bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved immobilization of Re(VII) from aqueous solutions via bimetallic Ni/Fe0 nanoparticles: Implications towards Tc(VII) removal
Authors: Maamoun Ibrahim , Tokunaga Kohei , Dohi Terumi , Kanno Futoshi , Falyouna Omar , Eljamal Osama , Tanaka Kazuya
Published: March 2023

Introduction: In this work, bimetallic nickel/iron nanoparticles (Ni/Fe0) were prepared to enhance rhenium (Re(VII)) immobilization from aqueous solutions, as the surrogate of technetium (Tc(VII)).

Methods: Two synthesis approaches of Ni/Fe0, pre-, and post-nucleation, were investigated towards Re(VII) removal. Different characterization techniques were considered to elucidate the physicochemical features of the fresh and reacted materials, such as scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDX), X-ray diffraction (XRD), and X-ray absorption near edge spectroscopy (XANES). The influence of several reaction parameters on Re(VII) removal was investigated, including Ni/Fe0 ratio, dosage, initial pH, temperature, and initial concentration.

Results and discussion: Results showed a promising potential of Ni/Fe0, either pre- or post-nucleation synthesized, in Re(VII) removal, especially at the early stage of the reaction, where Ni/Fe0: 0.4 yielded almost full removal efficiency of initial 15.0 μM-Re(VII) within the first 10 min of reaction. Even at low Ni/Fe0 dosages, such as 0.25 and 0.5 g/L, reasonable removal efficiency was achieved after 2 h reaction time of ∼73% and ∼98%, respectively. Unlike acidic/neutral pH, alkaline conditions were not favorable for Re(VII) removal by Ni/Fe0 owing to the delayed aqueous corrosion of Fe0-core resulting in insufficiency of electrons available for Re(VII) reduction. The reductive abilities were confirmed by XANES, revealing Re(VII) reduction to Re(IV)/(III) by the released electrons from Fe0-core in both Fe0 and Ni/Fe0 materials. Pseudo-first- and second-order kinetic models were suitable to describe Re(VII) removal by Ni/Fe0, implying physical and/or chemical processes were involved. Zeta potential measurements depicted the point of zero charge (pHPZC) of Fe0 and Ni/Fe0 to be 8.24 and 7.63, respectively, suggesting the involvement of electrostatic sorption of ReO4− on the positively charged surface of Ni/Fe0. The occurrence of multi- and mono-layer sorption within Re(VII) removal process was implicated, following Freundlich and Sips isotherm models. The presence of Ni0/NiO on Fe0-surface resulted in providing an efficient electron-transfer medium that facilitated Re(VII) reduction, leading to impressive kinetic rates. Overall, our study provided valuable insights into the use of Ni/Fe0 for Re(VII) removal from water and offered guidance for future research in such an aspect towards the pilot-scale applications of Tc(VII) removal from nuclear wastewater.
Risk of malignancy in adrenal tumors in patients with a history of cancer
Authors: Samsel Radosław , Nowak Karolina , Papierska Lucyna , Karpeta Edyta , Roszkowska-Purska Katarzyna , Smiertka Wacław , Ostrowski Tomasz , Chrapowicki Eryk , Grabowski Alan , Leszczyńska Dorota , Cichocki Andrzej
Published: March 2023

Purpose

Adrenal gland is a common site of metastasis and on the other hand, metastases are the most frequent malignant adrenal tumors. The aim of this study was to estimate the risk of malignancy in suspicious adrenal mass in patients with a history of cancer.

Methods

This is a single-center retrospective analysis of patients with adrenal tumors treated previously for different types of cancers. Between 2004 and 2021 a hundred and six such patients were identified. Mean age of patients was 62.6 years (30-78), and mean time from oncologic treatment was 55.8 months (0-274). The most common primary cancer was kidney (RCC): 29 (27.4%), colon/rectum (CRC): 20 (18.9%) and lung (NSCLC): 20 (18.9%).

Results

Of 106 patients, 12 had hormonally active (HA) (11,3%) and 94 (88,7%) non active (HNA) tumors In group of patients with HA tumours 4 had hypercortisolaemia and 8 had elevation of urinary metanephrines. In the first group of HA patients pathology confirmed preoperative diagnosis of adrenocortical cancer and no metastasis was found. In all patients from the second group pheochromocytomas were confirmed. Primary (PM) and secondary (SM) malignancies were found in 50 patients (47.2%). In hormone inactive group only SM - 46/94 (48.9%) were diagnosed. The odds that adrenal lesion was a metastasis were higher if primary cancer was RCC (OR 4.29) and NSCLC (OR 12.3). Metastases were also more likely with high native tumor density, and bigger size in CT. The cut-off values for tumor size and native density calculated from receiver operating characteristic (ROC) curves were 37mm and 24, respectively.

Conclusion

Risk of malignancy of adrenal mass in a patient with a history of cancer is high (47,2%), regardless of hormonal status. 47,2% risk of malignancy. In preoperative assessment type of primary cancer, adrenal tumour size and native density on CT should be taken into consideration as predictive factors of malignancy. Native density exceeding 24 HU was the strongest risk factor of adrenal malignancy (RR 3.23), followed by history of lung or renal cancer (RR 2.82) and maximum tumor diameter over 37 mm (RR 2.14).
Extracorporeal membrane oxygenation in critical airway interventional therapy: A review
Authors: Wu Hongxia , Zhuo Kaiquan , Cheng Deyun
Published: March 2023

Introduction

Extracorporeal membrane oxygenation (ECMO) is widely used during refractory cardiac or respiratory failure, and some case reports described ECMO utilization in critical airway interventional therapy.

Methods

Eligible reports about patients receiving airway interventional therapy under ECMO were retrieved from Web of Science, Embase, Medline, and Cochrane databases up to 1 August 2022.

Results

Forty-eight publications including 107 patients who underwent ECMO for critical airway problems met the inclusion criteria. The critical airway problem that was reported the most was tumor-associated airway obstruction (n = 66, 61.7%). The second most reported etiology was postoperative airway collapse or stenosis (n = 19, 17.8%). The main interventional therapies applied were airway stent placement or removal (n = 61, 57.0%), mass removal (n = 22, 20.6%), and endotracheal intubation (n = 12, 11.2%) by bronchoscopy. The median ECMO duration was 39.5 hours. Eleven patients had ECMO-associated complications, including seven cases of airway hemorrhage, one case of arteriovenous fistula, one case of vein rupture and hematoma, one case of foot ischemia, and one case of neuropraxia of the cannulation site. In total, 91.6% of the patients survived and were discharged from the hospital.

Conclusion

ECMO appears to be a viable form of life support for patients undergoing interventional therapy for critical airway problems.
Clinical features and prognosis of pulmonary enteric adenocarcinoma: A retrospective study in China and the SEER database
Authors: Wang Qike , Zhang Lu , Li Huahua , Liu Linlin , Sun Xu , Liu Huaimin
Published: March 2023

Objective

Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of pulmonary adenocarcinoma that lacks effective treatment. The purpose of this research was to investigate the clinical characteristics, treatment, and prognosis of PEAC, as well as the impact of relevant factors on survival, thus providing a reference for the clinical management of patients with this disease.

Methods

For this study, we gathered clinical data from 26 patients with PEAC in the Affiliated Cancer Hospital of Zhengzhou University from June 2014 to June 2021. We used SEER*Stat software V8.3.5 to download the PEAC patients from the Surveillance, Epidemiology, and End Results (SEER) database. In total, 20 patients were identified. Clinical data, including general information, imaging findings, and treatment protocols, were obtained, together with a follow-up of disease regression. The relevant clinical data were then analyzed.

Results

It included 12 males and 14 females out of 26 patients from China, whose mean age was (62.73 ± 11.89) years; 20 were in the lower lung, 11 were stage I-II, and 15 were stage III-IV. Five had EGFR mutations, and four had KRAS mutations. In terms of treatment, patients with stage I-II were primarily treated by surgery, and patients with stage III-IV were treated mostly by chemotherapy. We extended the follow-up date to January 2022. On completion of the follow-up visit, 11 patients died, and the remaining 15 patients survived. The overall survival (OS) of 26 patients was 2.0-76.0 months, while the mean was 53.1 months, and the median OS (mOS) was 38.0 months (95% CI:1.727-74.273). In the case of progression-free survival (PFS) times, it was 2.0-76.0 months, with a mean PFS of 31.0 months and a median PFS (mPFS) of 8.0 months (95% CI:4.333-11.667). The PFS of the 15 patients in stage III-IV was 2.0-17 months, while the mean PFS was 6.5 months and the mPFS was 6.0 months (95% CI:4.512-7.488). Out of the 20 patients identified in the SEER database, the average age was 69.9 years, with 14 males and 6 females. Of these patients, 8 were diagnosed with stage I-II, while the remaining 11 were diagnosed with stage III-IV. 10 underwent surgery, 4 received radiation therapy, and 9 received chemotherapy. The mean OS of the 20 patients was 67.5 months, mOS was 28.0 months (95% CI: 9.664- 46.336). For patients diagnosed with stage III-IV, the mean OS was 14.8 months and mOS was 20 months (95% CI: 4.713-35.287).

Conclusion

PEAC is rare, and the prognosis is determined mainly by the stage; patients who undergo surgery in stage I-II have a better prognosis.
Towards targeted colorectal cancer biopsy based on tissue morphology assessment by compression optical coherence elastography
Authors: Plekhanov Anton A. , Sirotkina Marina A. , Gubarkova Ekaterina V. , Kiseleva Elena B. , Sovetsky Alexander A. , Karabut Maria M. , Zagainov Vladimir E. , Kuznetsov Sergey S. , Maslennikova Anna V. , Zagaynova Elena V. , Zaitsev Vladimir Y. , Gladkova Natalia D.
Published: March 2023

Identifying the precise topography of cancer for targeted biopsy in colonoscopic examination is a challenge in current diagnostic practice. For the first time we demonstrate the use of compression optical coherence elastography (C-OCE) technology as a new functional OCT modality for differentiating between cancerous and non-cancerous tissues in colon and detecting their morphological features on the basis of measurement of tissue elastic properties. The method uses pre-determined stiffness values (Young’s modulus) to distinguish between different morphological structures of normal (mucosa and submucosa), benign tumor (adenoma) and malignant tumor tissue (including cancer cells, gland-like structures, cribriform gland-like structures, stromal fibers, extracellular mucin). After analyzing in excess of fifty tissue samples, a threshold stiffness value of 520 kPa was suggested above which areas of colorectal cancer were detected invariably. A high Pearson correlation (r =0.98; p <0.05), and a negligible bias (0.22) by good agreement of the segmentation results of C-OCE and histological (reference standard) images was demonstrated, indicating the efficiency of C-OCE to identify the precise localization of colorectal cancer and the possibility to perform targeted biopsy. Furthermore, we demonstrated the ability of C-OCE to differentiate morphological subtypes of colorectal cancer – low-grade and high-grade colorectal adenocarcinomas, mucinous adenocarcinoma, and cribriform patterns. The obtained ex vivo results highlight prospects of C-OCE for high-level colon malignancy detection. The future endoscopic use of C-OCE will allow targeted biopsy sampling and simultaneous rapid analysis of the heterogeneous morphology of colon tumors.
Fibrinogen-to-prealbumin ratio: A new prognostic marker of resectable pancreatic cancer
Authors: Li Chengqing , Fan Zhiyao , Guo Wenyi , Liang Feng , Mao Xincheng , Wu Jiahao , Wang Haodong , Xu Jianwei , Wu Dong , Liu Han , Wang Lei , Li Feng
Published: March 2023

Background

The fibrinogen-to-prealbumin ratio (FPR), a novel immune-nutritional biomarker, has been reported to be associated with prognosis in several types of cancer, but the role of FPR in the prognosis of resectable pancreatic cancer has not been elucidated.

Methods

A total of 263 patients with resectable pancreatic cancer were enrolled in this study and were randomly divided into a training cohort (n = 146) and a validation cohort (n = 117). Receiver operating characteristic curve (ROC) was used to calculate the cut-off values of immune-nutritional markers. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were performed in the training cohort to identify the independent risk factors, based on which the nomogram was established. The performance of the nomogram was evaluated and validation by the training and validation cohort, respectively.

Results

The optimal cutoff value for FPR was 0.29. Multivariate analysis revealed that FPR, controlling nutritional status (CONUT), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and tumor node metastasis (TNM) stage were independent predictors of overall survival (OS). The nomogram was established by involving the five factors above. The C-index of the training cohort and validation cohort were 0.703 (95% CI: 0.0.646-0.761) and 0.728 (95% CI: 0.671-0.784). Decision curve analysis and time-dependent AUC showed that the nomogram had better predictive and discriminative ability than the conventional TNM stage.

Conclusion

FPR is a feasible biomarker for predicting prognosis in patients with resectable pancreatic cancer. The nomogram based on FPR is a useful tool for clinicians in making individualized treatment strategies and survival predictions.
Low HER2 expression is a predictor of poor prognosis in stage I triple-negative breast cancer
Authors: Sanomachi Tomomi , Okuma Hitomi Sumiyoshi , Kitadai Rui , Kawachi Asuka , Yazaki Shu , Tokura Momoko , Arakaki Motoko , Saito Ayumi , Kita Shosuke , Yamamoto Kasumi , Maejima Aiko , Kojima Yuki , Nishikawa Tadaaki , Sudo Kazuki , Shimoi Tatsunori , Noguchi Emi , Fujiwara Yasuhiro , Sugino Hirokazu , Shiino Sho , Suto Akihiko , Yoshida Masayuki , Yonemori Kan
Published: March 2023

Introduction

Triple-negative breast cancer (TNBC) is negative for hormone receptors and human epidermal growth factor receptor 2 (HER2). In stage I TNBC, adjuvant therapy or follow-up are performed according to risk factors, but clinical trial data is scarce. In recent years, it has been reported that HER2-low cases (1+/2+ and in situ hybridization negative) have different prognoses than HER2-0 cases. However, the risk of recurrence and risk factors in this HER2-low population for stage I TNBC have not yet been investigated.

Methods

Herein, out of 174 patients with TNBC who underwent surgery from June 2004 to December 2009 at the National Cancer Center Hospital (Tokyo), we retrospectively examined 42 cases diagnosed as T1N0M0 TNBC after excluding those treated with preoperative chemotherapy.

Results

All patients were female, the median age was 60.5 years, and 11 cases were HER2-low and 31 cases were HER2-0. The median follow-up period was 121 months. Postoperative adjuvant therapy was administered in 30 patients and recurrence occurred in 8 patients. HER2-low cases showed a significantly shorter disease-free survival (HR: 7.0; 95% CI: 1.2– 40.2; P=0.0016) and a trend towards shorter overall survival (hazard ratio [HR]: 4.2, 95% confidence interval [CI]: 0.58–31.4) compared with that of HER2-0 cases. HER2 was also identified as a factor for poor prognosis from the point- estimated values in univariate and multivariate analyses after confirming that there was no correlation between the other factors.

Conclusion

For patients with stage I TNBC, the HER2-low population had a significantly worse prognosis than the HER2-0 population.
MACC1-induced migration in tumors: Current state and perspective
Authors: Hohmann Tim , Hohmann Urszula , Dehghani Faramarz
Published: March 2023

Malignant tumors are still a global, heavy health burden. Many tumor types cannot be treated curatively, underlining the need for new treatment targets. In recent years, metastasis associated in colon cancer 1 (MACC1) was identified as a promising biomarker and drug target, as it is promoting tumor migration, initiation, proliferation, and others in a multitude of solid cancers. Here, we will summarize the current knowledge about MACC1-induced tumor cell migration with a special focus on the cytoskeletal and adhesive systems. In addition, a brief overview of several in vitro models used for the analysis of cell migration is given. In this context, we will point to issues with the currently most prevalent models used to study MACC1-dependent migration. Lastly, open questions about MACC1-dependent effects on tumor cell migration will be addressed.
Doing palliative care research on hematologic cancer patients: A realist synthesis of literature and experts’ opinion on what works, for whom and in what circumstances
Authors: Tanzi Silvia , Martucci Gianfranco
Published: March 2023

Background

Research in PC (Palliative Care) is frequently challenging for patient’s frailty, study design, professional misconceptions, and so on. Little is known about specificity in PC research on Hematologic cancer patients, who have distinct characteristics that might influence the enrollment process.

Aims

What works, how and for whom, in increasing enrollment in studies in PC on patients with hematologic malignancies?

Methods

Realist review: a qualitative review whose goal is to identify and explain the interaction between Contexts, Mechanisms, and Outcomes (CMOs). The theory was informed by a narrative, theory-based literature research, including an initialsystematic research, and the addition of papers suggested by experts of the field. We also used 7 interviews with experts in PC about patients with hematologic malignancies research and our own experience from a PC pilot study on patients with hematologic malignancies to refine the initial theory.

Results

In our initial theory we hypothesize that:

 - Access to palliative care could be beneficial to hematologic patients, even in early stages

 - Hematologists tend to under-use palliative care services in general, due to unpredictable disease trajectories and cultural barriers.

 - These factors may negatively impact the patients’ enrollment in PC research

We included secondary literature as narrative reviews, if they presented interesting propositions useful for our theoretical construction. 23 papers met our inclusion criteria.

We also searched for relevant CMOs impacting referral in palliative care, and we selected a list of CMOs that could be relevant also in hematology. We accordingly theorized a group of interventions that could increase the enrollment in PC research and presented them using “social exchange theory” (SET) as a theoretical framework.

Prominent researchers in PC in hematologic malignancies were interviewed on their opinion on our results, and additional CMOs.

Conclusions

Before conducting research in PC on patients with hematologic malignancies, it’s probably advisable to assess:

 - The perception of the different actors (physicians, nurses, other professionals involved), in particular the hematologists, in terms of pros and cons of referral to PC and enrollment in PC trials

 - The existing relationship between PC and the Hematology department

Accordingly, it’s possible to tailor different interventions on the various actors and choose a model of trial to increase the perception of benefits from PC and, consequently, enrollment.
Vaccination following the expanded programme on immunization schedule could help to reduce deaths in children under five hospitalized for pneumonia and severe pneumonia in a developing country
Authors: Shahid Abu Sadat Mohammed Sayeem Bin , Rahman Ahmed Ehsanur , Shahunja K. M. , Afroze Farzana , Sarmin Monira , Nuzhat Sharika , Alam Tahmina , Chowdhury Fahmida , Sultana Mst Shahin , Ackhter Mst Mahmuda , Parvin Irin , Saha Haimanti , Islam Shoeb Bin , Shahrin Lubaba , Ahmed Tahmeed , Chisti Mohammod Jobayer
Published: March 2023

Background

Worldwide, pneumonia is the leading cause of mortality in children under the age of five. An expanded program on immunization (EPI) is one kind of evidence-based tool for controlling and even eradicating infectious diseases.

Objectives

This study aimed to explore the impact of EPI vaccination, including BCG, DPT-Hib-Hep B, OPV, IPV, and PCV-10, among children from the age of 4 to 59 months hospitalized for pneumonia and severe pneumonia. Additionally, we evaluated the role of 10 valent pneumococcal conjugate vaccines alone on clinical outcomes in such children.

Methods

In this retrospective chart review, children from the age of 4 to 59 months with WHO-defined pneumonia and severe pneumonia admitted to the Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) between August 2013 and December 2017 who had the information on immunization as per EPI schedule by 4 months of age were included in the analysis. A comparison was made between the children who were fully immunized (immunization with BCG, DPT-Hib-Hep B, OPV, and IPV from 2013 to 2015 and PCV-10 from 2015 to 2017) and who were not immunized (consisting of partial immunization and no immunization) during the study period.

Results

A total of 4,625 children had pneumonia and severe pneumonia during the study period. Among them, 2,605 (56.3%) had received the information on immunization; 2,195 (84.3%) were fully immunized by 4 months of age according to the EPI schedule and 410 were not immunized. In the log-linear binomial regression analysis, immunization of children from 4 to 59 months of age was found to be associated with a lower risk of diarrhea (p = 0.033), severe pneumonia (p = 0.001), anemia (p = 0.026), and deaths (p = 0.035). Importantly, the risk of developing severe pneumonia (1054/1,570 [67%] vs. 202/257 [79%], p < 0.001) and case-fatality rate (57/1,570 [3.6%] vs. 19/257 [7.4%], p = 0.005) was still significantly lower among those who were immunized with PCV-10 than those who were not.

Conclusion

Children immunized as per the EPI schedule were at a lower risk of diarrhea, severe pneumonia, anemia, and death, compared to unvaccinated children. In addition, PCV-10 was found to be protective against severe pneumonia and deaths in vaccinated children. The overall results underscored the importance of the continuation of immunization, scrupulously adhering to the EPI schedule to reduce the risk of morbidities and mortalities in children, especially in resource-limited settings.
The tricuspid valve in hypoplastic left heart syndrome: Echocardiography provides insight into anatomy and function
Authors: Bharucha Tara , Viola Nicola
Published: March 2023

Tricuspid regurgitation (TR) is commonly seen in surgically palliated patients with hypoplastic left heart syndrome, and when significant, is associated with an increase in both morbidity and mortality. Tricuspid valve dysfunction appears to be the result of a combination of inherent structural malformations and the unique physiological circumstances resulting from right ventricular pressure and volume overload. Valve dysfunction evolves rapidly, and manifests early on in the surgical pathway. Whilst traditional echocardiographic imaging can identify anatomical defects and dysfunction resulting in varying degrees of regurgitation even at early stages, more sophisticated investigations such as 3D echocardiography, strain imaging and transesophageal 3DE might prove useful to better demonstrate the complex interactions between abnormal anatomy of the valve complex, ventricular function, mechanical synchrony, and TR. Recognition of specific mechanisms of TR can enhance patient-specific care by directing precise surgical interventions and by informing the best timing for intervention on the valve.
Living in a box: Understanding acoustic parameters in the NICU environment
Authors: Reuter Christoph , Bartha-Doering Lisa , Czedik-Eysenberg Isabella , Maeder Marcus , Bertsch Matthias A. , Bibl Katharina , Deindl Philipp , Berger Angelika , Giordano Vito
Published: March 2023

Background

In the last years, a significant body of scientific literature was dedicated to the noisy environment preterm-born infants experience during their admission to Neonatal Intensive Care Units (NICUs). Nonetheless, specific data on sound characteristics within and outside the incubator are missing. Therefore, this study aimed to shed light on noise level and sound characteristics within the incubator, considering the following domain: environmental noise, incubator handling, and respiratory support.

Methods

The study was performed at the Pediatric Simulation Center at the Medical University of Vienna. Evaluation of noise levels inside and outside the incubator was performed using current signal analysis libraries and toolboxes, and differences between dBA and dBSPL values for the same acoustic noises were investigated. Noise level results were furthermore classed within previously reported sound levels derived from a literature survey. In addition, sound characteristics were evaluated by means of more than 70 temporal, spectral, and modulatory timbre features.

Results

Our results show high noise levels related to various real-life situations within the NICU environment. Differences have been observed between A weighted (dBA) and unweighted (dBSPL) values for the same acoustic stimulus. Sonically, the incubator showed a dampening effect on sounds (less high frequency components, less brightness/sharpness, less roughness, and noisiness). However, a strong tonal booming component was noticeable, caused by the resonance inside the incubator cavity. Measurements and a numerical model identified a resonance of the incubator at 97 Hz and a reinforcement of the sound components in this range of up to 28 dB.

Conclusion

Sound characteristics, the strong low-frequency incubator resonance, and levels in dBSPL should be at the forefront of both the development and promotion of incubators when helping to preserve the hearing of premature infants.
Relentless placoid chorioretinitis: A review of four cases in pediatric and young adult patients with a discussion of therapeutic strategies
Authors: Zaheer Haniah A. , Odden Jamie , Gagrani Meghal , Zaguia Fatma , Lowder Careen , Coca Andreea , Rosenkranz Margalit E. , Patil-Chhablani Preeti , Ores Raphaelle , Boussion Francois , Indermill Chad , Sahel José-Alain , Nischal Ken , Goldstein Debra A. , Errera Marie-Helene
Published: March 2023

Introduction

Relentless placoid chorioretinitis (RPC) is a rare, bilateral disease of the retinal pigment epithelium. The clinical course is prolonged and relapsing. No standard treatment has been established to date. The purpose of this case series is to report four cases of RPC in pediatric and young adult patients in which varying treatments were used, comparing them to previously published cases.

Methods

A literature review was conducted to investigate currently published presentations and treatment options for RPC. A multicenter retrospective chart review was also performed on four consecutive patients. These patients were diagnosed with RPC because of new chorioretinitis lesions continuing to appear without or despite therapy for 5–36 months (2 patients), with a clinical course prolonged and relapsing, or because of the atypical location of the multiple lesions (>50) extending from the posterior pole to the equator and mid-peripheral retina (all four patients), which were not consistent with other entities like acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis.

Results

All four cases of RPC received oral or IV steroids acutely, and three of these patients were transitioned to a steroid-sparing agent and biologic therapy: anti-TNF alpha or anti-IL-6. Quiescence of the chorioretinitis lesions was obtained after 7 months, 1 month, and 36 months; however, the latter had issues with treatment adherence. Mycophenolate mofetil was insufficient to control the disease in one patient, but tocilizumab and infliximab thereafter were effective after cessation of adalimumab due to side effects. Adalimumab when started the first month after the presentation was effective in controlling the disease in one patient. After the failure of interferon-alpha-2a, one patient displayed long-term control with infliximab. One patient did not require a steroid-sparing agent after oral prednisone taper as there was no evidence of progression or recurrence.

Conclusion

This case series adds to the current knowledge regarding potential treatments for RPC, specifically the use of anti-TNF-alpha treatment and anti-IL-6 tocilizumab. In this case study, relapses of RPC were found among patients on mycophenolate mofetil and interferon-alpha-2a, and one case did not relapse on oral steroids without a steroid-sparing agent. Our findings suggest that adalimumab, infliximab, and tocilizumab may be useful medications to obtain quiescence of RPC.
Small molecules targeting Pin1 as potent anticancer drugs
Authors: Zhang Jing , Zhou Wenwen , Chen Yunyu , Wang Yanchang , Guo Zongru , Hu Wenhui , Li Yan , Han Xiaomin , Si Shuyi
Published: March 2023

Background: Pin1 is a member of the evolutionarily conserved peptidyl-prolyl isomerase (PPIase) family of proteins. Following phosphorylation, Pin1-catalyzed prolyl-isomerization induces conformational changes, which serve to regulate the function of many phosphorylated proteins that play important roles during oncogenesis. Thus, the inhibition of Pin1 provides a unique means of disrupting oncogenic pathways and therefore represents an appealing target for novel anticancer therapies.

Methods: As Pin1 is conserved between yeast and humans, we employed budding yeast to establish a high-throughput screening method for the primary screening of Pin1 inhibitors. This effort culminated in the identification of the compounds HWH8-33 and HWH8-36. Multifaceted approaches were taken to determine the inhibition profiles of these compounds against Pin1 activity in vitro and in vivo, including an isomerization assay, surface plasmon resonance (SPR) technology, virtual docking, MTT proliferation assay, western blotting, cell cycle analysis, apoptosis analysis, immunofluorescence analysis, wound healing, migration assay, and nude mouse assay.

Results:In vitro, HWH8-33 and HWH8-36 could bind to purified Pin1 and inhibited its enzyme activity; showed inhibitory effects on cancer cell proliferation; led to G2/M phase arrest, dysregulated downstream protein expression, and apoptosis; and suppressed cancer cell migration. In vivo, HWH8-33 suppressed tumor growth in the xenograft mice after oral administration for 4 weeks, with no noticeable toxicity. Together, these results show the anticancer activity of HWH8-33 and HWH8-36 against Pin1 for the first time.

Conclusion: In summary, we identified two hit compounds HWH8-33 and HWH8-36, which after further structure optimization have the potential to be developed as antitumor drugs.
Endothelial activation impairs the function of small extracellular vesicles
Authors: Herrera-Zelada Nicolas , Zúñiga-Cuevas Úrsula , Ramírez-Reyes Andrés , Norambuena-Soto Ignacio , Venegas-Zamora Leslye , Troncoso Mayarling F. , Hernández Alejandra , Sánchez Gina , Pedrozo Zully , Lavandero Sergio , Riquelme Jaime A.
Published: March 2023

Small extracellular vesicles are nanosized vesicles (30–200 nm) that can ferry proteins, nucleic acids, and lipids between cells and therefore, have significant potential as biomarkers, drug delivery tools or therapeutic agents. SEVs of endothelial origin have been shown to -among other functions-reduce in vitro ischemia/reperfusion (I/R) injury in cardiomyocytes, but whether a pro-inflammatory state of the endothelium impairs the functionality of these SEVs remains to be elucidated. To test this, human umbilical vein endothelial cells cells were treated with TNF-α 10 ng/mL and the expression of the pro-inflammatory parameters VCAM-1, ICAM-1 and eNOS were determined by Western blot. SEVs were isolated from endothelial cells treated with or without TNF-α 10 ng/mL using size exclusion chromatography. The size and concentration of SEVs was measured by Nanoparticle Tracking Analysis. The expression of the surface marker CD81 was determined by immunoassay, whereas their morphology was assessed by electron microscopy. The function of endothelial SEVs was assessed by evaluating their cardioprotective effect in an ex vivo model of global I/R using isolated hearts from adult C57BL/6 mice. Treatment of HUVECs with TNF-α induced the expression of VCAM-1 and ICAM-1, whereas eNOS levels were decreased. TNF-α did not affect the production, size, morphology, or expression of CD81. SEVs significantly reduced the infarct size as compared with untreated mice hearts, but SEVs isolated from TNF-α treated cells were unable to achieve this effect. Therefore, a pro-inflammatory state induced by TNF-α does not alter the production of endothelial SEVs but impairs their function in the setting of I/R injury.
Differential effects of ELX/TEZ/IVA on organ-specific CFTR function in two patients with the rare CFTR splice mutations c.273+1G>A and c.165-2A>G
Authors: Pallenberg Sophia T. , Held Inka , Dopfer Christian , Minso Rebecca , Nietert Manuel M. , Hansen Gesine , Tümmler Burkhard , Dittrich Anna-Maria
Published: March 2023

Introduction: Evidence for the efficiency of highly-effective triple-CFTR-modulatory therapy with elexacaftor/tezacaftor/ivacaftor (ETI), either demonstrated in clinical trials or by in vitro testing, is lacking for about 10% of people with cystic fibrosis (pwCF) with rare mutations. Comprehensive assessment of CFTR function can provide critical information on the impact of ETI on CFTR function gains for such rare mutations, lending argument of the prescription of ETI. The mutation c.165-2A>G is a rare acceptor splice mutation that has not yet been functionally characterized. We here describe the functional changes induced by ETI in two brothers who are compound heterozygous for the splice mutations c.273+1G>C and c.165-2A>G.

Methods: We assessed the effects of ETI on CFTR function by quantitative pilocarpine iontophoresis (QPIT), nasal potential difference measurements (nPD), intestinal current measurements (ICM), β-adrenergic sweat secretion tests (SST) and multiple breath washout (MBW) prior to and 4 months after the initiation of ETI.

Results: Functional CFTR analysis prior to ETI showed no CFTR function in the respiratory and intestinal epithelia and in the sweat gland reabsorptive duct in either brother. In contrast, β-adrenergic stimulated, CFTR-mediated sweat secretion was detectable in the CF range. Under ETI, both brothers continued to exhibit high sweat chloride concentration in QPIT, evidence of low residual CFTR function in the respiratory epithelia, but normalized β-adrenergically stimulated production of primary sweat.

Discussion: Our results are the first to demonstrate that the c.165-2A>G/c.273+1G>C mutation genotype permits mutant CFTR protein expression. We showed organ-specific differences in the expression of CFTR and consecutive responses to ETI of the c.165-2A>G/c.273+1G>C CFTR mutants that are probably accomplished by non-canonical CFTR mRNA isoforms. This showcase tells us that the individual response of rare CFTR mutations to highly-effective CFTR modulation cannot be predicted from assays in standard cell cultures, but requires the personalized multi-organ assessment by CFTR biomarkers.
Real-world disparities and ethical considerations with access to CFTR modulator drugs: Mind the gap!
Authors: Zampoli M. , Morrow B. M , Paul G
Published: March 2023

The third Sustainable Development Goal (SDG), to ensure healthy lives and promote well-being for all at all ages, has particular relevance and implementation challenges amongst people living with rare diseases such as cystic fibrosis (CF). Although the treatment and projected outcome of CF has significantly improved with the advent of CF transmembrane conductance regulator protein modulator (CFTRm) therapy, there remains significant global inequality with regards to access to these life-saving and life-altering drugs. Elexacaftor, tezacaftor, and ivacaftor (ETI) triple combination therapy, first licensed in the United States in 2019, has rapidly become the standard of care for children aged 6 years and older in most high-income countries for individuals with CFTR variants responsive to ETI. Negotiated agreements for access to ETI are currently in place in North America,Europe, Israel ,Australia and New Zealand. However, less priority has been given to negotiate agreements for access to CFTRm in low-middle income countries(LMIC) with significant CF populations such as Central and South America, India, the Middle East, and Southern Africa. These countries and individuals living with CF are therefore effectively being left behind, in direct conflict with the stated principle of the 2030 SDGs. In this review, we highlight the current global inequity in access to CFTRm drugs and its impact on widening disparities between high-income countries and LMIC in CF outcomes and survival. We further discuss the reasons for this inequity and explore the ethical- and human rights-based principles and dilemmas that clinicians, families, governments, and healthcare funders must consider when prioritizing fair and affordable access to expensive CFTRm drugs. Lastly, we propose possible solutions to overcoming the barriers to accessing affordable CFTRm drugs in LMIC and illustrate with examples how access to drug therapies for other conditions have been successfully negotiated in LMIC through innovative partnerships between governments and pharmaceutical industries.
Meta-analysis and trial sequential analysis of ezetimibe for coronary atherosclerotic plaque compositions
Authors: Chai Bofeng , Shen Youlu , Li Yuhong , Wang Xiaoyu
Published: March 2023

Background: Lipid aggregation, inflammatory cell infiltration, fibrous cap formation, and disruption are the major causes of atherosclerotic cardiovascular disease (ASCVD) and the pathologic features of atherosclerotic plaques. Although ezetimibe’s role in decreasing blood lipids is widely known, there are insufficient data to determine which part of the drug has an effect on atherosclerotic plaque compositions.

Objective: The study aimed to systematically evaluate the efficacy of ezetimibe for coronary atherosclerotic plaque compositions.

Methods: Two researchers independently searched the PubMed, Embase, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs) on the efficacy of ezetimibe for coronary atherosclerotic plaques from inception until 22 January 2023. The meta-analysis and trial sequential analysis (TSA) were performed using Stata 14.0 and TSA 0.9.5.10 Beta software, respectively.

Results: Four RCTs were finally included this study, which comprised 349 coronary artery disease patients. Meta-analysis findings showed that, compared with the control group, intervention measures could effectively reduce the fibro-fatty plaque (FFP) volume [WMD = −2.90, 95% CI (−4.79 and −1.00), and p = 0.003 < 0.05]; there were no significant difference in the reduction of fibrous plaque (FP) volume [WMD = −4.92, 95% CI (−11.57 and 1.74), and p = 0.15 > 0.05], necrotic core (NC) volume [WMD = −2.26, 95% CI (−6.99 and 2.46), and p = 0.35 > 0.05], and change dense calcification (change DC) volume [WMD = −0.07, 95% CI (−0.34 and 0.20), and p = 0.62 > 0.05] between the treatment group and the control group. TSA findings showed more studies are still required to confirm the efficacy of ezetimibe for FP and NC in the future.

Conclusion: Compared to the control group, ezetimibe significantly decreased FFP, but it had no statistically significant difference on FP, NC, or change DC. According to TSA, further research will be required to confirm the efficacy of ezetimibe for FP and NC in the future.
A multi-wavelength mid-IR laser based on BaGa4Se7 optical parametric oscillators
Authors: Deng Ying , Kang Minqiang , Wang Zhenguo , Li Jianbin , Jiang Xinying , Xiao Kaibo , Zhou Song , Zhang Fan , Xiang Xiangjun , Peng Zhitao , Yao Jiyong , Zhu Qihua , Feng Guoying
Published: March 2023

A multi-wavelength mid-IR laser consisting of 3.05 μm, 4.25 μm, and 5.47 μm BaGa4Se7(BGSe)optical parametric oscillators (OPOs) switched by DKDP electro-optic switches with one 10 Hz/7.6 ns pumping wave is demonstrated. Maximum energies at 3.05 μm, 4.25 μm, and 5.47 μm are 1.35 mJ, 1.03 mJ, and 0.56 mJ, respectively, corresponding to optical-to-optical conversion efficiencies of 9.4%, 7.6%, and 4.2%. To the best of our knowledge, this study is the first of generation of three mid-IR wavelength lasers using electro-optic switches. Furthermore, this study provides a viable solution for a high-energy or high-power, compact, or even portable multi-wavelength mid-IR laser device that employs a single pumping wave.
New insights into the pole parameters of the Λ(1380), the Λ(1405) and the Σ(1385)
Authors: Sadasivan D. , Mai M. , Döring M. , Meißner Ulf-G. , Amorim F. , Klucik J. , Lu Jun-Xu , Geng Li-Sheng
Published: March 2023

A coupled-channel S- and P-wave next-to-leading order chiral-unitary approach for strangeness S = −1 meson-baryon scattering is extended to include the new data from the KLOE and AMADEUS experiments as well as the Λπ mass distribution of the Σ(1385). The positions of the poles on the second Riemann sheet corresponding to the Σ(1385) pole and the Λ(1380) and Λ(1405) poles as well as the couplings of these states to various channels are calculated. We find that the resonance positions and branching ratios are on average determined with about 20% higher precision when including the KLOE and AMADEUS data. Additionally, for the first time, the correlations between the parameters of the poles are investigated and shown to be relevant. We also find that the Σ(1385) has negligible influence on the properties of the Λ states given the available data. Still, we identify isospin-1 cusp structures in the present solution in light of new measurements of π±Λ line-shapes by the Belle collaboration.
Multiplexed photoinjector optimization for high-repetition-rate free-electron lasers
Authors: Zhang Zhen , Ding Yuantao , Huang Zhirong , Zhou Feng
Published: March 2023

The multiplexing capabilities of superconducting X-ray free-electron lasers (FELs) have gained much attention in recent years. The demanding requirements for photon properties from multiple undulator lines necessitate more flexible beam manipulation techniques to achieve the goal of “beam on demand”. In this paper, we investigate a multiplexed configuration for the photoinjector of high-repetition-rate FELs that aims to simultaneously provide low-emittance electron beams of different charges. A parallel, multi-objective genetic algorithm is implemented for the photoinjector parameter optimization. The proposed configuration could drastically enhance the flexibility of beam manipulation to improve multiplexing capabilities and realize the full potential of the facility.
BAF-Net: Bidirectional attention fusion network via CNN and transformers for the pepper leaf segmentation
Authors: Fang Jiangxiong , Jiang Houtao , Zhang Shiqing , Sun Lin , Hu Xudong , Liu Jun , Gong Meng , Liu Huaxiang , Fu Youyao
Published: March 2023

The segmentation of pepper leaves from pepper images is of great significance for the accurate control of pepper leaf diseases. To address the issue, we propose a bidirectional attention fusion network combing the convolution neural network (CNN) and Swin Transformer, called BAF-Net, to segment the pepper leaf image. Specially, BAF-Net first uses a multi-scale fusion feature (MSFF) branch to extract the long-range dependencies by constructing the cascaded Swin Transformer-based and CNN-based block, which is based on the U-shape architecture. Then, it uses a full-scale feature fusion (FSFF) branch to enhance the boundary information and attain the detailed information. Finally, an adaptive bidirectional attention module is designed to bridge the relation of the MSFF and FSFF features. The results on four pepper leaf datasets demonstrated that our model obtains F1 scores of 96.75%, 91.10%, 97.34% and 94.42%, and IoU of 95.68%, 86.76%, 96.12% and 91.44%, respectively. Compared to the state-of-the-art models, the proposed model achieves better segmentation performance. The code will be available at the website: https://github.com/fangchj2002/BAF-Net.
Heterologous overexpression of Apocynum venetum flavonoids synthetase genes improves Arabidopsis thaliana salt tolerance by activating the IAA and JA biosynthesis pathways
Authors: Zhang Mengchao , Lu Xueli , Ren Tingting , Marowa Prince , Meng Chen , Wang Juying , Yang Hui , Li Chunhua , Zhang Li , Xu Zongchang
Published: March 2023

Salt stress is a serious abiotic stress that primarily inhibits plant growth, resulting in severe yield losses. Our previous research found that flavonoids play important roles in A. venetum salt stress tolerance. In response to salt stress, we noted that the flavonoid content was depleted in A. venetum. However, the detailed mechanism is still not clear. In this study, the expression patterns of three flavonoids synthetase genes, AvF3H, AvF3’H, and AvFLS were systemically analyzed under salt stress in A. venetum seedlings. The salt tolerance of transgenic Arabidopsis plants was improved by heterologous overexpression of these synthetase genes. The NBT and DAB staining results as well as H2O2 and O2•- content analysis revealed that under salt stress, ROS molecules were reduced in transgenic plants compared to WT plants, which corresponded to the activation of the antioxidant enzyme system and an increase in total flavonoid content, particularly rutin, eriodictyol, and naringerin in transgenic plants. External application of flavonoids reduced ROS damage in WT plants just like what we observed in the transgenic plants (without the external application). Additionally, our transcriptome analysis demonstrated that auxin and jasmonic acid biosynthesis genes, as well as signaling transduction genes, were primarily activated in transgenic plants under salt stress, leading to activation of the cell wall biosynthesis or modification genes that promote plant growth. As a result, we investigated the mechanism through flavonoids enhance the salt tolerance, offering a theoretical foundation for enhancing salt tolerance in plants.
Single-cell genetic models to evaluate orphan gene function: The case of QQS regulating carbon and nitrogen allocation
Authors: Wang Lei , Tonsager Andrew J. , Zheng Wenguang , Wang Yingjun , Stessman Dan , Fang Wei , Stenback Kenna E. , Campbell Alexis , Tanvir Rezwan , Zhang Jinjiang , Cothron Samuel , Wan Dongli , Meng Yan , Spalding Martin H. , Nikolau Basil J. , Li Ling
Published: March 2023

We demonstrate two synthetic single-cell systems that can be used to better understand how the acquisition of an orphan gene can affect complex phenotypes. The Arabidopsis orphan gene, Qua-Quine Starch (QQS) has been identified as a regulator of carbon (C) and nitrogen (N) partitioning across multiple plant species. QQS modulates this important biotechnological trait by replacing NF-YB (Nuclear Factor Y, subunit B) in its interaction with NF-YC. In this study, we expand on these prior findings by developing Chlamydomonas reinhardtii and Saccharomyces cerevisiae strains, to refactor the functional interactions between QQS and NF-Y subunits to affect modulations in C and N allocation. Expression of QQS in C. reinhardtii modulates C (i.e., starch) and N (i.e., protein) allocation by affecting interactions between NF-YC and NF-YB subunits. Studies in S. cerevisiae revealed similar functional interactions between QQS and the NF-YC homolog (HAP5), modulating C (i.e., glycogen) and N (i.e., protein) allocation. However, in S. cerevisiae both the NF-YA (HAP2) and NF-YB (HAP3) homologs appear to have redundant functions to enable QQS and HAP5 to affect C and N allocation. The genetically tractable systems that developed herein exhibit the plasticity to modulate highly complex phenotypes.