bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi‐organ single‐cell RNA sequencing in mice reveals early hyperglycemia responses that converge on fibroblast dysregulation
Authors: Braithwaite Adam T. , Akbar Naveed , Pezzolla Daniela , Paget Daan , Krausgruber Thomas , Bock Christoph , Carnicer Ricardo , Choudhury Robin P. 
Published: February 2024

AbstractDiabetes causes a range of complications that can affect multiple organs. Hyperglycemia is an important driver of diabetes‐associated complications, mediated by biological processes such as dysfunction of endothelial cells, fibrosis, and alterations in leukocyte number and function. Here, we dissected the transcriptional response of key cell types to hyperglycemia across multiple tissues using single‐cell RNA sequencing (scRNA‐seq) and identified conserved, as well as organ‐specific, changes associated with diabetes complications. By studying an early time point of diabetes, we focus on biological processes involved in the initiation of the disease, before the later organ‐specific manifestations had supervened. We used a mouse model of type 1 diabetes and performed scRNA‐seq on cells isolated from the heart, kidney, liver, and spleen of streptozotocin‐treated and control male mice after 8 weeks and assessed differences in cell abundance, gene expression, pathway activation, and cell signaling across organs and within organs. In response to hyperglycemia, endothelial cells, macrophages, and monocytes displayed organ‐specific transcriptional responses, whereas fibroblasts showed similar responses across organs, exhibiting altered metabolic gene expression and increased myeloid‐like fibroblasts. Furthermore, we found evidence of endothelial dysfunction in the kidney, and of endothelial‐to‐mesenchymal transition in streptozotocin‐treated mouse organs. In summary, our study represents the first single‐cell and multi‐organ analysis of early dysfunction in type 1 diabetes‐associated hyperglycemia, and our large‐scale dataset (comprising 67 611 cells) will serve as a starting point, reference atlas, and resource for further investigating the events leading to early diabetic disease.
Assess Severity of Low Anterior Resection Syndrome After Intersphincteric Resection for Ultralow Rectal Cancer: A Pilot Study Using an Exploratory Instrument
Authors: Zhang Bin , Zhuo Guang-Zuan , Liu Fei-Fan , Zhao Yu-Juan , Cao Yu , Xiang Jian-Bin , Ding Jian-Hua 
Published: February 2024

BACKGROUND:
The Delphi consensus identified eight symptoms and eight consequences as the highest priorities for defining low anterior resection syndrome.

OBJECTIVE:
To describe an exploratory scoring instrument that correlates the Delphi consensus on low anterior resection syndrome with functional and quality-of-life scores following intersphincteric resection for ultralow rectal cancer.

DESIGN:
This was a prospective pilot study. In accordance with the Wexner incontinence score, five frequency responses ranging from never (score 0) to always (score 4) were used to measure the severity of symptom- and consequence-specific variables.

SETTINGS:
Colorectal surgery referral center.

PATIENTS:
Among 161 eligible patients, 137 (85%) participants completed an electronic self-assessment survey regarding function and quality-of-life at scheduled follow-up, including 3 to 6, 12, and ≥ 24 months after ileostomy reversal.

MAIN OUTCOME MEASURES:
Outcome measures included patient-reported severity of these priorities, as well as its correlation with condition-specific quality-of-life.

RESULTS:
The most frequent symptom and consequence were “emptying difficulties” and “dissatisfaction with the bowels,” respectively. Aside from “emptying difficulties,” the proportions of negative symptom domains increased after reversal. In particular, both the frequency responses and the severity scores of “emptying difficulties” did not differ between groups. The percentages of “always option” for consequence domains improved at 12-months follow-up, whereas a higher rate was observed at 24-months later, except for “toilet dependence” and “dissatisfaction with the bowels.” We found significant improvements in the summary score of Fecal Incontinence Quality of Life Scale (p = 0.04) and our exploratory instrument (p = 0.009), but not in functional scores measured by traditional questionnaires. Furthermore, the condition-specific quality of life strongly correlated with the Delphi consensus severity score (r

s
= -0.73).

LIMITATIONS:
Single-institution data and limited sample size.

CONCLUSIONS:
The important priorities identified by the Delphi consensus might enable a comprehensive overview and a better assessment of low anterior resection syndrome after intersphincteric resection. See Video Abstract.
Tips, Tricks, and Pearls for a Superior Patient and Surgeon Experience for Wide-awake Dupuytren Surgery
Authors: Barone Natasha , Lalonde Donald H. , Brutus Jean Paul 
Published: February 2024

Summary:
Fasciectomy for Dupuytren disease is a common procedure traditionally performed with a tourniquet under general or regional anesthesia. Since the year 2001, the wide-awake local anesthesia no tourniquet (WALANT) approach has been applied successfully to Dupuytren surgery, with current excellent surgeon and patient satisfaction. However, using WALANT for Dupuytren surgery may be intimidating for hand surgeons who want to begin using this method. The purpose of this article is to offer a series of tips and tricks the authors have learned after having performed hundreds of WALANT fasciectomies, to make this technique easier for surgeons and a more pleasurable experience for patients.
Embracing Neuro-Inclusivity Within Physician Assistant/Associate Education: Challenging Organizational Cultural Norms and Navigating Communication Challenges
Authors: Frizell Carl A. , Graham Devin , DuVentre Amber , Brown Sheena D. 
Published: February 2024

Abstract
Effective communication in health care education is essential for creating an inclusive learning environment. This manuscript examines the crucial role of communication in physician assistant/associate (PA) education, particularly in the context of neurodiverse individuals, who constitute approximately 20% of the global population. A groundbreaking study by Nouri et al reveals a 3.1% overall disability prevalence among US practicing physicians, emphasizing the necessity for a comprehensive understanding of diversity in the health care profession. Considering the intersectionality of marginalized identities, this research sheds light on potential challenges health care providers face, underscoring the importance of promoting inclusivity and support for neurodiverse individuals in the PA profession. The increasing presence of neurodivergent students in postsecondary institutions, despite academic strengths, holds relevance for PA education. Recognizing the barriers and stigmas associated with neurodiversity is crucial for fostering inclusive environments within PA programs and sponsoring institutions. This manuscript explores the challenges faced by neurodiverse individuals in PA education and proposes strategies for cultivating a neuroinclusive culture through effective communication. With a focus on celebrating and using the strengths of all learners, regardless of neurodiversity, the overarching goal is to contribute to a paradigm shift in PA education, enriching the educational experience for students, educators, and support staff.
Diagnostic performance of serum galactomannan and β-D-glucan for invasive aspergillosis in suspected patients: A meta-analysis
Authors: Huang Qian-Yi , Li Peng-Cheng , Yue Jin-Rui 
Published: February 2024

Background:
Serum galactomannan (GM) and β-D-glucan (BG) are known markers of invasive aspergillosis (IA). The aim of this meta-analysis was to evaluate the efficiency of serum GM and BG as diagnostic markers of symptomatic IA infection and compare the performance of the combined tests with that of either test individually.

Methods:
A literature search was carried out using PubMed, Web of Science, and EMBASE databases to include relevant studies published in English up to May 2023. The quality assessment was performed using Review Manager 5.3 software. A bivariate model was applied to pool diagnostic parameters using Stata 14.0 software. We used Cochrane I
2 index to assess heterogeneity and identify the potential source of heterogeneity by meta-regression. Paired t tests were used to compare the value of GM and BG for IA diagnosis when used in combination or alone.

Results:
Sixteen studies were eligible for inclusion in the meta-analysis. For proven or probable IA, serum GM and BG yielded a pooled sensitivity of 0.53 (95% CI 0.40–0.66) vs 0.72 (95% CI 0.61–0.81) and a pooled specificity of 0.94 (95% CI 0.91–0.97) vs 0.82 (95% CI 0.73–0.88). The area under the curve (AUC) of ROC was 0.90 (95% CI 0.87–0.92) vs 0.83 (95% CI 0.80–0.86) for all studies. The pooled sensitivity and specificity for IA diagnosis by combined GM and BG assays (GM/BG) were 0.84 (95% CI 0.69–0.86) and 0.76 (95% CI 0.69–0.81), respectively. The sensitivity of the combined GM/BG test to diagnose IA was higher than of the GM or BG test alone.

Conclusion:
Serum GM and BG tests had a relatively high accuracy for IA diagnosis in suspected patients. The diagnostic accuracy of both assays is comparable, and the diagnostic sensitivity is further improved by the combined detection of the 2 markers.
Emergency hybrid surgery for transection of pancreas at the head and neck after blunt abdominal trauma: A case report and review of the literature
Authors: Xu Yanan , Ai Tao 
Published: February 2024

Introduction:
A complete disruption of main pancreatic duct (MPD) presents a significant challenge to the surgeon. Historically, the standard surgical approach for addressing a complete disruption of the MPD involved distal pancreatic resection and pancreaticojejunostomy Roux-en-Y anastomosis. Nevertheless, there have been no reported cases of hybrid surgery being employed for the complete disruption of the MPD.

Patient concerns:
A 63-year-old male patient presented with blunt trauma in the upper abdomen and was transferred to our trauma center 10 hours after injury. Upon arrival at the emergency department, he was conscious, hemodynamically stable, and complained of upper abdominal pain and distention. Physical examination revealed right upper abdominal tenderness and slight abdominal tension. Abdominal contrast-enhanced CT scan revealed a complete transection of pancreatic parenchyma at the junction of the head and neck.

Diagnoses:
Complete transection of pancreatic parenchyma at the junction of the head and neck combined with complete disruption of the MPD, AIS grade IV.

Interventions:
The hybrid surgery was initially utilized for complete MPD disruption, incorporating endoscope-assisted stent placement in the MPD along with primary repair of the pancreatic parenchyma and duct.

Outcomes:
The postoperative period went smoothly, and the patient recovered and was discharged 4 weeks after operation. The MPD stent was removed under endoscope 4 months after operation, and Endoscopic Retrograde Pancreatography examination showed that the MPD was patency and slight MPD stenosis without pancreatic leakage. At the most recent follow-up, the patient had returned to normal life and work without any pancreatic endocrine or exocrine dysfunction.

Lessons:
The hybrid surgery, incorporating endoscope-assisted MPD stent placement and primary repair of the pancreatic parenchyma and duct, emerges as a promising alternative for complete MPD disruption in hemodynamically stable patients. The challenge in this hybrid surgery is the precise localization of the distal end of the MPD.
Quadruplet Therapy in De Novo High-Volume Mixed Neuroendocrine Prostate Cancer Using 177Lu-PSMA
Authors: Askari Emran , Aryana Kamran , Jafarian Amir Hosein , Bari Alireza , Barashki Somaye 
Published: February 2024

Abstract
We present a case of de novo high-volume metastatic prostate cancer with high PSMA expression, partially PSMA-negative, using quadruplet therapy (PROMISE ver. 2 miTNM; miT4N2M1aM1b(dmi) PRIMARY score: 5, PSMA-expression score: 0–3). Because of our patient’s partial PSMA negativity and after a multidisciplinary tumor board discussion, we decided to use a modified protocol involving doublet hormonal therapy along with 177Lu-PSMA and radiation therapy to address the PSMA-negative disease. The patient responded well to this treatment, but recurrence was ultimately inevitable. This case represents a typical example of mixed neuroendocrine prostate carcinoma and highlights its resistant phenotype in response to quadruplet therapy.
MALT Lymphoma in Histologic Transformation
Authors: Tang Ranbie , Chen Xi , Liu Mengna , Shu Qiaoqiao , Cai Liang 
Published: February 2024

Abstract
An 81-year-old woman experienced compression symptoms due to diffuse enlargement of the thyroid gland. The cytopathological results of thyroid fine-needle suggested malignancy. Therefore, she underwent bilateral thyroidectomy. Postoperative pathology indicated mucosa-associated lymphoid tissue (MALT) lymphoma. Three months later, she found a progressively enlarged mass in her neck. The biopsy showed MALT lymphoma with highly aggressive B-cell lymphoma transformation. 18F-FDG PET/CT showed increased metabolism in multiple lymph nodes. However, some of these lymph nodes were negative in 68Ga-pentxafor PET/CT. Our case demonstrated that 68Ga-pentixafor may have limited value in evaluating MALT lymphoma transformation.
A Novel Therapeutic Approach using CXCR3 Blockade to Treat Immune Checkpoint Inhibitor-mediated Myocarditis
Authors: Huang Yuhsin Vivian , Lee Daniel , Sun Yin , Chou Harrison , Xu Bruce , Lin Zachary , Branche Corynn , Bayer Abraham , Waliany Sarah , Neal Joel , Wakelee Heather , Witteles Ronald , Nguyen Patricia , Graves Edward , Alcaide Pilar , Berry Gerald J. , Wu Sean M. , Zhu Han 
Published: February 2024

AbstractBackgroundImmune checkpoint inhibitors (ICIs) are successful in treating many cancers but may cause immune-related adverse events. ICI-mediated myocarditis has a high fatality rate of up to 40%, with severe cardiovascular consequences. Targeted therapies for ICI myocarditis are currently lacking.MethodsWe used a genetic mouse model ofPD-1deletion (MRL/Pdcd1-/-) along with a novel drug-treated ICI myocarditis mouse model to recapitulate the disease phenotype. We performed single-cell RNA-sequencing (scRNAseq), single-cell T-cell receptor sequencing (scTCR-seq), and cellular indexing of transcriptomes and epitopes (CITE-seq) on immune cells isolated fromMRLandMRL/Pdcd1-/-mice at serial timepoints. We assessed the impact of macrophage deletion inMRL/Pdcd1-/-mice, then inhibited CXC chemokine receptor 3 (CXCR3) in ICI-treated mice to assess therapeutic effect on myocarditis phenotype. Furthermore, we delineated functional effects of CXCR3 blockade on T-cell and macrophage interactions in a transwell assay. We then correlated the results in human single-cell multi-omics data from blood and heart biopsy data from patients with ICI myocarditis.ResultsSingle-cell multi-omics demonstrated expansion of CXCL9/10+CCR2+ macrophages and CXCR3hi CD8+ effector T-lymphocytes in the hearts ofMRL/Pdcd1-/-mice correlating with onset of myocarditis development. Both depletion of CXCL9/10+CCR2+ macrophages and CXCR3 blockade respectively led to decreased CXCR3hiCD8+ T-cell infiltration into the heart and significantly improved survival. A transwell assay showed that selective blockade of CXCR3 and its ligand, CXCL10 decreased CD8+ T-cell migration towards macrophages, implicating this interaction in T-cell cardiotropism towards cardiac macrophages. Cardiac biopsies from patients with confirmed ICI myocarditis demonstrated infiltrating CXCR3+ lymphocytes and CXCL9+/CXCL10+ macrophages. Both mouse cardiac immune cells and patient peripheral blood immune cells revealed expanded TCRs correlating with CXCR3hi CD8+ T-cells in ICI myocarditis samples.ConclusionsThese findings bring forth the CXCR3-CXCL9/10 axis as an attractive therapeutic target for ICI myocarditis treatment, and more broadly, as a druggable pathway in cardiac inflammation.
A gene-rich mitochondrion with a unique ancestral protein transport system
Authors: Moreira David , Blaz Jazmin , Kim Eunsoo , Eme Laura 
Published: February 2024

SummaryMitochondria originated from an ancient endosymbiotic event involving an alphaproteobacterium1–3. Over time, these organelles reduced their gene content massively, with most genes being transferred to the host nucleus before the last eukaryotic common ancestor (LECA)4. This process has yielded varying gene compositions in modern mitogenomes, including the complete loss of this organellar genome in some extreme cases5–14. At the other end of the spectrum, Jakobids harbor the largest mitogenomes, encoding 60-66 proteins8. Here, we introduce the mitogenome ofMantamonas sphyraenae, a protist from the deep-branching CRuMs supergroup15,16. Remarkably, it boasts the most gene-rich mitogenome outside of jakobids, by housing 91 genes, including 62 protein-coding ones. These include rare homologs of the four subunits of the bacterial-type cytochrome c maturation system I (CcmA, CcmB, CcmC, and CcmF), alongside a unique ribosomal protein S6. During the early evolution of this organelle, gene transfer from the proto-mitochondrial endosymbiont to the nucleus became possible thanks to systems facilitating the transport of proteins synthesized in the host cytoplasm back to the mitochondrion. In addition to the universally found eukaryotic protein import systems, jakobid mitogenomes were reported to uniquely encode the SecY transmembrane protein of the bacterial Type II secretion system; its evolutionary origin was however unclear. TheMantamonasmitogenome not only encodes SecY but also SecA, SecE, and SecG, making it the sole eukaryote known to house a complete mitochondrial Sec translocation system. Furthermore, our phylogenetic and comparative genomic analyses provide compelling evidence for the alphaproteobacterial origin of this system, establishing its presence in LECA.
Collagen organization and structure inFLBN5-/-, mice using label-free microscopy: implications for pelvic organ prolapse
Authors: Jennings Christian M. , Markel Andrew C. , Domingo Mari J.E. , Miller Kristin S. , Bayer Carolyn L. , Parekh Sapun H. 
Published: February 2024

AbstractPelvic organ prolapse (POP) is a gynecological disorder described by the descent of superior pelvic organs into or out of the vagina as a consequence of disrupted muscles and tissue. A thorough understanding of the etiology of POP is limited by the availability of clinically relevant samples, restricting longitudinal POP studies on soft-tissue biomechanics and structure to POP-induced models such as fibulin-5 knockout (FBLN5-/-) mice. Despite being a principal constituent in the extracellular matrix, little is known about structural perturbations to collagen networks in theFBLN5-/-mouse cervix. We identify significantly different collagen network populations in normal and prolapsed cervical cross-sections using two label-free, nonlinear microscopy techniques. Collagen in the prolapsed mouse cervix tends to be more isotropic, and displays reduced alignment persistence via 2-D Fourier Transform analysis of images acquired using second harmonic generation microscopy. Furthermore, coherent Raman hyperspectral imaging revealed elevated disorder in the secondary structure of collagen in prolapsed tissues. Our results underscore the need forin situmultimodal monitoring of collagen organization to improve POP predictive capabilities.
Onset of Mismatch Repair by the Human Mismatch Repair Protein, MutSbeta for a Biosensing Device
Authors: Devlin Jack , Madigan Jenna , Macwan Isaac 
Published: February 2024

AbstractDeficiency of MutSbeta protein has been proven to be a cause of Lynch Syndrome, which leads to hereditary colorectal cancer. In the absence of MutSbeta, or the energy source to initiate the conformational change of MutSbeta, the DNA repair pathway would not detect the DNA base pairing errors resulting in a failure to proceed. To examine the essential role of MutSbeta and the interface between MutSbeta and a mismatched DNA strand, 500ns of molecular dynamics simulations were performed and the results were compared with the controls. It is found that during the first 100ns, the outermost domain of MutSbeta (chain BP4) gets hold of the DNA, and the inner domains (AP1 and BP1) prepare to scan the DNA strand. An RMSD of 5-7Å for the control MutSbeta compared to 3-6.5Å in the presence of a mismatched DNA indicate that starting ∼75ns, MutSbeta stabilizes and initiates the scanning of the mismatched DNA. The reduction of the distance between the two biomolecules by ∼16Å, increase of Van der Waals energies by ∼75 kCal/mol and a crucial role played by the interfacial water molecules and their hydrogen bonds during the next 100ns also supports the manipulative nature and initiation of scanning by MutSbeta.Author SummaryAbout 1 and 23 men and 1 and 26 women have the chances of developing colorectal cancer and the chances only increase with old age. Cancer typically develops from mutated DNA, which emphasizes the importance of understanding how proteins a part of the DNA repair pathway process interact with a mutated strand of DNA. One such protein, MutSbeta, is the first protein that initiates the repair pathway process and scans DNA for any mutations. As the initiator, a deficiency of MutSbeta leads to higher chances of mutated DNA going undetected, and therefore forming cancerous cells. Using 3D simulations, we analyzed the interactions between MutSbeta and a mutated DNA strand. We found that the two outer domains, AP4 and BP4 grab hold of the DNA strand while the inner clamps, AP1 and BP1 scan the DNA strand. It was also discovered that Van der Waals play a more dominant role compared to electrostatics in terms of the driving force behind the interactions between DNA and MutSbeta. Overall, our data supported the attractive nature of MutSbeta towards DNA and its stability as it initiates the scanning process. Furthermore, this data was used to verify the presence of MutSbeta for a biosensor that was built previously; owing to the significance and applicatory effects of this work.
The influence of uncertainty on indulgent consumption: a chain mediation model of curiosity and positive emotion
Authors: Zhang Yi , Zhang Tianqi , Zhou Hang , Qin Jian 
Published: February 2024

PurposePeople usually try to avoid uncertainty. Recently, however, uncertainty has become an emerging marketing tool in the hedonic product industry. In the case of blind box consumption, for example, the consumers become addicted to the uncertainty created by businesses, leading to repeat purchases and even indulgences. Previous research has, yet, to focus on the impact of uncertainty on indulgence and the role of emotions.Design/methodology/approachThis paper constructs and validates a chain mediation model of uncertainty triggering indulgent consumption based on the information gap theory, positive emotion theory and uncertainty resolution theory and examines the difference between resolved and unresolved uncertainty. This study also explores differences in the impact of whether uncertainty is resolved on emotions. The uncertainty-resolved group elicited a more positive emotional response than the uncertainty-unresolved group, leading to a more indulgent consumption.FindingsThe results of three studies show that uncertainty influences indulgent consumption through curiosity and positive emotion, and that curiosity and positive emotion play separate and chain mediating roles between uncertainty and indulgent consumption, respectively. We validate our central hypothesis with questionnaires among blind box consumer groups, examining the moderating role of perceived luck and risk preferences.Originality/valueThe findings shed new light on firms' use of uncertainty to promote consumer purchases.