bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forty-year study of rates of homicide by people with schizophrenia and other homicides in the Chuvash Republic of the Russian Federation
Authors: Golenkov Andrei , Large Matthew , Nielssen Olav , Tsymbalova Alla 
Published: December 2021

BackgroundThe extent to which rates of homicide by people with or without schizophrenia vary over time has theoretical and practical implications in understanding homicide by people with mental illness.AimsThe aim was to report on the rates of homicide by people diagnosed with schizophrenia over time in a region in which there were dramatic changes in the overall rates of homicide.MethodsAn examination of homicide by people diagnosed with schizophrenia in the course of judicial psychiatric examination, and the rate of other homicide in the Chuvash Republic of the Russian Federation between 1981 and 2020 was undertaken.ResultsDuring the 40 years of the study a total of 5741 people faced legal proceedings for a homicide offence, of whom 179 (3.1%) were diagnosed with schizophrenia. During the study period the average annual total homicide rate rose from about 9 per 100 000 in the 1980s, peaked at 17 per 100 000 in the 1990s before falling to 13 per 100 000 in the 2000s and 6 per 100 000 in the 2010s. Rates of homicide by people with schizophrenia also rose and fell over this period and were significantly associated with the rates of other homicide (r = 0.503, d.f. = 38, P = 0.001).ConclusionsThe rise and fall in rates of homicide by people diagnosed with schizophrenia in parallel to total homicide suggests that homicidal behaviour might not be intrinsic to the clinical manifestations of the illness, and might instead reflect a heightened vulnerability to social factors that are associated with homicide by people without schizophrenia.
Orientational arrest in dense suspensions of elliptical particles under oscillatory shear flows
Authors: Yousefian Zakiyeh , Trulsson Martin 
Published: December 2021

Abstract
We study the rheological response of dense suspensions of elliptical particles, with an aspect ratio equal to 3, under oscillatory shear flows and imposed pressure by numerical simulations. Like for the isotropic particles, we find that the oscillatory shear flows respect the Cox-Merz rule at large oscillatory strains but differ at low strains, with a lower viscosity than the steady shear and higher shear jamming packing fractions. However, unlike the isotropic cases (i.e., discs and spheres), frictionless ellipses get dynamically arrested in their initial orientational configuration at small oscillatory strains. We illustrate this by starting at two different configurations with different nematic order parameters and the average orientation of the particles. Surprisingly, the overall orientation in the frictionless case is uncoupled to the rheological response close to jamming, and the rheology is only controlled by the average number of contacts and the oscillatory strain. Having larger oscillatory strains or adding friction does, however, help the system escape these orientational arrested states, which are evolving to a disordered state independent of the initial configuration at low strains and ordered ones at large strains.
Quantum simulation of PT-arbitrary-phase–symmetric systems
Authors: Zheng Chao 
Published: December 2021

Abstract
Parity-time-reversal (PT) symmetric quantum mechanics promotes the increasing research interest of non-Hermitian (NH) systems for the theoretical value, novel properties, and links to open and dissipative systems in various areas. Recently, anti-PT–symmetric systems and their featured properties have started to be investigated. In this work, we develop the PT and anti-PT symmetry to PT-arbitrary-phase symmetry (or PT-φ symmetry) for the first time, being analogous to bosons, fermions and anyons. It can also be seen as a complex extension of the PT symmetry, unifying the PT and anti-PT symmetries and having intermediate properties between them. Many of the established concepts and mathematics in the PT-symmetric system are still compatible. We mainly investigate quantum simulation of this novel NH system in two dimensions in detail and discuss for higher-dimensional cases in general using the linear combinations of unitaries in the scheme of duality quantum computing, enabling implementations and experimental investigations of novel properties on both small quantum devices and near-term quantum computers.
Attention-Deficit/Hyperactivity Disorder and Obesity: A National Study of 1.1 Million Israeli Adolescents
Authors: Pinhas-Hamiel Orit , Bardugo Aya , Reichman Brian , Derazne Estela , Landau Zohar , Tokatly Latzer Itay , Lerner-Geva Liat , Rotschield Jacob , Tzur Dorit , Ben-Zvi Danny , Afek Arnon , Twig Gilad 
Published: December 2021

Abstract

Purpose
The incidences of obesity and attention-deficit/hyperactivity disorder (ADHD) have increased in parallel over recent decades. We assessed the association between obesity and ADHD in a national sample of adolescents.

Method
In a nationwide population-based study of 1 118 315 adolescents (57% males; mean age 17 years), risks of obesity were compared between individuals with severe and mild ADHD and those without ADHD. Diagnoses of ADHD were confirmed by specialists in either neurology or psychiatry. Adolescents requiring regular and continuous treatment with stimulants with no improvement of symptoms under treatment were classified as having severe ADHD; data were available from 2004 to 2019. During 2015 to 2019, the diagnosis of ADHD was defined, and 65 118 (16.76%) of 388 543 adolescents with mild symptoms who required medications only for learning or who used stimulants irregularly were defined as having mild ADHD.

Results
The prevalence of severe and mild ADHD was 0.3% and 20.1%, respectively. Obesity was more prevalent among adolescents with severe ADHD than among those without ADHD (13.5% vs 7.5%). In the mild ADHD group 12.6% of males and 8.4% of females were diagnosed with obesity compared to 9.7% and 6.4%, respectively, in the non-ADHD group. The adjusted odds of severe ADHD for males and females with obesity were 1.77 (1.56-2.02) and 2.09 (1.63-2.66) times the odds for males and females with low-normal body mass index, respectively, and 1.42 (1.37-1.48) and 1.42 (1.34-1.50) for males and females with mild ADHD, respectively. The elevated risk persisted in several sensitivity analyses.

Conclusions
Both adolescents with severe and mild ADHD are at increased risk for obesity.
New Horizons: Next-Generation Insulin Analogues: Structural Principles and Clinical Goals
Authors: Jarosinski Mark A , Chen Yen-Shan , Varas Nicolás , Dhayalan Balamurugan , Chatterjee Deepak , Weiss Michael A 
Published: December 2021

AbstractDesign of “first-generation” insulin analogues over the past 3 decades has provided pharmaceutical formulations with tailored pharmacokinetic (PK) and pharmacodynamic (PD) properties. Application of a molecular tool kit—integrating protein sequence, chemical modification, and formulation—has thus led to improved prandial and basal formulations for the treatment of diabetes mellitus. Although PK/PD changes were modest in relation to prior formulations of human and animal insulins, significant clinical advantages in efficacy (mean glycemia) and safety (rates of hypoglycemia) were obtained. Continuing innovation is providing further improvements to achieve ultrarapid and ultrabasal analogue formulations in an effort to reduce glycemic variability and optimize time in range. Beyond such PK/PD metrics, next-generation insulin analogues seek to exploit therapeutic mechanisms: glucose-responsive (“smart”) analogues, pathway-specific (“biased”) analogues, and organ-targeted analogues. Smart insulin analogues and delivery systems promise to mitigate hypoglycemic risk, a critical barrier to glycemic control, whereas biased and organ-targeted insulin analogues may better recapitulate physiologic hormonal regulation. In each therapeutic class considerations of cost and stability will affect use and global distribution. This review highlights structural principles underlying next-generation design efforts, their respective biological rationale, and potential clinical applications.
Denosumab After Teriparatide in Premenopausal Women With Idiopathic Osteoporosis
Authors: Shane Elizabeth , Shiau Stephanie , Recker Robert R , Lappe Joan M , Agarwal Sanchita , Kamanda-Kosseh Mafo , Bucovsky Mariana , Stubby Julie , Cohen Adi 
Published: December 2021

Abstract

Context
We have previously reported that teriparatide is associated with substantial increases in bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) and small declines at the distal radius in 41 premenopausal women with idiopathic osteoporosis (IOP), all severely affected with low trauma fractures and/or very low BMD. Effects of teriparatide dissipate if not followed by antiresorptives.

Objective
To assess the effects of 12 and 24 months of denosumab in premenopausal women with IOP completing 24 months of teriparatide.

Methods
This was a preplanned phase 2B extension study. Premenopausal women with IOP who had completed a course of teriparatide received denosumab 60 mg every 6 months over 24 months. The main outcome measure was within-group change in BMD at the LS at 12 months. Secondary outcomes include change in 12-month BMD at other sites, 24-month BMD at all sites, trabecular bone score (TBS), and bone turnover markers (BTMs).

Results
After completing teriparatide, 32 participants took denosumab for 12 months and 29 for 24 months, with statistically significant increases in BMD at the LS (5.2 ± 2.6% and 6.9 ± 2.6%), TH (2.9 ± 2.4% and 4.6 ± 2.8%), and FN (3.0 ± 3.8% and 4.7 ± 4.9%). Over the entire 24-month teriparatide and 24-month denosumab treatment period, BMD increased by 21.9 ± 7.8% at the LS, 9.8 ± 4.6% at the TH, and 9.5 ± 4.7% at the FN (all P &lt; .0001). TBS increased by 5.8 ± 5.6% (P &lt; .001). Serum BTM decreased by 75% to 85% by 3 months and remained suppressed through 12 months of denosumab. Denosumab was generally well tolerated.

Conclusion
These data support the use of sequential teriparatide and denosumab to increase BMD in premenopausal women with severe osteoporosis.
Association of High-Affinity Autoantibodies With Type 1 Diabetes High-Risk HLA Haplotypes
Authors: Triolo Taylor M , Pyle Laura , Broncucia Hali , Armstrong Taylor , Yu Liping , Gottlieb Peter A , Steck Andrea K 
Published: December 2021

Abstract

Objective
Electrochemiluminescence (ECL) assays are high-affinity autoantibody (Ab) tests that are more specific than Abs detected by traditional radiobinding assays (RBA) for risk screening and prediction of progression to type 1 diabetes. We sought to characterize the association of high-risk human leukocyte antigen (HLA) haplotypes and genotypes with ECL positivity and levels in relatives of individuals with type 1 diabetes.

Methods
We analyzed 602 participants from the TrialNet Pathway to Prevention Study who were positive for at least 1 RBA diabetes-related Ab [glutamic acid decarboxylase autoantibodies (GADA) or insulin autoantibodies (IAA)] and for whom ECL and HLA data were available. ECL and RBA Ab levels were converted to SD units away from mean (z-scores) for analyses.

Results
Mean age at initial visit was 19.4 ± 13.7 years; 344 (57.1%) were female and 104 (17.3%) carried the high-risk HLA-DR3/4*0302 genotype. At initial visit 424/602 (70.4%) participants were positive for either ECL-GADA or ECL-IAA, and 178/602 (29.6%) were ECL negative. ECL and RBA-GADA positivity were associated with both HLA-DR3 and DR4 haplotypes (all Ps &lt; 0.05), while ECL and RBA-GADA z-score titers were higher in participants with HLA-DR3 haplotypes only (both Ps &lt; 0.001). ECL-IAA (but not RBA-IAA) positivity was associated with the HLA-DR4 haplotype (P &lt; 0.05).

Conclusions
ECL-GADA positivity is associated with the HLA-DR3 and HLA-DR4 haplotypes and levels are associated with the HLA-DR3 haplotype. ECL-IAA positivity is associated with HLA-DR4 haplotype. These studies further contribute to the understanding of genetic risk and islet autoimmunity endotypes in type 1 diabetes.
Continuous Glucose Monitoring and HbA1c in Cystic Fibrosis: Clinical Correlations and Implications for CFRD Diagnosis
Authors: Scully Kevin J , Sherwood Jordan S , Martin Kimberly , Ruazol Melanie , Marchetti Peter , Larkin Mary , Zheng Hui , Sawicki Gregory S , Uluer Ahmet , Neuringer Isabel , Yonker Lael M , Sicilian Leonard , Wexler Deborah J , Putman Melissa S 
Published: December 2021

Abstract

Context
The clinical utility and implications of continuous glucose monitoring (CGM) in cystic fibrosis (CF) are unclear.

Objective
We examined the correlation between CGM measures and clinical outcomes in adults with CF, investigated the relationship between hemoglobin A1c (HbA1c) and CGM-derived average glucose (AG), and explored CGM measures that distinguish cystic fibrosis–related diabetes (CFRD) from normal and abnormal glucose tolerance.

Methods
This prospective observational study included 77 adults with CF who had CGM and HbA1c measured at 2 to 3 time points 3 months apart.

Results
Thirty-one of the 77 participants met American Diabetes Association–recommended diagnostic criteria for CFRD by oral glucose tolerance testing and/or HbA1c. In all participants, CGM measures of hyperglycemia and glycemic variability correlated with nutritional status and pulmonary function. HbA1c was correlated with AG (R2 = 0.71, P &lt; 0.001), with no significant difference between this regression line and that previously established in type 1 and type 2 diabetes and healthy volunteers. Cutoffs of 17.5% time &gt; 140 mg/dL and 3.4% time &gt; 180 mg/dL had sensitivities of 87% and 90%, respectively, and specificities of 95%, for identifying CFRD. Area under the curve and percent of participants correctly classified with CFRD were higher for AG, SD, % time &gt; 140, &gt; 180, and &gt; 250 mg/dL than for HbA1c.

Conclusion
CGM measures of hyperglycemia and glycemic variability are superior to HbA1c in distinguishing those with and without CFRD. CGM-derived AG is strongly correlated with HbA1c in adults with CF, with a similar relationship to other diabetes populations. Future studies are needed to investigate CGM as a diagnostic and screening tool for CFRD.
Effect of Female and Male Body Mass Index on Cumulative Live Birth Rates in the Freeze-all Strategy
Authors: Shen Xi , Xie Yating , Chen Di , Guo Wenya , Feng Gang , Jiang Weiming , Long Hui , Lyu Qifeng , Jin Wei , Kuang Yanping , Wang Li 
Published: December 2021

AbstractContextThe impact of parental overweight/obese on cumulative live birth rate in in vitro fertilization/intracytoplasmic sperm injection using a freeze-all strategy is still unknown.ObjectiveTo explore the effect of parental body mass index (BMI) on cumulative live birth rate (CLBR) in a freeze-all strategy over 1.5 years.MethodsThis was a retrospective study in a tertiary care academic medical center; 23 482 patients (35 289 frozen–thawed embryo transfer cycles) were divided into 4 groups according to Asian BMI classification. The main outcome measure was CLBR.ResultsFemale overweight/obesity had a lower tendency in CLBR (groups 1-4: optimistic: 69.4%, 67.9%, 62.3%, and 65.7%; conservative: 62.9%, 61.1%, 55.4%, and 57.6%) and prolonged time (groups 1-4: 11.0, 12.2, 15.9, and 13.8 months for 60% CLBR in the optimistic method; 8.7, 9.5, 11.7, 11.0 months for 50% CLBR in the conservative method). The same trend to a lesser extent was also observed in male BMI groups. When combining parental BMI, “parental overweight/obesity” had lower CLBR and longer time for reaching CLBR &gt;50% (optimistic: 4.5 months for 60% CLBR; conservative: 3 months for 50% CLBR), followed by “only female high BMI” (optimistic: 2.1 months for 60% CLBR; conservative: 1.7 months for 50% CLBR), while “only male high BMI” had no influence.ConclusionOur results showed the importance of parental BMI, female BMI, and male BMI on the 1.5-year CLBR using a freeze-all strategy; the time to reach the CLBR (60% in optimistic, 50% in conservative) for overweight and obese patients was several months, but it is not as long as losing weight.
Teamwork, Targets, Technology, and Tight Control in Newly Diagnosed Type 1 Diabetes: the Pilot 4T Study
Authors: Prahalad Priya , Ding Victoria Y , Zaharieva Dessi P , Addala Ananta , Johari Ramesh , Scheinker David , Desai Manisha , Hood Korey , Maahs David M 
Published: December 2021

Abstract

Context
Youth with type 1 diabetes (T1D) do not meet glycated hemoglobin A1c (HbA1c) targets.

Objective
This work aimed to assess HbA1c outcomes in children with new-onset T1D enrolled in the Teamwork, Targets, Technology and Tight Control (4T) Study.

Methods
HbA1c levels were compared between the 4T and historical cohorts. HbA1c differences between cohorts were estimated using locally estimated scatter plot smoothing (LOESS). The change from nadir HbA1c (month 4) to 12 months post diagnosis was estimated by cohort using a piecewise mixed-effects regression model accounting for age at diagnosis, sex, ethnicity, and insurance type. We recruited 135 youth with newly diagnosed T1D at Stanford Children’s Health. Starting July 2018, all youth within the first month of T1D diagnosis were offered continuous glucose monitoring (CGM) initiation and remote CGM data review was added in March 2019. The main outcomes measure was HbA1c.

Results
HbA1c at 6, 9, and 12 months post diagnosis was lower in the 4T cohort than in the historic cohort (–0.54% to –0.52%, and –0.58%, respectively). Within the 4T cohort, HbA1c at 6, 9, and 12 months post diagnosis was lower in those patients with remote monitoring than those without (–0.14%, –0.18% to –0.14%, respectively). Multivariable regression analysis showed that the 4T cohort experienced a significantly lower increase in HbA1c between months 4 and 12 (P &lt; .001).

Conclusion
A technology-enabled, team-based approach to intensified new-onset education involving target setting, CGM initiation, and remote data review statistically significantly decreased HbA1c in youth with T1D 12 months post diagnosis.
Clinical Profiles and Genetic Spectra of 814 Chinese Children With Short Stature
Authors: Li Xin , Yao Ruen , Chang Guoying , Li Qun , Song Cui , Li Niu , Ding Yu , Li Juan , Chen Yao , Wang Yirou , Huang Xiaodong , Shen Yongnian , Zhang Hao , Wang Jian , Wang Xiumin 
Published: December 2021

Abstract

Context
Data and studies based on exome sequencing for the genetic evaluation of short stature are limited, and more large-scale studies are warranted. Some factors increase the likelihood of a monogenic cause of short stature, including skeletal dysplasia, severe short stature, and small for gestational age (SGA) without catch-up growth. However, whether these factors can serve as predictors of molecular diagnosis remains unknown.

Objective
We aimed to explore the diagnostic efficiency of the associated risk factors and their exome sequences for screening.

Methods
We defined and applied factors that increased the likelihood of monogenic causes of short stature in diagnostic genetic tests based on next-generation sequencing (NGS) in 814 patients with short stature and at least 1 other factor.

Results
Pathogenic/likely pathogenic (P/LP) variants in genes, copy number variations, and chromosomal abnormalities were identified in 361 patients. We found P/LP variants among 111 genes, and RASopathies comprised the most important etiology. Short stature combined with other phenotypes significantly increased the likelihood of a monogenic cause, including skeletal dysplasia, facial dysmorphism, and intellectual disability, compared with simple severe short stature (&lt;–3 SD scores). We report novel candidate pathogenic genes, KMT2C for unequivocal growth hormone insensitivity and GATA6 for SGA.

Conclusion
Our study identified the diagnostic characteristics of NGS in short stature with different risk factors. Our study provides novel insights into the current understanding of the etiology of short stature in patients with different phenotypes.
Pathological and Genetic Stratification for Management of Adrenocortical Carcinoma
Authors: Clay Michael R , Pinto Emilia M , Fishbein Lauren , Else Tobias , Kiseljak-Vassiliades Katja 
Published: December 2021

Abstract

Context
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that affects patients across the age spectrum. Although the overall survival in patients with ACC is poor, there is significant heterogeneity in terms of outcomes, presentation, and underlying genetic drivers.

Evidence Acquisition
This review is based on the evidence collected from primary research studies, expert reviews, and published guidelines. The studies were identified through PubMed search with key words “adrenocortical carcinoma,” “prognosis,” “pathology,” and “genetics.” The PubMed search was complemented by authors’ expertise, research, and clinical experience in the field of ACC.

Evidence Synthesis
Identification of biomarkers has been critical to gain better insight into tumor behavior and to guide therapeutic approach to patients. Tumor stage, resection status, and Ki67 are pathological tumor characteristics that have been identified as prognosticators in patients with ACC. Cortisol excess also correlates with worse prognosis. Clinical and histopathological characteristics help stratify patient outcomes, yet still up to 25% of patients have a different outcome than predicted. To bridge this gap, comprehensive genomic profiling studies have characterized additional profiles that correlate with clinical outcomes. In addition, studies of clinically applicable molecular markers are under way to further stratify outcomes in patients with ACC tumors.

Conclusions
Clinical predictors in combination with pathological markers play a critical role in the approach to patients with ACC. Recent advances in genetic prognosticators will help extend the stratification of these tumors and contribute to a personalized therapeutic approach to patients with ACC.
Heparin Effects on Serum Gonadotropins
Authors: Kohn Sarah A , Fought Angela J , Kuhn Katherine , Jones Slogett Kelsey , Bradford Andrew P , Santoro Nanette , Schauer Irene 
Published: December 2021

AbstractIntroductionStudies using lipid infusions to raise fatty acid levels require heparin to release lipoprotein lipase (LPL), thus calling into question the appropriate control infusion for this type of study: saline alone or saline plus heparin. We aimed to evaluate whether the addition of heparin alone, in doses needed to release LPL, would alter circulating free fatty acids (FFAs) and/or affect gonadotropins.Materials and MethodsThis was a secondary analysis using combined data from eumenorrheic normal-weight women subjected to “control” conditions in 1 of 2 separate studies. In 1 study, participants received saline alone (group 1) as a control, and in the other study participants received saline alone and/or saline plus heparin (groups 2-3) as a control. Both studies performed early follicular phase, frequent blood sampling. FSH and LH were compared across groups and in conditions with and without heparin. Linear mixed models were used to analyze the data.ResultsLH did not differ across any of the 3 groups. Estimated means (SE) for FSH differed between groups but this difference was marginal (P = .05) after adjusting for anti-Mullerian hormone and unrelated to heparin infusion (group 1: 4.47 IU/L [SE 1.19], group 2: 8.01 IU/L [SE 1.14], group 3: 7.94 IU/L [SE 1.13]).ConclusionsHeparin does not exert major effects on gonadotropins when infused in quantities sufficient to release LPL. However, because it can release other vascular membrane-bound proteins, heparin should be considered part of the control infusions in lipid infusion studies where increased FFA levels are the goal.