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Outcome correlates of approved CD19-targeted CAR T cells for large B cell lymphoma

Tetrapod species–area relationships across the Cretaceous–Paleogene mass extinction

Mass extinctions are rare but catastrophic events that profoundly disrupt biodiversity. Widely accepted consequences of mass extinctions, such as biodiversity loss and the appearance of temporary “disaster taxa,” imply that species–area relationships (SARs, or how biodiversity scales with area) should change dramatically across these events: Specifically, both the slope (the rate of accumulation of new species with increasing area) and intercept (the density of species at local scales) of the power–law relationship should decrease. However, these hypotheses have not been tested, and the contribution of variation in the SAR to diversity dynamics in deep time has been neglected. We use fossil data to quantify nested SARs in North American terrestrial tetrapods through the Cretaceous–Paleogene (K/Pg) mass extinction (Campanian–Ypresian). We show that SARs vary substantially through time and among groups. In the pre-extinction interval (Maastrichtian), unusually shallow SAR slopes (indicating low beta diversity or provinciality) drive low total regional diversity in dinosaurs, mammals, and other tetrapods. In the immediate postextinction interval (Danian), the explosive diversification of mammals drove high regional diversity via a large increase in SAR slope (indicating higher beta diversity or provinciality), and only a limited increase in SAR intercept. This contradicts the expectation that postextinction biotas should be regionally homogenized by the spread of disaster taxa and impoverished by diversity loss. This early postextinction increase in SAR slope was followed in the Thanetian–Selandian ( ∼ 4.4. myr later) by increases in the intercept, indicating that diversity dynamics at local and regional scales did not change in synchrony.

Meta-analytical approaches to ordinal outcome data in clinical interventional studies: A scoping review with reproducible research

Background Conducting meta-analyses on ordinal outcome data is more complex than on binary or continuous data. This study aims to summarise the current biomedical literature on meta-analytical methods for ordinal outcomes and attempts to reproduce the results of previous studies. Methods A systematic search was conducted in three databases, MEDLINE, EMBASE, and PsycINFO, from inception to 05/05/2024. Forward and backward citation searches were also performed. The screening was conducted in two phases using Covidence software. Studies were included if they reported or compared methods for meta-analysis of ordinal outcomes in clinical interventional studies. Relevant studies were summarised and discussed. If sufficient data for methods comparison were available, either in the retrieved reports or after contacting the authors, an attempt at reproducible research was made. Results 333 records were screened, yielding four methodological studies that met the inclusion criteria. These studies addressed meta-analytical methods for ordinal scales ranging from 5 to 20 ordered categories. The three primary approaches identified were (1) ordinal models (proportional odds and generalised odds), (2) binary models (dichotomisation of ordinal scales), and (3) continuous models (treating ordinal scales as continuous variables). None of the included studies provided a comprehensive comparison of all three approaches. Two studies compared different proportional odds models; one compared binary with proportional odds, but the full results were not published, and one compared continuous and generalised odds models using simulated data with one scenario. The latter study allowed for reproducibility, but our analysis produced different results, and attempts to clarify the discrepancy with the authors were unsuccessful. Conclusions A significant knowledge gap exists regarding the optimal meta-analytical method for ordinal outcomes in clinical interventional studies. Further methodological research is required to establish a robust evidence base for choosing the most appropriate approach.

A double blinded randomized placebo trial of Bifidobacterium animalis subsp. lactis BLa80 on sleep quality and gut microbiota in healthy adults

Observation of odd-parity superconductivity in UTe ₂

Symmetry properties of the order parameter are among the most fundamental characteristics of a superconductor. UTe 2 , which was found to feature an exceedingly large upper critical field and striking reentrant behavior at low temperatures, is widely believed to possess a spin-triplet pairing symmetry. However, unambiguous evidence for such a pairing symmetry is still lacking, especially at zero and low magnetic fields. The presence of an inversion crystalline symmetry in UTe 2 requires that, if it is indeed a spin-triplet superconductor, the order parameter must be of odd parity. We report here phase-sensitive measurements of the symmetry of the orbital part of the order parameter using the Josephson effect. The selection rule in the orientation dependence of the Josephson coupling between In, an s -wave superconductor, and UTe 2 suggests strongly that UTe 2 possesses the odd-parity pairing state of B 1 u symmetry near zero magnetic field, making it a spin-triplet superconductor. We also report the apparent formation of Andreev surface bound states on the (1−10) surface of UTe 2 .

Assessing construct reliability through open-ended survey response analysis

Online surveys often include quantitative attention checks, but inattentive participants might also be identified using their qualitative responses. We used the software Turnitin™ to assess the originality of open-ended responses in four mixed-method surveys that included validated multi-item rating scales (i.e., constructs). Across surveys, 18-35% of participants (n =  3,771) were identified as having copied responses from online sources. We assessed indicator reliability and internal consistency reliability and found that both were lower for participants identified as using copied text versus those who wrote more original responses. Those who provided more original responses also provided more consistent responses to the validated scales, suggesting that these participants were more attentive. We conclude that this process can be used to screen open-ended responses from online surveys. We encourage future research to replicate this screening process using similar tools, investigate strategies to reduce copying behaviour, and explore the motivation of participants to search for information online, including what sources they find compelling.

Impact of the sequence of system-environment interactions on the functionality and efficiency of quantum thermal machines

Abstract In this work, we investigate effects of the sequence of system-environment interactions on the functionality and performance of quantum thermal machines (QTMs). The working substance of our setup consists of two subsystems, each independently coupled to its local thermal reservoir and further interconnected with a common reservoir in a cascaded manner. We demonstrate the impact of the sequential interactions between the subsystems and the common reservoir by exchanging the temperatures of the two local reservoirs. Our findings reveal that, when the two subsystems are in resonance, such an exchange alters the efficiency of QTMs without changing their functional types. Conversely, when the two subsystems are detuned, this exchange not only changes the efficiency but also the types of QTMs. Our results indicate that the manners of system-reservoir interactions offer significant potential for designing QTMs with tailored functionalities and enhanced performance.

Artificial intelligence in digital pathology — time for a reality check

Cytoplasmic Mg ²⁺ supersedes carbon source preference to dictate <i>Salmonella</i> metabolism

Glucose is the preferred carbon source of most studied microorganisms. However, we now report that glucose loses preferred status when the intracellular pathogen Salmonella enterica serovar Typhimurium experiences cytoplasmic magnesium (Mg 2+ ) starvation. We establish that this infection-relevant stress drastically reduces synthesis of cyclic adenosine monophosphate (cAMP), the allosteric activator of the cAMP receptor protein (CRP), master regulator of carbon utilization. The resulting reduction in cAMP concentration, which is independent of carbon source, decreases transcription of CRP-cAMP-activated carbon utilization genes, hinders carbon source uptake, and restricts metabolism, rendering wild-type bacteria phenotypically CRP − . A cAMP-independent allele of CRP overcame the transcriptional, uptake, and metabolic restrictions caused by cytoplasmic Mg 2+ starvation and significantly increased transcription of the glucose uptake gene when S. Typhimurium was inside murine macrophages. The reduced preference for glucose exhibited by S. Typhimurium inside macrophages reflects that transcription of the glucose uptake gene requires higher amounts of active CRP-cAMP than transcription of uptake genes for preferred carbon sources, such as gluconate and glycerol. By reducing CRP-cAMP activity, low cytoplasmic Mg 2+ alters carbon source preference, adjusting metabolism and growth.

Optimism/pessimism and associations with life event perceptions

Optimism is the generalized sense that good things will happen in the future, and people higher in optimism typically experience a host of positive personal and relational outcomes. However, when ostensibly important life events happen to optimists and pessimists, they rarely change their perspective about the future. One potential reason optimists are resilient to life circumstances is that they might vary in how they perceive those circumstances. Another source of confusion is whether these perceptions are driven by optimistic thinking per se or the lack of pessimistic thinking. In the current study, we examined how optimists and pessimists differ in their perceptions of life events in a large sample (N =  929) of college students answering questions about hypothetical life events. The pessimism scale largely drove perceptions that life events are unlikely to change someone’s personality, such that the four findings from the composite scale were found for the pessimism subscale but only two were found for the optimism subscale. Nevertheless, pessimists tended to think that life events were unlikely to change their worldview, were more externally controlled, were less emotionally significant, and were more likely to negatively affect their social standing. Aside from these aggregate findings, optimism and pessimism were not systematically and consistently related to the perceptions of particular life events. These findings provide additional context for individual differences in life event perceptions and provide some future directions for why life events either do or do not motivate changes in optimism and pessimism.

Expression of miRNA-338-3p/miRNA-1250-5p/miRNA-3065-5p clusters in peripheral blood mononuclear cells of ischemic stroke

AI accurately identifies targetable alterations in lung cancer histological images

Correction for Ganguli et al., A culture-free biphasic approach for sensitive and rapid detection of pathogens in dried whole-blood matrix

Exploring the prevalence of chronic diseases and health status among international Hajj pilgrims

Background and aims Pilgrims with pre-existing Chronic Diseases are at high risk of physical stress that can lead to unexpected health outcomes, including multiple visits to the hospital, organ failure, or even death. In addition, the risk of mortality related to Chronic Diseases increases during mass gatherings due to these same reasons. Therefore, this study aims to evaluate the Prevalence of Chronic Diseases and clinical symptoms among pilgrims during Hajj 2024 in Saudi Arabia. Methods During the 2024 Hajj rituals, cross-sectional questionnaires were administered to pilgrims at the Jeddah International Airport. The questionnaire contained questions on sociodemographic information, the presence of Chronic Diseases, types of Chronic Diseases, and clinical symptoms. Results A total of 1920 pilgrims were included in the study, with a mean age of 52.03 ± 13.43 and a median of 53 years. Among those, 49.4% were males. The prevalence of Chronic Diseases (CDs) was 36.3% (n = 697). Among those, 16% (n = 308) of them reported hypertension, followed by diabetes 11.6% (n = 222), asthma (4%, n = 76), and cardiovascular diseases (3.4% n = 65). The most common symptoms associated with Chronic Diseases were cough (36.5%, n = 700), followed by fever (21.8%, n = 419), and sore throat (21.2%, n = 407). The presence of diabetes was significantly associated with gender (p = 0.019), while hypertension was more common among male pilgrims (n = 829) compared to female pilgrims (n = 783) (p = 001). Furthermore, the presence of coughing was significantly associated with the age and educational level of the pilgrims (p = 0.001). On the other hand, headaches were more common among females compared to male pilgrims (p = 0.001). Conclusion A considerable number of pilgrims suffer from Chronic Diseases, with hypertension being most common. Further interventions, such as education and management before Hajj, are recommended.

An examination of the effectiveness of mindfulness-integrated cognitive behavior therapy on depression, anxiety, stress and sleep quality in Iranian women with breast cancer: a randomized controlled trial

Rolling vesicles: From confined rotational flows to surface-enabled motion

Friction forces are essential for cell movement, yet they also trigger numerous active cellular responses, complicating their measurement in vivo. Here, we introduce a synthetic model designed to measure friction forces between biomimetic membranes and substrates. The model consists of a vesicle with precisely controlled properties, fabricated via microfluidics, encapsulating a single ferromagnetic particle that is magnetically driven to rotate. The rotation of the particle generates a confined rotational flow, setting the vesicle membrane into motion. By adjusting the magnetic field frequency and vesicle size, the rotation frequency of the vesicle can be finely controlled, resulting in a rolling vesicle that functions as an effective tribological tool across a wide frequency range. At low frequencies, molecular contact between the membrane and substrate dominates frictional interactions, which enables determination of the contact friction coefficient. At higher frequencies, lubrication becomes predominant, causing the vesicles to slip rather than roll. Adjusting membrane fluidity and incorporating specific ligand–receptor interactions within this model will enable detailed studies of frictional forces in more complex biomimetic systems, providing key insights into the mechanisms of cell movement and mechanotransduction.

The incidence and predictors of peripheral arterial disease among type 2 diabetes mellitus patients at Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia, 2023: A retrospective follow-up study

Background Peripheral arterial disease is a blockage or narrowing of arteries transporting blood from the heart to the legs and feet. Type 2 diabetes mellitus is the second most common risk factor for peripheral arterial disease. This condition is associated with patient mortality and morbidity. However, there is limited evidence on the time to develop peripheral arterial disease, its incidence, and its predictors in the Amhara region, Ethiopia. Objective To assess the incidence and predictors of peripheral arterial disease among adult type 2 diabetes mellitus patients at Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia, 2023. Methods A retrospective follow-up study was conducted using data from 552 type 2 diabetes mellitus patients, selected by simple random sampling from January 2006 to December 2021. Data from patient charts and follow-up forms were extracted using a standardized tool, entered into Epi-Data version 3.1, and analyzed in STATA version 14. Kaplan-Meier curves, life table, and Cox regression model were used to assess survival times, survival probabilities, and identify independent predictors of peripheral arterial disease, respectively. Results The final analysis included 552 records. The median time for peripheral arterial disease was 13.5 years (95% CI: 11, 14.5). Being female (Adjusted Hazard Ratio (AHR) =  2.18, 95% CI: 1.36, 3.51), age above 65 years (AHR =  1.66, 95% CI: 1.06, 2.61), and fasting blood sugar of over 140 mg/dl (AHR =  3.34, 95% CI: 1.62, 6.90) were predictors for time to peripheral arterial disease in type 2 diabetes mellitus patients. We observed an incidence rate of 29 cases of peripheral arterial disease per 1000 person-years of observation (95% CI: 24–36). Conclusion and Recommendation Most peripheral arterial disease occurs after 10 years of diagnosis of type 2 diabetes mellitus. The incidence rate of peripheral arterial disease was high. Female sex, older age, and elevated baseline fasting blood sugar predicted the time until peripheral arterial disease developed. Therefore, clinicians and other stakeholders shall emphasize those types of type 2 diabetes mellitus patients who are female, older age, and with raised fasting blood sugar.

Developing advanced datadriven framework to predict the bearing capacity of piles on rock

Cadonilimab is efficacious in HER2-negative advanced-stage G/GEJ adenocarcinomas

Structure of ATP synthase from an early photosynthetic bacterium <i>Chloroflexus aurantiacus</i>

F-type ATP synthase (F 1 F O ) catalyzes proton motive force-driven ATP synthesis in mitochondria, chloroplasts, and bacteria. Different from the mitochondrial and bacterial enzymes, F 1 F O from photosynthetic organisms have evolved diverse structural and mechanistic details to adapt to the light-dependent reactions. Although complete structure of chloroplast F 1 F O has been reported, no high-resolution structure of an F 1 F O from photosynthetic bacteria has been available. Here, we report cryo-EM structures of an intact and functionally competent F 1 F O from Chloroflexus aurantiacus ( Ca F 1 F O ), a filamentous anoxygenic phototrophic bacterium from the earliest branch of photosynthetic organisms. The structures of Ca F 1 F O in its ADP-free and ADP-bound forms for three rotational states reveal a previously unrecognized architecture of ATP synthases. A pair of peripheral stalks connect to the Ca F 1 head through a dimer of δ-subunits, and associate with two membrane-embedded a-subunits that are asymmetrically positioned outside and clamp Ca F O ’s c 10 -ring. The two a-subunits constitute two proton inlets on the periplasmic side and two proton outlets on the cytoplasmic side, endowing Ca F 1 F O with unique proton translocation pathways that allow more protons being translocated relative to single a-subunit F 1 F O . Our findings deepen understanding of the architecture and proton translocation mechanisms of F 1 F O synthases and suggest innovative strategies for modulating their activities by altering the number of a-subunit.