bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventing type 1 diabetes development and preserving beta-cell function
Authors: Mastrandrea Lucy D. , Quattrin Teresa 
Published: July 2022

Purpose of review
Type 1 diabetes (T1D) is the most common chronic disease of childhood presenting a significant burden, both in terms of day-to-day medical management and lifelong care. Studies aligned with diverse strategies to prevent or modify the course of T1D are reviewed.

Recent findings
The diagnosis of T1D precedes the classic clinical presentation when insulin dependence develops. With an increased understanding of the pathophysiology of the autoimmune process leading to T1D, treatment strategies to prevent the development of autoimmunity and/or modify the immune response have been trialed in persons at risk for developing the disease. Interventions prior to insulin dependence or very early after clinical diagnosis show some promise both in preventing disease onset and prolonging beta-cell insulin production.

Summary
Significant progress has been made in the treatment of T1D. However, suboptimal glycemic control remains a challenge impacting overall health and quality of life for patients with this chronic disease. Although physicians and basic sciences investigators continue to pursue the prevention of the autoimmune process, the advent of disease-modifying agents is a promising strategy. Further studies are needed to ensure that insulin preservation can be achieved longer term.
The 1 mg overnight dexamethasone suppression test: a danger to the adrenal gland?
Authors: Vanek Chaim , Loriaux Lynn 
Published: July 2022

Purpose of review
The 1 mg overnight dexamethasone suppression test (ONDST) with a cutoff cortisol value of 1.8 mcg/dl (50 nmol/l) is routinely used for the assessment of incidental, benign adrenal nodules. Patients with an abnormal test are diagnosed with mild autonomous cortisol secretion (MACS). This timely commentary reviews the origins of the ONDST, its relationship to the diagnoses of MACS, and whether this is clinically relevant for clinical care.

Recent findings
Millions of incidental adrenal nodules are found on CT scans annually. Several papers in the last three years discuss and advocate for the diagnose of MACS via the ONDST.

Summary
An ONDST cutoff of 1.8 mcg/dl (50 nmol/l) in patients with no clinical features of Cushing's syndrome will produce false positive results and a diagnosis of MACS that could result in unnecessary adrenalectomy.
Agreement and accuracy of shear-wave techniques (point shear-wave elastography and 2D-shear-wave elastography) using transient elastography as reference
Authors: Fernandes Flavia , Piedade Juliana , Freitas Gabriela , Area Philippe , Santos Ricardo , Grinsztejn Beatriz , Veloso Valdilea , Pereira Gustavo , Perazzo Hugo 
Published: July 2022

Objective
We aimed to evaluate the agreement/accuracy of point shear-wave elastography (p-SWE) and 2D-shear-wave elastography (2D-SWE) for liver fibrosis staging using transient elastography (TE) as the reference.

Methods
This retrospective study analyzed data from people with chronic liver diseases submitted to TE, p-SWE, and 2D-SWE. Liver fibrosis stages were defined using the TE’s ‘rule of five’: normal (<5 kPa); suggestive of compensated-advanced chronic liver disease (cACLD) (10–15 kPa); highly suggestive of cACLD (15–20 kPa); suggestive of clinically significant portal hypertension (>20 kPa). Agreement and accuracy of p-SWE and 2D-SWE were assessed. Optimal cutoffs for p-SWE and 2D-SWE were identified using the point nearest to the upper left corner of the ROC curves.

Results
A total of 289 participants were included. The correlation between TE and 2D-SWE (rho = 0.59; P < 0.001) or p-SWE (rho = 0.69; P < 0.001) was satisfactory. The AUROCs (95% CI) of 2D-SWE and p-SWE for TE ≥ 5 kPa; TE ≥ 10 kPa; TE ≥ 15 kPa and TE ≥ 20 kPa were 0.757 (0.685–0.829) and 0.741 (0.676–0.806); 0.819 (0.770–0.868) and 0.870 (0.825–0.915); 0.848 (0.803–0.893) and 0.952 (0.927–0.978); 0.851 (0.806–0.896) and 0.951 (0.920–0.982), respectively. AUROCs of 2D-SWE were significantly lower compared with p-SWE for detecting cACLD. Optimal thresholds of 2D-SWE and p-SWE for TE ≥ 15 kPa were 8.82 kPa (sensitivity = 86% and specificity = 79%) and 8.86 kPa (sensitivity = 90% and specificity = 92%), respectively.

Conclusion
LSM by p-SWE and 2D-SWE techniques were correlated with TE. LSM by p-SWE seems to be more accurate than 2D-SWE to identify patients with more advanced fibrosis.
Adherence to Pediatric Sepsis Treatment Recommendations at Emergency Departments
Authors: Fustiñana Ana , Yock-Corrales Adriana , Casson Nils , Galvis Laura , Iramain Ricardo , Lago Patricia , Da Silva Ana Paula Pereira , Paredes Fátima , Zamarbide María Pia , Aprea Valeria , Kohn-Loncarica Guillermo ,   on behalf of the Sepsis Working Group of the Red de Investigación y Desarrollo de la Emergencia Pediátrica Latinoamericana (RIDEPLA)
Published: July 2022

Objective
Sepsis is one of the most urgent health care issues worldwide. Guidelines for early identification and treatment are essential to decrease sepsis-related mortality. Our aim was to collect data on the epidemiology of pediatric septic shock (PSS) from the emergency department (PED) and to assess adherence to recommendations for its management in the first hour.

Methods
A multicenter, prospective, cross-sectional study was conducted evaluating children with PSS seen at the PED of 10 tertiary-care centers in Latin America. Adherence to guidelines was evaluated.

Results
We included 219 patients (median age, 3.7 years); 43% had comorbidities, 31% risk factors for developing sepsis, 74% clinical signs of “cold shock,” and 13% of “warm shock,” 22% had hypotension on admission. Consciousness was impaired in 55%. A peripheral line was used as initial access in 78% (median placement time, 10 minutes). Fluid and antibiotics infusion was achieved within a median time of 30 minutes (interquartile range [IQR], 20–60 minutes) and 40 minutes (IQR, 20–60 minutes), respectively; 40% responded inadequately to fluids requiring vasoactive drugs (median time at initiation, 60 minutes; IQR, 30–135 minutes). Delay to vasoactive drug infusion was significantly longer when a central line was placed compared to a peripheral line (median time, 133 minutes [59–278 minutes] vs 42 minutes [30–70 minutes], respectively [P < 0.001]). Adherence to all treatment goals was achieved in 13%. Mortality was 10%. An association between mortality and hypotension on admission was found (26.1% with hypotension vs 4.9% without; P < 0.001).

Conclusions
We found poor adherence to the international recommendations for the treatment of PSS in the first hour at the PED in third-level hospitals in Latin America.
Transcription factors dysregulated in three complex birth defects datasets
Authors: Chen Zhong-Zhong , Gao Yun-Qian , Xie Hua , Huang Yi-Chen , Chen Fang , Lei Yun-Ping 
Published: July 2022

Abstract

Objective:
To investigate the roles of transcription factors (TFs) in the etiology of complex human birth defects, including neural tube defects (NTDs), congenital heart diseases (CHDs), and hypospadias.

Methods:
We examined the overlap of genetically associated genes among NTDs, CHDs, and hypospadias. We then compared the expression profiles of these diseases based on all the detected genes and disease-associated TFs. The differentially expressed TFs that we obtained were further subjected to functional enrichment analysis to elucidate their role in the development of these birth defects.

Results:
TF genes were significantly enriched in complex birth defects (P = 5.95 × 10−24). NTDs, CHDs, and hypospadias showed distinct gene expression profiles compared with the controls. Although TFs could not efficiently separate CHDs from normal subjects, distinct gene expression profiles of TFs could distinguish NTDs and hypospadias from controls. Differentially expressed TFs can be used to characterize NTDs, hypospadias, and controls. The enriched TFs in biological processes (BPs) reflected the different morphological processes of NTDs, CHDs, and hypospadias.

Conclusions:
This study indicates that abnormal expression patterns of specific TFs may disrupt the normal requirements for developmental equilibrium through the related BPs. The investigation of genetically associated genes and gene expression profiles for the three different complex birth defects provides new insights into how the dysregulation of TFs influences their developmental process.
Measuring Quality of Life in Chronic Limb-threatening Ischemia Patients and Informal Carers: A Scoping Review
Authors: Shan Leonard L. , Shi Margaret D.Y. , Tew Michelle , Westcott Mark J. , Davies Alun H. , Choong Peter F. 
Published: July 2022

Objective:
To review quality of life (QOL) instruments for chronic limb-threatening ischemia (CLTI) patients and informal carers, and their use in QOL and cost-utility analysis (CUA) studies.

Background:
CLTI is a global health problem with significant morbidity affecting patients and informal carers. QOL is increasingly measured for holistic outcomes assessment and CUA. However, measurement instruments in CLTI are poorly understood.

Methods:
MEDLINE, EMBASE, PsycINFO, CINAHL, COSMIN, PROQOLID, CEA registry, and NHS EED databases were searched for all English language studies up to May 2021. Features of instruments, evidence of measurement property appraisal, and trends in use were assessed. Prospective protocol registration (Open Science Framework: https://doi.org/10.17605/OSF.IO/KNG9U).

Results:
A total of 146 studies on QOL instruments (n=43), QOL outcomes (n=97), and CUA (n=9) were included. Four disease-specific QOL instruments are available for lower extremity arterial disease (intermittent claudication or CLTI). VascuQoL-25 and VascuQoL-6 have been used in CLTI. There is no CLTI-specific instrument. Of 14 generic instruments, SF-36, EQ-5D-3L, NHP, and WHOQOL-BREF were most common. Studies reporting partial measurement property appraisal favored VascuQoL-25, VascuQoL-6, and SF-36. Feasibility considerations include mode of administration and responder burden. None of 4 available carer-specific instruments have been used in CLTI. Since 1992, the number of QOL studies has increased considerably, but CUA studies are scarce. Informal carers have not been assessed.

Conclusions:
This review provides a comprehensive reference for QOL measurement in CLTI that helps end-users with instrument selection, use, and interpretation. However, a CLTI-specific instrument is needed. There is an opportunity to benefit society through future CUA studies and evaluation of QOL in informal carers.
Improved Re-estimation of Perioperative Cardiac Risk Using the Surgical Apgar Score: A Retrospective Cohort Study
Authors: Daza Julian F. , Bartoszko Justyna , Van Klei Wilton , Ladha Karim S. , McCluskey Stuart A. , Wijeysundera Duminda N. 
Published: July 2022

Objective:
To assess whether the Surgical Apgar Score (SAS) improves re-estimation of perioperative cardiac risk.

Background:
The SAS is a novel risk index that integrates three relevant and easily measurable intraoperative parameters (blood loss, heart rate, mean arterial pressure) to predict outcomes. The incremental prognostic value of the SAS when used in combination with standard preoperative risk indices is unclear.

Methods:
We conducted a retrospective cohort study of adults (18 years and older) who underwent elective noncardiac surgery at a quaternary care hospital in Canada (2009–2014). The primary outcome was postoperative acute myocardial injury. The SAS (range 0–10) was calculated based on intraoperative estimated blood loss, lowest mean arterial pressure, and lowest heart rate documented in electronic medical records. Incremental prognostic value of the SAS when combined with the Revised Cardiac Risk Index was assessed based on discrimination (c-statistic), reclassification (integrated discrimination improvement, net reclassification index), and clinical utility (decision curve analysis).

Results:
The cohort included 16,835 patients, of whom 607 (3.6%) patients had acute postoperative myocardial injury. Addition of the SAS to the Revised Cardiac Risk Index improved risk estimation based on the integrated discrimination improvement [2.0%; 95% confidence interval (CI): 1.5%–2.4%], continuous net reclassification index (54%; 95% CI: 46%–62%), and c-index, which increased from 0.68 (95% CI: 0.65–0.70) to 0.75 (95% CI: 0.73–0.77). On decision curve analysis, addition of the SAS to the Revised Cardiac Risk Index resulted in a higher net benefit at all decision thresholds.

Conclusions:
When combined with a validated preoperative risk index, the SAS improved the accuracy of cardiac risk assessment for noncardiac surgery. Further research is needed to delineate how intraoperative data can better guide postoperative decision-making.
The Long-term Value of Bariatric Surgery Interventions for American Adults With Type 2 Diabetes Mellitus
Authors: Chaturvedi Ritika , Gracner Tadeja , Tysinger Bryan , Narain Kimberly , Goldman Dana , Sturm Roland 
Published: July 2022

Background:
Bariatric surgery can cause type 2 diabetes (diabetes) remission for individuals with comorbid obesity, yet utilization is <1%. Surgery eligibility is currently limited to body mass index (BMI) ≥35 kg/m2, though the American Diabetes Association recommends expansion to BMI ≥30 kg/m2.

Objective:
We estimate the individual-level net social value benefits of diabetes remission through bariatric surgery and compare the population-level effects of expanding eligibility alone versus improving utilization for currently eligible individuals.

Methods:
Using microsimulation, we quantified the net social value (difference in lifetime health/economic benefits and costs) of bariatric surgery-related diabetes remission for Americans with obesity and diabetes. We compared projected lifetime surgical outcomes to conventional management at individual and population levels for current utilization (1%) and eligibility (BMI ≥35 kg/m2) and expansions of both (>1%, and BMI ≥30 kg/m2).

Results:
The per capita net social value of bariatric surgery-related diabetes remission was $264,670 (95% confidence interval: $234,527–294,814) under current and $227,114 (95% confidence interval: $205,300–248,928) under expanded eligibility, an 11.1% and 9.16% improvement over conventional management. Quality-adjusted life expectancy represented the largest gains (current: $194,706; expanded: $169,002); followed by earnings ($51,395 and $46,466), and medical savings ($41,769 and $34,866) balanced against the surgery cost ($23,200). Doubling surgical utilization for currently eligible patients provides higher population gains ($34.9B) than only expanding eligibility at current utilization ($29.0B).

Conclusions:
Diabetes remission following bariatric surgery improves healthy life expectancy and provides net social benefit despite high procedural costs. Per capita benefits appear greater among currently eligible individuals. Therefore, policies that increase utilization may produce larger societal value than expanding eligibility criteria alone.
Bilateral Simultaneous Nonarteritic Anterior Ischemic Optic Neuropathy: Demographics, Risk Factors, and Visual Outcomes
Authors: Chung Jennifer E. , Singaravelu Janani , Wilson Bradley S. , Baykal Annah P. , Lee Michael S. , McClelland Collin M. , Chen John J. , Bhatti M. Tariq , Melson Andrew T. , Van Stavern Gregory P. 
Published: July 2022

Background:
Although nonarteritic anterior ischemic optic neuropathy is a well-known cause of vision loss, it typically presents unilaterally. Simultaneous, bilateral nonarteritic anterior ischemic optic neuropathy (sNAION) is rare and poorly studied in comparison. This study seeks to characterize the clinical features and risk factors of patients with sNAION compared with unilateral NAION (uNAION).

Methods:
In this retrospective case–control study, we reviewed 76 eyes (38 patients) with sNAION and 38 eyes (38 patients) with uNAION (controls) from 4 academic institutions examined between 2009 and 2020. Demographic information, medical history, medication use, symptom course, paraclinical evaluation, and visual outcomes were collected for all patients.

Results:
No significant differences were observed in demographics, comorbidities and their treatments, and medication usage between sNAION and uNAION patients. sNAION patients were more likely to undergo an investigative work-up with erythrocyte sedimentation rate measurement (P = 0.0061), temporal artery biopsy (P = 0.013), lumbar puncture (P = 0.013), and MRI (P < 0.0001). There were no significant differences between the 2 groups for visual acuity, mean visual field deviation, peripapillary retinal nerve fiber layer thickness, or ganglion cell-inner plexiform layer thickness at presentation, nor at final visit for those with ≥3 months of follow-up. The sNAION eyes with ≥3 months of follow-up had a smaller cup-to-disc ratio (CDR) at final visit (P = 0.033). Ten patients presented with incipient NAION, of which 9 suffered vision loss by final visit.

Conclusion:
Aside from CDR differences, the risk factor profile and visual outcomes of sNAION patients seem similar to those of uNAION patients, suggesting similar pathophysiology.
Modifying Pavlovian-To-Instrumental Transfer By Approach Avoidance Training In Healthy Subjects – A Proof of Concept Study
Authors: Rosenthal Annika , Chen Ke , Beck Anne , Romanczuk-Seiferth Nina 
Published: July 2022

AbstractThe modulation of instrumental action by conditioned Pavlovian cues is hypothesized to play a role in the emergence and maintenance of maladaptive behavior. The Pavlovian-to-instrumental transfer (PIT) task is designed to examine the magnitude of the influence of cues on behavior and we aim to manipulate the motivational value of Pavlovian cues to reduce their effect on instrumental responding. To this end, we utilized a joystick-based modification of approach and avoidance propensities that has shown success in clinical populations. In 35 healthy subjects, we examined changes in PIT after completion of either avoidance training or sham training. We found no effect of training on approach avoidance propensities but higher response rate towards negative stimuli during PIT after systematic avoidance training compared to sham training. On the other hand, we saw an increased PIT effect after sham training. These results imply that training can alter the strength of the influence of cues on instrumental behavior and suggest training to be beneficial in reducing environmental triggers of maladaptive behavior.
Mapping protein-DNA interactions with DiMeLo-seq
Authors: Maslan Annie , Altemose Nicolas , Mishra Reet , Marcus Jeremy , Brennan Lucy D. , Sundararajan Kousik , Karpen Gary , Straight Aaron F. , Streets Aaron 
Published: July 2022

AbstractWe recently developedDirectedMethylation withLong-readsequencing (DiMeLo-seq) to map protein-DNA interactions genome wide. DiMeLo-seq is capable of mapping multiple interaction sites on single DNA molecules, profiling protein binding in the context of endogenous DNA methylation, identifying haplotype specific protein-DNA interactions, and mapping protein-DNA interactions in repetitive regions of the genome that are difficult to study with short-read methods. With DiMeLo-seq, adenines in the vicinity of a protein of interest are methylated in situ by tethering the Hia5 methyltransferase to an antibody using protein A. Protein-DNA interactions are then detected by direct readout of adenine methylation with long-read, single-molecule, DNA sequencing platforms such as Nanopore sequencing. Here, we present a detailed protocol and practical guidance for performing DiMeLo-seq. This protocol can be run on nuclei from fresh, lightly fixed, or frozen cells. The protocol requires 1-2 days for performing in situ targeted methylation, 1-5 days for library preparation depending on desired fragment length, and 1-3 days for Nanopore sequencing depending on desired sequencing depth. The protocol requires basic molecular biology skills and equipment, as well as access to a Nanopore sequencer. We also provide a Python package,dimelo, for analysis of DiMeLo-seq data.Key papersAltemose, N., Maslan, A., Smith, O.K., Sundararajan, K., Brown, R.R., Mishra, R., Detweiler, A.M., Neff, N., Miga, K.H., Straight, A.F. and Streets, A., 2022. DiMeLo-seq: a long-read, single-molecule method for mapping protein–DNA interactions genome wide.Nature Methods, pp.1-13. (https://doi.org/10.1038/s41592-022-01475-6)
Sharp cell-type-identity changes differentiate the retrosplenial cortex from the neocortex
Authors: Sullivan Kaitlin E. , Kraus Larissa , Wang Lihua , Stach Tara R. , Lemire Andrew L. , Clements Jody , Cembrowski Mark S. 
Published: July 2022

ABSTRACTThe laminae of the neocortex are fundamental processing layers of the mammalian brain. Notably, such laminae are believed to be relatively stereotyped across short spatial scales, such that shared laminae between nearby brain regions exhibit similar constituent cells. Here, we considered a potential exception to this rule by studying the retrosplenial cortex (RSC), a brain region known for sharp cytoarchitectonic differences across its granular-dysgranular border. Using a variety of transcriptomics techniques, we identified, spatially mapped, and interpreted the excitatory cell-type landscape of the mouse RSC. In doing so, we surprisingly uncovered that RSC gene expression and cell types change sharply at the granular-dysgranular border. Additionally, supposedly homologous laminae between the RSC and neocortex are effectively wholly distinct in their cell-type composition. In collection, the RSC exhibits a variety of intrinsic cell-type specializations, and embodies a new neocortical organizational principle wherein cell-type identities vary sharply within and between brain regions.
Age at separation, residential mobility, and depressive symptoms among twins in late adolescence and young adulthood: a FinnTwin12 cohort study
Authors: Wang Zhiyang , Whipp Alyce , Heinonen-Guzejev Marja , Kaprio Jaakko 
Published: July 2022

AbstractObjectivesLeaving the parental home at an early age represents a major life event for an adolescent and may predispose them to poor mental health. This study aims to examine the effect of age at separation and residential mobility (from residential records) on depressive symptoms among twins in late adolescence and young adulthood. Age at separation of twins in a twin pair was used as a proxy indicator for the age of leaving the parental homeMethodsThe participants (n=3055) are from the FinnTwin12 cohort. Residential mobility consisted of the number and total distance of moves before age 17. First, we used linear regression to assess the association of age at separation and residential mobility with log-transformed General Behavior Inventory (GBI) scores at age 17 and in young adulthood. Then, the mixed model for repeated measures (MMRM) was used to visualize the GBI scores’ trajectory and test the associations, controlling for “baseline” state.ResultsIn the adjusted linear regression, compared to twins separated before age 17, twins who separated in the later three groups all were significantly lower on log-transformed GBI scores at age 17. The two groups of twins who separated after age 19.5 scored lower GBIs in young adulthood. Compared to twins who never moved before age 17, moving twice led to a lower GBI score. In MMRM, twins who separated later all had lower GBI scores in young adulthood. Twins who moved twice or more had lower GBI scores in young adulthood.ConclusionThe current study provides valid evidence of the family influence on depressive symptoms in later adolescence and young adulthood. A strong association between residential mobility and depressive symptoms was affirmed, although further research is still needed in the future.