bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemodynamic analysis for endovascular treatment in small unruptured intracranial aneurysms: a matched comparison study of flow diverter versus LVIS
Authors: Liu Jian , Li Wenqiang , Zhang Yisen , Wang Kun , Yang Xinjian , Zhang Ying
Published: December 2021

Background

We compared the treatment of small unruptured intracranial aneurysms (UIAs) with flow diverter and LVIS-assisted coiling to determine the effects of hemodynamic changes caused by different stent and coil packing in endovascular treatment.

Methods

Fifty-one UIAs in 51 patients treated with pipeline embolization device (PED) were included in this study and defined as the PED group. We matched controls 1:1 and enrolled 51 UIAs who were treated with LVIS stent, which were defined as the LVIS group. Computational fluid dynamics were performed to assess hemodynamic alterations between PED and LVIS. Clinical analysis was also performed between these two groups after the match.

Results

There was no difference in procedural complications between the two groups (P = 0.558). At the first angiographic follow-up, the complete occlusion rate was significantly higher in the LVIS group compared with that in the PED group (98.0% vs. 82.4%, P = 0.027). However, during the further angiographic follow-up, the complete occlusion rate in the PED group achieved 100%, which was higher than that in the LVIS group (98.0%). Compared with the LVIS group after treatment, cases in the PED group showed a higher value of velocity in the aneurysm (0.03 ± 0.09 vs. 0.01 ± 0.01, P = 0.037) and WSS on the aneurysm (2.32 ± 5.40 vs. 0.33 ± 0.47, P = 0.011). Consequently, the reduction ratios of these two parameters also showed statistical differences. These parameters in the LVIS group showed much higher reduction ratios. However, the reduction ratio of the velocity on the neck plane was comparable between two groups.

Conclusions

Both LVIS and PED were safe and effective for the treatment of small UIAs. However, LVIS-assisted coiling produced greater hemodynamic alterations in the aneurysm sac compared with PED. The hemodynamics in the aneurysm neck may be a key factor for aneurysm outcome.
Peer review reduces spin in PCORI research reports
Authors: Mayo-Wilson Evan , Phillips Meredith L. , Connor Avonne E. , Vander Ley Kelly J. , Naaman Kevin , Helfand Mark
Published: December 2021

Background

The Patient-Centered Outcomes Research Institute (PCORI) is obligated to peer review and to post publicly “Final Research Reports” of all funded projects. PCORI peer review emphasizes adherence to PCORI’s Methodology Standards and principles of ethical scientific communication. During the peer review process, reviewers and editors seek to ensure that results are presented objectively and interpreted appropriately, e.g., free of spin.

Methods

Two independent raters assessed PCORI peer review feedback sent to authors. We calculated the proportion of reports in which spin was identified during peer review, and the types of spin identified. We included reports submitted by April 2018 with at least one associated journal article. The same raters then assessed whether authors addressed reviewers’ comments about spin. The raters also assessed whether spin identified during PCORI peer review was present in related journal articles.

Results

We included 64 PCORI-funded projects. Peer reviewers or editors identified spin in 55/64 (86%) submitted research reports. Types of spin included reporting bias (46/55; 84%), inappropriate interpretation (40/55; 73%), inappropriate extrapolation of results (15/55; 27%), and inappropriate attribution of causality (5/55; 9%). Authors addressed comments about spin related to 47/55 (85%) of the reports.

Of 110 associated journal articles, PCORI comments about spin were potentially applicable to 44/110 (40%) articles, of which 27/44 (61%) contained the same spin that was identified in the PCORI research report. The proportion of articles with spin was similar for articles accepted before and after PCORI peer review (63% vs 58%).

Discussion

Just as spin is common in journal articles and press releases, we found that most reports submitted to PCORI included spin. While most spin was mitigated during the funder’s peer review process, we found no evidence that review of PCORI reports influenced spin in journal articles. Funders could explore interventions aimed at reducing spin in published articles of studies they support.
Evaluation of the determinants of food security within the COVID-19 pandemic circumstances- a particular case of Shaanxi, China
Authors: Sarkar Apurbo , Hongyu Wang , Jony Abdul Azim , Das Jiban Chandro , Memon Waqar Hussain , Qian Lu
Published: December 2021

Background

Agricultural food production and distribution industries may play a vital role in determining the current conditions of any country’s food security and sustainable development goals. This paper examined the determinants of food security within three distinct aspects (effective utilization of food, food availability, and food access) within the COVID-19 epidemic situation.

Methods

The qualitative set-up of the study comprised with the identification of drivers by critical analysis of published papers and discussion held with some practitioners. The quantitative data used in this research were collected from a survey covering the agricultural food supply industry in China (Shaanxi Province). The survey was conducted from November to December 2020 and we mainly focus on three aspects of food security (effective utilization of food, food availability, and food access). The core analytical assumptions were made by employing exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and structural equation modeling (SEM).

Results

After analyzing the data collected from 257 agricultural food productions and distribution personnel along with the hypothesis testing, it found that the determinants of the effective utilization of food were positively related to the determinants of food access (β = 0.291, p = 0.029) and food availability (β = 0.298, p = 0.011), and the determinants of food availability were positively related to the food access determinants (β = 0.128, p = 0.002). The association and variance values between food availability and food access were 0.659 and 0.407; the association and variance values between for effective utilization of food and food availability aspects were 0.465 and 0.298, and between effective utilization of food and economy were 0.508 and 0.475.

Conclusion

The study critically evaluated the interconnection among the crucial determinants within the banner of three dimensions, which will act as a major contribution to existing literature. This research will help the government and industry to develop policies and strategies for the successful implementation of all the associated determinants of food security in terms of the epidemic situation.
The effects of straw-returning and inorganic K fertilizer on the carbon–nitrogen balance and reproductive growth of cotton
Authors: HU Wei , YU Chaoran , ZHAO Wenqing , LIU Ruixian , YANG Changqin , ZHOU Zhiguo
Published: December 2021

Background

Many studies have indicated that straw-returning could meet part or even all of the potassium (K) demand for crop growth in the field, but few have compared the effects of crop straw as K source and inorganic K fertilizer on carbon–nitrogen (C–N) balance of cotton and the reproductive growth. To address this, field experiments were conducted using the cotton cultivar, Siza 3, under there treatments (CK as control group one, no crop straw and inorganic K fertilizer were applied; K150 as control group two, 150 kg·ha−1 of K2O was applied; and W9000, 9 000 kg·ha−1 wheat straw, which could provide K2O about 150 kg·ha−1, was incorporated into soil).

Results

Although the final reproductive organ biomass did not differ between W9000 and K150, W9000 had a higher ratio of reproductive organ biomass to total biomass (RRT), suggesting that straw-returning was more conducive to the allocation of biomass to reproductive organs. The theoretical maximum biomass of reproductive organ was higher, but the average and maximum accumulation rates of reproductive organ biomass were 2.8%∼8.3% and 2.5%∼8.2% lower under W9000 than K150. Also, the duration of rapid-accumulation period for reproductive organ biomass (T) was 2.0∼2.8 d longer under W9000 than K150, which was a reason for the higher RRT under W9000. Straw-returning altered the dynamics of leaf K with the growth period, so that W9000 had a more drastic effect on leaf C metabolism than K150. Consequently, lower soluble sugar/free amino acid and C/N ratios were measured under W9000 than K150 at boll-setting (BSS) and boll-opening (BOS) stages. Higher leaf net photosynthetic rate, sucrose phosphate synthase and sucrose synthase activities, and lower acid invertase activity were observed under W9000 than K150 at BSS and BOS and these were more conducive to sucrose accumulation. However, less sucrose was measured under W9000 than K150 at these stages. This should be because straw-returning promoted the assimilate transport capacity when compared with inorganic K fertilizer application, which also explained the higher RRT under W9000 than K150. The lower acid invertase activity under W9000 inhibited the conversion of sucrose to other sugars, hence lower contents of soluble sugar and starch were measured under W9000 than K150.

Conclusion

Under low K condition, crop straw as K source can increase the assimilate transport from source to sink, leading to lower C/N ratio in leaf and higher allocation of biomass to reproductive organs than inorganic K fertilizer.
Evaluation of five algorithms in predicting the sublocalisation of right ventricular outflow tract arrhythmia (RVOTA) when compared to 3D electroanatomical mapping origin
Authors: Prisecaru Raluca Sirbu , Leatu Cristina , Riahi Leila , Costache Victor
Published: December 2021

Purpose

To compare the predictive accuracy of five different algorithms as verified by successful ablation site using 3D electroanatomical non-contact mapping in patients with symptomatic and asymptomatic but high ventricular burden RVOT tachycardias.

Methods

28 Consecutive patients admitted for radiofrequency catheter ablation for symptomatic and asymptomatic, but high ventricular burden idiopathic VPC were recruited for this study. All patients had previous failed or intolerant to beta-blocker and/or at least one class IC anti-arrhythmic agents, and they had normal left ventricular ejection fraction. All patients had documented monomorphic VPC with left bundle branch block morphology and an inferior axis. Concordance of the arrhythmia origin based on ECG algorithm and 3D mapping system site were further evaluated. Of the five algorithms, two algorithms with easy‐applicability and having a memorable design (Dixit and Joshi) and three algorithms with more complex and detailed design (Ito, Zhang, Pytkowski) were selected for comparisons.

Results

Assessment of the diagnostic accuracy showed that each of the five algorithms had only moderate accuracy, and the greatest accuracy was observed in the algorithm proposed by Pytkowski algorithm when assessed by a general cardiologist and Dixit algorithm when evaluated by the electrophysiologist. However, when the algorithms were compared for their accuracy, specificity, sensitivity, no significant differences were found (p = 0.99).

Conclusions

The ECG based algorithms for precise localising RVOTA origin simplify the mapping process, reduce the procedural and fluoroscopic time, and improve clinical outcomes, resulting in greater clinical utility. All the five published 12-lead ECG algorithms for ROTVA differentiation were similar in terms of the diagnostic accuracy, specificity, sensitivity and LRs.
The mildly decreased preoperative bilirubin level is a risk factor for periprosthetic joint infection after total hip and knee arthroplasty
Authors: Fu Jun , Chen Xiyue , Ni Ming , Li Xiang , Hao Libo , Zhang Guoqiang , Chen Jiying
Published: December 2021

Background

Many serologic markers are routinely tested prior to joint arthroplasty, but only few are commonly used to guide surgeons in determining patients most at risk of periprosthetic joint infection (PJI). The objective of this study was to investigate the association between preoperative bilirubin level and PJI after primary hip and knee arthroplasty.

Methods

A retrospective analysis was performed on patients undergoing revision hip and knee arthroplasty at our hospital from January 2016 to December 2019. Laboratory biomarkers were collected before the primary arthroplasty, as well as general patient information. The association between the above serologic markers and postoperative PJI was analyzed.

Results

A total of 72 patients (30 hips/42 knees) were analyzed, including 39 patients with PJI and 33 patients without PJI. Except for total bilirubin (TB) and direct bilirubin (DB), there was no significant difference between the remaining laboratory biomarkers. The preoperative TB and DB in the PJI group were 10.84 ± 0.61 μmol/L and 3.07 ± 0.19 μmol/L, respectively, which were lower than those in the non-PJI group (14.68 ± 0.75 μmol/L and 4.70 ± 0.39 μmol/L, P < 0.001). The area under the curve (AUC) of preoperative TB to predict PJI was 0.755 (P < 0.001, cutoff = 11.55 μmol/L, sensitivity = 66.67%, specificity = 75.76%). Meanwhile, the AUC of preoperative DB was 0.760 (P < 0.001, cutoff = 4.00 μmol/L, sensitivity = 84.62%, specificity = 54.45%).

Conclusions

The serum levels of TB and DB before the primary arthroplasty were lower in PJI patients than in non-PJI patients, and the preoperative values lower than 11.55 μmol/L and 4.00 μmol/L could be considered as a risk factor for postoperative PJI.
Endoscopic retrieval of ingested magnets in children and role of magnetic retrievers
Authors: Elzeneini Wael M. , Cusick Eleri
Published: December 2021

Background

Various high-powered magnetic toy sets constitute a major hazard as the small magnets can be easily swallowed or aspirated by young children. Multiple ingested magnets or the ingestion of a magnet with another metallic object can pose a serious threat as this may lead to bowel perforation, fistulation, intestinal volvulus, bowel obstruction and death.

Main body

Retrieval of ingested magnets from the stomach is routinely performed endoscopically but can become a painstaking quest involving many tedious attempts to secure the magnet(s). Historically, pre-routine endoscopy, magnetic retrievers were used under fluoroscopic control for the removal of metallic objects in the stomach. With the advent of endoscopic retrieval instruments, they fell out of favour and are no longer readily available on the market. Despite this, conventional endoscopic instruments are likely to be less effective than endoscopic-assisted magnetic retrievers due to confounding weak bonds which form between the metal retrieval device and the magnet.

Preoperative testing, and selection of the retrieval instrument with the strongest coupling effect with a magnet, might be beneficial. A simple, endoscopic-assisted magnetic retriever created in theatre can allow for more effective, time-efficient and safe removal of ingested magnets under direct vision.

Conclusion

Urgent removal of multiple ingested magnets or a single ingested magnet coupled with another ingested metallic object should be highlighted. Stricter implementation of a widespread ban over loose magnetic toys is needed. Standardised protocols for the surgical management of ingested magnets should be available in every hospital.
Multicentre randomised controlled trial of a group psychological intervention for postnatal depression in British mothers of South Asian origin (ROSHNI-2): study protocol
Authors: Husain Nusrat , Lovell Karina , Chew-Graham Carolyn A. , Lunat Farah , McPhillips Rebecca , Atif Najia , Aseem Saadia , Begum Jasmin , Bee Penny , Bhui Kamaldeep , Bower Peter , Brugha Traolach , Bhatti Nafeesa , Chaudhry Nasim , Davies Linda , Gire Nadeem , Islam Anharul , Kai Joe , Morrison Jill , Mohmed Naeem , Neelam Jyothi , Rahman Atif , Rathod Shanaya , Siddiqi Najma , Shah Sadia , Shiri Tinevimbo , Waheed Waquas , Mirza Ilyas , Williams Chris , Zaidi Nosheen , Emsley Richard , Morriss Richard
Published: December 2021

Background

In the UK, postnatal depression is more common in British South Asian women than White Caucasion women. Cognitive–behavioural therapy (CBT) is recommended as a first-line treatment, but there is little evidence for the adaptation of CBT for postnatal depression to ensure its applicability to different ethnic groups.

Aims

To evaluate the clinical and cost-effectiveness of a CBT-based positive health programme group intervention in British South Asian women with postnatal depression.

Method

We have designed a multicentre, two-arm, partially nested, randomised controlled trial with 4- and 12-month follow-up, comparing a 12-session group CBT-based intervention (positive health programme) plus treatment as usual with treatment as usual alone, for British South Asian women with postnatal depression. Participants will be recruited from primary care and appropriate community venues in areas of high South Asian density across the UK. It has been estimated that randomising 720 participants (360 into each group) will be sufficient to detect a clinically important difference between a 55% recovery rate in the intervention group and a 40% recovery rate in the treatment-as-usual group. An economic analysis will estimate the cost-effectiveness of the positive health programme. A qualitative process evaluation will explore barriers and enablers to study participation and examine the acceptability and impact of the programme from the perspective of British South Asian women and other key stakeholders.
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

Background

The 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.

Aims

The 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.

Methods

An 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.

Results

During 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).

Conclusions

The 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

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

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

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

Design 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

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 < .0001). TBS increased by 5.8 ± 5.6% (P < .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

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 < 0.05), while ECL and RBA-GADA z-score titers were higher in participants with HLA-DR3 haplotypes only (both Ps < 0.001). ECL-IAA (but not RBA-IAA) positivity was associated with the HLA-DR4 haplotype (P < 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

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 < 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 > 140 mg/dL and 3.4% time > 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 > 140, > 180, and > 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

Context

The 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.

Objective

To explore the effect of parental body mass index (BMI) on cumulative live birth rate (CLBR) in a freeze-all strategy over 1.5 years.

Methods

This 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.

Results

Female 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 >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.

Conclusion

Our 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

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 < .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

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 (<–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

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

Introduction

Studies 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 Methods

This 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.

Results

LH 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]).

Conclusions

Heparin 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.
A novel fission yeast platform to model N-glycosylation and the bases of congenital disorders of glycosylation type I
Authors: Gallo Giovanna L. , Valko Ayelen , Herrera Aguilar Nathalia , Weisz Ariel D. , D'Alessio Cecilia
Published: December 2021

Congenital disorders of glycosylation type I (CDG-I) are inherited human diseases caused by deficiencies in lipid-linked oligosaccharide (LLO) synthesis or the glycan transfer to proteins during N-glycosylation. We constructed a platform of 16 Schizosaccharomyces pombe strains that synthesize all possible theoretical combinations of LLOs containing three to zero glucose (Glc) residues and nine to five mannose (Man) residues. The occurrence of unexpected LLOs suggested the requirement of specific Man residues for glucosyltransferase activities. We then quantified protein hypoglycosylation in each strain and found that in S. pombe the presence of Glc in the LLO is more relevant to the transfer efficiency than the number of Man residues. Surprisingly, a decrease in the number of Man residues in glycans somehow improved the glycan transfer. The most severe hypoglycosylation was produced in cells that synthesized LLOs completely lacking Glc and having a high number of Man residues. This deficiency could be reverted by expressing a single-subunit oligosaccharyltransferase with a broad range of substrate specificity. Our work shows the usefulness of this new S. pombe set of mutants as a platform to model the molecular bases of human CDG-I diseases.

This article has an associated First Person interview with the first authors of the paper.
La liberté de religion entre droit européen des droits de l’homme et droit national
Authors: Τσεβάς Χρήστος
Published: December 2021

Στην πρόσφατη παγκόσμια ιστορία, το δόγμα των ανθρωπίνων δικαιωμάτων ασχολήθηκε πρωτίστως με την προστασία της ανθρώπινης αξιοπρέπειας. Δεδομένου ότι τα κράτη είναι οι «δημιουργοί και παραβάτες» του διεθνούς δικαίου, η ανάγκη καθορισμού κριτηρίων των ανθρωπίνων δικαιωμάτων φαίνεται να είναι μια συνεχής μάχη μεταξύ της θεωρίας και της αποτελεσματικής εφαρμογής τους. Επιπλέον, όταν το δίκαιο και η θρησκεία συναντώνται, δεν υπάρχει κοινός ορισμός της τελευταίας στο πλαίσιο των συμβάσεων ανθρωπίνων δικαιωμάτων και είναι δύσκολο να εντοπιστεί στις εθνικές έννομες τάξεις. Η έρευνα οργανώθηκε γύρω από τρεις άξονες: α) τη θρησκευτική ελευθερία, ως πρότυπο στο πλαίσιο του «σκληρού» και του «ήπιου» δικαίου, αλλά και ως ερμηνευτική έννοια στην ευρωπαϊκή και εθνική νομολογία, β) την αλληλεπίδραση μεταξύ του ευρωπαϊκού δικαίου των δικαιωμάτων του ανθρώπου και του εθνικού και ειδικότερα του συνταγματικού δικαίου ή, με άλλα λόγια, μεταξύ των αρχών που πηγάζουν από την οικουμενικότητα και εκείνων που απορρέουν από τη διαφορετικότητα ή την εθνική ιδιαιτερότητα και γ) τη σύγκριση ως μεθοδολογία που αναπτύσσεται, αφενός, μεταξύ της Τουρκίας και της Γαλλίας, ως δύο νομικά και συνταγματικά συστήματα των οποίων ο σκληρός πυρήνας είναι η ανεξιθρησκία και η θρησκευτική ουδετερότητα του κράτους και, από την άλλη πλευρά, μεταξύ αυτών των συστημάτων και του ευρωπαϊκού επιπέδου, δηλαδή κυρίως του Συμβουλίου της Ευρώπης και της Ευρωπαϊκής Ένωσης. Στο πλαίσιο της θεωρίας της θρησκευτικής ελευθερίας και με βάση την εξέλιξη των αρχών της από το εθνικό στο ευρωπαϊκό επίπεδο και αντίστροφα, η έρευνα αναλύει τις «μετα-αρχές» της ασφάλειας δικαίου, της οικουμενικότητας της ελευθερίας της θρησκείας, την εθνική διαφορετικότητα και τη δυναμική ουδετερότητα.
Ecological diversity of Pliocene to Pleistocene Palaearctic cercopithecids (Primates, Mammalia)
Authors: Πλαστήρας Χρήστος-Αλέξανδρος
Published: December 2021

Ο σκοπός της παρούσας εργασίας είναι η διερεύνηση της οικολογίας των κερκοπιθήκων του Πλειοκαίνου και Πλειστοκαίνου του Ευρωπαϊκού χώρου, αναλύοντας την διατροφική τους οικολογία, η οποία θα συμβάλει στη γνώηση της εξέλιξης των Cercopithecidae στην περιοχή της Ευρώπης κατά την χρονική περίοδο μελέτης. Αυτό επιτεύχθηκε με τη συνδυαστική χρήση δύο μεθοδολογιών: οδοντική τοπογραφία - ανάλυση πάχους αδαμαντίνης και ανάλυση υφής μικροτριβής (DMTA). Η μελέτη επικεντρώνεταί σε απολιθωμένο οδοντικό υλικό που βρίσκεται σε διάφορες συλλογές μουσείων και πανεπιστημιών της Ευρώπης, από το Mesopithecus monspessulanus που ανήκει στο απολιθωμένο γένος Mesopithecus, και απολιθωμένους αντιπροσώπους των γενών Dolichopithecus, Paradolichopithecus και Macaca. Τα αποτελέσματα της εν λόγω εργασίας αναμένεται να αυξήσουν την πληθώρα πληροφοριών όσων αφορά το οικολογικό υπόβαθρο των απολιθωμένων αντιπρόσωπων της οικογένειας Cercopithecidae του Ευρωπαϊκού χώρου. Επιπλέον, συμβάλλουν περαιτέρω στην καλύτερη κατανόηση του τρόπου με τον οποίο οικολογικές διαδικασίες, όπως ο ανταγωνισμός για χώρο και διατροφικούς πόρους, έχουν επηρεάσει την εξέλιξη αυτής της οικογένειας πρωτευόντων στην εν λόγω γεωγραφική περιοχή την χρονική περίοδο μελέτης. Όλα τα παραπάνω αναμένεται να τροφοδοτήσουν περισσότερους ερευνητές στο μέλλον να διερευνήσουν πιθανές επιπτώσεις αυτών των οικολογικών αλληλεπιδράσεων σε κοινωνίες πρωτευόντων σήμερα αλλά και στο παρελθόν.