bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homogeneity in Motor Competence Among Youths With Intellectual Disability With and Without Down Syndrome
Authors: Pitetti Ken , Bertapelli Fabio , Miller Ruth A. , Jaeger Adam , Loovis E. Michael , do Amaral-Junior Wilson D. , de Barros-Filho Marcos M. , Guerra-Junior Gil 
Published: April 2024

Purpose:
To determine if there is a homogeneity of scores for youth with intellectual disability (ID) with and without Down syndrome (DS) in 19 test items of motor competence from the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition (BOT-2). Homogeneity was defined as the means for each of the 19 test items scores by sex and the presence or absence of DS sharing the same population mean.

Method:
Participants were 622 youth with ID aged 6 to 21 years. Items for bilateral coordination, balance, and upper limb coordination were examined using the BOT-2.

Results:
For all 19 BOT-2 items, means between youth with and without DS did not differ from the population mean.

Conclusion:
These results potentiate the development of expected BOT-2 motor competence scores for youth with ID independent of the presence of DS for clinical practice.
Introducing the i-Rainbow©: An Evidence-Based, Parent-Friendly Care Pathway Designed for Critically Ill Infants in the NICU Setting
Authors: Byrne Eilish M. , Hunt Katherine , Scala Melissa 
Published: April 2024

Purpose:
This study investigated the feasibility and effectiveness of a novel, evidence-based developmental care pathway to be used by health care providers and parents in the neonatal intensive care unit (NICU) setting. The i-Rainbow is based on current evidence and responds to individual infant health status. It is not based on infant age.

Methods:
After development and implementation of the i-Rainbow, pre- and postimplementation nurse and parent survey data were collected and pre- and post–developmental care rates were compared.

Results:
After i-Rainbow implementation, disagreement among providers on appropriate developmental care interventions significantly decreased, total minutes of daily developmental care and swaddled holding increased significantly, and parents reported that they would recommend the tool.

Conclusion:
The i-Rainbow is a unique, parent-friendly, infant-based tool that guides sensory interventions in the NICU by staging infants based on cardiorespiratory status and physiologic maturity, not age. The i-Rainbow improved the delivery of developmental care activities in our unit and was well received by parents and nurses.

Video Abstract:
Supplemental Digital Content available at: http://links.lww.com/PPT/A516
Reducing Rigid Immobilization for Toddler’s Fractures: A Quality Improvement Initiative
Authors: Chen Stephanie N. , Holstine Jessica B. , Samora Julie Balch 
Published: April 2024

Background:
Toddler’s fractures are one of the most common orthopedic injuries in young walking-age children. They are defined as nondisplaced spiral-type metaphyseal fractures involving only the tibia without any injury to the fibula and are inherently stable. We aimed to use quality improvement methodology to increase the proportion of patients with toddler’s fractures treated without cast immobilization at a large tertiary referral pediatric orthopedic center from a baseline of 45.6%–75%.

Methods:
Baseline data on patient volume and treatment regimens for toddler’s fractures were collected starting in February 2019. Monthly data were collected from the electronic medical record and reviewed to determine treatment (cast versus noncast immobilization) and tracked using statistical process control charts (p-chart). After determining the root causes of treatment using immobilization, interventions tested and adopted included physician alignment of expectations for treatment, sharing unblinded compliance data with providers, updating patient education materials, and updating resident education and reference materials.

Results:
After interventions were in place, the percentage of patients treated without CAST immobilization increased from 45.6% to 90% (P ≤ 0.001). We also observed improvement in our process measure to increase the percentage of this population receiving boot immobilization during new patient visits in our orthopedic clinics (4.15% to 52%, P ≤ 0.001).

Conclusions:
By aligning provider and family expectations for treatment, demonstrating no clinical need for cast immobilization, and bringing awareness of compliance to appropriate guidelines, our institution was able to improve care for patients with toddler’s fractures and reduce financial and care burdens for families.
Differential effects of sertraline and cognitive behavioural therapy on behavioural inhibition in patients with obsessive compulsive disorder
Authors: Reid Jemma E. , Pellegrini Luca , Drummond Lynne , Varlakova Yana , Shahper Sonia , Baldwin David S. , Manson Christopher , Chamberlain Samuel R. , Robbins Trevor W. , Wellsted David , Fineberg Naomi A. 
Published: April 2024

Patients with obsessive compulsive disorder (OCD) randomised to sertraline, manualised cognitive behavioural therapy (CBT), or combination (sertraline + CBT), underwent cognitive assessment. Cognitive testing was conducted at baseline and at week 16. The stop signal reaction time task (SSRT) was used to evaluate motor impulsivity and attentional flexibility was evaluated using the intra/extra-dimensional set shifting task. Paired-samples t-tests or nonparametric variants were used to compare baseline and posttreatment scores within each treatment group.
Forty-five patients were tested at baseline (sertraline n = 14; CBT n = 14; sertraline + CBT n = 17) and 23 patients at week 16 (sertraline n = 6; CBT n = 7; sertraline + CBT n = 10). The mean dosage of sertraline was numerically higher in those taking sertraline as a monotherapy (166.67 mg) compared with those taking sertraline in combination with CBT (100 mg). Analysis of pre-post treatment scores using an intent-to-treat-analysis found a significant reduction in the SSRT in those treated with sertraline, whilst there was no significant change on this task for those treated with CBT or the combination. This study found that motor inhibition improved significantly following sertraline monotherapy. Suboptimal sertraline dosing might explain the failure to detect an effect on motor inhibition in the group receiving combination of sertraline + CBT. Higher dose sertraline may have broader cognitive effects than CBT for OCD, motor impulsivity may have value as a measure of treatment outcome and, by extension, the SSRT could serve as a biomarker for personalising care.
Comparative virulome analysis of four Staphylococcus epidermidis strains from human skin and platelet concentrates using whole genome sequencing
Authors: Yousuf Basit , Flint Annika , Weedmark Kelly , Pagotto Franco , Ramirez-Arcos Sandra 
Published: April 2024

Graphical Abstract
Virulome profile of four Staphylococcus epidermidis strains isolated from platelet concentrates and human skin.
Long-read sequencing reveals the RNA isoform repertoire of neuropsychiatric risk genes in human brain
Authors: Paoli-Iseppi Ricardo De , Joshi Shweta , Gleeson Josie , Joseph Prawer Yair David , You Yupei , Agarwal Ria , Li Anran , Hull Anthea , Whitehead Eloise Marie , Seo Yoonji , Kujawa Rhea , Chang Raphael , Dutt Mriga , McLean Catriona , Parker Benjamin Leo , Clark Michael Ben 
Published: April 2024

AbstractNeuropsychiatric disorders are highly complex conditions and the risk of developing a disorder has been tied to hundreds of genomic variants that alter the expression and/or products (isoforms) made by risk genes. However, how these genes contribute to disease risk and onset through altered expression and RNA splicing is not well understood. Combining our new bioinformatic pipeline IsoLamp with nanopore long-read amplicon sequencing, we deeply profiled the RNA isoform repertoire of 31 high-confidence neuropsychiatric disorder risk genes in human brain. We show most risk genes are more complex than previously reported, identifying 363 novel isoforms and 28 novel exons, including isoforms which alter protein domains, and genes such asATG13andGATAD2Awhere most expression was from previously undiscovered isoforms. The greatest isoform diversity was present in the schizophrenia risk geneITIH4. Mass spectrometry of brain protein isolates confirmed translation of a novel exon skipping event in ITIH4, suggesting a new regulatory mechanism for this gene in brain. Our results emphasize the widespread presence of previously undetected RNA and protein isoforms in brain and provide an effective approach to address this knowledge gap. Uncovering the isoform repertoire of neuropsychiatric risk genes will underpin future analyses of the functional impact these isoforms have on neuropsychiatric disorders, enabling the translation of genomic findings into a pathophysiological understanding of disease.
Unlocking the mentally ill in Indonesia: An empirical study of the effectiveness of a “Bebas Pasung” program in Central Java
Authors: Tyas Tri H. , Good Mary-Jo D. , Pratikno Bambang , Subandi M.A. , Marchira Carla R. , Good Byron J. 
Published: April 2024

AbstractBackgroundLocking or confinement of persons with severe mental illness has been common in Indonesia. In 2010, the Ministry of Health declared a policy that persons who were locked (pasung) should be unlocked or freed (bebas) from confinement and provided mental health services. This study is an empirical evaluation of the effectiveness of oneBebas Pasungprogram in Indonesia at two-year follow-up.MethodsFrom medical records in Soerojo Mental Hospital, Magelang, Central Java, 114 persons with severe mental illness who had been unlocked, treated, and returned to the community from four districts served by the hospital were identified. At two-year follow-up, 62 caregivers were able to be contacted and willing to participate in a study. Data were collected from hospital records about condition of the patient at time of ‘unlocking’ and at discharge, and primary caregivers were interviewed about the previous locking and care of the patient since return, as well as experiences of caregiving.ResultsWe provide descriptive data concerning history of illness, reasons for locking, type of confinement, and care of the individual since return. 58% of those unlocked were men, 80% had diagnoses of schizophrenia, and mean age was 35. At follow-up, 24% of this sample had been re-locked; only 44% took medications regularly, including 33% of those re-locked and 47% of those not relocked. A majority cared for themselves, half were partially or fully productive, and the quality of life of family caregivers improved significantly since their family member was unlocked, treated, and returned home.ConclusionsThis program successfully unlocked, treated, and returned to their homes persons with severe mental illness living inpasungor restraints. Findings suggest such unlocking programs need to be linked more closely to community-based mental health and rehabilitation services, maintain care of the patient, and provide a path toward recovery.
Metabolomics Signatures of serotonin reuptake inhibitor (Escitalopram), serotonin norepinephrine reuptake inhibitor (Duloxetine) and Cognitive Behavior Therapy on Key Neurotransmitter Pathways in Major Depressive Disorder
Authors: Bhattacharyya Sudeepa , MahmoudianDehkordi Siamak , Sniatynski Matthew J , Belenky Marina , Marur Vasant R. , Rush A. John , Craighead W. Edward , Mayberg Helen S. , Dunlop Boadie W. , Kristal Bruce S , Kaddurah-Daouk Rima ,   Mood Disorder Precision Medicine Consortium
Published: April 2024

ABSTRACTMetabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive Behavior Therapy (CBT) in 163 treatment-naïve outpatients with major depressive disorder. Serum samples from baseline and 12 weeks post-treatment were analyzed using targeted liquid chromatography-electrochemistry for metabolites related to tryptophan, tyrosine metabolism and related pathways. Changes in metabolite concentrations related to each treatment arm were identified and compared to define metabolic signatures of exposure. In addition, association between metabolites and depressive symptom severity (assessed with the 17-item Hamilton Rating Scale for Depression [HRSD17]) and anxiety symptom severity (assessed with the 14-item Hamilton Rating Scale for Anxiety [HRSA14]) were evaluated, both at baseline and after 12 weeks of treatment.Significant reductions in serum serotonin level and increases in tryptophan-derived indoles that are gut bacterially derived were observed with escitalopram and duloxetine arms but not in CBT arm. These include indole-3-propionic acid (I3PA), indole-3-lactic acid (I3LA) and Indoxyl sulfate (IS), a uremic toxin. Purine-related metabolites were decreased across all arms. Different metabolites correlated with improved symptoms in the different treatment arms revealing potentially different mechanisms between response to antidepressant medications and to CBT.
Combined detrimental effect of male sex and GBA1 variants on cognitive decline in Parkinson’s Disease
Authors: Caminiti Silvia Paola , Avenali Micol , Galli Alice , Malito Rachele , Cuconato Giada , Pilotto Andrea , Padovani Alessandro , Blandini Fabio , Perani Daniela , Tassorelli Cristina , Valente Enza Maria ,   Parkinson’s Progression Markers Initiative (PPMI)
Published: April 2024

AbstractBackground and ObjectiveHeterozygous variants in the glucocerebrosidase gene (GBA1) are the major genetic risk factor for Parkinson’s Disease (PD). GBA-PD has been associated with worse progression and higher risk of cognitive decline. Here we took advantage of the Parkinson’s Progression Markers Initiative (PPMI) to investigate whether sex could interact withGBA1carrier status in determining the clinical phenotype, with a special focus on cognitive decline.MethodsWe evaluated 118 PD subjects carryingGBA1variants (GBA-PD) and 450 with wild-type alleles (nonGBA-PD) included in the PPMI. Dopaminergic activity was assessed in a subset of 248 subjects (65%) with available123I-FP-CIT SPECT scans. Clinical features and dopaminergic activity were investigated in GBA-PD vs. nonGBA-PD groups, upon stratification by sex. PD subjects were followed for up to 6.5Dyears (median 6Dyears). Cox regression was used to model the hazard ratio (HR) of (1)GBA1genotype, (2) sex, (3) gene-by-sex interaction on cognitive decline at follow-up.ResultsRegardless of genotype, men suffering from PD exhibited higher motor disability while women showed more autonomic dysfunction. At baseline, GBA-PD showed more severe motor and non-motor features, and reduced dopamine uptake in the bilateral ventral putamen compared to nonGBA-PD. Within the GBA-PD group, males had higher occurrence of REM sleep behavior disorder and memory deficits. Of note, GBA-PD females showed a greater striatal dopaminergic deficit compared to males, despite presenting similar motor impairment. In longitudinal assessment, Cox Regression revealed that male sex (HR = 1.7),GBA1carrier status (HR =1.6) and, most importantly, GBA-by-male sex interaction (HR = 2.3) were significantly associated with a steeper cognitive decline. Upon stratification forGBA1variant class, both “severe” and “mild” variants were associated with increased risk of cognitive decline, again more relevant in males (HR = 2.3).DiscussionWe show, for the first time, that male sex andGBA1carrier status have an additive value in increasing the risk of cognitive decline in PD, despite the heightened dopaminergic vulnerability observed in GBA-PD females. The effect of sex onGBA1-related pathology warrants further examination and should be considered in future trials design and patients’ selection.
PersistentMycobacterium tuberculosisbioaerosol release in a tuberculosis-endemic setting
Authors: Dinkele Ryan , Gessner Sophia , Patterson Benjamin , McKerry Andrea , Hoosen Zeenat , Vazi Andiswa , Seldon Ronnett , Koch Anastasia , Warner Digby F. , Wood Robin 
Published: April 2024

AbstractPioneering studies linking symptomatic disease and cough-mediated release ofMycobacterium tuberculosis(Mtb) established the infectious origin of tuberculosis (TB), simultaneously informing the pervasive notion that pathology is a prerequisite forMtbtransmission. Our prior work has challenged this assumption: by sampling TB clinic attendees, we detected equivalent release ofMtb-containing bioaerosols by confirmed TB patients and individuals not receiving a TB diagnosis, and we demonstrated a time-dependent reduction inMtbbioaerosol positivity during six-months’ follow-up, irrespective of anti-TB chemotherapy. Now, by extending bioaerosol sampling to a randomly selected community cohort, we show thatMtbrelease is common in a TB-endemic setting: of 89 participants, 79.8% (71/89) producedMtbbioaerosols independently of QuantiFERON-TB Gold status, a standard test forMtbinfection; moreover, during two-months’ longitudinal sampling, only 2% (1/50) were seriallyMtbbioaerosol negative. These results necessitate a reframing of the prevailing paradigm ofMtbtransmission and infection, and may explain the current inability to elucidateMtbtransmission networks in TB-endemic regions.SummaryElucidating chains ofMycobacterium tuberculosistransmission is limited by a dependence on linking sputum-positive tuberculosis cases. Here, we report persistentM. tuberculosisbioaerosol release in the majority of a randomly selected community cohort. The contribution to tuberculosis transmission is unknown.
Elevating levels of the endocannabinoid 2-arachidonoylglycerol blunts opioid reward but not analgesia
Authors: Martínez-Rivera Arlene , Fetcho Robert N. , Birmingham Lizzie , Jiu Jin X , Yang Ruirong , Foord Careen , Scala-Chávez Diego , Mekawy Narmin , Pleil Kristen , Pickel Virginia M. , Liston Conor , Castorena Carlos M. , Levitz Joshua , Pan Ying-Xian , Briand Lisa A. , Rajadhyaksha Anjali M. , Lee Francis S. 
Published: April 2024

AbstractConverging findings have established that the endocannabinoid (eCB) system serves as a possible target for the development of new treatments for pain as a complement to opioid-based treatments. Here we show in male and female mice that enhancing levels of the eCB, 2-arachidonoylglycerol (2-AG), through pharmacological inhibition of its catabolic enzyme, monoacylglycerol lipase (MAGL), either systemically or in the ventral tegmental area (VTA) with JZL184, leads to a substantial attenuation of the rewarding effects of opioids in male and female mice using conditioned place preference and self-administration paradigms, without altering their analgesic properties. These effects are driven by CB1 receptors (CB1Rs) within the VTA as VTA CB1R conditional knockout, counteracts JZL184’s effects. Conversely, pharmacologically enhancing the levels of the other eCB, anandamide (AEA), by inhibition of fatty acid amide hydrolase (FAAH) has no effect on opioid reward or analgesia. Using fiber photometry with fluorescent sensors for calcium and dopamine (DA), we find that enhancing 2-AG levels diminishes opioid reward-related nucleus accumbens (NAc) activity and DA neurotransmission. Together these findings reveal that 2-AG counteracts the rewarding properties of opioids and provides a potential adjunctive therapeutic strategy for opioid-related analgesic treatments.
Microbial ecology and site characteristics underlie differences in salinity-methane relationships in coastal wetlands
Authors: Bueno de Mesquita Clifton P. , Hartman Wyatt H. , Ardón Marcelo , Bernhardt Emily S. , Neubauer Scott C. , Weston Nathaniel B. , Tringe Susannah G. 
Published: April 2024

AbstractMethane (CH4) is a potent greenhouse gas emitted by archaea in anaerobic environments such as wetland soils. Tidal freshwater wetlands are predicted to become increasingly saline as sea levels rise due to climate change. Previous work has shown that increases in salinity generally decrease CH4emissions, but with considerable variation, including instances where salinization increased CH4flux. We measured microbial community composition, biogeochemistry, and CH4flux from field samples and lab experiments from four different sites across a wide geographic range. We sought to assess how site differences and microbial ecology affect how CH4emissions are influenced by salinization. CH4flux was generally, but not always, positively correlated with CO2flux, soil carbon, ammonium, phosphate, and pH. Methanogen guilds were positively correlated with CH4flux across all sites, while methanotroph guilds were both positively and negatively correlated with CH4depending on site. There was mixed support for negative relationships between CH4fluxes and concentrations of alternative electron acceptors and abundances of taxa that reduce them. CH4/salinity relationships ranged from negative, to neutral, to positive and appeared to be influenced by site characteristics such as pH and plant composition, which also likely contributed to site differences in microbial communities. The activity of site-specific microbes that may respond differently to low-level salinity increases is likely an important driver of CH4/salinity relationships. Our results suggest several factors that make it difficult to generalize CH4/salinity relationships and highlight the need for paired microbial and flux measurements across a broader range of sites.