bluuebunny/crossref_metadata_2025_split huggingface dataset:
Target organ damage and incident type 2 diabetes mellitus: the Strong Heart Study
Authors: de Simone Giovanni , Wang Wenyu , Best Lyle G. , Yeh Fawn , Izzo Raffaele , Mancusi Costantino , Roman Mary J. , Lee Elisa T. , Howard Barbara V. , Devereux Richard B. 
Published: May 2017

Abstract
Background
Recent analyses in a registry of hypertensive patients suggested that preceding left ventricular (LV) hypertrophy (LVH) and/or carotid atherosclerosis are associated with incident type 2 diabetes, independent of confounders. We assess the relation between prevalent cardio-renal target organ damage (TOD) and subsequent incident type 2 diabetes in a population-based study with high prevalence of obesity.

Methods
We selected 2887 non-diabetic participants from two cohorts of the Strong Heart Study (SHS). Clinical exam, laboratory tests and echocardiograms were performed. Adjudicated TODs were LVH, left atrium (LA) dilatation, and high urine albumin/creatinine ratio (UACR). Multivariable logistic regression models were used to identify variables responsible for the association between initial TODs and incident diabetes at 4-year follow-up (FU).

Results
After 4 years, 297 new cases of diabetes (10%) were identified, 216 of whom exhibited baseline impaired fasting glucose (IFG, 73%, p < 0.0001). Participants developing type 2 diabetes exhibited higher inflammatory markers, fat-free mass and adipose mass and higher prevalence of initial LVH and LA dilatation than those without (both p < 0.04). In multivariable logistic regression, controlling for age, sex, family relatedness, presence of arterial hypertension and IFG, all three indicators of TOD predicted incident diabetes (all p < 0.01). However, the effects of TOD was offset when body fat and inflammatory markers were introduced into the model.

Conclusions
In this population-based study with high prevalence of obesity, TOD precedes clinical appearance of type 2 diabetes and is related to the preceding metabolic status, body composition and inflammatory status.
Trial registration Trial registration number: NCT00005134, Name of registry: Strong Heart Study, URL of registry: https://clinicaltrials.gov/ct2/show/NCT00005134, Date of registration: May 25, 2000, Date of enrolment of the first participant to the trial: September 1988
Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials
Authors: Lahuerta Juan-Jose , Paiva Bruno , Vidriales Maria-Belen , Cordón Lourdes , Cedena Maria-Teresa , Puig Noemi , Martinez-Lopez Joaquin , Rosiñol Laura , Gutierrez Norma C. , Martín-Ramos María-Luisa , Oriol Albert , Teruel Ana-Isabel , Echeveste María-Asunción , de Paz Raquel , de Arriba Felipe , Hernandez Miguel T. , Palomera Luis , Martinez Rafael , Martin Alejandro , Alegre Adrian , De la Rubia Javier , Orfao Alberto , Mateos María-Victoria , Blade Joan , San-Miguel Jesus F. ,   on behalf of the GEM (Grupo Español de Mieloma)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group
Published: May 2017

Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of “operational cure” was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with MM.
Clonal History and Genetic Predictors of Transformation Into Small-Cell Carcinomas From Lung Adenocarcinomas
Authors: Lee June-Koo , Lee Junehawk , Kim Sehui , Kim Soyeon , Youk Jeonghwan , Park Seongyeol , An Yohan , Keam Bhumsuk , Kim Dong-Wan , Heo Dae Seog , Kim Young Tae , Kim Jin-Soo , Kim Se Hyun , Lee Jong Seok , Lee Se-Hoon , Park Keunchil , Ku Ja-Lok , Jeon Yoon Kyung , Chung Doo Hyun , Park Peter J. , Kim Joon , Kim Tae Min , Ju Young Seok 
Published: May 2017

Purpose Histologic transformation of EGFR mutant lung adenocarcinoma (LADC) into small-cell lung cancer (SCLC) has been described as one of the major resistant mechanisms for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the molecular pathogenesis is still unclear. Methods We investigated 21 patients with advanced EGFR-mutant LADCs that were transformed into EGFR TKI–resistant SCLCs. Among them, whole genome sequencing was applied for nine tumors acquired at various time points from four patients to reconstruct their clonal evolutionary history and to detect genetic predictors for small-cell transformation. The findings were validated by immunohistochemistry in 210 lung cancer tissues. Results We identified that EGFR TKI–resistant LADCs and SCLCs share a common clonal origin and undergo branched evolutionary trajectories. The clonal divergence of SCLC ancestors from the LADC cells occurred before the first EGFR TKI treatments, and the complete inactivation of both RB1 and TP53 were observed from the early LADC stages in sequenced tumors. We extended the findings by immunohistochemistry in the early-stage LADC tissues of 75 patients treated with EGFR TKIs; inactivation of both Rb and p53 was strikingly more frequent in the small-cell–transformed group than in the nontransformed group (82% v 3%; odds ratio, 131; 95% CI, 19.9 to 859). Among patients registered in a predefined cohort (n = 65), an EGFR mutant LADC that harbored completely inactivated Rb and p53 had a 43× greater risk of small-cell transformation (relative risk, 42.8; 95% CI, 5.88 to 311). Branch-specific mutational signature analysis revealed that apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)–induced hypermutation was frequent in the branches toward small-cell transformation. Conclusion EGFR TKI–resistant SCLCs are branched out early from the LADC clones that harbor completely inactivated RB1 and TP53. The evaluation of RB1 and TP53 status in EGFR TKI–treated LADCs is informative in predicting small-cell transformation.
The New Genomics: What Molecular Databases Can Tell Us About Human Population Variation and Endocrine Disease
Authors: Rotwein Peter 
Published: May 2017

AbstractMajor recent advances in genetics and genomics present unique opportunities for enhancing our understanding of human physiology and disease predisposition. Here I demonstrate how analysis of genomic information can provide new insights into endocrine systems, using the human growth hormone (GH) signaling pathway as an illustrative example. GH is essential for normal postnatal growth in children, and plays important roles in other biological processes throughout life. GH actions are mediated by the GH receptor, primarily via the JAK2 protein tyrosine kinase and the STAT5B transcription factor, and inactivating mutations in this pathway all lead to impaired somatic growth. Variation in GH signaling genes has been evaluated using DNA sequence data from the Exome Aggregation Consortium, a compendium of information from &gt;60,000 individuals. Results reveal many potential missense and other alterations in the coding regions ofGH1,GHR,JAK2, andSTAT5B, with most changes being uncommon. The total number of different alleles per gene varied by ~threefold, from 101 forGH1 to 338 forJAK2. Several known disease-linked mutations inGH1,GHR, andJAK2 were present but infrequent in the population; however, three amino acid changes inGHR were sufficiently prevalent (~4% to 44% of chromosomes) to suggest that they are not disease causing. Collectively, these data provide new opportunities to understand how genetically driven variability in GH signaling and action may modify human physiology and disease.
Pancreas Atrophy and Islet Amyloid Deposition in Patients With Elderly-Onset Type 2 Diabetes
Authors: Xin An , Mizukami Hiroki , Inaba Wataru , Yoshida Taro , Takeuchi Yu-ki , Yagihashi Soroku 
Published: May 2017

Abstract

Context
With prolonged life expectancy, we often encounter patients with elderly-onset type 2 diabetes mellitus (eT2DM). Although the clinical features of eT2DM are suggested to be different from those in patients with middle-age–onset type 2 diabetes mellitus (mT2DM), the islet pathologic features in eT2DM have not been addressed.

Objective
We attempted to characterize the pancreatic pathology in eT2DM and sought its clinical implications.

Materials and Methods
Pancreata from 13 young nondiabetic (age, 20 to 29 years), 27 patients with mT2DM (age, 45 to 87 years), 22 middle-age subjects without T2DM, 15 subjects with eT2DM (age, 85 to 100 years), and 30 elderly subjects without T2DM were investigated. Together with conventional microscopic observations, morphometric analysis on the islet, islet endocrine cells, and amyloid deposition was conducted on immunostained sections.

Results
The estimated age of diabetes onset was 80.8 ± 1.4 years (mean ± standard error) in the eT2DM group and that of the mT2DM group was 48.3 ± 2.4 years. The pancreatic weight was nearly 50% less in the eT2DM group than in the other groups, showing duct obstruction with epithelial hyperplasia, marked acinar atrophy, fibrosis, and amyloid deposition in the islet. The islet mass was significantly reduced in the eT2DM group. The amyloid volume density correlated inversely with the β-cell volume density but not with the body mass index in the eT2DM group. Laboratory data showed mild elevation of serum amylase in the eT2DM group, although clinical signs and symptoms of pancreatitis were not apparent.

Conclusions
eT2DM is distinct from mT2DM and characterized by pancreas atrophy, ductal lesions, and amyloid deposition.
Molybdenum Dithiolene Complexes: Trinuclear Mixed-Valence Complexes and Geometrical Isomers of Dinuclear Complexes
Authors: Akashi Haruo , Machida Norihiko , Kamada Takahiro , Nihashi Hiroki , Aya Dai , Yamaguchi Kazuya , Takagi Hideaki , Shibahara Takashi 
Published: May 2017

Abstract
The reaction of an oxygen- and sulfur-bridged incomplete cubane-type molybdenum complex [Mo3(µ3-S)(µ-S)2(µ-O)(dtp)3(µ-dtp)(CH3CN)] (3) (dtp, diethyl dithiophosphate) with methyl propiolate (HC≡CCOOCH3, MP) and phenyl acetylene (HC≡CC6H5, PA) yields trinuclear mixed-valence Mo3(IV, V, V) complexes [Mo3(O)2(µ3-S)(µ3-SCH=C(COOCH3)S)(dtp)3(µ-OAc)] (3MP) and [Mo3(O)2(µ3-S)(µ3-SCH=C(C6H5)S)(dtp)3(µ-OAc)] (3PA), respectively, and also dinuclear Mo2(V, V) complexes [Mo2(O)2(µ-S)(µ-SCH=C(COOCH3)S)(dtp)2] (2aMP and 2bMP (a geometrical isomer of 2aMP)) and [Mo2(O)2(µ-S)(µ-SCH=C(C6H5)S)(dtp)2] (2aPA and 2bPA (a geometrical isomer of 2aPA)), respectively. The origin of the geometrical isomerism of the dimers comes from the unsymmetric nature of the acetylene derivatives. All of the structures were determined by X-ray crystallography, which revealed that each complex has two carbon-sulfur (µ-S) bonds arising from the adduct formation reaction between complex 3 and an acetylene derivative MP or PA. 1H NMR spectroscopy has proven that the dinuclear complexes are formed via the trinuclear complexes. The XPS spectra of 3MP show that the peaks of Mo 3d3/2 and Mo 3d5/2 are clearly split into two in the ratio of two to one, respectively, while those of 3 show no splitting, which indicates that 3MP is a mixed-valence complex with Mo3(IV, V, V) oxidation states. Cyclic voltammograms of 3MP and 3PA show chemically reversible one-electron oxidation processes at E1/2 = 0.21 V and E1/2 = 0.15 V vs. Ag/Ag+, respectively, and irreversible reduction peaks at −0.92 V and −1.00 V vs. Ag/Ag+, respectively. The dinuclear complexes, especially 2aPA and 2bPA having phenyl groups, are photosensitive to give their isomeric counter parts.
Immunoprofiling of human uterine mast cells identifies three phenotypes and expression of ERβ and glucocorticoid receptor
Authors: De Leo Bianca , Esnal-Zufiaurre Arantza , Collins Frances , Critchley Hilary O.D. , Saunders Philippa T.K. 
Published: May 2017

Background:Human mast cells (MCs) are long-lived tissue-resident immune cells characterised by granules containing the proteases chymase and/or tryptase. Their phenotype is modulated by their tissue microenvironment. The human uterus has an outer muscular layer (the myometrium) surrounding the endometrium, both of which play an important role in supporting a pregnancy. The endometrium is a sex steroid target tissue consisting of epithelial cells (luminal, glandular) surrounded by a multicellular stroma, with the latter containing an extensive vascular compartment as well as fluctuating populations of immune cells that play an important role in regulating tissue function. The role of MCs in the human uterus is poorly understood with little known about their regulation or the impact of steroids on their differentiation status.The current study had two aims: 1) To investigate the spatial and temporal location of uterine MCs and determine their phenotype; 2) To determine whether MCs express receptors for steroids implicated in uterine function, including oestrogen (ERα, ERβ), progesterone (PR) and glucocorticoids (GR).Methods:Tissue samples from women (n=46) were used for RNA extraction or fixed for immunohistochemistry.Results:Messenger RNAs encoded byTPSAB1(tryptase) andCMA1(chymase) were detected in endometrial tissue homogenates. Immunohistochemistry revealed the relative abundance of tryptase MCs was myometrium>basal endometrium>functional endometrium. We show for the first time that uterine MCs are predominantly of the classical MC subtypes: (positive, +; negative, -) tryptase+/chymase- and tryptase+/chymase+, but a third subtype was also identified (tryptase-/chymase+). Tryptase+ MCs were of an ERβ+/ERα-/PR-/GR+ phenotype mirroring other uterine immune cell populations, including natural killer cells.Conclusions:Endometrial tissue resident immune MCs have three protease-specific phenotypes. Expression of both ERβ and GR in MCs mirrors that of other immune cells in the endometrium and suggests that MC function may be altered by the local steroid microenvironment.
The knee meniscus: management of traumatic tears and degenerative lesions
Authors: Beaufils Philippe , Becker Roland , Kopf Sebastian , Matthieu Ollivier , Pujol Nicolas 
Published: May 2017

Meniscectomy is one of the most popular orthopaedic procedures, but long-term results are not entirely satisfactory and the concept of meniscal preservation has therefore progressed over the years. However, the meniscectomy rate remains too high even though robust scientific publications indicate the value of meniscal repair or non-removal in traumatic tears and non-operative treatment rather than meniscectomy in degenerative meniscal lesions In traumatic tears, the first-line choice is repair or non-removal. Longitudinal vertical tears are a proper indication for repair, especially in the red-white or red-red zones. Success rate is high and cartilage preservation has been proven. Non-removal can be discussed for stable asymptomatic lateral meniscal tears in conjunction with anterior cruciate ligament (ACL) reconstruction. Extended indications are now recommended for some specific conditions: horizontal cleavage tears in young athletes, hidden posterior capsulo-meniscal tears in ACL injuries, radial tears and root tears. Degenerative meniscal lesions are very common findings which can be considered as an early stage of osteoarthritis in middle-aged patients. Recent randomised studies found that arthroscopic partial meniscectomy (APM) has no superiority over non-operative treatment. Thus, non-operative treatment should be the first-line choice and APM should be considered in case of failure: three months has been accepted as a threshold in the ESSKA Meniscus Consensus Project presented in 2016. Earlier indications may be proposed in cases with considerable mechanical symptoms. The main message remains: save the meniscus! Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160056. Originally published online at www.efortopenreviews.org
Articular impaction injuries in the lower limb
Authors: Pountos Ippokratis , Giannoudis Peter V. 
Published: May 2017

The effective management of articular impacted fractures requires the successful elevation of the osteochondral fragment to eliminate joint incongruency and the stable fixation of the fragments providing structural support to the articular surface. The anatomical restoration of the joint can be performed either with elevation through a cortical window, through balloon-guided osteoplasty or direct visualisation of the articular surface. Structural support of the void created in the subchondral area can be achieved through the use of bone graft materials (autologous tricortical bone), or synthetic bone graft substitutes. In the present study, we describe the available techniques and materials that can be used in treating impacted osteochondral fragments with special consideration of their epidemiology and treatment options. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160072. Originally published online at www.efortopenreviews.org
The adult cavus foot
Authors: Maynou Carlos , Szymanski Christophe , Thiounn Alexis 
Published: May 2017

Cavovarus deformity can be classified by the severity of malalignment ranging from a subtle and flexible to a severe and fixed cavovarus deformity of the foot. In the mild cavovarus foot, careful clinical assessment is required to identify the deformity. Weight-bearing radiographs are necessary to indicate the apex of the deformity and quantify the correction required. Surgery is performed when conservative measures fail and various surgical procedures have been described, including a combination of soft-tissue releases, tendon transfers and osteotomies, all with the aim of achieving a plantigrade and balanced foot. Joint-sparing surgery is the best option in flexible cavovarus foot even in Charcot-Marie-Tooth (CMT) disease (peroneal muscular atrophy). Arthrodesis is indicated in severe rigid cavus foot or in degenerative cases. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160077. Originally published online at www.efortopenreviews.org
Malignant tumours of the foot and ankle
Authors: Mascard E. , Gaspar N. , Brugières L. , Glorion C. , Pannier S. , Gomez-Brouchet A. 
Published: May 2017

Most of tumours of the foot are tumour-like (synovial cyst, foreign body reactions and epidermal inclusion cyst) or benign conditions (tenosynovial giant cells tumours, planta fibromatosis). Malignant tumours of the soft-tissue and skeleton are very rare in the foot and their diagnosis is often delayed with referral to specialised teams after initial inappropriate procedures or unplanned excisions. The adverse effect of these misdiagnosed tumours is the increasing rate of amputation or local recurrences in the involved patients. In every lump, imaging should be discussed before any local treatment. Every lesion which is not an obvious synovial cyst or plantar fibromatosis should have a biopsy performed. After the age of 40 years, chondrosarcoma is the most usual malignant tumour of the foot. In young patients bone tumours such as osteosarcoma or Ewing’s sarcoma, are very unusually located in the foot. Synovial sarcoma is the most frequent histological diagnosis in soft tissues. Epithelioid sarcoma or clear cell sarcoma, involve more frequently the foot and ankle than other sites. The classic local treatment of malignant conditions of the foot and ankle was below-knee amputation at different levels. Nowadays, with the development of adjuvant therapies, some patients may benefit from conservative surgery or partial amputation after multidisciplinary team discussions. The prognosis of foot malignancy is not different from that at other locations, except perhaps in chondrosarcoma, which seems to be less aggressive in the foot. The anatomy of the foot is very complex with many bony and soft tissue structures in a relatively small space making large resections and conservative treatments difficult to achieve. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160078. Originally published online at www.efortopenreviews.org
The patellofemoral joint: from dysplasia to dislocation
Authors: Zaffagnini Stefano , Grassi Alberto , Zocco Gianluca , Rosa Michele Attilo , Signorelli Cecilia , Muccioli Giulio Maria Marcheggiani 
Published: May 2017

Patellofemoral dysplasia is a major predisposing factor for instability of the patellofemoral joint. However, there is no consensus as to whether patellofemoral dysplasia is genetic in origin, caused by imbalanced forces producing maltracking and remodelling of the trochlea during infancy and growth, or due to other unknown and unexplored factors. The biomechanical effects of patellofemoral dysplasia on patellar stability and on surgical procedures have not been fully investigated. Also, different anatomical and demographic risk factors have been suggested, in an attempt to identify the recurrent dislocators. Therefore, a comprehensive evaluation of all the radiographic, MRI and CT parameters can help the clinician to assess patients with primary and recurrent patellar dislocation and guide management. Patellofemoral dysplasia still represents an extremely challenging condition to manage. Its controversial aetiology and its complex biomechanical behaviour continue to pose more questions than answers to the research community, which reflects the lack of universally accepted guidelines for the correct treatment. However, due to the complexity of this condition, an extremely personalised approach should be reserved for each patient, in considering and addressing the anatomical abnormalities responsible for the symptoms. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160081. Originally published online at www.efortopenreviews.org
How to deal with a glenoid fracture
Authors: Frich Lars Henrik , Larsen Morten Schultz 
Published: May 2017

The glenoid fossa is involved in approximately 10% of all scapular fractures. Glenoid fossa incongruity is surprisingly well tolerated. Surgery is recommended when 20% or more of the anterior glenoid fossa is involved. Glenoid rim fractures often lead to chronic shoulder instability. Unstable glenoid neck fractures need surgical treatment and stable fractures can be treated conservatively. CT examination with 3D reformations of the glenoid fossa has improved insight into fracture morphology and fracture patterns and is very helpful for clinical decision makers.Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160082. Originally published online at www.efortopenreviews.org