bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conventional disease-modifying antirheumatic drugs therapy may not slow spinal radiographic progression in ankylosing spondylitis: results from an 18-year longitudinal dataset
Authors: Lee Tae-Han , Koo Bon San , Nam Bora , Oh Ji Seon , Park Seo Young , Lee Seunghun , Joo Kyung Bin , Kim Tae-Hwan 
Published: November 2020

Objectives: The clinical benefit of conventional disease-modifying antirheumatic drugs (cDMARDs) for treating ankylosing spondylitis (AS) is generally limited to improvements in peripheral arthritis. However, cDMARDs could be conditionally considered as alternatives to established drugs for improving axial manifestations in exceptional circumstances. However, there are few studies of the impact of cDMARDs on radiographic progression outcomes. Therefore, we investigated the effectiveness of cDMARDs on radiographic progression in AS. Methods: Among 1280 AS patients at a single hospital from 2000 to 2018, 301 who had been treated with sulfasalazine (SSZ) or methotrexate (MTX) were enrolled. For each patient, the entire follow-up period was split into 1-year intervals. Each interval was classified as either an “on-cDMARD” interval, which was a period of treatment with SSZ alone, MTX alone, or a combination of SSZ and MTX, or an “off-cDMARD” interval, which was a period without cDMARD treatment. Radiographic progression was scored using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The relationship between cDMARD use and radiographic progression within the intervals, defined as the rate of mSASSS progression, was investigated using linear models with adjustment for potential confounding covariates and for clustering among observations from the same patient. Results: The 732 on-cDMARD intervals and 1027 off-cDMARD intervals were obtained from enrolled patients. In multivariable regression analysis, there was no significant association between cDMARDs and the rate of mSASSS progression (β = −0.081, p = 0.418). The mean adjusted mSASSS change per year was 0.610 from on-cDMARD intervals and 0.691 from off-cDMARD intervals. Conclusion: Treatment with cDMARDs may not reduce radiographic progression in AS patients.
Hemiscrotal agenesis: a novel phenotype of a rare malformation
Authors: Mansy Mohamed , Kotb Mostafa , Abdelmeguid Yasmine , Raafat Shaymaa , Abdelaziz Marwa 
Published: November 2020

Abstract
Background
Hemiscrotal agenesis (HSA) is an exceedingly rare congenital anomaly in scrotal development. It is characterized by unilateral absence of scrotal skin with intact midline raphe. In the English literature, only seven patients were diagnosed with HSA. Herein, we report a 14-month-old boy with HSA, unilateral cryptorchidism and a perineal skin tag. Additionally, the patient had a monodactylous limb, unilateral cerebellar hypoplasia, and a cardiac septal defect.

Case presentation
A 14-month-old boy presented with right HSA and ectopic scrotal skin in the right perineal region. Extra-genital examination showed right monodactylous lower limb, without dysmorphic facial features or any other skeletal anomalies. His karyotype was 46, XY, while his hormonal profile showed prepubertal LH and FSH. Skeletal survey showed right monodactylous lower limb (with only a big toe which had 2 phalanges) and normal spine alignment. A previous echocardiography was done and showed a small muscular ventricular septal defect (VSD) that closed on follow-up. Magnetic resonance imaging of the brain showed posterior fossa malformation. The patient had his right testis fixed in the right scrotum. The pathological examination of the perineal lesion showed fibro-epithelial polyp (skin tag), with no testicular tissue or atypia.

Conclusion
We believe that this is the first case to be reported with hemiscrotal agenesis and ipsilateral cryptorchidism, associated with a perineal skin tag, unilateral monodactylous lower limb on the same side, unilateral cerebellar hypoplasia, and VSD. Interestingly, further genetic analysis is required to reach a final diagnosis. However, regrettably, advanced molecular diagnostic studies for this patient is not available in our country.
Cardiac resynchronization therapy and its effects in patients with type 2 DIAbetes mellitus OPTimized in automatic vs. echo guided approach. Data from the DIA-OPTA investigators
Authors: Sardu Celestino , Paolisso Pasquale , Ducceschi Valentino , Santamaria Matteo , Sacra Cosimo , Massetti Massimo , Ruocco Antonio , Marfella Raffaele 
Published: November 2020

Abstract
Objectives
To evaluate the effects of cardiac resynchronization therapy (CRTd) in patients with type 2 diabetes mellitus (T2DM) optimized via automatic vs. echocardiography-guided approach.

Background
The suboptimal atrio-ventricular (AV) and inter-ventricular (VV) delays optimization reduces CRTd response. Therefore, we hypothesized that automatic CRTd optimization might improve clinical outcomes in T2DM patients.

Methods
We designed a prospective, multicenter study to recruit, from October 2016 to June 2019, 191 consecutive failing heart patients with T2DM, and candidate to receive a CRTd. Study outcomes were CRTd responders rate, hospitalizations for heart failure (HF) worsening, cardiac deaths and all cause of deaths in T2DM patients treated with CRTd and randomly optimized via automatic (n 93) vs. echocardiography-guided (n 98) approach at 12 months of follow-up.

Results
We had a significant difference in the rate of CRTd responders (68 (73.1%) vs. 58 (59.2%), p 0.038), and hospitalizations for HF worsening (12 (16.1%) vs. 22 (22.4%), p 0.030) in automatic vs. echocardiography-guided group of patients. At multivariate Cox regression analysis, the automatic guided approach (3.636 [1.271–10.399], CI 95%, p 0.016) and baseline highest values of atrium pressure (automatic SonR values, 2.863 [1.537–6.231], CI 95%, p 0.006) predicted rate of CRTd responders. In automatic group, we had significant difference in SonR values comparing the rate of CRTd responders vs. non responders (1.24 ± 0.72 g vs. 0.58 ± 0.46 g (follow-up), p 0.001), the rate of hospitalizations for HF worsening events (0.48 ± 0.29 g vs. 1.18 ± 0.43 g, p 0.001), and the rate of cardiac deaths ( 1.13 ± 0.72 g vs. 0.65 ± 0.69 g, p 0.047).

Conclusions
Automatic optimization increased CRTd responders rate, and reduced hospitalizations for HF worsening. Intriguingly, automatic CRTd and highest baseline values of SonR could be predictive of CRTd responders. Notably, there was a significant difference in SonR values for CRTd responders vs. non responders, and about hospitalizations for HF worsening and cardiac deaths.
Clinical trial ClinicalTrials.gov Identifier NCT04547244.
Long noncoding RNAs: functions and mechanisms in colon cancer
Authors: Chen Sian , Shen Xian 
Published: November 2020

AbstractEvidence indicates that long non-coding RNAs (lncRNAs) play a crucial role in the carcinogenesis and progression of a wide variety of human malignancies including colon cancer. In this review, we describe the functions and mechanisms of lncRNAs involved in colon oncogenesis, such as HOTAIR, PVT1, H19, MALAT1, SNHG1, SNHG7, SNHG15, TUG1, XIST, ROR and ZEB1-AS1. We summarize the roles of lncRNAs in regulating cell proliferation, cell apoptotic death, the cell cycle, cell migrative and invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells and drug resistance in colon cancer. In addition, we briefly highlight the functions of circRNAs in colon tumorigenesis and progression, including circPPP1R12A, circPIP5K1A, circCTIC1, circ_0001313, circRNA_104916 and circRNA-ACAP2. This review provides the rationale for anticancer therapy via modulation of lncRNAs and circular RNAs (circRNAs) in colon carcinoma.
Nonparametric estimation of a primary care production function in urban Brazil
Authors: Wichmann Bruno , Wichmann Roberta 
Published: November 2020

Abstract
Background
The Brazilian public health system is one of the largest health systems in the world, with a mandate to deliver medical care to more than 200 million Brazilians. The objective of this study is to estimate a production function for primary care in urban Brazil. Our goal is to use flexible estimates to identify heterogeneous returns and complementarities between medical capital and labor.

Methods
We use a large dataset from 2012 to 2016 (with more than 400 million consultations, 270 thousand physicians, and 11 thousand clinics) to nonparametrically estimate a primary care production function and calculate the elasticity of doctors’ visits (output) to two inputs: capital stock (number of clinics) and labor (number of physicians). We benchmark our nonparametric estimates against estimates of a Cobb-Douglas (CD) production function. The CD model was chosen as a baseline because it is arguably the most popular parametric production function model. By comparing our nonparametric results with those from the CD model, our paper shed some light on the limitations of the parametric approach, and on the novelty of nonparametric insights.

Results
The nonparametric results show significantly heterogeneity of returns to both capital and labor, depending on the scale of operation. We find that diseconomies of scale, diminishing returns to scale, and increasing returns to scale are possible, depending on the input range.

Conclusions
The nonparametric model identifies complementarities between capital and labor, which is essential in designing efficient policy interventions. For example, we find that the response of primary care consultations to labor is steeper when capital level is high. This means that, if the goal is to allocate labor to maximize increases in consultations, adding physicians in cities with a high number of clinics is preferred to allocating physicians to low medical infrastructure municipalities. The results highlight how the CD model hides useful policy information by not accounting for the heterogeneity in the data.
Inoculation of native symbiotic effective Sinorhizobium spp. enhanced soybean [Glycine max (L.) Merr.] grain yield in Ethiopia
Authors: Temesgen Diriba , Assefa Fassil 
Published: November 2020

AbstractBackgroundSoybean [Glycine max(L) Merr.] is an annual leguminous crop serving as a source of food and feed, green manure, biodiesel and fiber. It is nodulated by diverse slow growing and fast growing rhizobia belonging to the genusBradyrhizobiumandSinorhizobium, respectively. In Ethiopia, it has been cultivated since 1950s with lower grain yield history. Yield improvement efforts have been more concentrated on agronomic studies, inoculation of exoticBradyrhizobium japonicumincluding TAL379 and/or fertilizer application. The results have usually been unsatisfactory and inconsistent. This study was initiated to identify promising indigenous soybean rhizobial inoculant that can enhance yield of the crop in the country.MethodsNative soybean rhizobia, designated GMR forGlycine maxrhizobia, were trapped using soybean (cv. Ethio-Yugoslavia) from soils collected across agro-ecologies of Ethiopia. They were screened for in vitro tolerance against physico-chemical stresses, plant growth promoting (PGP) traits and symbiotic performances at greenhouse and field levels. A referenceB. japonicum(TAL379) was included in all experiments. A soybean plant growth promotingAchromobactersp. was also included in field trials for co-inoculation. Quantitative data were assessed by analysis of variance (ANOVA) employing SAS computer software package version 9.3. Mean separations were undertaken using Duncan’s Multiple Range Test at p ≤ 0.05. Phenotypic variability of the test bacteria was undertaken using PAST4.03 Computer Software.ResultGMR that produced acid and grew faster with larger colonies were identified asSinorhizobiumspp. and those which produced alkali and grew slowly with smaller colonies were identified asBradyrhizobiumspp. though further genetic analysis should be performed for verification and identification of their genus and species, respectively. TwoSinorhizobiumspp. (GMR120C and GMR125B) profoundly nodulated different soybean cultivars under greenhouse conditions and significantly improved grain yield (p ≤ 0.05; maximum 3.98 tons ha−1) compared to 2.41, 2.82 and 2.69 recorded as maximum grain yield (tons ha−1) for TAL379 inoculation, positive control and negative control, respectively in field trials. Higher yield was recorded when GMR125B was co-inoculated withAchromobactersp., but when GMR120C was inoculated singly. These GMR also showed efficient utilization of numerous substrates, some PGP traits and potential adaptation to various ecological stresses.ConclusionThe twoSinorhizobiumspp. (GMR120C and GMR125B) are promising soybean inoculants that can be used to enhance the productivity of the crop in the country.
Building a rapid autopsy program – a step-by-step logistics guide
Authors: Bacon Eliza R. , Ihle Kena , Lee Peter P. , Waisman James R. 
Published: November 2020

Abstract
Background
Rapid Autopsy Programs offer an opportunity to collect tissue from patients immediately after death, providing critical biological material necessary to develop more effective therapies and improve patient outcomes. Here, we present a step-by-step guide to build a cancer-focused Rapid Autopsy Program, based on our own experiences building “The Legacy Project” at the City of Hope Comprehensive Cancer Center.

Methods
The linear timeline of events is separated into four phases: 1) Building the Infrastructure, 2) Recruiting and Consenting, 3) Preparing for Death, and 4) Tissue Collection and Follow up. Important considerations and methods for adaptation are discussed throughout the protocol.

Discussion
Using these methods, we successfully collected a total of 533 specimens from 9 subjects. The average time from death to last specimen acquisition was 6.1 h (range: 4.03–7.66 h; median: 5.71 h). A diverse team with various areas of expertise is critical for successful program implementation. Our goal herein this protocol is to provide a comprehensive framework and foundation for other institutions to use as a model.
Mechanical thrombectomy for pulmonary embolism in patients with patent foramen Ovale
Authors: Nezami Nariman , Chockalingam Arun , Cornman-Homonoff Joshua , Marino Angelo , Pollak Jeffrey , Mojibian Hamid 
Published: November 2020

Abstract
Background
The current level of evidence for mechanical thrombectomy (MT) of pulmonary embolism (PE) in patients with patent foramen ovale (PFO) is limited.

Results
This was a retrospective analysis of 9 patients with PFO and acute high-risk or intermediate-high-risk PE, 6 with intermediate-high risk and 3 with high-risk PE. All underwent MT using the Inari FlowTriever System from Dec 2018 to November 2019. Six of these patients had confirmed deep venous thrombosis. The technical and clinical success rate for MT in all patients was 100% and 77.8%, respectively. Right-heart strain improved in 6/8 patients on follow-up echocardiography. Mean main pulmonary artery (MPA) pressure significantly decreased after MT (p < 0.012). One patient presented with altered mental status (somnolence and disorientation) prior to coronary artery angiogram and thrombectomy, developed a middle cerebral artery embolic stroke 1 day after MT, and recovered with minor sequalae and later was discharged. There was no in-hospital mortality.

Conclusions
MT using FlowTriever was feasible and safe, successfully improving MPA pressure in patients presenting with concurrent PFO and PE.
Aldosterone Induces Vasoconstriction in Individuals with Type 2 Diabetes: Effect of Acute Antioxidant Administration
Authors: Finsen Stine Høyer , Hansen Mie Rytz , Hansen Pernille B Lærkegaard , Mortensen Stefan P 
Published: November 2020

Abstract

Context
Individuals with type 2 diabetes have an increased risk of endothelial dysfunction and cardiovascular disease. Plasma aldosterone could contribute by reactive oxygen species–dependent mechanisms by inducing a shift in the balance between a vasoconstrictor and vasodilator response to aldosterone.

Objective
We aimed to investigate the acute vascular effects of aldosterone in individuals with type 2 diabetes compared with healthy controls and if infusion of an antioxidant (n-acetylcysteine [NAC]) would alter the vascular response.

Methods
In a case–control design, 12 participants with type 2 diabetes and 14 healthy controls, recruited from the general community, were studied. Leg hemodynamics were measured before and during aldosterone infusion (0.2 and 5 ng min–1 [L leg volume]–1) for 10 minutes into the femoral artery with and without coinfusion of NAC (125 mg kg–1 hour–1 followed by 25 mg kg–1 hour–1). Leg blood flow and arterial blood pressure was measured, and femoral arterial and venous blood samples were collected.

Results
Compared with the control group, leg blood flow and vascular conductance decreased during infusion of aldosterone at the high dose in individuals with type 2 diabetes, whereas coinfusion of NAC attenuated this response. Plasma aldosterone increased in both groups during aldosterone infusion and there was no difference between groups at baseline or during the infusions.

Conclusion
These results suggests that type 2 diabetes is associated with a vasoconstrictor response to physiological levels of infused aldosterone and that the antioxidant NAC diminishes this response.
Description of the Follicular Fluid Cytokine and Hormone Profiles in Human Physiological Natural Cycles
Authors: Piccinni Marie-Pierre , Vicenti Rossella , Logiodice Federica , Fabbri Raffaella , Kullolli Ornela , Pallecchi Marco , Paradisi Roberto , Danza Giovanna , Macciocca Maria , Lombardelli Letizia , Seracchioli Renato 
Published: November 2020

AbstractPurposeExogenous gonadotrophins administration during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles could significantly alter the endogenous follicular regulation system and could influence oocyte quality. The analysis of the follicular fluid (FF) cytokine and hormone profiles in physiological natural cycles is crucial to appreciate the role of FF milieu on follicle development. So far, the FF cytokine profile has been analyzed only in controlled ovarian stimulation cycles and in modified natural cycles. Our study defines, in physiological natural cycles, the cytokine and hormone profiles of individual FF aspirated from antral follicles.MethodsA total of 203 FFs obtained from 83 women with regular menstrual cycles undergoing ovarian tissue cryopreservation were analyzed: 115 FFs from Group 1 (10 to 29 years of age) and 88 FFs from Group 2 (30 to 40 years of age). In individual FF, 27 cytokines were measured with xMAP technology, and progesterone, estrone, estradiol, testosterone, androstenedione concentrations were determined by liquid chromatography–tandem mass spectrometry.ResultsFF hormone profiles were not different in follicular and luteal phase, suggesting that FF hormones are regulated independently of the endogenous gonadotrophins—possibly because 74% of the punctured follicles, which were ≤6 mm, did not require cyclic pituitary function. The follicle size was influenced not only by the FF cytokine profile but also by the FF hormone profile, both of which are dependent on age.Main ConclusionsIn physiological natural cycles, FF hormones seems to be regulated independently of the endogenous gonadotropins. Age influences FF hormone and cytokine profiles and the compelling relationship between FF hormones and FF cytokines could influence the follicle development.
Primary Adrenal Insufficiency in Childhood: Data From a Large Nationwide Cohort
Authors: Capalbo Donatella , Moracas Cristina , Cappa Marco , Balsamo Antonio , Maghnie Mohamad , Wasniewska Malgorzata Gabriela , Greggio Nella Augusta , Baronio Federico , Bizzarri Carla , Ferro Giusy , Di Lascio Alessandra , Stancampiano Marianna Rita , Azzolini Sara , Patti Giuseppa , Longhi Silvia , Valenzise Mariella , Radetti Giorgio , Betterle Corrado , Russo Gianni , Salerno Mariacarolina 
Published: November 2020

Abstract

Context
Primary adrenal insufficiency (PAI) is a rare and potentially life-threatening condition that is poorly characterized in children.

Objective
To describe causes, presentation, auxological outcome, frequency of adrenal crisis and mortality of a large cohort of children with PAI.

Patients and Methods
Data from 803 patients from 8 centers of Pediatric Endocrinology were retrospectively collected.

Results
The following etiologies were reported: 85% (n = 682) congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD); 3.1% (n = 25) X-linked adrenoleukodystrophy; 3.1% (n = 25) autoimmune polyglandular syndrome type 1; 2.5% (n = 20) autoimmune adrenal insufficiency; 2% (n = 16) adrenal hypoplasia congenital; 1.2% (n = 10) non-21-OHD CAH; 1% (n = 8) rare syndromes; 0.6% (n = 5) familial glucocorticoid deficiency; 0.4% (n = 3) acquired adrenal insufficiency; 9 patients (1%) did not receive diagnosis. Since 21-OHD CAH has been extensively characterized, it was not further reviewed. In 121 patients with a diagnosis other than 21-OHD CAH, the most frequent symptoms at diagnosis were fatigue (67%), hyperpigmentation (50.4%), dehydration (33%), and hypotension (31%). Elevated adrenocorticotropic hormone (96.4%) was the most common laboratory finding followed by hyponatremia (55%), hyperkalemia (32.7%), and hypoglycemia (33.7%). The median age at presentation was 6.5 ± 5.1 years (0.1-17.8 years) and the mean duration of symptoms before diagnosis was 5.6 ± 11.6 months (0-56 months) depending on etiology. Rate of adrenal crisis was 2.7 per 100 patient-years. Three patients died from the underlying disease. Adult height, evaluated in 70 patients, was −0.70 ± 1.20 standard deviation score.

Conclusions
We characterized one of the largest cohorts of children with PAI aiming to improve the knowledge on diagnosis of this rare condition.
A Novel Loss of Function Melanocortin-4-Receptor Mutation (MC4R-F313Sfs*29) in Morbid Obesity
Authors: Trevellin Elisabetta , Granzotto Marnie , Host Cristina , Grisan Francesca , De Stefani Diego , Grinzato Alessandro , Lefkimmiatis Konstantinos , Pagano Claudio , Rizzuto Rosario , Vettor Roberto 
Published: November 2020

AbstractContextMelanocortin receptor-4 (MC4R) gene mutations are associated with early-onset severe obesity, and the identification of potential pathological variants is crucial for the clinical management of patients with obesity.ObjectiveTo explore whether and how a novel heterozygous MC4R variant (MC4R-F313Sfs*29), identified in a young boy (body mass index [BMI] 38.8 kg/m2) during a mutation analysis conducted in a cohort of patients with obesity, plays a determinant pathophysiological role in the obesity development.Design Setting and PatientsThe genetic screening was carried out in a total of 209 unrelated patients with obesity (BMI ≥ 35 kg/m2). Structural and functional characterization of the F313Sfs*29-mutated MC4R was performed using computational approaches and in vitro, using HEK293 cells transfected with genetically encoded biosensors for cAMP and Ca2+.ResultsThe F313Sfs*29 was the only variant identified. In vitro experiments showed that HEK293 cells transfected with the mutated form of MC4R did not increase intracellular cAMP or Ca2+ levels after stimulation with a specific agonist in comparison with HEK293 cells transfected with the wild type form of MC4R (∆R/R0 = -90% ± 8%; P &lt; 0.001). In silico modeling showed that the F313Sfs*29 mutation causes a major reorganization in the cytosolic domain of MC4R, thus reducing the affinity of the putative GalphaS binding site.ConclusionsThe newly discovered F313Sfs*29 variant of MC4R may be involved in the impairment of α-MSH-induced cAMP and Ca2+ signaling, blunting intracellular G protein-mediated signal transduction. This alteration might have led to the dysregulation of satiety signaling, resulting in hyperphagia and early onset of obesity.