S100A1, a calcium-binding protein, plays a crucial role in regulating Ca2+ signaling pathways in skeletal and cardiac myocytes via interactions with the ryanodine receptor (RyR) to affect Ca2+ release and contractile performance. Biophysical studies strongly suggest that S100A1 interacts with RyRs but have been inconclusive about both the nature of this interaction and its competition with another important calcium-binding protein, calmodulin (CaM). Thus, high-resolution cryo-EM studies of RyRs in the presence of S100A1, with or without additional CaM, were needed. The elegant work by Weninger et al. demonstrates the interaction between S100A1 and RyR1 through various experiments and confirms that S100A1 activates RyR1 at sub-micromolar Ca2+ concentrations, increasing the open probability of RyR1 channels.

UNASSIGNED: Cancer often causes reduced resilience, quality of life (QoL) and poorer overall well-being. To mitigate these problems, complementary and alternative medicine (CAM) is widely used among patients with cancer. This study aimed to evaluate the long-term effects of an interdisciplinary integrative oncology group-based program (IO-GP) on the resilience and use of CAM in patients with cancer.
UNASSIGNED: This was a prospective, observational, single-center study. Resilience (RS-13), CAM usage (I-CAM-G), QoL (SF-12) and health-related lifestyle factor (nutrition, smoking, alcohol consumption and physical exercise) data were collected for 70 patients who participated in a 10-week IO-GP between January 2019 and June 2022 due to cancer. The IO-GP is offered at the setting of a university hospital and is open to adult patients with cancer. It contains elements from mind-body medicine and positive psychology, as well as recommendations on healthy diet, exercise and CAM approaches. Patients who completed the IO-GP at least 12 months prior (1-4.5 years ago) were included in this study. Statistical analysis included descriptive analysis and parametric and nonparametric tests to identify significant differences (P < .05).
UNASSIGNED: Resilience increased significantly ≥12 months after participation in the IO-GP (n = 44, P = .006, F = 8.274) and had a medium effect size (r = .410). The time since the IO-GP was completed (\"12-24 months,\" \"24-36 months,\" and \">36 months\") showed no statistically significant interaction with changes in resilience (P = .226, F = 1.544). The most frequently used CAM modalities within the past 12 months were vitamins/minerals (85.7%), relaxation techniques (54.3%), herbs and plant medicine (41.1%), yoga (41.4%) and meditation (41.4%). The IO-GP was the most common source informing study participants about relaxation techniques (n = 24, 64.9%), meditation (n = 21, 72.4%) and taking vitamin D (n = 16, 40.0%). Significantly greater levels of resilience were found in those practicing meditation (P = .010, d = -.642) or visualization (P = .003, d = -.805) compared to non-practitioners.
UNASSIGNED: IO-GPs have the potential to empower patients with cancer to continue using CAM practices-especially from mind-body medicine-even 1 to 4.5 years after completing the program. Additionally, resilience levels increased. These findings provide notable insight into the long-term effects of integrative oncology interventions on resilience and the use of CAM, especially in patients with breast cancer.

BACKGROUND: Complementary and alternative (CAM) cancer treatment is often expensive and not covered by insurance. As a result, many people turn to crowdfunding to access this treatment.
OBJECTIVE: The aim of this study is to identify the rationales of patients with cancer seeking CAM treatment abroad by looking specifically at crowdfunding campaigns to support CAM cancer treatment in Tijuana, Mexico.
METHODS: We scraped the GoFundMe.com and GiveSendGo.com crowdfunding platforms for campaigns referencing CAM cancer clinics in Tijuana, initiated between January 1, 2022, and February 28, 2023. The authors created a coding framework to identify rationales for seeking CAM treatment in Tijuana. To supplement campaign metadata, we coded the beneficiary\'s cancer stage, type, age, specific treatment sought, whether the beneficiary died, gender, and race.
RESULTS: Patients sought CAM cancer treatment in Tijuana because the (1) treatment offers the greatest efficacy (29.9%); (2) treatment offered domestically was not curative (23.2%); (3) the clinic treats the whole person, and addresses the spiritual dimension of the person (20.1%); (4) treatments are nontoxic, natural, or less invasive (18.2%); and (5) clinic offers the newest technology (8.5%). Campaigns raised US $5,275,268.37 and most campaign beneficiaries were women (69.7%) or White individuals (71.1%).
CONCLUSIONS: These campaigns spread problematic misinformation about the likely efficacy of CAM treatments, funnel money and endorsements to CAM clinics in Tijuana, and leave many campaigners short of the money needed to pay for CAM treatments while costing beneficiaries and their loved one\'s time, privacy, and dignity. This study affirms that Tijuana, Mexico, is a very popular destination for CAM cancer treatment.

UNASSIGNED: Dynamic interaction of cam and pincer deformities can result in pathological contact forces in femoroacetabular impingement (FAI) syndrome. Similar deformities were noted during acetabular fracture reconstruction. We hypothesise that the prevalence of FAI deformity is higher in patients sustaining acetabular fractures than in a control group.
UNASSIGNED: This retrospective radiographic study compared the parameters that define FAI deformity in 100 patients consecutively admitted to a trauma unit with an acetabular fracture and a control group of 100 patients with lateral compression pelvic fracture without acetabular injury. Both underwent identical clinical imaging. Centre-edge angles (CEA) and alpha angles were used to define patients with pincer, cam, or mixed FAI deformity.
UNASSIGNED: There were significantly more patients with FAI deformity in the acetabular fracture group than in the control group (71% vs. 18%, p < 0.0001). There were considerably more fractures involving both anterior and posterior acetabular columns in patients with \'pincer\' sockets (p = 0.02, OR = 2.95, 95% CI, 1.12-7.78).
UNASSIGNED: There is a high prevalence of cam and pincer deformities in patients with acetabular fractures, particularly bi-column fractures.

IQ motif-containing proteins can be recognized by calmodulin (CaM) and are essential for many biological processes. However, the role of IQ motif-containing proteins in spermatogenesis is largely unknown. In this study, we identified a loss-of-function mutation in the novel gene IQ motif-containing H (IQCH) in a Chinese family with male infertility characterized by a cracked flagellar axoneme and abnormal mitochondrial structure. To verify the function of IQCH, Iqch knockout (KO) mice were generated via CRISPR-Cas9 technology. As expected, the Iqch KO male mice exhibited impaired fertility, which was related to deficient acrosome activity and abnormal structures of the axoneme and mitochondria, mirroring the patient phenotypes. Mechanistically, IQCH can bind to CaM and subsequently regulate the expression of RNA-binding proteins (especially HNRPAB), which are indispensable for spermatogenesis. Overall, this study revealed the function of IQCH, expanded the role of IQ motif-containing proteins in reproductive processes, and provided important guidance for genetic counseling and genetic diagnosis of male infertility.

Precise segmentation for skin cancer lesions at different stages is conducive to early detection and further treatment. Considering the huge cost of obtaining pixel-perfect annotations for this task, segmentation using less expensive image-level labels has become a research direction. Most image-level label weakly supervised segmentation uses class activation mapping (CAM) methods. A common consequence of this method is incomplete foreground segmentation, insufficient segmentation, or false negatives. At the same time, when performing weakly supervised segmentation of skin cancer lesions, ulcers, redness, and swelling may appear near the segmented areas of individual disease categories. This co-occurrence problem affects the model\'s accuracy in segmenting class-related tissue boundaries to a certain extent. The above two issues are determined by the loosely constrained nature of image-level labels that penalize the entire image space. Therefore, providing pixel-level constraints for weak supervision of image-level labels is the key to improving performance. To solve the above problems, this paper proposes a joint unsupervised constraint-assisted weakly supervised segmentation model (UCA-WSS). The weakly supervised part of the model adopts a dual-branch adversarial erasure mechanism to generate higher-quality CAM. The unsupervised part uses contrastive learning and clustering algorithms to generate foreground labels and fine boundary labels to assist segmentation and solve common co-occurrence problems in weakly supervised skin cancer lesion segmentation through unsupervised constraints. The model proposed in the article is evaluated comparatively with other related models on some public dermatology data sets. Experimental results show that our model performs better on the skin cancer segmentation task than other weakly supervised segmentation models, showing the potential of combining unsupervised constraint methods on weakly supervised segmentation.

Wheat yellow mosaic virus (WYMV) causes severe viral wheat disease in Asia. The WYMV P1 protein encoded by RNA2 has viral suppressor of RNA silencing (VSR) activity to facilitate virus infection, however, VSR activity has not been identified for P2 protein encoded by RNA2. In this study, P2 protein exhibited strong VSR activity in Nicotiana benthamiana at the four-leaf stage, and point mutants P70A and G230A lost VSR activity. Protein P2 interacted with calmodulin (CaM) protein, a gene-silencing associated protein, while point mutants P70A and G230A did not interact with it. Competitive bimolecular fluorescence complementation and competitive co-immunoprecipitation experiments showed that P2 interfered with the interaction between CaM and calmodulin-binding transcription activator 3 (CAMTA3), but the point mutants P70A and G230A could not. Mechanical inoculation of wheat with in vitro transcripts of WYMV infectious cDNA clone further confirmed that VSR-deficient mutants P70A and G230A decreased WYMV infection in wheat plants compared with the wild type. In addition, RNA silencing, temperature, ubiquitination and autophagy had significant effects on accumulation of P2 protein in N. benthamiana leaves. In conclusion, WYMV P2 plays a VSR role in N. benthamiana and promotes virus infection by interfering with calmodulin-related antiviral RNAi defense.

BACKGROUND: The co-occurrence of C4 and CAM photosynthesis in a single species seems to be unusual and rare. This is likely due to the difficulty in effectively co-regulating both pathways. Here, we conducted a comparative transcriptomic analysis of leaves and cotyledons of the C4-like species Sesuvium sesuvioides (Aizoaceae) using RNA-seq.
RESULTS: When compared to cotyledons, phosphoenolpyruvate carboxylase 4 (PEPC4) and some key C4 genes were found to be up-regulated in leaves. During the day, the expression of NADP-dependent malic enzyme (NADP-ME) was significantly higher in cotyledons than in leaves. The titratable acidity confirmed higher acidity in the morning than in the previous evening indicating the induction of weak CAM in cotyledons by environmental conditions. Comparison of the leaves of S. sesuvioides (C4-like) and S. portulacastrum (C3) revealed that PEPC1 was significantly higher in S. sesuvioides, while PEPC3 and PEPC4 were up-regulated in S. portulacastrum. Finally, potential key regulatory elements involved in the C4-like and CAM pathways were identified.
CONCLUSIONS: These findings provide a new species in which C4-like and CAM co-occur and raise the question if this phenomenon is indeed so rare or just hard to detect and probably more common in succulent C4 lineages.

Delirium is highly prevalent among hospitalized older adults and is associated with unfavorable outcomes. However, delirium often remains undiagnosed in the hospital context. Having a valid, simple, and fast screening tool could help in limiting the additional workload for healthcare professionals, without leaving delirium undetected. The aim of this study was to estimate the sensitivity and specificity of the Recognizing Acute Delirium As part of your Routine (RADAR) scale in an Italian hospital. An observational cross-sectional study was conducted. A total of 150 patients aged ≥70 years were enrolled. Receiver operating characteristic (ROC) curves using the Confusion Assessment Method (CAM) criterion-defined delirium as the gold standard were plotted to evaluate the performance of the RADAR scale. The cut-off suggested by previous research was used to estimate the sensitivity, specificity, and positive and negative predictive values of the RADAR scale. The involved patients were mostly females (60%; n = 90), with a median age of 84 years (I-III quartiles: 80-88). According to the CAM and the RADAR scale, 37 (25%) and 58 (39%) patients were classified as experiencing delirium, respectively. The area under the ROC curve of the RADAR scale was 0.916. Furthermore, the RADAR scale showed robust sensitivity (95%), specificity (80%), and positive (60%) and negative predictive values (98%). The RADAR scale is thus suggested to be a valid tool for screening assessment of delirium in hospitalized older adults.

BACKGROUND: Calliptamus italicus L. is a major pest in Xinjiang grassland. The diapause overwintering strategy is one of the important reasons for the large population of this pest. This study investigated the function of the genes associated with the release of diapause (DIB, JHE and CAM) in Calliptamus italicus by RNA interference (RNAi) technology to aid in its biological control.
RESULTS: The expression levels of DIB and its downstream-associated genes (EcR and FTZ-F1) in the eggs injected with dsDIB for 12 h decreased by 96.6%, 55.8% and 81.8%, respectively. Diapause began to terminate on day 3, and development was almost complete on day 6. However, the head was significantly smaller. The expression levels of JHE and its downstream-associated genes (JHEH and VgR) at 48 h after dsJHE treatment decreased by 76.5%, 85.6% and 85.9%, respectively. The termination of diapause occured on day 3 of incubation. The development was basically complete on day 6, but the yolk had been incompletely absorbed. The expression of CAM and its downstream-associated genes (CAMK4 and MYL) at 24 h after dsCAM treatment decreased by 42.4%, 95.3% and 82.7%, respectively. Diapause termination was completed on day 4 for incubation, and development was abnormal on day 6. The absorption of yolk was incomplete.
CONCLUSIONS: DIB, JHE and CAM can delay the diapause termination of Calliptamus italicus eggs to different degrees and can be developed as potential target genes for its biological control. © 2024 Society of Chemical Industry.