bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting complement in IgA nephropathy
Authors: Caravaca-Fontán Fernando , Gutiérrez Eduardo , Sevillano Ángel M , Praga Manuel 
Published: December 2023

ABSTRACT
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Recent years have witnessed significant improvements in the understanding of the pathogenesis of IgAN and particularly, the pathogenic role of complement activation. The alternative complement pathway is the major complement cascade activator in IgAN, and glomerular C3 deposition has been shown to correlate with disease progression. In addition, several studies have provided insight into the pathogenic role of factor H–related proteins -1 and -5 in IgAN, as independent players in complement dysregulation. The lectin pathway has also been shown to be associated with the severity of IgAN. Glomerular deposition of C4d has been associated with increased histologic disease activity, faster decline in estimated glomerular filtration rate and higher risk of kidney failure. On the other hand, although overlooked in the Oxford classification, numerous studies have shown that the coexistence of thrombotic microangiopathy in IgAN is a significant indicator of a poorer prognosis. All the breakthroughs in the understanding of the contributing role of complement in IgAN have paved the way for the development of new complement-targeted therapies in this disease. Several ongoing trials are evaluating the efficacy of new agents against factor B (iptacopan, Ionis-FB-LRX), C3 (pegcetacoplan), factor D (vemircopan, pelecopan), C5 (ravulizumab, cemdisiran) and C5a receptor 1 (avacopan). In this study, we provide a comprehensive review of the role of complement in IgAN, including the emerging mechanisms of complement activation and the promising potential of complement inhibitors as a viable treatment option for IgAN.
Microscopic hematuria as a risk factor for IgAN progression: considering this biomarker in selecting and monitoring patients
Authors: Zand Ladan , Fervenza Fernando C , Coppo Rosanna 
Published: December 2023

ABSTRACT
Hematuria—either macroscopic hematuria or asymptomatic microscopic hematuria—is a clinical feature typical but not specific for immunoglobulin A nephropathy (IgAN). The only biomarker supported by the Kidney Disease: Improving Global Outcomes group as a predictor of progression, identifying patients needing treatment, is proteinuria &gt;1 g/day persistent despite maximized supportive care. However, proteinuria can occur in the setting of active glomerulonephritis or secondary to sclerotic renal lesions. Microscopic hematuria is observed in experimental models of IgAN after IgA–IgG immunocomplex deposition, activation of inflammation and complement pathways. Oxidative damage, triggered by hemoglobin release, is thought to contribute to the development of proteinuria and progression. Despite being a clinical hallmark of IgAN and having a rational relationship with its pathophysiology, the value of microscopic hematuria in assessing activity and predicting outcomes in patients with IgAN is still debated. This was partly due to a lack of standardization and day-to-day variability of microhematuria, which discouraged the inclusion of microhematuria in large multicenter studies. More recently, several studies from Asia, Europe and the USA have highlighted the importance of microhematuria assessment over longitudinal follow-up, using a systematic approach with either experienced personnel or automated techniques.
We report lights and shadows of microhematuria evaluation in IgAN, looking for evidence for a more consistent consensus on its value as a marker of clinical and histological activity, risk assessment and prediction of treatment response. We propose that hematuria should be included as part of the clinical decision-making process when considering when to use immunosuppressive therapy and as part of criteria for enrollment into clinical trials to test drugs targeting the inflammatory reaction elicited by immune pathway activation in IgAN.
History and evidence for state of the art of lymphadenectomy in esophageal cancer surgery
Authors: Schuring Nannet , van Berge Henegouwen Mark I , Gisbertz Suzanne S 
Published: December 2023

Summary
The current curative multimodal treatment of advanced esophageal cancers consists of neoadjuvant or perioperative chemo(radio)therapy followed by a radical surgical resection of the primary tumor and a 2- or 3-field lymphadenectomy. One of the most important predictors of long-term survival of esophageal cancer patients is lymph node involvement. The distribution pattern of lymph node metastases in esophageal cancer is unpredictable and depends on the primary tumor location, histology, T-stage and application of neoadjuvant or perioperative treatment. The optimal extent of the lymphadenectomy remains controversial; there is no global consensus on this topic yet. Some surgeons advocate an aggressive and extended lymph node dissection to remove occult metastatic disease, to optimize oncological outcomes. Others promote a more restricted lymphadenectomy, since the benefit of an extended lymphadenectomy, especially after neoadjuvant chemoradiotherapy, has not been clearly demonstrated, and morbidity may be reduced. In this review, we describe the development of lymphadenectomy, followed by a summary of current evidence for lymphadenectomy in esophageal cancer treatment.
Enhancement of bicycle exercise capacity in patients with chronotropic incompetence through closed-loop stimulation: a randomized crossover trial
Authors: Chua Su-Kiat , Chen Wen-Ling , Chen Lung-Ching , Shyu Kou-Gi , Hung Huei-Fong , Lee Shih-Huang , Wang Tzu-Lin , Lai Wei-Ting , Chen Kuan-Jen , Liao Zhen-Yu , Chuang Cheng-Yen , Chou Ching-Yao 
Published: December 2023

Abstract

Aims
This study aimed to investigate the effectiveness of closed-loop stimulation (CLS) pacing compared with the traditional DDD mode in patients with chronotropic incompetence (CI) using bicycle-based cardiopulmonary exercise testing (CPET).

Methods and results
This single-centre, randomized crossover trial involved 40 patients with CI. Patients were randomized to receive either DDD-CLS or DDD mode pacing for 2 months, followed by a crossover to the alternative mode for an additional 2 months. Bicycling-based CPET was conducted at the 3- and 5-month follow-up visits to assess exercise capacity. Other cardiopulmonary exercise outcome measures and health-related quality of life (QoL) were also assessed. DDD-CLS mode pacing significantly improved exercise capacity, resulting in a peak oxygen uptake (14.8 ± 4.0 vs. 12.0 ± 3.6 mL/kg/min, P &lt; 0.001) and oxygen uptake at the ventilatory threshold (10.0 ± 2.2 vs. 8.7 ± 1.8 mL/kg/min, P &lt; 0.001) higher than those of the DDD mode. However, there were no significant differences in other cardiopulmonary exercise outcome measures such as ventilatory efficiency of carbon dioxide production slope, oxygen uptake efficiency slope, and end-tidal carbon dioxide between the two modes. Patients in the DDD-CLS group reported a better QoL, and 97.5% expressed a preference for the DDD-CLS mode.

Conclusion
DDD-CLS mode pacing demonstrated improved exercise capacity and QoL in patients with CI, highlighting its potential as an effective pacing strategy for this patient population.
Autothreshold algorithm feasibility and safety in left bundle branch pacing
Authors: Sola-García Elena , Molina-Lerma Manuel , Jiménez-Jáimez Juan , Macías-Ruiz Rosa , Sánchez-Millán Pablo J , Tercedor Luis , Álvarez Miguel 
Published: December 2023

Abstract

Aims
Autothreshold algorithms enable remote monitoring of patients with conventional pacing, but there is limited information on their performance in left bundle branch pacing (LBBP). Our objective was to analyse the behaviour of the autothreshold algorithm in LBBP and compare it with conventional pacing and manual thresholds during initial device programming (acute phase), after 1–7 days (subacute), and 1–3 months later (chronic).

Methods and results
A prospective, non-randomized, single-centre comparative study was conducted. Consecutive patients with indication for cardiac pacing were enrolled. Implants were performed in the left bundle branch area or the right ventricle endocardium at the discretion of the operator. Left bundle branch pacing was determined according to published criteria. Autothreshold algorithm was activated in both groups whenever allowed by the device. Seventy-five patients were included, with 50 undergoing LBBP and 25 receiving conventional pacing. Activation of the autothreshold algorithm was more feasible in later phases, showing a favourable trend towards bipolar pacing. Failures in algorithm activation were primarily due to insufficient safety margins (82.8% in LBBP and 90% in conventional pacing). The remainder was attributed to atrial tachyarrhythmias (10.3% and 10%, respectively) and electrical noise (the remaining 6.9% in the LBBP group). In the LBBP group, there were not statistically significant differences between manual and automatic thresholds, and both remained stable during follow-up (mean increase of 0.50 V).

Conclusion
The autothreshold algorithm is feasible in LBBP, with a favourable trend towards bipolar pacing. Automatic thresholds are similar to manual in patients with LBBP, and they remain stable during follow-up.
Improving data use in trachomatous trichiasis programmes: operationalisation of the TT Tracker
Authors: Bartlett Sarah , Ngom Babacar , Olobio Nicholas , Badiane Mouctar Dieng , Tarboh Godwin , Diagne Aliou , Nwosu Christian 
Published: December 2023

Abstract
Trachoma is a disease of the eye and the leading infectious cause of blindness worldwide. Years of repeated infections can cause in-turning of the lashes so that they rub against the eyeball, causing pain, discomfort and, if left untreated, blindness. This is known as trachomatous trichiasis (TT) and can be remedied by surgery. To improve oversight and reporting of TT outreach, Sightsavers developed a mobile phone application called the TT Tracker so that TT surgeons, assistants and supervisors can collect and analyse information about surgical outcomes and performance and determine when and where follow-up appointments are required. The TT Tracker is being used by seven national programmes. Examples of use and programme improvements from Nigeria, Benin and Senegal are discussed here.
Expanding a photographic grading system for trachomatous scarring
Authors: Nayel Yassin , Muñoz Beatriz E , Mkocha Harran , West Sheila K , Wolle Meraf A 
Published: December 2023

Abstract

Background
The purpose was to assess an expansion of a previously published photographic four-step severity grading scale for trachomatous scarring (TS).

Methods
Images of everted eyelids of adult women in Tanzania were graded for the presence and severity of TS. The previous S3 grade was subdivided into two categories: S3A, one-third to &lt;50% of the upper eyelid conjunctiva scarred; and S3B, 50% to &lt;90%. The reliability and ease of use were evaluated. This new categorisation was then applied to images taken of the same women 5 y prior to evaluate whether it could help detect previously undetected progression.

Results
In total, 142 eyes at baseline and 418 eyes at follow-up after 5 y were graded as S3. Interobserver agreement using the expanded scarring grading scale was a kappa of 0.86. At baseline, 51 (35.9%) eyes were S3A and 91 (64.1%) were S3B. At follow-up after 5 y, 36.6% of the eyes that were previously documented as not having progressed were now detected as having progressed from S3A to S3B. S3B images were more likely to progress to S4 compared with S3A (OR 4.6, 95% CI 2.1 to 9.9).

Conclusions
Adding S3A and S3B is reliable and detects more scarring progression. It will be beneficial for future studies analysing TS in photographs.
Effectiveness of plant-based hand sanitizer incorporatingQuercus infectoriagall extract
Authors: Waen-ngoen Tassanai , Wunnoo Suttiwan , Nwabor Ozioma Forstinus , Bilhman Siwaporn , Dumjun Krittima , Ongarj Jomkwan , Pinpathomrat Nawamin , Lethongkam Sakkarin , Voravuthikunchai Supayang Piyawan , Paosen Supakit 
Published: December 2023

AbstractAimsQuercus infectoria (Qi), a traditional herbal plant with a broad spectrum of activities on multidrug-resistant bacteria, has been developed for hand sanitizer applications.Methods and ResultsAntimicrobial activity was evaluated using agar-well diffusion and broth microdilution method. Bactericidal activity was determined following the European Standard 1276 antibacterial suspension test. Neutralization assay was performed to assess antirespiratory syncytial virus. Safety, stability, and skin permeation of Qi hand gel was investigated. Qi hand sanitizer gel inhibited microorganisms ranging from 99.9% to 99.999% against Enterococcus faecalis, Staphylococcus aureus, methicillin-resistant Staph. aureus, Staph. epidermidis, Staph. pseudintermedius, Staph. saprophyticus, Streptococcus pyogenes, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans. A significant reduction in main human dermatophytes including Microsporum canis, M. gypseum, and Talaromyces marneffei of ∼50% was observed (P &lt; .05). Qi hand sanitizer gel inactivated &gt;99% viral particles entering human laryngeal epidermoid carcinoma cells in a dose-dependent manner. Scanning electron micrographs further illustrated that Qi hand sanitizer gel disrupted microbial cell membrane after 1-min contact time resulting in cell death. Qi hand sanitizer gel delivered emollient compounds through simulated human skin layers and showed no cytotoxicity on fibroblast cells. Moreover, Qi hand sanitizer gel demonstrated stability under extreme conditions.ConclusionsQi hand sanitizer gel was able to inhibit various microorganisms including bacteria, dermatophytes, and virus.
Solriamfetol and m-chlorophenylpiperazine cause false positive amphetamine results on urine drug screening
Authors: Rackow Ashley R , Knezevic Claire E 
Published: December 2023

Abstract
Urine drug screening by immunoassay is a common method to quickly identify drug exposures in the emergency setting and to detect unexpected drug exposures in a variety of patient care and occupational health settings. Although they provide rapid results, immunoassays are susceptible to cross-reactivity with other medications and metabolites. Herein we evaluate the performance of the Thermo Scientific DRI Amphetamines immunoassay for reactivity with trazodone, aripiprazole, atomoxetine, solriamfetol and relevant metabolites. Each of these compounds were spiked into drug-free urine across a range of concentrations and assessed for positivity on amphetamine screen. We demonstrate that the Thermo Scientific DRI assay is susceptible to interferences from m-chlorophenylpiperazine (mCPP), the main metabolite of trazodone, and solriamfetol. Characterization of assay-specific interferences in toxicology screening is instrumental for accurate interpretation of toxicology results, evaluation of patients in emergent settings and supporting patient care.
Aerosols are not spherical cows: using discrete dipole approximation to model the properties of fractal particles
Authors: Lodge M G , Wakeford H R , Leinhardt Z M 
Published: December 2023

ABSTRACT
The optical properties of particulate-matter aerosols, within the context of exoplanet and brown dwarf atmospheres, are compared using three different models: Mie theory, modified mean field (MMF) theory, and discrete dipole approximation (DDA). Previous results have demonstrated that fractal haze particles (MMF and DDA) absorb much less long-wavelength radiation than their spherical counterparts (Mie), however it is shown here that the opposite can also be true if a more varying refractive index profile is used. Additionally, it is demonstrated that absorption/scattering cross-sections, and the asymmetry parameter, are underestimated if Mie theory is used. Although DDA can be used to obtain more accurate results, it is known to be much more computationally intensive; to avoid this, the use of low-resolution aerosol models is explored, which could dramatically speed up the process of obtaining accurate computations of optical cross-sections within a certain parameter space. The validity of DDA is probed for wavelengths of interest for observations of aerosols within exoplanet and brown dwarf atmospheres ($0.2-15~\mu$m). Finally, novel code is presented to compare the results of Mie, MMF, and DDA theories (coral: Comparison Of Radiative AnaLyses), as well as to increase and decrease the resolution of DDA shape files accordingly (spherify). Both codes can be applied to a range of other interesting astrophysical environments in addition to exoplanet atmospheres, for example dust grains within protoplanetary discs.
Alternative cleavage and polyadenylation of the Ccnb1 mRNA defines accumulation of cyclin protein during the meiotic cell cycle
Authors: Wang Xiaotian , Leung Fang-Shiuan , Bush Jeffrey O , Conti Marco 
Published: December 2023

Abstract
Progression through the mitotic and meiotic cell cycle is driven by fluctuations in the levels of cyclins, the regulatory subunits controlling the localization and activity of CDK1 kinases. Cyclin levels are regulated through a precise balance of synthesis and degradation. Here we demonstrate that the synthesis of Cyclin B1 during the oocyte meiotic cell cycle is defined by the selective translation of mRNA variants generated through alternative cleavage and polyadenylation (APA). Using gene editing in mice, we introduced mutations into the proximal and distal polyadenylation elements of the 3′ untranslated region (UTR) of the Ccnb1 mRNA. Through in vivo loss-of-function experiments, we demonstrate that the translation of mRNA with a short 3′ UTR specifies Cyclin B1 protein levels that set the timing of meiotic re-entry. In contrast, translation directed by a long 3′ UTR is necessary to direct Cyclin B1 protein accumulation during the MI/MII transition. These findings establish that the progression through the cell cycle is dependent on the selective translation of multiple mRNA variants generated by APA.
Present and Future of Immunotherapy in Patients With Glioblastoma: Limitations and Opportunities
Authors: Maccari Marta , Baek Chooyoung , Caccese Mario , Mandruzzato Susanna , Fiorentino Alba , Internò Valeria , Bosio Alberto , Cerretti Giulia , Padovan Marta , Idbaih Ahmed , Lombardi Giuseppe 
Published: December 2023

Abstract
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. Standard therapies, including surgical resection, chemoradiation, and tumor treating fields, have not resulted in major improvements in the survival outcomes of patients with GBM. The lack of effective strategies has led to an increasing interest in immunotherapic approaches, considering the success in other solid tumors. However, GBM is a highly immunosuppressive tumor, as documented by the presence of several mechanisms of immune escape, which may represent a reason why immunotherapy clinical trials failed in this kind of tumor. In this review, we examine the current landscape of immunotherapy strategies in GBM, focusing on the challenge of immunoresistance and potential mechanisms to overcome it. We discussed completed and ongoing clinical trials involving immune checkpoint inhibitors, oncolytic viruses, vaccines, and CAR T-cell therapies, to provide insights into the efficacy and outcomes of different immunotherapeutic interventions. We also explore the impact of radiotherapy on the immune system within the GBM microenvironment highlighting the complex interactions between radiation treatment and the immune response.
Credit Allocation and Macroeconomic Fluctuations
Authors: Müller Karsten , Verner Emil 
Published: December 2023

Abstract
We study the relationship between credit expansions, macroeconomic fluctuations, and financial crises using a novel database on the sectoral distribution of private credit for 117 countries since 1940. We document that, during credit booms, credit flows disproportionately to the non-tradable sector. Credit expansions to the non-tradable sector, in turn, systematically predict subsequent growth slowdowns and financial crises. In contrast, credit expansions to the tradable sector are associated with sustained output and productivity growth without a higher risk of a financial crisis. To understand these patterns, we show that firms in the non-tradable sector tend to be smaller, more reliant on loans secured by real estate, and more likely to default during crises. Our findings are consistent with models in which credit booms to the non-tradable sector are driven by easy financing conditions and amplified by collateral feedbacks, contributing to increased financial fragility and a boom–bust cycle.
Impact of gender on baseline presentation and outcome in adult IgA vasculitis
Authors: Baud Kim-Liên , Hankard Antoine , Ramdani Yanis , Maisons Valentin , Pillebout Evangeline , Augusto Jean François , Jourde-Chiche Noémie , Faguer Stanislas , Ferreira-Maldent Nicole , Maillot François , Halimi Jean-Michel , Terrier Benjamin , Audemard-Verger Alexandra 
Published: December 2023

Abstract

Objectives
Adult IgA vasculitis (IgAV) is more common in males, but the potential impact of gender remains unclear. We aimed to describe the impact of gender on presentation and outcome in adult IgAV.

Methods
We retrospectively analysed data from a multicentre retrospective cohort of 260 patients (IGAVAS). Comparisons were made according to gender status.

Results
Data from 259 patients (95 females and 164 males) were analysed. Compared with females, baseline presentation in males was similar for cutaneous involvement (100% vs 100%, P = 1.0), joint involvement (60% vs 63%, P = 0.7), gastrointestinal involvement (57% vs 45%, P = 0.093) and glomerulonephritis (73% vs 64%, P = 0.16). Glomerulonephritis was more severe at baseline in males than in females, with a lower median estimated glomerular filtration rate (eGFR) [90 (IQR 59–105) vs 97 ml/min/1.73 m2 (76–116), P = 0.015] and increased median proteinuria (0.84 vs 0.58 g/day, P = 0.01). There were no differences in histological findings in patients who had a kidney biopsy. Methylprednisolone was more frequently used in males (40% vs22%, P = 0.015), as were immunosuppressants, especially cyclophosphamide (24% vs 6%, P = 0.0025) and azathioprine (10% vs 2%, P = 0.038). Analysis of treatment response showed that males had more frequent refractory disease (30% vs 13%, P = 0.004). Long-term outcomes (mortality and progression to chronic kidney failure) did not differ.

Conclusion
Kidney involvement in IgAV appears to be more severe in males, which is supported by more intensive treatment contrasting with a lower response rate. This study raises the question of gender as a new prognostic factor in adult IgAV.