bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive Outcomes in Nonacute Patients With Schizophrenia Treated With Long-Acting Injectable Antipsychotics Versus Oral Antipsychotics
Authors: Petric Paula Simina , Teodorescu Andreea , Miron Ana Aliana , Manea Mihnea Costin , Ifteni Petru 
Published: May 2024

Background:
Patients with schizophrenia often face challenges related to cognitive function, affecting their daily functioning and overall quality of life. The choice of antipsychotic treatment may play a crucial role in determining cognitive outcomes.

Study Question:
Our study aimed to investigate whether there was a difference in cognitive ability between the patients with schizophrenia receiving oral antipsychotics (OAP) versus long-acting injectable antipsychotics (LAI-APs).

Study Design:
We conducted a cross-sectional study using analytical methods between January 1, 2020, and January 1, 2022. Participants were divided into 2 groups: patients undergoing treatment with OAP and patients undergoing treatment with LAI-AP. All participants underwent version A of Brief Assessment of Cognition in Schizophrenia (BACS).

Measures and Outcomes:
The primary objective was to compare cognitive function in patients with schizophrenia treated with LAI antipsychotics versus OAP using BACS. Primary outcome measures include overall BACS score, with secondary measures focusing on specific cognitive domains. This study contributes to the understanding of the cognitive effects of different antipsychotic formulations in schizophrenia treatment.

Results:
Although there was a slightly higher intelligence quotient in the LAI-AP group (102.2 vs. 101.32, P = 0.5401), it was not statistically significant. Olanzapine was the most commonly prescribed antipsychotic, with 48% of patients in the LAI-AP group and 40% in the OAP group. The LAI-AP group outperformed in all BACS evaluations. The most notable difference was in the token motor task (57.78 ± 17.03 vs. 50.04 ± 18.82, P = 0.0335), while the Tower of London test showed the smallest difference (17.26 ± 2.61 vs. 15.48 ± 3.47, P = 0.0046). Regression analysis revealed no significant variance in intelligence quotient scores; however, a significant discrepancy in BACS scores was evident, favoring the LAI treatment for better cognitive outcomes.

Conclusions:
The use of long-acting antipsychotic treatment in individuals with schizophrenia offers promising advantages in preserving cognitive function.
Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis
Authors: Singh Priya , Belliveau Paul , Towle Jennifer , Neculau Andrea Elena , Dima Lorena 
Published: May 2024

Background:
Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone.

Mechanism of Action:
The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals.

Pharmacokinetics:
Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5–9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates.

Clinical Trials:
The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure.

Therapeutic advance:
Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.
The Risk of Kidney Injury in Patients With Sickle Cell Disease Treated With Ketorolac for Acute Pain
Authors: Harris Emily M. , Oni Morohuntodun O. , Donado Carolina , Heeney Matthew M. , Solodiuk Jean , Greco Christine , Archer Natasha M. 
Published: May 2024

Ketorolac, a nonsteroidal anti-inflammatory drug, is used in combination with opioids to manage vaso-occlusive episodes (VOEs). The relationship between ketorolac use and kidney injury in pediatric patients with sickle cell disease (SCD) remains incompletely understood. We hypothesize that ketorolac is associated with acute kidney injury (AKI) in patients with SCD presenting with pain. All nonsurgical hospitalizations for VOEs treated with ketorolac between January 2014 and December 2022 were included. We used optimal matching methodology to identify control admissions (2:1 ratio) and used nonparametric tests to compare ketorolac administration between cases and controls. A total of 1319 encounters/253 patients were included in this study. AKI was noted in 1.1% of encounters and 5.5% of patients. Cases had significantly higher initial BUN than controls (9.0 vs. 6.0 mg/dL, P=0.012). In cases versus controls, there was significantly lower serum sodium (136.0 vs. 138.0 mmol/L, P=0.021). There was no association between ketorolac dose and development of AKI among children with SCD. Higher BUN and lower sodium in cases suggest that patients with AKI were more volume depleted on admission than controls. This highlights the need for strict assessment of fluid status upon admission for VOE.
Counting your chickens before they hatch: improvements in an untreated chronic pain population, beyond regression to the mean and the placebo effect
Authors: Sean Monica , Coulombe-Lévêque Alexia , Nadeau William , Charest Anne-Catherine , Martel Marylie , Léonard Guillaume , Tétreault Pascal 
Published: May 2024

Abstract

Introduction:
Isolating the effect of an intervention from the natural course and fluctuations of a condition is a challenge in any clinical trial, particularly in the field of pain. Regression to the mean (RTM) may explain some of these observed fluctuations.

Objectives:
In this paper, we describe and quantify the natural trajectory of questionnaire scores over time, based on initial scores.

Methods:
Twenty-seven untreated chronic low back pain patients and 25 healthy controls took part in this observational study, wherein they were asked to complete an array of questionnaires commonly used in pain studies during each of 3 visits (V1, V2, V3) at the 2-month interval. Scores at V1 were classified into 3 subgroups (extremely high, normal, and extremely low), based on z-scores. The average delta (∆ = V2 − V1) was calculated for each subgroup, for each questionnaire, to describe the evolution of scores over time based on initial scores. This analysis was repeated with the data for V2 and V3.

Results:
Our results show that high initial scores were widely followed by more average scores, while low initial scores tended to be followed by similar (low) scores.

Conclusion:
These trajectories cannot be attributable to RTM alone because of their asymmetry, nor to the placebo effect as they occurred in the absence of any intervention. However, they could be the result of an Effect of Care, wherein participants had meaningful improvements simply from taking part in a study. The improvement observed in patients with high initial scores should be carefully taken into account when interpreting results from clinical trials.
Intramuscular Granular Cell Tumor Detected on 68Ga-PSMA PET/CT
Authors: Engin Muge N. , Boz Adil 
Published: May 2024

Abstract
Finding of the prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer (PC) cells that have made it possible to evaluate the patients with PC with a single imaging method. 68Ga-PSMA PET/CT is now part of the routine in patients with PC. After several years of clinical experience with PSMA tracers, the specificity is satisfactory; however, concerns about the specificity are raising day by day due to the newly laid out nonprostatic malignant and benign lesions with high PSMA expression. Herein, we present an incidental 68Ga-PSMA uptake in an intramuscular granular cell tumor.
PSMA and FDG PET/CT Findings in Patient With Dedifferentiated Liposarcoma and Prostate Cancer Metastases
Authors: Liao Xuhe , Sun Hongwei , Chen Xueqi , Fan Yan , Zhang Jianhua 
Published: May 2024

Abstract
Dedifferentiated liposarcoma is an extremely rare and highly malignant tumor. We demonstrated a case of a 75-year-old man with significantly PSMA-avid and mildly FDG uptake–dedifferentiated liposarcoma in the retroperitoneal area. The double-tracer (PSMA and FDG) PET scans could further contribute to differential diagnosis and the following treatment strategy for patients who were suspected with prostate cancer metastases and other malignant tumors simultaneously.
Gender Is a Spectrum: Evaluating Current and Novel Ways to Inquire About Gender Identity in the Health Care Setting
Authors: Song Siyou , Phong Kiet T. , Davis Greta , Kim Esther A. 
Published: May 2024

PurposeThe use of visuals to inquire about gender in the clinical setting has been rare. We developed a survey that included a visual spectrum to assess perceptions about the most and least inclusive ways of inquiring about gender in patients with gender dysphoria.MethodsThe survey included a multiple-choice question (MCQ), free-response question, and a visual spectrum on which respondents were asked to select one box that best depicts their gender. The survey was administered to all patients diagnosed with gender dysphoria at our institution between April and June 2022.ResultsA total of 223 of 856 patients responded. Those with more masculine gender identities selected boxes near the visual spectrum corner of “man,” whereas responses were more variable for more feminine genders. The free-response question was identified by 59% of respondents as the most inclusive. The MCQ was identified as least inclusive by 70.4%. The visual spectrum was considered the most inclusive method by the majority of patients who self-identified as woman and demiwoman/demifemale. Being asked about pronouns was extremely or very important in the health care setting for 52% of respondents, but 68.6% indicated that they are rarely or sometimes asked about their pronouns in this setting.ConclusionsThe traditional MCQ format for self-identifying gender may be lacking in inclusivity and fails to represent the nuances of gender identity. Free response was considered the most inclusive way to inquire about gender among our respondents. These findings highlight the importance of formatting gender identity questionnaires to foster inclusivity for transgender patients.
Current diagnosis and management of necrotizing soft tissue infections: What you need to know
Authors: Bisgaard Erika K. , Bulger Eileen M. 
Published: May 2024

ABSTRACTNecrotizing soft tissue infections are rare bacterial infections of the skin and soft tissues with a high morbidity and mortality rate, requiring prompt diagnosis and surgical intervention. These represent a spectrum of disease resulting in tissue necrosis that is rapidly progressive; however, they remain a diagnostic challenge because the average surgeon or emergency medicine provider may only see one or two over the course of their career. Diagnosis is largely clinical and based on subtle physical examination findings, physiologic instability, and laboratory derangements. Aids to diagnosis such as scoring systems and cross-sectional imaging may be used; however, the findings are not specific, so management should not be based on these alone. The most common cause of necrotizing soft tissue infection is polymicrobial infection; however, specific bacteria such as clostridial species, group A streptococcal, methicillin resistantStaphylococcus aureus, and aquatic bacteria may also be causative. Initial management includes broad spectrum antibiotics, fluid resuscitation for severe sepsis, and early aggressive surgical debridement. Often, these patients require multiple operative debridement to achieve source control, and a low threshold for repeat debridement should be maintained because these infections can progress rapidly. Once source control is achieved, patients may be left with extensive wounds requiring multidisciplinary care and wound management. Necrotizing infections have long been viewed based on mortality outcomes alone because of their rarity and severity. Over recent years, more reports have shown a decrease in the mortality rates from those previously reported, allowing for a focus on methods to improve morbidity of these infections.
Whole-exome-based single nucleotide variants and copy number analysis for prenatal diagnosis of compound heterozygosity of SMPD4
Authors: Du Jun , Li Lin , Fu Dinghu 
Published: May 2024

Background
Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder. These variants have been identified in a group of children with neurodevelopmental disorders with microcephaly, arthrogryposis, and structural brain anomalies. SMPD4 encodes a sphingomyelinase that hydrolyzes sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope and interacts with nuclear pore complexes.

Materials and methods
For the efficient prenatal diagnosis of rare and undiagnosed diseases, the parallel detection of copy number variants (CNVs) and single nucleotide variants using whole-exome analysis is required. A physical examination of the parents was performed. Karyotype and whole-exome analysis were performed for the fetus and the parents.

Results
A fetus with microcephaly and arthrogryposis; biallelic null variants (c.387-1G>A; Chr2[GRCh38]: g.130142742_130202459del) were detected by whole-exome sequencing (WES). We have reported for the first time the biallelic loss-of-function mutations in SMPD4 in patients born to unrelated parents in China.

Conclusion
WES could replace chromosomal microarray analysis and copy number variation sequencing as a more cost-effective genetic test for detecting CNVs and diagnosing highly heterogeneous conditions.
Essentiality and dynamic expression of the human tRNA pool during viral infection
Authors: Aharon-Hefetz Noa , Schwartz Michal , Dahan Orna , Stern-Ginossar Noam , Pilpel Yitzhak 
Published: May 2024

AbstractHuman viruses depend on the translation resources of the host cell. A significant translation resource is the tRNA pool of the cell, as human viruses do not encode tRNA genes. Through tRNA sequencing, we inspected the human tRNA pool upon infection of human Cytomegalovirus (HCMV) and SARS-CoV-2. HCMV-induced alterations in tRNA expression were predominantly virus-driven, with minimal influence from the cellular immune response. Notably, specific tRNA post-transcriptional modifications appeared to modulate stability and were susceptible to HCMV manipulation. In contrast, SARS-CoV-2 infection did not significantly impact tRNA expression or modifications. We compared the codon usage of viral genes to the proliferation-differentiation codon-usage signatures of human genes. We found a marked difference between the viruses, with HCMV genes aligning with differentiation codon usage and SARS-CoV-2 genes reflecting proliferation codon usage. We further found that codon usage of structural and gene expression-related viral genes displayed high adaptation to host cell tRNA pools. Through a systematic CRISPR screen targeting human tRNA genes and modification enzymes, we identified specific tRNAs and enzymes that improve or reduce HCMV infectivity and cellular growth. These findings highlight the dynamic interplay between the tRNA pool and viral infection dynamics, shedding light on mechanisms governing host-virus interactions.
Prediction of anti-freezing proteins from their evolutionary profile
Authors: Kumar Nishant , Choudhury Shubham , Bajiya Nisha , Patiyal Sumeet , Raghava Gajendra P. S. 
Published: May 2024

1.AbstractPrediction of antifreeze proteins (AFPs) holds significant importance due to their diverse applications in healthcare. An inherent limitation of current AFP prediction methods is their reliance on unreviewed proteins for evaluation. This study evaluates proposed and existing methods on an independent dataset containing 81 AFPs and 73 non-AFPs obtained from Uniport, which have been already reviewed by experts. Initially, we constructed machine learning models for AFP prediction using selected composition-based protein features and achieved a peak AUC of 0.90 with an MCC of 0.69 on the independent dataset. Subsequently, we observed a notable enhancement in model performance, with the AUC increasing from 0.90 to 0.93 upon incorporating evolutionary information instead of relying solely on the primary sequence of proteins. Furthermore, we explored hybrid models integrating our machine learning approaches with BLAST-based similarity and motif-based methods. However, the performance of these hybrid models either matched or was inferior to that of our best machine-learning model. Our best model based on evolutionary information outperforms all existing methods on independent/validation dataset. To facilitate users, a user-friendly web server with a standalone package named “AFPropred” was developed (https://webs.iiitd.edu.in/raghava/afpropred).HighlightsPrediction of antifreeze proteins with high precisionEvaluation of prediction models on an independent datasetMachine learning based models using sequence compositionEvolutionary information based prediction modelsA webserver for predicting, scanning, and designing AFPs.Author’s BiographyNishant Kumar is currently working as Ph.D. in Computational biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.Shubham Choudhury is currently working as Ph.D. in Computational biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, IndiaNisha Bajiya is currently working as Ph.D. in Computational biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, IndiaSumeet Patiyal is currently working as a postdoctoral visiting fellow Cancer Data Science Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.Gajendra P. S. Raghava is currently working as Professor and Head of Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.
Venom-inspired somatostatin receptor 4 (SSTR4) agonists as new drug leads for peripheral pain conditions
Authors: Bjørn-Yoshimoto Walden E. , Ramiro Iris Bea L. , Koch Thomas Lund , Engholm Ebbe , Yeung Ho Yan , Sørensen Kasper K. , Goddard Carolyn M. , Jensen Kathrine L. , Smith Nicholas A. , Martin Laurent F. , Smith Brian J. , Madsen Kenneth L. , Jensen Knud J. , Patwardhan Amol , Safavi-Hemami Helena 
Published: May 2024

AbstractPersistent pain affects one in five people worldwide, often with severely debilitating consequences. Current treatment options, which can be effective for mild or acute pain, are ill-suited for moderate-to-severe persistent pain, resulting in an urgent need for new therapeutics. In recent years, the somatostatin receptor 4 (SSTR4), which is expressed in sensory neurons of the peripheral nervous system, has emerged as a promising target for pain relief. However, the presence of several closely related receptors with similar ligand-binding surfaces complicates the design of receptor-specific agonists. In this study, we report the discovery of a potent and selective SSTR4peptide, consomatin Fj1, derived from extensive venom gene datasets from marine cone snails. Consomatin Fj1 is a mimetic of the endogenous hormone somatostatin and contains a minimized binding motif that provides stability and drives peptide selectivity. Peripheral administration of synthetic consomatin Fj1 provided analgesia in mouse models of postoperative and neuropathic pain. Using structure-activity studies, we designed and functionally evaluated several Fj1 analogs, resulting in compounds with improved potency and selectivity. Our findings present a novel avenue for addressing persistent pain through the design of venom-inspired SSTR4-selective pain therapeutics.One Sentence SummaryVenom peptides from predatory marine mollusks provide new leads for treating peripheral pain conditions through a non-opioid target.