bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpreting the constitution: The use and abuse of history
Authors: Tan Kevin Y L
Published: February 2023

The interpretation of written constitutions is a legal rather than an historical enterprise, and history is but one of the judge’s many interpretive tools. This article looks at the question of when and how historical facts are used in constitutional interpretation, rather than whether they should be used. I argue that two fundamental canons of interpretation—the need to treat constitutions as sui generis and not as ordinary legislation, and the dictum that rights provisions should be given a generous interpretation in favor of the individual—require judges to use whatever tools they have at their disposal to interpret constitutions accordingly. As a tool, history is neutral and nondialectical. It may thus be used both in favor of and against a given interpretive stance. Sometimes, a recourse to history may also yield contradictory positions. Through five case studies I try to show: (a) that there is no inevitability in outcomes even when history is used in interpretation, and that it may in fact be relied on by both sides without yielding an obvious result; (b) that history may be used to restrict rather than promote liberties; (c) that history may also be abused to introduce “unwritten customary constitutional law” contrary to the words of the constitution; (d) where history was cited but proved unuseful; and (e) where history could helpfully have been used but was not.
A Metagenomic Based Approach on Abundance and Diversity of Bacterial Communities Across the Life Stages ofCulicoides peregrinus(Diptera: Ceratopogonidae) a Vector of Bluetongue Virus
Authors: Banerjee Paramita , Sarkar Ankita , Ghosh Koushik , Mazumdar Abhijit
Published: February 2023

During larval rearing of Culicoides peregrinus Kieffer (Diptera: Ceratopogonidae) it was obligatory to add a small quantity of mud from larval habitat to nutrient broth in culture plates. This initiated microbial growth in rearing plates which facilitated growth and development of immature. The primary aim was to enumerate gut microbial communities across the different life stages of C. peregrinus. Amplicon sequencing of the V3–V4 hypervariable region (16S rDNA) was done on Illumina Miseq platform to detect gut bacterial communities at different life stages, while ITS regions (18S rRNA) were targeted for fungal communities of the 4th instar larvae. The major findings were: 1) Phylum Proteobacteria and Firmicutes were the most abundant throughout the life stages, along with the highest bacterial alpha diversity in the egg, 2) bacterial compositions were similar to laboratory reared and field collected adults, and 3) abundant fungal phyla associated with the larval gut were Ascomycota and Basidiomycota. Furthermore, analyses of the gut microbiome with METAGENassist might be indicative of their likely function in the natural habitat. Abundant gut-associated bacteria and/or fungal genera detected in the present study could be used as dietary supplements to establish laboratory colonies for further vectorial research. While, individual roles of the bacteria or fungi in paratransgenesis are warned for their possible utilization to frame the management strategy in upcoming works.
Spatiotemporal resolution in high-speed atomic force microscopy for studying biological macromolecules in action
Authors: Umeda Kenichi , McArthur Steven J , Kodera Noriyuki
Published: February 2023

High-speed atomic force microscopy (HS-AFM) is a unique approach that allows direct real-time visualization of biological macromolecules in action under near-physiological conditions, without any chemical labeling. Typically, the temporal resolution is sub-100 ms, and the spatial resolution is 2–3 nm in the lateral direction and ∼0.1 nm in the vertical direction. A wide range of biomolecular systems and their dynamic processes have been studied by HS-AFM, providing deep mechanistic insights into how biomolecules function. However, the level of mechanistic detail gleaned from an HS-AFM experiment critically depends on the spatiotemporal resolution of the system. In this review article, we explain the principle of HS-AFM and describe how the resolution is determined. We also discuss recent attempts to improve the resolution of HS-AFM to further extend the observable range of biological phenomena.
Independent Innexin Radiation Shaped Signaling in Ctenophores
Authors: Ortiz Jennifer , Bobkov Yuriy V , DeBiasse Melissa B , Mitchell Dorothy G , Edgar Allison , Martindale Mark Q , Moss Anthony G , Babonis Leslie S , Ryan Joseph F
Published: February 2023

Innexins facilitate cell–cell communication by forming gap junctions or nonjunctional hemichannels, which play important roles in metabolic, chemical, ionic, and electrical coupling. The lack of knowledge regarding the evolution and role of these channels in ctenophores (comb jellies), the likely sister group to the rest of animals, represents a substantial gap in our understanding of the evolution of intercellular communication in animals. Here, we identify and phylogenetically characterize the complete set of innexins of four ctenophores: Mnemiopsis leidyi, Hormiphora californensis, Pleurobrachia bachei, and Beroe ovata. Our phylogenetic analyses suggest that ctenophore innexins diversified independently from those of other animals and were established early in the emergence of ctenophores. We identified a four-innexin genomic cluster, which was present in the last common ancestor of these four species and has been largely maintained in these lineages. Evidence from correlated spatial and temporal gene expression of the M. leidyi innexin cluster suggests that this cluster has been maintained due to constraints related to gene regulation. We describe the basic electrophysiological properties of putative ctenophore hemichannels from muscle cells using intracellular recording techniques, showing substantial overlap with the properties of bilaterian innexin channels. Together, our results suggest that the last common ancestor of animals had gap junctional channels also capable of forming functional innexin hemichannels, and that innexin genes have independently evolved in major lineages throughout Metazoa.
SPINDLYO-fucosylates nuclear and cytoplasmic proteins involved in diverse cellular processes in plants
Authors: Zentella Rodolfo , Wang Yan , Zahn Emily , Hu Jianhong , Jiang Liang , Shabanowitz Jeffrey , Hunt Donald F , Sun Tai-ping
Published: February 2023

SPINDLY (SPY) is a novel nucleocytoplasmic protein O-fucosyltransferase that regulates target protein activity or stability via O-fucosylation of specific Ser/Thr residues. Previous genetic studies indicate that AtSPY regulates plant development during vegetative and reproductive growth by modulating gibberellin and cytokinin responses. AtSPY also regulates the circadian clock and plant responses to biotic and abiotic stresses. The pleiotropic phenotypes of spy mutants point to the likely role of AtSPY in regulating key proteins functioning in diverse cellular pathways. However, very few AtSPY targets are known. Here, we identified 88 SPY targets from Arabidopsis (Arabidopsis thaliana) and Nicotiana benthamiana via the purification of O-fucosylated peptides using Aleuria aurantia lectin followed by electron transfer dissociation-MS/MS analysis. Most AtSPY targets were nuclear proteins that function in DNA repair, transcription, RNA splicing, and nucleocytoplasmic transport. Cytoplasmic AtSPY targets were involved in microtubule-mediated cell division/growth and protein folding. A comparison with the published O-linked-N-acetylglucosamine (O-GlcNAc) proteome revealed that 30% of AtSPY targets were also O-GlcNAcylated, indicating that these distinct glycosylations could co-regulate many protein functions. This study unveiled the roles of O-fucosylation in modulating many key nuclear and cytoplasmic proteins and provided a valuable resource for elucidating the regulatory mechanisms involved.
Shared Identities and the Structure of Exchange Distinctly Shape Cooperation
Authors: Harrell Ashley , Quinn Joseph M
Published: February 2023

People frequently engage in preferential treatment toward those with whom they share category memberships. At the same time, sociologists have long understood that the structure of ongoing relations shapes micro-level interactions. Here, we ask whether—and if so, how—same-identity bias in cooperation interacts with key structural features of exchange relations. Specifically, we use the affect theory of social exchange (ATSE) to make predictions about cooperation in productive, reciprocal, and generalized exchange when people are embedded in networks where identities are either known and homogeneous, known and heterogenous, or unknown. Results from our experiment support both past work demonstrating same-identity bias in cooperation and the ATSE’s predictions that productive exchange yields the highest levels of cooperation and affective attachment, followed by reciprocal and generalized exchange. More importantly, we find that shared identities and the structure of exchange are two orthogonal factors that distinctly promote cooperation in the presence of each other. Structures with known homogeneous identities are more cooperative and develop higher levels of affective attachment across all forms of exchange, and different types of exchange produce different levels of cooperation and affective attachment in line with the ATSE, but the identity and structural mechanisms do not interact. We conclude by discussing the theoretical implications of our findings for the ATSE and scholarship on social identity biases as well as the practical implications for facilitating cooperation in diverse groups.
The green anaesthesia dilemma: to which extent is it important to preserve as many drugs available as possible
Authors: Gonzalez-Pizarro Patricio , Muret Jane , Brazzi Luca
Published: February 2023

Purpose of review

This article aims to summarize the current literature describing the availability of different anaesthetic drugs, and to discuss the advantages and limitations of a self-imposed restriction on the scarcely existing anaesthetic drugs.

Recent findings

Earth temperature has risen 1.2°C since the beginning of industrial age, and it is expected to exceed a 1.5°C increase by 2050. The Intergovernmental Panel on Climate Change depicts five different scenarios depending on how these increased temperatures will be controlled in the future. The European Commission has formulated a proposal to regulate fluorinated greenhouse gases (F-gases), among which desflurane, isoflurane and sevoflurane belong to, due to their high global warming potential. This proposal shall ban, or severely restrict, the use of desflurane starting January 2026. It is not clear what might happen with other F-gas anaesthetics in the future. Due to climate change, a higher number of health crisis are expected to happen, which might impair the exiting supply chains, as it has happened in previous years with propofol scarcity.

There are just a handful number of available anaesthetics that provide for a safe hypnosis. Major stakeholders should be consulted prior making such severe decisions that affect patient safety.
Foreign body aspiration in children – being safe and flexible
Authors: Keil Oliver , Schwerk Nicolaus
Published: February 2023

Purpose of review

Anesthesia for foreign body removal in children can be quite challenging. Even though rigid bronchoscopy is considered the gold standard for foreign body removal, there is increasing evidence for successful foreign body removal using flexible bronchoscopy. This review discusses the recent implications for flexible bronchoscopy for the purpose of foreign body removal and will compare these findings to rigid bronchoscopy.

Recent findings

During the last few years, several observational studies on foreign body removal by flexible bronchoscopy have been published, with promising results.

Flexible bronchoscopy is a feasible and safe method for removing aspirated foreign bodies in children. In order to improve patient safety during the procedure, it is necessary for a pediatric anesthetist and a pediatric pulmonologist to work closely together. The anesthetist can take care of the administration of the anesthetic and maintenance of the vital functions, and the pulmonologist can carry out a safe and fast bronchoscopy. In the case of foreign body removal by flexible bronchoscopy, the anesthesiological procedure of choice should be general anesthesia with controlled ventilation via a laryngeal mask.
Physiological Effects of Handling in Moderate to Late Preterm Infants Receiving Neonatal Intensive Care
Authors: Brashear Nancy , D'Errico Ellen , Truax Fayette Nguyen , Pentecost Alena , Tan John B. C. , Bahjri Khaled , Angeles Danilyn
Published: February 2023

Background:

Of all preterm births, approximately 82% are moderate to late preterm. Moderate to late preterm infants are often treated like full-term infants despite their physiological and metabolic immaturity, increasing their risk for mortality and morbidity.

Purpose:

To describe the relationship between routine caregiving methods and physiological markers of stress and hypoxemia in infants born between 32 and 366/7 weeks' gestation.

Methods:

This descriptive study used a prospective observational design to examine the relationship between routine caregiving patterns (single procedure vs clustered care) and physiological markers of stress and hypoxemia such as regional oxygen saturation, quantified as renal and cerebral regional oxygen saturation (StO2), systemic oxygen saturation (Spo
2), and heart rate (HR) in moderate to late preterm infants. Renal and cerebral StO2 was measured using near-infrared spectroscopy during a 6-hour study period. Spo
2 and HR were measured using pulse oximetry.

Results:

A total of 231 procedures were captured in 37 participants. We found greater alterations in cerebral StO2, renal StO2, Spo
2, and HR when routine procedures were performed consecutively in clusters than when procedures were performed singly or separately.

Implications for Practice and Research:

Our results suggest that the oxygen saturation and HR of moderate to late preterm infants were significantly altered when exposed to routine procedures that were performed consecutively, in clusters, compared with when exposed to procedures that were performed singly or separately. Adequately powered randomized controlled trials are needed to determine the type of caregiving patterns that will optimize the health outcomes of this vulnerable population.
The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent
Authors: Goikoetxea-Usandizaga Naroa , Bravo Miren , Egia-Mendikute Leire , Abecia Leticia , Serrano-Maciá Marina , Urdinguio Rocío G. , Clos-García Marc , Rodríguez-Agudo Rubén , Araujo-Legido Raquel , López-Bermudo Lucía , Delgado Teresa C. , Lachiondo-Ortega Sofía , González-Recio Irene , Gil-Pitarch Clàudia , Peña-Cearra Ainize , Simón Jorge , Benedé-Ubieto Raquel , Ariño Silvia , Herranz Jose M. , Azkargorta Mikel , Salazar-Bermeo Julio , Martí Nuria , Varela-Rey Marta , Falcón-Pérez Juan M. , Lorenzo Óscar , Nogueiras Rubén , Elortza Félix , Nevzorova Yulia A. , Cubero Francisco J. , Saura Domingo , Martínez-Cruz Luis Alfonso , Sabio Guadalupe , Palazón Asís , Sancho-Bru Pau , Elguezabal Natalia , Fraga Mario F. , Ávila Matías A. , Bataller Ramón , Marín José J.G. , Martín Franz , Martínez-Chantar María Luz
Published: February 2023

Background and Aims:

Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage.

Approach and Results:

C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD+/NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation.

Conclusions:

Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.
Resiliency-based adaptations used by primary care physicians during the COVID-19 pandemic
Authors: Hoff Timothy , Neff Leah
Published: February 2023

Background

The COVID-19 pandemic is a profound change event for U.S. primary care physicians and their medical practices.

Purpose

We examined how a group of U.S. primary care physicians and their medical practices used resiliency-based strategies, tactics, and mindsets to navigate pandemic-related change over the time period early 2020 through mid-2021.

Methodology

A 15-month longitudinal qualitative study of the same 10 physicians interviewed a total of 42 times at four time intervals during the 2020–2021 COVID-19 pandemic. Data were analyzed using a systematic coding approach consisting of first- and second-order code categories feeding into an overall interpretive framework of resiliency-based adaptations.

Results

Primary care physicians and their practices engaged in two main resiliency-based strategic adaptations during the pandemic. These adaptations were labeled “keeping the business afloat” and “keeping primary care relevant for patients.” Each consisted of different strategies and tactics that shared common features including proactiveness, innovativeness, and pragmatism. Specific resiliency-based mindsets were identified that helped physicians both initially engage in needed strategies and tactics while continuing to engage in them over time.

Conclusions

The results demonstrate how physicians use resiliency-based adaptation in response to profound change in their environments, defined by behavioral variety and motivated by self-interested and patient-centered imperatives.

Practice Implications

Physicians are proactive and possess multiple adaptive capabilities. Seen in this more positive light, health care organizations should focus on greater engagement of their physician-employees in implementing innovation in care delivery and managing change, that is, as responsible partners rather than resistors to meeting organizational imperatives.
FS-LASIK for the treatment of moderate-to-high hyperopia
Authors: Alió del Barrio Jorge L. , Milán-Castillo Roberto , Canto-Cerdan Mario , Molina-Lespron Aleyda , Alió Jorge L.
Published: February 2023

Purpose:

To report modern outcomes of femtosecond laser–assisted cataract surgery (FS-LASIK) for the correction of moderate-to-high hyperopia (≥3.50 diopters [D] and ≤6.50 D), excluding low or very high hyperopia.

Setting:

Vissum, Alicante, Spain.

Design:

Monocentric retrospective case series study.

Methods:

Visumax-500 kHz femtosecond laser and Amaris-750 excimer-laser were used. Eyes with at least 6 months of follow-up were included. 36-month data was collected when available. Primary outcome measure was short term efficacy and safety. Secondary outcome measure was long term stability.

Results:

6-month data of 92 eyes was collected (68 eyes at 36 months). Mean age was 34.6 ± 10.4 years. Mean treated sphere was 4.69 ± 0.87. Efficacy index was 0.91 and 0.90 at 6 months and 36 months respectively. Safety index was 1.00. Uncorrected distance visual acuity was 20/20 or better in 72%, postoperative spherical equivalent within 0.5 D in 80% (93% within 1 D), and loss of 1 line of corrected distance visual acuity (CDVA) occurred in 13% (2 or more lines in 0%). Gain of 1 or more CDVA lines occurred in 17%. A slight but significant regression was observed at 36 months. Postoperatively, 21.73% required flap lift for laser enhancement, and 11.95% an orthoptic visual rehabilitation due to accommodative disorders.

Conclusions:

Modern LASIK provides good efficacy and safety levels for the management of moderate to high hyperopia (up to +6.5 D), with levels close to those previously reported with refractive lens exchange for young hyperopia patients without presbyopia, where we defend the maintenance of LASIK as first line therapy. Risk of requiring a refractive enhancement or an orthoptic visual rehabilitation remains relevant and needs to be discussed with patients preoperatively.
Double-flanged polypropylene technique: 5-year results
Authors: Canabrava Sérgio , Carvalho Marina Santana
Published: February 2023

Purpose:

To assess the long-term (5-year) results and complications of the double-flanged polypropylene technique in patients with capsular tension segment fixation, nonfoldable intraocular lens (IOL) scleral fixation, and foldable IOL scleral fixation.

Setting:

Santa Casa de Belo Horizonte and Centro Oftalmológico de Minas Gerais.

Design:

Prospective case series.

Methods:

Eyes that underwent treatment using the double-flanged polypropylene technique between September 2016 to September 2021 were included. LogMAR visual acuity was recorded, as well as complications such as long-term polypropylene resistance, conjunctival erosion, conjunctival inflammation, flange exposure, internalization, endophthalmitis, retinal detachment, and cystoid macular edema.

Results:

71 eyes of 61 patients were evaluated. The mean follow-up period for these eyes was 28.2 ± 14.3 (min: 4; max: 60; median: 26) months. 173 flanges were performed. 13 cases with sub-Tenon flanges (7.5%) were observed. 5 exposed flanges (2.89%), presented after a mean of 1.8 weeks postoperatively, were observed. 1 patient with large flanges presented with conjunctival inflammation and hyperemia. 2 late internalized flanges (1.1%) and 2 recently internalized flanges (1.1%) were observed. 3 eyes (4.22%) had retinal detachment. Moreover, cystoid macular edema was detected in 3 eyes (4.22%). No cases of endophthalmitis were observed.

Conclusions:

The double-flanged technique was proven to be stable when the correct technical procedure was followed. However, complications can be observed, especially with short scleral tunnels and in eyes where the flanges were not buried inside the sclera.
Predicting corneal cross-linking treatment efficacy with real-time assessment of corneal riboflavin concentration
Authors: Lombardo Marco , Bernava Giuseppe Massimo , Serrao Sebastiano , Roszkowska Anna Maria , Lombardo Giuseppe
Published: February 2023

Purpose:

To assess predictability of tissue biomechanical stiffening induced by UV-A light-mediated real-time assessment of riboflavin concentration during corneal crosslinking (CXL) of human donor tissues.

Setting:

Studio Italiano di Oftalmologia, Rome, Italy.

Design:

Laboratory study.

Methods:

20 sclerocorneal tissues were randomly stratified to undergo CXL with either the epithelium intact (n = 12) or removed (n = 8). Samples underwent corneal soaking with 0.22% riboflavin formulation (RitSight) with dosing time of t = 10 minutes and t = 20 minutes in epithelium-off and epithelium-on protocols, respectively. All tissues underwent 9-minute UV-A irradiance at 10 mW/cm2 using theranostic device (C4V CHROMO4VIS). The device used controlled UV-A light irradiation to induce both imaging and treatment of the cornea, providing a real-time measure of corneal riboflavin concentration and treatment efficacy (ie, theranostic score) during surgery. Tissue biomechanics were assessed with an air-puff device (Corvis), which was performed before and after treatment. A 3-element viscoelastic model was developed to fit the corneal deformation response to air-puff excitation and to calculate the mean corneal stiffness parameter (kc).

Results:

Significant corneal tissue stiffening (P < .05) was induced by the theranostic UV-A device in either CXL treatment protocol. Significant correlation was found between the theranostic score and the increase in kc (R = 0.75; P = .003). The score showed high accuracy (94%) and precision (94%) to predict correctly samples that had improved tissue biomechanical strengthening.

Conclusions:

Real-time assessment of corneal riboflavin concentration provided a predictive and precise approach for significant improvement of tissue strength on individual corneas, regardless of CXL treatment protocol.
Sirolimus Early Treatment in Vascular Anomalies Leads to a Better Response
Authors: Triana Paloma , Díez-Sebastián Jesús , Rodriguez-Laguna Lara , Martinez-Glez Victor , Lopez-Gutierrez Juan Carlos
Published: February 2023

Objectives:

Sirolimus has become a relevant drug in the treatment of vascular anomalies, initially relegated to rescue therapy for refractory lesions but more recently has become first line. Our objective is to determine when it is best to start sirolimus treatment.

Methods:

A retrospective review of patients with vascular anomalies treated with sirolimus during a 9-year period was performed. The variables analyzed included subtype of vascular anomaly, age at the start of treatment, sirolimus dosage and levels, response, and duration of treatment among others.

Results:

One hundred twenty-two patients were included and classified according to ISSVA in: tumor (7), lymphatic malformation (60), venous malformation (16), combined malformations (18), associated overgrowth (8), and others (15). Overall response was positive in 90.8%. Median duration of treatment was 32 months (0–116). Response was not influenced by dosage or levels, neither by the subtype of vascular anomaly, location, extension, symptoms, genetic testing nor previous treatments. However, the lower the age of starting sirolimus, the better the response, mainly under 5 years of age (P = 0.004). At 6 months, 67% of patients had responded while at 12 months >84% did. By age, patients <5 years showed positive response at a median time of 2 months, compared to >5 months from older patients. Time until a positive response was not influenced by subtype or severity.

Conclusion:

Overall response to sirolimus was good and most patients responded irrespective of their severity in location, extension or symptoms. Patients <5 years old respond better and faster making our goal to attempt for an early treatment.
Developing a Genital Training Associate Program
Authors: Zorn Jennifer
Published: February 2023

Genitourinary training associates (GTAs) are individuals educated to teach medical learners invasive exams and procedures using their own body. Through specified protocols, the GTA teaches exam techniques to students in a supportive environment while giving feedback to the learner to optimize skill acquisition. Additionally, this experience can teach best practices for future provider-patient communication. To help ensure access to GTAs for medical learners, physician assistant (PA) programs should consider developing a GTA training program at their institution. The purpose of this article is to outline the necessary steps to educate GTAs and develop a GTA training program.
SATB2 as a Marker of the Proximal Nephron: Expression in Nephrogenic Adenoma and Correlation With Other Renal Tubular Markers
Authors: Ortiz-Rey José-Antonio , Álvarez-Sarria Miguel , Conde-Ferreirós Marta , Morellón-Baquera Raquel , Bellas-Pereira Alejandro , Baltazar Sara T. , García-Acuña Silvia , San-Miguel Fraile Pilar , Suárez-Peñaranda José-Manuel , Fernández-Baltar Carlos , Vieytes-Molares Montserrat , Domínguez-Arístegui Patricia , Gómez-de María Carolina , Fachal-Bermúdez Carmen , González-Carreró Joaquín
Published: February 2023

Nephrogenic adenoma (NA) is an infrequent reactive urothelial lesion. The expression of immunohistochemical renal tubular markers has been reported in NA, although a proximal or distal nephron phenotype has not been established. Special AT-rich sequence-binding protein 2 (SATB2) is a marker of a colorectal origin of adenocarcinomas, occasionally reported in renal samples. We have analyzed SATB2 expression in NA, with correlation with other tubular markers, as well as in the normal kidney. Fifty cases of NA were immunostained with PAX8, SATB2, proximal nephron markers [CD10, renal cell carcinoma (RCC) marker, alpha-methylacyl-CoA racemase (AMACR), and CD15], and distal markers (Ksp cadherin, cytokeratin 7, E-cadherin (E-cad), and cytokeratin 19). Ten normal kidney sections were stained with a double method combining SATB2 plus CD10, RCC marker, AMACR, Ksp cadherin, cytokeratin 7, or E-cad. All NA were immunoreactive for PAX8 and 57% for SATB2. Every case was positive for proximal and distal nephron markers: 100% for cytokeratins 7 and 19, 84.1% E-cad +, 81.6% AMACR +, 68.9% Ksp cadherin +, 63% CD15 +, 53.3% CD10 +, and 28.6 % RCC +. In the normal kidney, SATB2 was detected in the straight part of the proximal tubules and the thin descending loops of Henle. NA shows a multiphenotypic pattern with coexpression of both proximal and distal nephron markers, and constant expression of PAX8, cytokeratins 7 and 19. SATB2 is often positive in NA, which should be kept in mind to avoid a possible misdiagnosis of intestinal adenocarcinoma. SATB2 is a marker of the normal proximal nephron.
Prognostic Value of the Radiomics-Based Model in the Disease-Free Survival of Pretreatment Uveal Melanoma: An Initial Result
Authors: Su Yaping , Xu Xiaolin , Wang Fang , Zuo Panli , Chen Qinghua , Wei Wenbin , Xian Junfang
Published: February 2023

Objective

The aim of this study was to develop a pretreatment magnetic resonance imaging (MRI)–based radiomics model for disease-free survival (DFS) prediction in patients with uveal melanoma (UM).

Methods

We randomly assigned 85 patients with UM into 2 cohorts: training (n = 60) and validation (n = 25). The radiomics model was built from significant features that were selected from the training cohort by applying a least absolute shrinkage and selection operator to pretreatment MRI scans. Least absolute shrinkage and selection operator regression and the Cox proportional hazard model were used to construct a radiomics score (rad-score). Patients were divided into a low- or a high-risk group based on the median of the rad-score. The Kaplan-Meier analysis was used to evaluate the association between the rad-score and DFS. A nomogram incorporating the rad-score and MRI features was plotted to individually estimate DFS. The model's discrimination power was assessed using the concordance index.

Results

The radiomics model with 15 optimal radiomics features based on MRI performed well in stratifying patients into the high- or a low-risk group of DFS in both the training and validation cohorts (log-rank test, P = 0.009 and P = 0.02, respectively). Age, basal diameter, and height were selected as significant clinical and MRI features. The nomogram showed good predictive performance with concordance indices of 0.741 (95% confidence interval, 0.637–0.845) and 0.912 (95% confidence interval, 0.847–0.977) in the training and validation cohorts, respectively. Calibration curves demonstrated good agreement.

Conclusion

The developed clinical-radiomics model may be a powerful predictor of the DFS of patients with UM, thereby providing evidence for preoperative risk stratification.
Quantitative Study of Vertebral Body and Paravertebral Muscle Degeneration Based on Dual-Energy Computed Tomography: Correlation With Bone Mineral Density
Authors: Liu Zhenghua , Zhang Yuting , Huang Dageng , Ma Xiaowen , Duan Yaqing , Jiang Yonghong
Published: February 2023

Objectives

This study aimed to quantify the degeneration of the vertebral body and paravertebral muscles using dual-energy computed tomography (DECT) and study its relationship with osteoporosis.

Methods

A total of 130 patients with chronic low back pain were included in this study, and DECT scanning of the lumbar region was undertaken prospectively. By placing a standard quantitative computed tomography corrected phantom under the waist during the DECT procedure, bone mineral density (BMD) and the following quantitative parameters were obtained: calcium density (CaD), vertebral fat fraction (VFF), psoas major area, psoas major fat fraction, erector spinalis area, and erector spinalis fat fraction (ESFF). Independent sample t test and 1-way analysis of variance were used between different age-BMD groups. Pearson test was applied to determine correlations for all measurements, and a mathematical model of BMD was established through regression analysis.

Results

Calcium density, VFF, psoas major area, psoas major fat fraction, erector spinalis area, and ESFF were significantly different among the age-BMD groups (P < 0.05), and BMD was significantly correlated with these parameters (P < 0.05). Calcium density, VFF, and ESFF were included in the BMD regression equation: BMD = 69.062 + 11.637 × CaD − 1.018 × VFF − 0.726 × ESFF (R
2 = 0.860, F = 125.979, P < 0.001).

Conclusions

Degeneration of the vertebral body and paravertebral muscles can be quantitatively analyzed using DECT, and CaD, VFF, and ESFF were independent influencing factors of BMD.
Physical Performance Decline During the Early Posttransplantation Period Affects Survival After Living Donor Liver Transplantation
Authors: Kim Deok-Gie , Hwang Shin , Lee Kwang-Woong , Choi Gyu-seong , You Young Kyoung , Ryu Je Ho , Kim Bong-Wan , Nah Yang Won , Kim Dong-Sik , Cho Jai Young , Kang Koo Jeong , Hong Geun , Yu Hee Chul , Ju Man ki , Suh Suk-Won , Kim Kwan Woo , Choi Dongho , Jeong Jaehong , Choi Soo Jin Na , Moon Ju Ik , Lee Jae Geun , Kim Myoung soo , Choi Donglak , Joo Dong Jin
Published: February 2023

Background.

Patient physical performance has been emphasized in liver transplant recipients; however, evidence for living donor liver transplantation (LDLT) patients is lacking. This study investigated the impact of physical performance decline during the early posttransplantation period on survival and risk factors for this decline in LDLT recipients.

Methods.

From national registry data, 2703 LDLT patients were divided into 2 groups based on the change in their Karnofsky performance status (KPS) between 1 and 6 mo posttransplantation: declined KPS (n = 188) and control (n = 2515). Multivariable analyses were conducted to control for confounders, including posttransplantation complications.

Results.

Estimated 5-y patient survival rates were 91.6% in the declined KPS group and 96.3% in the control group, favoring the latter (P = 0.003). The survival hazard of KPS decline was significant in a baseline covariates-adjusted Cox model (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.37-4.95) and an adjusted model accounting for posttransplantation complications (HR, 3.38; 95% CI, 1.70-6.72). In subgroup analyses, KPS decline independently reduced survival in patients without complications (HR, 3.95; 95% CI, 1.67-9.34), and the trend was similar in patients with complications, although significance was marginal (HR, 3.02; 95% CI, 0.98-9.27). We found that only posttransplantation complications, such as rejection, infection, bile duct complication, and vascular complication, were significant risk factors for KPS decline after LDLT.

Conclusions.

Physical performance decline during the early posttransplantation period independently reduced survival rates, and posttransplantation complications were the only significant risk factors for physical performance decline in LDLT recipients.
Development and Validation of an Alpha-Fetoprotein Tumor Burden Score Model to Predict Post-Recurrence Survival among Patients with Hepatocellular Carcinoma
Authors: Ding Hong-Fan , Yang Tian , Lv Yi , Zhang Xu-Feng , Pawlik Timothy M ,   and the International Hepatocellular Carcinoma Study Group
Published: February 2023

Background:

To establish a prognostic model to predict post-recurrence survival (PRS) probability after initial resection of hepatocellular carcinoma (HCC).

Study Design:

Patients with recurrent HCC after curative resection were identified through a multi-center consortium (training cohort, TC); data were from a separate institution was utilized as validation cohort (VC). The alpha-fetoprotein (AFP)-tumor burden score (ATS) was defined as the distance from the origin on a three-dimensional Cartesian coordinate system that incorporated 3 variables: largest tumor diameter (x-axis), number of tumors (y-axis) and ln AFP (z-axis). ATS was calculated using the Pythagorean theorem: [ATS

2

= (largest tumor diameter)
2

+(number of tumors)
2

+(ln AFP)
2
]. ATSd and ATSr represent ATS at time of initial diagnosis and at time of recurrence, respectively. The final model was “ATS
m
= ATS

d

+4×ATS

r
”. Predictive performance and discrimination of ATS model were evaluated and compared with traditional staging systems.

Results:

The ATS model demonstrated strong predictive performance to predict PRS in both the TC (AUC 0.70) and VC (AUC 0.71). An ATS-based nomogram was able to stratify patients accurately into low- and high-risk categories relative to PRS (TC: ATSm≤27, 74.9 mon vs. ATSm≥28, 23.3 mon; VC: ATSm≤27, 59.4 mon vs. ATSm≥28, 15.1 mon; both p<0.001). The ATS model predicted PRS among patient undergoing curative or non-curative treatments of HCC recurrence (both p<0.05). Of note, the ATS model outperformed the BCLC, CNLC, AJCC staging systems relative to 1-, 2-, 3-, 4- and 5-year PRS (AUC 0.70, vs. BCLC, AUC 0.50, vs. CNLC, AUC 0.54, vs. AJCC, AUC 0.51).

Conclusions:

The ATS model had excellent prognostic discriminatory power to stratify patients relative to PRS.
Gender Disparity in the Earliest Phase of Academic Surgical Training: An Area for Intervention
Authors: Zheng Hui , Al-Refaie Waddah , Chou Jiling , Galli Francesca , Lai Victoria , Felger Erin A
Published: February 2023

Background:

To overcome persistent gender disparities in academic surgery, it is critical to examine the earliest phase of surgical training. This national study sought to assess whether gender disparities also existed among surgical interns, as a proxy for medical school research experience in both quantity and quality.

Method:

Using the 2021-2022 public information of 1,493 US-graduated categorical general surgery interns, a bibliometric evaluation was conducted to assess medical school research experience. Multivariable linear regressions with response log-transformed were performed to evaluate the impact of intern gender on 1) total number of peer-reviewed publications, 2) total impact factor (TIF), and 3) adjusted TIF based on authorship placement (aTIF). Back transformed estimates were presented.

Results:

52.3% were Female. Significant differences were observed in TIF (male 6.4 vs female 5.3, p=0.029), aTIF (male 10.8 vs female 8.7, p=0.035), gender concordance with senior authors (male 79.9% vs female 34.1%, p<0.001), Hirsch index (male 21.0 vs female 18.0, p=0.026), and the geographic region of their medical schools (p=0.036). Multivariable linear regressions revealed that female were associated with lower TIF (0.858, p=0.033) and aTIF (0.851, p=0.044). Due to a significant gender-by-region interaction, adjusted pairwise comparisons showed that male in the Northeast had approximately 70% higher TIF (1.708, p=0.003) and aTIF (1.697, p=0.013) than female in the South.

Conclusion:

Gender disparities existed in the quality of research experience in the earliest phase of surgical training. These timely results call for additional interventions by the stakeholders of graduate medical education.
Assessing the role of family level variation and heat shock gene expression in the thermal stress response of the mosquito
Aedes aegypti
Authors: Ware-Gilmore Fhallon , Novelo Mario , Sgrò Carla M. , Hall Matthew D. , McGraw Elizabeth A.
Published: February 2023

The geographical range of the mosquito vector for many human disease-causing viruses,
Aedes aegypti
, is expanding, in part owing to changing climate. The capacity of this species to adapt to thermal stress will affect its future distributions. It is unclear how much heritable genetic variation may affect the upper thermal limits of mosquito populations over the long term. Nor are the genetic pathways that confer thermal tolerance fully understood. In the short term, cells induce a plastic, protective response known as 'heat shock'. Using a physiological ‘knockdown’ assay, we investigated mosquito thermal tolerance to characterize the genetic architecture of the trait. While families representing the extreme ends of the distribution for knockdown time differed from one another, the trait exhibited low but non-zero broad-sense heritability. We then explored whether families representing thermal performance extremes differed in their heat shock response by measuring gene expression of heat shock protein-encoding genes
Hsp
26, Hsp83
and
Hsp70.
Contrary to prediction, the families with higher thermal tolerance demonstrated less
Hsp
expression. This pattern may indicate that other mechanisms of heat tolerance, rather than heat shock, may underpin the stress response, and the costly production of HSPs may instead signal poor adaptation.

This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.
Mechanistic models to meet the challenge of climate change in plant–pathogen systems
Authors: Jiranek Juliana , Miller Ian F. , An Ruby , Bruns Emme , Metcalf C. Jessica E.
Published: February 2023

Evidence that climate change will impact the ecology and evolution of individual plant species is growing. However, little, as yet, is known about how climate change will affect interactions between plants and their pathogens. Climate drivers could affect the physiology, and thus demography, and ultimately evolutionary processes affecting both plant hosts and their pathogens. Because the impacts of climate drivers may operate in different directions at different scales of infection, and, furthermore, may be nonlinear, abstracting across these processes may mis-specify outcomes. Here, we use mechanistic models of plant–pathogen interactions to illustrate how counterintuitive outcomes are possible, and we introduce how such framing may contribute to understanding climate effects on plant–pathogen systems. We discuss the evidence-base derived from wild and agricultural plant–pathogen systems that could inform such models, specifically in the direction of estimates of physiological, demographic and evolutionary responses to climate change. We conclude by providing an overview of knowledge gaps and directions for future research in this important area.

This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.
Genome-wide analysis of genes involved in efflux function and regulation within Escherichia coli and Salmonella enterica serovar Typhimurium
Authors: Holden Emma R. , Yasir Muhammad , Turner A. Keith , Wain John , Charles Ian G. , Webber Mark A.
Published: February 2023

The incidence of multidrug-resistant bacteria is increasing globally, with efflux pumps being a fundamental platform limiting drug access and synergizing with other mechanisms of resistance. Increased expression of efflux pumps is a key feature of most cells that are resistant to multiple antibiotics. Whilst expression of efflux genes can confer benefits, production of complex efflux systems is energetically costly and the expression of efflux is highly regulated, with cells balancing benefits against costs. This study used TraDIS-Xpress, a genome-wide transposon mutagenesis technology, to identify genes in

Escherichia coli

and

Salmonella

Typhimurium involved in drug efflux and its regulation. We exposed mutant libraries to the canonical efflux substrate acriflavine in the presence and absence of the efflux inhibitor phenylalanine-arginine β-naphthylamide. Comparisons between conditions identified efflux-specific and drug-specific responses. Known efflux-associated genes were easily identified, including acrAB, tolC, marRA, ramRA and soxRS, confirming the specificity of the response. Further genes encoding cell envelope maintenance enzymes and products involved with stringent response activation, DNA housekeeping, respiration and glutathione biosynthesis were also identified as affecting efflux activity in both species. This demonstrates the deep relationship between efflux regulation and other cellular regulatory networks. We identified a conserved set of pathways crucial for efflux activity in these experimental conditions, which expands the list of genes known to impact on efflux efficacy. Responses in both species were similar and we propose that these common results represent a core set of genes likely to be relevant to efflux control across the Enterobacteriaceae.
Triptolide ameliorates renal tubulointerstitial fibrosis through EZH2
Authors: Wang Yanzhe , Jing Ying , Huang Di , Wu Ming , Ye Chaoyang
Published: February 2023

Renal fibrosis is the final pathological pathway of various kidney disease in progression to the end stage of renal failure. Recent studies showed that the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulator of renal fibrosis by promoting epithelial-mesenchymal transition (EMT) and activation of TGF-β/Smad3 signaling pathway in fibrotic kidneys. Triptolide is component extracted from radix tripterygium wilfordii, which provides renal benefits to patients with renal diseases in China. Recently, triptolide was identified as an inhibitor of EZH2. Thus, we hypothesized that triptolide inhibits renal fibrosis through EZH2. In this study, we found that triptolide reduced the deposition of extracellular matrix in the kidney of unilateral ureteral obstruction (UUO) mice. The anti-fibrotic effect of triptolide was further confirmed in TGF-β stimulated HK2 cells, a human renal epithelial cell line. Moreover, treatment of triptolide blocked the up-regulation of EZH2 in UUO kidneys and reduced the expression of EZH2 in TGF-β stimulated HK2 cells. Down-regulation of EZH2 by triptolide was correlated with reduced expression of EMT markers and phosphorylation of Smad3 in UUO kidneys and TGF-β stimulated HK2 cells. Finally, we showed that inhibition of EZH2 by 3-DZNep attenuated the inhibitory effect of triptolide on the expression of extracellular matrix protein, EMT markers and activation of Smad3 in TGF-β stimulated HK2 cells.

In conclusion, triptolide inhibits renal tubulointerstitial fibrosis through EZH2 in obstructive kidneys.