Background: Recent publications underscore the need for updated recommendations addressing less radical surgery for <2 cm tumors, induction chemotherapy, or immunotherapy for locally advanced stages of cervical cancer, as well as for the systemic therapy for recurrent or metastatic cervical cancer. Aim: To summarize the current evidence for the diagnosis, treatment, and follow-up of cervical cancer and provide evidence-based clinical practice recommendations. Methods: Developed according to AGREE II standards, the guidelines classify scientific evidence based on the Agency for Health Technology Assessment and Tariff System criteria. Recommendations are graded by evidence strength and consensus level from the development group. Key Results: (1) Early-Stage Cancer: Stromal invasion and lymphovascular space involvement (LVSI) from pretreatment biopsy identify candidates for surgery, particularly for simple hysterectomy. (2) Surgical Approach: Minimally invasive surgery is not recommended, except for T1A, LVSI-negative tumors, due to a reduction in life expectancy. (3) Locally Advanced Cancer: concurrent chemoradiation (CCRT) followed by brachytherapy (BRT) is the cornerstone treatment. Low-risk patients (fewer than two metastatic nodes or FIGO IB2-II) may consider induction chemotherapy (ICT) followed by CCRT and BRT after 7 days. High-risk patients (two or more metastatic nodes or FIGO IIIA, IIIB, and IVA) benefit from pembrolizumab with CCRT and maintenance therapy. (4) Metastatic, Persistent, and Recurrent Cancer: A PD-L1 status from pretreatment biopsy identifies candidates for Pembrolizumab with available systemic treatment, while triplet therapy (Atezolizumab/Bevacizumab/chemotherapy) becomes a PD-L1-independent option. Conclusions: These evidence-based guidelines aim to improve clinical outcomes through precise treatment strategies based on individual risk factors, predictors, and disease stages.

UNASSIGNED: Persistent, mobile and toxic (PMT), or very persistent and very mobile (vPvM) substances are a wide class of chemicals that are recalcitrant to degradation, easily transported, and potentially harmful to humans and the environment. Due to their persistence and mobility, these substances are often widespread in the environment once emitted, particularly in water resources, causing increased challenges during water treatment processes. Some PMT/vPvM substances such as GenX and perfluorobutane sulfonic acid have been identified as substances of very high concern (SVHCs) under the European Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) regulation. With hundreds to thousands of potential PMT/vPvM substances yet to be assessed and managed, effective and efficient approaches that avoid a case-by-case assessment and prevent regrettable substitution are necessary to achieve the European Union\'s zero-pollution goal for a non-toxic environment by 2050.
UNASSIGNED: Substance grouping has helped global regulation of some highly hazardous chemicals, e.g., through the Montreal Protocol and the Stockholm Convention. This article explores the potential of grouping strategies for identifying, assessing and managing PMT/vPvM substances. The aim is to facilitate early identification of lesser-known or new substances that potentially meet PMT/vPvM criteria, prompt additional testing, avoid regrettable use or substitution, and integrate into existing risk management strategies. Thus, this article provides an overview of PMT/vPvM substances and reviews the definition of PMT/vPvM criteria and various lists of PMT/vPvM substances available. It covers the current definition of groups, compares the use of substance grouping for hazard assessment and regulation, and discusses the advantages and disadvantages of grouping substances for regulation. The article then explores strategies for grouping PMT/vPvM substances, including read-across, structural similarity and commonly retained moieties, as well as the potential application of these strategies using cheminformatics to predict P, M and T properties for selected examples.
UNASSIGNED: Effective substance grouping can accelerate the assessment and management of PMT/vPvM substances, especially for substances that lack information. Advances to read-across methods and cheminformatics tools are needed to support efficient and effective chemical management, preventing broad entry of hazardous chemicals into the global market and favouring safer and more sustainable alternatives.

A comprehensive pangenomic approach was employed to analyze the genomes of 75 type II methylotrophs spanning various genera. Our investigation revealed 256 exact core gene families shared by all 75 organisms, emphasizing their crucial role in the survival and adaptability of these organisms. Additionally, we predicted the functionality of 12 hypothetical proteins. The analysis unveiled a diverse array of genes associated with key metabolic pathways, including methane, serine, glyoxylate, and ethylmalonyl-CoA (EMC) metabolic pathways. While all selected organisms possessed essential genes for the serine pathway, Methylooceanibacter marginalis lacked serine hydroxymethyltransferase (SHMT), and Methylobacterium variabile exhibited both isozymes of SHMT, suggesting its potential to utilize a broader range of carbon sources. Notably, Methylobrevis sp. displayed a unique serine-glyoxylate transaminase isozyme not found in other organisms. Only nine organisms featured anaplerotic enzymes (isocitrate lyase and malate synthase) for the glyoxylate pathway, with the rest following the EMC pathway. Methylovirgula sp. 4MZ18 stood out by acquiring genes from both glyoxylate and EMC pathways, and Methylocapsa sp. S129 featured an A-form malate synthase, unlike the G-form found in the remaining organisms. Our findings also revealed distinct phylogenetic relationships and clustering patterns among type II methylotrophs, leading to the proposal of a separate genus for Methylovirgula sp. 4M-Z18 and Methylocapsa sp. S129. This pangenomic study unveils remarkable metabolic diversity, unique gene characteristics, and distinct clustering patterns of type II methylotrophs, providing valuable insights for future carbon sequestration and biotechnological applications.
OBJECTIVE: Methylotrophs have played a significant role in methane-based product production for many years. However, a comprehensive investigation into the diverse genetic architectures across different genera of methylotrophs has been lacking. This study fills this knowledge gap by enhancing our understanding of core hypothetical proteins and unique enzymes involved in methane oxidation, serine, glyoxylate, and ethylmalonyl-CoA pathways. These findings provide a valuable reference for researchers working with other methylotrophic species. Furthermore, this study not only unveils distinctive gene characteristics and phylogenetic relationships but also suggests a reclassification for Methylovirgula sp. 4M-Z18 and Methylocapsa sp. S129 into separate genera due to their unique attributes within their respective genus. Leveraging the synergies among various methylotrophic organisms, the scientific community can potentially optimize metabolite production, increasing the yield of desired end products and overall productivity.

Biofilm-associated infections caused by drug-resistant and persistent bacteria remain a significant clinical challenge. Here we report that farnesol, commercially available as a cosmetic and flavoring agent, shows significant anti-biofilm properties when dissolved in ethanol using a proprietary formulation emulsion technique. Farnesol in the new formulation inhibits biofilm formation and disrupts established biofilms for Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, including their polymicrobial biofilms, and, moreover, kills S. aureus persister cells that have developed tolerance to antibiotics. No resistance to farnesol was observed for S. aureus after twenty continuous passages. Farnesol combats biofilms by direct killing, while also facilitating biofilm detachment. Furthermore, farnesol was safe and effective for preventing and treating biofilm-associated infections of both types of bacteria in an ex vivo burned human skin model. These data suggest that farnesol in the new formulation is an effective broad-spectrum anti-biofilm agent with promising clinical potential. Due to its established safety, low-cost, versatility, and excellent efficacy-including ability to reduce persistent and resistant microbial populations-farnesol in the proprietary formulation represents a compelling transformative, translational, and commercial platform for addressing many unsolved clinical challenges.

The relationship of PAX1/JAM3 methylation as well as HPV viral load (VL) with cervical lesions has been reported, but their role in persistent HPV infection without cervical high-grade lesions has not been fully elucidated. A total of 231 females diagnosed with persistent HPV infection and pathologically confirmed absence of high-grade cervical lesions were selected from the Colposcopy Outpatient Clinic of Peking University People\'s Hospital, from March 2023 to December 2023. They were categorized into two groups based on the duration of HPV infection: the HPV persistent less than 3 years group and the more than 3 years group. PAX1/JAM3 methylation and HPV VL were determined by real-time PCR and BioPerfectus Multiplex Real-Time (BMRT)-HPV reports type-specific VL/10,000 cells, respectively. The average age of individuals with HPV infection lasting more than 3 years was higher compared to those with less than 3 years (48.9 vs. 45.1 years), with a statistically significant difference. Among the participants, 81.8% (189/231) had no previous screening. The methylation levels of JAM3 and PAX1 were significantly higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, with a statistically significant difference (p < 0.05). There was a significant correlation between PAX1 and JAM3 methylation (p < 0.001), which could be used as cumulative evidence of HPV infection duration before the occurrence of precancerous lesions. The incidence of vaginal intraepithelial lesions was higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, and HPV VL can be used as an indicative biomarker for concurrent cervical-vaginal lesions, especially for HPV other than 16/18 genotypes.

Port-A-Cath (port), a single-lumen, tunneled catheter, is routinely placed into the superior vena cava (SVC) for cancer patients undergoing chemotherapy. We present a case of a port placement in which variant anatomy was discovered during the fluoroscopy-guided procedure and confirmed by venogram of a persistent left-sided SVC (PLSVC). Upon further investigation into the patient\'s previous computed tomography (CT) scans, the diagnosis was further confirmed. Patients with PLSVC are typically asymptomatic; however, some are associated with increased congenital heart defects (CHD), which increase the risk for complications during invasive procedures. Diagnosing PLSVCs and knowing the clinical implications/complications can improve patient care; by not removing catheters unnecessarily and being prepared to treat/minimize complications.

Initial antibiotics for true Staphylococcus epidermidis bacteremia include vancomycin or linezolid, but if bacteremia persists, consideration should be made for salvage combination therapy regimes such as daptomycin with ceftaroline.

Background and Objectives: Left atrial (LA) remodelling and dilatation predicts atrial fibrillation (AF) recurrences after catheter ablation. However, whether right atrial (RA) remodelling and dilatation predicts AF recurrences after ablation has not been fully evaluated. Materials and Methods: This is an observational study of 85 consecutive patients (aged 57 ± 9 years; 70 [82%] men) who underwent cardiac magnetic resonance before first catheter ablation for AF (40 [47.1%] persistent AF). Four-chamber cine-sequence was selected to measure LA and RA area, and ventricular end-systolic image phase to obtain atrial 3D volumes. The effect of different variables on event-free survival was investigated using the Cox proportional hazards model. Results: In patients with persistent AF, combined LA and RA area indexed to body surface area (AILA + RA) predicted AF recurrences (HR = 1.08, 95% CI 1.00-1.17, p = 0.048). An AILA + RA cut-off value of 26.7 cm2/m2 had 72% sensitivity and 73% specificity for predicting recurrences in patients with persistent AF. In this group, 65% of patients with AILA + RA > 26.7 cm2/m2 experienced AF recurrence within 2 years of follow-up (median follow-up 11 months), compared to 25% of patients with AILA + RA ≤ 26.7 cm2/m2 (HR 4.28, 95% CI 1.50-12.22; p = 0.007). Indices of LA and RA dilatation did not predict AF recurrences in patients with paroxysmal AF. Atrial 3D volumes did not predict AF recurrences after ablation. Conclusions: In this pilot study, the simple measurement of AILA + RA may predict recurrences after ablation of persistent AF, and may outperform measurements of atrial volumes. In paroxysmal AF, atrial dilatation did not predict recurrences. Further studies on the role of RA and LA remodelling are needed.

UNASSIGNED: Recurrent/persistent primary hyperparathyroidism in patients who have undergone previous parathyroidectomy is a challenging condition. Imaging is important for localizing the parathyroid adenoma for re-exploration and 18F-Fluorocholine (18F-FCH) positron emission tomography/computed tomography (PET/CT) seems ideal for this purpose.
UNASSIGNED: This prospective study attempted to ascertain the utility of 18F-FCH PET/CT as an investigation in preoperative localization of abnormal parathyroid tissue in recurrent/persistent primary hyperparathyroidism while comparing it with 99mTc-Sestamibi dual-phase scintigraphy with early single-photon emission CT (SPECT)/CT and neck ultrasonography (USG).
UNASSIGNED: Twenty patients with biochemical features of recurrent/persistent primary hyperparathyroidism were enrolled into this study. They underwent neck USG, 99mTc-Sestamibi dual-phase scintigraphy with early SPECT/CT and 18F-FCH PET/CT for localization of parathyroid lesions. Six patients underwent surgical resection of the detected lesions, 3 were awaiting surgery, and 11 were managed conservatively. One patient died due to COVID.
UNASSIGNED: The calculated positive predictive values on a per-lesion basis of neck USG, 99mTc-sestamibi scintigraphy and early SPECT/CT and 18F-FCH PET/CT in the cohort of the 5 operated patients were 75% (3/4), 71.4% (5/7), and 71.4% (5/7), respectively. On a per-patient basis, the lesion detection rate was 100% for 99mTc-sestamibi scan and FCH PET (5/5) and 80% on neck USG (4/5).
UNASSIGNED: 18F-FCH PET/CT is a highly accurate imaging modality for the detection of parathyroid lesions in patients with recurrent/persistent primary hyperparathyroidism.

UNASSIGNED: Sustained opioid use is a well-known complication after surgery. Our objective was to determine whether there is any association between a patient\'s race or ethnicity and the sustained use of opioids in the year following surgery. Opioid use over the initial 3, 6, and 12 postoperative months was categorized as \"sustained early\", persistent, and chronic, respectively.
UNASSIGNED: Single-institution retrospective study of adults (≥18 years) who had undergone open abdominal surgery for cancer. Multivariable logistic regression was used to evaluate the association between race/ethnicity and opioid use.
UNASSIGNED: Of the 3523 patients included in the study, 2543 (72.2%) were non-Hispanic (NH) White, 476 (13.5%) were Hispanic or Latino, 262 (7.4%) were NH-Black, 186 (5.3%) were Asian, and 56 (1.6%) belonged to other racial or ethnic groups. The overall rates of sustained early, persistent, and chronic opioid use were 15.9%, 7.1%, and 2.6%, respectively. In the multivariable analysis, patient race/ethnicity was associated with sustained early postoperative opioid use (p-value=0.037), with Hispanics/Latinos having significantly higher odds than NH-Whites (OR = 1.382 [95% CI: 1.057-1.808]; p = 0.018). However, neither persistent nor chronic opioid use was associated with race/ethnicity (p = 0.697 and p = 0.443, respectively).
UNASSIGNED: In this retrospective study of adults who had undergone open abdominal surgery, patient race/ethnicity was not consistently associated with the development of sustained opioid use over the first 12 postoperative months.