bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful treatment of low‐risk myelodysplastic syndrome‐related anemia in patients with chronic kidney disease with daprodustat: A report of two cases
Authors: Kunimoto Hiroyoshi , Sakuma Takayuki , Ohashi Takuma , Shirafuta Mayoko , Teranaka Hiroshi , Nakajima Hideaki 
Published: November 2024

AbstractAnemia is a major clinical manifestation seen in myelodysplastic syndromes (MDS). Treatment options for anemia in low‐risk MDS are limited. Especially, oral medication which is uniformly effective for anemia in low‐risk MDS is required. Hypoxia‐inducible factor (HIF) prolyl hydroxylase (HIF‐PH) inhibitors, such as daprodustat, are oral tablets effective for renal anemia. Pharmacological restoration of HIF activity by HIF‐PH inhibitors may be beneficial for MDS‐related anemia as well. Yet, their efficacy and safety against low‐risk MDS are unclear. Here, we report two cases of low‐risk MDS complicated with chronic kidney disease whose anemia responded to daprodustat treatment.
Synthesis of 5‐Aryltetrahydrobenzazepines
Authors: Thoti Naveenkumar , Gupta Deepika , Lal Heera , Aidhen Indrapal Singh 
Published: November 2024

ABSTRACTEnvisaging 5‐aryltetrahydrobenzazepinone and 5‐aryltetrahydrobenzazepines as conformationally locked potential B0AT1 inhibitors, a convenient synthetic route has been developed for their access. The synthetic route banks on using the Schmidt reaction for quick access to symmetrical/unsymmetrical 5‐aryltetrahydrobenzazepinone and 5‐aryltetrahydrobenzazepines.
Streamlining diuresis: A quality improvement approach to implementing a sodium‐based predictive diuresis protocol
Authors: Rai Karan , Western Hillary Landau , Patel Moksha , Porter Samuel 
Published: November 2024

AbstractDiuresis for hospitalized patients with acute decompensated heart failure is a routine clinical practice but one that remains reliant on error‐prone and resource‐intensive intake and output and weight measurements and is subject to wide provider variation. We sought to use quality improvement approaches to implement a data‐driven predictive diuresis protocol based on natriuresis using the electronic health record to titrate dosing. Our initiative did not result in significant reductions in length of stay but did demonstrate a significant increase in the use of urine studies to guide diuresis and signals toward more aggressive diuretic dosing without an increase in adverse outcomes.
Human glyoxylate metabolism revisited: New insights pointing to multi‐organ involvement with implications for siRNA‐based therapies in primary hyperoxaluria
Authors: Wanders Ronald J. A. , Groothoff Jaap W. , Deesker Lisa J. , Salido Eduardo , Garrelfs Sander F. 
Published: November 2024

AbstractGlyoxylate is a toxic metabolite because of its rapid conversion into oxalate, as catalyzed by the ubiquitous enzyme lactate dehydrogenase. This requires the presence of efficient glyoxylate detoxification systems in multiple subcellular compartments, as glyoxylate is produced in peroxisomes, mitochondria, and the cytosol. Alanine glyoxylate aminotransferase (AGT) and glyoxylate reductase/hydroxypyruvate reductase (GRHPR) are the key enzymes involved in glyoxylate detoxification. Bi‐allelic mutations in the genes coding for these enzymes cause primary hyperoxaluria type 1 (PH1) and 2 (PH2), respectively. Glyoxylate is derived from various sources, including 4‐hydroxyproline, which is degraded in mitochondria, generating pyruvate and glyoxylate, as catalyzed by the mitochondrial enzyme 4‐hydroxy‐2‐oxoglutarate aldolase (HOGA); however, counterintuitively, a defect in HOGA1 is the molecular basis of primary hyperoxaluria type 3 (PH3). Irrespective of its underlying cause, hyperoxaluria in humans leads to nephrocalcinosis, recurrent urolithiasis, and kidney damage, which may culminate in kidney failure requiring combined liver‐kidney transplantation in severely affected patients. In the past few years, therapeutic options, especially for primary hyperoxaluria type 1 (PH1), have greatly been improved thanks to the introduction of two RNAi‐based therapies that inhibit either the production of glycolate oxidase (lumasiran) or lactate dehydrogenase (nedosiran). While lumasiran only targets PH1 patients, nedosiran was specifically developed to target all three subtypes of PH. Inspired by the findings reported in the literature that nedosiran effectively reduced urinary oxalate excretion in PH1 patients but not in PH2 or PH3 patients, we have now revisited glyoxylate metabolism in humans and performed a thorough literature study which revealed that glyoxylate/oxalate metabolism is not confined to the liver but instead involves multiple different organs. This new view on glyoxylate/oxalate metabolism in humans may well explain the disappointing results of nedosiran in PH2 and PH3, and provides new clues for the future generation of new therapeutic strategies for PH2 and PH3.
My path to citrin deficiency
Authors: Walker John E. 
Published: November 2024

AbstractCitrin belongs to the SLC25 transport protein family found mostly in inner mitochondrial membranes. The family prototype, the ADP–ATP carrier, delivers ATP made inside mitochondria to the cellular cytoplasm and returns ADP to the mitochondrion for resynthesis of ATP. In pre‐genomic 1981, I noticed that the protein sequence of the bovine ADP–ATP carrier consists of three related sequences, each containing two transmembrane α‐helices traveling in opposite senses. Colleagues and I demonstrated that two other mitochondrial carriers had similar features. From emergent genomic sequences, it became apparent that they represented a large family of transport proteins with the same characteristic threefold repeats. The human genome encodes 53 members, but the functions of many were unknown. So, colleagues and I determined how to make these proteins in Escherichia coli and introduce them into liposomes to allow exploration of their transport functions. The 27 human family members to have been thus identified include citrin and the closely related protein aralar. Both exchange aspartate from the mitochondrial matrix for cytosolic glutamate plus a proton. Citrin is expressed predominantly in liver and non‐excitable tissues, whereas aralar is the dominant form in the brain. Each has a membrane extrinsic N‐terminal Ca2+‐binding domain, a transport domain, and a C‐terminal amphipathic α‐helix. Human mutations in citrin impair the urea cycle, malate–aspartate shuttle, gluconeogenesis, amino acid breakdown, and energy metabolism leading to citrin deficiency. Currently, the complex etiology of this condition is poorly understood and new knowledge would help to improve diagnosis, therapies, and finding a cure. My aims are to seek a basic understanding of the etiology of citrin deficiency and to use that knowledge in improving diagnostic procedures and in developing new treatments and a cure.
The clinical utility in hospital‐wide use of growth differentiation factor 15 as a biomarker for mitochondrial DNA‐related disorders
Authors: Fernández Andrea Cortés , Estrella Jane , Oglesbee Devin , Larson Austin A. , Van Hove Johan L.K. 
Published: November 2024

AbstractClinical recognition of primary mitochondrial disorders (PMD) is difficult due to the clinical and genetic heterogeneity. Whereas lactate has low sensitivity and specificity, in structured clinical studies growth differentiation factor 15 (GDF15) has shown promise with elevations in mitochondrial DNA (mtDNA)‐related PMD, but its specificity has been questioned. In a tertiary care hospital‐wide study, medical records were retrospectively reviewed from 418 cases where GDF15 levels were obtained by clinicians. Patients were classified into patients with PMD due to mtDNA‐related defects (mtDNA maintenance, mtDNA deletions, and mtDNA‐encoded tRNA variants), PMD due to structural defects or other nuclear causes, and in non‐mitochondrial disease. Patients with liver disease or systemic critical illness were excluded. GDF15 was assayed in a clinical laboratory with a cutoff of 750 ng/L. There were 38 mtDNA‐related PMD (GDF15 >750 pg/mL in 76%), 35 other nuclear DNA‐encoded PMD or structural subunits (31% elevated GDF15), 309 non‐mitochondrial disorders (13% elevated GDF15). Based on the highest Youden J‐index, the optimal cut‐off value to identify these target mtDNA‐related disorders was 815 pg/mL, with sensitivity 76%, specificity 88%, positive predictive value of 41% and negative predictive value of 97%. At this optimized cutoff level, mtDNA‐encoded PMD patients had elevated GDF15 in 76%, nuclear DNA‐encoded PMD in 26%, and non‐mitochondrial disorders in 11% of patients. Thus, in a real‐life clinical setting, after excluding abnormal liver function and critical illness, GDF15 had good clinical utility increasing the odds at predicting mtDNA‐related primary mitochondrial disorders 14‐fold, but not for structural or other nuclear‐encoded primary mitochondrial disorders.
Telehealth noninferior to in person for vocational counseling: A comparison study of “Asking for Help” group intervention to improve soft skills
Authors: Lu Weili , Oursler Janice , Herrick Samantha J. , Gao Ni , Silberman Harosh Ariella , Wang Ke , Beninato John , Morales Maritza , Diviney Jason , Mevawala Janki 
Published: November 2024

AbstractEmployment success often hinges on crucial work‐related soft skills, such as the ability to seek help and solve problems. This pilot study aimed to assess the practicality of a group intervention based upon a direct skills teaching (DST) approach to teach work‐related help‐seeking skills to individuals with disabilities. The “Asking for Help” intervention, conducted in either in person or via telehealth, involved 152 participants with disabilities. Both modalities showed improvement in participants’ perceptions of work‐related soft skill of asking for help. Participants experienced increased confidence in asking for help at employment settings and expressed high satisfaction with the intervention. Both groups increased career adaptabilities, while the telehealth group also increased occupational self‐efficacy, and the in‐person group showed increased work‐related soft skills. Both groups showed comparable positive results, supporting their effectiveness in teaching help‐seeking skills using a preplanned curriculum. Implications of findings are discussed.
Time‐dependent changes in medial meniscus kinematics and attachment strength after anterior root injury and repair in a large animal model
Authors: Meadows Kyle D. , Peloquin John M. , Boyes Madeline , Stoeckl Brendan D. , Benson Jamie , Bansal Sonia , Steinberg David R. , Zgonis Miltiadis H. , Schaer Thomas P. , Mauck Robert L. , Elliott Dawn M. 
Published: November 2024

AbstractThis study investigated joint kinematics and attachment tensile mechanics following resection of the medial meniscus anterior attachment. A secondary objective investigated the repair of the attachment. Yucatan minipigs underwent unilateral surgery for either Injury (en bloc) resection of the anterior attachment of the insertional ligament, (a portion of the cranial medial meniscotibial ligament) or Repair (immediate repair with a suture anchor), with the contralateral knee as Intact control. Evaluation at 6 weeks and 6 months included joint kinematics measured from MRI acquired under knee compression and tensile testing of the attachment. Injury resulted in large levels of meniscus extrusion, despite the development of a fibrovascular scar. At 6 weeks, the meniscus extruded 1.95 mm more than Intact; at 6 months, this extrusion was reduced to 0.77 mm. Under an applied 1× body weight load, the meniscus further extruded and was not different with treatment or time. During attachment tensile testing, elongation was 0.6 mm for Intact, following Injury, elongation was 2.7 mm at 6 weeks and was partially restored to 1.5 mm at 6 months. Despite this, the cartilage wear worsened over time. Repair was inadequate to avoid the extrusion or cartilage wear seen in the injury group at 6 weeks, so it was not continued for the 6‐month group. This study demonstrates that while meniscus injury is useful to study cartilage degeneration, a holistic consideration of the role of the meniscus itself, including its changing material properties and its impact on joint mechanics during injury, repair, and rehabilitation, are key factors contributing to overall joint health.
Clinical Characteristics and Variation in Musculoskeletal Complexity of Different Ethnic Populations Accessing Sandwell and West Birmingham Hospital's MSK Service: A Service Evaluation
Authors: Shah Wasim , Newham Roger , Casey Carolyn , Burgess Roanna 
Published: November 2024

ABSTRACTIntroductionHealth inequality is a global public health challenge, limited by insufficient high‐quality data and analysis. Musculoskeletal (MSK) pain disorders are more prevalent among ethnic minority groups disproportionately affected by socioeconomic disparities and poor health outcomes. Ethnicity data collection enables NHS organisations and policymakers to understand specific healthcare needs and ensure equitable access and care provision.ObjectiveTo understand the baseline clinical characteristics across ethnic population groups accessing MSK care at Sandwell and West Birmingham (SWB) NHS Trust.MethodsRetrospective analysis of routine data collected using patient self‐report surveys (August 2020–February 2023). Core metrics included demographics, pain characteristics, and Patient Reported Outcome Measures (PROMs) including the Musculoskeletal Health Questionnaire (MSK‐HQ) and Numeric Pain Rating Scale (NPRS). Descriptive statistics and statistical tests were undertaken, with means, percentage values and variation by ethnic groups across baseline MSK‐HQ and pain scores reported.ResultsSurvey data were provided by 13,248 patients, with 7295 (55.06%) stating their ethnicity. Statistical differences were found between baseline MSK‐HQ and NPRS scores between ethnic groups. The mean MSK‐HQ score was 24.1 overall, lowest in the Asian group (22.3) and highest in the Mixed group (24.8). Mean baseline pain intensity was (7.8), highest in the Asian group (8.3). One or more comorbidities were present in 46% of patients, with the highest percentage in the White and Black groups sequentially.ConclusionBaseline health inequalities exist among ethnic groups accessing the SWB MSK service. Disparities may be associated with patient or system barriers and require further exploration.
In vivo rat brain mapping of multiple gray matter water populations using nonparametric D(ω)‐R1‐R2 distributions MRI
Authors: Yon Maxime , Narvaez Omar , Topgaard Daniel , Sierra Alejandra 
Published: November 2024

AbstractMassively multidimensional diffusion magnetic resonance imaging combines tensor‐valued encoding, oscillating gradients, and diffusion‐relaxation correlation to provide multicomponent subvoxel parameters depicting some tissue microstructural features. This method was successfully implemented ex vivo in microimaging systems and clinical conditions with tensor‐valued gradient waveform of variable duration giving access to a narrow diffusion frequency (ω) range. We demonstrate here its preclinical in vivo implementation with a protocol of 389 contrast images probing a wide diffusion frequency range of 18 to 92 Hz at b‐values up to 2.1 ms/μm2 enabled by the use of modulated gradient waveforms and combined with multislice high‐resolution and low‐distortion echo planar imaging acquisition with segmented and full reversed phase‐encode acquisition. This framework allows the identification of diffusion ω‐dependence in the rat cerebellum and olfactory bulb gray matter (GM), and the parameter distributions are shown to resolve two water pools in the cerebellum GM with different diffusion coefficients, shapes, ω‐dependence, relaxation rates, and spatial repartition whose attribution to specific microstructure could modify the current understanding of the origin of restriction in GM.
Potential application of andrographolide in vital pulp therapy by inducing expression of human β defensin 4
Authors: Zhai Yue , Lv Yue , Li Yue , Yu Guoxia 
Published: November 2024

AbstractAimThis study aimed to investigate the ability of andrographolide to induce human β defensin 4 (HBD4) expression in dental pulp stem cells and its effect on inflammatory pulp tissue in rats in vivo.MethodsThe expression of HBD4 in andrographolide‐induced dental pulp stem cells was examined using quantitative polymerase chain reaction and immunofluorescence staining. High‐throughput analysis of protein acetylation was conducted to screen the mechanism of andrographolide‐induced HBD4 expression. Colony‐forming unit methods were used to study the antimicrobial ability of andrographolide‐induced HBD4 on Porphyromonas gingivalis. Finally, the ability of andrographolide to preserve vital pulp was examined using Wistar rats with irreversible pulpitis.ResultsHBD4 expression level increased after andrographolide stimulation, which was related to histone acetylation modification, as revealed by acetylome analyses. Antibacterial testing confirmed that andrographolide‐induced HBD4 was sensitive to P. gingivalis. Furthermore, andrographolide controlled pulp inflammation in a Wistar rat irreversible pulpitis model and induced the restorative dentin formation.ConclusionWe concluded that andrographolide induced the expression of HBD4 in dental pulp stem cells through histone acetylation modification and exerted inhibitory effects on pulp tissue inflammation in vivo.
Mandibular cortical morphology in patients with osteoporosis using computer‐aided detection with dental panoramic imaging: A pilot study of the relation to age and bone‐modifying agents
Authors: Shirai Ai , Ogawa Ruri , Kobayashi Eizaburo , Ogura Ichiro 
Published: November 2024

AbstractAimMandibular cortical morphology with panoramic radiography is considered to be a useful technique for identifying at risk of osteoporosis. The aim of the study was to investigate the mandibular cortical morphology in patients with osteoporosis using computer‐aided detection (CAD) with dental panoramic imaging, especially the relation to age and bone‐modifying agents.MethodsOne hundred and thirteen patients with osteoporosis were underwent panoramic radiography. The mandibular cortical morphology, such as mandibular cortical index (MCI) and degree of deformation of mandibular inferior cortex, was analyzed automatically with a CAD with dental panoramic imaging “PanoSCOPE.” Those were analyzed in relation to age and bone‐modifying agents.ResultsRegarding Class 3 (severely eroded) of the MCI classifications, the frequency in 61–70, 71–80, and 81–90 years were 22.2%, 38.6%, and 26.3%, respectively, and the MCI in bisphosphonate and denosumab were 29.8% and 42.1%, respectively. The degree of deformation in 61–70, 71–80, and 81–90 years were 45.9 ± 22.6, 58.8 ± 20.0, and 52.6 ± 21.5, respectively, and those in bisphosphonate and denosumab were 54.1 ± 20.6 and 57.5 ± 25.0, respectively. The MCI and degree of deformation in patients with osteoporosis were not significant differences for age and bone‐modifying agents.ConclusionThis study suggests that the CAD using PanoSCOPE can perform a quantitative analysis of mandibular cortical morphology in patients with osteoporosis.
Synthesis and Properties of a Shape Memory–Assisted Self‐Healing Supramolecular Polyurethane Coating Based on Quadrupole Hydrogen Bonding
Authors: Karimi Alavijeh Soheila , Khorasani Saied Nouri , Masoomi Mahmood , Neisiany Rasoul Esmaeely , Dinari Mohammad , Gomes Diego Ribas , Pei Yutao , Raffa Patrizio 
Published: November 2024

ABSTRACTIn this research, the synthesis and characterization of a shape memory–assisted self‐healing polyurethane (SHSMPU) coating based on strong quadrupole hydrogen bonding interaction have been investigated. The coating was fabricated with an acrylic polyol, an isocyanate functionalized ureidopyrimidinone (UPy‐NCO) as a hydrogen bonding provider, and methylene diphenyl diisocyanate (MDI) as chain extender. Fourier‐transform infrared spectroscopy (FT‐IR) confirmed that by incorporating the UPy‐NCO dimer in the polyurethane (PU) structure, strong hydrogen bonding appears, which can provide the healing function of the polymer. In addition, differential scanning calorimetry (DSC) showed that by increasing the UPy‐NCO amount, the overall Tg decreased and the material becomes more flexible. A rheometric investigation revealed that a sample containing 45% of UPy‐NCO as total diisocyanate shows good shape recovery and an healing efficiency of macroscale cracks of around 94.2%, which is much higher than the corresponding sample without UPy‐NCO (50.4%). Even better performances were obtained with microcracks, where tested samples were significantly healed at around 80°C in 10 min. Furthermore, the introduction of polyethylene glycol 400 (PEG400) into the polymer's backbone led to a reduced Tg and thus higher flexibility at room temperature. The combination of the observed properties makes these materials promising for application as durable and flexible polyurethane coatings.
Proteomic analysis of non‐muscle invasive and muscle invasive bladder cancer highlights distinct subgroups with metabolic, matrisomal, and immune hallmarks and emphasizes importance of the stromal compartment
Authors: Dinh Thien‐Ly Julia , Rogg Manuel , Cosenza‐Contreras Miguel , Li Mujia , Zirngibl Max , Pinter Niko , Kurowski Konrad , Hause Frank , Pauli Lena , Imberg Fiona , Huynh Alana , Schmid Marlene , Glavinsky Ievgen , Braun Luisa , Van Wymersch Clara , Bergmann Luise , Ungefug Xenia , Kunz Marion , Werner Tilman , Bernhard Patrick , Espadas Guadalupe , Brombacher Eva , Schueler Julia , Sabido Eduard , Kreutz Clemens , Gratzke Christian , Werner Martin , Grabbert Markus , Bronsert Peter , Schell Christoph , Schilling Oliver 
Published: November 2024

AbstractWe present the proteomic profiling of 79 bladder cancers, including treatment‐naïve non‐muscle‐invasive bladder cancer (NMIBC, n = 17), muscle‐invasive bladder cancer (MIBC, n = 51), and neoadjuvant‐treated MIBC (n = 11). Proteins were extracted from formalin‐fixed, paraffin‐embedded samples and analyzed using data‐independent acquisition, yielding >8,000 quantified proteins. MIBC, compared to NMIBC, shows an extracellular matrix (ECM) and immune response signature as well as alteration of the metabolic proteome together with concomitant depletion of proteins involved in cell–cell adhesion and lipid metabolism. Neoadjuvant treatment did not consistently impact the proteome of the residual tumor mass. NMIBC presents two proteomic subgroups that correlate with histological grade and feature signatures of cell adhesion or lipid/DNA metabolism. Treatment‐naïve MIBC presents three proteomic subgroups with resemblance to the basal‐squamous, stroma‐rich, or luminal subtypes and signatures of metabolism, immune functionality, or ECM. The metabolic subgroup presents an immune‐depleted microenvironment, whereas the ECM and immune subgroups are enriched for markers of M2‐like tumor‐associated macrophages and dendritic cells. Markers for natural killer cells are exclusive for the ECM subgroup, and markers for cytotoxic T cells are a hallmark of the immune subgroup. Endogenous proteolysis is increased in MIBC alongside upregulation of matrix metalloproteases, including MMP‐14. Genomic panel sequencing yielded the prototypical profile of prevalent FGRF3 alterations in NMIBC and TP53 alterations in MIBC. Tumor–stroma interactions of MIBC were investigated by proteomic analysis of patient‐derived xenografts, highlighting specific tumor and stroma contributions to the matrisome and tumor‐induced stromal proteome phenotypes. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.