bluuebunny/crossref_metadata_2025_split huggingface dataset:
Merging perspectives: genotype‐directed molecular therapy for hereditary diffuse gastric cancer (HDGC) and E‐cadherin–EGFR crosstalk
Authors: Li Dandan , Lo Winifred , Rudloff Udo 
Published: February 2018

AbstractHereditary diffuse gastric cancer is a cancer predisposition syndrome associated with germline mutations of the E‐cadherin gene (CDH1; NM_004360). Male CDH1 germline mutation carriers have by the age of 80 years an estimated 70% cumulative incidence of gastric cancer, females of 56% for gastric and of 42% for lobular breast cancer. Metastatic HDGC has a poor prognosis which is worse than for sporadic gastric cancer. To date, there have been no treatment options described tailored to this molecular subtype of gastric cancer. Here we review recent differential drug screening and gene expression results in c.1380del CDH1‐mutant HDGC cells which identified drug classes targeting PI3K (phosphoinositide 3‐kinase), MEK (mitogen‐activated protein kinase), FAK (focal adhesion kinase), PKC (protein kinase C), and TOPO2 (topoisomerase II) as selectively more effective in cells with defective CDH1 function. ERK1‐ERK2 (extracellular signal regulated kinase) signaling measured as top enriched network in c.1380delA CDH1‐mutant cells. We compared these findings to synthetic lethality and pharmacological screening results in isogenic CDH1−/− MCF10A mammary epithelial cells with and without CDH1 expression and current knowledge of E‐cadherin/catenin–EGFR cross‐talk, and suggest different rationales how loss of E‐cadherin function activates PI3K, mTOR, EGFR, or FAK signaling. These leads represent molecularly selected treatment options tailored to the treatment of CDH1‐deficient familial gastric cancer.
The IRB structure and medical research reform
Authors: Babyar Julie 
Published: February 2018

AbstractOptimal Independent Review Board (IRB) structure encompasses ongoing process improvement, ethics policies and continuous relationship building, all sound in evidence. With optimal IRB structure, a global research infrastructure will flourish. Evidence for IRB structure must be detailed and expert operational recommendations should guide. Too, health service research oversight should assist in funding as well as collaboration. A national and international research agenda will only benefit from best operations, guided in evidence, supported in best regulatory and research leadership practice. It is imperative that the IRB structure be reformed.
FGF2-dependent mesenchyme and laminin-111 are niche factors in salivary gland organoids
Authors: Hosseini Zeinab F. , Nelson Deirdre A. , Moskwa Nicholas , Sfakis Lauren M. , Castracane James , Larsen Melinda 
Published: February 2018

ABSTRACT
Epithelial progenitor cells are dependent upon a complex 3D niche to promote their proliferation and differentiation during development, which can be recapitulated in organoids. The specific requirements of the niche remain unclear for many cell types, including the proacinar cells that give rise to secretory acinar epithelial cells that produce saliva. Here, using ex vivo cultures of E16 primary mouse submandibular salivary gland epithelial cell clusters, we investigated the requirement for mesenchymal cells and other factors in producing salivary organoids in culture. Native E16 salivary mesenchyme, but not NIH3T3 cells or mesenchymal cell conditioned medium, supported robust protein expression of the progenitor marker Kit and the acinar/proacinar marker AQP5, with a requirement for FGF2 expression by the mesenchyme. Enriched salivary epithelial clusters that were grown in laminin-enriched basement membrane extract or laminin-111 together with exogenous FGF2, but not with EGF, underwent morphogenesis to form organoids that displayed robust expression of AQP5 in terminal buds. Knockdown of FGF2 in the mesenchyme or depletion of mesenchyme cells from the organoids significantly reduced AQP5 levels even in the presence of FGF2, suggesting a requirement for autocrine FGF2 signaling in the mesenchyme cells for AQP5 expression. We conclude that basement membrane proteins and mesenchyme cells function as niche factors in salivary organoids.
Visceral leishmaniasis cyclical trends in Bihar, India – implications for the elimination programme.
Authors: Deb Rinki M , Stanton Michelle C , Foster Geraldine M , Das Gupta Rudra K , Roy Nupur , Das Pradeep , Dhariwal Akshay C , Coleman Michael 
Published: February 2018

Background:Visceral leishmaniasis (VL) is a vector-borne disease of public health importance in India, with the highest burden of disease in the states of Bihar, Jharkhand, West Bengal and Uttar Pradesh. The disease is currently targeted for elimination (annual incidence to less than one per 10,000 population) using indoor residual spraying, active case detection and treatment. Historically the disease trend in India has been regarded as cyclical with case resurgence characteristically occurring every 15 years. Understanding this pattern is essential if the VL elimination gains are to be sustained. To better understand the cyclical trends, annual climatic indicators including rainfall, temperature and humidity over time were compared with annual VL case incidence data. Methods:Annual climate data (rainfall, average and maximum temperature and specific humidity) from 1956-2004 were used to identify potential factors influencing VL incidence. Months relevant to the VL life-cycle were identified and defined (Monsoon, Sand-fly Peak, Pre-Sand-fly Peak and Annual) for analysis. The Kruskall-Wallis test was used to determine significant difference between categorical rainfall and VL incidence, whilst univariate negative binomial regression models were used to determine predictors of disease incidence.Results:The negative binomial regression model showed statistically significant associations (p <0.05) for VL incidence and maximum temperature, and average temperature, when considering annual and pre-sand fly peak time periods. No other associations between humidity, rainfall or temperature and VL incidence were detected (all values p >0.05). Conclusion:The VL programme in Bihar has made significant progress in adopting best practices for improved treatment and vector control, with the aim to achieve VL elimination. However, open access granular programme data for indoor residual spray activities and case detection is required to fully understand the role of climate in disease transmission and potential resurgence.
Dynamic Atomic Congestion Games with Seasonal Flows
Authors: Scarsini Marco , Schröder Marc , Tomala Tristan 
Published: February 2018

We propose a model of discrete time dynamic congestion games with atomic players and a single source-destination pair. The latencies of edges are composed of free-flow transit times and possible queuing time due to capacity constraints. We give a precise description of the dynamics induced by the individual strategies of players and of the corresponding costs, either when the traffic is controlled by a planner, or when players act selfishly. In parallel networks, optimal and equilibrium behavior eventually coincide, but the selfish behavior of the initial players has consequences that cannot be undone and are paid by all future generations. In more general topologies, our main contributions are threefold. First, we illustrate a new dynamic version of Braess paradox: the presence of initial queues in the network may decrease the long-run costs in equilibrium. This paradox can arise in networks for which no Braess paradox was previously known. Second, we show that equilibria are not unique and can induce very different long-run costs. In particular, we give a sequence of networks such that the price of stability is equal to 1, and the price of anarchy is equal to n − 1, where n is the number of vertices. Third, we propose an extension to model seasonalities by assuming that departure flows fluctuate periodically over time. We introduce a measure that captures the queues induced by periodicity of inflows. For optimal and equilibrium flows in parallel networks this measure is the increase in cost compared to uniform departures. The electronic companion is available at https://doi.org/10.1287/opre.2017.1683 .
THE BONE BLOCK METHOD FOR RECURRENT DISLOCATION OF THE SHOULDER JOINT
Authors: Palmer Ivar , WideÌn Anders , Sweden Stockholm 
Published: February 2018

The purpose of this paper is to call attention to the anterior bone block method of Hybbinette-Eden for recurrent dislocation of the shoulder joint. 1. The operative technique is not difficult, and the after-treatment is short and relatively agreeable for the patient. 2. Sixty of our own cases are described, with four recurrences. The recurrences all occurred as the result of real trauma. In a total of 128 Scandinavian cases there were eight recurrencesâthat is 6Â·3 per cent. 3. In our opinion, based on the observations of radiography, arthrography, and operation, it is the compression fracture of the head of the humerus which deserves the name "essential lesion." Destruction of the anterior rim of the glenoid may be very slight, or entirely lacking. No false joint cavity or rupture big enough to receive the head of the humerus was ever observed by arthrography or by inspection during operative exploration. Recurrent dislocation is an intracapsular subluxation, which occurs when the anterior rim of the glenoid slides into the hollow in the humeral head.
FATIGUE FRACTURES OF THE FIBULA
Authors: Burrows H. Jackson 
Published: February 2018

1. A hope expressed in 1940, that further cases of spontaneous fracture of the lowest third of the apparently normal fibula would be described, has been fulfilled. The literature is here reviewed. Five further personal cases are added. 2. The clinical and radiographic features, diagnosis, treatment and results are considered in the light of the information so far available. Special note is made of misleading freedom of ankle and tarsal movements and the occasional absence of tenderness. 3. It is established that fractures of the lowest third occur particularly in two groups of subjects: 1) young male runners and skaters; 2) active and hard-pressed women of middle age and over. 4. In male runners and skaters the fracture usually occurs through slender, mainly cortical bone, two inches or more above the tip of the lateral malleolus; in middle-aged women the fracture is usually distal to the interosseous ligament through thicker, mainly cancellous bone, one and a half inches from the tip of the lateral malleolus. 5. The most convenient name for both groups of fractures in the lowest third is low fatigue fracture of the fibula. 6. A review of the literature of fatigue fracture of the uppermost third of the fibula shows that it is very often precipitated by jumping. The most convenient name for it is high fatigue fracture of the fibula. 7. Like all clinical classifications this distinction between low and high fractures has exceptions (a low fracture of one fibula in a runner was followed later by a high fracture of the other; most military fractures were high, but a few may have occurred at other levels). 8. Fatigue fracture of the fibula, high or low, may be bilateral. 9. A fracture similarly situated to the high fatigue fracture of the fibula has been frequent in parachute schools. It is a speculative possibility that military and parachutist fractures of the upper third of the fibula indicate the link between true fatigue fractures (as exemplified by march fractures with minimal trauma often repeated) and purely traumatic fractures (with adequate trauma applied once only).
POSITIVE PRESSURE IN ARTHRODESIS OF THE KNEE JOINT
Authors: Charnley John C. 
Published: February 2018

1. The technique of compression-arthrodesis of the knee joint is described. 2. Fifteen consecutive cases are reported in which clinical union was detected at the first inspection from twelve days to six weeks after operation. By this method the total period of disability is reduced to three months. 3. Three mechanical factors which might be responsible for this very early clinical union are examined: compression is believed to be the main factor, although fixation is also important. 4. A fallacy is exposed in the use of bone grafts for arthrodesis of the knee; the graft is less osteogenic than the substance of the bones which form the joint, and it provides inefficient internal fixation. 5. A theory is suggested that compression, even in the presence of slight movement, acts by producing a fixed "hinge" without shearing movement; at this point a bridgehead of flexible osteoid tissue is established in which ossification inevitably takes place despite slight bending movement. 6. A second theory is suggested that high compression forces stimulate early union by liberating bone salts at points of maximum pressure through the action of osteoclasts, and that the local excess of bone salts is redeposited under cellular activity within a range of a few millimetres where there is no pressure.
TRACTION INJURIES OF THE BRACHIAL PLEXUS IN ADULTS
Authors: Barnes Roland 
Published: February 2018

1. Sixty-three traction injuries of the brachial plexus in adults are reviewed. Most of the patients were seen at regular intervals for more than three years after injury. 2. The mechanism of injury is described. Forcible separation of the head and shoulder is the essential factor, but the type of lesion is determined by the position of the upper limb at the time of the accident. 3. In traction injuries the main damage is intraneural, and the lesions are of considerable extent. Extraneural scarring is a conspicuous feature of old injuries, but it does not cause any damage to uninjured parts of the plexus. 4. The prognosis of each type of lesion of the plexus is discussed. Satisfactory recovery occurs in most lesions of the upper three roots. Degenerative lesions of the whole plexus never recover completely. Cases with Horner's syndrome always have severe residual paralysis. 5. Conservative treatment is advocated for traction injuries of the plexus and evidence is cited against early or late operations on the plexus. Reconstructive surgical procedures are sometimes indicated.
SCOLIOSIS WITH PARAPLEGIA
Authors: McKenzie K. G. , Dewar F. P. 
Published: February 2018

1. Five cases of scoliosis with paraplegia are reported, and thirty-six comparable cases from the literature are reviewed. These forty-one cases have been studied with the object of determining the etiology of scoliosis, the reason why cord compression sometimes develops, and the results of conservative and operative treatment of such compression of the cord. 2. The cause of paraplegia is nearly always compression of the spinal cord by the dura, which, in severe scoliosis, is under longitudinal tension because of its firm attachment to the foramen magnum above and the sacrum below. Such tension, resisting displacement of the spinal cord from the straight line, may be shown to cause incomplete spinal block even when there is no paralysis. 3. When paralysis occurs it usually develops during the years of most rapid growth, the tight dura being unable to accommodate itself to the rate of growth of the spinal column; cord compression is probably increased by narrowing of the dural sac by rotational displacement. 4. The most striking results have been secured by laminectomy with section of the dura and sometimes division of dentate ligaments and tight nerve roots. After such division there is evidence of release of compression: the cord herniates through the dural slit; and spinal pulsation returns. 5. It is important to control bleeding in order to avoid post-operative compression by blood clot; and to prevent leakage of cerebro-spinal fluid through the arachnoid. 6. It is unwise to perform spinal fusion at the same time as decompression because it increases the danger of haematoma formation. Moreover the improvement gained by decompression is maintained even if no fusion of the spine is performed. 7. Conservative treatment of scoliosis with paraplegia should not be continued for long periods unless there is evidence of early and progressive improvement because prolonged compression causes irreversible changes in the cord. 8. In three cases, paraplegia was not due to dural compression: one turned out later to be a case of syringomyelia; one, reported by Heyman, was due to the pressure of a bone spur; and one, reported in this series, was due to a congenital tight band of developmental origin which might have caused the scoliosis as well as the paralysis, and in which, after resection of the band, recovery from the paralysis was complete.
POLYOSTOTIC FIBROUS DYSPLASIAâALBRIGHT'S SYNDROME
Authors: Warrick C. K. 
Published: February 2018

1. Four cases of polyostotic fibrous dysplasia are presented. 2. All are males, all show cutaneous pigmentation, and in two there has been precocious puberty. 3. The literature has been reviewed, and present conceptions of the pathology and etiology of the disease have been discussed. 4. The dysplasia if often confused with parathyroid osteodystrophy and sometimes the parathyroid glands are needlessly explored. This confusion should not arise if it is remembered that no general skeletal decalcification, and no constant changes in the blood calcium or phosphorus, occur in polyostotic fibrous dysplasia. The radiographic appearances of healing parathyroid osteodystrophy are, however, indistinguishable. 5. No effective therapy has been discovered for this disease. Pathological fractures and deformities may require treatment.
TROCHANTERIC FRACTURES OF THE FEMUR
Authors: Murray R. C. , Frew J. F. M. 
Published: February 2018

1. A series of one hundred consecutive cases of trochanteric fractures treated conservatively by the authors has been reviewed. 2. Analysis of the results obtained and a study of the relevant literature has led us to the firm conclusion that the routine treatment of this group of fractures should be conservative. 3. Internal fixation should be reserved for those exceptional cases where traction is found to be inadequate: this is specially likely in cases associated with an upper motor neuron lesion, where difficulty is experienced in maintaining reduction owing to muscle spasm. 4. The basal type of fracture offers a special problem because it merges imperceptibly into that of the true transcervical fracture. No difficulty has been experienced in this series in the conservative treatment of such fractures, but we recognise that they might well be regarded as a variety of transcervical fracture and treated by nailing in order to avoid the risk of non-union.
THE FATE OF VOLUNTARY MUSCLE AFTER VASCULAR INJURY IN MAN
Authors: Bowden Ruth E. M. , Gutmann E. 
Published: February 2018

1. Biopsies of muscle were taken during the course of operation from sixteen patients with vascular injuries to the limbs. Three types of histological change were found. 2. In the first, there was massive necrosis of muscle fibresâa group of cases in which there had always been serious damage to the main artery of the limb or to the vessel supplying the affected muscles. 3. In the second type there was dense interstitial fibrosis, the muscle fibres sometimes being normal and sometimes showing necrosis or denervationâa group of cases in which the vascular injury varied from severance of the vessels by gunshot wounds to trivial damage, causing slow haemorrhage within fascial-bound spaces. 4. The third type showed scattered foci of necrosis together with patchy interstitial fibrosisâdue to the pressure of tight plasters, crushing of the limb, fractures with arterial contusion, or slow haemorrhage or extravascular transfusion within fascial planes. The rise of tension within the muscles was probably sufficient to occlude the smaller arterioles with resultant patchy necrosis. 5. The vulnerability of certain muscles to vascular damage is partly related to the intramuscular vascular pattern, of which five types have been described. 6. In ischaemic muscles the intramuscular nerve trunks may be normal or they may show evidence of degeneration or necrosis; but in favourable circumstances there may be regeneration of axons. 7. In some cases there was evidence of regeneration of muscle fibres in man, the regeneration being dependent to some extent upon the efficiency of intramuscular anastomoses. 8. The prognosis, in cases of ischaemia of human voluntary muscle, depends upon the extent and the reversibility of damage to both muscle and nerve fibres and upon the extent of regeneration of muscle fibres.
THE PAINFUL SHOULDER Significance of Radiographic Changes in the Upper End of the Humerus
Authors: Harrison Stewart H. 
Published: February 2018

1. Degenerative lesions of the shoulder joint can often be demonstrated radiographically before there is actual rupture of the musculo-tendinous cuff. 2. The characteristic pathological, clinical and radiographic features of degenerative lesionsare described. 3. All injuries of the shoulder joint, however trivial, occurring in patients over middle age, should be studied carefully by radiographic examination. 4. In injuries of the shoulder joint the presence of a degenerative lesion prolongs the duration of symptoms, and the prognosis is less satisfactory than when there is no radiographic evidence of abnormality.
LEÌRI'S PLEONOSTEOSIS, CARPAL TUNNEL COMPRESSION OF THE MEDIAN NERVES AND MORTON'S METATARSALGIA
Authors: Watson-Jones Reginald 
Published: February 2018

1. LeÌri's pleonosteosis is characterised by broadening and deformity of the thumbs and great toes, flexion contracture of the interphalangeal joints, limited movement of other joints, and often a Mongoloid facies. Four such cases are described. 2. A review of the twenty reports in the literature, and the cases now described, shows that the deformities are due to capsular contracture rather than deformity of bone. 3. In one patient there was striking evidence of fibro-cartilaginous thickening of the anterior carpal ligaments. It is suggested that the primary pathological change in pleonosteosis may be in the joint capsules rather than in the epiphyses. 4. The patient with thickening of the anterior carpal ligaments had bilateral median palsy from carpal tunnel compression. 5. The causes of carpal tunnel compression of the median nerve are reviewed. Acute compression may be due not only to dislocation of the semilunar bone but to haemorrhage in the palm. Late compression by bone may occur twenty to fifty years after injury. Late compression without bone abnormality has been attributed to occupational stress, but it is suggested that pathological thickening of the anterior carpal ligament may be the cause. 6. The patient with pleonosteosis and bilateral median palsy had also bilateral Morton's metatarsalgia with large digital neuromata. 7. Plantar digital neuritis has already been shown to be an ischaemic nerve lesion preceded by degenerative changes in the digital artery. The significance of the fibrous tunnel through which the artery passes to reach the digital cleft is considered.
DYSCHONDROPLASIA WITH HAEMANGIOMATA (MAFFUCCI'S SYNDROME)
Authors: Strang Christopher , Rannie Ian 
Published: February 2018

1. Maffucci's syndrome consists of dyschondroplasia (Ollier's disease) in association with cavernous haemangiomata and phlebectasia. Twenty-two cases have hitherto been described. 2. A further case is recorded with autopsy findings showing the characteristic features of the syndrome. Death was caused by a chondrosarcoma of the sphenoid, which led to subarachnoid haemorrhage, cranial nerve palsies, crossed hemiplegia and cavernous sinus thrombosis with almost total pituitary necrosis.