In Science Journals.

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In Science Journals.

Highlights from the Science family of journals.

In Other Journals.

Editors' selections from the current scientific literature.

Metabolic, cardiac, and bone health testing in patients with prostate cancer on androgen-deprivation therapy: A population-based assessment of adherence to therapeutic monitoring guidelines.

BACKGROUND: Androgen-deprivation therapy (ADT) remains a cornerstone in treatment for patients with advanced prostate cancer. ADT is associated with several adverse effects, including osteoporosis, metabolic syndrome, and cardiovascular events, leading to guidelines recommending routine testing to monitor for these toxicities. There is a lack of data assessing adherence to these recommendations. METHODS: The authors conducted a retrospective cohort study using administrative data from Ontario, Canada between 2008 and 2021. They identified all older men (aged 65 years and older) who received ADT for prostate cancer using comprehensive provincial health databases. The primary outcomes were the use of testing for lipids, dysglycemia (glucose), bone health serum, and bone density between 6 weeks before and 1 year after the initiation of ADT. RESULTS: In total, 29,097 patients were examined, of whom 52.8% were prescribed ADT by urologists, 37.9% were prescribed ADT by radiation oncologists, 2.8% were prescribed ADT by medical oncologists, and 2.4% were prescribed ADT by other physicians. Adherence to guidelines was low: only 21.3% of patients received a bone density scan, 41.2% underwent bone health-related serum tests, 51.3% completed a lipid profile, and 65.9% underwent dysglycemia testing within 1 year of diagnosis. Overall, only 11.9% of patients received all of the recommended investigations. Adherence to testing did not appear to improve over time (2008-2021) or with guideline publication. Patient (age) and physician (specialty) factors had important associations with adherence to testing. CONCLUSIONS: Most patients receiving ADT for prostate cancer do not receive recommended testing to monitor for treatment-related toxicity. Further study is required to address barriers to therapeutic monitoring of men on ADT and to reduce treatment-associated adverse events.

Assessment of the Incidence and Risk Factors of Stress Urinary Incontinence in Women after Cervical Cancer Surgery: A Single-Centre Retrospective Study.

BACKGROUND: Stress urinary incontinence (SUI) is a common postoperative complication that significantly affects the quality of life in women who have undergone radical hysterectomy for cervical cancer. This study evaluates the incidence and risk factors associated with SUI in women after cervical cancer surgery. METHODS: This case-control study included women diagnosed with cervical cancer who underwent radical hysterectomy at our hospital between May 2020 and May 2023. Participants were divided into two groups based on the presence of postoperative SUI, namely the SUI group and the SUI-free group. Inclusion criteria required the absence of preoperative urinary incontinence and stable vital signs. Data were collected on demographic characteristics, tumour histology and staging, urodynamic parameters, and intraoperative and postoperative factors. RESULTS: Ninety-seven patients with cervical cancer who underwent radical hysterectomy were divided into two groups: The SUI group (n = 27) and the SUI-free group (n = 70), with an SUI incidence of 27.8% in the study population. Significant differences between the SUI and SUI-free groups were observed in menopausal status (p = 0.026), chronic constipation (p = 0.011), and tumour diameter (p < 0.001). Urodynamic assessments revealed a higher maximum urinary flow rate (Qmax) in the SUI group compared to the SUI-free group (21.36 ± 6.41 vs. 17.38 ± 5.18 mL/s; p = 0.002). Logistic regression analysis identified menopause (odds ratio (OR) = 7.700, 95% confidence interval (CI) = 1.256-47.192), chronic constipation (OR = 9.918, 95% CI = 1.387-70.911), Qmax (OR = 1.302, 95% CI = 1.061-1.598), and surgery duration (OR = 1.040, 95% CI = 1.001-1.081) as independent protective factors. CONCLUSIONS: SUI is a significant postoperative complication in women undergoing cervical cancer surgery. Menopause, chronic constipation, tumour diameter, Qmax, and surgery duration were independent risk factors.

Light-Promoted Extraction of Precious Metals Using a Porphyrin-integrated One-dimensional Covalent Organic Framework.

Precious metals are valuable materials for the chemical industry, but they are scarce and pose a risk of supply disruption. Recycling precious metals from waste is a promising strategy, here we tactfully utilize light irradiation as an environmental-friendly and energy-saving adjunctive strategy to promote the reduction of precious metal ions, thereby improving the adsorption capacity and kinetics. A newly light-sensitive covalent organic framework (PP-COF) was synthesized to illustrate the effectiveness and feasibility of this light auxiliary strategy. The equilibrium adsorption capacities of PP-COF with light irradiation towards gold, platinum, and silver ions are 4729, 573, and 519 mg g-1, which are 3.3, 1.9, and 1.2 times the adsorption capacities under dark condition. Significantly, a filtration column with PP-COF can recover more than 99.8% of the gold ions in the simulated e-waste leachates with light irradiation, and 1 gram of PP-COF can recover gold from up to 0.15 tonne of e-waste leachates. Interestingly, the captured precious metals by PP-COF with light irradiation mainly exist in the micron-sized particles, which can be easily separated by extraction. We believe this work can contribute to precious metal recovery and circular economy for recycling resources.

A Simplified Version of the Chinese Tinnitus Disorder Scale and its Psychometric Characteristics.

OBJECTIVE: This study aims to design a Concise and Practical Chinese Tinnitus Disorder Scale (CPCTDS), evaluate its psychometric measurement characteristics, and help doctors in making diagnoses and treatments. METHODS: A sample of 482 tinnitus patients completed CPCTDS. The patients also completed the Center for Epidemiologic Studies-Depression Scale (CES-D), the Beck Anxiety Inventory (BAI), and the Tinnitus Functional Index (TFI). RESULTS: The eight items of CPCTDS were extracted through its exploratory factor analysis, which had strong internal consistency (Cronbach's α = 0.855). The correlations between the total scores of CPCTDS and Tinnitus Disability Inventory (TDI; r = 0.960, P < 0.05) and TFI (r = 0.749, P < 0.05) indicated a good criterion validity. The correlation of the CPCTDS emotional subscale with the TFI emotional subscale (r = 0.650, P < 0.05), CES-D (r = 0.488, P < 0.05), and BAI (r =.384, p< 0.05) showed that the convergent validity of CPCTDS was satisfactory. CONCLUSIONS: CPCTDS and the original Chinese version of TDI were highly reliable and valid. This finding shows that the two scales can be reliably used to assess the severity of tinnitus in clinical areas.

Ferroptosis-related oxaliplatin resistance in multiple cancers: Potential roles and therapeutic Implications.

Oxaliplatin (OXA)-based therapy is effective in the treatment of multiple cancers. However, primary or acquired OXA resistance remains an emerging challenge for its clinical application. Ferroptosis is an iron-dependent mode of cell death that has been demonstrated to play an essential role in the chemoresistance of many drugs, including OXA. In particular, dysregulation of SLC7A11-GPX4, one of the major antioxidant systems of ferroptosis, was found in the OXA resistance of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). In addition, Nrf2, the upstream regulator of GPX4 and many other antioxidant factors, is also involved in the OXA resistance of CRC and HCC. Inhibition of SLC7A11-GPX4 or Nrf2 by genetic deletion of pharmaceutical inhibition could significantly reverse OXA resistance. Long noncoding RNA (lncRNA) also participates in chemoresistance and ferroptosis of cancer cells. Specifically, LINC01134 promotes the recruitment of Nrf2 to the promoter of GPX4, thereby exerting transcriptional regulation of GPX4, which eventually increases the OXA sensitivity of HCC through upregulation of ferroptosis. On the other hand, a novel lncRNA DACT3-AS1 sensitizes gastric cancer cells to OXA through miR-181a-5p/sirtuin 1(SIRT1)-mediated ferroptosis. Therapies based on ferroptosis or a combination of OXA and ferroptosis enhancers could provide new therapeutic insights to overcome OXA resistance. In the present review, we present the current understanding of ferroptosis-related OXA resistance, highlight ferroptosis pathogenesis in OXA chemoresistance, and summarize available therapies that target OXA resistance by enhancing ferroptosis.

In Science Journals.

Highlights from the Science family of journals.

Comparison of Industry-Sponsored Trials (IST) and Investigator-Initiated Trials (IIT) in Advanced Genitourinary Cancers in the United States, Canada, United Kingdom and France.

BACKGROUND: Clinical trials are categorized as industry sponsored trials (ISTs) or investigator-initiated trials (IITs) based on the source of funding and sponsor of the trial. ISTs are usually run by pharmaceutical companies, and are primarily aimed at developing new drugs that ultimately gain regulatory approval. IITs are developed by academic investigators or cooperative groups, often sparked by a clinical need. Both are vital in advancing the field of oncology. To date, little has been published about current trends in ISTs or IITs in genitourinary (GU) oncology. The aim of this study was to assess growth trends of GU oncology ISTs and IITs in 4 countries with similar healthcare infrastructures. METHODS: We searched ClinicalTrials.gov for bladder, kidney, and prostate cancer trials conducted in the United States (US), Canada, France, and United Kingdom (UK) from January 2007 to December 2021. Trials were determined to be ISTs or IITs based on their funding source and sponsor. Trials were characterized based on type, purpose, phase, participants, masking, assignment, and allocation. RESULTS: Overall, 5,834 GU trials were identified, with a balanced distribution of ISTs (n = 3064, n = 52.5%) and IITs (n = 2770, 47.4%). By country, the US conducted the most GU trials (n = 3814) followed by Canada (n = 709), France (n = 677), and the UK (n = 634). Most ISTs were phase 3 trials with over 500 participants while most IITs were open-label phase 2 studies with only 20-49 participants. From 2017 onwards, there was a shift towards more ISTs, most noticeably in Canada and the UK. The COVID-19 pandemic did not have a major impact on the growth of ISTs and IITs. CONCLUSION: The gap between ISTs and IITs continues to widen, likely driven by resource and funding challenges faced by investigators. Barriers to completing IITs need to be better understood to promote IIT development and maintain their academically driven intentions.

Understanding the hierarchical structure of collagen fibers of the human periodontal ligament: Implications for biomechanical characteristics.

The periodontal ligament (PDL) is a unique fibrous connective tissue that regulates periodontal homeostasis mechanisms. Its biomechanical properties primarily reside in the hierarchical and non-uniform collagenous network. This study aimed to investigate the region-specific structure and composition of collagen fibers in the PDL at various scales and to explore their relationship with mechanical properties in a split-mouth design. Fresh human cadaver transverse PDL specimens of maxillary anterior teeth were categorized into cervical, middle, and apical groups. These specimens were analyzed via Masson's trichrome staining, scanning electron microscopy, picrosirius red (PSR) staining, three-dimensional (3D) reconstruction, Raman spectroscopy, and uniaxial tensile test. Statistical analyses were performed to compare the structural, compositional, and tensile properties among the groups. Notably, the middle PDL samples exhibited superior tensile strength and higher fiber area fraction than the other two transverse sections. Despite a higher mineral-to-matrix ratio and a different collagen secondary structure, the apical PDL demonstrated a relatively weaker tensile strength, possibly associated with its discovered sparser collagen fiber areal fraction. The cervical region, characterized by a mediocre fiber areal fraction, displayed diminished tensile strength. The 3D reconstructed collagenous network model and PSR staining exposed the fiber interaction and the micropores. Microscale porosity and variations in collagen secondary structure, particularly in the apical region, suggest adaptive mechanisms for accommodating compressive forces and maintaining functional integrity. Variance in the tensile properties of samples in different force directions indicated the significant influence of fiber orientation and root level on tissue mechanics. STATEMENT OF SIGNIFICANCE: This study provides critical insights into the biomechanical and structural properties of the human periodontal ligament (PDL), particularly focusing on the underexplored anterior teeth. Through advanced techniques like SEM, histological staining, 3D reconstruction, Raman spectroscopy, and tensile testing, we reveal significant regional variations in PDL collagen organization, composition, and biomechanical properties. Our findings address a crucial knowledge gap concerning the material mechanics of the PDL, offering a foundational understanding for future periodontal tissue engineering and biomimetic material development. This multi-scale analysis underscores the importance of both mesoscale structural characteristics and nanoscale molecular structures in maintaining PDL mechanical integrity.

A brief model evaluated outcomes after liver transplantation based on the matching of donor graft and recipient.

BACKGROUND: A precise model for predicting outcomes is needed to guide perioperative management. With the developments of liver transplantation (LT) discipline, previous models may become inappropriate or noncomprehensive. Thus, we aimed to develop a novel model integrating variables from donors and recipients for quick assessment of transplant outcomes. METHODS: The risk model was based on Cox regression in a randomly selected derivation cohort and verified in a validation cohort. Perioperative data and overall survival were compared between stratifications grouped by X-tile. Receiver operating characteristic curve and decision curve analysis were used to compare the models. Violin and raincloud plots were generated to present post-LT complications distributed in different stratifications. RESULTS: Overall, 528 patients receiving LT from 2 centers were included with 2/3 in the derivation cohort and 1/3 in the validation cohort. Cox regression analysis showed that cold ischemia time (CIT) (P=0.012) and the Model for End-Stage Liver Disease (MELD) (P=0.007) score were predictors of survival. After comparison with the logarithmic models, the primitive algorithms of CIT and MELD were defined as the CIT-MELD Index (CMI). CMI was stratified by X-tile (grade 1 ≤1.06, 1.06< grade 2 ≤1.87, grade 3 >1.87). In both cohorts, CMI performed better in calculating transplant outcomes than the balance of risk score, including perioperative incidents and prevalence of complications. CONCLUSIONS: Model integrating variables from graft and recipient made the prediction more accurate and available. CMI provided new sight in outcome evaluation and risk factor management of LT.

In Science Journals.

Highlights from the Science family of journals.

Optimization and Stability Assessment of Monochamus alternatus Antimicrobial Peptide MaltAtt-1 in Komagataella phaffii GS115 for the Control of Pine Wood Nematode.

MaltAtt-1 is an antimicrobial peptide isolated from Monochamus alternatus with nematocidal activity against pine wood nematode. In this study, a eukaryotic expression system based on Komagataella phaffii GS115 was established, and its secretory expression of MaltAtt-1 was realized. The basic properties and secondary and tertiary structures of the antimicrobial peptide MaltAtt-1 were identified by bioinformatics analysis. MaltAtt-1 is a hydrophilic stable protein, mainly composed of an α-helix (Hh), ß-folds (Ee), and irregular curls (Cc). The optimal fermentation conditions for MaltAtt-1 were determined by a single-factor test and the Box-Behnken response surface method, including an induction time of 72 h, induction temperature of 30 °C, culture medium of pH 7.6, methanol volume fraction of 2.0%, and an initial glycerol concentration of 1%. The stability of MaltAtt-1 indicated its resistant to UV irradiation and repeated freezing and thawing, but the antibacterial activity decreased significantly under the influence of high temperature and a strong acid and base, and it decreased significantly to 1.1 cm and 0.83 cm at pH 2.0 and pH 10.0, respectively. The corrected mortality of B. xylophilus achieved 71.94% in 3 h at a concentration of 300 mg·L-1 MaltAtt-1 exposure. The results provide a theoretical basis for the antimicrobial peptide MaltAtt-1 to become a new green and efficient nematicide.

In Science Journals.

Highlights from the Science family of journals.

In Science Journals.

Highlights from the Science family of journals.

Testicular Germ Cell Tumors with Venous Tumor Thrombus: Prevalence, Presentation, and Management.

BACKGROUND AND OBJECTIVE: There are limited data on the prevalence and management of testicular germ cell tumor (TGCT) cases presenting with venous tumor thrombus (VTT). Our objectives were to describe the prevalence of TGCT with VTT, to identify a multicenter retrospective cohort, and to ascertain expert opinion regarding optimal management of this entity. METHODS: Using the IBM Marketscan database, we identified men with testicular cancer who underwent retroperitoneal lymph node dissection (RPLND) with concurrent VTT or inferior vena cava (IVC) tumor thrombectomy to estimate the prevalence of VTT in TGCT. To identify a multicenter retrospective cohort of patients, we surveyed surgeons and described the presentation, management, and outcomes for the cohort. KEY FINDINGS AND LIMITATIONS: The prevalence of TGCT with VTT in the IBM Marketscan database was 0.3% (n = 7/2517) when using stringent criteria and 3.1% (n = 79/2517) when using broad criteria. In response to our survey, 16 surgeons from ten centers contributed data for 34 patients. Most patients (n = 29, 85%) presented with nonseminomatous germ cell tumor. Surgical management was used for 93.9% (n = 31), including postchemotherapy tumor thrombectomy with primary cavorrhaphy in 63%. The Marketscan analysis was limited to insured individuals and did not include clinicopathological details, and use of billing codes may have included patients with stromal tumors. In addition, lack of responses to the anonymous survey limited data capture, and the RedCap survey did not address symptoms specific to IVC obstruction or allow central review of the imaging leading to VTT diagnosis. CONCLUSIONS AND CLINICAL IMPLICATIONS: VTT among males with TGCT is rare and requires complex multidisciplinary management, including venous tumor thrombectomy at the time of postchemotherapy RPLND. PATIENT SUMMARY: Using a medical database, we estimated that the frequency of testicular cancer cases in which the tumor extends into a blood vessel (called venous tumor thrombus, VTT) is just 0.3-3.1%. We carried out a survey of surgeons with experience of this condition. Our results indicate that although testicular cancers respond well to chemotherapy, VTT is less responsive and complex surgery is necessary for this rare condition.

Primary retroperitoneal lymph node dissection for metastatic non-seminomatous germ cell tumours: outcomes and adjuvant chemotherapy.

OBJECTIVES: To compare the outcomes and treatment burden of primary retroperitoneal lymph node dissection (pRPLND) alone versus pRPLND + adjuvant chemotherapy (AC) in patients with pathological stage II (PSII) non-seminomatous germ cell tumours (NSGCT). PATIENTS AND METHODS: Retrospective review of the Princess Margaret Cancer Center eTestes cancer database identified patients with PSII NSGCT after pRPLND between 1995 and 2020. The primary outcome was relapse-free survival (RFS). Secondary outcomes included disease-specific survival (DSS), burden of relapse treatment, and factors associated with relapse. RESULTS: A total of 109 PSII patients were included in the study. There were 96 patients treated with pRPLND alone and 13 treated with pRPLND + AC. The median follow-up was 61 months. The 5-year RFS was 72% for the pRPLND-only group vs 92% for the pRPLND + AC group (hazard ratio [HR] 4.372, 95% confidence interval [CI] 0.59-32.36; P = 0.11). Within the pRPLND-only group the 5-year RFS differed by pN stage (pN1 = 94% vs pN2/N3 = 67%, P = 0.03). Despite a higher relapse rate within the pRPLND-only group, the DSS was similar at 5 years (98% pRPLND only vs 100% pRPLND + AC, P = 0.48). Only 24 (25%) of the patients in the pRPLND-only group required any subsequent chemotherapy. Despite achieving similar survival, the cumulative post-RPLND treatment burden was less for the pRPLND-only group than the pRPLND+AC group overall (average 1.23 vs 2.46 cycles of chemotherapy per patient in group). CONCLUSION: The majority of patients with PSII NSGCT treated with pRPLND alone do not experience a recurrence or require chemotherapy. Despite a lower relapse risk when AC is given, no difference in survival was seen but higher chemotherapy burden was entertained. AC may constitute overtreatment for most patients with PSII NSGCT treated with pRPLND.

Bioanalysis of free antisense oligonucleotide payload from antibody-oligonucleotide conjugate by hybridization LC-MS/MS.

Background: Antisense oligonucleotides (ASOs) have been conjugated to various moieties, such as peptides, antibodies or Fab regions of antibodies, to enhance their delivery to target tissues. The quantitation of free ASO (ASO payload) is critical to characterize its pharmacokinetics/pharmacodynamics (PK/PD) properties and biodistribution after delivery of the peptide/antibody/Fab ASO conjugates.Results: We developed a hybridization-based LC-MS/MS methodology for quantification of free ASO in tissues in the presence of Fab-ASO and ASO with linker (ASO-linker).Conclusion: The developed method was applied to measure accurately the free ASO concentrations in liver and gastrocnemius in mice that were dosed with Fab-ASO. This methodology has also been applied to free ASO bioanalysis for other antibody-ASO and Fab-ASO conjugates in various tissues and plasma/serum samples.

[Box: see text].

In Science Journals.

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