bluuebunny/crossref_metadata_2025 huggingface dataset:
Talaromyces marneffei infection and complicate manifestation of respiratory system in HIV-negative children
Authors: Yang Qin , Wu Yue , Li Xiaonan , Bao Yanmin , Wang Wenjian , Zheng Yuejie
Published: March 2023

Background

Respiratory symptoms are the earliest clinical manifestation of Talaromyces marneffei (TM) infection. In this study, we aimed to improve the early identification of TM infection in human immunodeficiency virus (HIV)-negative children with respiratory symptoms as the first manifestation, analyze the risk factors, and provide evidence for diagnosis and treatment.

Methods

We retrospectively analyzed six cases of HIV-negative children with respiratory system infection symptoms as the first presentation.

Results

All subjects (100%) had cough and hepatosplenomegaly, and five subjects (83.3%) had a fever; other symptoms and signs included lymph node enlargement, rash, rales, wheezing, hoarseness, hemoptysis, anemia, and thrush. Additionally, 66.7% of the cases had underlying diseases (three had malnutrition, one had severe combined immune deficiency [SCID]). The most common coinfecting pathogen was Pneumocystis jirovecii, which occurred in two cases (33.3%), followed by one case of Aspergillus sp. (16.6%). Furthermore, the value of β-D-glucan detection (G test) increased in 50% of the cases, while the proportion of NK decreased in six cases (100%). Five children (83.3%) were confirmed to have the pathogenic genetic mutations. Three children (50%) were treated with amphotericin B, voriconazole, and itraconazole, respectively; three children (50%) were treated with voriconazole and itraconazole. All children were tested for itraconazole and voriconazole plasma concentrations throughout antifungal therapy. Two cases (33.3%) relapsed after drug withdrawal within 1 year, and the average duration of antifungal treatment for all children was 17.7 months.

Conclusion

The first manifestation of TM infection in children is respiratory symptoms, which are nonspecific and easily misdiagnosed. When the effectiveness of anti-infection treatment is poor for recurrent respiratory tract infections, we must consider the condition with an opportunistic pathogen and attempt to identify the pathogen using various samples and detection methods to confirm the diagnosis. It is recommended the course for anti-TM disease be longer than one year for children with immune deficiency. Monitoring the blood concentration of antifungal drugs is important.
Understanding of healthcare professionals towards the roles and competencies of clinical pharmacists in South Africa
Authors: Crafford L , Kusurkar RA , Bronkhorst E , Gous AGS , Wouters A
Published: March 2023

Background

Incorporating clinical pharmacists in collaborative medical teams results in better patient treatment and health outcomes. In addition, the understanding of other healthcare professionals (HCPs) towards the role of clinical pharmacists can either facilitate or hinder the implementation and expansion of these services. The main distinction between pharmacists and clinical pharmacists lie in their different scope of duties. This study set out to explore other HCPs’ understanding towards the role of the clinical pharmacists in South Africa, and to identify associated factors.

Methods

An exploratory, survey-based, quantitative study was conducted. A survey assessing HCPs’ understanding based on the competencies and role of a clinical pharmacist was distributed to 300 doctors, nurses, pharmacists and clinical pharmacists. An exploratory factor analysis was carried out to determine the construct validity of the measurement. Items were analysed for grouping into subscales through principal components analysis. Differences in the variable scores for gender, age, work experience and previous experience working with a clinical pharmacist were analyzed using independent t-tests. Analysis of variance was used to analyze differences in the variable scores for the different HCPs and the different departments of work in the hospital.

Results

The factor analysis yielded two separate subscales, measuring HCPs’ (n = 188) understanding towards the role of a clinical pharmacist, as well as the competencies of a clinical pharmacist. Doctors (85, n = 188) (p = 0.004) and nurses (76, n = 188) (p = 0.022), working in both surgical and non-surgical units, had significantly poorer understanding of the role of clinical pharmacists than clinical pharmacists (8, n = 188) and pharmacists (19, n = 188) (p = 0.028). Where specific clinical pharmacist activities were described, 5–16% of pharmacists were unsure whether an activity forms part of a clinical pharmacist’s role. Over 50% of the clinical pharmacists disagreed that their role also includes pharmacist’s activities, like stock procurement and control, pharmacy and administrative work, and hospital pharmacy-medication dispensing activities.

Conclusion

The findings highlighted the possible impact of role expectations and lack of understanding among HCPs. A standard job description with recognition from statutory bodies could promote other HCPs, as well as clinical pharmacists’ understanding of their roles. Findings further suggested the need for interventions like interprofessional education opportunities, staff induction programmes and regular interprofessional meetings to foster acknowledgement of clinical pharmacy services, promoting the acceptance and growth of the profession.
A qualitative study to explore the healthcare-seeking experiences of men who have sex with men (MSM) and transgender women (TGW) in Rwanda
Authors: Isano Sandra , Yohannes Tsion , Igihozo Gloria , Ndatinya Grace Iliza , Wong Rex
Published: March 2023

Background

Globally, men who have sex with men (MSM) and transgender women (TGW) encounter many challenging experiences when accessing health services compared to the general population. Stigma, discrimination, and punitive laws against same-sex relationships in some sub-Saharan African countries have made MSM and TGW more prone to depression, suicidal ideation, anxiety disorders, substance abuse, non-communicable diseases, and HIV. None of the prior studies in Rwanda on MSM and TGW had explored their lived experience in accessing health services. Accordingly, this study aimed at exploring the healthcare-seeking experiences of MSM and TGW in Rwanda.

Methods

This study utilized a qualitative research method employing a phenomenological design. Semi-structured in-depth interviews were conducted with 16 MSM and 12 TGW. Participants were recruited via purposive and snowball sampling approaches in five districts in Rwanda.”

Results

Data were analyzed using a thematic analysis approach. Three main themes emerged from the study: (1) The healthcare experiences of MSM and TGW were generally dissatisfactory, (2) MSM and TGW hesitated to seek care unless they were severely ill, (3) MSM and TGW’s perspectives on how to improve their health-seeking behavior.

Conclusion

MSM and TGW in Rwanda continue to face negative experiences within the healthcare delivery settings. These experiences include mistreatment, refusal of care, stigma, and discrimination. Provision of services for MSM and TGW and On-the-job cultural competence training in the care of MSM and TGW patients is needed. Including the same training in the medical and health sciences curriculum is recommended. Furthermore, awareness and sensitization campaigns to improve the understanding of the existence of MSM and TGW and to foster acceptance of gender and sexual diversity in society are necessary.
A transcriptomic pan-cancer signature for survival prognostication and prediction of immunotherapy response based on endothelial senescence
Authors: Wu Zhengquan , Uhl Bernd , Gires Olivier , Reichel Christoph A.
Published: March 2023

Background

The microvascular endothelium inherently controls nutrient delivery, oxygen supply, and immune surveillance of malignant tumors, thus representing both biological prerequisite and therapeutic vulnerability in cancer. Recently, cellular senescence emerged as a fundamental characteristic of solid malignancies. In particular, tumor endothelial cells have been reported to acquire a senescence-associated secretory phenotype, which is characterized by a pro-inflammatory transcriptional program, eventually promoting tumor growth and formation of distant metastases. We therefore hypothesize that senescence of tumor endothelial cells (TEC) represents a promising target for survival prognostication and prediction of immunotherapy efficacy in precision oncology.

Methods

Published single-cell RNA sequencing datasets of different cancer entities were analyzed for cell-specific senescence, before generating a pan-cancer endothelial senescence-related transcriptomic signature termed EC.SENESCENCE.SIG. Utilizing this signature, machine learning algorithms were employed to construct survival prognostication and immunotherapy response prediction models. Machine learning-based feature selection algorithms were applied to select key genes as prognostic biomarkers.

Results

Our analyses in published transcriptomic datasets indicate that in a variety of cancers, endothelial cells exhibit the highest cellular senescence as compared to tumor cells or other cells in the vascular compartment of malignant tumors. Based on these findings, we developed a TEC-associated, senescence-related transcriptomic signature (EC.SENESCENCE.SIG) that positively correlates with pro-tumorigenic signaling, tumor-promoting dysbalance of immune cell responses, and impaired patient survival across multiple cancer entities. Combining clinical patient data with a risk score computed from EC.SENESCENCE.SIG, a nomogram model was constructed that enhanced the accuracy of clinical survival prognostication. Towards clinical application, we identified three genes as pan-cancer biomarkers for survival probability estimation. As therapeutic perspective, a machine learning model constructed on EC.SENESCENCE.SIG provided superior pan-cancer prediction for immunotherapy response than previously published transcriptomic models.

Conclusions

We here established a pan-cancer transcriptomic signature for survival prognostication and prediction of immunotherapy response based on endothelial senescence.
Aldose reductase inhibition alleviates diabetic cardiomyopathy and is associated with a decrease in myocardial fatty acid oxidation
Authors: Gopal Keshav , Karwi Qutuba G. , Tabatabaei Dakhili Seyed Amirhossein , Wagg Cory S. , Zhang Liyan , Sun Qiuyu , Saed Christina T. , Panidarapu Sai , Perfetti Riccardo , Ramasamy Ravichandran , Ussher John R. , Lopaschuk Gary D.
Published: March 2023

Background

Cardiovascular diseases, including diabetic cardiomyopathy, are major causes of death in people with type 2 diabetes. Aldose reductase activity is enhanced in hyperglycemic conditions, leading to altered cardiac energy metabolism and deterioration of cardiac function with adverse remodeling. Because disturbances in cardiac energy metabolism can promote cardiac inefficiency, we hypothesized that aldose reductase inhibition may mitigate diabetic cardiomyopathy via normalization of cardiac energy metabolism.

Methods

Male C57BL/6J mice (8-week-old) were subjected to experimental type 2 diabetes/diabetic cardiomyopathy (high-fat diet [60% kcal from lard] for 10 weeks with a single intraperitoneal injection of streptozotocin (75 mg/kg) at 4 weeks), following which animals were randomized to treatment with either vehicle or AT-001, a next-generation aldose reductase inhibitor (40 mg/kg/day) for 3 weeks. At study completion, hearts were perfused in the isolated working mode to assess energy metabolism.

Results

Aldose reductase inhibition by AT-001 treatment improved diastolic function and cardiac efficiency in mice subjected to experimental type 2 diabetes. This attenuation of diabetic cardiomyopathy was associated with decreased myocardial fatty acid oxidation rates (1.15 ± 0.19 vs 0.5 ± 0.1 µmol min−1 g dry wt−1 in the presence of insulin) but no change in glucose oxidation rates compared to the control group. In addition, cardiac fibrosis and hypertrophy were also mitigated via AT-001 treatment in mice with diabetic cardiomyopathy.

Conclusions

Inhibiting aldose reductase activity ameliorates diastolic dysfunction in mice with experimental type 2 diabetes, which may be due to the decline in myocardial fatty acid oxidation, indicating that treatment with AT-001 may be a novel approach to alleviate diabetic cardiomyopathy in patients with diabetes.
Proteins in pregnant swine serum promote the African swine fever virus replication: an iTRAQ-based quantitative proteomic analysis
Authors: Yang Jinke , Yuan Xingguo , Hao Yu , Shi Xijuan , Yang Xing , Yan Wenqian , Chen Lingling , Zhang Dajun , Shen Chaochao , Li Dan , Zhu Zixiang , Liu Xiangtao , Zheng Haixue , Zhang Keshan
Published: March 2023

African swine fever (ASF) is a severe infectious disease caused by the African swine fever virus (ASFV), seriously endangering the global pig industry. ASFV possesses a large genome, strong mutation ability, and complex immune escape mechanisms. Since the first case of ASF was reported in China in August 2018, it has had a significant impact on social economy and food safety. In the present study, pregnant swine serum (PSS) was found to promote viral replication; differentially expressed proteins (DEPs) in PSS were screened and identified using the isobaric tags for relative and absolute quantitation technology and compared with those in non-pregnant swine serum (NPSS). The DEPs were analyzed using Gene Ontology functional annotation, Kyoto Protocol Encyclopedia of Genes and Genome pathway enrichment, and protein–protein interaction networks. In addition, the DEPs were validated via western blot and RT-qPCR experiments. And the 342 of DEPs were identified in bone marrow-derived macrophages cultured with PSS compared with the NPSS. The 256 were upregulated and 86 of DEPs were downregulated. The primary biological functions of these DEPs involved signaling pathways that regulate cellular immune responses, growth cycles, and metabolism-related pathways. An overexpression experiment showed that the PCNA could promote ASFV replication whereas MASP1 and BST2 could inhibit it. These results further indicated that some protein molecules in PSS were involved in the regulation of ASFV replication. In the present study, the role of PSS in ASFV replication was analyzed using proteomics, and the study will be provided a basis for future detailed research on the pathogenic mechanism and host interactions of ASFV as well as new insights for the development of small-molecule compounds to inhibit ASFV.
TSWIFT: Tower Spectrometer on Wheels for Investigating Frequent Timeseries for high-throughput phenotyping of vegetation physiology
Authors: Wong Christopher Y. S. , Jones Taylor , McHugh Devin P. , Gilbert Matthew E. , Gepts Paul , Palkovic Antonia , Buckley Thomas N. , Magney Troy S.
Published: March 2023

Background

Remote sensing instruments enable high-throughput phenotyping of plant traits and stress resilience across scale. Spatial (handheld devices, towers, drones, airborne, and satellites) and temporal (continuous or intermittent) tradeoffs can enable or constrain plant science applications. Here, we describe the technical details of TSWIFT (Tower Spectrometer on Wheels for Investigating Frequent Timeseries), a mobile tower-based hyperspectral remote sensing system for continuous monitoring of spectral reflectance across visible-near infrared regions with the capacity to resolve solar-induced fluorescence (SIF).

Results

We demonstrate potential applications for monitoring short-term (diurnal) and long-term (seasonal) variation of vegetation for high-throughput phenotyping applications. We deployed TSWIFT in a field experiment of 300 common bean genotypes in two treatments: control (irrigated) and drought (terminal drought). We evaluated the normalized difference vegetation index (NDVI), photochemical reflectance index (PRI), and SIF, as well as the coefficient of variation (CV) across the visible-near infrared spectral range (400 to 900 nm). NDVI tracked structural variation early in the growing season, following initial plant growth and development. PRI and SIF were more dynamic, exhibiting variation diurnally and seasonally, enabling quantification of genotypic variation in physiological response to drought conditions. Beyond vegetation indices, CV of hyperspectral reflectance showed the most variability across genotypes, treatment, and time in the visible and red-edge spectral regions.

Conclusions

TSWIFT enables continuous and automated monitoring of hyperspectral reflectance for assessing variation in plant structure and function at high spatial and temporal resolutions for high-throughput phenotyping. Mobile, tower-based systems like this can provide short- and long-term datasets to assess genotypic and/or management responses to the environment, and ultimately enable the spectral prediction of resource-use efficiency, stress resilience, productivity and yield.
Melatonin and endothelial cell-loaded alginate-fibrin hydrogel promoted angiogenesis in rat cryopreserved/thawed ovaries transplanted to the heterotopic sites
Authors: Izadpanah Melika , Del Bakhshayesh Azizeh Rahmani , Bahroudi Zahra , Seghinsara Abbas Majdi , Beheshti Rahim , Mahdipour Mahdi , Zarnaghi Mahsa Rezaii , Hassanpour Parisa , Mardi Narges , Rahbarghazi Reza , Abedelahi Ali
Published: March 2023

Background

Ischemic niche can promote follicular atresia following the transplantation of cryopreserved/thawed ovaries to the heterotopic sites. Thus, the promotion of blood supply is an effective strategy to inhibit/reduce the ischemic damage to ovarian follicles. Here, the angiogenic potential of alginate (Alg) + fibrin (Fib) hydrogel enriched with melatonin (Mel) and CD144+ endothelial cells (ECs) was assessed on encapsulated cryopreserved/thawed ovaries following transplantation to heterotopic sites in rats.

Methods

Alg + Fib hydrogel was fabricated by combining 2% (w/v) sodium Alg, 1% (w/v) Fib, and 5 IU thrombin at a ratio of 4: 2: 1, respectively. The mixture was solidified using 1% CaCl2. Using FTIR, SEM, swelling rate, and biodegradation assay, the physicochemical properties of Alg + Fib hydrogel were evaluated. The EC viability was examined using an MTT assay. Thirty-six adult female rats (aged between 6 and 8 weeks) with a normal estrus cycle were ovariectomized and enrolled in this study. Cryopreserved/thawed ovaries were encapsulated in Alg + Fib hydrogel containing 100 µM Mel + CD144+ ECs (2 × 104 cells/ml) and transplanted into the subcutaneous region. Ovaries were removed after 14 days and the expression of Ang-1, and Ang-2 was monitored using real-time PCR assay. The number of vWF+ and α-SMA+ vessels was assessed using IHC staining. Using Masson’s trichrome staining, fibrotic changes were evaluated.

Results

FTIR data indicated successful interaction of Alg with Fib in the presence of ionic cross-linker (1% CaCl2). Data confirmed higher biodegradation and swelling rates in Alg + Fib hydrogel compared to the Alg group (p < 0.05). Increased viability was achieved in encapsulated CD144+ ECs compared to the control group (p < 0.05). IF analysis showed the biodistribution of Dil+ ECs within hydrogel two weeks after transplantation. The ratio of Ang-2/Ang-1 was statistically up-regulated in the rats that received Alg + Fib + Mel hydrogel compared to the control-matched groups (p < 0.05). Based on the data, the addition of Mel and CD144+ ECs to Alg + Fib hydrogel reduced fibrotic changes. Along with these changes, the number of vWF+ and α-SMA+ vessels was increased in the presence of Mel and CD144+ ECs.

Conclusions

Co-administration of Alg + Fib with Mel and CD144+ ECs induced angiogenesis toward encapsulated cryopreserved/thawed ovarian transplants, resulting in reduced fibrotic changes.
Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis
Authors: Sun Silei , Wang Daosheng , Dong Danfeng , Xu Lili , Xie Mengqi , Wang Yihui , Ni Tongtian , Jiang Weisong , Zhu Xiaojuan , Ning Ning , Sun Qian , Zhao Shuyuan , Li Mengjiao , Chen Peili , Yu Meiling , Li Jian , Chen Erzhen , Zhao Bing , Peng Yibing , Mao Enqiang
Published: March 2023

Background

The gut microbiome plays a pivotal role in the progression of sepsis. However, the specific mechanism of gut microbiota and its metabolites involved in the process of sepsis remains elusive, which limits its translational application.

Method

In this study, we used a combination of the microbiome and untargeted metabolomics to analyze stool samples from patients with sepsis enrolled at admission, then microbiota, metabolites, and potential signaling pathways that might play important roles in disease outcome were screened out. Finally, the above results were validated by the microbiome and transcriptomics analysis in an animal model of sepsis.

Results

Patients with sepsis showed destruction of symbiotic flora and elevated abundance of Enterococcus, which were validated in animal experiments. Additionally, patients with a high burden of Bacteroides, especially B. vulgatus, had higher Acute Physiology and Chronic Health Evaluation II scores and longer stays in the intensive care unit. The intestinal transcriptome in CLP rats illustrated that Enterococcus and Bacteroides had divergent profiles of correlation with differentially expressed genes, indicating distinctly different roles for these bacteria in sepsis. Furthermore, patients with sepsis exhibited disturbances in gut amino acid metabolism compared with healthy controls; namely, tryptophan metabolism was tightly related to an altered microbiota and the severity of sepsis.

Conclusion

Alterations in microbial and metabolic features in the gut corresponded with the progression of sepsis. Our findings may help to predict the clinical outcome of patients in the early stage of sepsis and provide a translational basis for exploring new therapies.
Changing patient preferences toward better trial recruitment: an ethical analysis
Authors: Al Pepijn , Hey Spencer , Weijer Charles , Gillies Katie , McCleary Nicola , Yee Mei-Lin , Inglis Juliette , Presseau Justin , Brehaut Jamie
Published: March 2023

While randomized controlled trials are essential to health research, many of these trials fail to recruit enough participants. Approaching recruitment through the lens of behavioral science can help trialists to understand influences on the decision to participate and use them to increase recruitment. Although this approach is promising, the use of behavioral influences during recruitment is in tension with the ethical principle of respect for persons, as at least some of these influences could be used to manipulate potential participants. In this paper, we examine this tension by discussing two types of behavioral influences: one example involves physician recommendations, and the other involves framing of information to exploit cognitive biases. We argue that despite the apparent tension with ethical principles, influencing trial participants through behavior change strategies can be ethically acceptable. However, we argue that trialists have a positive obligation to analyze their recruitment strategies for behavioral influences and disclose these upfront to the research ethics committee. But we also acknowledge that since neither trialists nor ethics committees are presently well equipped to perform these analyses, additional resources and guidance are needed. We close by outlining a path toward the development of such guidance.
The maladaptive domains according to the alternative model of personality disorders (AMPD) criterion B in patients with affective disorders and temperamental triads related to these domains: two unique profiles
Authors: Komasi Saeid , Jananeh Minoo , Mahdavi Sahar , Shademan Tahereh , Vaysi Anis , Shahlaee Mehrnoosh , Mirani Atefeh , Chamandoust Zahra , Saeidi Mozhgan
Published: March 2023

Objectives

The study aimed to (i) compare the maladaptive domains and facets according to the Alternative Model of Personality Disorders (AMPD) Criterion B in patients with a type II bipolar disorder (BD-II) or major depressive disorder (MDD) with healthy controls (HCs), and (ii) investigating the relationship between affective temperaments and these domains and facets in the total sample.

Methods

Outpatients diagnosed with current BD-II (n = 37; female 62.2%) or MDD (n = 17; female 82.4%) based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria and community HCs (n = 177; female 62.1%) in Kermanshah from July to October 2020 included this case-control study. All participants completed the Personality Inventory for DSM-5 (PID-5), the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A), and the second version of the Beck Depression Inventory (BDI-II). Data were analyzed using analysis of variance (ANOVA), Pearson correlation, and multiple regression.

Results

The score of patients with BD-II in all five domains and those with MDD in three domains including negative affectivity, detachment, and disinhibition are significantly higher than the HCs (p < 0.05). Depressive temperament (related to negative affectivity, detachment, and disinhibition) and cyclothymic temperament (related to antagonism and psychoticism) were the most important correlates of the maladaptive domains.

Conclusions

Two unique profiles are proposed, including three domains of negative affectivity, detachment, and disinhibition associated with the depressive temperament for MDD, and two domains of antagonism and psychoticism related to cyclothymic temperament for BD-II.
Biotic and abiotic effects of soil organic matter on the phytoavailable phosphorus in soils: a review
Authors: Jindo Keiji , Audette Yuki , Olivares Fabio Lopez , Canellas Luciano Pasqualoto , Smith D. Scott , Paul Voroney R.
Published: March 2023

Soil organic matter (SOM) has a critical role in regulating soil phosphorus (P) dynamics and producing phytoavailable P. However, soil P dynamics are often explained mainly by the effects of soil pH, clay contents, and elemental compositions, such as calcium, iron, and aluminum. Therefore, a better understanding of the mechanisms of how SOM influences phytoavailable P in soils is required for establishing effective agricultural management for soil health and enhancement of soil fertility, especially P-use efficiency. In this review, the following abiotic and biotic mechanisms are discussed; (1) competitive sorption between SOM with P for positively charged adsorption sites of clays and metal oxides (abiotic reaction), (2) competitive complexations between SOM with P for cations (abiotic reaction), (3) competitive complexations between incorporation of P by binary complexations of SOM and bridging cations with the formation of stable P minerals (abiotic reaction), (4) enhanced activities of enzymes, which affects soil P dynamics (biotic reaction), (5) mineralization/immobilization of P during the decay of SOM (biotic reaction), and (6) solubilization of inorganic P mediated by organic acids released by microbes (biotic reaction).

Graphical Abstract
Finite element analysis on dynamic behavior of sheet pile quay wall dredged and improved seaside subsoil using cement deep mixing
Authors: Nguyen Anh-Dan , Nguyen Viet-Thanh , Kim Young-Sang
Published: March 2023

Sheet pile wall structures are commonly applied in coastal projects, particularly for the quay wall. This structural type normally is used in places where the ground has a low bearing capacity and is easily penetrable. Many sheet pile quay walls constructed in the past had low front water depth and did not satisfy the requirements of current standards. This issue could be addressed by improving the ground in front of the wall using cement deep mixing (CDM) and then excavating to increase the water depth in front of the wall. This paper numerically evaluated the dynamic behavior of the sheet pile wall after renovation. The numerical model was performed based on the finite element method (FEM) using the PLAXIS 2D program. The study focused on investigating typical parameters of the quay wall improved using the CDM, such as bending moment and displacement of sheet pile and the development of excess pore water pressure (EPWP) in the backfill. These results were compared to those of the quay wall without the CDM to elucidate the advantages of this method. In addition, the influence of some factors on the quay wall behavior, such as earthquake excitation characteristics, CDM area, and CDM strength, was also evaluated. The results demonstrated that the ground improvement using the CDM significantly decreased the bending moment and displacement of the sheet pile wall. The excitation characteristics did not affect the deformed shape of the sheet pile. With the constant CDM depth, the sheet pile displacement decreased with an increase in the improvement width until it reached a limitation. The increasing CDM strength also decreased the displacement of the wall until it raised a certain value. This demonstrated that this method was technically feasible, and it could be considered to study further by experiment before applying in practice.
Improved seismic envelope full-waveform inversion
Authors: Xiong Kai , Lumley David , Zhou Wei
Published: March 2023

The envelope full-waveform-inversion method has the potential to greatly improve the estimation of long-wavelength components of subsurface seismic velocity, and simultaneously avoid or reduce inversion cycle skipping, by fitting the envelopes of observed and modeled seismic waveform data, rather than fitting the waveforms directly. However, some issues such as instability of the adjoint source and gradient term make it challenging to use in practice for many seismology applications. We examine the envelope inversion (EI) methods with different envelope function exponent p values from an adjoint source analysis perspective and reveal the adverse effects of the adjoint source weighting term on the data residuals, which degrade or mute important inversion gradient contributions, especially from reflected or scattered phases in the seismic data. We develop the theory and implementation for an improved EI (IEI) method by adding an upshift constant (zero-frequency direct current [DC] bias term) to the seismic waveform data before calculating the envelope functions, which can help solve the instability issue of the adjoint source of the EI with power value p = 1. Our approach is different than the common but simple addition of a “water-level” damping constant in the denominator of the data residual-weighting term, which can ignore important information contained in the data residuals. Our IEI method becomes a mixed envelope-waveform objective function, which introduces a new adjoint source weighting term that can preserve all of the information contained in the data residuals, by boosting the low-amplitude phases of the seismic waveform, while simultaneously preserving the correct envelope (energy shape) of the high-amplitude phases. We test the performance of all three methods in detail using the highly realistic SEAM4D model and data and find the advantages of our new IEI method compared with conventional EI and full-waveform inversion methods.
Re-Evaluation of Pathologic Complete Response as a Surrogate for Event-Free and Overall Survival in Human Epidermal Growth Factor Receptor 2–Positive, Early Breast Cancer Treated With Neoadjuvant Therapy Including Anti–Human Epidermal Growth Factor Receptor 2 Therapy
Authors: Squifflet Pierre , Saad Everardo D. , Loibl Sibylle , van Mackelenbergh Marion T. , Untch Michael , Rastogi Priya , Gianni Luca , Schneeweiss Andreas , Conte Pierfranco , Piccart Martine , Bonnefoi Hervé , Jackisch Christian , Nekljudova Valentina , Tang Gong , Valagussa Pinuccia , Neate Colin , Gelber Richard , Poncet Coralie , Heinzmann Dominik , Denkert Carsten , Geyer Charles E. , Cortes Javier , Guarneri Valentina , de Azambuja Evandro , Cameron David , Ismael Gustavo , Wolmark Norman , Cortazar Patricia , Buyse Marc ,   on behalf of the CTNeoBC Project
Published: March 2023

PURPOSE

Pathologic complete response (pCR) has prognostic importance and is frequently used as a primary end point, but doubts remain about its validity as a surrogate for event-free survival (EFS) and overall survival (OS) in human epidermal growth factor receptor 2 (HER2)–positive, early breast cancer.

METHODS

We obtained individual-patient data from randomized trials of neoadjuvant anti-HER2 therapy that enrolled at least 100 patients, had data for pCR, EFS, and OS, and a median follow-up of at least 3 years. We quantified the patient-level association between pCR (defined as ypT0/Tis ypN0) and both EFS and OS using odds ratios (ORs, with ORs >1.00 indicating a benefit from achieving a pCR). We quantified the trial-level association between treatment effects on pCR and on EFS and OS using R2 (with values above 0.75 considered as indicating strong associations).

RESULTS

Eleven of 15 eligible trials had data for analysis (3,980 patients, with a median follow-up of 62 months). Considering all trials, we found strong patient-level associations, with ORs of 2.64 (95% CI, 2.20 to 3.07) for EFS and 3.15 (95% CI, 2.38 to 3.91) for OS; however, trial-level associations were weak, with an unadjusted R2 of 0.23 (95% CI, 0 to 0.66) for EFS and 0.02 (95% CI, 0 to 0.17) for OS. We found qualitatively similar results when grouping trials according to different clinical questions, when analyzing only patients with hormone receptor–negative disease, and when using a more stringent definition of pCR (ypT0 ypN0).

CONCLUSION

Although pCR may be useful for patient management, it cannot be considered as a surrogate for EFS or OS in neoadjuvant trials of HER2-positive, operable breast cancer.
Leveraging Prior Healthy Participant Pharmacokinetic Data to Evaluate the Impact of Renal and Hepatic Impairment on Ritlecitinib Pharmacokinetics
Authors: Purohit Vivek , Huh Yeamin , Wojciechowski Jessica , Plotka Anna , Salts Stephanie , Antinew Jeremias , Dimitrova Angela , Nicholas Timothy
Published: March 2023

Ritlecitinib is a selective, covalent, irreversible inhibitor of Janus kinase 3 (JAK3) and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinases. Pharmacokinetics and safety of ritlecitinib in participants with hepatic (Study 1) or renal (Study 2) impairment were to be characterized from two phase I studies. Due to a study pause caused by the COVID-19 pandemic, the study 2 healthy participant (HP) cohort was not recruited; however, the demography of the severe renal impairment cohort closely matched the study 1 HP cohort. We present results from each study and two innovative approaches to utilizing available HP data as reference data for study 2: a statistical approach using analysis of variance and an in silico simulation of an HP cohort created using a population pharmacokinetics (POPPK) model derived from several ritlecitinib studies. For study 1, the observed area under the curve for 24-h dosing interval and maximum plasma concentration for HPs and their observed geometric mean ratios (participants with moderate hepatic impairment vs HPs) were within 90% prediction intervals from the POPPK simulation-based approach, thereby validating the latter approach. When applied to study 2, both the statistical and POPPK simulation approaches demonstrated that patients with renal impairment would not require ritlecitinib dose modification. In both phase I studies, ritlecitinib was generally safe and well tolerated. These analyses represent a new methodology for generating reference HP cohorts in special population studies for drugs in development with well-characterized pharmacokinetics in HPs and adequate POPPK models.

Trial Registration

ClinicalTrials.gov NCT04037865, NCT04016077, NCT02309827, NCT02684760, and NCT02969044.

Graphical Abstract
Approach to the Patient With Prolactinoma
Authors: Auriemma Renata S , Pirchio Rosa , Pivonello Claudia , Garifalos Francesco , Colao Annamaria , Pivonello Rosario
Published: March 2023

Prolactinomas are the most common pituitary tumor histotype, with microprolactinomas being prevalent in women and macroprolactinomas in men. Hyperprolactinemia is among the most common causes of hypogonadotropic hypogonadism in both sexes, prompting medical advice for hypogonadism (infertility, oligo-amenorrhea, impotence, osteoporosis/osteopenia) in both sexes, and for signs and symptoms of mass effects (hypopituitarism, visual loss, optic chiasm compression, cranial nerve deficits, headaches) predominantly in men. Diagnostic workup involves a single prolactin measurement and pituitary imaging, but some laboratory artifacts (ie, the “hook effect” and macroprolactin) can complicate or delay the diagnosis. The treatment of choice for prolactinomas is represented by dopamine agonists, mainly cabergoline, which are able to induce disease control, restore fertility in both sexes, and definitively cure one-third of patients, thus permitting treatment discontinuation. Pregnancy and menopause may promote spontaneous prolactin decline and anticipate cabergoline discontinuation in women. Surgery and/or radiotherapy are indicated in case of resistance to cabergoline not overcome by the increase in drug dose up to the maximally tolerated or the patient's personal choice of surgery. The evidence of resistance to cabergoline in invasive and proliferative tumors may indicate biological aggressiveness, thus requiring alternative therapeutic approaches mainly based on temozolomide use as monotherapy or combined with radiotherapy. In uncontrolled patients, new medical approaches (alternative hormonal treatments, cytotoxic drugs, peptide receptor radionuclide therapy, mTOR/Akt inhibitors, tyrosine kinase inhibitors, or immunotherapy) may be offered but the experience collected to date is still very scant. This article reviews different facets of prolactinomas and discusses approaches to the condition in more common clinical situations.
Prevalence of Cortisol Cosecretion in Patients With Primary Aldosteronism: Role of Metanephrine in Adrenal Vein Sampling
Authors: Buffolo Fabrizio , Pieroni Jacopo , Ponzetto Federico , Forestiero Vittorio , Rossato Denis , Fonio Paolo , Nonnato Antonello , Settanni Fabio , Mulatero Paolo , Mengozzi Giulio , Monticone Silvia
Published: March 2023

Context

Adrenal venous sampling (AVS) is the gold standard procedure for subtype diagnosis in patients with primary aldosteronism (PA). Cortisol is usually adopted for the normalization of aldosterone levels in peripheral and adrenal samples. However, asymmetrical cortisol secretion can potentially affect the lateralization index, leading to subtype misdiagnosis.

Objective

We aimed to assess the prevalence of asymmetrical cortisol secretion in patients undergoing AVS and whether variations in adrenal vein cortisol might influence AVS interpretations. We then evaluated the use of metanephrines for the normalization of aldosterone levels for lateralization index.

Methods

We retrospectively included 101 patients with PA who underwent AVS: 49 patients underwent unstimulated AVS, while 52 patients underwent both unstimulated and cosyntropin-stimulated AVS. Eighty-eight patients had bilateral successful AVS according to metanephrine ratio. We assessed the prevalence of asymmetrical cortisol secretion through the cortisol to metanephrine (C/M) lateralization index (LI). We then evaluated whether the use of aldosterone to metanephrine (A/M) LI can improve the diagnostic accuracy of AVS compared with aldosterone to cortisol (A/C) LI.

Results

Asymmetrical cortisol secretion is present in 18% of patients with PA. Diagnosis with A/M LI and A/C LI is discordant in 14% of patients: 9% had a diagnosis of unilateral PA with A/M LI instead of bilateral PA with A/C LI and 5% had a diagnosis of bilateral PA with A/M LI instead of unilateral PA.

Conclusion

The assessment of metanephrine levels in AVS is useful for the determination of selectivity and lateralization, allowing an accurate diagnosis, especially in patients with asymmetrical cortisol secretion.
Efficacy and association of hyperbaric oxygen therapy combined with butylphthalide and oxiracetam with serum levels of inflammatory markers in vascular cognitive impairment after acute ischemic stroke
Authors: Dong Quanbin , Wu Mingxiu , Hu Wenge
Published: March 2023

Objectives: This study evaluated the efficacy of hyperbaric oxygen therapy (HBOT) combined with butylphthalide (NBP) and oxiracetam (OXR) for vascular cognitive impairment after acute ischemic stroke and investigated the association between such combination therapy and the serum levels of inflammatory markers.

Methods: This was a prospective study which included eighty patients with post-AIS cognitive impairment (PAISCI) treated in Dongguan City People’s Hospital from January 2020 to January 2022. They were randomized into study group and control group. The control group was provided with conventional therapy consisting of NBP for intravenous transfusion and oral OXR, while the study group received combination therapy of HBOT, NBP, and OXR. A comparison was drawn between the two groups regarding clinical outcomes, levels of recovery of cognitive and neurological function and intelligence, changes in inflammatory markers, and incidence of adverse drug reactions (ADRs).

Results: The response rate of the study group was significantly higher than that of the control group (p=0.04). The cognitive function scores of the study group were significantly better than those of the control group at the end of treatment (p<0.05). The post-treatment levels of inflammatory markers were significantly reduced in the study group when compared with the control group (p<0.05). At two weeks after treatment, the ADR rate of study group was significantly lower than the control group (p=0.03).

Conclusions: The combination therapy of HBOT, NBP, and OXR demonstrates robust efficacy in patients with PAISCI. It is deemed to be a safe and effective treatment regimen.

doi: https://doi.org/10.12669/pjms.39.3.6828

How to cite this: Dong Q, Wu M, Hu W. Efficacy and association of hyperbaric oxygen therapy combined with butylphthalide and oxiracetam with serum levels of inflammatory markers in vascular cognitive impairment after acute ischemic stroke. Pak J Med Sci. 2023;39(3):829-834.  doi: https://doi.org/10.12669/pjms.39.3.6828

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Η χρήση του υαλουρονικού οξέος και της κλαριθρομυκίνης στην αντιμετώπιση της ψευδομεμβρανώδους τριγωνίτιδας σε γυναίκες αναπαραγωγικής ηλικίας
Authors: Σταυρόπουλος Μάριος
Published: March 2023

Σκοπός: Ο καθορισμός της αποτελεσματικότητας και της ασφάλειας της ενδοκυστικής χορήγησης υαλουρονικού οξέος (HA) σε συμπτωματικές γυναίκες με ψευδομεμβρανώδη τριγωνίτιδα και η συσχέτιση της σοβαρότητας των συμπτωμάτων με τα ενδοσκοπικά και ιστοπαθολογικά ευρήματα.Ασθενείς και μέθοδοι: Συνολικά συμπεριλήφθηκαν 37 γυναίκες ασθενείς ηλικίας 20-46 ετών. Όλες οι ασθενείς υποβλήθηκαν αρχικά σε κυστεοσκόπηση και βιοψία του τριγώνου της ουροδόχου κύστης και στη συνέχεια έλαβαν ενδοκυστική θεραπεία με εγχύσεις διαλύματος υαλουρονικού νατρίου 40mg/ml, μία φορά την εβδομάδα για 10 εβδομάδες και στη συνέχεια μία φορά το μήνα για 10 μήνες. Η κλινική ανταπόκριση στη θεραπεία αξιολογήθηκε με την χρήση του ερωτηματολογίου συμπτωμάτων για τον Πόνο και την Επιτακτικότητα/Συχνουρία (Pain and Urgency / Frequency Symptom Scale - PUF), την Οπτική Αναλογική Κλίμακα (Visual Analogue Scale - VAS) για τον πόνο και την επιτακτικότητα και τη λειτουργική χωρητικότητα της κύστης μέσω ενός ημερολόγιου ούρησης. Μετά την ολοκλήρωση της θεραπείας, οι ασθενείς υποβλήθηκαν σε επαναληπτική κυστεοσκόπηση και νέα βιοψία από το τρίγωνο της ουροδόχου κύστης. Τα συμπτώματα των ασθενών συσχετίστηκαν με τα κυστεοσκοπικά και τα παθολογοανατομικά ευρήματα τόσο πριν όσο και μετά την θεραπεία. Αποτελέσματα: Το αρχικό μέσο σκορ για τον πόνο μειώθηκε από 5.5 σε 2.8 στις 10 εβδομάδες (τέλος σχήματος εισαγωγής) (p<0.001) και περαιτέρω σε 2.4 στους 12 μήνες (τέλος σχήματος συντήρησης) (p<0.001). Το μέσο σκορ για την επιτακτικότητα εμφάνισε μείωση από 6.9 αρχικά, σε 3.8 στις 10 εβδομάδες (p<0.001) και επιπλέον σε 3.3 μετά το τέλος της θεραπείας (p<0.001). Το μέσο σκορ συμπτωμάτων PUF αρχικά μειώθηκε σημαντικά από 20.5 σε 12.1 στις 10 εβδομάδες (p<0.001) και εμφάνισε περαιτέρω μείωση σε 10.1 στους 12 μήνες (p=0.21). Η μέση λειτουργική χωρητικότητα της ουροδόχου κύστης αυξήθηκε από 125ml πριν την έναρξη της θεραπείας, σε 204ml μετά το πέρας του θεραπευτικού πρωτοκόλλου (p<0.001). Δεν παρατηρήθηκε στατιστικά σημαντική συσχέτιση μεταξύ του αρχικού σκορ συμπτωμάτων PUF και της έκτασης της τριγωνίτιδας κατά την αρχική διαγνωστική κυστεοσκόπηση (p=0.87). Επιπλέον, δεν παρατηρήθηκε στατιστικά σημαντική διαφορά στη μεταβολή του σκορ συμπτωμάτων PUF μεταξύ των ασθενών με βελτιωμένα κυστεοσκοπικά ευρήματα και εκείνων των οποίων η εικόνα της τριγωνίτιδας παρέμεινε αμετάβλητη στην επαναληπτική κυστεοσκόπηση (p=0.74). Τέλος, δεν αναφέρθηκαν σημαντικές διαφορές μεταξύ της αρχικής και τελικής βιοψίας του τριγώνου της κύστης σε όλες τις ασθενείς.Συμπέρασμα: Η ενδοκυστική θεραπεία με ΗΑ είναι μια αποτελεσματική και ασφαλής μέθοδος για την αντιμετώπιση των συμπτωμάτων σε γυναίκες αναπαραγωγικής ηλικίας με ψευδομεμβρανώδη τριγωνίτιδα, αν και δεν ήταν δυνατό να τεκμηριωθεί μια ξεκάθαρη σχέση μεταξύ των συμπτωμάτων και της κλινικής αυτής οντότητας.
Ausgrabungen am Basler Murus Gallicus / Teil 3
Authors: Rodel Sylvia
Published: March 2023

Die Publikation umfasst die Auswertung des gesamten Fundmaterials aus den spätlatènezeitlichen Horizonten der Grabungen 1990–1993 im Bereich des Murus Gallicus auf dem Münsterhügel. Besondere Aufmerksamkeit gilt der Frage, welche Faktoren für die unterschiedlichen Zusammensetzung des Fundspektrums in den einzelnen Horizonten verantwortlich sind und ob sich chronologisch deutbare Entwicklungstendenzen innerhalb der sieben spätlatènezeitlichen Horizonte abzeichnen.