bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of flurbiprofen cataplasms versus loxoprofen sodium cataplasms in knee osteoarthritis: a randomized controlled trial
Authors: Li Dong , Cheng Yinchu , Yuan Ping , Wu Ziyang , Liu Jiabang , Kan Jinfu , Zhang Kun , Wang Zhanguo , Zhang Hui , Zhang Guangwu , Xue Tao , Jia Junxiu , Zhai Suodi , Guan Zhenpeng 
Published: August 2023

Abstract

Background:
Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA.

Methods:
This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0–10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events.

Results:
Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147–0.681); P <0.001 for non-inferiority; P = 0.001 for superiority). Similar results were observed of the VAS scores for the current pain and pain during exercise. WOMAC scores were also lower in the FPC group at week 4 (12.50 [8.00–22.50] vs. 16.00 [11.00–27.00], P = 0.010), mainly driven by the dimension of daily activity difficulty. In addition, the FPC group experienced a significantly lower incidence of adverse events (5.6% [7/124] vs. 33.6% [42/125], P <0.001), including irritation, rash and pain of the skin, and sticky hair uncovering pain.

Conclusions:
This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief, joint function improvement, and safety profile.
The Effect of Hand Reflexology Massage on Pain and Anxiety After Coronary Artery Bypass Graft Surgery
Authors: Göktuna Gizem , Dağcan Necibe , Arslan Gülşah Gürol 
Published: August 2023

Background
Pain and anxiety are common postoperative problems that impair recovery and quality of life in patients undergoing coronary artery bypass graft (CABG) surgery. Reflexology is a nonpharmacologic method used to control pain and anxiety.

Objective
The aim of this study was to examine the effects of reflexology hand massage and stroking massage on pain and anxiety in patients in the immediate postoperative period after CABG.

Methods
In this double-blind, randomized, placebo-controlled study, we compared the effects of a 20-minute hand-reflexology massage to placebo stroking massage on pain and anxiety in newly extubated patients in the intensive care unit who had undergone CABG surgery. Pain was measured by visual analog scale and anxiety by the State-Trait Anxiety Inventory before and at 5, 30, and 60 minutes post intervention.

Results
A total of 48 patients were enrolled: 24 in the intervention group and 24 in the placebo. Mean pain scores were significantly reduced in the group who received reflexology compared with the placebo group (F = 36.569, P = .000). Mean anxiety scores were significantly reduced at 60 minutes for the reflexology group compared with the control group (P = .000).

Conclusions
We found that hand reflexology massage was effective in reducing pain and anxiety in patients during the immediate postoperative period after CABG.
The Changing Landscape of Intercultural Mindset in 616 Doctor of Physical Therapy Students Over the Past 7 Years and the Implications for Doctor of Physical Therapy Cultural Competence Education
Authors: VanHoose Lisa , Eigsti Heidi 
Published: August 2023

Introduction.
This prospective longitudinal study will report the results of a quantitative analysis of the change in Intercultural Development Inventory (IDI) scores and the distribution of students in 5 orientations along the Intercultural Developmental Continuum (IDC) in 8 cohorts of Doctor of Physical Therapy (DPT) students during their academic preparation.

Review of Literature.
The expanding interest in developing intercultural sensitivity in an increasingly more complex and diverse health care environment calls for the dissemination of research on the effectiveness of innovative curricular models that include psychometrically strong outcome measures. Research suggests that health care providers can develop intercultural sensitivity when provided with didactic knowledge, experiential learning, self-reflection, mentoring, and a systematic individualized development plan.

Subjects.
The participants were from a sample of convenience of 616 DPT students from the graduating classes of 2015–2022.

Methods.
The study is a repeated-measure design. The IDI was selected to guide targeted intervention and assessment of intercultural sensitivity at an individual level and group level and was administered in semesters 3 and 8 as part of the DPT program course requirements.

Results.
There was significant improvement in the IDI Perceived and Developmental Orientation (DO; P < .001) scores between semesters 3 and 8. There was a significant change (P = .0001) in the distribution of students along the 5 DOs of the IDC with 10% of students regressing 1 orientation, 51.7% of students remaining the same, 33.3% of students advancing 1 orientation, and 5% of students advancing 2 orientations along the IDC. Nearly 40% of participants had a positive shift along the IDC.

Discussion and Conclusion.
The results of this study suggest that intercultural sensitivity or mindset, as measured by the IDI, can be developed in DPT students who participate in a targeted intercultural development curriculum based on the Process Model of Cultural Competence by Deardorff and the Developmental Model of Intercultural Sensitivity by Bennett.
An Autopsy Analysis of a Patient With Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency Caused by Compound Heterozygous HADHA Gene Mutations
Authors: Zhang Qinjian , Yao Nan , Liu Zunzhong , Xu Changmiao , Ding Zijiao 
Published: August 2023

Abstract
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare mitochondrial disease characterized by lipid oxidation disorder. It is an autosomal recessive disease induced by a mutation in the HADHA gene, which encodes the LCHAD deficiency. The clinical manifestations of this disease are diverse, primarily affecting the heart, liver, and skeletal muscles. Common symptoms include cardiomyopathy, peripheral neuropathy, retinopathy, and even lead to death in severe cases.
Herein, we report a patient who was hospitalized due to flatulence, crying, irritability, and died of acute cardiopulmonary failure after 8 days in hospital. An autopsy was performed to determine the cause of death. Clinical examination revealed abnormal liver and kidney function, and the genetic metabolic disease profile indicated significantly elevated levels of long-chain acyl-carnitine and long-chain 3-OH-acyl-carnitine. Histopathological examination revealed diffuse hepatic steatosis, and the genetic sequencing results detected compound heterozygous mutations in the HADHA gene (c.1528G>C [p.E510Q] and c.703_704dupCG [p.T236Gfs*3]). Of note, the mother had a history of acute fatty liver during pregnancy. Collectively, our study may contribute to understanding the HADHA gene mutation profile and the clinical phenotype of LCHAD deficiency, emphasizing the importance of genetic testing in forensic pathology.
Acute 1,2-Dichloropropane Poisoning due to Ingestion of Rubber Cement
Authors: Pang Qiuyu , Zheng Lexin , Huang Ruoyu , Xu Heng , Pan Chong , Wang Zhiyong , Wang Tao 
Published: August 2023

Abstract
1,2-Dichloropropane (1,2-DCP) is a common industrial solvent and chemical intermediate that can cause acute poisoning to humans through exposure during its production and industrial use. The target organs of 1,2-DCP include the eyes, respiratory system, liver, kidney, central nervous system, and skin. Forensic identification of 1,2-DCP poisoning is difficult because of the lack of characteristic pathological changes. This article reports an autopsy case of acute 1,2-DCP poisoning caused by self-ingestion of rubber cement. A woman developed seizures and coagulation dysfunction after ingesting approximately 10 mL of rubber cement and died 43 hours later. Autopsy revealed generalized subcutaneous hemorrhage, cardiopulmonary multifocal hemorrhage, bronchopneumonia, severe cerebral edema, focal hepatic necrosis, granular deposition in the glomerular capsule and renal tubules, and delipidation of the adrenal cortex. These findings indicate that 1,2-DCP poisoning can induce central nervous system dysfunction, respiratory system damage, liver and kidney function damage, hemolytic anemia, disseminated intravascular coagulation, and adrenal damage. This case may provide useful perspectives for forensic identification of 1,2-DCP poisoning in the future.
Prognosis and personalizedin-silicoprediction of treatment efficacy in cardiovascular and chronic kidney disease: a proof-of-concept study
Authors: Jaimes Campos Mayra Alejandra , Andújar Iván , Keller Felix , Mayer Gert , Rossing Peter , Staessen Jan A , Delles Christian , Beige Joachim , Glorieux Griet , Clark Andrew L , Mullen William , Schanstra Joost P , Vlahou Antonia , Rossing Kasper , Peter Karlheinz , Ortiz Alberto , Campbell Archie , Persson Frederik , Latosinska Agnieszka , Mischak Harald , Siwy Justyna , Jankowski Joachim 
Published: August 2023

Abstract(1)Backgroundkidney and cardiovascular diseases are responsible for a large fraction of population morbidity and mortality. Early, targeted, personalized intervention represents the ideal approach to cope with this challenge. Proteomic/peptidomic changes are largely responsible for onset and progression of these diseases and should hold information about optimal means for treatment and prevention.(2)Methodswe investigated prediction of renal or cardiovascular events using previously defined urinary peptidomic classifiers CKD273, HF2 and CAD160 in a cohort of 5585 subjects in a retrospective study.(3)Resultswe demonstrate highly significant prediction of events with HR of 2.59, 1.71, and 4.12 for HF, CAD and CKD respectively. We applied in silico treatment, implementing on each patient urinary profile, changes onto the classifiers corresponding to exactly defined peptide abundance changes following commonly used interventions (MRA, SGLT2i, DPP4i, ARB, GLP1RA, olive oil and exercise), as defined in previous studies. Applying the proteomic classifiers after in silico treatment indicated individual benefits of specific interventions on a personalized level.(4)Conclusionsthein-silicoevaluation may provide information on the future impact of specific drugs and intervention on endpoints, opening the door to a precision medicine approach. Investigation of the extent of the benefit of this approach in a prospective clinical trial is warranted.
Deciphering the Genetic Code of Neuronal Type Connectivity Through Bilinear Modeling
Authors: Qiao Mu 
Published: August 2023

AbstractUnderstanding how different neuronal types connect and communicate is critical to interpreting brain function and behavior. However, it has remained a formidable challenge to decipher the genetic underpinnings that dictate the specific connections formed between neuronal types. To address this, we propose a novel bilinear modeling approach that leverages the architecture similar to that of recommendation systems. Our model transforms the gene expressions of presynaptic and postsynaptic neuronal types, obtained from single-cell transcriptomics, into a covariance matrix. The objective is to construct this covariance matrix that closely mirrors a connectivity matrix, derived from connectomic data, reflecting the known anatomical connections between these neuronal types. When tested on a dataset ofCaenorhabditis elegans, our model achieved a performance comparable to, if slightly better than, the previously proposed spatial connectome model (SCM) in reconstructing electrical synaptic connectivity based on gene expressions. Through a comparative analysis, our model not only captured all genetic interactions identified by the SCM but also inferred additional ones. Applied to a mouse retinal neuronal dataset, the bilinear model successfully recapitulated recognized connectivity motifs between bipolar cells and retinal ganglion cells, and provided interpretable insights into genetic interactions shaping the connectivity. Specifically, it identified unique genetic signatures associated with different connectivity motifs, including genes important to cell-cell adhesion and synapse formation, highlighting their role in orchestrating specific synaptic connections between these neurons. Our work establishes an innovative computational strategy for decoding the genetic programming of neuronal type connectivity. It not only sets a new benchmark for single-cell transcriptomic analysis of synaptic connections but also paves the way for mechanistic studies of neural circuit assembly and genetic manipulation of circuit wiring.
TRAFfic signals: High-throughput CAR discovery in NK cells reveals novel TRAF-binding endodomains that drive enhanced persistence and cytotoxicity
Authors: Williams Maddie D. , Chen Aye T. , Stone Matthew R. , Guo Lan , Belmont Brian J. , Turk Rebekah , Bogard Nick , Kearns Nora , Young Mary , Daines Bryce , Darnell Max 
Published: August 2023

AbstractNatural killer (NK) cells are a promising alternative therapeutic platform to CAR T cells given their favorable safety profile and potent killing ability. However, CAR NK cells suffer from limited persistencein vivo, which is, in part, thought to be the consequence of limited cytokine signaling. To address this challenge, we developed an innovative high-throughput screening strategy to identify CAR endodomains that could drive enhanced persistence while maintaining potent cytotoxicity. We uncovered a family of TRAF-binding endodomains that outperform benchmarks in primary NK cells along dimensions of persistence and cytotoxicity, even in low IL-2 conditions. This work highlights the importance of cell-type-specific cell therapy engineering and unlocks a wide range of high-throughput molecular engineering avenues in NK cells.
Cellular Senescence Affects ECM Regulation in COPD Lung Tissue
Authors: Woldhuis R.R. , Bekker N.J. , van Nijnatten J.L.L. , Meuleman R.A. , Kooistra W. , Wolters J.C. , Horvatovich P.L. , Guryev V. , van den Berge M. , Timens W. , Brandsma CA. 
Published: August 2023

ABSTRACTRationaleHigher levels of senescence have been demonstrated in COPD patients, including severe early onset (SEO)-COPD. Recently we demonstrated a link between senescence and extracellular matrix (ECM) changes in lung fibroblasts. Whether thisin vitroobservation also translatesin vivohas not been demonstrated.ObjectivesTo determine whether senescence can contribute to COPD-associated ECM-related changes in lung tissue.MethodsTranscriptomics and proteomics analyses were performed on lung tissue from 60 COPD patients (including 18 SEO-COPD patients) and 32 controls. Transcript and protein levels of 471 ECM-related proteins were compared between (SEO-)COPD and control. Differentially expressed genes and proteins were correlated with six major senescence markers. Significant correlations were validated at single cell level andin vitro.ResultsWe identified 15 COPD- and 61 SEO-COPD-associated changes in ECM-related proteins, of which 12 and 57 at transcript and 4 and 9 at protein level, respectively. More than half (36 out of 68) of the (SEO-)COPD-associated ECM-related proteins were significantly correlated with one or more senescence markers at transcript level, with the most and strongest correlations with p21. The correlation of 6 ECM-related genes, including THBS1, ADAMTS1, and ADAMTS4, with p21 was validated at single cell level and ADAMTS1 in senescent lung fibroblastsin vitro.ConclusionsMany of the (SEO-)COPD-associated ECM-related changes in lung tissue were correlated with the senescence marker p21. As many of these ECM-related proteins are involved in ECM organization and include proteases, these results indicate a role for cellular senescence in disturbed ECM organization and protease-antiprotease imbalance in COPD.What is already known on this topicAccelerated ageing, including cellular senescence, has been recognized as a feature of COPD, while the functional implications of higher levels of senescence on lung tissue are largely unclear. Previously, we demonstrated a link between senescence and extracellular matrix (ECM) dysregulation in primary lung fibroblasts, but whether this translatesin vivohas not been demonstrated yet.What this study addsHere, we demonstrate that cellular senescence is linked to ECM dysregulationin vivoin COPD lung tissue mainly by impacting the regulators of ECM organization and contributing to the protease-antiprotease imbalance in COPD.How this study might affect research, practice or policyOur study points towards an important functional consequence of increased senescence on disease pathology in COPD patients, including the protease-antiprotease imbalance and dysregulated elastogenesis. Our findings support the development of new therapeutic strategies of targeting senescence to restore ECM regulation in COPD.
Compound models and Pearson residuals for single-cell RNA-seq data without UMIs
Authors: Lause Jan , Ziegenhain Christoph , Hartmanis Leonard , Berens Philipp , Kobak Dmitry 
Published: August 2023

AbstractRecent work employed Pearson residuals from Poisson or negative binomial models to normalize UMI data. To extend this approach to non-UMI data, we model the additional amplification step with a compound distribution: we assume that sequenced RNA molecules follow a negative binomial distribution, and are then replicated following an amplification distribution. We show how this model leads to compound Pearson residuals, which yield meaningful gene selection and embeddings of Smart-seq2 datasets. Further, we suggest that amplification distributions across several sequencing protocols can be described by a broken power law. The resulting compound model captures previously unexplained overdispersion and zero-inflation patterns in non-UMI data.
Determinants of COVID-19 vaccine uptake in the Netherlands: a nationwide registry-based study
Authors: Pijpers Joyce , van Roon Annika , van Roekel Caren , Labuschagne Lisanne , Smagge Bente , Ferreira José A. , de Melker Hester , Hahné Susan 
Published: August 2023

AbstractBy September 2022, uptake of at least one dose of COVID-19 vaccine in the Dutch adult population was 84%. Ecological studies have indicated lower uptake in certain population groups. We aimed to investigate determinants of COVID-19 vaccine uptake in the Netherlands at individual level to evaluate and optimize implementation of the vaccination program and generate hypotheses for research on drivers of and barriers to vaccination. A retrospective database study was performed including the entire Dutch population ≥18. Vaccination data (5 January 2021 – 18 November 2021) were at individual level linked to sociodemographic data. Random forest analyses ranked sociodemographic determinants of COVID-19 vaccine uptake. The most important determinant was age; uptake increased until the age of 80 (67% in 18-35 years, 92% in 67-79 years and 88% in those >80). Personal income and socioeconomic position ranked second and third, followed by migration status. Uptake was lower among individuals in the lowest income group (69%), receiving social benefits (56%), and individuals with two parents born abroad (59%). Our finding that age is the most important determinant for uptake likely reflects the prioritisation of elderly in the programme and the general understanding of their increased vulnerability. However, our findings also reveal important other disparities in vaccine uptake. How to best address this inequity in future vaccination campaigns requires further research.
Comprehensive genome editing confers ‘off-the-shelf’ CAR-T cells superior efficacy against solid tumors
Authors: Murray Ryan , Navarrete Nuria Roxana Romero , Desai Kashvi , Chowdhury Md Raihan , Chilakapati Shanmuga Reddy , Chong Brian , Messana Angelica , Sobon Hanna , Rocha Joe , Musenge Faith , Camblin Adam , Ciaramella Giuseppe , Sitkovsky Michail , Maldini Colby , Hatfield Stephen 
Published: August 2023

AbstractBiochemical and immunological negative regulators converge to inhibit tumor-reactive Chimeric Antigen Receptor T (CAR-T) cells, which may explain clinical failures of CAR-T cell therapies against solid tumors. Here, we developed a multifaceted approach to genetically engineer allogeneic (‘off -the-shelf’) CAR-T cells resistant to both biochemical (adenosine) and immunological (PD-L1 and TGF-β) inhibitory signaling. We multiplexed an adenine base editor with a CRISPR-Cas12b nuclease to manufacture a CAR-T cell product comprising six gene edits to evade allorejection (B2M, CIITA), prevent graft-versus-host disease (CD3E) and resist major biochemical (ADORA2A) and immunological (PDCD1,TGFBR2) immunosuppressive barriers in solid tumors. Combinatorial genetic disruption in CAR-T cells enabled superior anti-tumor efficacy leading to improved tumor elimination and survival in humanized mouse models that recapitulated the suppressive features of a human tumor microenvironment (TME). This novel engineering strategy conferred CAR-T cells resistance to a diverse TME, which may unlock the therapeutic potential of CAR-T cells against solid tumors.One Sentence SummaryMultiplex genome engineered CAR-T cells resistant to allorejection and the convergence of biochemical and immunological negative regulators within the tumor microenvironment exhibit superior efficacy against solid tumors.
Super-resolution optical imaging reveals accumulation of small mitochondria in the nucleoli of mouse embryos and stem cells
Authors: Qin Kezhou , Wu Xinyi 
Published: August 2023

AbstractThe nuclear mitochondrial DNA (NUMT) is found in cancer cells, but the mitochondrial DNAs entering the nuclei in normal cells have not been captured. Here, we utilized super-resolution optical imaging to capture the phenomenon by the probe PicoGreen and found mitochondrial DNAs and mitochondria accumulated in the nucleoli by four probes and overexpressing the MRPL58-DsRed. Our results provide an new explanation for mtDNA carryover and lay the foundation for the involvement of nuclear export of nucleoli in de novo mitochondrial biogenesis in another of our unpublished articles.