bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Utility of Stepwise Bronchoalveolar Lavage Fluid Analysis in Diagnosing and Managing Lung Infiltrates in Leukemia/Lymphoma Patients With Febrile Neutropenia
Authors: Thorat Jayashree , Bhat Surabhi , Sengar Manju , Baheti Akshay , Bothra Sweta , Bhaskar Maheema , Tandon Sandeep Prakashnarain , Biswas Sanjay K. , Salunke Gaurav V. , Karimundackal George , Tiwari Virendra Kumar , Pramesh C.S. , Sharma Neha , Kapu Venkatesh , Eipe Thomas , Bagal Bhausaheb Pandurang , Nayak Lingaraj , Bonda Avinash , Janu Amit , Shetty Alok , Jain Hasmukh 
Published: February 2024

PURPOSE Febrile neutropenia (FN) is a serious complication in hematologic malignancies, and lung infiltrates (LIs) remain a significant concern. An accurate microbiological diagnosis is crucial but difficult to establish. To address this, we analyzed the utility of a standardized method for performing bronchoalveolar lavage (BAL) along with a two-step strategy for the analysis of BAL fluid. PATIENTS AND METHODS This prospective observational study was conducted at a tertiary cancer center from November 2018 to June 2020. Patients age 15 years and older with confirmed leukemia or lymphomas undergoing chemotherapy, with presence of FN, and LIs observed on imaging were enrolled. RESULTS Among the 122 enrolled patients, successful BAL was performed in 83.6% of cases. The study used a two-step analysis of BAL fluid, resulting in a diagnostic yield of 74.5%. Furthermore, antimicrobial therapy was modified in 63.9% of patients on the basis of BAL reports, and this population demonstrated a higher response rate (63% v 45%; P = .063). CONCLUSION Our study demonstrates that a two-step BAL fluid analysis is safe and clinically beneficial to establish an accurate microbiological diagnosis. Given the crucial impact of diagnostic delays on mortality in hematologic malignancy patients with FN, early BAL studies should be performed to enable prompt and specific diagnosis, allowing for appropriate treatment modifications.
PIVOT-006: A phase 3, randomized study of cretostimogene grenadenorepvec versus observation for the treatment of intermediate risk non-muscle invasive bladder cancer (IR-NMIBC) following transurethral resection of bladder tumor (TURBT).
Authors: Svatek Robert S. , Bivalacqua Trinity , Keegan Kirk A. , Daneshmand Siamak 
Published: February 2024

TPS715 Background: Guidelines for Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) recommend adjuvant intravesical (IVE) therapy or surveillance. Despite this, 30–60% of patients still recur, and these Guideline recommendations are lacking level-1 evidence. Thus, there is a considerable gap in knowledge and an unmet medical need for improved therapies in the adjuvant setting. Cretostimogene Grenadenorepvec is an oncolytic adenovirus designed to preferentially replicate in and kill cancer cells. The vector is transcriptionally regulated by the E2F promoter that is up-regulated in retinoblastoma (Rb) pathway-defective tumor cells, common in most IR-NMIBC bladder tumors. Additionally, the virus is engineered to selectively express GM-CSF, in order to induce a robust systemic anti-tumor immune response. PIVOT-006 is an open-label, multi-center, randomized Phase 3 study designed to assess the efficacy and safety of intravesical Cretostimogene after TURBT versus TURBT alone. Methods: Eligibility criteria: age ≥18 years, Eastern Cooperative Oncology Group performance status of 0-2, histologically confirmed IR-NMIBC with absence of nodal or metastatic disease at screening. IR-NMIBC, as defined by American Urologic Association-Society of Urologic Oncology Guidelines on NMIBC, is either a Low Grade (LG) stage Ta tumor that recurs within 12 months of prior LG or High Grade (HG) bladder cancer, a solitary LGTa tumor >3cm in size, multifocal LGTa tumors, primary HGTa lesion < 3cm in size, or a LGT1 tumor. Participants will be stratified by receipt of perioperative chemotherapy and tumor grade. Pts (N~450) will be randomized 1:1 to receive intravesical Cretostimogene (Cohort 1) adjuvant to TURBT or TURBT alone (Cohort 2). Single dose perioperative intravesical chemotherapy at the time of TURBT is permitted. If intravesical NMIBC recurrence is noted in Cohort 2, participants will be eligible to receive intravesical Cretostimogene. In Cohort 1, intravesical Cretostimogene will be instilled in combination with n-dodecyl-B-D-maltoside (DDM, an inactive detergent) for 6 weekly doses during the induction phase, followed by 3 weekly maintenance cycles at months 3 and 6, and culminating in single intravesical doses at months 9 and 12. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and centralized review of pathologic samples. The primary outcome measure is recurrence free survival. Secondary outcome measures include safety, tolerability, progression free survival, and time to next intervention. Exploratory outcome measures include patient-reported quality of life, biomarker analyses, coxsackie adenovirus receptor and E2F promoter expression, neutralizing antibodies, and markers of immunogenicity. Clinical trial information: Pending.
Fulminant Type 1 Diabetes Caused by DIHS Could Be Affected by the Reactivation of HHV-6
Authors: Makino Hideichi , Tohyama Mikiko , Kawamura Ryoichi , Takata Yasunori , Osawa Haruhiko , Onuma Hiroshi 
Published: February 2024

Abstract

Context
In the previous issue of this journal, we reported that the incidence of fulminant type 1 diabetes (FT1D) due to the drug-induced hypersensitivity syndrome (DIHS) in Japan is higher than that in the general population and is associated with HLAB62. On the other hand, the reactivation of human herpesvirus 6 (HHV-6), which has been reported to be associated with DIHS, was observed at a higher frequency, but its association with the development of FT1D was unclear.

Objective
We aimed to clarify the relationship between the onset of FT1D and the reactivation of HHV-6.

Methods
We conducted a literature search for cases of DIHS-induced FT1D in addition to previously reported cases and investigated the changes in the HHV-6 antibody titer before and after the onset of FT1D.

Results
The HHV-6 antibody titer was increased just before or after the onset of FT1D in all 8 cases. In 1 case, HHV-6 DNA was also identified shortly before the onset of FT1D.

Conclusion
These results indicate for the first time that the reactivation of HHV-6 is associated with the onset of FT1D caused by DIHS.
A Retrospective Study on Weaning Glucocorticoids and Recovery of the Hypothalamic–Pituitary–Adrenal Axis
Authors: Arshad Muhammad Fahad , Elder Charlotte , Newell-Price John , Ross Richard , Debono Miguel 
Published: February 2024

Abstract

Context
Glucocorticoids suppress the hypothalamic–pituitary–adrenal (HPA) axis, resulting in tertiary adrenal insufficiency (AI). When weaning patients off glucocorticoids there is no consensus on whether to maintain patients on prednisolone or convert to hydrocortisone.

Objective
To investigate HPA axis recovery in patients on long-term prednisolone and assess outcome after hydrocortisone conversion.

Methods
This was a retrospective cohort study at an outpatient endocrine steroid clinic. Patients were on long-term prednisolone and referred for HPA axis testing between 2015 and 2022. The main outcomes measured were (1) HPA axis recovery rate in patients on prednisolone demonstrated by a normal adrenocorticotrophic hormone (ACTH) stimulation test (AST) and (2) HPA axis recovery rate subanalysis of dose-matched patients with confirmed tertiary AI on prednisolone or hydrocortisone were measured.

Results
In total, 206 patients on prednisolone were tested for tertiary AI. Of these, 176 remained on prednisolone while 30 were converted to hydrocortisone. The overall HPA axis recovery rate for patients on prednisolone after interval testing was 137/206 (66.5%). The HPA axis recovery rate in dose-matched prednisolone and hydrocortisone conversion groups was 7/10 (70%) and 2/13 (15%) (P = .008), respectively. There was no difference in mean (SD) age (67.1 [12.2] vs 63.4 [11.1] years; P = .464) and baseline cortisol (5.3 [4.2] vs 4.6 [3.1] µg/dL; P = .648) and median [interquartile, IQR] glucocorticoid duration (1213 [1114] vs 2316 [4808] days; P = .693) and baseline ACTH (20.5 [29.0] vs 16.3 [14.8] ng/L; P = .905) between dose-matched prednisolone and hydrocortisone groups. Follow-up duration in the prednisolone group was significantly lower (median [IQR] 348 [975] vs 667 [884] days; P = .012).

Conclusion
Patients with glucocorticoid-induced AI maintained on once-daily prednisolone can recover HPA axis function when weaning. There is no apparent advantage to recover HPA axis function in converting to multiple-dosing hydrocortisone.
Loss of Fshr Prevents Testicular Maturation in Atlantic Salmon (Salmo salar L.)
Authors: Andersson Eva , Schulz Rüdiger W , Almeida Fernanda , Kleppe Lene , Skaftnesmo Kai Ove , Kjærner-Semb Erik , Crespo Diego , Fjelldal Per Gunnar , Hansen Tom Johnny , Norberg Birgitta , Edvardsen Rolf B , Wargelius Anna 
Published: February 2024

Abstract
Early puberty poses a significant challenge for male Atlantic salmon in aquaculture due to its negative impact on growth and welfare. The regulation of puberty in vertebrates involves 2 key reproductive hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and their gonadal receptors. In male mice lacking FSH receptor, testes size is reduced, but fertility is maintained, while medaka and zebrafish with a disrupted fshr gene exhibit near normal testis size and fertility. In these fishes both Fsh and Lh are present during puberty and Lh may rescue fertility, while in salmonid fish only Fsh is present in the circulation during puberty. Using CRISPR-Cas9, we produced crispants with a high prevalence of fshr mutations at the target site, which remained fertile, although more than half showed a testis development deviating from wild-type (wt) males. Crossing out these F0 crispants to each other produced a viable F1 generation showing frameshift (fshr−/−) or in-frame mutations (fshrif/if). Nearly all wt males matured while all fshr−/− males remained immature with small testes containing A spermatogonia as the furthest developed germ cell type and prepubertal plasma androgen levels. Also, the pituitary transcript levels of gnrhr2bba and lhb, but not for fshb, were reduced in the fshr−/− males compared with maturing males. More than half of the fshrif/if mutant males showed no or a delayed maturation. In conclusion, Atlantic salmon show the unique characteristic that loss of Fshr function alone results in male infertility, offering new opportunities to control precocious puberty or fertility in salmon.
Adrenal Abcg1 Controls Cholesterol Flux and Steroidogenesis
Authors: Liimatta Jani , Curschellas Evelyn , Altinkilic Emre Murat , Naamneh Elzenaty Rawda , Augsburger Philipp , du Toit Therina , Voegel Clarissa D , Breault David T , Flück Christa E , Pignatti Emanuele 
Published: February 2024

Abstract
Cholesterol is the precursor of all steroids, but how cholesterol flux is controlled in steroidogenic tissues is poorly understood. The cholesterol exporter ABCG1 is an essential component of the reverse cholesterol pathway and its global inactivation results in neutral lipid redistribution to tissue macrophages. The function of ABCG1 in steroidogenic tissues, however, has not been explored. To model this, we inactivated Abcg1 in the mouse adrenal cortex, which led to an adrenal-specific increase in transcripts involved in cholesterol uptake and de novo synthesis. Abcg1 inactivation did not affect adrenal cholesterol content, zonation, or serum lipid profile. Instead, we observed a moderate increase in corticosterone production that was not recapitulated by the inactivation of the functionally similar cholesterol exporter Abca1. Altogether, our data imply that Abcg1 controls cholesterol uptake and biosynthesis and regulates glucocorticoid production in the adrenal cortex, introducing the possibility that ABCG1 variants may account for physiological or subclinical variation in stress response.
Urinary Vitamin D Binding Protein: A Marker of Kidney Tubular Dysfunction in Patients at Risk for Type 2 Diabetes
Authors: Semnani-Azad Zhila , Wang Windy Z N , Cole David E C , Johnston Luke W , Wong Betty Y L , Fu Lei , Retnakaran Ravi , Harris Stewart B , Hanley Anthony J 
Published: February 2024

Abstract

Context
Recent studies have reported elevated urinary vitamin D binding protein (uVDBP) concentrations in patients with diabetic kidney disease, although the utility of uVDBP to predict deterioration of kidney function over time has not been examined.

Objective
Our objective was to assess the association of uVDBP with longitudinal changes in kidney function.

Methods
Adults at-risk for type 2 diabetes from the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 727). Urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were used as measures of kidney function. Measurements of uVDBP were performed with enzyme-linked immunosorbent assay and normalized to urine creatinine (uVDBP:cr). Generalized estimating equations (GEEs) evaluated longitudinal associations of uVDBP and uVDBP:cr with measures of kidney function, adjusting for covariates.

Results
Renal uVDBP loss increased with ACR severity at baseline. Individuals with normoalbuminuria, microalbuminuria, and macroalbuminuria had median log uVDBP:cr concentrations of 1.62 μg/mmol, 2.63 μg/mmol, and 2.48 μg/mmol, respectively, and ACR positively correlated with uVDBP concentrations (r = 0.37; P &lt; .001). There was no significant association between uVDBP and eGFR at baseline. Adjusted longitudinal GEE models indicated that each SD increase both in baseline and longitudinal uVDBP:cr was significantly associated with higher ACR over 6 years (β = 30.67 and β = 32.91, respectively). Conversely, neither baseline nor longitudinal uVDBP:cr measures showed a significant association with changes in eGFR over time. These results suggest that loss of uVDBP:cr over time may be a useful marker for predicting renal tubular damage in individuals at risk for diabetes.
The Prosaics of Weak Grammar: Novel Theory at the Crossroads of Linguistic Transformation
Authors: Lee Sookyoung 
Published: February 2024

Abstract
Novelistic sentences dramatically simplified in structure and contracted in length throughout the 1800s and early 1900s. This article places these changes within the longer process of grammatical “weakening” (the loss of inflection for regular order). Building on the linguist Otto Jespersen's theorization of the relationship between grammar and social change, the article argues that the grammar of modern novels, irrespective of their representational content or individuating style, has a proleptic relation to the rise of mass society. The problems that Georg Lukács and Theodor Adorno would articulate in terms of reification and alienation are already enacted grammatically as words break down into their linguistic properties and increasingly derive their meaning through placement. The article focuses on three pivotal moments of this development: the “prosification,” or the virtual conflation of poetic and prosaic syntax, in the Romantic era; the conspicuous intensification of uninflected prose that is generally taken to be the stylistic innovation of the modernist era exemplified by Virginia Woolf; and the sedimentation of syntax into generic idioms in subsequent decades in such writers as Doris Lessing and Samuel Beckett. Novelistic grammar, precisely by prefiguring the social changes to come, models a rationality that constrains the possibilities of moving past those changes. By analyzing the contradictions constitutive of novelistic grammar, this article questions what is reinforced or foreclosed in the endless generativity of grammar.
Making Meaning Meaningful: Intertextuality and Identification in Never Let Me Go and Daniel Deronda
Authors: Hack Daniel 
Published: February 2024

Abstract
This article reconsiders the relationship between identificatory and mimetic reading practices—so often viewed as naive or mystified—and attention to intertextuality, which has so often been seen as contrasting with and discrediting such practices. Such a reconsideration, made timely by growing dissatisfaction with a post-providential, disenchanted view of the world as devoid of meaning, is invited by and in turn illuminates one of the most celebrated novels of the twenty-first century, Kazuo Ishiguro's Never Let Me Go (2005). The narrator-protagonist of this novel, I argue, embodies a type that the most influential current of novel theory has made difficult to credit, perhaps even to recognize: the reverse quixote, a character who ostentatiously resists conflating literature and life or viewing the world and experience through the lens of literature—but who would benefit from doing so. Intertextual reading brings this reverse quixotism to light and reveals its dimensions, as the intertextual reader tracks the connections that the novel's anti-identificatory characters refuse to make and considers the motives for and costs of this refusal. The most significant intertext driving this shadow plot is George Eliot's Daniel Deronda (1876), itself a study of the meaning-making, life-shaping power of identificatory and mimetic reading, or what Eliot calls “the magic of quick comparison.”
Elevation of Depressed Skull Fracture in Neonates Using a Breast Pump and a Custom-Molded Flange
Authors: Martinez Emilie L. , Welscher Ashley , Shah Manish N. , Sandberg David I. 
Published: February 2024

BACKGROUND AND IMPORTANCE:
“Ping-pong fractures” (PPF) can occur in neonates and result in cosmetic deformity and local mass effect. Standard treatment involves surgical elevation of the depressed bone when the indentation is considerable or cosmetically apparent. Surgical correction of PPF subjects patients to the risks of surgery and general anesthesia. This article and corresponding video demonstrate a novel means of correcting PPF at bedside without surgery or anesthesia. We used a hospital-grade breast pump connected to a custom-fabricated flange to successfully elevate PPF in two neonates.

CLINICAL PRESENTATION:
Two moderately preterm infants were noted at birth to have large parietal PPF. To avoid surgical intervention, elevation using a suction device was attempted. A hospital-grade breast pump was used to provide suction. A custom device was fabricated out of a breast pump flange and molded Coloplast Brava® protective seal rings. This device was carefully applied to the skull to exactly match the diameter of the PPF and contour of the bone. Brief (15-30 seconds) periods of suction were applied several times until the PPF was successfully elevated as documented on subsequent computed tomography scans. Both infants achieved excellent cosmetic results with no adverse effects over 24- and 9-month follow-ups, respectively.

DISCUSSION:
This technique eliminates the risks of open surgical correction and corrected the PPF without general anesthesia or adverse effects to the infant. While there may be limitations due to patient age and/or location of the PPF, the use of widely available and inexpensive custom-fitted materials with a hospital grade breast pump achieves maximal efficacy without requiring higher negative pressure suction application.

CONCLUSION:
Elevation of PPF can be safely achieved in some neonates using readily available equipment: a hospital-grade breast pump, flange, and moldable adherent material. This technique is reasonable to attempt in lieu of surgical elevation.
Protein complexes from mouse and chick brain that interact with phospho-KXGS motif tau/microtubule associated protein antibody
Authors: Davies D. S. , Arthur A. T. , Aitken H. L. , Crossett B. , Goldsbury C. S. 
Published: February 2024

ABSTRACT
Mouse monoclonal 12E8 antibody, which recognises conserved serine phosphorylated KXGS motifs in the microtubule binding domains of tau/tau-like microtubule associated proteins (MAPs), shows elevated binding in brain during normal embryonic development (mammals and birds) and at the early stages of human Alzheimer’s disease (AD). It also labels ADF/cofilin-actin rods that form in neurites during exposure to stressors. We aimed to identify direct and indirect 12E8 binding proteins in postnatal mouse brain and embryonic chick brain by immunoprecipitation (IP), mass spectrometry and immunofluorescence. Tau and/or MAP2 were major direct 12E8-binding proteins detected in all IPs, and actin and/or tubulin were co-immunoprecipitated in most samples. Additional proteins were different in mouse versus chick brain IP. In mouse brain IPs, FSD1l and intermediate filament proteins – vimentin, α-internexin, neurofilament polypeptides – were prominent. Immunofluorescence and immunoblot using recombinant intermediate filament subunits, suggests an indirect interaction of these proteins with the 12E8 antibody. In chick brain IPs, subunits of eukaryotic translation initiation factor 3 (EIF3) were found, but no direct interaction between 12E8 and recombinant Eif3e protein was detected. Fluorescence microscopy in primary cultured chick neurons showed evidence of co-localisation of Eif3e and tubulin labelling, consistent with previous data demonstrating cytoskeletal organisation of the translation apparatus. Neither total tau or MAP2 immunolabelling accumulated at ADF/cofilin-actin rods generated in primary cultured chick neurons, and we were unable to narrow down the major antigen recognised by 12E8 antibody on ADF/cofilin-actin rods.
How studies in developmental epithelial-mesenchymal transition and mesenchymal-epithelial transition inspired new research paradigms in biomedicine
Authors: Thiery Jean Paul , Sheng Guojun , Shu Xiaodong , Runyan Raymond 
Published: February 2024

ABSTRACT
Epithelial-mesenchymal transition (EMT) and its reverse mechanism, mesenchymal-epithelial transition (MET), are evolutionarily conserved mechanisms initially identified in studies of early metazoan development. EMT may even have been established in choanoflagellates, the closest unicellular relative of Metazoa. These crucial morphological transitions operate during body plan formation and subsequently in organogenesis. These findings have prompted an increasing number of investigators in biomedicine to assess the importance of such mechanisms that drive epithelial cell plasticity in multiple diseases associated with congenital disabilities and fibrosis, and, most importantly, in the progression of carcinoma. EMT and MET also play crucial roles in regenerative medicine, notably by contributing epigenetic changes in somatic cells to initiate reprogramming into stem cells and their subsequent differentiation into distinct lineages.