bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes
Authors: Aterido Adrià , López-Lasanta María , Blanco Francisco , Juan-Mas Antonio , García-Vivar María Luz , Erra Alba , Pérez-García Carolina , Sánchez-Fernández Simón Ángel , Sanmartí Raimon , Fernández-Nebro Antonio , Alperi-López Mercedes , Tornero Jesús , Ortiz Ana María , Fernández-Cid Carlos Marras , Palau Núria , Pan Wenjing , Byrne-Steele Miranda , Starenki Dmytro , Weber Daniel , Rodriguez-Nunez Ivan , Han Jian , Myers Richard M. , Marsal Sara , Julià Antonio 
Published: March 2024

AbstractBackgroundIn rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA.ResultsIn comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool.ConclusionsSimultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.
Streamlined, single-step non-viral CRISPR-Cas9 knockout strategy enhances gene editing efficiency in primary human chondrocyte populations
Authors: Ponta Simone , Bonato Angela , Neidenbach Philipp , Bruhin Valentino F. , Laurent Alexis , Applegate Lee Ann , Zenobi-Wong Marcy , Barreto Goncalo 
Published: March 2024

Abstract
Background
CRISPR-Cas9-based genome engineering represents a powerful therapeutic tool for cartilage tissue engineering and for understanding molecular pathways driving cartilage diseases. However, primary chondrocytes are difficult to transfect and rapidly dedifferentiate during monolayer (2D) cell culture, making the lengthy expansion of a single-cell-derived edited clonal population not feasible. For this reason, functional genetics studies focused on cartilage and rheumatic diseases have long been carried out in cellular models that poorly recapitulate the native molecular properties of human cartilaginous tissue (e.g., cell lines, induced pluripotent stem cells). Here, we set out to develop a non-viral CRISPR-Cas9, bulk-gene editing method suitable for chondrocyte populations from different cartilaginous sources.

Methods
We screened electroporation and lipid nanoparticles for ribonucleoprotein (RNP) delivery in primary polydactyly chondrocytes, and optimized RNP reagents assembly. We knocked out RELA (also known as p65), a subunit of the nuclear factor kappa B (NF-κB), in polydactyly chondrocytes and further characterized knockout (KO) cells with RT-qPCR and Western Blot. We tested RELA KO in chondrocytes from diverse cartilaginous sources and characterized their phenotype with RT-qPCR. We examined the chondrogenic potential of wild-type (WT) and KO cell pellets in presence and absence of interleukin-1β (IL-1β).

Results
We established electroporation as the optimal transfection technique for chondrocytes enhancing transfection and editing efficiency, while preserving high cell viability. We knocked out RELA with an unprecedented efficiency of ~90%, confirming lower inflammatory pathways activation upon IL-1β stimulation compared to unedited cells. Our protocol could be easily transferred to primary human chondrocytes harvested from osteoarthritis (OA) patients, human FE002 chondroprogenitor cells, bovine chondrocytes, and a human chondrocyte cell line, achieving comparable mean RELA KO editing levels using the same protocol. All KO pellets from primary human chondrocytes retained chondrogenic ability equivalent to WT cells, and additionally displayed enhanced matrix retention under inflamed conditions.

Conclusions
We showcased the applicability of our bulk gene editing method to develop effective autologous and allogeneic off-the-shelf gene therapies strategies and to enable functional genetics studies in human chondrocytes to unravel molecular mechanisms of cartilage diseases.
Forkhead box O proteins: steering the course of stem cell fate
Authors: Cheng Mengdi , Nie Yujie , Song Min , Chen Fulin , Yu Yuan 
Published: March 2024

AbstractStem cells are pivotal players in the intricate dance of embryonic development, tissue maintenance, and regeneration. Their behavior is delicately balanced between maintaining their pluripotency and differentiating as needed. Disruptions in this balance can lead to a spectrum of diseases, underscoring the importance of unraveling the complex molecular mechanisms that govern stem cell fate. Forkhead box O (FOXO) proteins, a family of transcription factors, are at the heart of this intricate regulation, influencing a myriad of cellular processes such as survival, metabolism, and DNA repair. Their multifaceted role in steering the destiny of stem cells is evident, as they wield influence over self-renewal, quiescence, and lineage-specific differentiation in both embryonic and adult stem cells. This review delves into the structural and regulatory intricacies of FOXO transcription factors, shedding light on their pivotal roles in shaping the fate of stem cells. By providing insights into the specific functions of FOXO in determining stem cell fate, this review aims to pave the way for targeted interventions that could modulate stem cell behavior and potentially revolutionize the treatment and prevention of diseases.
Comparative analysis on root exudate and rhizosphere soil bacterial assembly between tomatoes and peppers infected by Ralstonia
Authors: Yan Mengyuan , Wu Meng , Liu Ming , Li Guilong , Liu Kai , Qiu Cunpu , Bao Ying , Li Zhongpei 
Published: March 2024

Abstract
Background
The rhizosphere environment regulated by root secretory activity and rhizosphere microbial interactions plays an essential role in resisting soil-borne diseases, while the host species is an important factor that affects the composition of root exudates and rhizosphere microbiomes. However, few studies have been done on the characteristics of root exudates and bacterial communities in terms of composition, diversity, and functional potential when host plants of different species are subjected to the same disease.

Results
In this study, we examined the rhizosphere soil bacteria and root exudates of both healthy and diseased tomatoes and peppers employing metabolomics and amplicon techniques. Our findings indicated that variations existed in both root exudates and the bacterial community among different host species and health states. The diversities of both rhizosphere metabolites and bacterial communities were significantly reduced in different diseased plants. Although pepper and tomato resisted the invasion of Ralstonia by recruiting different potentially beneficial bacteria, their rhizosphere bacterial communities had the same functional potential. In comparison to diseased rhizosphere soil, healthy rhizosphere soil had many more functional pathways associated with disease suppression and plant growth.

Conclusions
This study highlighted the crucial role of host plants in shaping the rhizosphere environment and revealed the variation characteristics of root exudates and rhizosphere bacteria of different host plants induced by the same disease.

Graphical Abstract
Successful removal of an intra-pericardic Kirschner wire via fluoroscopy-guided minimal invasive approach: a case report
Authors: Georges Olivier , De Dominicis Florence , Rahal Malek Ben , Le Pessot Jules , Berna Pascal , Arab Osama Abou , Beyls Christophe 
Published: March 2024

Abstract
Background
Kirschner wires are widely used in trauma surgery. Their migration into the pericardium is a rare but often fatal phenomenon, requiring urgent management.

Case presentation
We describe the case of a 65-year-old patient who underwent Kirschner wire placement to treat a humeral head fracture. Three months after the operation, pleural and pericardial effusions with cardiac tamponade were observed, leading to the diagnosis of wire migration within the pericardium. A minimally invasive approach guided by fluoroscopy allowed emergency wire extraction without needing a median sternotomy. The postoperative clinical course was uncomplicated.

Conclusions
The use of pre- and per-operative multimodal imaging allowed for the safe extraction of an intra-pericardial Kirschner wire through a minimally invasive approach.
Pulmonary cyst newly formed after lobectomy in various underlying lung conditions
Authors: Tanaka Satona , Date Naoki , Imamura Yoshito , Kabuto Takafumi , Kayawake Hidenao , Motoyama Hideki , Aoyama Akihiro , Date Hirohi 
Published: March 2024

Abstract
Background
It has been recently recognized that pulmonary cyst may develop after pulmonary resection, causing various symptoms. Most previously reported cases were after upper lobectomy in patients with chronic obstructive lung disease (COPD).

Case presentation
Case 1 was a man in his 70 s with interstitial pneumonia (IP). Right lower lobectomy was performed for metastatic lung tumor using video-assisted thoracoscopic surgery (VATS). On postoperative day (POD) 19, computed tomography (CT) revealed a large cyst at the upper interlobular surface of the middle lobe, with pneumoderma and pneumomediastinum. The cyst was incised, polyglycolic acid (PGA) sheet and fibrin glue were applied, and the cyst was sutured. The sutured line was covered again with PGA sheet and fibrin glue. Case 2 was a man in his 70 s with COPD. Right upper lobectomy for primary lung cancer was performed using VATS. On POD 17, CT revealed a large pulmonary cyst at the apex of S6 and massive air leakage was observed. The same surgical procedure as that used in case 1 was performed. Cases 3 and 4 were healthy donors for living-donor lung transplantation. Two months after the right lower lobectomy in Case 3 and 3 months after the left lower lobectomy in Case 4, the patients had respiratory symptoms such as dyspnea and hemosputum. CT revealed a large cyst on the diaphragmatic surface of the right middle lobe in Case 3 and on the posterior mediastinal surface of the left upper lobe in Case 4. Cyst incision, soft coagulation, and application of PGA sheet with fibrin glue were performed in both cases. CT performed 1 year after surgery showed no development of a pulmonary cyst or air space in these four cases.

Conclusions
Pulmonary cysts newly formed after lobectomy can develop not only in COPD or IP but also in healthy lungs. Our findings suggest that incision of the cyst and application of fibrin glue and PGA sheet with or without suturing the cyst wall is effective for management.
An innovative machine learning workflow to research China’s systemic financial crisis with SHAP value and Shapley regression
Authors: Wang Da , Zhou YingXue 
Published: March 2024

AbstractThis study proposed a cutting-edge, multistep workflow and upgraded it by addressing its flaw of not considering how to determine the index system objectively. It then used the updated workflow to identify the probability of China’s systemic financial crisis and analyzed the impact of macroeconomic indicators on the crisis. The final workflow comprises four steps: selecting rational indicators, modeling using supervised learning, decomposing the model’s internal function, and conducting the non-linear, non-parametric statistical inference, with advantages of objective index selection, accurate prediction, and high model transparency. In addition, since China’s international influence is progressively increasing, and the report of the 19th National Congress of the Communist Party of China has demonstrated that China is facing severe risk control challenges and stressed that the government should ensure that no systemic risks would emerge, this study selected China’s systemic financial crisis as an example. Specifically, one global trade factor and 11 country-level macroeconomic indicators were selected to conduct the machine learning models. The prediction models captured six risk-rising periods in China’s financial system from 1990 to 2020, which is consistent with reality. The interpretation techniques show the non-linearities of risk drivers, expressed as threshold and interval effects. Furthermore, Shapley regression validates the alignment of the indicators. The final workflow is suitable for categorical and regression analyses in several areas. These methods can also be used independently or in combination, depending on the research requirements. Researchers can switch to other suitable shallow machine learning models or deep neural networks for modeling. The results regarding crises could provide specific references for bank regulators and policymakers to develop critical measures to maintain macroeconomic and financial stability.
Learning from the implementation of a surgical opioid reduction initiative in an integrated health system: a qualitative study among providers and patients
Authors: Schäfer Willemijn L. A. , Johnson Julie K. , Ager Meagan S. , Iroz Cassandra B. , Huang Reiping , Balbale Salva N. , Stulberg Jonah J. 
Published: March 2024

Abstract
Background
Surgical opioid overprescribing can result in long-term use or misuse. Between July 2018 and March 2019, the multicomponent intervention, Minimizing Opioid Prescribing in Surgery (MOPiS) was implemented in the general surgery clinics of five hospitals and successfully reduced opioid prescribing. To date, various studies have shown a positive outcome of similar reduction initiatives. However, in addition to evaluating the impact on clinical outcomes, it is important to understand the implementation process of an intervention to extend sustainability of interventions and allow for dissemination of the intervention into other contexts. This study aims to evaluate the contextual factors impacting intervention implementation.

Methods
We conducted a qualitative study with semi-structured interviews held with providers and patients of the general surgery clinics of five hospitals of a single health system between March and November of 2019. Interview questions focused on how contextual factors affected implementation of the intervention. We coded interview transcripts deductively, using the Consolidated Framework for Implementation Research (CFIR) to identify the relevant contextual factors. Content analyses were conducted using a constant comparative approach to identify overarching themes.

Results
We interviewed 15 clinicians (e.g., surgeons, nurses), 1 quality representative, 1 scheduler, and 28 adult patients and identified 3 key themes. First, we found high variability in the responses of clinicians and patients to the intervention. There was a strong need for intervention components to be locally adaptable, particularly for the format and content of the patient and clinician education materials. Second, surgical pain management should be recognized as a team effort. We identified specific gaps in the engagement of team members, including nurses. We also found that the hierarchical relationships between surgical residents and attendings impacted implementation. Finally, we found that established patient and clinician views on opioid prescribing were an important facilitator to effective implementation.

Conclusion
Successful implementation of a complex set of opioid reduction interventions in surgery requires locally adaptable elements of the intervention, a team-centric approach, and an understanding of patient and clinician views regarding changes being proposed.
Classification of Congenital Leptin Deficiency
Authors: von Schnurbein Julia , Zorn Stefanie , Nunziata Adriana , Brandt Stephanie , Moepps Barbara , Funcke Jan-Bernd , Hussain Khalid , Farooqi I Sadaf , Fischer-Posovszky Pamela , Wabitsch Martin 
Published: March 2024

AbstractPurposeBiallelic pathogenic leptin gene variants cause severe early-onset obesity usually associated with low or undetectable circulating leptin levels. Recently, variants have been described resulting in secreted mutant forms of the hormone leptin with either biologically inactive or antagonistic properties.MethodsWe conducted a systematic literature research supplemented by unpublished data from patients at our center as well as new in vitro analyses to provide a systematic classification of congenital leptin deficiency based on the molecular and functional characteristics of the underlying leptin variants and investigated the correlation of disease subtype with severity of the clinical phenotype.ResultsA total of 28 distinct homozygous leptin variants were identified in 148 patients. The identified variants can be divided into 3 different subtypes of congenital leptin deficiency: classical hormone deficiency (21 variants in 128 patients), biologically inactive hormone (3 variants in 12 patients), and antagonistic hormone (3 variants in 7 patients). Only 1 variant (n = 1 patient) remained unclassified. Patients with biological inactive leptin have a higher percentage of 95th body mass index percentile compared to patients with classical hormone deficiency. While patients with both classical hormone deficiency and biological inactive hormone can be treated with the same starting dose of metreleptin, patients with antagonistic hormone need a variant-tailored treatment approach to overcome the antagonistic properties of the variant leptin.Main ConclusionCategorization of leptin variants based on molecular and functional characteristics helps to determine the most adequate approach to treatment of patients with congenital leptin deficiency.
Artificial Intelligence in Endocrinology: On Track Toward Great Opportunities
Authors: Assié Guillaume , Allassonnière Stéphanie 
Published: March 2024

Abstract
In endocrinology, the types and quantity of digital data are increasing rapidly. Computing capabilities are also developing at an incredible rate, as illustrated by the recent expansion in the use of popular generative artificial intelligence (AI) applications. Numerous diagnostic and therapeutic devices using AI have already entered routine endocrine practice, and developments in this field are expected to continue to accelerate. Endocrinologists will need to be supported in managing AI applications. Beyond technological training, interdisciplinary vision is needed to encompass the ethical and legal aspects of AI, to manage the profound impact of AI on patient/provider relationships, and to maintain an optimal balance between human input and AI in endocrinology.
Cardiovascular Risk in Women With Nonclassical Congenital Adrenal Hyperplasia
Authors: Costa Fernanda Cavalieri , Gomes Larissa Garcia , de Lima Thais Martins , Bortolotto Luiz Aparecido , Hong Valeria , Verardino Renata , de Souza Rocha Manoel , Ueda Serli Kiyomi Nakao , de Miranda Mirela Costa , de Souza Heraldo Possolo , Latronico Ana Claudia , Mendonca Berenice Bilharinho , Bachega Tania A S S 
Published: March 2024

Abstract

Context
The outcomes related to cardiovascular risk (CVR) in patients with the nonclassical form of congenital adrenal hyperplasia (NCAH) are unknown, especially those related to therapeutic options, including low doses of glucocorticoids or oral contraceptive pills.

Objectives
To analyze CVR by markers of atherosclerosis in females with the nonclassical form according to therapeutic options.

Design and Setting
A cross-sectional study at a tertiary center.

Patients and Methods
Forty-seven females with NCAH (33.4 ± 10 years) were subdivided into group 1 (G1) (n = 28) treated with dexamethasone (0.14 ± 0.05 mg/m2/day), group 2 (G2) (n = 19) treated with oral contraceptive pills, and group 3 (G3) (30 matched controls). CVR was analyzed through serum lipids, the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), inflammatory cytokines levels, and quantitative image evaluations [pulse wave velocity (PWV), endothelial function by flow-mediated dilatation (FMD), carotid intima media thickness (CIMT), and visceral fat (VAT) by abdominal tomography].

Results
There were no statistically significant differences in BMI, HOMA-IR, high-density lipoprotein-cholesterol, or triglyceride levels among groups (P &gt; .05). Serum interleukin 6 (IL-6) levels were higher in G1 than in G2 (P = .048), and interleukin 8 (IL-8) levels were higher in G1 than in G2/3 (P = .008). There were no statistically significant differences in VAT, PWV, FMD, or CIMT among groups (P &gt; .05). In multivariable regression analysis, there was no statistically significant association between glucocorticoid dose and evaluated outcomes.

Conclusion
Adult females with NCAH did not show increased CVR using methodologies for detection of precocious atherosclerosis. Although patients receiving dexamethasone therapy had increased IL-6 and IL-8 levels, these data were not associated with radiological markers of atherosclerosis. Our cohort was composed of young adults and should be reevaluated in a long-term follow-up.
Impaired polyamine metabolism causes behavioral and neuroanatomical defects in a mouse model of Snyder–Robinson syndrome
Authors: Akinyele Oluwaseun , Munir Anushe , Johnson Marie A. , Perez Megan S. , Gao Yuan , Foley Jackson R. , Nwafor Ashley , Wu Yijen , Murray-Stewart Tracy , Casero Robert A. , Bayir Hülya , Kemaladewi Dwi U. 
Published: March 2024

ABSTRACT
Snyder–Robinson syndrome (SRS) is a rare X-linked recessive disorder caused by a mutation in the SMS gene, which encodes spermine synthase, and aberrant polyamine metabolism. SRS is characterized by intellectual disability, thin habitus, seizure, low muscle tone/hypotonia and osteoporosis. Progress towards understanding and treating SRS requires a model that recapitulates human gene variants and disease presentations. Here, we evaluated molecular and neurological presentations in the G56S mouse model, which carries a missense mutation in the Sms gene. The lack of SMS protein in the G56S mice resulted in increased spermidine/spermine ratio, failure to thrive, short stature and reduced bone density. They showed impaired learning capacity, increased anxiety, reduced mobility and heightened fear responses, accompanied by reduced total and regional brain volumes. Furthermore, impaired mitochondrial oxidative phosphorylation was evident in G56S cerebral cortex, G56S fibroblasts and Sms-null hippocampal cells, indicating that SMS may serve as a future therapeutic target. Collectively, our study establishes the suitability of the G56S mice as a preclinical model for SRS and provides a set of molecular and functional outcome measures that can be used to evaluate therapeutic interventions for SRS.
Tirzepatide-induced ketoacidosis in non-diabetic patients
Authors: Iqbal Pathan Mohamad Rafe , Maadarani Ossama Sajeh , Bitar Zouheir Ibrahim 
Published: March 2024

Background: Tirzepatide is a novel glucagon-like peptide 1/glucose-dependent insulinotropic peptide (GLP-1/GIP) receptor agonist. It was recently approved for diabetes control and weight reduction in non-diabetic patients. Case description: We report the first case of ketoacidosis after the use of tirzepatide in an obese non-diabetic patient, secondary to the possibility of starvation ketoacidosis and insulin resistance. Conclusion: The dual-acting GLP-1 and GIP receptor agonists, tirzepatide, can induce ketoacidosis in obese non-diabetic patients.