Investigating the Influence Factors of Quality of Life in Thyroid Eye Disease: Insights from Machine Learning Approaches.

Aims: Thyroid eye disease (TED) is an autoimmune orbital disorder that diminishes the quality of life (QOL) for affected individuals. The Graves' ophthalmopathy (GO)-QOL questionnaire effectively assesses TED's impact on patients. This study aims to investigate factors influencing visual functioning (QOL-VF) and physical appearance (QOL-AP) scores in Chinese TED patients using innovative data analysis methods.

Discovery of Trypanosoma brucei inhibitors enabled by a unified synthesis of diverse sulfonyl fluorides.

Sets of electrophilic probes are generally prepared using a narrow toolkit of robust reactions, which tends to limit both their structural and functional diversity. A unified synthesis of skeletally-diverse sulfonyl fluorides was developed that relied upon photoredox-catalysed dehydrogenative couplings between hetaryl sulfonyl fluorides and hydrogen donor building blocks. A set of 32 diverse probes was prepared, and then screened against Trypanosoma brucei.

Assessment of hearing dysfunction in patients with Graves' disease and thyroid eye disease without or with teprotumumab.

Importance: Thyroid eye disease (TED) negatively impacts quality of life. TED occurs predominantly in Graves' disease (GD). Teprotumumab improves TED but concern for hearing adverse events (AEs) has emerged.

A rapid on-site loop-mediated isothermal amplification technology as an early warning system for the detection of Shiga toxin-producing in water.

Shiga toxin-producing (STEC) is an important waterborne pathogen capable of causing serious gastrointestinal infections with potentially fatal complications, including haemolytic-uremic syndrome. All STEC serogroups harbour genes that encode at least one Shiga toxin ( and/or ), which constitute the primary virulence factors of STEC. Loop-mediated isothermal amplification (LAMP) enables rapid real-time pathogen detection with a high degree of specificity and sensitivity.

TSHR-IGF-IR complex drives orbital fibroblast misbehavior in thyroid eye disease.

Purpose Of Review: Evolving understanding of thyroid eye disease (TED) has led to rapidly advancing therapeutic options. Most new treatments under development or recently available to patients are predicated on insights into disease mechanism.

Recent Findings: TED, a disfiguring process, involves inflammation and remodeling of the connective tissues around the eye.

Revisiting the dipeptidyl carboxypeptidase inhibitor captopril as a source of pan anti-trypanosomatid agents.

The protozoan parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are responsible for continued propagation of neglected tropical diseases such as African sleeping sickness, Chagas disease and leishmaniasis respectively. Following a report that captopril targets Leishmania donovani dipeptidyl carboxypeptidase, a series of simple proline amides and captopril analogues were synthesized and found to exhibit 1-2 μM in vitro inhibition and selectivity against Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp.

Cryo-EM structure of the R388 plasmid conjugative pilus reveals a helical polymer characterized by an unusual pilin/phospholipid binary complex.

Bacterial conjugation is a process by which DNA is transferred unidirectionally from a donor cell to a recipient cell. It is the main means by which antibiotic resistance genes spread among bacterial populations. It is crucially dependent upon the elaboration of an extracellular appendage, termed "pilus," by a large double-membrane-spanning secretion system termed conjugative "type IV secretion system.

Sterol 14-alpha demethylase (CYP51) activity in Leishmania donovani is likely dependent upon cytochrome P450 reductase 1.

Liposomal amphotericin B is an important frontline drug for the treatment of visceral leishmaniasis, a neglected disease of poverty. The mechanism of action of amphotericin B (AmB) is thought to involve interaction with ergosterol and other ergostane sterols, resulting in disruption of the integrity and key functions of the plasma membrane. Emergence of clinically refractory isolates of Leishmania donovani and L.

Long-Term Efficacy of Teprotumumab in Thyroid Eye Disease: Follow-Up Outcomes in Three Clinical Trials.

Thyroid eye disease (TED) is an autoimmune process characterized by extraocular muscle and orbital fat remodeling/expansion resulting in swelling, pain, redness, proptosis, and diplopia. Teprotumumab, an insulin-like growth factor-I receptor inhibitor, demonstrated improvements in TED signs and symptoms in three adequately powered clinical trials of 24 weeks duration. Here we analyze the long-term maintenance of responses with teprotumumab from these trials.

Bridging and Validation of the Specific Graves Ophthalmopathy Quality of Life Questionnaire With Health State Utility Values.

Objective: In thyroid eye disease (TED), inflammation and expansion of orbital muscle and periorbital fat result in diplopia and proptosis, severely impacting patient quality of life (QOL). The reported health state utility (HSU) scores, which are QOL measures, allow quantification of TED impact and improvement with therapies; however, no current QOL instrument has been validated with HSU scores for TED. Here, we used the disease-specific Graves Ophthalmopathy Quality of Life (GO-QOL) questionnaire and HSU scores to validate QOL impact.

The role of ion dissolution in metal and metal oxide surface inactivation of SARS-CoV-2.

Anti-viral surface coatings are under development to prevent viral fomite transmission from high-traffic touch surfaces in public spaces. Copper's anti-viral properties have been widely documented, but the anti-viral mechanism of copper surfaces is not fully understood. We screened a series of metal and metal oxide surfaces for anti-viral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19).

Glycemic Trends in Patients with Thyroid Eye Disease Treated with Teprotumumab in 3 Clinical Trials.

Purpose: Assess incidence, severity, and glucose excursion outcomes in thyroid eye disease (TED) patients receiving the insulin-like growth factor-1 receptor inhibitor teprotumumab from 3 clinical trials.

Design: Analysis of pooled glycemic data over time.

Participants: Eighty-four teprotumumab- and 86 placebo-treated active TED patients from the phase 2 and phase 3 (OPTIC) controlled clinical trials and 51 teprotumumab-treated patients from the OPTIC extension (OPTIC-X) trial.

miRNA-378 Is Downregulated by XBP1 and Inhibits Growth and Migration of Luminal Breast Cancer Cells.

X-box binding protein 1 (XBP1) is a transcription factor that plays a crucial role in the unfolded protein response (UPR), a cellular stress response pathway involved in maintaining protein homeostasis in the endoplasmic reticulum (EnR). While the role of XBP1 in UPR is well-characterised, emerging evidence suggests its involvement in endocrine resistance in breast cancer. The transcriptional activity of spliced XBP1 (XBP1s) is a major component of its biological effects, but the targets of XBP1s in estrogen receptor (ER)-positive breast cancer are not well understood.

A type VII-secreted lipase toxin with reverse domain arrangement.

The type VII protein secretion system (T7SS) is found in many Gram-positive bacteria and in pathogenic mycobacteria. All T7SS substrate proteins described to date share a common helical domain architecture at the N-terminus that typically interacts with other helical partner proteins, forming a composite signal sequence for targeting to the T7SS. The C-terminal domains are functionally diverse and in Gram-positive bacteria such as Staphylococcus aureus often specify toxic anti-bacterial activity.

Real-time single-base specific detection of the Haemonchus contortus S168T variant associated with levamisole resistance using loop-primer endonuclease cleavage loop-mediated isothermal amplification.

Haemonchus contortus is a parasitic haematophagous nematode that primarily affects small ruminants and causes significant economic loss to the global livestock industry. Treatment of haemonchosis typically relies on broad-spectrum anthelmintics, resistance to which is an important cause of treatment failure. Resistance to levamisole remains less widespread than to other major anthelmintic classes, prompting the need for more effective and accurate surveillance to maintain its efficacy.

Fibrocyte Participation in Thyroid-Associated Ophthalmopathy Suggests New Approaches to Therapy.

Purpose: Review the historical context of research and changing therapeutic landscape of thyroid-associated ophthalmopathy (TAO) by focusing on the relationship between TAO, CD34+ fibrocytes, thyrotropin receptor (TSHR), and insulin-like growth factor-I receptor (IGF-IR).

Methods: A literature review using search terms, including fibrocytes, IGF-IR, TSHR, TAO, and thyroid eye disease.

Results: The mechanisms involved in TAO have been partially identified.

How patients experience thyroid eye disease.

Objective: To determine the impact of thyroid eye disease (TED) on patients in various stages of the disease.

Background: TED is a debilitating and potentially sight-threatening inflammatory autoimmune disease that is frequently misdiagnosed. Challenging quality-of-life (QoL) issues can persist long after the active phase of disease has subsided.

Multidisciplinary Support To Access living donor Kidney Transplant (MuST AKT): A Clinical Research Protocol for a Pilot Randomized Controlled Trial to Increase Living Kidney Donation.

Background: Living donor kidney transplantation (LDKT) is the optimal treatment for eligible patients with kidney failure, although it is underutilized. Contextually tailored patient- and family-centered interventions may be effective to increase LDKT.

Objective: We outline a protocol to test the feasibility of the Multidisciplinary Support To Access living donor Kidney Transplant (MuST AKT) intervention designed to increase LDKT.

Adipocyte lipolysis protects mice against Trypanosoma brucei infection.

Trypanosoma brucei causes African trypanosomiasis, colonizing adipose tissue and inducing weight loss. Here we investigated the molecular mechanisms responsible for adipose mass loss and its impact on disease pathology. We found that lipolysis is activated early in infection.