bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of DNA content as quality control in decellularized tissues: challenges and pitfalls
Authors: Philips Charlot , Terrie Lisanne , Muylle Ewout , Thorrez Lieven 
Published: October 2024

Abstract
Decellularized organs and tissues are emerging within the field of regenerative medicine to meet the growing demand for organ and tissue transplantation. Quality control of these acellular matrices prior to transplantation is of paramount importance to ensure the absence of an adverse reaction. In particular, thorough evaluation of the DNA content is essential but also poses technical challenges. Therefore, in this study, we compared different methods for quantitative and qualitative evaluation of DNA content in native and decellularized skeletal muscle tissue to identify strengths and weaknesses for each. Histological analysis revealed that Feulgen staining is more sensitive and robust than the commonly used hematoxylin–eosin and 4′,6-diamidino-2-phenylindole staining for detection of remaining nuclear material. Furthermore, gel electrophoresis allowed to identify the quality and length of remaining DNA fragments. The results of the quantitative analysis indicated that direct measurement of DNA content in tissue lysates is preferred over silica-based extraction methods, since the latter resulted in the loss of small DNA fragments during extraction. Moreover, a weight loss correction factor should be implemented to take into account the impact of the decellularization on the extracellular matrix. With regard to the detection method, the results revealed that a fluorescence-based approach is more accurate than the use of UV/VIS absorbance. Through combination of the proposed methods, it should be possible to achieve a more standardized evaluation of novel acellular matrices in terms of DNA content and to enhance the predictability of clinical success.
Injectable drug-loaded thermosensitive hydrogel delivery system for protecting retina ganglion cells in traumatic optic neuropathy
Authors: Wang Lei , Jiang Yan , Yao Yili , Deng Yudan , Liu Zhiqiang , Ding Jiangtao , Wang Wenwen , Chen Hao , Nan Kaihui , Li Lingli 
Published: October 2024

Abstract
Currently, generalized therapy for traumatic optic neuropathy (TON) is lacking. Various strategies have been developed to protect and regenerate retinal ganglion cells (RGCs) after TON. Intravitreal injection of supplements has been approved as a promising approach, although serious concerns, such as low delivery efficacy and pain due to frequent injections, remain. In this study, we tested an injectable thermosensitive hydrogel drug delivery system engineered to deliver ciliary neurotrophic factor (CNTF) and triamcinolone acetonide (TA). The results of rheological studies showed that the prepared drug-loaded hydrogel possessed a suitable mechanical modulus of ∼300 Pa, consistent with that of vitreum. The hydrogel exhibited thermosensitive with sustained drug release performance. In vitro co-culture of the CNTF-loaded hydrogel system with primary RGCs also induced significant axon regeneration, with 38.5% increase in neurite length, indicating the regenerative response of the thermosensitive hydrogel drug delivery system. A Sprague-Dawley rat optic nerve crush model was constructed and applied to determine the neuroprotective and regenerative capacities of the system. The results demonstrated that a single intravitreal injection of the drug-loaded hydrogel (PLGA-PEG-PLGA + TA or PLGA-PEG-PLGA + CNTF) significantly increased RGC survival at both 14 and 28 days. The RGC survival rate was 31.05 ± 1.41% for the drug-loaded hydrogel system (the control group was 16.79 ± 1.50%) at Day 28. These findings suggest that the injectable drug-loaded thermosensitive hydrogel delivery system is a promising therapeutic tool for treating optic nerve degeneration.
Impact of baseline proteinuria level on long-term outcomes in lupus nephritis
Authors: Kharouf Fadi , Li Qixuan , Whittall Garcia Laura P , Gladman Dafna D , Touma Zahi 
Published: October 2024

Abstract

Objectives
Proteinuria is a marker of lupus nephritis (LN) activity and damage. We aimed to explore the impact of baseline proteinuria level on long-term outcomes.

Methods
We included 249 patients diagnosed with their first biopsy-proven LN. We divided patients based on baseline proteinuria into low-level (≤1 g/day, group 1; 62 patients), moderate-level (&gt;1 and &lt;3 g/day, group 2; 90 patients) and high-level proteinuria (≥3 g/day, group 3; 97 patients). Outcomes included complete proteinuria recovery (CPR) at 1 year, an adverse composite outcome (ESKD, a sustained ≥40% decline in eGFR, or death) and LN flares. Cox proportional hazard models were used to examine the association between baseline characteristics and long-term outcomes.

Results
At baseline, the median [IQR] age was 33.2 [26.4, 42.4] years; median proteinuria level was 2.2 [1.0, 3.8] g/day. A total of 177 (71%) patients had proliferative lesions on biopsy; 59.7% in group 1, 78.9% in group 2 and 71.4% in group 3. The rate of achievement of CPR at 1 year was highest for group 1 and lowest for group 3. For long-term outcomes (median follow-up 8.4 years), the frequency of the adverse composite outcome was 27.4%, 26.7% and 48.5% in groups 1, 2 and 3, respectively; P = 0.003. The corresponding frequency of flares was 27.4%, 38.2% and 61.9%, respectively; P &lt; 0.001. In the multivariable model for factors associated with long-term outcomes, there was no significant difference between groups 1 and 2; group 3 was associated with the worst prognosis.

Conclusions
Low-level proteinuria is commonly associated with proliferative LN and adverse long-term outcomes.
Age-inclusive leadership and intrinsic work motivation: the moderating role of the leader–member age difference
Authors: De Boom Laura , De Meulenaere Kim 
Published: October 2024

Abstract
As workforces become more age-diverse, organizations and their leaders encounter the challenge of nurturing intrinsic work motivation across employees of varying ages. Integrating self-determination theory (SDT) with relational demography theory, we propose a link between age-inclusive leadership (AIL) and employees’ intrinsic work motivation, with a focus on how the leader–member’s age difference moderates this relationship. A study with 100 Belgian employee–leader dyads reveals that employees’ perceived level of their leaders’ AIL positively affects their intrinsic work motivation, especially with a great leader–member age difference (Study 1). An online experiment with 360 U.S. participants further supports the moderated mediation relationship via the SDT-related needs (Study 2): AIL helps stimulate employees’ intrinsic work motivation through the satisfaction of their need for relatedness and autonomy (and to a lesser extent, competence), especially when employees differ greatly from their leader in terms of age. Our research yields both valuable theoretical insights and practical implications for organizational management.
The desulfinylation enzyme sulfiredoxin-1 attenuates HSC activation and liver fibrosis by modulating the PTPN12-NLRP3 axis
Authors: Kim Jong-Won , Tung Hung-Chun , Ke Mengyun , Xu Pengfei , Cai Xinran , Xi Yue , Xu Meishu , Ren Songrong , Huang Yixian , Bhowmik Amit , Carroll Kate S. , Bae Yun Soo , Li Song , Xie Wen 
Published: October 2024

Background and Aims:
Liver fibrosis is characterized by the progressive scarring of liver tissue. Oxidative stress is a critical causal factor of HSC activation and subsequent liver fibrogenesis, but the mechanism is not fully understood. Cysteine sulfinic acid (Cys-SO2H), a modification of reactive cysteine residues, is a unique form of oxidative response that alters the structure and function of proteins. Sulfiredoxin-1 (SRXN1) is responsible for the ATP-dependent reduction of the Cys-SO2H to sulfenic acid (Cys-SOH).

Approach and Results:
We found that the expression of SRXN1 was increased in activated HSCs and in human and mouse fibrotic livers. HSC-specific ablation of Srxn1 or pharmacological inhibition of Srxn1 exacerbated HSC activation and sensitized mice to liver fibrosis. Mechanistically, SRXN1 inhibited HSC activation by desulfinylating the phosphatase protein tyrosine phosphatase nonreceptor type 12 (PTPN12), which enhanced its phosphatase activity and protein stability, leading to decreased tyrosine phosphorylation and reduced activation of the profibrotic inflammasome protein NLRP3 (nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3). The antifibrotic effect of SRXN1 was abolished when NLRP3 was inhibited. In contrast, overexpression of PTPN12 attenuated NLRP3 activation, and this effect was further amplified by the C164A S-sulfinylation–resistant mutant of PTPN12.

Conclusions:
Our findings have uncovered an important role of SRXN1 and protein S-sulfinylation in HSC activation and liver fibrosis. The SRXN1-PTPN12-NLRP3 axis represents potential therapeutic targets for liver fibrosis.
Revolutionizing LVH detection using artificial intelligence: the AI heartbeat project
Authors: Suchal Zafar Aleem , Ain Noor ul , Mahmud Azra 
Published: October 2024

Many studies have shown the utility and promise of artificial intelligence (AI), for the diagnosis of left ventricular hypertrophy (LVH). The aim of the present study was to conduct a meta-analysis to compare the accuracy of AI tools to electrocardiographic criteria, including Sokolow–Lyon and the Cornell, most commonly used for the detection of LVH in clinical practice.
Nine studies meeting the inclusion criteria were selected, comprising a sample size of 31 657 patients in the testing and 100 271 in the training datasets. Meta-analysis was performed using a hierarchal model, calculating the pooled sensitivity, specificity, accuracy, along with the 95% confidence intervals (95% CIs). To ensure that the results were not skewed by one particular study, a sensitivity analysis using the ‘leave-out-one approach’ was adopted for all three outcomes.
AI was associated with greater pooled estimates; accuracy, 80.50 (95% CI: 80.4–80.60), sensitivity, 89.29 (95% CI: 89.25–89.33) and specificity, 93.32 (95% CI: 93.26–93.38). Adjusting for weightage of individual studies on the outcomes, the results showed that while accuracy and specificity were unchanged, the adjusted pooled sensitivity was 53.16 (95% CI: 52.92–53.40).
AI demonstrates higher diagnostic accuracy and sensitivity compared with conventional ECG criteria for LVH detection. AI holds promise as a reliable and efficient tool for the accurate detection of LVH in diverse populations. Further studies are needed to test AI models in hypertensive populations, particularly in low resource settings.
Clinical indications associated with new opioid use for pain management in the United Kingdom: using national primary care data
Authors: Ramirez Medina Carlos Raul , Lyon Max , Davies Elinor , McCarthy David , Reid Vanessa , Khanna Ashwin , Jani Meghna 
Published: October 2024

Abstract
Prescription opioids for noncancer pain in the United Kingdom have increased over the past 2 decades, alongside associated harms. Policies addressing opioid prescribing must be tailored to individual patient needs with specific disease systems. The aim of this study was to evaluate clinical conditions associated with new opioid initiation in noncancer pain using nationally representative UK data. Primary care electronic health records from January 1, 2006, to September 31, 2021, were used from the Clinical Research Practice Datalink to identify incident opioid prescriptions. Patient histories were reviewed using code lists for opioid-related conditions with a 5-year look-back for chronic conditions and a 1-year look-back for surgical indications before opioid initiation. In total, 3,030,077 new opioid use episodes in 2,027,402 patients were identified, with 61% being women, 77% aged 45 years and older, and 48% from the highest deprivation quintile. Ten systems associated with opioid initiation were identified, which were not mutually exclusive, as patients could have opioids prescribed for multiple indications. The most common were musculoskeletal (80.8%), respiratory (57.6%), infections (30.4%), trauma/injury (20.4%), neurology (19.9%), and postsurgical indications (5.5%). Osteoarthritis (60.7%) and low back pain (41.0%) were the most frequent musculoskeletal conditions. Orthopedic surgeries accounted for 41.2% of all postsurgical indications. This is the first study in the United Kingdom evaluating large-scale national data to assess indications associated with opioid initiation. Nearly 3 quarters of new opioid prescriptions for noncancer pain were in patients with musculoskeletal conditions, often for conditions with limited evidence for opioid efficacy. These findings could inform targeted interventions and future policies to support nonpharmacological interventions in the most common conditions where opioid harms outweigh benefits.
Is the combination of two automated rapid assays for diagnosis of heparin-induced thrombocytopenia necessary?
Authors: Jani Erika , Bozzola Margherita , Zagler Elmar Marco , Daves Massimo 
Published: October 2024

Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition characterized by a decrease in platelet count and an increased thrombotic risk. HIT event is caused by antiplatelet factor/heparin (PF4/H) antibodies that can activate the platelets. The diagnosis of HIT is based on a clinical evaluation and laboratory results. Aim of our study was to evaluate whether the combined use of two rapid assays for diagnosis of HIT provides a diagnostic advantage over the use of a single automate assay.
We extracted from the laboratory informatic system all the determinations requested for the detection of antibodies against heparin/PF4 complexes from July 2020 to June 2024 (n. 229). In our laboratory, total antibodies against heparin/PF4 complex [HemosIL HIT-Ab-(PF4-H), Instrumentation Laboratory] and IgG Ab (HemosIL AcuStar HIT-IgG, Instrumentation Laboratory) are measured simultaneously with two different instruments.
Two hundred six samples tested negative for both methods, 23 samples tested positive for at least one method and nine samples tested positive for both methods. The grade of concordance between the two assays shows a weighted Kappa of 0.536 (moderate agreement). No sample tested positive only for IgG-Ab. The sensitivity of HIT-Ab-(PF4-H) was 1, whereas the specificity was 0.95. For the HIT-IgG (PF4-H) method, sensibility and specificity were 0.77 and 1, respectively.
Our results suggest that performing these two tests simultaneously does not provide additional useful information in patients with suspicion of HIT. The total Ab assay seems to be sufficient, as it shows higher sensitivity although at the expense of lower specificity.
Nephrocalcinosis, distal renal tubular acidosis and skeletal abnormality in two siblings with ROGDI-related Kohlschütter-Tönz syndrome
Authors: Nerakh Gayatri , Koneru Swetha , Dhareneni Prashanth Rao 
Published: October 2024

Introduction
Kohlschütter-Tönz (KTS) is a rare autosomal recessive, genetically heterogeneous disorder characterized by a triad of early-onset seizures, global developmental delay or regression, and amelogenesis imperfecta of both temporary and permanent teeth. To date, 66 cases have been reported in the literature, of which 44 with genetic confirmation.

Case report
Here we report the observation of sibling pairs in a family from a small village in India who presented with nephrocalcinosis, distal renal tubular acidosis, and skeletal abnormality. Nephrocalcinosis has only been reported once before in an individual affected with KTS.

Results
Trio exome sequencing revealed a novel, homozygous, likely pathogenic variant, c.646-2_649del, in exon 9 of the ROGDI gene (NM_024589.3) in the first child. Sanger sequencing confirmed homozygosity in both children. Both parents are heterozygous carriers of the same variant.

Conclusion
Further research needs to be done to identify the exact mechanism by which ROGDI-encoded protein deficiency leads to nephrocalcinosis and distal renal tubular acidosis.
Planetary Health in Rehabilitation
Authors: Bateman Emma A. , Fortin Christian D. , Ghuman Arjun , Neferu Ramona , Guo Meiqi 
Published: October 2024

Abstract
Sometimes out of necessity and sometimes out of convenience, medicine is wasteful. Resource stewardship is a critical and expanding field for reducing wasteful practices. Numerous international organizations are driving resource stewardship globally, including >20 countries worldwide participating in Choosing Wisely initiatives. However, opportunities for environmental stewardship have been long overlooked. Planetary health, climate action, and environmental stewardship in medicine consider opportunities which offer a co-benefit to the planet while improving or maintaining appropriate patient care across the healthcare continuum, including acute care, transitions in care, and postacute care, as well as in primary, secondary, and tertiary care settings. As rehabilitation is necessary across all healthcare settings, developing a culture among rehabilitation care providers that is conscientious about planetary health is imperative for sustainability of rehabilitation medicine and the health of our planet. We devised a recommendation for Choosing Wisely Canada’s planetary health focus: don’t dispose of adaptive equipment, mobility devices, orthoses, and prostheses that could be reused or recycled. This brief report discusses 1) why rehabilitation providers should engage with planetary health and climate action; 2) the rationale for the Choosing Wisely Canada Physical Medicine & Rehabilitation planetary health recommendation; and 3) existing avenues and novel opportunities for rehabilitation care providers worldwide to reduce waste in rehabilitation.
TARGETING S100A9-TLR2 AXIS CONTROLS MACROPHAGE NLRP3 INFLAMMASOME ACTIVATION IN FATTY LIVER ISCHEMIA REPERFUSION INJURY
Authors: Sheng Mingwei , Liu Weihua , Cao Yingli , Wang Shixuan , Lin Yuanbang , Yu Wenli 
Published: October 2024

ABSTRACT
Liver ischemia reperfusion (IR) injury significantly impacts clinical outcomes by increasing the risk of hepatic dysfunction after liver surgery. Fatty livers are more susceptible to IR stress. Recent studies have demonstrated that S100A9 plays a crucial role in both IR injury and the progression of liver steatosis. Nevertheless, the precise mechanisms underlying these effects remain unclear. In our study, transcriptome analysis of fatty livers subjected to IR insult in mice identified S100A9 as an important mediator. Employing loss-of-function approaches, we investigated the immune regulatory function of S100A9 and its downstream signaling in fatty liver IR injury. As expected, S100A9 emerged as one of the most significantly upregulated genes during the reperfusion stage in fatty livers. Genetic knockdown of S100A9 markedly ameliorated liver pathological damage, evidenced by reduced macrophage/neutrophil infiltration as well as the decreased expression of proinflammatory factors. Transcriptome/functional studies revealed that S100A9 triggered liver inflammatory response via regulating toll-like receptor 2 (TLR2)/activating transcription factor 4 (ATF4) signaling. Additionally, TLR2 expression was notably increased in macrophages from ischemic fatty livers. In vitro, recombinant S100A9-stimulated macrophages exhibited the elevated production of proinflammatory factors and TLR2/ATF4 pathway activation. Intriguingly, S100A9 facilitated ATF4 nuclear translocation and enhanced NEK7/NLRP3 inflammasome activation in macrophages. In conclusion, our study identified S100A9 as a key regulator responsible for macrophage NLRP3 inflammasome activation and subsequent inflammatory injury in fatty liver IR process. Targeting TLR2/ATF4 signaling may offer a novel therapeutic strategy for mitigating S100A9-mediated liver injury.
COMPARISON OF CONTINUOUS VITAL SIGNS DATA ANALYSIS VERSUS VENOUS LACTATE FOR THE PREDICTION OF LIFESAVING INTERVENTIONS IN PATIENTS WITH TRAUMATIC SHOCK
Authors: Yang Shiming , Hu Peter , Teeter William , Floccare Douglas J. , Hu Howard , Galvagno Samuel M. 
Published: October 2024

ABSTRACT

Introduction: The prehospital environment is fraught with operational constraints, making it difficult to assess the need for resources such as lifesaving interventions (LSI) for adults with traumatic injuries. While invasive methods such as lactate have been found to be highly predictive for estimating injury severity and resource requirements, noninvasive methods, to include continuous vital signs (VS), have the potential to provide prognostic information that can be quickly acquired, interpreted, and incorporated into decision making. In this work, we hypothesized that an analysis of continuous VS would have predictive capacity comparable to lactate and other laboratory tests for the prediction of injury severity, need for LSIs and intensive care unit admission. Methods: In this preplanned secondary analysis of 300 prospectively enrolled patients, venous blood samples were collected in the prehospital environment aboard a helicopter and analyzed with a portable lab device. Patients were transported to the primary adult resource center for trauma in the state of Maryland. Continuous VS were simultaneously collected. Descriptive statistics were used to describe the cohort and predictive models were constructed using a regularized gradient boosting framework with 10-fold cross-validation with additional analyses using Shapley additive explanations (SHAP). Results: Complete VS and laboratory data from 166 patients were available for analysis. The continuous VS models had better performance for prediction of receiving LSIs and intensive care unit length of stay compared to single (initial) VS measurements. The continuous VS models had comparable performance to models using only laboratory tests in predicting discharge within 24 h (continuous VS model: area under the receiver operating curve [AUROC] 0.71; 95% CI, 0.68–0.75 vs. lactate model: AUROC, 0.65; 95% CI, 0.68; 95% CI, 0.66–0.71). The model using all laboratory data yielded the highest sensitivity and sensitivity (AUROC, 0.77; 95% CI, 0.74–0.81). Discussion: The results from this study suggest that continuous VS obtained from autonomous monitors in an aeromedical environment may be helpful for predicting LSIs and the critical care requirements for traumatically injured adults. The collection and use of noninvasively obtained physiological data during the early stages of prehospital care may be useful for in developing user-friendly early warning systems for identifying potentially unstable trauma patients.