Additive effect of the root-lesion nematode Pratylenchus penetransand the fungus Rhizoctonia solanion potato yield and damage

The significance of nematodes for disease development caused by other soil-borne pathogens has been demonstrated in many crops throughout the world and specifically prevalent are interactions between plant-parasitic nematodes and species of plant pathogenic fungi. Here, the interaction between the fungusRhizoctonia solani(AG2) and the migratory endoparasitic root-lesion nematodePratylenchus penetranswas investigated on potato. The hypotheses were that the combination ofR. solaniandP. penetranswould result in more severe canker lesions, reduced quality of the tubers and lower tuber yield, and we also expected higher nematode levels to render more nematode damage. To test this, potato plants were grown in pots in two replicate experiments and the presence and/or abundance of the two pathogens were controlled. The first three hypotheses were rejected as (1) the tuber yield decreased when the fungus and nematode occurred together but not more than the sum of their separate effects, i.e. additive, (2) there was no effect of presence of nematodes on the incidence of stem canker, and (3) the quality of tubers was actually partly improved as the presence of the nematodes reduced the likelihood of elephant hide on the tubers in one of the experiments. As expected, there were more visible nematode damages with addition of more nematodes, but beyond that the different nematode levels rendered in most cases similar responses. To have knowledge about interactions between pathogens, as the one showed here, is essential for disease control through appropriate management methods

Design of a cybernetic hand for perception and action

Strong motivation for developing new prosthetic hand devices is provided by the fact that low functionality and controllability—in addition to poor cosmetic appearance—are the most important reasons why amputees do not regularly use their prosthetic hands. This paper presents the design of the CyberHand, a cybernetic anthropomorphic hand intended to provide amputees with functional hand replacement. Its design was bio-inspired in terms of its modular architecture, its physical appearance, kinematics, sensorization, and actuation, and its multilevel control system. Its underactuated mechanisms allow separate control of each digit as well as thumb–finger opposition and, accordingly, can generate a multitude of grasps. Its sensory system was designed to provide proprioceptive information as well as to emulate fundamental functional properties of human tactile mechanoreceptors of specific importance for grasp-and-hold tasks. The CyberHand control system presumes just a few efferent and afferent channels and was divided in two main layers: a high-level control that interprets the user’s intention (grasp selection and required force level) and can provide pertinent sensory feedback and a low-level control responsible for actuating specific grasps and applying the desired total force by taking advantage of the intelligent mechanics. The grasps made available by the high-level controller include those fundamental for activities of daily living: cylindrical, spherical, tridigital (tripod), and lateral grasps. The modular and flexible design of the CyberHand makes it suitable for incremental development of sensorization, interfacing, and control strategies and, as such, it will be a useful tool not only for clinical research but also for addressing neuroscientific hypotheses regarding sensorimotor control

Automated Medical Coding on MIMIC-III and MIMIC-IV: A Critical Review and Replicability Study

Medical coding is the task of assigning medical codes to clinical free-text documentation. Healthcare professionals manually assign such codes to track patient diagnoses and treatments. Automated medical coding can considerably alleviate this administrative burden. In this paper, we reproduce, compare, and analyze state-of-the-art automated medical coding machine learning models. We show that several models underperform due to weak configurations, poorly sampled train-test splits, and insufficient evaluation. In previous work, the macro F1 score has been calculated sub-optimally, and our correction doubles it. We contribute a revised model comparison using stratified sampling and identical experimental setups, including hyperparameters and decision boundary tuning. We analyze prediction errors to validate and falsify assumptions of previous works. The analysis confirms that all models struggle with rare codes, while long documents only have a negligible impact. Finally, we present the first comprehensive results on the newly released MIMIC-IV dataset using the reproduced models. We release our code, model parameters, and new MIMIC-III and MIMIC-IV training and evaluation pipelines to accommodate fair future comparisons.Comment: 11 pages, 6 figures, to be published in Proceedings of the 46th International ACM SIGIR Conference on Research and Development in Information Retrieval (SIGIR '23), July 23--27, 2023, Taipei, Taiwa

Photodynamic Therapy as Novel Treatment for Halitosis in Adolescents: A Case Series Study

Introduction: Halitosis is a common problem that affects a large portion of the population worldwide. The origin of this condition is oral in 90% of cases and systemic in 10% of cases. The foul odor is caused mainly by volatile sulfur compounds produced by Gram-negative bacteria. However, it has recently been found that anaerobic Gram-positive bacteria also produce hydrogen sulfide (H2S) in the presence of amino acids, such as cysteine. Light with and without the combination of chemical agents has been used to induce therapeutic and antimicrobial effects. In photodynamic therapy, the antimicrobial effect is confined to areas covered by the photosensitizing dye. The aim of the present case series study was to evaluate the antimicrobial effect of photodynamic therapy on halitosis in adolescents through the analysis of volatile sulfur compounds measured using a sulfide meter (Halimeter®).Methods: Five adolescents aged 14 to 16 years were evaluated using a sulfide meter before and one hour after photodynamic therapy, which involved the use of methylene blue 0.005% on the middle third and posterior thirds of the dorsum of the tongue and nine points of laser irradiation in the red band (660 nm) with an energy dose of 9 J, power output of 100 mW and 90-seconds exposure time.Results: A 31.8% reduction in the concentration of volatile sulfur compounds was found in the comparison of the initial and final readings. The statistically significant reduction (p = 0.0091) led to an absence of halitosis following treatment (mean: 58.2 ppb).Conclusion: Photodynamic therapy seems to be effective on reduction the concentration of volatile sulfur compounds.Considering the positive effects of photodynamic therapy in this case series, further studies involving microbiological analyses should be conducted to allow comparisons of the results

Condizionalità europea e identità costituzionali

La presente Sezione monografica trae origine dall’omonimo seminario organizzato presso l’Università degli Studi di Udine nel marzo 2023. Il tema della call for papers alla base del seminario – condizionalità europea e identità costituzionali – è stato scelto in quanto la condizionalità, o meglio le condizionalità, costituiscono meccanismi, di diversa matrice, sempre più presenti e pervasivi nel processo di integrazione europea, sia dal punto di vista quantitativo che da quello qualitativo. Essi agiscono sul versante orizzontale dei fini propri dell’Unione e dei rapporti tra i suoi organi, sul versante verticale dei rapporti tra Unione e Stati membri, sul versante esterno dei rapporti tra Unione e Stati candidati all’adesione, futuri candidati o Stati terzi. Gli strumenti di condizionalità rappresentano, così, uno stress test per alcuni dei tratti caratterizzanti dell’ordinamento sovranazionale, quali il limite delle competenze attribuite, il principio di parità tra Stati, la persistente oscillazione tra modello intergovernativo e modello comunitario, oggi unionale, fino a toccare, nelle più recenti evoluzioni, la stessa capacità prescrittiva dei valori di cui all’art. 2 TUE e la loro tenuta rispetto alle identità costituzionali degli Stati membri. Di qui la scelta di un tema che tocca il cuore dell’integrazione europea da molteplici sfaccettature. La Sezione si apre con un contributo di carattere generale su “L’utilizzo della condizionalità e la trasformazione dello spazio europeo” (A. Baraggia). I successivi contributi si possono raggruppare attorno a quattro nuclei tematici distinti che, tuttavia, si intersecano fra loro in maniera significativa. La condizionalità di bilancio connessa alla protezione dello Stato di diritto è analizzata da Adriano Dirri e Ylenia Guerra – che hanno scritto sulla controversa genesi e sulla «contestata applicazione» del Regolamento 2020/2092, evidenziando sia gli aspetti giuridici che le dinamiche politiche – e da Nicola Maffei, con un contributo che ne offre una lettura in chiave di evoluzione costituzionale dell’Unione, in correlazione con il piano Next Generation EU (NGEU). Il secondo nucleo di riflessione è costituito dalla condizionalità relativa all’utilizzo delle risorse finanziarie, in rapporto con la forma di governo nazionale: Federico Musso mette in luce la diversa incidenza dei vincoli sovranazionali di natura macroeconomica sulle decisioni finanziarie degli Stati membri, mentre Giulio Santini riprende l’elaborazione teorica sul concetto di indirizzo politico, proponendone l’utilizzo come chiave di lettura dell’efficacia dei meccanismi di condizionalità in ambito europeo. Ci si concentra poi su obiettivi settoriali di particolare rilevanza perseguiti dall’Unione con lo strumento della condizionalità. Paola Valerio descrive l’emergere del suo utilizzo per finalità di carattere ambientale, dalla politica di coesione alla politica agricola comune, sino al Dispositivo per la ripresa e la resilienza (cd. Recovery Fund). Roberto Vinceti, invece, approfondisce come il «formante negoziale» sotteso alla condizionalità possa spingere all’armonizzazione degli ordinamenti giudiziari nazionali, pur in assenza di competenze normative dell’Unione, facendo emergere un modello comune che i soli interventi della giurisprudenza sovranazionale non avrebbero potuto forgiare. L’ultima forma di condizionalità esaminata dai contributi della Sezione è quella insita nel procedimento di adesione ed è rivolta agli Stati candidati o potenziali candidati: Edin Skrebo analizza l’esperienza dei Balcani occidentali, e in particolare dei quattro Stati che erano parte della Repubblica Federale di Yugoslavia (Bosnia ed Erzegovina, Serbia, Montenegro e Macedonia del Nord), mentre Tatiana-Maria Cernicova-Dragomir parla dell’«associated trio» di Stati che, nel 2022, ha espresso la volontà di diventare parte dell’Unione: Ucraina, Moldavia e Georgia

High Tumour Cannabinoid CB1 Receptor Immunoreactivity Negatively Impacts Disease-Specific Survival in Stage II Microsatellite Stable Colorectal Cancer

BACKGROUND: There is good evidence in the literature that the cannabinoid system is disturbed in colorectal cancer. In the present study, we have investigated whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated with disease severity and outcome. METHODOLOGY/PRINCIPAL FINDINGS: CB(1)IR was assessed in formalin-fixed, paraffin-embedded specimens collected with a consecutive intent during primary tumour surgical resection from a series of cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and the data was analysed as a median split i.e. CB(1)IR <2 and ≥2. In microsatellite stable, but not microsatellite instable tumours (as adjudged on the basis of immunohistochemical determination of four mismatch repair proteins), there was a significant positive association of the tumour grade with the CB(1)IR intensity. The difference between the microsatellite stable and instable tumours for this association of CB(1)IR was related to the CpG island methylation status of the cases. Cox proportional hazards regression analyses indicated a significant contribution of CB(1)IR to disease-specific survival in the microsatellite stable tumours when adjusting for tumour stage. For the cases with stage II microsatellite stable tumours, there was a significant effect of both tumour centre and front CB(1)IR upon disease specific survival. The 5 year probabilities of event-free survival were: 85±5 and 66±8%; tumour interior, 86±4% and 63±8% for the CB(1)IR<2 and CB(1)IR≥2 groups, respectively. CONCLUSIONS/SIGNIFICANCE: The level of CB(1) receptor expression in colorectal cancer is associated with the tumour grade in a manner dependent upon the degree of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in stage II microsatellite stable tumour patients

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049