Insights into Free Drug Release from Efficacious -Acyl -Aminophenol Duocarmycin Prodrugs.

Acyclic and cyclic -acyl -aminophenol prodrugs of duocarmycin analogues were reported as members of a unique class of reductively cleaved prodrugs that map seamlessly onto the duocarmycin family of natural products. Although these prodrugs were explored with the expectations that they may be cleaved selectively within hypoxic tumor environments that have intrinsically higher concentrations of reducing nucleophiles, the remarkable stability of some such prodrugs suggests another mechanism of free drug release is operative. The prototype of such chemically unreactive -acyl -aminophenol prodrugs is , which proved remarkably efficacious in vertebrate tumor models; was found to lack the toxicity that is characteristic of traditional chemotherapeutic drugs as well as the free drugs in the class (e.

Dynamic reciprocal morphological changes in insect hosts and bacterial symbionts.

Symbiotic interactions, central to most life on Earth, are interwoven associations that vary in intimacy and duration. Some of the most well-known examples of symbioses occur between animals and gut bacteria. These associations lead to physiological integration of host and symbionts.

Development of a portable testing chamber to assess imaging performance of laparoscopes in low- and middle-income countries.

Significance: Laparoscopic surgery is generally unavailable in low- and middle-income countries (LMICs) due to the high cost of installation and lack of qualified personnel to maintain and repair equipment. We developed a low-cost, durable, reusable laparoscopic system, called the KeyScope laparoscope, for use in LMICs. To reliably build and service the KeyScope in LMICs, a portable testing chamber (PTC) is needed to assess image performance.

Multi-level Factors to Build Confidence and Support in Active Surveillance for Low-Risk Prostate Cancer: A Qualitative Study.

Background: Active surveillance (AS) is the guideline-recommended treatment for low-risk prostate cancer and involves routine provider visits, lab tests, imaging, and prostate biopsies. Despite good uptake, adherence to AS, in terms of receiving recommended follow-up testing and remaining on AS in the absence of evidence of cancer progression, remains challenging.

Objective: We sought to better understand urologist, primary care providers (PCPs), and patient experiences with AS care delivery to identify opportunities to improve adherence.

Mandibular hybrid odontogenic tumor.

Background: Hybrid Odontogenic Tumors (HOT) are defined by the presence of two or more independent odontogenic tumors that originate from and affect the same maxillofacial site.

Methods: The present study is the first case report of a mandibular HOT consisting of Ameloblastoma, Calcifying Epithelial Odontogenic Tumor, and Ameloblastic Fibroma.

Case Report: A 37-year-old otherwise healthy male presented with the chief complaint of swelling in the right mandibular body.

The conformational landscape of human transthyretin revealed by cryo-EM.

Transthyretin (TTR) is a natively tetrameric thyroxine transporter in blood and cerebrospinal fluid whose misfolding and aggregation causes TTR amyloidosis. A rational drug design campaign identified the small molecule tafamidis (Vyndamax) as a stabilizer of the native TTR fold, and this aggregation inhibitor is regulatory agency approved for the treatment of TTR amyloidosis. Here we used cryo-EM to investigate the conformational landscape of this 55 kDa tetramer in the absence and presence of one or two ligands, revealing inherent asymmetries in the tetrameric architecture and previously unobserved conformational states.

Decreased DNA density is a better indicator of a nuclear bleb than lamin B loss.

Nuclear blebs are herniations of the nucleus that occur in diseased nuclei and cause nuclear rupture leading to cellular dysfunction. Chromatin and lamins are two of the major structural components of the nucleus that maintain its shape and function, but their relative roles in nuclear blebbing remain elusive. To determine the composition of nuclear blebs, we compared the immunofluorescence intensity of DNA and lamin B in the main nucleus body to that in the nuclear bleb across cell types and perturbations.

Endocapillary proliferative glomerulonephritis associated with Q fever endocarditis: A case report.

Acute Coxiella burnetti (Q fever) infection is known to activate the autoimmune inflammatory response. We report a rare case of glomerulonephritis associated with the Coxiella infection. An elderly male first presented with recurrent fevers of unknown origin and was subsequently diagnosed with Q fever infection and treated with doxycycline.

Magnetic resonance-guided focused ultrasound thalamotomy for tremor.

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has emerged as an effective treatment for tremor, particularly in those patients who are excluded from deep brain stimulation. The authors illustrate an example of MRgFUS thalamotomy, targeting the ventralis intermedius nucleus, in a 78-year-old patient with tremor who had features of essential tremor and tremor-predominant Parkinson's disease. Significant tremor improvement was seen during the procedure.

Supercharged Phosphotriesterase for improved Paraoxon activity.

Phosphotriesterases (PTEs) represent a class of enzymes capable of efficient neutralization of organophosphates (OPs), a dangerous class of neurotoxic chemicals. PTEs suffer from low catalytic activity, particularly at higher temperatures, due to low thermostability and low solubility. Supercharging, a protein engineering approach via selective mutation of surface residues to charged residues, has been successfully employed to generate proteins with increased solubility and thermostability by promoting charge-charge repulsion between proteins.

A strong priority effect in the assembly of a specialized insect-microbe symbiosis.

Unlabelled: Specialized host-microbe symbioses are ecological communities, whose composition is shaped by various processes. Microbial community assembly in these symbioses is determined in part by interactions between taxa that colonize ecological niches available within habitat patches. The outcomes of these interactions, and by extension the trajectory of community assembly, can display priority effects-dependency on the order in which taxa first occupy these niches.

Radiologic anatomic study of the humeral medullary canal.

Hypothesis/background: Patient-specific implants have become an increasingly researched area to improve surgical outcomes. Patient-specific implants have been suggested to provide advantages for better implant alignment and thus improve surgical outcomes. One such area for application is in the use of intramedullary nails for humeral fracture stabilization.

Clinical review of substitutions or alternatives for critical chemotherapy drug shortages in hematologic malignancies.

Purpose: Over the past decade, drug shortages have become increasingly more problematic for clinicians, with over 300 drug shortages reported in the first quarter of 2023. Shortages of chemotherapy drugs can have a negative impact on patient care, as omission or delay of treatment can lead to worse outcomes. Although many articles have been published on this topic, currently no review articles discuss strategies for using alternative regimens or substitutions in the event of severe chemotherapy drug shortages.

Correction: Novel aerosol treatment of airway hyper-reactivity and inflammation in a murine model of asthma with a soluble epoxide hydrolase inhibitor.

[This corrects the article DOI: 10.1371/journal.pone.

Robot-assisted deep brain stimulation of the centromedian nucleus of the thalamus for generalized epilepsy: targeting and operative video.

The centromedian (CM) nucleus of the thalamus is a promising target for a range of brain diseases including drug-resistant generalized and multifocal epilepsy. CM is highly connected to cortical and subcortical regions including frontoparietal/sensorimotor cortex, striatum, brainstem, and cerebellum, which are involved in some generalized epilepsy syndromes like Lennox-Gastaut syndrome (LGS). In this video, the authors describe their methodology for targeting CM for deep brain stimulation (DBS).

The Case for Neurosurgical Intervention in Cancer Neuroscience.

The emerging field of cancer neuroscience reshapes our understanding of the intricate relationship between the nervous system and cancer biology; this new paradigm is likely to fundamentally change and advance neuro-oncological care. The profound interplay between cancers and the nervous system is reciprocal: Cancer growth can be induced and regulated by the nervous system; conversely, tumors can themselves alter the nervous system. Such crosstalk between cancer cells and the nervous system is evident in both the peripheral and central nervous systems.

Systematic Review-Role of MRI in Cervical Cancer Staging.

A systematic review of the diagnostic accuracy of MRI in the staging of cervical cancer was conducted based on the literature from the last 5 years. A literature search was performed in the Cochrane Library, EMBASE, MEDLINE and PubMed databases using the MeSH terms "cervical cancer", "MRI" and "neoplasm staging". A total of 110 studies were identified, of which 8 fit the inclusion criteria.

Case Report: Low-grade glioma with loss of function mimicking diffuse intrinsic pontine glioma.

Intrinsic, expansile pontine tumors typically occur in the pediatric population. These tumors characteristically present as diffuse intrinsic pontine glioma (DIPG), which is now considered as diffuse midline glioma (DMG), H3K27-mutated of the pons. DIPG has limited treatment options and a poor prognosis, and the value of tissue diagnosis from an invasive biopsy remains controversial.

Toxicities associated with tyrosine kinase inhibitor maintenance following allogeneic hematopoietic cell transplantation in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Allogeneic hematopoietic cell transplantation (HCT) offers a potential cure in Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); nonetheless, relapses are common and the major cause of mortality. One strategy to prevent relapse is tyrosine kinase inhibitor (TKI) maintenance post-HCT, but published clinical experience is primarily with the first-generation TKI imatinib while data with newer generation TKIs are limited. We conducted a retrospective analysis of 185 Ph+ ALL patients who underwent HCT followed by TKI maintenance from 2003 to 2021 at City of Hope.