bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promoting health and social equity through family navigation to prevention and early intervention services: a proof of concept study
Authors: Waid Jeffrey , Tomfohrde Olivia , Kutzler Courtney 
Published: October 2022

Abstract
Background
Health and social inequality are associated with multiple adverse childhood experiences including poverty, mental illness, and child maltreatment. While effective interventions currently exist for many health and social problems, large segments of the population experience barriers accessing needed services. In alignment with broader public health efforts to reduce health and social inequality in one state in the U.S.A., the current study describes the development and formative evaluation of a brief, low cost, portable model of prevention-oriented family service navigation called Navigate Your Way.

Methods
Caregivers of children experiencing significant unmet health or social service needs were recruited to the study. Participants completed an initial and closing telephone interview which included measures of past and current family health and social service utilization, service barriers, parenting stress, and child internalizing/externalizing behaviors. Between interviews participants created a family service plan and received 10 weeks of telephone and web-mediated family navigation, at which time process and fidelity of implementation data were collected. Frequency and descriptive statistics are provided for participant demographic characteristics, service barriers, intervention engagement, and primary and secondary study outcomes. Paired samples t-tests examined changes in study outcomes between initial and closing telephone interviews.

Results
Thirty two caregivers enrolled, twenty-nine completed the study. The age range was 20–59 (M = 39.5, SD = 10.0). The majority identified as female (96.9%, n = 31), racial/ethnic minority (56.2%, n = 18), and reported an average 10 barriers to care (M = 10.4, SD = 4.1). The most frequently reported service needs were mental health care, housing, food security, transportation, and health insurance. The mean duration of intervention delivery was 83 days. Most participants (82.8%, n = 24) were connected to one or more health or social services. Caregivers reported significant improvements to youth internalizing behaviors (d = 2.5, p = .05) and high levels of overall satisfaction with the navigation approach.

Conclusion
Telephone and web-mediated service navigation is a feasible and practical approach to supporting families in rapidly connecting to health and social care. Future research investigating the efficacy and implementation of Navigate Your Way in routine settings is indicated.
A case report: anatomical translocation in tibial insertion of semitendinosus tendon after tibial lengthening
Authors: Xu Juncai , Fu Dejie , Peng Yang , Yang Pengfei , Xiong Ran , Lei Kai , Guo Lin 
Published: October 2022

Abstract
Background
There is the most common method for arthroscopic anterior cruciate ligament (ACL) reconstruction by using the semitendinosus and gracilis tendons and single-tunnel technique. However, anatomic translocation of hamstring tendon attachment is very rare.

Case presentation
A 45-year-old male who need to receive right knee ACL reconstruction due to sprain injury while playing table tennis was found to have a translocation at tibial attachment of semitendinosus tendon. The tibial insertion of left semitendinosus was then explored by ultrasound and found to be identical to the contralateral limb. The patient has a history of bilateral tibial lengthening.

Conclusions
This is the first case as far as we know that reported anatomic translocation of the tibial attachment of the hamstring tendon after tibial lengthening. Surgeons should be aware of this specific situation when hamstring tendon need to be harvested to avoid unnecessary complications.
Cognitive enhancing supplements and medications in United States Resident Physicians
Authors: Etheridge Tyler , Kennedy Brandon , Millar Morgan M. , Brintz Ben J. , Wu Chaorong , Pettey Jeff 
Published: October 2022

Abstract
Background:
The use of cognitive-enhancing medications and supplements among healthy adults continues to rise. Limited data exists on their use among resident physicians. Given their highly competitive and stressful lifestyle, we sought to evaluate the prevalence, motivations, and side effects of using cognitive-enhancing supplements and medications among resident physicians at a large United States academic institution.

Methods:
An anonymous web-based survey was circulated to resident physicians inquiring about using cognitive-enhancing supplements and medications, as well as personal characteristics such as gender, marital and parental status, medical diagnoses, and medical specialty. Before circulation, we performed a pilot study. Weighted logistic regression analyses estimated the impact of personal characteristics on the probability of using both supplements and medications.

Results:
Survey response rate was 46.4%. Of respondents, 48.6% were female, 45.9% were married, 70.9% were without children, and 67.2% were in a non-surgical medical specialty. Few respondents had a related medical diagnosis, with attention deficit hyperactivity disorder being the most common (7.1%). Male, non-married, surgical residents were more likely to take supplements (odds ratio (OR) = 1.06, 1.05, and 1.05). Males, without children, and those who felt pressure to perform well, were afraid of being left behind, felt pressure because colleagues take them, or felt they could not reach their current level of training without medications were more likely to take medications (OR = 1.11, 1.04, 1.05, and 1.08). Adverse effects with medications were common.

Conclusion:
Supplement and medication use for cognitive enhancement was high among resident physicians at a single institution despite few having a related medical diagnosis. This study raises awareness of the growing pressure in competitive residency environments to use cognitive enhancement regardless of the potential side effects.
Clinical impact of lipid injectable emulsion in internal medicine inpatients exclusively receiving parenteral nutrition: a propensity score matching analysis from a Japanese medical claims database
Authors: Takagi Kosei , Murotani Kenta , Kamoshita Satoru , Kuroda Akiyoshi 
Published: October 2022

AbstractBackgroundAlthough guidelines recommend lipid injectable emulsions (ILEs) be used as a part of parenteral nutrition, many patients in Japan receive lipid-free parenteral nutrition. Furthermore, little is known about the effect of ILEs on clinical outcomes in medical inpatients managed with parenteral nutrition. The aim of this study was to investigate the clinical impact of ILEs on internal medicine inpatients receiving parenteral nutrition.MethodsA propensity score matching (PSM) analysis was performed using a medical claims database covering 451 hospitals in Japan. Participants included the following internal medicine inpatients, ages ≥ 18 years, fasting > 10 days, and receiving exclusively parenteral nutrition, between 2011 and 2020. Participants were divided into 2 groups: those who did and did not receive ILEs. The primary endpoint was in-hospital mortality. The secondary endpoints included intravenous catheter infection, activities of daily living (ADL), hospital length of stay (LOS), and total medical costs. To adjust for energy doses, logistic or multiple regression analyses were performed using energy dose as an additional explanatory variable.ResultsAfter PSM, 19,602 matched pairs were formed out of 61,437 patients. The ILE group had significantly lower incidences than the non-ILE group of in-hospital mortality (20.3% vs. 26.9%; odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66–0.72;p< 0.001), deteriorated ADL (10.8% vs. 12.5%; OR, 0.85; 95% CI, 0.79–0.92;p< 0.001), and shorter LOS (regression coefficient, − 0.8; 95% CI, − 1.6–0.0;p= 0.045). After adjusting for energy dose, these ORs or regression coefficients demonstrated the same tendencies and statistical significance. The mean total medical costs were $21,009 in the ILE group and $21,402 in the non-ILE group (p= 0.08), and the adjusted regression coefficient for the ILE vs. the non-ILE group was − $860 (95% CI, − $1252 to − $47).ConclusionsILE use was associated with improved clinical outcomes, including lower in-hospital mortality, in internal medicine inpatients receiving parenteral nutrition.
Apicoplast ribosomal protein S10-V127M enhances artemisinin resistance of a Kelch13 transgenic Plasmodium falciparum
Authors: Kampoun Tanyaluck , Srichairatanakool Somdet , Prommana Parichat , Shaw Philip J. , Green Judith L. , Knuepfer Ellen , Holder Anthony A. , Uthaipibull Chairat 
Published: October 2022

Abstract
Background
The resistance of Plasmodium falciparum to artemisinin-based (ART) drugs, the front-line drug family used in artemisinin-based combination therapy (ACT) for treatment of malaria, is of great concern. Mutations in the kelch13 (k13) gene (for example, those resulting in the Cys580Tyr [C580Y] variant) were identified as genetic markers for ART-resistant parasites, which suggests they are associated with resistance mechanisms. However, not all resistant parasites contain a k13 mutation, and clearly greater understanding of resistance mechanisms is required. A genome-wide association study (GWAS) found single nucleotide polymorphisms associated with ART-resistance in fd (ferredoxin), arps10 (apicoplast ribosomal protein S10), mdr2 (multidrug resistance protein 2), and crt (chloroquine resistance transporter), in addition to k13 gene mutations, suggesting that these alleles contribute to the resistance phenotype. The importance of the FD and ARPS10 variants in ART resistance was then studied since both proteins likely function in the apicoplast, which is a location distinct from that of K13.

Methods
The reported mutations were introduced, together with a mutation to produce the k13-C580Y variant into the ART-sensitive 3D7 parasite line and the effect on ART-susceptibility using the 0−3 h ring survival assay (RSA0−3 h) was investigated.

Results and conclusion
Introducing both fd-D193Y and arps10-V127M into a k13-C580Y-containing parasite, but not a wild-type k13 parasite, increased survival of the parasite in the RSA0−3 h. The results suggest epistasis of arps10 and k13, with arps10-V127M a modifier of ART susceptibility in different k13 allele backgrounds.
Cytoplasmic delivery of siRNA using human-derived membrane penetration-enhancing peptide
Authors: Nakamura Momoko , Fujiwara Kei , Doi Nobuhide 
Published: October 2022

Abstract
Background
Although protein-based methods using cell-penetrating peptides such as TAT have been expected to provide an alternative approach to siRNA delivery, the low efficiency of endosomal escape of siRNA/protein complexes taken up into cells by endocytosis remains a problem. Here, to overcome this problem, we adopted the membrane penetration-enhancing peptide S19 from human syncytin 1 previously identified in our laboratory.

Results
We prepared fusion proteins in which the S19 and TAT peptides were fused to the viral RNA-binding domains (RBDs) as carrier proteins, added the RBD-S19-TAT/siRNA complex to human cultured cells, and investigated the cytoplasmic delivery of the complex and the knockdown efficiency of target genes. We found that the intracellular uptake of the RBD-S19-TAT/siRNA complex was increased compared to that of the RBD-TAT/siRNA complex, and the expression level of the target mRNA was decreased. Because siRNA must dissociate from RBD and bind to Argonaute 2 (Ago2) to form the RNA-induced silencing complex (RISC) after the protein/siRNA complex is delivered into the cytoplasm, a dilemma arises: stronger binding between RBD and siRNA increases intracellular uptake but makes RISC formation more difficult. Thus, we next prepared fusion proteins in which the S19 and TAT peptides were fused with Ago2 instead of RBD and found that the efficiencies of siRNA delivery and knockdown obtained using TAT-S19-Ago2 were higher than those using TAT-Ago2. In addition, we found that the smallest RISC delivery induced faster knockdown than traditional siRNA lipofection, probably due to the decreased time required for RISC formation in the cytoplasm.

Conclusion
These results indicated that S19 and TAT-fused siRNA-binding proteins, especially Ago2, should be useful for the rapid and efficient delivery of siRNA without the addition of any endosome-disrupting agent.
Hyper-responsiveness to warfarin in a young patient with the VKORC1 -1639GA/CYP2C9*1*46 genotype: a case report
Authors: Aldiban Weam , Altawil Yara , Hussein Samir , Aljamali Majd , Youssef Lama A. 
Published: October 2022

Abstract
Background
Warfarin is the most widely used oral anticoagulant; nevertheless, dosing of warfarin is problematic for clinicians worldwide. Inter-individual variability in response to warfarin is attributed to genetic as well as non-genetic factors. Pharmacogenomics studies have identified variants in CYP2C9 and VKORC1 genes as significant predictors of warfarin dose, however, phenotypes of rare variants are not well characterized.

Case presentation
We report a case of hyper-responsiveness to warfarin in a 22-year-old outpatient with Crohn's disease who presented with a swollen, red, and painful left calf. Deep venous thrombosis (DVT) in the left lower extremity was confirmed via ultrasonography, and hence, anticoagulation therapy of heparin and concomitant warfarin was initiated. Warfarin dose of 7.5 mg/day was estimated by the physician based on clinical factors. Higher than the expected international normalized ratio (INR) value of 4.5 necessitated the reduction of the warfarin dose to 5 and eventually to 2.5 mg/day to reach a therapeutic INR value of 2.6. Pharmacogenetic profiling of the VKORC1 -1639G > A and CYP2C9 *2, *3, *4, *5, *8, *14, *20, *24, *26, *33, *40, *41, *42, *43, *45, *46, *55, *62, *63, *66, *68, *72, *73 and *78 revealed a VKORC1-1639GA/CYP2C9*1*46 genotype. The lower catalytic activity of the CYP2C9*46 (A149T) variant was previously reported in in vitro settings.

Conclusions
This is the first report on a case of warfarin hyper-responsive phenotype of a patient with the heterozygous CYP2C9*1*46 polymorphism.
Bone marrow mesenchymal stem cells regulate the dysfunction of NK cells via the T cell immunoglobulin and ITIM domain in patients with myelodysplastic syndromes
Authors: Liu Zhaoyun , Guo Yixuan , Huang Lei , Jia Yue , Liu Hui , Peng Fengping , Duan Lixiang , Zhang Hongkai , Fu Rong 
Published: October 2022

Abstract
Background
Myelodysplastic syndrome (MDS) is a clonal disease of hematopoietic cells, characterized by hematopoietic cell hematopoiesis and a high risk of transformation into acute myeloid leukemia (AML). Although the underlying mechanism is unclear, MDS is often associated with immune system disorders, especially cellular immune abnormalities. We analyzed the number of lymphocyte subsets by flow cytometry assay and explored the alteration of lymphocyte subsets in MDS.

Methods
Healthy controls, inpatients with primary MDS and patients with AML diagnosed from January 2017 to July 2021 were included. Flow cytometry assays were used to study lymphocyte subsets obtained from the bone marrow of the participants as well as changes in natural killer (NK) cell function. One-way analysis of variance and Student’s t-test were used to analyze the data.

Results
We found a reduction in the number and function of NK cells in patients with MDS. By further measuring the activating and inhibitory receptors on the surface of NK cells, we found that the T cell immunoglobulin and ITIM domain (TIGIT) was the highest expressed marker on NK cells. Additionally, the expression of CD155, which is the ligand of TIGIT, was significantly higher than expressions of CD112 and CD113 on bone marrow mesenchymal stem cells (BMSCs).

Conclusions
The co-culture results of BMSCs and NK cells demonstrated that BMSCs regulate NK cells through the TIGIT/CD155 interaction, indicating that NK cells play a vital role in MDS progression. BMSCs regulate the function of NK cells via TIGIT/CD155.
Early remission in multiple sclerosis is linked to altered coherence of the Cerebellar Network
Authors: Tahedl Marlene , Levine Seth M. , Weissert Robert , Kohl Zacharias , Lee De-Hyung , Linker Ralf A. , Schwarzbach Jens V. 
Published: October 2022

Abstract
Background
The development of permanent disability in multiple sclerosis (MS) is highly variable among patients, and the exact mechanisms that contribute to this disability remain unknown.

Methods
Following the idea that the brain has intrinsic network organization, we investigated changes of functional networks in MS patients to identify possible links between network reorganization and remission from clinical episodes in MS. Eighteen relapsing–remitting MS patients (RRMS) in their first clinical manifestation underwent resting-state functional MRI and again during remission. We used ten template networks, identified from independent component analysis, to compare changes in network coherence for each patient compared to those of 44 healthy controls from the Human Connectome Project test–retest dataset (two-sample t-﻿test of pre-post differences). Combining a binomial test with Monte Carlo procedures, we tested four models of how functional coherence might change between the first clinical episode and remission: a network can change its coherence (a) with itself (“one-with-self”), (b) with another network (“one-with-other”), or (c) with a set of other networks (“one-with-many”), or (d) multiple networks can change their coherence with respect to one common network (“many-with-one”).

Results
We found evidence supporting two of these hypotheses: coherence decreased between the Executive Control Network and several other networks (“one-with-many” hypothesis), and a set of networks altered their coherence with the Cerebellar Network (“many-with-one” hypothesis).

Conclusion
Given the unexpected commonality of the Cerebellar Network’s altered coherence with other networks (a finding present in more than 70% of the patients, despite their clinical heterogeneity), we conclude that remission in MS may result from learning processes mediated by the Cerebellar Network.
Transcriptome-based network analysis related to M2-like tumor-associated macrophage infiltration identified VARS1 as a potential target for improving melanoma immunotherapy efficacy
Authors: Wu Zhengquan , Lei Ke , Li Huaizhi , He Jiali , Shi Enxian 
Published: October 2022

Abstract
Rationale
The M2-like tumor-associated macrophages (TAMs) are independent prognostic factors in melanoma.

Methods
We performed weighted gene co-expression network analysis (WGCNA) to identify the module most correlated with M2-like TAMs. The Cancer Genome Atlas (TCGA) patients were classified into two clusters that differed based on prognosis and biological function, with consensus clustering. A prognostic model was established based on the differentially expressed genes (DEGs) of the two clusters. We investigated the difference in immune cell infiltration and immune response-related gene expression between the high and low risk score groups.

Results
The risk score was defined as an independent prognostic value in melanoma. VARS1 was a hub gene in the M2-like macrophage-associated WGCNA module that the DepMap portal demonstrated was necessary for melanoma growth. Overexpressing VARS1 in vitro increased melanoma cell migration and invasion, while downregulating VARS1 had the opposite result. VARS1 overexpression promoted M2 macrophage polarization and increased TGF-β1 concentrations in tumor cell supernatant in vitro. VARS1 expression was inversely correlated with immune-related signaling pathways and the expression of several immune checkpoint genes. In addition, the VARS1 expression level helped predict the response to anti-PD-1 immunotherapy. Pan-cancer analysis demonstrated that VARS1 expression negatively correlated with CD8 T cell infiltration and the immune response-related pathways in most cancers.

Conclusion
We established an M2-like TAM-related prognostic model for melanoma and explored the role of VARS1 in melanoma progression, M2 macrophage polarization, and the development of immunotherapy resistance.
Case report: BA.1 subvariant showing a BA.2-like pattern using a variant-specific PCR assay due to a single point mutation downstream the spike 69/70 deletion
Authors: Daviña-Nuñez Carlos , Pérez-Castro Sonia , Martínez-Lamas Lucía , Cabrera-Alvargonzález Jorge Julio , Rey-Cao Sonia , Carballo-Fernandez Raquel , Godoy-Diz Montse , López-Bóveda Leticia , del Campo-Pérez Victor , Suárez-Luque Silvia , Regueiro-García Benito 
Published: October 2022

Abstract
Background:
SARS-CoV-2 variant tracking is key to the genomic surveillance of the COVID-19 pandemic. While next-generation sequencing (NGS) is commonly used for variant determination, it is expensive and time-consuming. Variant-specific PCR (vsPCR) is a faster, cheaper method that detects specific mutations that are considered variant-defining. These tests usually rely on specific amplification when a mutation is present or a specific melting temperature peak after amplification.

Case presentation:
A discrepant result between vsPCR and NGS was found in seventeen SARS-CoV-2 samples from Galicia, Spain. A cluster of BA.1 Omicron SARS-CoV-2 variant showed a BA.2-like melting temperature pattern due to a point mutation (C21772T) downstream the deletion of the spike amino acids 69/70. As the 69/70 deletion is widely used for differentiation between BA.1 and BA.2 by vsPCR, C21772T can cause BA.1 samples to be misinterpreted as BA.2. Over a thousand BA.1 sequences in the EpiCoV database contain this mutation.

Conclusions:
To our knowledge, this is the first case of a point mutation causing a vsPCR algorithm to misclassify BA.1 samples as BA.2. This is an example of how mutations in the probe target area of vsPCR tests based on melting curve analysis can lead to variant misclassification. NGS confirmation of vsPCR results is relevant for the accuracy of the epidemiological surveillance. In order to overcome the possible impact of novel mutations, diagnostic tools must be constantly updated.
Performance of the nonstructural 1 Antigen Rapid Test for detecting all four DENV serotypes in clinical specimens from Bangkok, Thailand
Authors: Poltep Kanaporn , Phadungsombat Juthamas , Kosoltanapiwat Nathamon , Hanboonkunupakarn Borimas , Wiriyarat Witthawat , Suwanpakdee Sarin , Prompiram Phirom , Nakayama Emi E. , Suzuki Keita , Iwamoto Hisahiko , Shioda Tatsuo , Leaungwutiwong Pornsawan 
Published: October 2022

Abstract
Background:
Dengue is an arboviral disease that has a large effect on public health in subtropical and tropical countries. Rapid and accurate detection of dengue infection is necessary for diagnosis and disease management. We previously developed highly sensitive immunochromatographic devices, the TKK 1st and TKK 2nd kits, based on dengue virus (DENV) nonstructural protein 1 detection. However, these TKK kits were evaluated mainly using DENV type 2 clinical specimens collected in Bangladesh, and further validation using clinical specimens of other serotypes was needed.

Methods:
In the present study, one of the TKK kits, TKK 2nd, was evaluated using 10 DENV-1, 10 DENV-2, 4 DENV-3, 16 DENV-4, and 10 zika virus-infected clinical specimens collected in Bangkok, Thailand.

Results:
The TKK 2nd kit successfully detected all four DENV serotypes in patient serum specimens and did not show any cross-reactivities against zika virus serum specimens. The IgM and/or IgG anti-DENV antibodies were detected in seven serum specimens, but did not seem to affect the results of antigen detection in the TKK 2nd kit.

Conclusion:
The results showed that the TKK 2nd kit successfully detected all four DENV serotypes in clinical specimens and confirmed the potential of the kit for dengue diagnosis in endemic countries.