotid artery,10)16 ) and high internal blood pressure.7 ) moreover , the fact that the basilar artery is the sole source of blood for most of the brain precludes prolonged temporary clipping to aid in safe dissection around the aneurysm.13 ) thus , these aneurysms have been recently treated with endovascular procedures using soft platinum coils .
there have been several reports have showing excellent results of endovascular embolization for the basilar tip aneurysms in patients with moyamoya disease and bilateral ica occlusion.4)6)7)10)12)17 ) of course , if increased blood burden through the vertebrobasilar system is not alleviated , the aneurysm will probably regrow .
thus , in our case , regular follow - up angiograms are essential and additional embolization with extra - intracranial revascularization may be needed even though there was no perfusion defect seen on the perfusion ct scans .
proximal bilateral ica occlusion is rare but often shows similar clinical features with moyamoya disease such as abnormal collateral vascular networks from posterior circulation and accompanying saccular aneurysms .
differential diagnosis between idiopathic and atherosclerotic occlusion may be needed for further cardiovascular work - up .
the basilar tip aneurysm associated with proximal bilateral ica occlusion is more rare and dangerous , but curable disease .
endovascular embolization for such aneurysms is safe and useful even without the assistance of balloon or stent .

Answer:
we report here on a rare case of a ruptured basilar tip aneurysm that was successfully treated with coil embolization in the bilateral cervical internal carotid artery ( ica ) occlusions with abnormal vascular networks from the posterior circulation . a 43-year old man with a familial history of moyamoya disease presented with subarachnoid hemorrhage .
 digital subtraction angiography demonstrated complete occlusion of the bilateral icas at the proximal portion and a ruptured aneurysm at the basilar artery bifurcation .
 each meningeal artery supplied the anterior cranial base , but most of both hemispheres were supplied with blood from the basilar artery and the posterior cerebral arteries through a large number of collateral vessels to the ica bifurcation as well as the anterior cerebral and middle cerebral arteries .
 the perfusion computed tomography ( ct ) scans with acetazolamide ( acz ) injection revealed no reduction of cerebral blood flow and normal cerebrovascular reactivity to acz .
 an abdominal ct aortogram showed no other extracranial vessel abnormalities .
 a ruptured basilar tip aneurysm was successfully treated with coil embolization without complications .
 endovascular embolization may be a good treatment option with excellent safety for a ruptured basilar tip aneurysm that accompanies proximal ica occlusion with vulnerable collateral flow .


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:
in the early 1960s ross and barratt - boyes introduced the use of human allograft cardiac heart valves , or homografts , into clinical practice [ 1 , 2 ] . in 2012 the 50th anniversary of the first so - called ross operation was celebrated .
the ross operation encompasses implantation of a pulmonary autograft in the aortic position , while an allograft is transplanted in the pulmonary position .
ever since , there has been a need to store available donor grafts , so that they can be prepared , stored in a tissue bank , and used for implantation , either in elective or in emergency patients . from the end of the sixties and into the eighties tissue banks were founded all over europe .   in the same period studies about the techniques and successes of homograft implantation in larger series of patients
were published , followed in the nineties by studies which covered more than a decade .   because , over time , they were the only successful biological heart valve prostheses beside the mechanical ones , the results were very satisfactory .
the advantages were clear : a low rate of thromboembolic events , thus avoiding a lifetime of anticoagulation therapy .
in addition , their hemodynamic properties were superior to those of mechanical valves , especially those available in the early 1960s and 1970s .
as time went by , it became clear that the availability and cardiectomy techniques to obtain cardiovascular tissues were a problem as suitable donors were recipients of heart transplants , organ donors whose hearts were not accepted , or donors who were autopsied and their relatives had agreed to their tissues being used .
in the last 20 years , the european cardiovascular tissue banks have invested a great deal of finances and effort in improving the safety and quality of their tissue banking methods and facilities .
issues such as donor selection , validation of testing methods , the improvement of sterility systems and clean rooms were addressed .
regulations based on directives   of the european union became law in all member states .
the foundation of european tissue banks initiated a survey to obtain an assessment and quantification of the situation in the field of cardiovascular tissue banks , after implementation of the european directives into national legislation .
in 2011 , questionnaires were sent out to 30 cardiovascular tissue banks , 18 of which completed and returned them .
one cardiovascular tissue bank had started its activities in early 2011 ; hence no data could be reported as yet .
three additional questionnaires were received after the statistical analysis was closed , and these data are not included .
ranges and means were calculated and tabulated giving insight into the level of activities of these cardiovascular tissue banks .
percentages of detected positive serology were assembled , and a break - down of microbiological contamination as the reason for discarding tissue should yield information on the reasons for tissues being discarded during the process .
the statistics in table 1 are based on the assumption that every heart received in the cardiovascular tissue banks provided two grafts .
out of 18 tissue banks , 11 had registered the number of donor reports rather than the hearts actually received in the bank . in these 11 tissue banks , 67% of the donors reported resulted in the receipt of a heart in the bank .
table 1 shows that from the total of 1640 hearts received by 18 tissue banks in 2010 , only 46.9% provided suitable grafts ; hence the discard rate is 53.1% .
the cardiovascular tissue banks show a considerable difference in their activities : while in 2010 the highest number of grafts received was 262 , the smallest bank processed only 17 grafts . when it comes to issuing grafts , similar differences are observed . as shown in table 2 ,
the statistics in table 2 confirm that the demand for pulmonary grafts is about twice as high as the demand for aortic valves : 67% of all grafts issued were pulmonary valves .   the data provided by the 18 cardiovascular banks show that , in 2010 , exporting of tissues to other countries was done by 7 banks , with the proportion varying from 1% to 72% of the annual number of processed grafts .
the average donor age ranges from 40 ( in 2007 ) to 42 in 2010 .
fifty - seven percent of the hearts originated from organ donors of whom the heart could not be transplanted , 28% from non - organ donors ( those who become donors after an extended period of cardiac arrest , and are thus unsuitable as organ donors ) and 15% were retrieved from so called  domino donors  .
domino donors are people who undergo a heart transplantation , and whose native heart may still have valves that are transplantable as tissue grafts .   the criteria for the time between cardiac arrest and cardiectomy , as observed by the tissue banks in this study , ranged from 2 to 48 hours .
in reality , the average time until cardiectomy was between 8 hours in 2007 , and 11 hours in 2010 .
after receipt in the tissue bank , the valvular grafts are excised from the heart and decontaminated . also here , the criteria differed greatly between the banks and the time varied from 18 hours to 72 hours , while the average number of hours in practice was 24 .
table 4 shows the reasons for discarding donor tissue . in 2010 , 45.3% of the tissue grafts had to be discarded . in many cases
there was more than one reason for not accepting the heart , or its tissue grafts , for transplantation .
heart valve discards in 2010 , average % of all cardiovascular banks . in 32.7% of the cases
the reason for discard was that there were contraindications for transplantation of the tissue in the donor s medical history . during processing 35.8% of the cardiovascular tissue
was found to be unsuitable because of its morphology . in 17.65% and 4.2% of the cases , respectively , microbiology or serology test results were a reason not to accept the grafts for transplantation .
technical and unknown reasons were responsible for 7.3% and 7.8% , respectively , of the discards .
substantial differences can be observed in the number of hours during which the tissue banks culture the tissue to detect and/or eliminate micro - organisms ; the range is 5 - 72 hrs .
also , the temperature under which incubation takes place shows a large variety : from 4o c to 37o c. the banks use 25 different antibiotics in many different concentrations .   in table 6
a breakdown of other tissues provided by the banks in this study shows that pericardium , arteries and veins are processed alongside valvular allografts .
the level of activity in cardiovascular tissue banks is determined by the numbers of donors .
this study shows that the range of donor hearts received in 18 banks varied from 1640 in 2010 to 1700 in 2007 .   as the number of hearts received represents only 67% of the number of donors referred , it may be worthwhile to analyze the reasons why the hearts of 33% of the reported donors were eventually not allocated to the tissue bank . by eliminating factors preventing the donation from materializing
on the other hand the statistics document that in 2010 45.3% were not suitable for transplantation and had to be discarded .
better donor screening beforehand , and a more effective process from cardiectomy to excision and for decontamination in the bank are three factors which could decrease this high number of discards .
this study shows in statistics what cardiovascular tissue bankers have known for a long time , that the demand for pulmonary valves is about twice as high as the demand for aortic valves : 66% of all grafts are pulmonary valves .
although this study does not extend to the use of grafts , the literature shows that for many centers the pulmonary valve is the allograft of choice in congenital as well as in acquired cardiac diseases .
the activity of the banks varies from processing less than 20 to 262 donor hearts in 2010 .
one has to wonder about the routine capabilities of personnel as well as about the optimal use of the investment and costs of maintenance of a class a laboratory .
the donor age ( table 3 ) has gradually increased from an average of 40 in 2007 to 42 years in 2010 .
as the average age in the european population increases , the donor age increases accordingly .
the reason is twofold : some authorities forbid the use of non - organ donors;to set up a cardiectomy team on a 24/365 basis requires additional organizational constraints and investments which some banks wish to avoid .
some authorities forbid the use of non - organ donors ; to set up a cardiectomy team on a 24/365 basis requires additional organizational constraints and investments which some banks wish to avoid .
the dependency on the receipt of organ donor and domino donor hearts brings them into a vulnerable position .
the need for additional cardiovascular grafts could be compensated by an effort to set up a non - organ donor program .
however , the differences in decontamination methods , use of antibiotics and their concentrations , as well as temperature should be a subject to cause concern in the cardiovascular tissue banks participating in this study .   in 2010 , a conference of these tissue bankers and their microbiologists was organized by the foundation of european tissue banks .
substructuring and validation methods were exchanged , and some arguments were proven to be right . at that conference , and from the questionnaire in this study , no adverse events were reported by any of the participating tissue banks . while most of the cardiovascular tissue banks in this study concentrate on the processing and distribution of the  classic  homograft heart valves , nine banks showed activities with respect to processing tissues such as arteries , veins and pericardium .
correspondence with different tissue bank representatives revealed that the demand for arterial grafts is growing throughout europe . while veins are used in access surgery ( shunts ) , pericardium serves as patching material to bridge larger gaps of deficient tissue during cardiothoracic operations .
the numbers of these tissues issued over the period 2007 - 2010 also show a considerable increase .
for the first time since the start of the clinical use of human allogeneic heart valves , data from a number of european cardiovascular tissue banks could be accumulated .
statistics with respect to numbers , discard and use of cardiovascular tissue provide insight into the magnitude of their activities as well as into some of the parameters they use .
first of all , looking at the number of tissue grafts issued for transplantation , one can conclude that the demand for tissues has not decreased during the period of 4 years encompassed in this study . apparently the demand
the results show that cardiovascular tissue bank activities have remained relatively stable over the years , though the number of donors has somewhat decreased ( 3.5% ) .
while the demand for pulmonary grafts still increased from 810 to 981 ( 21.1% ) , only 505 aortic grafts were issued in 2010 .
what happens with all the aortic grafts which are not issued is a logistical as well as an ethical question .   in order to cope with the persistently high demand for pulmonary grafts and arteries ,
those cardiovascular tissue banks which do not retrieve hearts from non - organ donors should seriously consider initiating such a donor program .
although not clinically proven , studies show that stem cell techniques may eventually contribute to the quality and availability of human heart valves , yet none of the cardiovascular tissue banks indicated that they are in any way involved in stem cell research .
the differences in accepted time lapses from death to cardiectomy , and from cardiectomy until excision of the valves and further processing find their origin in view - points with respect to quality and safety . a consensus between the tissue banks contributing to this study should be based on data with respect to the potential loss of tissue quality starting at cardiac arrest and measured over time .
as there are very large methodological differences with respect to microbiology testing , incubation and decontamination of cardiovascular tissue between the 17 contributing tissue banks , there is a necessity to validate procedures and room for improvement .
this survey shows an increased demand for other tissues , which may be worth further exploration .
after all , where alternatives seem to fail or are absent , it is the task of tissue banks to satisfy the clinical demand for tissue grafts .

Answer:
introductionin the past 50 years , human cardiovascular tissue allografts , also called homografts , have been implanted into patients with different valvular diseases .
 the use of these allografts and   the number of cardiovascular tissue banks and their respective techniques increased .
 we conducted a survey to establish the quantity of allografts processed , and issued by , european tissue banks .
 the survey also included the collection of other relevant statistics.methodsin 2011 , the foundation of european tissue banks collected data from 19 different cardiovascular tissue banks in 11 european countries.resultsfrom   2007 to 2010 the   data show a decrease in the number of hearts received , from 1700 to 1640 in 18 tissue banks ; the average number of hearts received for cardiovascular tissue processing decreased from 113 to 91 .
 the number of heart valves issued for transplantation increased from 1272 in 2007 to 1486 in 2010 .
 the average rate of discard because of microbiological contamination was 20.7% , while 4.2% of the grafts were not used because of positive serology .
 half of the tissue banks issued arterial grafts , while 3 banks also issued veins and pericardium .
 an overview of decontamination methods shows considerable methodological differencesbetween 17 cardiovascular tissue banks.conclusionsfrom the experience in europe , it can be concluded that cardiovascular tissue banks have an established place in the domain of cardiovascular surgery .
 the statistics show fluctuating data concerning the demand for human cardiovascular allografts and methodological questions .
 there is room for growth and improvement with respect to validation of decontamination methods .


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:
oroantral fistula ( oaf ) is an abnormal communication between the oral cavity and the maxillary sinus .
the chances of occurrence of oroantral communication increases , if there is an underlying peripical infection or a preexisting sinus disease .
the chronic long standing nature of oaf may be due to fungal infection like mucormycosis .
the sinus pathology is a predisposing factor for chronic non - healing nature of oaf .
many times this aspect is overlooked and simply the diagnosis of non - specific maxillary sinusitis is given , which leads to improper treatment .
the case we present here is a 34-year - old female patient [ figure 1a ] who was complaining about non - healing opening in the upper left front region and exposure of root of one tooth .
the lesion started as a small swelling in the left maxillary anterior vestibular area in the region of canine eminence .
after few days , patient noticed the area where the swelling ruptured was not healing and instead , it was showing small aperture .
the aperture went on increasing to the present size of 0.5 cm  0.5 cm .
patient revealed the history of trauma in maxillary left front teeth region during field work 2 years back .
( a ) a 34-year - old female patient presenting with mild to moderate swelling in left maxillary sinus area ( arrow ) .
( b ) intraoral examination revealed the oroantral communication ( arrow ) in maxillary left anterior labial vestibule at mucogingival junction in the area of canine .
( c ) the dorsal surface of tongue was coated with white leathery coat with central rhomboidal shaped erythematous area ( arrow ) .
( d ) the cytosmear revealed pas positive numerous long thin filaments of candidal organism ( arrow ) .
budding yeast cells were seen scattered along the with pseudohyphae ( pas , 200 ) extraoral examination revealed a mild swelling in the left maxillary sinus area [ figure 1a ] . on intraoral examination
[ figure 1b ] oroantral communication was noticed in maxillary left anterior labial vestibule at mucogingival junction in the area of canine .
the opening was around 0.5 cm  0.5 cm in size exposing the apical third portion of root of canine .
the dorsal surface of the tongue was coated with white leathery coat with central rhomboidal shape erythematous area [ figure 1c ] .
no caries was detected in all maxillary left anterior teeth . on pulp vitality test maxillary left lateral incisor and canine was found to be non - vital .
the clinical diagnosis of oaf secondary to chronic periapical abscess in relation to maxillary left canine was established .
the conventional approach was undertaken to close the fistula and access opening was created in maxillary left canine .
patient was followed up for observation of healing at closure of oaf and also to continue with root canal treatment of maxillary left canine .
after 4 weeks of primary closure of oaf , still there were no signs of healing and instead the oaf was re - established as it was before commencing the treatment .
patient also complained of dull gnawing pain in the maxillary sinus area and more heaviness in the same region .
looking at non - healing chronic nature of oaf , the incisional biopsy from the margin of oaf was planned to seek histological changes in the region of oaf .
based on histopathological diagnosis , reclosure of oaf was planned . for chronic maxillary sinusitis antibiotics and nasal wash
the patient was followed - up regularly to assess for healing at oaf and check for the status of chronic maxillary sinusitis .
patient reported with non - healing of oaf and even chronic maxillary sinusitis did not respond to treatment . this time to avoid surgical trauma , a cytological smear was prepared by swabbing the unhealed oaf .
cytosmear stained with periodic acid schiff stain , revealed a pale homogenous stroma , with abundant acute inflammatory cells .
numerous long thin filaments of candidal organism having budding yeast cells were seen scattered along with pseudohyphae [ figure 1d ] . based on the cytological features , the diagnosis of oaf with superadded candidiasis was given .
after about 5 - 6 weeks patient was completely all right and clinical healing was complete .
there were no sign of candida organism on repeated cytological examination at the site of closure .
present case is an example for clinicians where they can learn that , sinus disease secondary to oaf is not only of bacterial origin but it could be also of fungal origin . since there is no history of extraction of tooth , oaf would have arisen due to periapical pathology secondary to trauma .
the candida organisms from oral cavity might have colonized the oaf leading to sinus pathology .
candida organisms can be easily detected at tissue level as candida hyphae at superficial epithelial surface , but sometime these superficial hyphae are washed away from tissue during processing in various chemicals .
this might be the reason why candida organisms were not detected and diagnosed in biopsied tissue .
mere presence of this fungus in oral cavity is not sufficient to produce the disease .
there must be actual penetration of fungus in to the tissue , although such invasion is superficial and occurs only when there is breach in the continuity of epithelium .
in present case , oaf must have become reason for the colonization of candida organisms over the maxillary sinus lining .
the other predisposing factors for candidiasis can be prolonged intake of antibiotics , corticosteroids ; anemia , etc . since initially patient was diagnosed with non - specific maxillary sinusitis .
so inadvertent use of antibiotics could also be responsible for occurrence of superadded infection of candidiasis with oaf .
according to katzenstein , sinus mycoses can be classified as
 non - invasive chronic mycoses ( fungus ball),allergic mycosis , chronic indolent invasive mycosis , andfulminating invasive mycoses .

non - invasive chronic mycoses ( fungus ball ) , chronic indolent invasive mycosis , and fulminating invasive mycoses .
types 3 and 4 are found in the immunosuppressed where as in immunocompetent , types 1 and 2 are common , with a granulomatous inflammatory response and necrosis .
candida organism can grow as opportunistic pathogen especially in presence of human immunodeficiency virus ( hiv ) infection .
since there was no hiv associated periodontal disease in patient , the remote possibility of hiv as cause for candida growth and occurrence of oaf could be ruled out .
furthermore , the mucosa of the dorsum surface of the tongue ( filiform papillae ) may represent a site of residual colonization and reservoir of organisms .
since patient 's dorsal surface of tongue was showing white coat with central erythematous area [ figure 1c ] .
this would have been possible source for colonization of candida organisms in maxillary sinus through oaf .
the mycetes most often involved was aspergillus fumigatus ( 76.9% ) . even after extensive literature search , no report was found for sinus formation with candida .
this case is good learning lesson for clinicians and histopathologists for stepwise approach in diagnosing oaf associated with sinus disease .
it is understood that sinus pathology should be primarily treated for the successful closure of oaf . for the proper treatment of sinus disease identification of causative agent ( pathogen )
therefore , sinus disease secondary to oroantral communication should be primarily screened for pathogen through simple cytological approach .

Answer:
oroantral fistula ( oaf ) and oral candidiasis are common to come across as separate individual lesions .
 however when candida organisms infect maxillary sinus through oaf then diagnosis should not be limited to clinical diagnosis only .
 in such situation role of cytological examination can prove to be fruitful .
 a female with chronic long standing oaf , not responding to conventional treatment approach is reported .
 on incisional biopsy , the case was diagnosed as chronic maxillary sinusitis with oaf .
 however patient did not respond to any treatment approach and later presented with a more progressive lesion involving maxillary sinus .
 a cytosmear stained with periodic acid schiff stain , revealed the presence of numerous candidal hyphae .
 finally , case was diagnosed as oaf with a superadded candidal infection .
 patient responded well to antifungal treatment followed by reclosure of oaf .
 we should not neglect a simple cytological examination which may prevent wrong diagnosis and wrong 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:
west nile encephalitis is a mosquito - borne disease endemic to africa , asia , australia , and europe and the west nile virus is a single - stranded rna virus which belongs to the japanese encephalitis serogroup of flaviviruses ( 1 ) .
it could be accompanied with various neurologic symptoms and signs including headache , mental confusion , optic neuritis , and muscle weakness ( 2 , 3 , 4 ) .
after the first two cases of west nile encephalitis were diagnosed in 1999 in new york ( 5 ) , many neurological abnormalities were noted in patients of west nile encephalitis , and the flaccid muscle weakness is a distinctive feature of this disease ( 2 , 3 , 6 ) . until now
, west nile encephalitis was never diagnosed in korea , and it is the first report of west nile encephalitis in korea .
a 58-yr - old man was admitted with headache for 2 months in june 2012 .
the patient had been on a business trip in guinea , west africa since 7 months ago .
he denied other symptoms such as nausea , vomiting , neck stiffness , and dizziness .
the headache and cognitive impairment had been worsening and accompanied general weakness and weight loss 10 kg for 2 months .
he had no hypertension , cardiac diseases , chronic renal disease , and liver disease .
he had a 20 pack - year history of smoking and no recent alcohol intake .
the patient denied using any medications except for antimalarial drug ( sulfadoxine 500 mg , pyrimethamine 25 mg , artemether 80mg / ml ) and analgesics in africa . at admission to our hospital , he was afebrile ( 36.4 ) and his vital signs were blood pressure 121/78 mmhg , heart rate 97/min , and respiratory rate 20/min with normal findings of physical examinations .
findings on initial neurologic examinations were normal except minimental state examination ( mmse ) with score 20 .
admission complete blood count revealed hemoglobin of 12.7 g / dl , leukocyte count of 16.2  10/l with 79% neutrophils , and a platelet count of 388  10/l . the patient 's calcium level , chemistries , and liver function tests were normal and crp was slightly increased .
analysis of cerebrospinal fluid ( csf ) demonstrated 0 rbc/l , 214 wbcs/l ( with 80% lymphocytes and 12% neutrophils ) , a protein level of 161.9 mg / dl , a glucose level of 93 mg / dl and ada level of 4.8 .
a brain magnetic resonance imaging ( mri ) revealed multifocal patchy t2 high signal lesions in both temporal lobes , basal ganglia , internal capsule posterior limb , and corona radiata , which suggested encephalitis .
electroencephalogram showed frequent semirrhythmic medium amplitude delta slowing on both hemispheres , with frontal dominancy . on hospital day 1 , his body temperature was 38.0 and malaria test was negative .
follow up csf tapping was done on hospital day 3 and 6 rbc/l , 340 wbcs/l ( with 67% neutrophils and 28% lymphocytes ) , a protein level of 164.6 mg / dl , a glucose level of 70 mg / dl and ada level of 6.0 .
the patient complained of both leg weakness and the motor strength of bilateral lower extremity was 4+/4 + .
he also complained of both leg pain and paresthesia , deep tendon reflex on both lower extremities were areflexia .
there was no remarkable finding on nerve conduction study ( ncs ) and needle electromyogram ( emg ) , but arachnoiditis and myelitis were observed on lumbar spine mri ( fig .
polymerase chain reactions ( pcr ) for hsv , vzv , ebv , cmv , enterovirus , tuberculosis , and mycoplasma pneumonia were negative in csf .
serological test for brucellosis , lyme disease , leptospirosis , hantann virus and tsutsugamuchi disease were negative at admission
an additional serological study for specific antibody for west nile virus was done , the total antibody titer of west nile virus was 1:337 , and follow up titer after 2 weeks was 1:1,632 in serum by plaque reduction neutralization test .
treatment with interferon- 3mu was started and maintained for 2 weeks . follow up csf tapping was done after one month later and 9 rbc/l , 9 wbcs/l ( with 16% neutrophils and 67% lymphocytes ) , a protein level of 99.9 mg / dl and a glucose level of 66 mg / dl .
encephalitis with severe muscle weakness is a common symptom and may provide a diagnostic clue . to confirm a diagnosis , it needs identification of west nile virus in serum or csf .
igm antibody is usually detectable only during a few days of illness ( 7 ) .
another method is the identification of a change by a factor of four or more in the antibody titer or virus - neutralization tests ( 7 ) , the case was positive for the virus - neutralization tests .
serological test and pcr for other infectious agents were all negative and autoimmune encephalitis such as nmda receptor encephalitis was excluded by clinical symptoms ( 8) .
many studies indicated that the weakness was probably caused by infection and inflammation in the anterior horn cells of the spinal cord and brainstem like poliomyelitis ( 6 , 9 , 10 ) .
electrophysiologic studies showed reduced compound muscle action potentials , and normal sensory nerve action potentials , which is distinguished from guillain - barre syndrome ( 3 , 6 , 9 , 10 ) .
a few autopsy studies demonstrated that the inflammatory changes with severe leukocytic inflammation of the anterior horns with striking loss of motor neurons ( 4 , 11 ) . but this case did not present any abnormalities in the electrophysiologic study .
he complained about severe sensory symptoms with leg pain and arachnoiditis was observed in lumbar mri .
only a few reports noted a caudal equine enhancement ( 4 ) and weakness due to acute radiculitis ( 12 ) .
it 's hard to say that his weakness was caused by only radiculopathy , because paralysis of the west nile encephalitis generally results from anterior horn cell damage .
but in this case , radiculopathy also contributes the motor weakness of the west nile encephalitis . at present
there is no established treatment for west nile encephalitis and basic treatment is a supportive care .
but because it 's a fatal disease , sometimes it was treated with plasmapheresis or administration of iv immunoglobulin ( 5 ) .
interferon- has been reported to inhibit west nile virus replication , and some successful cases were reported using of interferon- to treat west nile encephalitis ( 13 ) .
korea is not an endemic area of west nile virus , but an increasing overseas trip poses a risk of the influx of overseas diseases and may contribute to the global spread of infectious diseases .

Answer:
west nile encephalitis was first identified in 1937 , but until now , it was never diagnosed in korea .
 a 58-yr - old korean man was admitted with headache and cognitive dysfunction .
 the patient had been on a business trip in guinea .
 cerebrospinal fluid ( csf ) showed pleocytosis .
 the patient complained of both leg weakness , and arachnoiditis and myelitis were observed on lumbar magnetic resonance imaging ( mri ) .
 a specific neutralizing antibody for west nile virus was positive in serum .
 after a treatment with interferon- 3mu , follow up csf findings recovered completely after 3 months later .
 the first case of west nile encephalitis in korea was imported from guinea , and was cured successfully.graphical abstract


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:
MINEs: open access databases of computationally predicted enzyme promiscuity products for untargeted metabolomics

Paper sections:
Background

Metabolomics, the study of the population of small molecules in a cell, has drawn intense interest in fields from medicine to synthetic biology because it can provide a fine-grain representation of cellular state and activity [1–4]. Of particular interest is untargeted metabolomics, which seeks to measure as much of the metabolome as possible by limiting methodological detection bias. The dominant analysis technique for untargeted metabolomics is chromatography coupled with mass spectrometry (MS) but this method is hindered by a large number of unknown peaks [5] and the limited number of reference spectra available to identify the peaks [6]. A number of tools have been developed to propose structural matches for unannotated peaks [7–11] but in practice these tools either return too many candidates when drawing from large chemical databases such as PubChem [12] or miss compounds not yet present in curated biochemical database [13, 14].This has the effect of locking untargeted metabolomics in a unfortunate paradox: compounds that are not present in biochemical databases are not identified and in the absence of experimental identification, new compounds cannot be added to databases [15].

There is a growing consensus that many enzymes mediate undocumented side-reactions (known as promiscuous activities) as a result of exposure to diverse cellular metabolites [16, 17]. These activities may explain unannotated peaks in metabolomics datasets [18, 19] but are difficult to detect as they may be overshadowed by a known function [20] or be dependent on intracellular conditions [21]. Predicting novel chemical reactions based on broad enzyme specificity has been utilized by a number of tools for the prediction of new biochemical pathways [22–24]. Recently, this technique has also been used to expand structure databases for metabolomics by the MyCompoundID tool [25] the In Vivo/In Silico Metabolites Database (IIMDB) [15], LipidHome [26] and others [27, 28].

Here we present Metabolic In silico Network Expansions (MINEs) that utilize the Biochemical Network Integrated Network Explorer (BNICE) [29, 30] to expand on general biochemical databases as well as organism-specific databases for Escherichia coli and yeast. The focus on endogenously present and organism-specific metabolites has been cited as critical to improving the confidence of compound matches [5] and thus we complement existing resources that focus on human metabolism. In principle, these predictions could also be made using Reaction Difference Matching (RDM) [23], machine learning methods [31, 32], or other rule-based methods such as ChemAxon's Metabolizer. Each of these approaches has their benefits; the output really depends on the quality and coverage of the reaction rules used in the analysis. We selected BNICE because we have a set of BNICE reaction rules that have been demonstrated to reproduce a large fraction of known biochemical reactions [24], as well as to predict enzyme reactions that were subsequently verified experimentally [33]. Importantly, we also have the right to re-distribute BNICE output. No license is required for academic users to access the website or APIs and all BNICE predicted compounds are available for download in SDF format from the website.

MINE database construction and access methods. The process of constructing a MINE database from the curated source databases is depicted on the left. The methods for accessing the database are shown on the right.

Construction and content

Compound information was obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) (Release 68.0) [36], the Yeast Metabolome Database (YMDB) (Version 1.0) [37] and EcoCyc (Version 17.0) [38]. Generalized (containing R groups), inorganic compounds, and disconnected fragments were removed using the Pybel toolkit [39]. Generalized structures are of very limited utility, as they cannot be assigned an accurate mass or represented in a canonical form. Where possible, we encourage developers to avoid ambiguity by enumerating all possible structures in their databases. Additionally, biochemical databases often contain numerous duplicate compounds [40] and these were identified by Standard InChIKey [41] comparison and removed for computational efficiency.

Generalizing a BNICE reaction rule from known biochemical reactions. The common motif of the hydrolysis of the 1,3-diketone is shaded for emphasis.

Construction and content

BNICE products may take a variety of tautomeric forms depending on the source structure and the nature of the operator applied. Therefore, products were processed with ChemAxon's Standardizer & Structure Checker (JChem 6.0.4, 2013) to ensure canonical valences and placement of charge. Natural Product Likeness scores [42] and estimated logP values were calculated with a standalone Java ARchive (JAR) package and ChemAxon's Calculator Plugins (JChem 6.0.4, 2013) respectively. Estimated Kováts Retention Indices were calculated using the NIST RI algorithm [43].

Compounds were matched to PubChem [44] and KEGG COMPOUND databases with the connectivity block of InChIKeys for annotation. Generated compounds are assigned identifiers based on hash of the canonical SMILES [45] for internal use and a numeric MINE ID for human readability. Finally, the exact mass and chemical fingerprints of structures were calculated with Pybel.

Compound and reaction data is stored as collections in a Mongo Database (v2.6.2). A compound entry contains the chemical formula, exact mass, InChIKey canonical SMILES [45], FP2 and FP4 fingerprints and lists of reactions in which the compound is predicted to participate as a reactant or product. A compound may also be annotated with additional information such as common names or database links if it matches a KEGG or PubChem entry. Reactions are uniquely identified by an 'R' followed by the SHA1 hash of the sorted chemical reaction. Reactions entries contain arrays of reactants and products as tuples of the stoichiometric coefficient and the compound ID as well as a list of the operators that predicted the reaction.

Comparison of MINEs generated from various source databases and other databases containing computationally predicted metabolites

Histogram of Natural Product Likeness. This plot shows the distribution of Natural Product Likeness Scores for the KEGG Database (mean score 0.77), the KEGG MINE (mean score 0.98) and a random sample of 500,000 PubChem compounds (mean score −0.52). A more positive score indicates more natural atomic features.

Screenshot of Metabolomics search results. This screenshot displays features of the metabolomics results including filtering by attributes and highlighting (blue) of compound present in a specified KEGG genome reconstruction.

Annotation of MassBank data

Use case: annotation of accurate mass datasets

Finally, to demonstrate the practical utility of MINE databases, we utilized the EcoCyc MINE to annotate untargeted metabolomics data from an E. coli knockout study analyzed by LC–MS. The protocols for sample extraction, data acquisition and post processing are available in the supplementary information. 493 distinct exact MS features were extracted, 30 of which were identified following a traditional annotation workflow using NIST MSPepsearch (see Additional file 2); in contrast, the EcoCyc MINE database proposed candidates for 132 of the accurate masses when searching with 5 mDa precision and with [M+]+, [M+H]+, [M+Na]+ adducts. The resulting MINE candidates were consistent with 93% of the NIST MSPepsearch results.

Positive MS spectrum (a), positive MS/MS spectrum (b) and negative MS/MS spectrum (c). The positive MS spectrum provides the mass of the precursor ion [M+H]+ = 690.5099 Da and its isotopic abundance pattern. The prominent ion in the positive MS/MS spectrum corresponds to the neutral loss of the phosphoethanolamine head group. The negative MS/MS spectrum shows the molecular ion [M−H]− as well as a pair of ions corresponding to the (16:0) and (16:1) side chains.

Further development

In addition to the existing web tools, the underlying MINE databases are accessible through free, developer-friendly APIs. Clients are available for integration into Python, Perl and JavaScript frameworks at https://github.com/JamesJeffryes/MINE-API. This API allows the databases to be integrated into existing candidate ranking algorithms and pipelines. Future versions of these databases will incorporate transformation rules for spontaneous chemical reactions of metabolites, and improved filtering and prioritization of candidate structures.

In addition to expanding the scope for the metabolome, the MINE framework also offers a pipeline for illuminating the synthesis and degradation of poorly annotated secondary metabolites. While applied very broadly to nearly all of metabolism in this study, BNICE expansions may be focused on a region of interest in the metabolic network by adjusting the starting compounds and permissible transformations in a manner similar to that recently demonstrated by Ridder et al. [27]. These targeted MINEs will integrate the generation of plausible pathways by BNICE with the tools to detect the presence of predicted pathway intermediates with accurate mass spectrometry thereby accelerating the process of proposing and evaluating hypothetical enzymatic synthesis routes for a number of compounds of interest.

Conclusions

Here we have presented Metabolic In silico Network Expansions (MINEs) that utilizes generalized biochemical transformations to propose structures for use in untargeted metabolomics. The resulting compounds are rarely found in PubChem but are structurally similar to natural products. We have demonstrated the utility of these databases for proposing correct metabolite structures that stymied a standard annotation workflow. MINE data are accessible without licensing restrictions for non-commercial users through a user-friendly web interface and API for developers in several common scripting languages.

Availability and requirements

MINE databases are freely accessible at: http://minedatabase.mcs.anl.gov and API clients are available at https://github.com/JamesJeffryes/MINE-API. There are no restrictions for Academic Use. Commercial users must obtain a license from Pathway Solutions Inc. (www.pathway.jp) and explicit permission from the authors.

Transformations of High and low Natural Product Likeness compounds.

Sample extraction, LC–MS data collection and processing protocols and repository access.

Metabolic In Silico Network Expansions

natural products

liquid chromatography–mass spectrometry

Biochemical Network Integrated Computational Explorer

Kyoto Encyclopedia of Genes and Genomes

International Union of Pure and Applied Chemistry

IUPAC International Chemical Identifier

Application Programing Interface

Answer: BackgroundIn spite of its great promise, metabolomics has proven difficult to execute in an untargeted and generalizable manner. Liquid chromatography–mass spectrometry (LC–MS) has made it possible to gather data on thousands of cellular metabolites. However, matching metabolites to their spectral features continues to be a bottleneck, meaning that much of the collected information remains uninterpreted and that new metabolites are seldom discovered in untargeted studies. These challenges require new approaches that consider compounds beyond those available in curated biochemistry databases.DescriptionHere we present Metabolic In silico Network Expansions (MINEs), an extension of known metabolite databases to include molecules that have not been observed, but are likely to occur based on known metabolites and common biochemical reactions. We utilize an algorithm called the Biochemical Network Integrated Computational Explorer (BNICE) and expert-curated reaction rules based on the Enzyme Commission classification system to propose the novel chemical structures and reactions that comprise MINE databases. Starting from the Kyoto Encyclopedia of Genes and Genomes (KEGG) COMPOUND database, the MINE contains over 571,000 compounds, of which 93% are not present in the PubChem database. However, these MINE compounds have on average higher structural similarity to natural products than compounds from KEGG or PubChem. MINE databases were able to propose annotations for 98.6% of a set of 667 MassBank spectra, 14% more than KEGG alone and equivalent to PubChem while returning far fewer candidates per spectra than PubChem (46 vs. 1715 median candidates). Application of MINEs to LC–MS accurate mass data enabled the identity of an unknown peak to be confidently predicted.ConclusionsMINE databases are freely accessible for non-commercial use via user-friendly web-tools at http://minedatabase.mcs.anl.gov and developer-friendly APIs. MINEs improve metabolomics peak identification as compared to general chemical databases whose results include irrelevant synthetic compounds. Furthermore, MINEs complement and expand on previous in silico generated compound databases that focus on human metabolism. We are actively developing the database; future versions of this resource will incorporate transformation rules for spontaneous chemical reactions and more advanced filtering and prioritization of candidate structures.Graphical abstractMINE database construction and access methods. The process of constructing a MINE database from the curated source databases is depicted on the left. The methods for accessing the database are shown on the right.Electronic supplementary materialThe online version of this article (doi:10.1186/s13321-015-0087-1) contains supplementary material, which is available to authorized users.


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:
when you hear hoofbeats , think of horses not zebras , the art of medicine is based on soundness : the higher the pretest probability , the sounder the diagnosis .
the problem with this medical aphorism is that it actively encourages the clinician to turn a deaf ear ( and a blind eye ) to the possibility of lesser known and , therefore , more easily overlooked disease states that mimic or
this report presents a case in point : a 47-year - old woman with triple - negative breast cancer on a clinical trial called primetime ( nct02518958 ) who received the anti - pd-1 inhibitor nivolumab and the experimental anticancer agent rrx-001 for 18 weeks ; initially treated for pneumonitis , an
expected autoimmune complication of nivolumab , based on the development of dyspnea and ct abnormalities . the overall clinical picture , nevertheless , was atypical , which prompted the investigating team to aggressively pursue alternate possibilities , ultimately leading to the correct diagnosis : pulmonary tumor thrombotic microangiopathy or pttm .
this example highlights the importance of exercising due diligence and not automatically jumping to conclusions with regard to the diagnosis of immune - related adverse events ( iraes ) such as pneumonitis during treatment with pd-1 or ctla-4 inhibitors .
analogous to another pulmonary medical aphorism ,  all that wheezes is not asthma , the differential diagnosis for breathlessness in the context of immune checkpoint inhibition is broader than only pneumonitis and should involve a systematic investigation for other etiologies , including the rare and rapidly progressive disorder pttm . a case history and review of the literature
are presented for pttm , which we propose to define as a paraneoplastic syndrome ( pns ) . in addition , a potential treatment option based on its pathophysiology is discussed .
the goal of cytotoxic t - lymphocyte antigen-4 ( ctla-4 ) and programmed death-1 ( pd-1 ) pathway blockade , including nivolumab approved for the treatment of melanoma , squamous - cell lung cancer   and renal cell carcinoma , is to overcome the t - cell suppression mediated by these inhibitory receptors ( fig .
1 ) ; a potential side effect of revving up the immune system to attack malignant tumors is the breaking of self - tolerance and the induction of iraes , which include rash , colitis , hepatotoxicities , endocrinopathies , and interstitial pneumonitis . as the most serious irae ,
reportedly responsible for 5 total fatalities across the spectrum of nivolumab - treated patients , the incidence of pneumonitis increased from 3.4% on a melanoma trial to 6% on a nsclc clinical trial , according to a recent bristol myers squibb press release ; this increase in incidence should raise the suspicion that increased awareness of and , consequently , narrowed focus on pneumonitis by oncologists has resulted in erroneous overdiagnosis .
the clinical manifestations of pneumonitis are protean and include fever , chills , malaise , cough , chest tightness , hypoxia , and dyspnea , while the nonspecific radiological characteristics   of ground glass opacities ( i.e. , lung opacities that do not obscure the associated vessels ) , consolidations ( i.e. , lung opacities that do obscure the associated vessels ) , and effusions also overlap with multiple other disease entities including acute respiratory distress syndrome , pneumonia , pulmonary embolism ( pe ) , congestive heart failure , and the subject of this case report , pttm .
pttm is a rare and possibly underdiagnosed   extrapulmonary sequella of metastatic cancer , specifically adenocarcinomas , formally described in 1990 by von herbay et al .
that presents as acute cor pulmonale , a maladaptive response to pulmonary hypertension , resulting in dyspnea and hypoxemia as well as ground - glass opacity ( or diffuse consolidation ) and pulmonary edema on ct [ 12 , 13 ] .
the available literature on pttm is sparse , existing mostly as case reports or small case series from japan , with a lack of higher - order treatment studies .
adenocarcinomas , and gastric cancer in particular , have been linked with pttm in these japanese case reports , which is not surprising , given the high incidence rate of gastric cancer in japan .
the etiologic mechanism of pttm is related to the intravasation of circulating tumor cells in the pulmonary vasculature ; these circulating tumor cells release a plethora of vascular remodeling factors   including vascular endothelial growth factor ( vegf ) , fibroblast growth factor , osteopontin , and platelet derived growth factor ( pdgf ) associated with abnormal endothelial proliferation , the local activation of the coagulation cascade , and the development of pulmonary hypertension from resultant stenosis of the pulmonary capillaries and arterioles ( fig .
which is only rarely diagnosed antemortem , due to a nearly uniform fatality rate , ( almost all reported patients have died within 2 weeks of dyspnea onset ) , may be suspected in cancer patients ruled out for pe who develop acute or subacute right - sided heart failure , pulmonary hypertension , and abnormal coagulation parameters .
our nivolumab - treated patient with metastatic triple - negative breast cancer who is the subject of this case report recapitulated these clinical and laboratory abnormalities almost  to a t , including , unfortunately , the time interval between onset of first symptoms and death .
while the term  textbook example is not applicable in the context of pttm , since no textbooks on it have been written ( only case reports ) , this patient 's clinical course and trajectory were indeed
textbook for pttm , even though a default diagnosis of nivolumab - induced pneumonitis was initially made .
however , in light of the atypical presentation , discussed below , and findings that did not quite
add up , the team , suspecting that pneumonitis was a red herring , decided to trust their intuition , and pursued a further work - up , which ultimately led to the diagnosis of pttm .
a 47-year - old female with rapidly progressive refractory triple - negative metastatic breast cancer , metastatic to the lungs , was treated at walter reed on a clinical trial called primetime ( nct02518958 ) where she received the anti - pd-1 inhibitor nivolumab , 3 mg / kg , every other week in combination with weekly rrx-001 , an experimental epi - immunologic agent . during her week 18 infusion on december 3 , 2015 ,
she developed fever ( 101f , 38.3c ) , headache , palpitations , and diaphoresis ; the presence of fever prompted a sepsis work - up consisting of complete blood count , routine blood culture , urinalysis , and chest x - ray in the hospital to determine the source of the fever and rule out an infection .
her labs were otherwise significant only for anemia ( hemoglobin 9.4 g / dl and hematocrit 30.6% ) and a normal leukocyte count ( 5.8  10/l ) with a high percentage of segmented neutrophils on the differential ( normal 4373% ) and no bandemia . as part of the work - up for sinus tachycardia ,
thyroid function tests were performed but thyroid - stimulating hormone ( tsh ) and free t4 were within normal limits .
her symptoms progressed to dyspnea and hypoxia the next day ( on december 4 , 2015 ) after administration of isotonic normal saline to restore volume .
chest ct , which had been clear on admission , revealed interlobular septal thickening , diffuse ground - glass attenuation , and bilateral effusions ( fig .
3 ) . a shortened list of differential diagnoses included atypical viral or bacterial pneumonia , cardiogenic pulmonary edema ( since the patient had received doxorubicin in the past ) , and treatment - induced pneumonitis . on that basis ,
fluids were withheld , the patient was discontinued from the trial and combination treatment with broad - spectrum empiric antibiotics ( vancomycin , zosyn and levaquin ) and 1 mg / kg prednisone was started .
however , the antibiotics and corticosteroids were withdrawn a week later due to worsening dyspnea and hypoxia .
a ventilation - perfusion scan was performed on december 14 , 2015 and read as low probability for pe ( no perfusion defects ) . to identify the cause of the edema ,
a transthoracic echocardiography was ordered , which revealed a normal left ventricular ejection fraction with right ventricular dilatation and severely reduced right ventricular function secondary to pulmonary hypertension ( a pressure > 50 mm hg is generally accepted as severe   and her estimated right ventricular systolic pressure exceeded 65 mm hg ) .
probnp was also drawn ; it was elevated at 3,226.0 pg / ml , indicative of heart failure ( 5125 nl range ) .
the presence of acute cor pulmonale pointed away from pneumonitis and strongly suggested three rare possibilities : ( 1 ) occlusion of the pulmonary vessels from microscopic tumor emboli ( also known as pulmonary tumor embolism ) , leading to pulmonary arterial hypertension ( pah ) ; ( 2 ) pttm , a related but even rarer pulmonary vasculopathy , associated with adenocarcinomas of the stomach , pancreas , breast , lung , and liver , in which minute tumor emboli in the peripheral pulmonary arteries damage the vascular endothelium , leading to accelerated coagulation   and pah , and ( 3 ) pulmonary venous occlusive disease , the venous form of pah [ 19 , 20 ] , due to fibrous occlusion of the post - capillary vessels , which may or may not be associated with an autoimmune process   ( the association is only anecdotal ) . the pulmonary hypertension was managed with diuretics ( furosemide 40 mg i.v . ) , bosentan 62.5 mg , and oxygen ( 2 liters by nasal cannula ) as well as intravenous epoprostenol , norepinephrine , and dobutamine ; however , no improvement was observed .
since a lung biopsy carried too much risk , the patient was catheterized ; pulmonary artery catheter - derived blood samples were negative for the presence of tumor emboli .
blood was also drawn for the measurement of coagulation parameters , since pttm is associated with coagulopathy .
the results were as follows : elevated d - dimer ( or serum fibrin degradation products ) of 1.04 g / ml ( normal < 0.5 g / ml ) and a prolonged prothrombin time of 16.5 s ( normal 1114 s ) .
platelets were never outside of the normal range . the partial thromboplastin time and thrombin time
were both prolonged at 67.2 s ( normal 2535 s ) and 48 s ( normal 1420 s ) , respectively , due to treatment with a heparin gtt for potential venous clots . in the setting of adenocarcinoma , pulmonary hypertension , and a negative ct and ventilation - perfusion scan for pe ,
pttm is distinct from simple embolic obstruction because it is characterized by ( 1 ) the systemic activation of coagulation with the generation of intravascular fibrin and the consumption of procoagulants , leading to a disseminated intravascular coagulation - like picture , present in this case and ( 2 ) remodeling of the pulmonary vasculature   due to expression of vegf and pdgf from embolic tumor cells ( see fig .
2 ) . based on the proposed involvement of vegf and pdgf in the pathogenesis of pttm , the primary investigator planned to treat the patient with sunitinib , which dually inhibits vegf and pdgf pathways
the observations in this case study strongly suggest that pd-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default , requiring a thorough work - up to rule out conditions that may mimic it , including pe , atypical pneumonia , pulmonary venous occlusive disease , congestive heart failure , and pttm . in the case of this acutely dyspneic patient , who initially received a
 pneumonitis by default diagnosis , pttm was only identified when her shortness of breath deteriorated despite treatment with high dose steroids , alerting the principal investigator to the possibility of heart failure , which led to further investigation .
the treating oncologist must be alert to the development or presence of pns , defined as a  pathology caused by tumor cells , which systematically produce a large amount of hormones , growth factors , cytokines and a variety of specific symptoms .
these include : cushing syndrome , carcinoid syndrome , dermatomyositis - polymyositis , myasthenia gravis and syndrome of inappropriate antidiuretic hormone . to this list
, we would add pttm , since its pathogenesis is related to the local release of mitogenic factors associated with vascular remodeling and coagulopathy . as a heretofore unrecognized pns
, pttm requires background knowledge and a high index of clinical suspicion . in the absence of a biopsy ,
even though the case under discussion was refractory to standard therapies and the patient died before sunitinib , the multitargeted tyrosine kinase selective for vegf and pdgf receptors , could be started , it is reasonable to assume that early diagnosis and treatment would have resulted in a better outcome .
the patient described in this case report has given his informed consent as part of the primetime clinical study ( nct02518958 ) .
this study protocol has been approved by the walter reed national military medical center institutional review board .

Answer:
a case report of a 47-year - old woman with triple - negative breast cancer on a clinical trial called primetime ( nct02518958 ) who received the anti - pd-1 inhibitor nivolumab and the experimental anticancer agent rrx-001 is presented . although initially diagnosed and treated for anti - pd-1-induced pneumonitis , clinical and radiological abnormalities triggered further investigation , leading to the diagnosis of pulmonary tumor thrombotic microangiopathy ( pttm ) .
 this example highlights the importance of exercising due diligence in determining immune - related adverse events and suggests that pd-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default .
 a case history and review of the literature are presented for pttm , which we propose to define as a paraneoplastic syndrome .


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:
myofascial pain syndrome ( mps ) can be caused by frequent muscle or fascial stiffness as a
 result of prolonged tension and muscle fatigue due to repetitive stress of muscles or
 overuse of particular muscles1 , 2 .
mps activates trigger points in 54% of women and 45% of men , and is regarded as
 the most common cause of pain in the musculoskeletal system3 . in particular , the upper trapezius requires head movement according
 to the direction of view , but it can be vulnerable to damage when the hands and arms are
 used repetitively in work that requires precise control4,5,6 . once myofascial trigger points are activated , changes in the
 structural characteristics and contraction function of the muscle will occur .
the most
 distinctive changes are taut bands , tender nodules , referred pain , local twitch response ,
 muscle weakness , and restricted range of motion3 .
to evaluate the contraction function of skeletal muscle , various methods can be used . among
 them ,
surface electromyography ( emg ) analyzes functional changes in muscle by measuring
 quantitative changes in motor unit action potential that is activated by muscle
 contraction7 , 8 .
surface emg is widely used in kinetic analysis to diagnose normal
 or abnormal function in muscles and nerves according to amplitude and frequency9 .
it has several advantages , as it is
 noninvasive and convenient , and can perform measurement even during dynamic motion10 , 11 .
although a number of clinical reports on the pathologic mechanisms or clinical diagnosis
 and treatment of mps can be found , few studies have been conducted on the changes in
 contraction function in myofascial trigger point areas or on the electrophysiological
 characteristics and neuromuscular physiological information .
this study aimed to compare the
 electrophysiological characteristics of normal muscles versus muscles with latent or active
 myofascial trigger points , and to identify their neuromuscular physiological
 characteristics , in order to provide a quantitative evaluation of mps and clinical
 foundational data for its diagnosis .
this study was approved by the
 research agency , and all participants provided written informed consent .
subjects were
 selected among those with no known neurologic disease , no regular exercise habit , and no
 drug use that could affect the experimental result .
subjects in the active myofascial trigger point group were those diagnosed with mps
 by a physician and whose clinical characteristics were pain in the upper trapezius during
 rest , taut bands , tender nodules , referred pain , local twitch response , and muscle weakness .

subjects in the latent myofascial trigger point group were those not diagnosed with mps but
 who felt tenderness when the upper trapezius was stimulated .
mean age , height , and weight , respectively , were 23.27
  4.21  years , 172.32  8.44  cm , and 64.14  6.54  kg in the active trigger point group ; 23.74
  6.47  years , 174.76  6.22  cm , and 66.74  5.74  kg in the latent trigger point group ; and
 24.17  3.14  years , 171.21  9.64  cm , and 63.44  7.51  kg in the control group . to measure maximum voluntary isometric contraction ( mvic ) , the shoulders and heads of the
 subjects were firmly fixed and pulled as the dynamometer as maximum power , thereby measuring
 mvic against the upper trapezius .
endurance time was measured from the start of mvic to a
 50% reduction in contraction force .
median frequency ( mdf ) was measured by using emg at the
 muscle belly of the upper trapezius during mvic .
muscle fatigue index was calculated by
 obtaining the mdf at a section where the mvic force was reduced from 100% to 50% , and remove
 the 50% mdf from 100% mdf was divided into 100% mdf .
the sampling rate for the surface emg
 signal was set at 1,000  hz , and the frequency band filter was set at 20 to 450  hz , using one
 channel .
storage and analysis of the emg signals was performed using acqknowledge 3.8.1
 ( biopac systems , goleta , ca , usa ) .
the average of three measurements was calculated and used
 in the analyses ; 10 minutes of rest was given between measurements to prevent muscle
 fatigue .
statistical analyses were performed using spss version 18.0 for windows ( spss , inc .

one - way analysis of variance was conducted to examine differences among
 groups with respect to the measured items , while the tukey test was conducted for post hoc
 analysis .
there were no significant differences in mvic or endurance time among the three groups .
 however , mdf was significantly different among all three groups ( p < 0.05 ) ( table 1table 1.comparison of mvic , et , mdf , and fi among the three groupsgroup a ( n = 30)group b ( n = 30)group c ( n = 30)post hocmvic ,  kg19.811.5 * 22.19.423.510.2/et , s48.59.749.510.251.28.8/mdf ,  hz102.521.488.523.184.517.4a <
cmfi0.150.070.080.040.060.04a < cdata are presented as mean  sd . * significant difference among the three groups ( p
 < 0.05 ) .
group a : active myofascial trigger points ; group b : latent myofascial
 trigger points ; group c : control .
et : endurance time ; mdf : median frequency ; mfi :
 muscle fatigue index ; mvic : maximal voluntary isometric contraction ) .
tukey post hoc results showed that the active myofascial
 trigger point group was significantly different from the control group .
muscle fatigue index
 also was significantly different among all three groups ( p < 0.05 ) ( table 1 ) .
tukey post hoc results showed
 that the active myofascial trigger point group was significantly different from the control
 group .
data are presented as mean  sd . * significant difference among the three groups ( p
 < 0.05 ) .
group a : active myofascial trigger points ; group b : latent myofascial
 trigger points ; group c : control .
et : endurance time ; mdf : median frequency ; mfi :
 muscle fatigue index ; mvic : maximal voluntary isometric contraction
this study aimed to measure mvic , endurance , mdf , and muscle fatigue index of normal
 muscles versus muscles with latent or active myofascial trigger points , thereby identifying
 the neuromuscular physiological characteristics of muscles with active myofascial trigger
 points and providing clinical foundational data that are applicable for the quantitative
 evaluation and diagnosis of mps .
surface emg , which was used to evaluate the functionality of trigger points in this study ,
 is nonintrusive and convenient ; thus , it is widely used in studies on the functional
 characteristics of muscle , by analyzing the electrical activity of muscle .
the results of
 mdf according to surface emg show changes in recruitment of fast - twitch muscle fibers and
 conduction velocity of motor unit action potential12 .
in addition , increases in mdf reflect recruitment of type ii
 fibers , and muscle fatigue index can be analyzed according to the relationship between type
 ii fibers and mdf13 , 14 . in the present experiment ,
mdf was significantly higher in the
 active trigger point muscles than in normal muscles .
the above results indicate that as
 trigger points were activated , recruitment of motor unit action potential of type ii fibers
 also increased .
in addition , muscle fatigue index also increased due to the increased
 distribution of type ii fibers .
however , mvic was lower in active trigger point muscles than
 in normal muscles .
although a high correlation between muscle strength and mdf has been
 reported15 , 16 , the same correlation was not found in this study .
this result was
 due to increased recruitment of motor unit action potential of type ii fibers in active
 trigger point muscles , which more easily induced muscle fatigue as a physiological
 phenomenon , thereby reducing muscle strength .
in other words , the greater the fatigue , the
 weaker the muscle strength17 ; endurance
 also was decreased due to muscle weakening .
therefore , this study s results will be effective in complementing the physical therapy
 diagnosis of mps  which , until now , has focused on physical examination only  by understanding
 not only the usefulness of electrophysiological analysis in mps diagnosis , but also the
 neuromuscular physiological characteristics of active trigger point muscles .

Answer:
[ purpose ] this study compared the differences in electrophysiological characteristics of
 normal muscles versus muscles with latent or active myofascial trigger points , and
 identified the neuromuscular physiological characteristics of muscles with active
 myofascial trigger points , thereby providing a quantitative evaluation of myofascial pain
 syndrome and clinical foundational data for its diagnosis . [ subjects ] ninety adults in
 their 20s participated in this study .
 subjects were equally divided into three groups : the
 active myofascial trigger point group , the latent myofascial trigger point group , and the
 control group . [ methods ]
 maximum voluntary isometric contraction ( mvic ) , endurance , median
 frequency ( mdf ) , and muscle fatigue index were measured in all subjects .
 [ results ] no
 significant differences in mvic or endurance were revealed among the three groups .

 however , the active trigger point group had significantly different mdf and muscle fatigue
 index compared with the control group . [ conclusion ] given that muscles with active
 myofascial trigger points had an increased mdf and suffered muscle fatigue more easily ,
 increased recruitment of motor unit action potential of type ii fibers was evident .

 therefore , electrophysiological analysis of these myofascial trigger points can be applied
 to evaluate the effect of physical therapy and provide a quantitative diagnosis of
 myofascial pain syndrome .