MRD-guided zanubrutinib, venetoclax and obinutuzumab in relapsed CLL: primary endpoint analysis from the CLL2-BZAG trial.

The phase 2 CLL2-BZAG trial tested a measurable residual disease (MRD)-guided combination treatment of zanubrutinib, venetoclax and obinutuzumab after an optional bendamustine debulking in patients with relapsed/refractory CLL. In total, 42 patients were enrolled and two patients with ≤2 induction cycles were excluded from the analysis population per protocol. Patients had a median of one prior therapy (range 1-5), 18 patients (45%) had already received a BTK inhibitor (BTKi), seven patients (17.

User-Oriented Requirements for Artificial Intelligence-Based Clinical Decision Support Systems in Sepsis: Protocol for a Multimethod Research Project.

Background: Artificial intelligence (AI)-based clinical decision support systems (CDSS) have been developed for several diseases. However, despite the potential to improve the quality of care and thereby positively impact patient-relevant outcomes, the majority of AI-based CDSS have not been adopted in standard care. Possible reasons for this include barriers in the implementation and a nonuser-oriented development approach, resulting in reduced user acceptance.

Role of Superlattice Phonons in Charge Localization Across Quantum Dot Arrays.

Understanding charge transport in semiconductor quantum dot (QD) assemblies is important for developing the next generation of solar cells and light-harvesting devices based on QD technology. One of the key factors that governs the transport in such systems is related to the hybridization between the QDs. Recent experiments have successfully synthesized QD molecules, arrays, and assemblies by directly fusing the QDs, with enhanced hybridization leading to high carrier mobilities and coherent band-like electronic transport.

Geosocial Media's Early Warning Capabilities Across US County-Level Political Clusters: Observational Study.

Background: The novel coronavirus disease (COVID-19) sparked significant health concerns worldwide, prompting policy makers and health care experts to implement nonpharmaceutical public health interventions, such as stay-at-home orders and mask mandates, to slow the spread of the virus. While these interventions proved essential in controlling transmission, they also caused substantial economic and societal costs and should therefore be used strategically, particularly when disease activity is on the rise. In this context, geosocial media posts (posts with an explicit georeference) have been shown to provide a promising tool for anticipating moments of potential health care crises.

Long-Term Treatment With Ocrelizumab in Patients With Early-Stage Relapsing MS: Nine-Year Data From the OPERA Studies Open-Label Extension.

Background And Objectives: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS).

Methods: Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies.

Characterization of Factors Associated With Death in Deceased Patients With Mitochondrial Disorders: A Multicenter Cross-Sectional Survey.

Background And Objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.

Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023.

Surrogate End Points for Overall Survival in Neoadjuvant Randomized Clinical Trials for Early Breast Cancer.

Purpose: To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC).

Methods: Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points.

Biomimetic Silk Nanoparticle Manufacture: Calcium Ion-Mediated Assembly.

Silk has emerged as an interesting candidate among protein-based nanocarriers due to its favorable properties, including biocompatibility and a broad spectrum of processing options to tune particle critical quality attributes. The silk protein conformation during storage in the middle silk gland of the silkworm is modulated by various factors, including the most abundant metallic ion, calcium ion (Ca). Here, we report spiking of liquid silk with calcium ions to modulate the silk nanoparticle size.

Natural variations in and its neighboring confer yellow seed with elevated oil content in .

Seed color is a critical quality trait in numerous plant species. In oilseed crops, including rapeseed and mustard, yellow seeds are distinguished by their significantly higher oil content and faster germination rates compared to black or brown counterparts. Despite the agronomic significance of the yellow seeds being a prime breeding target, the mechanisms underlying elevated oil content remain obscure.

Suppressed Degradation Process of PBDB-TF-T1:BTP-4F-12-Based Organic Solar Cells with Solid Additive Atums Green.

Solid additives have garnered significant attention due to their numerous advantages over liquid additives. This study explores the potential of the green-fluorescent conjugated polymer denoted Atums Green as a solid additive in green-solvent-based PBDB-TF-T1:BTP-4F-12 solar cells. Even tiny amounts of Atums Green doping significantly improve the device performance.

Global natural history infrastructure requires international solidarity, support, and investment in local capacity.

Amid global challenges like climate change, extinctions, and disease epidemics, science and society require nuanced, international solutions that are grounded in robust, interdisciplinary perspectives and datasets that span deep time. Natural history collections, from modern biological specimens to the archaeological and fossil records, are crucial tools for understanding cultural and biological processes that shape our modern world. At the same time, natural history collections in low and middle-income countries are at-risk and underresourced, imperiling efforts to build the infrastructure and scientific capacity necessary to tackle critical challenges.

Intra-articular Median Nerve Entrapment of the Elbow After Medial Epicondyle Fracture: A Case Report.

Case: We describe a 13-year-old adolescent girl experiencing persistent pain and reduced grip strength following nonoperative treatment of a medial epicondyle fracture-dislocation with closed reduction over 5 years before her referral to our clinic. Neurological examination and magnetic resonance imaging of the elbow revealed damage to the median nerve due to an entrapment within the elbow. Surgical release of the nerve resulted in complete pain relief and improved neurological function with normalized nerve conduction.

The Sikkim flood of October 2023: Drivers, causes and impacts of a multihazard cascade.

On 3 October 2023, a multihazard cascade in the Sikkim Himalaya, India, was triggered by 14.7 million m of frozen lateral moraine collapsing into South Lhonak Lake, generating an ~20 m tsunami-like impact wave, breaching the moraine, and draining ~50 million m of water. The ensuing Glacial Lake Outburst Flood (GLOF) eroded ~270 million m of sediment, which overwhelmed infrastructure, including hydropower installations along the Teesta River.

A framework for managing infectious diseases in rural areas in low- and middle-income countries in the face of climate change-East Africa as a case study.

Climate change is having unprecedented impacts on human health, including increasing infectious disease risk. Despite this, health systems across the world are currently not prepared for novel disease scenarios anticipated with climate change. While the need for health systems to develop climate change adaptation strategies has been stressed in the past, there is no clear consensus on how this can be achieved, especially in rural areas in low- and middle-income countries that experience high disease burdens and climate change impacts simultaneously.

Genome recombination on demand.

Large genome rearrangements in mammalian cells can be generated at scale.

Ancient genomics and the origin, dispersal, and development of domestic sheep.

The origins and prehistory of domestic sheep () are incompletely understood; to address this, we generated data from 118 ancient genomes spanning 12,000 years sampled from across Eurasia. Genomes from Central Türkiye ~8000 BCE are genetically proximal to the domestic origins of sheep but do not fully explain the ancestry of later populations, suggesting a mosaic of wild ancestries. Genomic signatures indicate selection by ancient herders for pigmentation patterns, hornedness, and growth rate.

Conformational dynamics of a multienzyme complex in anaerobic carbon fixation.

In the ancient microbial Wood-Ljungdahl pathway, carbon dioxide (CO) is fixed in a multistep process that ends with acetyl-coenzyme A (acetyl-CoA) synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). In this work, we present structural snapshots of the CODH/ACS from the gas-converting acetogen , characterizing the molecular choreography of the overall reaction, including electron transfer to the CODH for CO reduction, methyl transfer from the corrinoid iron-sulfur protein (CoFeSP) partner to the ACS active site, and acetyl-CoA production. Unlike CODH, the multidomain ACS undergoes large conformational changes to form an internal connection to the CODH active site, accommodate the CoFeSP for methyl transfer, and protect the reaction intermediates.

Pilin antigenic variants impact gonococcal lifestyle and antibiotic tolerance by modulating interbacterial forces.

Type 4 pili (T4P) are multifunctional filaments involved in adhesion, surface motility, biofilm formation, and horizontal gene transfer. These extracellular polymers are surface-exposed and, therefore, act as antigens. The human pathogen Neisseria gonorrhoeae uses pilin antigenic variation to escape immune surveillance, yet it is unclear how antigenic variation impacts most other functions of T4P.

Extended receptor repertoire of an adenovirus associated with human obesity.

Human adenovirus type 36 (HAdV-D36) has been putatively linked to obesity in animals and has been associated with obesity in humans in some but not all studies. Despite extensive epidemiological research there is limited information about its receptor profile. We investigated the receptor portfolio of HAdV-D36 using a combined structural biology and virology approach.

Prevalence of soil-transmitted helminths infection and associated risk factors among residents of Jigjiga town, Somali region, Eastern Ethiopia.

Background: One of the tropical illnesses that is often overlooked is soil-transmitted helminths, or STHs. In tropical and subtropical nations, where poor sanitation and contaminated water sources are common, they mostly impact the most vulnerable populations.

Objective: The aim of this study was to ascertain the prevalence of STHs and related risk factors among the people living in Jigjiga town, Somali region, Eastern Ethiopia.

Influence of Messa di Voce speed on vocal stability of untrained, healthy subjects.

Introduction: Despite its importance in voice training, comprehensive research into sustained vowel phonation with constant pitch and increasing and decreasing loudness, the so-called Messa di Voce, is lacking. The study examines the laryngeal behavior during Messa di Voce, regarding the impact of the speed of execution on voice stability parameters.

Materials And Methods: Nine untrained, healthy subjects (5 female, 4 male) were asked to perform Messa di Voce exercises on the vowel [i:], involving a gradual increase and decrease of volume.

Tailoring anaesthetic strategies for diabetes research: Acepromazine vs. medetomidine in Aachen minipigs.

Pre-established anaesthetic protocols in animal models might unexpectedly interfere with the main outcome of scientific projects and therefore they need to account for the specific research goals. We aimed to optimize the anaesthetic protocol and animal handling strategies in a diabetes-related-study exemplifying how the anaesthetic approach must be adjusted for individual research targets. Aachen minipigs were used as a model to test long-lasting skin glucose sensors for diabetic human patients.

Ovarian cancer prevention through opportunistic salpingectomy during abdominal surgeries: A cost-effectiveness modeling study.

Background: There is indication that the fallopian tubes might be involved in ovarian cancer pathogenesis and their removal reduces cancer risk. Hence, bilateral salpingectomy during hysterectomy or sterilization, so called opportunistic salpingectomy (OS), is gaining wide acceptance as a preventive strategy. Recently, it was discussed whether implementation of OS at other gynecologic surgery, e.

Social ecology of artisanal sand mining in the Niger River around Bamako, Mali.

Sand, shaping both natural waterways and urban infrastructure, has recently seen a major surge in extraction, particularly in rapidly urbanizing regions like West Africa. To assess the organization, quantification, and socio-ecological implications of sand mining around Mali's capital Bamako, we employed a mixed methods approach including structured and unstructured interviews, truck counts, turbidity analyses, and river depth measurements. Our study identified five artisanal systems for mining sand and gravel from the Niger River, using tied-up pirogues, single pirogues, carts, tractors, and trucks.

Comparing imputation approaches to handle systematically missing inputs in risk calculators.

Risk calculators based on statistical and/or mechanistic models have flourished and are increasingly available for a variety of diseases. However, in the day-to-day practice, their usage may be hampered by missing input variables. Certain measurements needed to calculate disease risk may be difficult to acquire, e.