bluuebunny/crossref_metadata_2025 huggingface dataset:
Update on follicular lymphoma
Authors: Friedberg Jonathan W.
Published: June 2023

The past two decades have seen remarkable progress in both biological understanding and optimizing treatment of follicular lymphoma. Historically considered an incurable disease, long‐term follow‐up of several induction approaches demonstrates that up to 40% of patients enjoy remission durations of 10 or more years, and risk of dying of lymphoma continues to fall. This update will focus on progress in follicular lymphoma over the past 3 years, which has included refinements in staging and prognosis, novel immunotherapy treatment approaches for relapsed and refractory disease, and long‐term follow‐up of pivotal trials. Ongoing trials will define the optimal sequence for these novel treatments, including whether earlier incorporation of these approaches may result in definitive cure of this disease. Through ongoing and planned correlative studies, we are poised to ultimately achieve the goal of a precision management approach to follicular lymphoma.
Mantle cell lymphoma—Update on molecular biology, prognostication and treatment approaches
Authors: Silkenstedt Elisabeth , Dreyling Martin
Published: June 2023

Mantle cell lymphoma (MCL) is clinically characterized by its heterogenous behavior with courses ranging from indolent cases that do not require therapy for years to highly aggressive MCL with very limited prognosis. The development and implementation of new targeted and immunotherapeutic approaches have already improved therapeutic options especially for refractory or relapsed disease. Nevertheless, to further optimize MCL treatment, early identification of individual risk profile and risk‐adapted, patient‐tailored choice of therapeutic strategy needs to be prospectively incorporated in clinical patient management. This review summarizes the current knowledge and standard of care regarding biology and clinical management of MCL, highlighting the implementation of new therapeutic approaches especially targeting the immune system.
The evolving therapy of DLBCL: Bispecific antibodies
Authors: Hutchings Martin
Published: June 2023

Bispecific antibodies have been successfully introduced into the management of relapsed or refractory B‐cell lymphomas, including DLBCL. Phase 1 studies of the different CD3/CD20 bispecifics have shown manageable safety profile and promising activity in a range of B‐cell lymphomas, and recent phase 2 studies confirm the favourable safety and show frequent and durable complete responses even in heavily pre‐treated and high‐risk patients. This paper discusses the future potential role of these new agents as single agents and in combinations, and their position in the current and future treatment landscape, also in relation to chimeric antigen receptor T‐cell therapy.
Patients' preference regarding inpatient versus outpatient setting ‐ A systematic review
Authors: Schneeberger Andres R. , Werthmueller Sarah , Barco Santiago , Heuss Sabina C.
Published: June 2023

Objectives

Continuously rising healthcare costs have led to financial pressure on the healthcare systems. One of the trends for the reduction of costs is the shift towards outpatient treatment. However, research has not focused on the patients' preferences regarding inpatient versus outpatient treatment settings. The purpose of this review is to examine existing studies surveying patients' preferences related to inpatient and outpatient treatment methods. The aim is to find out whether patients' wishes were queried and considered in the decision‐making process.

Design

Therefore, the reviewers performed a systematic approach utilizing the PRISMA standards and screened 1′646 articles out of 5′606 articles from the systematic search.

Results and Conclusion

The screening resulted in 4 studies that analyzed exclusively the patient's choice of treatment setting. The search showed an apparent paucity of current literature and highlights the need for further research. The authors' recommendation includes a better involvement of patients in the decision‐making process as well as adding preferred treatment settings to advanced treatment directives and patient satisfaction questionnaires.
Liposomal delivery system/adjuvant for tuberculosis vaccine
Authors: Moradi Melika , Vahedi Farzaneh , Abbassioun Arian , Ramezanpour Shahi Arash , Sholeh Mohammad , Taheri‐Anganeh Mortaza , Dargahi Zahra , Ghanavati Roya , Khatami Seyyed Hossein , Movahedpour Ahmad
Published: June 2023

As reported by the World Health Organization, about 10 million individuals were infected with tuberculosis (TB) worldwide. Moreover, approximately 1.5 million people died of TB, of which 214,000 were infected with HIV simultaneously. Due to the high infection rate, the need for effective TB vaccination is highly felt. Until now, various methodologies have been proposed for the development of a protein subunit vaccine for TB. These vaccines have shown higher protection than other vaccines, particularly the Bacillus culture vaccine. The delivery system and safety regulator are common characteristics of effective adjuvants in TB vaccines and the clinical trial stage. The present study investigates the current state of TB adjuvant research focusing on the liposomal adjuvant system. Based on our findings, the liposomal system is a safe and efficient adjuvant from nanosize to microsize for vaccinations against TB, other intracellular infections, and malignancies. Clinical studies can provide valuable feedback for developing novel TB adjuvants, which ultimately enhance the impact of adjuvants on next‐generation TB vaccines.
China special issue on gastrointestinal tumors‐Improved survival after multidisciplinary team decision for patients with advanced gastrointestinal cancer: A multicenter, noninterventional, controlled study
Authors: Zhang Qi , Zhou Ye , Song Lijie , Fang Weijia , Qiu Meng , Gu Yanhong , Yang Yang , Zhang Jingdong , Liu Jing , Li Jian , Lu Ming , Gong Tianxiao , Wang Xin , Li Yan , Yang Jun , Ye Yingjiang , Shen Lin
Published: June 2023

Formal multidisciplinary team (MDT) discussions in clinical practice require time and space but have unclear survival benefits for advanced gastrointestinal cancer patients. Our study aimed to investigate the long‐term survival of patients with advanced gastrointestinal cancer after MDT decision. From June 2017 to June 2019, continuous MDT discussions on advanced gastrointestinal cancer were conducted in 13 medical centers in China. MDT decisions and actual treatment received by patients were prospectively recorded. The primary endpoint was the difference in overall survival (OS) between patients in the MDT decision implementation and nonimplementation groups. The secondary endpoints included the implementation rate of MDT decisions and subgroup survival analysis. A total of 461 MDT decisions of 455 patients were included in our study. The implementation rate of MDT decisions was 85.7%. Previous treatment had an impact on MDT decision‐making. The OS was 24.0 months and 17.0 months in the implementation and nonimplementation groups, respectively. The implementation of MDT decisions significantly reduced the risk of death in multivariate analyses (hazard ratio = 0.518; 95% confidence interval: 0.304‐0.884, P = .016). Subgroup analysis showed a significant difference in survival of patients with colorectal cancer, but not in survival of patients with gastric cancer. The rate of secondary MDT discussion was only 5.6% among patients who the MDT decisions were discontinued due to changes in their condition. MDT discussion can prolong the OS of patients with advanced gastrointestinal cancer, especially those with colorectal cancer. Timely scheduling of the subsequent MDT discussion is necessary when the disease condition changes.
Cannabinoid receptor type 1 regulates sequential stages of migration and morphogenesis of neural crest cells and derivatives in chicken and frog embryos
Authors: Mahomed Amira , Girn Daljit , Pattani Afrin , Wells Brian K. , King Chloe C. , Patel Sonya , Kaur Harsimran , Noravian Christina M. , Sieminski Jessica , Pham Chi , Dante Halley , Ezin Max , Elul Tamira
Published: June 2023

The main cannabinoid receptor CB1R first shows expression during early neurula stage in chicken (Gallus gallus) embryos, and at early tailbud stage in the frog (Xenopus laevis) embryos. This raises the question of whether CB1R regulates similar or distinct processes during the embryonic development of these two species. Here, we examined whether CB1R influences the migration and morphogenesis of neural crest cells and derivatives in both chicken and frog embryos. Early neurula stage chicken embryos were exposed to arachidonyl‐2ʹ‐chloroethylamide (ACEA; a CB1R agonist), N‐(Piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide (AM251; a CB1R inverse agonist) or Blebbistatin (nonmuscle Myosin II inhibitor) in ovo and examined during migration of neural crest cells and at condensing cranial ganglia stage. Early tailbud stage frog embryos were bathed in ACEA, AM251 or Blebbistatin, and analyzed at late tailbud stage for changes in craniofacial and eye morphogenesis, and in patterning and morphology of melanophores (neural crest‐derived pigment cells). In chicken embryos exposed to ACEA and Myosin II inhibitor, cranial neural crest cells migrated erratically from the neural tube, and the right, but not the left, ophthalmic nerve of the trigeminal ganglia was affected in ACEA‐ and AM251‐treated embryos. In frog embryos with inactivation or activation of CB1R, or inhibition of Myosin II, the craniofacial and eye regions were smaller and/or less developed, and the melanophores overlying the posterior midbrain were more dense, and stellate in morphology, than the same tissues and cells in control embryos. This data suggests that despite differences in the time of onset of expression, normal activity of CB1R is required for sequential steps in migration and morphogenesis of neural crest cells and derivatives in both chicken and frog embryos. In addition, CB1R may signal through Myosin II to regulate migration and morphogenesis of neural crest cells and derivatives in chicken and frog embryos.
Patellofemoral joint geometry and osteoarthritis features 3–10 years after knee injury compared with uninjured knees
Authors: Macri Erin M. , Whittaker Jackie L. , Toomey Clodagh M. , Jaremko Jacob L. , Galarneau Jean‐Michel , Ronsky Janet L. , Kuntze Gregor , Emery Carolyn A.
Published: June 2023

In this cross‐sectional study, we compared patellofemoral geometry in individuals with a youth‐sport‐related intra‐articular knee injury to uninjured individuals, and the association between patellofemoral geometry and magnetic resonance imaging (MRI)‐defined osteoarthritis (OA) features. In the Youth Prevention of Early OA (PrE‐OA) cohort, we assessed 10 patellofemoral geometry measures in individuals 3–10 years following injury compared with uninjured individuals of similar age, sex, and sport, using mixed effects linear regression. We also dichotomized geometry to identify extreme (>1.96 standard deviations) features and assessed likelihood of having extreme values using Poisson regression. Finally, we evaluated the associations between patellofemoral geometry with MRI‐defined OA features using restricted cubic spline regression. Mean patellofemoral geometry did not differ substantially between groups. However, compared with uninjured individuals, injured individuals were more likely to have extremely large sulcus angle (prevalence ratio [PR] 3.9 [95% confidence interval, CI: 2.3, 6.6]), and shallow lateral trochlear inclination (PR 4.3 (1.1, 17.9)) and trochlear depth (PR 5.3 (1.6, 17.4)). In both groups, high bisect offset (PR 1.7 [1.3, 2.1]) and sulcus angle (PR 4.0 [2.3, 7.0]) were associated with cartilage lesion, and most geometry measures were associated with at least one structural feature, especially cartilage lesions and osteophytes. We observed no interaction between geometry and injury. Certain patellofemoral geometry features are correlated with higher prevalence of structural lesions compared with injury alone, 3–10 years following knee injury. Hypotheses generated in this study, once further evaluated, could contribute to identifying higher‐risk individuals who may benefit from targeted treatment aimed at preventing posttraumatic OA.
Compensation strategy of shoulder synergist muscles is not stereotypical in patients with rotator cuff repair
Authors: Umehara Jun , Yagi Masahide , Ueda Yasuyuki , Nojiri Shusuke , Kobayashi Kotono , Tachibana Takashi , Nobuhara Katsuya , Ichihashi Noriaki
Published: June 2023

Rotator cuff tear is a common shoulder injury that causes shoulder dysfunction and pain. Although surgical repair is the primary treatment for rotator cuff tear, it is well recognized that impaired force exertion of muscles connecting to the involved tendon and subsequent complemental change in the force exertion of synergist muscles persist even after repair. This study aimed to identify the compensation strategy of shoulder abductors by examining how synergist muscles respond to supraspinatus (SSP) muscle force deficit in patients with rotator cuff repair. Muscle shear modulus, an index of muscle force, was assessed for SSP, infraspinatus, upper trapezius, and middle deltoid muscles in repaired and contralateral control shoulders of 15 patients with unilateral tendon repair of the SSP muscle using ultrasound shear wave elastography while the patients passively or actively held their arm in shoulder abduction. In the repaired shoulder, the shear modulus of the SSP muscle declined, whereas that of other synergist muscles did not differ relative to that of the control. To find the association between the affected SSP and each of the synergist muscles, a regression analysis was used to assess the shear moduli at the population level. However, no association was observed between them. At the individual level, there was a tendency of variation among patients with regard to a specific muscle whose shear modulus complementarily increased. These results suggest that the compensation strategy for SSP muscle force deficit varies among individuals, being nonstereotypical in patients with rotator cuff injury.
Prognostic indicators for colorectal peritoneal metastases are different for patients with complete versus incomplete cytoreductive surgery
Authors: Ghabra Shadin , Chang David , Sugarbaker Paul H.
Published: June 2023

Background

In the management of peritoneal metastases in patients with colorectal cancer, the completeness of cytoreduction has consistently been the most prominent prognostic indicator. Other clinical and histologic features have been described that may also have an impact on survival.

Methods

The colorectal peritoneal metastases patients treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy were divided into two groups. One group had complete CRS and the second group had an incomplete CRS. The prognostic variables in these two groups of patients were statistically analyzed for their impact on survival.

Results

In the complete CRS group of 124 patients lymph node positivity, poorly differentiated histopathology, asymptomatic status following treatment with systemic chemotherapy, incomplete response to systemic chemotherapy, and moderate to high peritoneal cancer index showed a significantly reduced survival. All five of these prognostic variables ceased to show statistical significance in the group of 82 patients with incomplete cytoreduction.

Conclusion

The cause for significance of five prognostic indicators identified in patients with complete cytoreduction versus loss of significance of these indicators in patients with incomplete cytoreduction has not been determined. An absence of residual disease in complete CRS patients and a widely variable extent of residual disease in incomplete CRS patients may be important. Prognostic indicators in patients with colorectal peritoneal metastases find their greatest usefulness in patients who have had a complete cytoreduction.
Thyroarytenoid Oxidative Metabolism and Synaptic Signaling Dysregulation in the Female Pink1−/− Rat
Authors: Barnett David G. S. , Lechner Sarah A. , Gammie Stephen C. , Kelm‐Nelson Cynthia A.
Published: June 2023

Objectives and hypothesis

Vocal dysfunction, including hypophonia, in Parkinson disease (PD) manifests in the prodromal period and significantly impacts an individual's quality of life. Data from human studies suggest that pathology leading to vocal deficits may be structurally related to the larynx and its function. The Pink1−/− rat is a translational model used to study pathogenesis in the context of early‐stage mitochondrial dysfunction. The primary objective of this work was to identify differentially expressed genes in the thyroarytenoid muscle and examine the dysregulated biological pathways in the female rat.

Methods

RNA sequencing was used to determine thyroarytenoid (TA) muscle gene expression in adult female Pink1−/− rats compared with controls. A bioinformatic approach and the ENRICHR gene analysis tool were used to compare the sequencing dataset with biological pathways and processes, disease relationships, and drug‐repurposing compounds. Weighted Gene Co‐expression Network Analysis was used to construct biological network modules. The data were compared with a previously published dataset in male rats.

Results

Significant upregulated pathways in female Pink1−/− rats included fatty acid oxidation and muscle contraction, synaptic transmission, and neuromuscular processes. Downregulated pathways included anterograde transsynaptic signaling, chemical synaptic transmission, and ion release. Several drug treatment options including cetuximab, fluoxetine, and resveratrol are hypothesized to reverse observed genetic dysregulation.

Conclusions

Data presented here are useful for identifying biological pathways that may underlie the mechanisms of peripheral dysfunction including neuromuscular synaptic transmission to the TA muscle. These experimental biomarkers have the potential to be targeted as sites for improving the treatment for hypophonia in early‐stage PD.

Level of Evidence

NA Laryngoscope, 133:3412–3421, 2023
Exogene und endogene Einflussfaktoren auf die Bildung von Acrylamid‐Expositionsbiomarkern
Authors: Goerke Katharina , Richling Elke
Published: June 2023

Acrylamid ist eine α,β‐ungesättigte Carbonylverbindung, die beim Erhitzen von Lebensmitteln durch die Maillard‐Reaktion aus Aminosäuren wie Asparagin und reduzierenden Zuckern gebildet wird. Da für diese prozessbedingte Lebensmittelkontaminante neuro‐ und gentoxische Effekte beschrieben sind und die mittlere alimentäre Exposition in Europa auf 0,4‐1,9 μg/kg KG/d geschätzt wurde, ist Acrylamid von Bedeutung für die Risikobewertung von Lebensmitteln.

Acrylamid und sein gentoxischer Metabolit Glycidamid werden zu den Mercaptursäuren N‐Acetyl‐5‐ (2‐carbamoylethyl)‐L‐cystein (AAMA) bzw. N‐Acetyl‐5‐(2‐hydroxy‐2‐carbamoylethyl)‐L‐cystein (GAMA) metabolisiert, die als renale Biomarker zur Abschätzung der internen Exposition Verwendung finden. Frühere Befunde deuteten bereits auf eine potentielle endogene Bildung hin, die einer AcrylamidExposition von 0,2‐0,7 μg/kg KG entsprach und somit nennenswert zur Biomarker‐Ausscheidung beitragen kann, die exogen durch Acrylamid‐Aufnahme durch Lebensmittel, Tabakrauch oder Exposition am Arbeitsplatz beeinflusst werden kann. Um diese verschiedenen Einflussfaktoren weiter zu untersuchen, wurden zwei Humanstudien durchgeführt.

Im Rahmen einer Duplikat‐Studie unter streng kontrollierten Bedingungen wurde die Toxikokinetik der Mercaptursäuren und Hämoglobin‐Addukte nach Acrylamid‐Aufnahme durch den Verzehr von Kaffee (0,15‐0,17 μg/kg KG/d) bzw. hitzebehandelten Lebensmitteln (14,1‐15,9 μg/kg KG/d) in sechs Probanden untersucht. Während der Kaffeekonsum nur zu einer leicht erhöhten Mercaptursäure‐ Antwort führte, konnte die renale Ausscheidungskinetik nach Aufnahme von 14,1‐15,9 μg/kg KG/d Acrylamid erfasst werden. Weitere sechs Probanden erhielten eine Acrylamid‐minimierte Diät, die eine Acrylamid‐Aufnahme von 0,05‐0,06 μg/kg KG/d nicht überschritt (Washout), und zusätzlich einen einmaligen Bolus von 1 μg/kg KG isCsDs‐Acrylamid. Am Ende des 13‐tägigen Washout wurde ein AAMA‐ Level erfasst, das einer Hintergrundbelastung von 0,3‐0,4 μg/kg KG/d entsprach, während die Ausscheidung von 13C3D3‐Acrylamid als 13C3D3‐AAMA innerhalb von 72‐96 h praktisch abgeschlossen war, welches die Hypothese einer anhaltenden endogenen Acrylamid‐Bildung in vivo unterstützt. Dies wurde durch Modell‐Reaktionen untermauert, die eine Acrylamid‐Bildung unter physiologischen Bedingungen zeigten.

Eine zweite Duplikat‐Studie mit Gemischtköstlern und Veganern befasste sich mit dem Einfluss der Ernährung und Lebensstils auf die Acrylamid‐Exposition und Ausscheidung von AAMA, GAMA sowie Tabakrauch‐Expositionsbiomarkern. Die mittlere Acrylamid‐Aufnahme betrug 0,32±0,19 μg/kg KG/d, es zeigten sich jedoch deutliche Variabilitäten zwischen den Tagen und den Probanden. So nahmen Veganer mehr Acrylamid auf (0,38±0,23 μg/kg KG/d) als Gemischtköstler (0,26±0,10 μg/kg KG/d). Die Ausscheidungskinetik von AAMA und GAMA im Urin stimmte im Wesentlichen mit der jeweiligen alimentären Acrylamid‐Aufnahme überein. Erhöhte Werte konnten auf eine umwelt‐bezogene Belastung mit Tabakrauch zurückgeführt werden.
Assessing the concern for airway complications introduced by Wendler's glottoplasty
Authors: Root Zachary T. , Loomis Bradley D. , Smith Thomas J. , Matrka Laura A.
Published: June 2023

Objective

Wendler's glottoplasty (WG) is a pitch‐elevating surgery performed by laryngologists providing gender‐affirming care. The surgery creates an anterior glottic web that could theoretically cause airway concerns, either perioperatively or at the time of future procedures; such concerns are not well‐described in the literature. We seek to assess surgeon opinions on airway concerns regarding WG.

Method

A survey of laryngologists assessing opinions on airway considerations in glottoplasty.

Results

A total of 19 physicians responded, representing approximately 193 surgeries. 52.6% performed glottoplasty and the remainder responded based on experience with anterior glottic webs. Two perioperative airway complications were reported, both mild stridor that did not prevent same‐day discharge. No long‐term sequela was reported. All surveyed laryngologists endorsed an altered general anesthetic approach for future procedures, with 73.7% advocating for use of a smaller endotracheal tube. 72.2% did not have “major concerns” about future intubations, and only 5.3% thought the immediate risk of airway compromise was a “real concern.” 91.9% counsel their patients routinely but briefly on airway concerns. Open‐ended comments conveyed themes of concern for post‐operative disruption of the web more than of airway compromise.

Conclusion

Because glottoplasty is performed in the anterior glottis and does not significantly impact airway patency, the risk of serious airway complications appears to be minimal. Laryngologists believe future intubations require a modified approach with a smaller tube, partly due to concern for glottic web trauma. Based on this pilot study, the topic deserves greater work to standardize care and anesthetic alterations for patients with WG.

Level of Evidence

5
Largest comparative analysis: Novel large spot size 595 nm, high‐energy, pulsed dye laser reduces number of treatments for improvement of adult and pediatric port wine birthmarks
Authors: Sodha Pooja , Wang Jordan V. , Aboul‐Fettouh Nader , Martin Katherine , Geronemus Roy G. , Friedman Paul M.
Published: June 2023

Objective

Port wine birthmarks (PWBs) are vascular malformations affecting 0.3%–0.5% of newborns with the tendency to persist into adulthood without adequate treatment of the heterogenous ectatic vessels. This study compares treatment outcomes and parameters of the prior generation pulsed dye laser (PPDL) and the larger spot novel generation pulsed dye laser (NPDL) to establish whether a larger spot size laser provides greater clearance with fewer treatments.

Methods

One hundred and sixty patients were treated with either the PPDL (80 patients) and NPDL (80 patients) with retrospective review of age, body site, laser treatment parameters, number of treatments, and improvement following laser therapy.

Results

Patients treated with PPDL were older on average than patients treated with NPDL (mean 24.8 ± 19.7 vs. mean 17.1± 19.3 years, p < 0.05). The majority of lesions treated with PPDL were located on the face and neck, whereas truncal and extremity sites were more frequently treated with the NPDL. Use of NPDL was associated with a mean maximum spot size of 13.1 mm and mean maximum fluence of 7.3 J/cm2 with pulse durations of 0.45–3 ms, whereas use of the PPDL was associated with a mean spot size of 10.8 mm and mean maximum fluence of 8.8 J/cm2 with pulse durations of 0.45–6 ms. Fifty percent improvement was seen with 8.8 PPDL treatments compared to 4.3 NPDL treatments (p ≤ 0.01) with no significant difference in overall mean improvement between both devices at the chosen parameters. Multiple regression analysis showed that device type, not age or lesion location, was the only statistically significant independent variable to affect the endpoint of at least 50% improvement of the lesion.

Conclusions

Use of the larger spot NPDL is associated with achieving 50% improvement with fewer treatments.
Mitochondria Targeted Nanoparticles Potentiate Tumor Chemo‐Phototherapy by Toxic Oxidative Stress Mediated Oxeiptosis
Authors: Lu Zhuoting , Li Jingyu , Chen Baohong , Feng Jiayu , Hu Qinglian , Jin Yuanxiang , Fu Zhengwei
Published: June 2023

Insufficient accumulation of drug at the tumor site and the low drug response are the main reason for the unsatisfactory effect of cancer therapy. Delivery drugs exquisitely to subcellular level can be employed to reduce side effects, and expand the therapeutic window. Herein, a triphenylphosphine (TPP) modified lipid nanoparticles is designed which are loaded with the photosensitizer indocyanine green (ICG) and chemotherapeutic paclitaxel (PTX) for mitochondria‐targeted chemo‐phototherapy. Owing to the movement of majority mitochondria along microtubules in cytoplasm, mitochondrial targeting may enable PTX to act more effectively. Meanwhile, the existence of chemo‐drug potentiates the phototherapy to achieve synergistic anti‐tumor activity. As expected, mitochondria targeting nanomedicine (M‐ICG‐PTX NPs) showed improved mitochondria targeted cellular distribution and enhanced cell cytotoxicity in vitro. Also, M‐ICG‐PTX NPs exhibited higher tumor growth inhibition ability by promoting cell apoptosis and oxeiptosis pathway, and high effective inhibition of primary tumor growth and tumor metastasis. Taken together, M‐ICG‐PTX NPs may be promising nanoplatforms to achieve potent therapeutic effect for the combination of chemo‐ and photo‐therapy (PTT).
Social credit and corporate leverage: Evidence from a natural experiment in China
Authors: Sun Nan , Tao Yunqing , Leng Xuan , Li Jiaxuan
Published: June 2023

The rapid growth of leverage is one of the risk factors for China's economy. To explore social credit's impact on corporate leverage's growth rate, we conduct the staggered difference‐in‐difference (DID) approach based on a quasi‐natural experiment of the social credit system reform. Our findings indicate that social credit significantly suppresses the growth rate of corporate leverage, which remains robust after some robustness checks. In addition, this effect can be attributed to alleviating agency costs and information asymmetry. Finally, our analysis reveals that the above effects are significant only for firms with poor corporate governance, high bankruptcy risk, low investment efficiency, and a low proportion of tangible assets. In summary, our study provides micro‐level evidence on the economic consequences of social credit system reform in China and policy insights on how the government can effectively control the growth rate of corporate leverage to prevent risk.
‘Year of Mental Health’ in danger of going unrealized in Wisconsin
Authors: Enos Gary
Published: June 2023

Wisconsin Gov. Tony Evers set a high bar for mental health‐related initiatives earlier this year when he declared that 2023 would be the Year of Mental Health in the state. But with just a couple of weeks to go before a new budget year is scheduled to begin, significant concern remains that much of the governor's vision for mental health services will go unrealized.
Dielectric, AC conductivity, and complex impedance spectroscopy studies of Ti2CTx MXene reinforced polyvinyl alcohol nanocomposites
Authors: Panda Subhasree , Deshmukh Kalim , Pasha S. K. Khadheer
Published: June 2023

Herein, Ti2CTx MXene‐Polyvinyl alcohol (PVA)  nanocomposite films with different weight percent (wt%) of MXene loadings were successfully prepared using the facile solution casting method. The structural, morphological, optical, thermal, and tensile properties of the nanocomposite films were analyzed using FTIR, XRD, Raman, SEM, UV–Vis spectroscopy, TG‐DTA, mechanical tests, and so forth. The variation in dielectric constant, loss tangent, and AC conductivity of the nanocomposite films was analyzed in the range of 1 Hz to 10 MHz with the variation of temperature (30–150°C) and MXene concentrations (5–20 wt%) using impedance spectroscopy. The nanocomposite films showed a very high dielectric constant in the range of ~105 for lower frequency and very low dielectric loss in the range of 0–1 for higher frequency (100 kHz–10 MHz). The dielectric constant, loss tangent, and AC conductivity values increased at a certain temperature and further decreased with increase in temperature. The increase in filler concentration increased the values of these investigated electrical parameters but at a concentration of 20 wt%, the nanocomposite films reached the percolation limit, and hence a slight reduction in the dielectric properties was noticed. Moreover, the complex impedance spectroscopy studies of the nanocomposite films were also carried out and their corresponding circuit diagrams were fitted according to the obtained cole‐cole plots.
Extracellular vesicles arising from apoptosis: forms, functions, and applications
Authors: Gregory Christopher D , Rimmer Michael P
Published: June 2023

Extracellular vesicles (EVs) are lipid bilayer‐enclosed subcellular bodies produced by most, if not all cells. Research over the last two decades has recognised the importance of EVs in intercellular communication and horizontal transfer of biological material. EVs range in diameter from tens of nanometres up to several micrometres and are able to transfer a spectrum of biologically active cargoes – from whole organelles, through macromolecules including nucleic acids and proteins, to metabolites and small molecules – from their cells of origin to recipient cells, which may consequently become physiologically or pathologically altered. Based on their modes of biogenesis, the most renowned EV classes are (1) microvesicles, (2) exosomes (both produced by healthy cells), and (3) EVs from cells undergoing regulated death by apoptosis (ApoEVs). Microvesicles bud directly from the plasma membrane, while exosomes are derived from endosomal compartments. Current knowledge of the formation and functional properties of ApoEVs lags behind that of microvesicles and exosomes, but burgeoning evidence indicates that ApoEVs carry manifold cargoes, including mitochondria, ribosomes, DNA, RNAs, and proteins, and perform diverse functions in health and disease. Here we review this evidence, which demonstrates substantial diversity in the luminal and surface membrane cargoes of ApoEVs, permitted by their very broad size range (from around 50 nm to >5 μm; the larger often termed apoptotic bodies), strongly suggests their origins through both microvesicle‐ and exosome‐like biogenesis pathways, and indicates routes through which they interact with recipient cells. We discuss the capacity of ApoEVs to recycle cargoes and modulate inflammatory, immunological, and cell fate programmes in normal physiology and in pathological scenarios such as cancer and atherosclerosis. Finally, we provide a perspective on clinical applications of ApoEVs in diagnostics and therapeutics. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Selective serotonin reuptake inhibitors, post‐treatment sexual dysfunction and persistent genital arousal disorder: A systematic review
Authors: Tarchi Livio , Merola Giuseppe Pierpaolo , Baccaredda‐Boy Ottone , Arganini Francesca , Cassioli Emanuele , Rossi Eleonora , Maggi Mario , Baldwin David S. , Ricca Valdo , Castellini Giovanni
Published: June 2023

Purpose

Adverse effects of selective serotonin reuptake inhibitors (SSRIs) on sexual function have been an important area of research for many years. However, the duration of SSRI‐associated sexual adverse effects, and their possible persistence after treatment discontinuation, is still uncertain. The aims of the current systematic review were first to identify existing evidence of sexual dysfunction following SSRI discontinuation, and to provide an account of reported symptoms and proposed treatment options; and second, to establish whether current literature allows accurate estimates of the prevalence of such sexual dysfunction.

Methods

A systematic review was conducted on PubMed, Embase, and Google Scholar; papers with clinical data regarding patients with persistent sexual dysfunction after SSRI treatment suspension were included.

Results

Overall, two retrospective interventional studies, six observational studies and 11 case reports were judged eligible for inclusion. It was not possible to determine reliable estimates of prevalence. Similarly, a cause‐effect relationship between SSRI exposure and persistent sexual impairment could not be ascertained. Nonetheless, the potential for continued sexual disturbances despite discontinuation could not be entirely ruled out.

Conclusions

There is a need to investigate a possible dose–response relationship between SSRI exposure and persistent sexual adverse effects. Treatment options for persistent dysfunctions remain limited, but novel therapeutic approaches may be required in order to address an otherwise neglected need for sexual well‐being.
Modified lung ultrasound score for bronchopulmonary dysplasia predicts late respiratory outcomes in preterm infants
Authors: Shen Jieru , Du Yang , Sun Yinghua , Huang Xiangyuan , Zhou Jianguo , Chen Chao
Published: June 2023

Objective

Lung ultrasound (LUS) is a useful and radiation‐free diagnostic tool for predicting bronchopulmonary dysplasia, which is a risk factor for late respiratory disease. However, data on the relationship of LUS with late respiratory disease was scarce. This study aims to determine whether LUS is associated with late respiratory disease during early childhood.

Methods

This prospective cohort study enrolled preterm infants born before 32 weeks of gestation. LUS was performed at 36 weeks' postmenstrual age. The predictive values of a modified lung ultrasound (mLUS) score based on eight standard sections were assessed to predict late respiratory disease, defined as a physician diagnosis of bronchopulmonary dysplasia deterioration, asthma, reactive airway disease, bronchiolitis, pneumonia, or respiratory‐related hospitalization during the first 2 years of life.

Results

A total of 94 infants completed follow‐up, of whom 74.5% met the late respiratory disease criteria. The mLUS scores were significantly associated with late respiratory disease (adjusted odds ratio: 1.23, CI: 1.10–1.38, p < 0.001). The mLUS scores also well predicted late respiratory disease (AUC = 0.820, 95% CI: 0.733–0.907). These scores were superior to the classic lung ultrasound score (p = 0.02) and as accurate as the modified NICHD‐defined bronchopulmonary dysplasia classification (p = 0.91). A mLUS score ≥14 was the optimal cutoff point for predicting late respiratory disease.

Conclusion

The modified lung ultrasound score correlates significantly with late respiratory disease and well predicts it in preterm infants during the first 2 years of life.
Prevalence of tracheobronchomalacia is higher than previously reported in children with cystic fibrosis
Authors: Depiazzi Julie , Bourke Crystal , Stick Stephen , Withers Adelaide
Published: June 2023

Background

Tracheobronchomalacia (TBM) is estimated to be present in 1 in 2100 children. Previous reports suggest the prevalence is higher in children with cystic fibrosis (CF). This has clinical implications with potential to influence airway clearance and lung health.

Aim

To determine the prevalence and clinical associations of TBM in Western Australian children with CF.

Methods

Children with CF born between 2001 and 2016 were included. Operation reports from bronchoscopies performed until the age of 4 were retrospectively reviewed. Data were collected on the presence, persistence defined as a repeat diagnosis, and severity of TBM. Data on genotype, pancreatic status, and symptoms at CF diagnosis were extracted from the medical record. Associations between categorical variables were compared using χ2 and Fisher's exact test.

Results

Of 167 children (79 male), 68 (41%) were diagnosed with TBM at least once, with TBM persistent in 37 (22%) and severe in 31 (19%). TBM was significantly associated with pancreatic insufficiency (χ2 = 7.874, p < 0.05, odds ratio [OR] 3.4), delta F508 gene mutation (χ2 = 6.489, p < 0.05, OR 2.3), and a presentation of meconium ileus (χ2 = 8.615, p < 0.05, OR 5.0). Severe malacia was less likley in females (χ2 = 4.523, p < 0.05, OR 0.42) . No significant relationship was found with respiratory symptoms at the time of CF diagnosis (χ2 = 0.742, p = 0.39).

Conclusions

TBM was common in this group of children under the age of 4 with CF. A high index of suspicion for airway malacia should be considered in children with CF, particularly those who present with meconium ileus and have gastrointestinal symptoms at diagnosis.
A systematic review of southern rice black‐streaked dwarf virus in the age of omics
Authors: Wu Zilin , Luo Dan , Zhang Shanqi , Zhang Chun , Zhang Yong , Chen Moxian , Li Xiangyang
Published: June 2023

Southern rice black‐streaked dwarf virus (SRBSDV) is one of the most damaging rice viruses. The virus decreases rice quality and yield, and poses a serious threat to food security. From this perspective, this review performed a survey of published studies in recent years to understand the current status of SRBSDV and white‐backed planthopper (WBPH, Sogatella furcifera) transmission processes in rice. Recent studies have shown that the interactions between viral virulence proteins and rice susceptibility factors shape the transmission of SRBSDV. Moreover, the transmission of SRBSDV is influenced by the interactions between viral virulence proteins and S. furcifera susceptibility factors. This review focused on the molecular mechanisms of key genes or proteins associated with SRBSDV infection in rice via the S. furcifera vector, and the host defense response mechanisms against viral infection. A sustainable control strategy using RNAi was summarized to address this pest. Finally, we also present a model for screening anti‐SRBSDV inhibitors using viral proteins as targets. © 2023 Society of Chemical Industry.
Mode‐of‐action of the natural herbicide radulanin A as an inhibitor of photosystem II
Authors: Thuillier Simon , Viola Stefania , Lockett‐Walters Bruce , Nay Bastien , Bailleul Benjamin , Baudouin Emmanuel
Published: June 2023

BACKGROUND

Radulanin A is a natural 2,5‐dihydrobenzoxepin synthesized by several liverworts of the Radula genus. Breakthroughs in the total synthesis of radulanin A paved the way for the discovery of its phytotoxic activity. Nevertheless, its mode‐of‐action (MoA) has remained unknown so far and thus was investigated, in Arabidopsis thaliana.

RESULTS

Radulanin A phytotoxicity was associated with cell death and partially depended on light exposure. Photosynthesis measurements based on chlorophyll‐a fluorescence evidenced that radulanin A and a Radula chromene inhibited photosynthetic electron transport with IC50 of 95 and 100 μm, respectively. We established a strong correlation between inhibition of photosynthesis and phytotoxicity for a range of radulanin A analogs. Based on these data, we also determined that radulanin A phytotoxicity was abolished when the hydroxyl group was modified, and was modulated by the presence of the heterocycle and its aliphatic chain. Thermoluminescence studies highlighted that radulanin A targeted the QB site of the Photosystem II (PSII) with a similar MoA as 3‐(3,4‐dichloropheny)‐1,1‐dimethylurea (DCMU).

CONCLUSION

We establish that radulanin A targets PSII, expanding QB sites inhibitors to bibenzyl compounds. The identification of an easy‐to‐synthesize analog of radulanin A with similar MoA and efficiency might be useful for future herbicide development. © 2023 Society of Chemical Industry.
Exploring bilateral pneumothorax leading to a rare diagnosis in a young lady
Authors: Bandara Harshana , Madegedara Dushantha
Published: June 2023

Key message

Bilateral pneumothorax is a rare occurrence and vigilant clinical examination is mandatory to suspect that during the presentation. This case illustrates a young lady presented with bilateral pneumothorax, new identification of lung cysts and chylous pleural effusion leading to diagnosis of lymphangioleiomyomatosis.
Practical exponential stability of hybrid impulsive stochastic functional differential systems with delayed impulses
Authors: Yang Bo , Ma Weijun , Zheng Yuanshi
Published: June 2023

This paper is concerned with the problem of practical exponential stability for hybrid impulsive stochastic functional differential systems with delayed impulses, which comprise three classes of systems: the systems with unstable continuous stochastic dynamics and stable discrete dynamics, the systems with stable continuous stochastic dynamics and unstable discrete dynamics, and the systems where both the continuous stochastic dynamics and the discrete dynamics are stable. By using the Lyapunov‐Razumikhin approach, several new sufficient conditions for the practical exponential stability are established for each class of systems. It shows that the stabilizing and destabilizing delayed impulses that satisfy some conditions on their frequency and amplitude can stabilize the systems with unstable continuous stochastic dynamics in the practical exponential stability sense and ensure the practical exponential stability of the systems with stable continuous stochastic dynamics, respectively. Conversely, if the continuous stochastic dynamics are practically exponentially stable and the delayed impulses are stabilizing, then the systems can be practically exponentially stable regardless of the restrictions on the delayed impulses frequency and amplitude. Finally, two numerical examples are presented to illustrate the efficiency of the results.
The Impact of a Novel Digital Sun Protection Campaign on Sun-Related Attitudes and Behaviours of Healthcare Workers: A Prospective Observational Study
Authors: Porter Emma , Rafferty Siobhan , Dolan Michelle , McMahon David , Sheikhi Ali , Field Sinead , Power Evelyn
Published: June 2023

Background

13 000 cases of skin cancer are diagnosed annually in Ireland, with ultraviolet (UV) radiation exposure the strongest risk factor. Public health primary prevention campaigns focus on encouraging safe sun protective measures and skin cancer awareness. We designed a novel, digitally-animated hospital-based campaign targeting all aspects of sun-protective behaviour.

Objectives

To explore the sun-protective attitudes and behaviours of healthcare workers, and the effect of a digital hospital-based campaign on these findings.

Methods

This was a cross-sectional prospective observational study involving hospital staff across the six hospitals that form the University of Limerick Hospital Group (ULHG). A two-phase online survey, the first taking place before campaign launch, and the second upon campaign completion. The digital campaign was displayed across all hospital sites from June to September 2021. Surveys comprised questions on sun-related attitudes and behaviours, including the internationally validated Sun Exposure Protection Index (SEPI) questionnaire.

Results

Eight hundred fifty-seven staff members completed survey 1 and 704 completed survey 2; 90% in each were female; 79% were aged 25–54; 71% reported skin types I–III. Best sun-protective habits pre-campaign included sunscreen use and avoiding sunburn, while wearing hats, protective clothing and seeking shade were least adopted. For 177 matched participants, there were small improvements in SEPI scores. SEPI Part 1 scores, reflecting improved risk behaviour, pre-campaign had a median of 11 (IQR 7), and 11 (IQR 6) post campaign. SEPI Part 2 scores, reflecting readiness to adopt sun-protective behaviours, improved from median 7 (IQR 8) to 6 (IQR 6). Post-campaign, small improvements were seen across some individual sun-protective behaviours and attitudes, particularly reducing time spent in the midday sun and on sun-seeking holidays, and improved readiness to seek shade and reduce sunbathing; 79% of all respondents post-campaign (n = 556) reported raised skin cancer awareness, and 65% (n = 458) said it influenced them to discuss sun protection with others.

Conclusions

Positive improvements in attitudes and behaviours related to sun protection were seen following the digital campaign in this population of healthcare workers. These improvements along with increased willingness to discuss sun protection with others, including patients, has the potential to further benefit wider society, and supports future digital health promotion initiatives.
Efficient Synthesis of Highly Substituted N‐Arylamino quinolone‐based Pyrrolo[3,4‐b]pyridines and Pyrazolone‐based Pyrrolo[3,4‐b]pyridines Through a One‐Pot Three‐Component Reaction
Authors: Alizadeh Abdolali , Moterassed Reihaneh , Rostampoor Azar
Published: June 2023

In this research, a simple and efficient strategy for the straightforward synthesis of multisubstituted N‐arylamino quinolone‐based pyrrolo[3,4‐b]pyridine derivatives and pyrazolone‐based pyrrolo[3,4‐b]pyridine derivatives is presented by a sequential three‐component reaction of α‐aminomaleimides, 2‐chloroquinoline‐3‐carbaldehyde/5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde and malononitrile/ethyl 2‐cyanoacetate as readily available starting materials in EtOH at room temperature. The merit of this sequential Michael addition/intramolecular cyclization is highlighted by its high energy conserving (short reaction times at room temperature) excellent yields, metal‐free catalyst, and green and mild conditions in a one‐pot reaction. With this synthesis, group‐assistant‐purification (GAP) chemistry can be simplified by eliminating chromatography and recrystallization, and the pure products can be obtained by washing the crude products with 95 % ethanol. Their structures were characterized by spectroscopic data IR, MS, 1H, and 13C NMR analysis.
Fluorescent Carbon Dots Appended with Barbituric Acid for the Recognition of ATP in Living Plants in Aqueous Media: The Organic Precursor Sensing the Bisulfate Anion in Real Samples
Authors: Jindal Gitanjali , Kaur Navneet
Published: June 2023

Fabrication of fluorescent water‐soluble citric acid‐urea based carbon dots have been done using an organic pioneer possessing barbituric acid for the recognition of adenosine triphosphate (ATP). The carbon dots has been characterized through various techniques, such as, powder X‐ray diffraction (PXRD), Fourier‐transform infrared spectroscopy (FTIR), high‐resolution transmission electron microscopy (HRTEM), UV‐visible (UV‐vis), and Fluorescence (FL) spectroscopy. The emissive nature of carbon dots made them worthwhile for the detection of ATP in different plant samples, for instance, curry leaves, coriander, tulsi and jasmine flower leaves. Also, the barbituric acid precursor (1) has been successfully applied for the detection of bisulfate anion in real samples with good recovery. The absorption responses for bisulfate ion permitted it to be used as effective colorimetric sensor in water and the color changes have been scrutinized using smartphone application.