bluuebunny/crossref_metadata_2025_split huggingface dataset:
A brain structural connectivity biomarker for autism spectrum disorder diagnosis in early childhood
Authors: Jiang Xi , Shou Xiao-Jing , Zhao Zhongbo , Chen Yuzhong , Meng Fan-Chao , Le Jiao , Song Tian-Jia , Xu Xin-Jie , Guo Weitong , Ke Xiaoyan , Cai Xiao-E , Zhao Weihua , Kou Juan , Huo Ran , Liu Ying , Yuan Hui-Shu , Xing Yan , Han Ji-Sheng , Han Song-Ping , Li Yun , Lai Hua , Zhang Lan , Jia Mei-Xiang , Liu Jing , Liu Xuan , Kendrick Keith M , Zhang Rong 
Published: April 2023

Abstract

Background
Autism spectrum disorder (ASD) is associated with altered brain development, but it is unclear which specific structural changes may serve as potential diagnostic markers, particularly in young children at the age when symptoms become fully established. Furthermore, such brain markers need to meet the requirements of precision medicine and be accurate in aiding diagnosis at an individual rather than only a group level.

Objective
This study aimed to identify and model brain-wide differences in structural connectivity using diffusion tensor imaging (DTI) in young ASD and typically developing (TD) children.

Methods
A discovery cohort including 93 ASD and 26 TD children and two independent validation cohorts including 12 ASD and 9 TD children from three different cities in China were included. Brain-wide (294 regions) structural connectivity was measured using DTI (fractional anisotropy, FA) together with symptom severity and cognitive development. A connection matrix was constructed for each child for comparisons between ASD and TD groups. Pattern classification was performed on the discovery dataset and the resulting model was tested on the two independent validation datasets.

Results
Thirty-three structural connections showed increased FA in ASD compared to TD children and associated with both autistic symptom severity and impaired general cognitive development. The majority (29/33) involved the frontal lobe and comprised five different networks with functional relevance to default mode, motor control, social recognition, language and reward. Overall, classification achieved very high accuracy of 96.77% in the discovery dataset, and 91.67% and 88.89% in the two independent validation datasets.

Conclusions
Identified structural connectivity differences primarily involving the frontal cortex can very accurately distinguish novel individual ASD from TD children and may therefore represent a robust early brain biomarker which can address the requirements of precision medicine.
A formula for predicting postoperative functional decline using routine medical data in elderly patients after hip fracture surgery
Authors: Fukuda Taeko , Imai Shinobu , Maruo Kazushi , Horiguchi Hiromasa 
Published: April 2023

Background:
If functional decline after hip surgery can be predicted without special assessment, the effects of new treatments and rehabilitation practices can be easily compared with previous cases or those in other countries. The purpose of this study was to develop and examine a formula for such prediction.

Methods:
Data of 3,120 patients older than 65 yr with hip fracture were analyzed. The Barthel Index was used for evaluating activities of daily living (ADL). Low ADL was defined as patients with a lower score at discharge than the score at admission and patients with complete dependence at admission that did not change until discharge. Three models were developed in a training sample: Basic, Comorbidity, and Laboratory & Vital Signs models were created by inputting basic patient data, the basic data plus comorbidities, the basic data and comorbidities plus 8 laboratory test results and 5 vital signs, respectively. All potential variables with statistical significance < 0.2 on univariate analyses and some variables that may be clinically meaningful were included in multivariable models. The final model was developed by stepwise logistic regression.

Results:
The c-statistic of the Laboratory & Vital Signs formula was 0.701 and the predictive value was 76.9%. The c-statistics of the Basic and Comorbidity formulas were 0.643 and 0.664, respectively. Applying the Laboratory & Vital Signs formula to the validation sample, the c-statistic was 0.663.

Conclusions:
The formula developed from the medical data collected routinely before surgery could predict low ADL following hip fracture surgery in elderly patients.

Level of Evidence:
IVb
Newborn Screening Conditions: Early Intervention and Probability of Developmental Delay
Authors: Reynolds Elizabeth , Blanchard Sheresa , Jalazo Elizabeth , Chakraborty Pranesh , Bailey Donald B. 
Published: April 2023

Abstract:

Objectives:
The purpose of this study is to explore which newborn screening (NBS) conditions are automatically eligible for early intervention (EI) across states and to determine the extent to which each disorder should automatically qualify for EI because of a high probability of developmental delay.

Methods:
We examined each state's EI eligibility policy and reviewed the literature documenting developmental outcomes for each NBS condition. Using a novel matrix, we assessed the risk of developmental delay, medical complexity, and risk of episodic decompensation, revising the matrix iteratively until reaching consensus. Three NBS conditions (biotinidase deficiency, severe combined immunodeficiency, and propionic acidemia) are presented in detail as examples.

Results:
Most states (88%) had Established Conditions lists to autoqualify children to EI. The average number of NBS conditions listed was 7.8 (range 0–34). Each condition appeared on average in 11.7 Established Conditions lists (range 2–29). After the literature review and consensus process, 29 conditions were likely to meet national criteria for an Established Condition.

Conclusion:
Despite benefiting from NBS and timely treatment, many children diagnosed with NBS conditions are at risk for developmental delays and significant medical complexity. The results demonstrate a need for more clarity and guidance regarding which children should qualify for EI. We suggest that most NBS conditions should automatically qualify based on the probability of resulting in a developmental delay. These findings suggest a future opportunity for collaboration between NBS and EI programs to create a consistent set of Established Conditions, potentially expediate referrals of eligible children, and streamline children's access to EI services.
A Model of Ischaemia-Induced Renal Interstitial Fibrosis in Mice with Established Diabetes
Authors: Ma Frank Y , Tesch Greg H , Grynberg Keren , Ozols Elyce , Mulley William R , Nikolic-Paterson David J 
Published: April 2023

ABSTRACT

Background:
Diabetes is a well-established clinical risk factor for the development of acute kidney injury (AKI) following an episode of renal ischaemia. However, we lack a robust animal model to investigate the pathological mechanisms underpinning the increased susceptibility of the diabetic kidney to ischaemia-induced AKI and the transition to chronic kidney disease. The aim of this study was to develop a mouse model in which renal ischaemia induces renal interstitial fibrosis in diabetic mice, but not in control mice.

Methods:
C57BL6/J mice were made diabetic via 5 low dose streptozotocin injections. 8 weeks later, diabetic mice underwent 12 min of bilateral renal ischaemia and were killed on days 1, 7 or 28 after reperfusion. For comparison, groups of age-matched non-diabetic mice underwent the same renal ischaemia/reperfusion injury (IRI) protocol.

Results:
Non-diabetic mice developed AKI on day 1 which showed a virtually complete recovery of structure and function by day 7. By contrast, diabetic mice exhibited a state of chronic renal inflammation and developed a much more severe AKI on day 1 after IRI. Diabetic mice showed a marked delay in the repair response on day 7, and exhibited chronic tubular damage, inflammation and robust interstitial fibrosis on day 28.

Conclusion:
We have developed a mouse model suitable for the dissection of the mechanisms by which diabetes makes the kidney highly susceptible to an ischaemic insult and the transition to chronic kidney disease.
Antidepressive Effectiveness of Amisulpride, Aripiprazole, and Olanzapine in Patients With Schizophrenia Spectrum Disorders
Authors: Kjelby Eirik , Gjestad Rolf , Fathian Farivar , Sinkeviciute Igne , Alisauskiene Renata , Anda Liss , Løberg Else-Marie , Reitan Solveig Klæbo , Joa Inge , Larsen Tor Ketil , Rettenbacher Maria , Berle Jan Øystein , Fasmer Ole Bernt , Kroken Rune Andreas , Johnsen Erik 
Published: April 2023

Abstract

Background
Depressive symptoms are frequent in schizophrenia and associated with a poorer outcome. Currently, the optimal treatment for depressive symptoms in schizophrenia remains undetermined. Amisulpride, aripiprazole, and olanzapine all have antidepressive pharmacodynamic properties, ranging from serotonergic affinities to limbic dopaminergic selectivity. Consequently, in a 12-month pragmatic, randomized clinical trial, we aimed to investigate differences in antidepressive effectiveness among amisulpride, aripiprazole, and olanzapine as a secondary outcome, measured by change in the Calgary Depression Scale for Schizophrenia sum score in patients within the schizophrenia spectrum.

Methods
Psychotic patients within the schizophrenia spectrum were included, and effectiveness was analyzed with latent growth curve modeling.

Results
Of the 144 patients, 51 (35%) were women, the mean age was 31.7 (SD 12.7), and 39% were antipsychotic naive. At inclusion, 68 (47%) participants had a Calgary Depression Scale for Schizophrenia sum score >6, indicating severe depressive symptoms. Across the 12-month follow-up, there was a depressive symptom reduction in all medication groups, but no statistically significant differences between the study drugs. Separate analyses of the subcohort with elevated depressive symptoms at inclusion also failed to find differences in depressive symptom reduction between study drugs. The reduction in depressive symptoms mainly occurred within 6 weeks after randomization.

Conclusions
There was a reduction in depressive symptoms under treatment with amisulpride, aripiprazole, and olanzapine in acutely psychotic patients with schizophrenia spectrum disorder, but no differences between the drugs.
Trough Concentration Response in Infliximab and Adalimumab Treated Children With Inflammatory Bowel Disease Following Treatment Adjustment: A Pharmacokinetic Model
Authors: Levy Rachel , Matar Manar , Zvuloni Maya , Shamir Raanan , Assa Amit 
Published: April 2023

Objectives:
In patients with inflammatory bowel diseases (IBD), data on trough concentration (TC) response to adjustments of anti-tumor necrosis factor (TNFα) are scarce.

Methods:
We included pediatric patients with IBD who were treated with anti-TNFα agents and had sequential monitoring of TC pre- and post-adjustment. Patients with positive anti-drug-antibodies or with concomitant change in immunomodulatory treatment were excluded.

Results:
For the entire cohort (86 patients), median age at diagnosis was 13.2 (interquartile range, 10.7–14.9) years [females, 48%; Crohn disease (CD), 72%]. For infliximab, 58 patients had 201 interval changes and 26 had dose increase. Increase in TC following dose increase could not be predicted due to significant variability (P = 0.9). For every 10% decrease in interval, TC was increased by 1.6 µg/mL or by 57.2% (P = 0.014). Perianal disease was associated with attenuated response. For every 10% increase in interval, TC was decreased by 0.66 µg/mL or by 4.2%. The diagnosis of CD was associated with reduced response to interval increase. For adalimumab, 28 patients had 31 and 12 events of interval decrease or increase, respectively. Interval decrease resulted in increased median TC from 4.5 (3.5–5.3) µg/mL to 8.1 (6.5–10.5) µg/mL (X1.8) while interval increase resulted in TC change from 15.5 (12.8–18.6) µg/mL to 9.7 (6.5–14.6) µg/mL (:1.6) (P < 0.001 for both). Increase in delta TC was associated with younger age, and with absence of perianal disease (P = 0.001).

Conclusion:
Changes in TC following treatment adjustment can be almost linearly predicted for adalimumab while response to infliximab adjustment are more variable.
Impact of organizational climate on the self-efficacy of operating room personnel
Authors: Amiri Fardin , Baghbani Mina , Hannani Sedigheh , Azadi Namam Ali 
Published: April 2023

Introduction:
Organizational climate is a set of characteristics of the work environment that are perceived directly and indirectly by employees and influence the behaviour of the organization’s employees. An appropriate organizational climate can be effective in motivating employees, improving morale and the staff’s participation in decision-making. So, it can be effective in increasing the staff’s creativity and innovation as well as productivity and self-efficacy of them. Therefore, the present study aimed to determine the association of organizational climate with the job self-efficacy of the operating room staff in the medical training centres of IUMS in 2020–2021.

Methods:
This study is descriptive and analytical research conducted in 2020–2021. The participants of this study include all the operating room. The research sample included 220 people. The data collection tools in this study are demographic characteristics form, questionnaire on organizational climate and Lyle Sussman and a job self-efficacy questionnaire by Riggs and Knight. Data analysis was performed using SPSS software through statistics of Spearman’s correlation, multiple regression model and Mann–Whitney.

Results:
More than half of the participants (50.5%) had a good organizational climate and high self-efficacy (58.2%). The results of Spearman’s rank correlation coefficient indicated that there was a significant relationship between organizational climate and self-efficacy (P<0.0001).

Conclusion:
Considering that there was a significant association between the organizational climate and self-efficacy, it is recommended that the officials of medical training centres improve the job self-efficacy and organizational climate of the operating room staff based on the conditions and rules governing the operating room by considering the following factors; knowing the organizational climate and personal characteristics of operating room staff, knowing the causes of various conflicts and knowing the ambiguities and challenges in the work environment.
Can Pyridoxine Successfully Reduce Behavioral Side Effects from Levetiracetam?
Authors: Chhabra Nikita , Vanood Aimen , Hoerth Matthew T. , Sanchez Cristina Valencia , O’Carroll Cumara B. 
Published: April 2023

Background:
Levetiracetam is a commonly used anti-seizure medication, with the development of neuropsychiatric symptoms being the most common side effect. Preliminary literature describes the improvement of these symptoms with pyridoxine, mostly within the pediatric population. However, randomized control trial data investigating this relationship is sparse.

Objective:
The objective of this study was to critically assess evidence regarding the role of pyridoxine in the treatment of neuropsychiatric symptoms from levetiracetam.

Methods:
The objective was addressed through the development of a structured, critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, medical librarians, clinical epidemiologists, and content experts in the field of epilepsy.

Results:
A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared pyridoxine versus placebo for the treatment of neuropsychiatric symptoms from levetiracetam in a pediatric population and included 105 patients (46/105 received pyridoxine, 59/105 received placebo). It found that both groups had a significant reduction in behavioral symptoms at the 2-,4-and 6-week time points (P<0.05). However, the authors noted that the pyridoxine group had almost double the relative reduction when compared with the placebo group at all time points: 1.9 at 2 weeks, 2.0 at 4 weeks, and 1.8 at 6 weeks (P=0.001).

Conclusions:
This study suggests that pyridoxine for the treatment of levetiracetam-induced behavioral side effects may result in modest improvement, although many limitations prevent conclusive results. There remains a need for a double-blinded, randomized control trial in both the adult and pediatric populations.
New Onset of Tuberculosis Complicating FDG PET/CT Evaluation in Patient With Recent Chimeric Antigen Receptor T-Cell Therapy
Authors: Wang Guanyun , Yang Xu , Wang Hongrong , Wang Wei , Yang Jigang 
Published: April 2023

AbstractA 16-year-old adolescent girl with CD19 chimeric antigen receptor (CAR) T-cell therapy for acute lymphoblastic leukemia experienced new onset of the fever.18F-FDG PET/CT studies acquired at 1 and 2 months, respectively, after CAR-T, showed foci of abnormal activity in the mediastinal lymph nodes not seen on the study before therapy. However, these foci of abnormal activity were later proven due to newly developed tuberculosis after CAR T-cell therapy.
Coronary Collateral Circulation: A New Predictor of Mortality in Heart Transplant Recipients With Allograft Vasculopathy
Authors: Civieri Giovanni , Masiero Giulia , Osto Elena , Gambino Antonio , Angelini Annalisa , Fraiese Angela , Fedrigo Marny , Toscano Giuseppe , Bottio Tomaso , Perazzolo Marra Martina , Iliceto Sabino , Gerosa Gino , Tona Francesco 
Published: April 2023

Background.
Coronary collateral arteries (CCAs) are anastomotic channels between vessels; although beneficial in atherosclerosis, their role in heart transplantation (HT) recipients is underinvestigated. CCAs initially develop as microcirculation and cardiac allograft vasculopathy (CAV), promoting immune-dependent proliferative angiogenic response, and play a role in their development. In our hypothesis, ischemia induced by coronary microvascular dysfunction (CMD) triggers the development of CCAs, which are, in turn, less functional as affected by CAV themselves.

Methods.
One hundred twenty-one patients receiving HT at our institution were retrospectively evaluated and were included if transthoracic echocardiography with coronary flow velocity reserve (CFVR) assessment and coronary angiography were performed. CMD was defined as CFVR of ≤2.5. Patients with CAV were enrolled, and their angiograms were reviewed to evaluate the presence of CCAs. Cardiovascular mortality was assessed as the main clinical outcome.

Results.
Forty patients were found to have CCAs. Patients with CCAs have lower CFVR than those without CCAs (2.22 ± 0.72 versus 2.69 ± 0.92;P = 0.003), reflecting in different rates of CMD in the 2 groups (72.5% versus 37%; P < 0.001). CMD is associated with higher CAV grades (P < 0.001), which are also associated with CCAs (P < 0.001). Patients with poorly developed CCAs have lower CFVR (P < 0.001). At multivariable analysis, CMD (P = 0.008) and higher CAV grades (P = 0.005) are independent predictors of CCAs. During the median follow-up time of 10.2 (6.6-13.3) y, patients with CCAs have been found to have higher mortality than those without CCAs (57.5% versus 32.1%; P = 0.007). CCAs are associated with a lower probability of survival also in patients with CMD (P < 0.001) and are independent predictors of mortality (P < 0.001).

Conclusions.
Our results demonstrate an interplay between CAV, CMD, and CCAs. We confirm that CAV is associated with CMD, and we show, for the first time, that CMD is associated with CCAs. CCAs are pathophysiologically associated with more severe graft vasculopathy and independently predict mortality after HT.
The Association Between Kidney Donor Profile Index and 1-y Graft Function
Authors: Foresto Renato Demarchi , Hazin Maria Amelia Aguiar , Cassão Bianca Cristina , de Morais Ana Paula Aquino , Felipe Claudia Rosso , Requião-Moura Lucio R. , Medina Pestana José , Tedesco-Silva Helio 
Published: April 2023

Background.
The association between Kidney Donor Profile Index (KDPI) and 1-y estimated glomerular filtration rate (eGFR) with long-term kidney graft survival is well known. Yet, the association between KDPI and 1-y eGFR remains uncertain considering the several concurrent competing risk factors.

Methods.
This single-center, retrospective cohort study analyzed data from 3059 consecutive deceased donor kidney transplant recipients with a 1-y follow-up from January 2013 to December 2017. The aim was to determine the association between the KDPI strata (0%–35%, 36%–50%, 51%–85%, 86%–100%) and 1-y eGFR estimated by the CKD-EPI equation.

Results.
The incidence of delayed graft function (50.6% versus 59.3% versus 62.7% versus 62.0%; P < 0.001) and cytomegalovirus infection (36.7% versus 36.6% versus 43.3% versus 57.8%; P < 0.001) increased with increasing KDPI strata but not biopsy-proven acute rejection (9.1% versus 9.8% versus 8.4% versus 9.1%; P = 0.736). The median 1-y eGFR decreased with increasing KDPI strata (64.8 versus 53.5 versus 46.9 versus 39.1 mL/min/1.73 m2; P < 0.001). In the Cox regression, the higher the KDPI was, the lower the probability of a lower 1-y eGFR was. Assuming the 0%–35% strata as the reference, the likelihood of eGFR <50 mL/min/1.73 m2 was increased by 76.6% (hazard ratio [HR] = 1.767, 95% confidence interval [CI] = 1.406–2.220), 2.24- and 2.87-fold higher for KDPI higher >35%–50% (HR = 2.239, 95% CI = 1.862–2.691), and >51%–85% (HR = 2.871, 95% CI = 2.361–3.491), respectively. Other variables associated with a lower graft function were donor sex (HR male versus female = 0.896, 95% CI = 0.813–0.989) and cold ischemia time (HR for each hour = 1.011, 95% CI = 1.004–1.019). This association was sustained after the Poisson mediation analysis, including delayed graft function, cytomegalovirus, and acute rejection as mediators.

Conclusions.
In this cohort of deceased donor kidney recipients, KDPI, and cold ischemia time were the major independent risk factors associated with lower 1-y kidney function.
Alloreactive T cells to Assess Acute Rejection Risk in Kidney Transplant Recipients
Authors: Mendoza Rojas Aleixandra , Verhoeven Jeroen G.H.P. , de Kuiper Ronella , Clahsen-van Groningen Marian C. , Boer Karin , Hesselink Dennis A. , van Gelder Teun , van Besouw Nicole M. , Baan Carla C. 
Published: April 2023

Background.
Memory T cells are important mediators of transplant rejection but are not routinely measured before or after kidney transplantation. The aims of this study were as follows: (1) validate whether pretransplant donor-reactive memory T cells are reliable predictors of acute rejection (AR) (2) determine whether donor-reactive memory T cells can distinguish AR from other causes of transplant dysfunction.

Methods.
Samples from 103 consecutive kidney transplant recipients (2018–2019) were obtained pretransplantation and at time of for-cause biopsy sampling within 6 mo of transplantation. The number of donor-reactive interferon gamma (IFN-γ) and interleukin (IL)-21-producing memory T cells was analyzed by enzyme-linked immunosorbent spot (ELISPOT) assay.

Results.
Of the 63 patients who underwent a biopsy, 25 had a biopsy-proven acute rejection (BPAR; 22 aTCMR and 3 aAMR), 19 had a presumed rejection, and 19 had no rejection. Receiver operating characteristic analysis showed that the pretransplant IFN-γ ELISPOT assay distinguished between patients who later developed BPAR and patients who remained rejection-free (area under the curve [AUC] 0.73; sensitivity 96% and specificity 41%). Both the IFN-γ and IL-21 assays were able to discriminate BPAR from other causes of transplant dysfunction (AUC 0.81; sensitivity 87% and specificity 76% and AUC 0.81; sensitivity 93% and specificity 68%, respectively).

Conclusions.
This study validates that a high number of donor-reactive memory T cells before transplantation is associated with the development of AR after transplantation. Furthermore, it demonstrates that the IFN-γ and IL-21 ELISPOT assays are able to discriminate between patients with AR and patients without AR at the time of biopsy sampling.