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IntroductionInduction of labour (IOL) is a commonly performed obstetric intervention, particularly when delivery is deemed more beneficial than continuing the pregnancy due to maternal or fetal indications. When the cervix is unfavourable for delivery, cervical ripening is performed prior to IOL. A wide variety of mechanical, pharmacological and combination methods are used, but the optimal approach balancing efficacy, safety and patient experience remains uncertain. Conventional aggregate data (AD) meta-analyses lack individual-level data, limiting exploration of patient-level factors for personalised medicine and do not address concerns about the trustworthiness of data presented in peer-reviewed randomised controlled trials (RCTs). This protocol describes an individual participant data (IPD) network meta-analysis (NMA) designed to evaluate and rank cervical ripening methods for IOL using only high quality, trustworthy data.Methods and analysisWe will identify eligible parallel-group RCTs enrolling pregnant women with a singleton, cephalic fetus at ≥34 weeks’ gestation requiring cervical ripening, through comprehensive searches of Ovid MEDLINE, Embase, Emcare, Scopus, Cochrane Pregnancy and Childbirth Register, WHO International Clinical Trials Registry Platform, clinicaltrials.gov and reference lists of prior reviews. The interventions we consider will be selected via Delphi consensus with international clinical experts. Eligible trial investigators will be invited to contribute de-identified IPD; AD will be used if IPD is unavailable. Trials will be assessed for trustworthiness using the Trustworthiness in RAndomised Clinical Trials checklist and the IPD Integrity Tool, with only eligible studies included in the primary analysis. All statistical analyses will follow a pre-specified statistical analysis plan (SAP) finalised before any analyses are conducted. A two-stage, contrast-based, frequentist IPD-NMA will compare cervical ripening methods for three co-primary outcomes: vaginal birth, composite adverse perinatal outcomes and composite adverse maternal outcomes. Subgroup analyses will assess effect modifiers (eg, parity, age and previous caesarean), with treatment rankings presented using the surface under the cumulative ranking curve and rank-heat plots. Sensitivity analyses will examine the impact of bias, missing data and population criteria.Ethics and disseminationThis study has been approved by the Monash University Human Research Ethics Committee (No. 48189). IPD will be de-identified and securely transferred for storage on a Monash University-hosted shared network drive. Findings will be disseminated via peer-reviewed publications, conference abstracts and the Cervical Ripening for Induction of Labour Collaborative Evidence Network Meta-Analysis (CIRCLE-NMA) website (https://circlenma.com). Patient and public involvement will guide the communication and interpretation of results.PROSPERO registration numberCRD420251077464.

Global climate models (GCMs) are critical tools for understanding and projecting climate variability and change, yet the performance of these models is notoriously weak over much of tropical Africa. To improve this situation, process-based studies of African climate dynamics and their representation in GCMs are required. Here, we focus on summer rainfall of eastern Africa (SREA), which is crucial to the Ethiopian Highlands and feeds the flow of the Blue Nile River. The SREA region is highly vulnerable to droughts, with El Niño–Southern Oscillation (ENSO) being a leading cause of interannual rainfall variability. Adequate understanding and accurate representation of climate features that influence regional variability is an important but often neglected issue when evaluating models. We perform a process-based evaluation of GCMs, focusing on the upper-troposphere tropical easterly jet (TEJ), which has been hypothesized to link ENSO to SREA. We find that most models have an ENSO–TEJ coupling similar to observed, but the models diverge in their representation of TEJ–SREA coupling. Differences in the latter explain the majority (80%) of variability in ENSO teleconnection simulation across the models. This is higher than the variance explained by rainfall coupling with the Somali jet (44%) and African easterly jet (55%). However, our diagnostics of the leading hypothesized mechanism in the models—variability in divergence in the TEJ exit region—are not consistent across models and suggest that a deeper understanding of the mechanisms of TEJ–precipitation coupling should be a priority for studies of climate variability and change in the region.

ChaC1 is a mammalian proapoptic protein of unknown function induced during endoplasmic reticulum stress. We show using in vivo studies and novel in vitro assays that the ChaC family of proteins function as γ‐glutamyl cyclotransferases acting specifically to degrade glutathione but not other γ‐glutamyl peptides. The overexpression of these proteins (but not the catalytically dead E>Q mutants) led to glutathione depletion and enhanced apoptosis in yeast. The ChaC family is conversed across all phyla and represents a new pathway for glutathione degradation in living cells, and the first cytosolic pathway for glutathione degradation in mammalian cells. This study identifies the pro‐apoptotic, ER stress‐induced ChaC family of proteins as γ‐glutamyl cyclotransferases acting specifically to degrade glutathione.

This paper examines the performance of a Gate-Engineered Gate-All-Around Charge Plasma Nanowire Field Effect Transistor (GAA-DMG-GS-CP NW-FET) and the implementation of a common source (CS) amplifier circuit. The proposed GAA-DMG-GS-CP NW-FET incorporates dual-material gate (DMG) and gate stack (GS) as gate engineering techniques and its analog/RF performance parameters are compared to those of the Gate-All-Around Single-Material Gate Charge Plasma Nanowire Field Effect Transistor (GAA-SMG-CP NW-FET) device. Both Gate-All-Around (GAA) devices are designed using the Silvaco TCAD tool. GAA structures have demonstrated good gate control because the gate holds the channel, which is an inherent advantage for both devices discussed herein. The charge plasma dopingless technique is used, in which the source and drain regions are formed using metal contacts and necessary work functions rather than doping. This dopingless technique eliminates the need for doping, reducing fluctuations caused by random dopants and lowering the device’s thermal budget. Gate engineering techniques such as DMG and GS significantly improved the current characteristics which played a crucial role in obtaining maximum gain for circuit designs. The lookup table (LUT) approach is used in the implementation of the CS amplifier circuit with the proposed device. The transient response of the circuit is analyzed with both the device structures where the gain achieved for the CS amplifier circuit using the proposed GAA-DMG-GS-CP NW-FET is 15.06 dB. The superior performance showcased by the proposed GAA-DMG-GS-CP NW-FET device with analog, RF and circuit analysis proves its strong candidature for future nanoscale and low-power applications.

In Wireless Sensor Networks (WSNs), routing algorithms can provide energy efficiency. However, due to unbalanced energy consumption for all nodes, the network lifetime is still prone to degradation. Hence, energy efficient routing was developed in this article by selecting cluster heads (CH) with the help of adaptive whale optimization (AWOA) which was used to reduce time-consumption delays. The multi-objective function was developed for CH selection. The clusters were then created using the distance function. After establishing groupings, the supercluster head (SCH) was selected using the benefit of a fuzzy inference system (FIS) which was used to collect data for all CHs and send them to the base station (BS). Finally, for the data-transfer procedure, hop count routing was used. An Oppositional-based Whale optimization algorithm (OWOA) was developed for multi-constrained QoS routing with the help of AWOA. The performance of the proposed OWOA methodology was analyzed according to the following metrics: delay, delivery ratio, energy, NLT, and throughput and compared with conventional techniques such as particle swarm optimization, genetic algorithm, and Whale optimization algorithm.

SUMOylation is one of the post-translational modifications that have recently been described as a key regulator of various cellular, nuclear, metabolic, and immunological processes. The process of SUMOylation involves the modification of one or more lysine residues of target proteins by conjugation of a ubiquitin-like, small polypeptide known as SUMO for their degradation, stability, transcriptional regulation, cellular localization, and transport. Herein, for the first time, we report the involvement of the host SUMOylation pathway in the process of infection of Leishmania donovani , a causative agent of visceral leishmaniasis. Our data revealed that infection of L. donovani to the host macrophages leads to upregulation of SUMOylation pathway genes and downregulation of a deSUMOylating gene, SENP1. Further, to confirm the effect of the host SUMOylation on the growth of Leishmania , the genes associated with the SUMOylation pathway were silenced and parasite load was analyzed. The knockdown of the SUMOylation pathway led to a reduction in parasitic load, suggesting the role of the host SUMOylation pathway in the disease progression and parasite survival. Owing to the effect of the SUMOylation pathway in autophagy, we further investigated the status of host autophagy to gain mechanistic insights into how SUMOylation mediates the regulation of growth of L. donovani . Knockdown of genes of host SUMOylation pathway led to the reduction of the expression levels of host autophagy markers while promoting autophagosome–lysosome fusion, suggesting SUMOylation-mediated autophagy in terms of autophagy initiation and autophagy maturation during parasite survival. The levels of reactive oxygen species (ROS) generation, nitric oxide (NO) production, and pro-inflammatory cytokines were also elevated upon the knockdown of genes of the host SUMOylation pathway during L. donovani infection. This indicates the involvement of the SUMOylation pathway in the modulation of protective immune responses and thus favoring parasite survival. Taken together, the results of this study indicate the hijacking of the host SUMOylation pathway by L. donovani toward the suppression of host immune responses and facilitation of host autophagy to potentially facilitate its survival. Targeting of SUMOylation pathway can provide a starting point for the design and development of novel therapeutic interventions to combat leishmaniasis.