Background: The perspectives of patients and healthcare professionals regarding deprescribing in surgical wards within hospital settings are unknown. Objective: To explore current practices, attitudes, and the enablers and barriers to deprescribing in hospital for older surgical inpatients from the perspectives of doctors, pharmacists, patients and carers. Methods: A mixed methods study was performed. Two surveys were administered Australia-wide (revised Patients’ Attitudes Towards Deprescribing questionnaire for patients/carers and Deprescribing Self-Efficacy Survey for doctors/pharmacists). Interviews, focus groups and observations of ward rounds were conducted with participants from five Australian hospitals. Quantitative data were analysed descriptively, while qualitative data were examined using a combined inductive and deductive approach, with results triangulated. Results: There were 109 survey participants (58 doctors/pharmacists and 51 patients/carers), 28 interview/focus group participants (15 doctors/pharmacists and 13 patients/carers) and eight ward round participants. Doctors and pharmacists reported low to moderate levels of confidence in deprescribing. While most patients and carers were satisfied with their medications, they expressed a willingness to consider deprescribing. Five themes were identified from the interviews, focus groups and ward round observations; 1) deprescribing is not a priority, 2) medication review occurs in response to triggers, 3) knowledge about deprescribing is limited, 4) deprescribing requires a team effort and 5) trust, rapport and communication are essential for successful deprescribing. Conclusions: Doctors working on surgical wards are unlikely to proactively deprescribe medications. A collaborative patient-centred approach involving geriatricians, clinical pharmacologists and pharmacists, along with educational interventions may facilitate deprescribing for surgical patients.

Mobile Phones are part of our life. It is the fastest and the easiest medium of communication. Battery life of mobile phone is always been a problem for manufacturers. People are complaining about their mobile's battery life, that they don't have long battery life and they have to charge their phone several times. In this paper a new idea is shown to charge your mobile phone anywhere you want without connecting its charger. This is done using microwaves. Microwaves are the radio waves which provide communication between two mobile phones. The microwave is sent with the message by the transmitter using antenna at the frequency of 2.45GHz. Here we are using Microwaves as the source of energy to charge the phone. We have to add a sensor, a rectenna circuit and a filer in our mobile phone to do the job. By adding these things we can charge our phone using microwave when we talk. So, as we talk more we can charge more!!

Conflict can induce negative affect, which may enhance performance in subsequent tasks. Our recent behavirol study showed that the subjective experience of conflict improved performance not only in subsequent conflict (incongruent) trials but also in non-conflict (congruent) trials. However, it remains unclear how fluctuations in conflict-induced negative affect influence performance adjustments. In this electroencephalography (EEG) study, we investigated the influences of subjective experience and implicit regulation of conflict-induced negative affect on subsequent performance, by comparing two conditions: ‘Experience-do’ where participants simply experienced the Stroop stimulus, and ‘Experience-Rating-do’ where they rated their emotional response to the stimulus before responding. Thirty-eight participants performed a modified color-word Stroop task under these conditions. Behaviorally, both experiencing and rating conflict-induced negative affect improved subsequent performance across conflict and non-conflict trials. At the ERP level, the ‘Experience-R-do’ condition showed increased Late Positive Potential (LPP) and P1amplitudes in the preceding phase and decreased conflict slow potential (SP) in the current phase, suggesting lower control demands. In contrast, the ‘Experience-do’ condition showed increased LPP, P1, and conflict SP amplitudes in the current phase, reflecting heightened emotional and cognitive engagement. Notably, improvements in conflict adjustments were linked to distinct mechanisms: increased P1 and reduced conflict SP facilitated performance under the ‘Expereicen-R-do’ condition, while larger LPP was associated with gains in the ‘Experiecne-do’ condition. These findings shed light on the distinct mechanisms by which subjective experience and implicit regulation nof conflict-induced negative affect contribute to adaptive performance adjustments.

Progressive balance exercises may change corticomotor excitability during the learning process of postural stability control. The primary purpose of the present study was to assess corticomotor excitability corresponding to the peroneus longus muscle under transcranial magnetic stimulation following 6 weeks of progressive balance exercises in individuals suffering from functional ankle instability. Eligible volunteers with functional ankle instability were randomly and equally assigned to either the intervention or control groups. The intervention group participated in progressive balance exercises every other day for 6 weeks, while the control group continued their daily activities and refrained from new physical activities. The variables were measured in the intervention group before and after the progressive balance exercises, and in the control group twice at an interval of 6 weeks. The primary variables included the active and resting corticomotor thresholds, motor evoked potential, and cortical silent period, which were measured using an electromyography device under a transcranial magnetic stimulator. The corticomotor thresholds and cortical silent period of the peroneus longus muscle significantly decreased in the intervention group following progressive balance exercises (p-value < 0.001), whereas the normalized motor evoked potential significantly increased in the same group (p-value < 0.001). Conversely, no significant changes were detected in the control group (p-value > 0.086). The present study revealed, for the first time, that 6 weeks of progressive balance exercises significantly increased corticomotor excitability corresponding to the peroneus longus muscle and improved balance control in individuals suffering from functional ankle instability.

Case Report：Psoas Abscess Caused by Carbapenem-Resistant Enterobacteriaceae in a CO Poisoning PatientXinyue Ma1; Chengxin Song1;Lijun Ma2; Jiacui Zhang3*;Ling Li3;Fengmei Zou3;1 Gansu University of Chinese Medicine, Lanzhou, Gansu, China.2 The NO.2 People’s Hospital of Lanzhou,Lanzhou, Gansu, China.3 Gansu Provincial People’s Hospital, Lanzhou, Gansu, China.*Corresponding author: Jiacui Zhang; Address: Gansu Provincial People’s Hospital, 204 Donggang West Road, Chengguan District, Lanzhou, Gansu, China; E-mail: zjc1504059310@163.com

TitleRole of cholesterol crystals in the etiological diagnosis of two episodes of middle cerebral artery occlusion: A case report

Purpose: To assess the prevalence and severity of transfusion-associated iron overload in survivors of childhood cancer. Patients and Methods: Serum iron, total iron binding capacity, percent iron saturation and ferritin were measured in 75 survivors of childhood cancer. In addition, blood bank records were reviewed to determine the volume of packed red blood cells (pRBCs) administered during cancer therapy. Patients who received > 120ml/kg of pRBCs or had a ferritin > 1,000mcg/L underwent hepatic R2 and cardiac T2* MRI for iron quantification, echocardiogram, assessment of liver and endocrine function, and genetic analysis for hereditary hemochromatosis. Results: Forty-nine patients qualified for second level studies. Of these, 35 completed the MRI scans. Fifteen patients had a liver iron concentration (LIC) >3mg iron/g (moderate hepatic iron overload), including eight patients who had an LIC greater than 7 mg iron/g (severe hepatic iron overload), with a mean LIC of 4.3 mg iron/g (0-15.6mg iron/g). LIC correlated with both total volume of pRBCs and ferritin. No patient had cardiac iron loading by MRI. Eleven patients were heterozygous and one was homozygous for mutations associated with hereditary hemochromatosis. There was no correlation between iron overload and hereditary hemochromatosis gene status. Conclusion: There is a high prevalence of transfusion-associated iron overload among survivors of childhood cancer. This is concerning given the overlap between organ toxicities associated with cancer treatment and those known to be associated with iron overload. The tight correlation between LIC and ferritin suggests ferritin may be a reliable indicator of iron load in this patient population.

Spatial visual attention prioritizes specific locations while disregarding others. The location of spatial attention can be deployed without overt movements (covertly). Spatial dynamics of covert attention is exceptionally difficult to measure due to its hidden nature. One way to implicitly index the location of covert attention is via pupillary light responses (PLR), as the strength of PLR is modulated by where attention is allocated. However, this method has so-far necessitated simplistic stimuli. Here we report on a novel pupillometric method that allows to track covert attention even with highly complex stimuli. Participants (n = 36) watched movie clips while they either passively viewed the movie, or they top-down shifted covert attention to targets in the left, right, or both sides of the visual field. Using a recent toolbox (Open-DPSM), we evaluated whether luminance changes in regions presumably receiving more attention contribute more strongly to the pupillary responses – and thereby reveal covert attention. Three independent and established effects of covert attention on pupil responses were found: (1) a bottom-up effect suggesting more attention drawn to more dynamic regions in the movie, (2) a top-down effect suggesting more attention towards the instructed direction, and (3) an overall tendency to attend the left side (i.e., pseudoneglect). These findings show that pupil responses can physiologically index covert attention with our approach, even in highly dynamic and complex environments. We see considerable potential in measuring covert attention with our method in many real-life scenarios that were impossible to study before.

Velocity and turbulence observations are used to estimate the forward cascade of kinetic energy from the internal tide to dissipation within a steep canyon. The semidiurnal tide is the only significant kinetic energy source within the canyon, simplifying the energetic pathway analysis. Two methods for computing cross-frequency kinetic energy flux are compared to observed dissipation. One method, coarse graining, allows strongly nonlinear dynamics while the other assumes weak nonlinearity. Fluxes from both methods are greater than dissipation estimates from the finescale parameterization which is often used in global climate models. Coarse graining reveals energy flux to dissipation from lower internal wave frequencies. These results support the idea that there may be greater kinetic energy cascade due to wave breaking near topography than accounted for by current parameterizations. Enhanced near boundary mixing and upwelling has implications for the rate and spatial distribution of the upwelling branch of the global overturning circulation.

not-yet-known not-yet-known not-yet-known unknown Objective To assess the prevalence of adverse perinatal outcomes - and evaluate the association between intrapartum-related neonatal encephalopathy (IP-NE) and i) emergency referrals and ii) emergency cesarean sections (CS) by obstetric risk factors. Design Cross-sectional with a nested case-control study. Setting Two hospitals in rural Eastern Uganda. Population Women giving birth to a live or stillborn baby weighing >2000 grams between June and December 2022. Methods We used prospectively collected perinatal e-registry data to assess the prevalence of adverse perinatal outcomes. Logistic regression with interaction was used to assess the association between IP-NE and emergency referral and emergency CS across risk groups of hypertensive disorders, antepartum hemorrhage, prolonged/ obstructed labor, and birth weight. Main outcome measures Adverse perinatal outcomes were stillbirths, 24-hour neonatal deaths, and IP-NE (defined as Apgar score <7 at 5 minutes, cord blood lactate ≥5.5 mmol/L, and Thompson score ≥5). Results Of 6,550 births, 10.2% had an adverse perinatal outcome: 3.8% stillbirths, 0.6% neonatal deaths, and 5.7% IP-NE. Adverse outcomes were high among neonates whose mothers had antepartum hemorrhage (31.3%) and prolonged or obstructed labor (27.2%). Emergency referral and CS did not change the association between IP-NE and obstetric risks, except in prolonged or obstructed labor. Without emergency CS, the predicted probability of IP-NE was 0.73 (95% CI: 0.51–0.95); with CS, it decreased to 0.45 (95% CI: 0.39–0.50). Conclusions Neonates born to mothers with obstetric emergencies had low healthy survival rates. Emergency referral and CS showed limited benefits in reducing IP-NE, indicating challenges in accessing appropriate care.

The prediction and treatment of spontaneous preterm labor (sPTL) are critical challenges in clinical practice due to obscure etiology and are lack of highly specific and sensitive testing methods. In the current study, we extended the application of non-invasive prenatal testing (NIPT) into the field of sPTL prediction, and using high-throughput small RNA-sequencing technique to screen the potential biomarkers for sPTL in maternal peripheral blood. We found that hsa-miR-150-5p and hsa-miR-512-3p were specifically decreased in the sPTL patients, compared to either term labor or term not labor patients. The change of hsa-miR-150-5p is validated using quantitative PCR with the AUROC of hsa-miR-150-5p around 0.8272, suggesting it’s a promising biomarker for sPTL prediction. In the discovery set, hsa-miR-150-5p exhibited an AUROC of approximately 0.8508, which was validated in an independent cohort, accurately classifying preterm samples with an AUROC of 0.8010. Moreover, we showed that miR-150-5p inhibited migration and invasion of chorionic cells by directly targeting ADAM19, a member of ADAM (a disintegrin and metalloprotease domain) family. The significant increase of ADAM19 in chorionic tissues from sPTL patients further indicates its inverse correlationship with miR-150-5p. ADAM19 is a sheddase of membrane-bound TNF-a and releases the TNF-a trimer into the extracellular environment, which reciprocally induces the expression of ADAM19 to form a regenerative cycle and augments the migration and invasion of fetal membrane cells. Our results suggested that miR-150-5p is not only an effective non-invasive biomarker for sPTL, but also plays an important biological role in the premature rupture of fetal membranes associated with spontaneous preterm labor.

The traditional synthetic aperture radar (SAR) imaging algorithm typically demands substantial computational resources due to its involvement in large-scale matrix operations, which presents challenges for imaging in expansive scenes. By leveraging the reversibility of the imaging process, a method that simulates the inverse process of generating echoes can be employed to expedite imaging. This approach shares the computational complexity of the matched filter algorithm, thereby enabling imaging of large scenes. However, the iteration-based algorithm necessitates manual parameter adjustments, which can be somewhat arbitrary and challenging to optimize effectively. Consequently, employing neural networks to train these parameters not only enhances imaging speed but also enhances imaging quality. Moreover, the Self-supervised Azimuth Ambiguity Suppression Network (SAAS-Net) introduced in this study effectively achieves azimuth ambiguity suppression without necessitating alterations to the hardware architecture. The experiments indicate that the algorithm proposed in this paper can achieve rapid imaging while maintaining computational accuracy consistent with matched filter algorithms such as chirp-scaling algorithm.

ABSTRACT Background: Narcissistic abuse, a manipulative psychological abuse often inflicted by individuals with narcissistic traits, profoundly impacts victims, resulting in symptoms similar to Complex Post-Traumatic Stress Disorder (C-PTSD), anxiety, and depression. This form of abuse is underrecognized in clinical settings despite its severe effects on mental health, manifesting through mechanisms such as trauma bonding and cognitive distortions. Research on narcissistic abuse lacks a formalized diagnosis, creating gaps in therapeutic support for survivors. Case Representation: This study explores Mrs. X’s experience as an illustrative case, revealing how narcissistic abuse within familial and romantic relationships caused chronic anxiety, hypervigilance, and derealization, exacerbated during periods of intense stress. Mrs. X’s case exemplifies the psychological toll of such abuse, including cycles of idealization, devaluation, and discard. Quantitative data further underscore the prevalence of severe anxiety and C-PTSD among victims, showing that 78% of survey respondents experienced significant trauma-related symptoms. Conclusion: Narcissistic abuse necessitates expanded therapeutic approaches, integrating trauma-informed methods such as Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) and Eye Movement Desensitization and Reprocessing (EMDR). Future research should prioritize large-scale studies to understand narcissistic abuse’s full impact and develop clinical protocols for effective recognition and treatment. Enhanced awareness, policy development, and digital health interventions are essential to support recovery and resilience in survivors. Keywords: Narcissistic abuse, Narcissistic Victim Syndrome, C-PTSD, trauma bonding, therapeutic interventions

Abstract Background This study explores Narcissistic Personality Disorder (NPD) by analyzing how grandiose and covert narcissistic traits impact family dynamics. Leveraging psychoanalytic theory and quantitative methodologies, it investigates empathy deficits as a core mechanism behind manipulative behaviors and relational dysfunction associated with NPD. The study employs the Narcissistic Personality Inventory (NPI) and the Interpersonal Reactivity Index (IRI) to quantitatively assess empathy and its relational effects across narcissistic subtypes. Case Representation A case analysis of a 65-year-old man with grandiose narcissism highlights significant family discord resulting from his manipulative interactions. Structural equation modeling (SEM) reveals that his empathy deficits are key in perpetuating relational dissatisfaction, underscoring the subtype-specific pathways through which narcissistic traits impact family cohesion. Conclusion The findings emphasize empathy deficits as a central mediator in the relationship between narcissistic traits and family dysfunction. This study advocates for subtype-specific therapeutic approaches—targeting behavioral regulation for grandiose narcissists and empathy development for covert narcissists—to improve relational outcomes. Future research should adopt longitudinal approaches to further investigate these dynamics across diverse cultural contexts. Keywords – cognitive empathy, covert narcissism, grandiose,

The Malaysian construction industry is experiencing rapid growth, driven by increasing demand for residential homes, commercial buildings, and business premises. Lightweight concrete, now an essential building material, has prompted further research into its development. The objective of this study is to identify suitable materials and optimal mixing ratios for producing lightweight concrete blocks using industrial waste products. Specifically, Expanded Polystyrene (EPS) and pressmud, a by-product of the sugar industry, were incorporated. In this study, a 1:2 mixing ratio was used to produce blocks measuring 500mm x 200mm x 100mm, incorporating EPS and pressmud. Research indicates that EPS is an effective lightweight material in concrete mixtures due to its favorable properties. Pressmud was also found to be a valuable additive, as its characteristics are similar to sand. Additionally, its moisture content enables a reduction in the required amount of both sand and water in the mix. The most favorable outcome was observed in the third sample, which used a mixing ratio of 8:16:6. The study successfully achieved its objectives, resulting in the production of lightweight concrete blocks. This sustainable approach not only offers an innovative building material but also provides a solution for the sugar industry by utilizing pressmud, reducing industrial waste and supporting environmental sustainability.

Avian pathogenic Escherichia coli (APEC) poses significant health risks in poultry, leading to infections that impact productivity. APEC strains exhibit antibiotic resistance, complicating treatment options. Current vaccination strategies are limited in their protective scope, necessitating the exploration of innovative alternatives such as probiotics, bacteriophages, immune stimulants, and antimicrobial peptides (AMPs). AMPs show promise due to their rapid action against resistant bacteria and minimal resistance development. Additionally, small molecules have demonstrated effectiveness against various APEC serotypes, supporting the development of new antimicrobial therapies. Overall, a multifaceted approach addressing APEC’s virulence factors and incorporating novel therapies is crucial for controlling colibacillosis in poultry and mitigating risks to human health.

Glycosyl sulfonamides have been identified as novel inhibitors of carbonic anhydrase, showing great potential for cancer treatment. However, previous approaches to synthesizing glycosyl sulfonamides require multi steps, resulting in low efficiency and being time-consuming. Herein, we disclose a reductive coupling strategy that enables the modular synthesis of glycosyl sulfonamide using readily accessible glycosyl sulfinates and feedstock chemical nitroarenes. This method allows for the construction of rarely reported N-aryl glycosyl sulfonamides and exhibits tolerance to a variety of functional groups.

As the environmental pollution caused by electronic products becomes increasingly severe, the development and application of biodegradable batteries have become more important. Traditional biodegradable batteries are limited by characteristics such as low power output, low capacity, and lack of flexibility and stretchability, restricting their range of applications. We propose a biodegradable battery made from magnesium-molybdenum electrodes and gelatin- organic acid electrolytes such as lactic acid (LA)-gelatine (gel) and the citric acid (CA)-gelatine (gel). The addition of organic acids to the gelatine increased the ionic conductivity of the electrolyte and promoted its reaction with the magnesium electrode, effectively enhancing battery performance. Experimental results showed that the LA-gel based electrolyte achieved a maximum conductivity of 2.37 × 10 -3 S/cm, while the CA-gel based electrolyte demonstrated a low activation energy of 11.04 kJ/mol. The highest open circuit voltage (OCV) was recorded for the CA-gel based electrolyte with the Mg anode and Mo cathode, which is 1.92 V. The maximum power and maximum capacity achieved by the Mg-based battery are 76.8 μW and 1.36 mAh/cm 2, respectively at 40 μA/cm 2 for LA-gel battery. Moreover, the battery structure can be designed in a serpentine shape, allowing it to be stretched to 180% of its original length while maintaining stable voltage. We integrate the biodegradable stretchable battery with a pressure sensor and demonstrate its applicability for wearable applications.

Rice self-sufficiency is a central goal for the Indonesian government, providing significant political benefits. However, achieving this goal is challenging due to the heavy reliance of rice production on water availability, which climate change can significantly alter. Our study investigates the relationship between Indonesia’s climate change policies and rice prices, considering the paradox of rice self-sufficiency. We hypothesize a correlation between climate policy and rice prices, assuming market forces primarily determine prices. Our findings reveal an unexpected result: there is no strong, direct correlation between local climate policy and rice self-sufficiency in Indonesia. This suggests that the dynamics of rice production and pricing may be influenced by other factors, particularly government interventions, warranting further investigation. These insights highlight the complexities in balancing climate strategies with agricultural goals in Indonesia.

This study aimed to comprehensively evaluate current policies and actions that public sectors in Iran are taking to create healthy food environments for the management of obesity, Non-Communicable Diseases, and their related inequalities compared to the best international practices to fill current policy gaps. Healthy Food Environment Policy Index was the principal tool and interactions with key stakeholders was the main approach applied. Data collection was conducted in 6 steps: Validation of the Food-EPI tool, Compilation of evidence report, Selection of expert panels, Validation of the evidence report, Rating process, and Identification of proposed actions. Based on the results, no indicator was rated as ”high” implementation and nearly two-thirds of the indicators were rated as low or very low. A total of 948 policy editing views were extracted from the content of the expert panel feedback that two third of them were classified into only 5 domains including ”Monitoring and intelligent”, ”Food provision”, ”Food labeling”, “Food promotion” and “Food prices”. These policy-editing views were summarized in 48 proposed actions that provide constructive recommendations for the future actions of the public sector. Strengthened Monitoring policies as a supportive infrastructure was the most obvious policy editing considered. This study highlights the extensive Iranian government landscape to create a healthy food environment. It emphasizes the need to improve current policies and infrastructures to shift to a health-promoting food environment.

The exponential increase in ransomware attacks has highlighted significant limitations in traditional detection and classification approaches, which often rely on static and behavior-based analysis insufficient for identifying novel, rapidly evolving threats. Introducing a framework with recursive temporal contextualization enhances threat detection accuracy and enables a resilient, real-time response mechanism that adapts to new patterns in ransomware activities. The proposed Deep Dynamic Ransomware Detection (DDRD) leverages deep learning models capable of examining time-sequenced data in a recursive manner, allowing it to discern complex behavioral indicators that static and traditional machine learning methods fail to capture. Experimental evaluations indicate high classification accuracy, minimal latency, and significant adaptability, positioning DDRD as a promising solution for the evolving ransomware landscape. Furthermore, DDRD's scalability in distributed systems and efficient resource utilization demonstrate its applicability across diverse network environments. The framework represents a substantial advancement in the field, merging advanced contextual analysis with robust classification performance to provide enhanced protection against both existing and emerging ransomware threats.

The Ovulidae family, closely related to Cypraeidae (cowries), comprises approximately 260–280 species predominantly inhabiting tropical and subtropical shallow marine environments. Traditional morphological classification within Ovulidae has been challenging due to significant variability influenced by their host organisms. In this study, we collected 15 Ovulidae species from China’s offshore waters, including the first regional record of Habuprionovolva aenigma (M. Azuma & C. N. Cate, 1971). We sequenced the mitochondrial genomes of 14 species and found that, except for H. aenigma, they exhibit typical metazoan mitochondrial structures. Phylogenetic analyses based on mitochondrial genome data were conducted to elucidate relationships among Ovulidae genera. Notably, we discovered that the subfamily Prionovolvinae exhibits a unique mitochondrial tRNA gene order. Our results suggest that mitochondrial gene rearrangements occurred after the divergence of the Prionovolvinae and Ovulinae subfamilies. Additionally, we found that Ovulidae species display significantly higher Ka/Ks ratios compared to Cypraeidae, indicating different selective pressures possibly linked to their unique feeding habits. Based on these findings, we propose reclassifying certain genera from the Simniinae subfamily to the Prionovolvinae subfamily. This research enhances the understanding of Ovulidae phylogeny and provides genomic resources for future studies.

Multispecific antibodies are increasingly being explored in the pharmaceutical industry for unmet patient needs. This work focuses on generating these molecules through an electrostatic-steering strategy, where two separate parent homodimer antibodies are expressed and purified, then combined into the heterodimer multispecific through reduction and oxidation chemistry. Traditional operations for electrostatic steering multispecifics can include complex processing steps. Therefore, a novel redox process to generate the multispecific has been explored. This process involves a column-based reduction reaction and a spike of oxidant in the elution pool to form the heterodimer. This new strategy can simplify the downstream purification process for electrostatic-steering based molecules. The method consists of simultaneously binding two separate parental homodimers to the protein A chromatography resin and applying a reductant wash to reduce the interchain disulfide bonds. The molecules are then eluted, neutralized, and oxidized to form the intact heterodimer. The mechanism and rates of reduction, heterodimerization, and oxidation have been characterized to maximize conversion and product quality. This strategy has been demonstrated successfully for five multispecifics with diverse specificity and IgG subclasses. Implementing this method for pharmaceutical bioprocesses in the production of multispecific molecules offers the potential for the reduction in manufacturing complexity while maintaining acceptable product quality and yield.

Multispecifics are increasingly being evaluated in the pharmaceutical industry due to the unique mechanisms of action of the molecules, which is enabled by the multiple antigen binding capability. The complexity of these molecules can make production difficult, therefore different approaches for the generation of these molecules have been developed. The approach employed in this study utilizes electrostatic-steering, wherein charge-based differences between two parental homodimer antibodies are used to drive correct heterodimerization during a redox reaction of the partially purified parental homodimers. This strategy results in high conversion to the heterodimer with minimal product-related impurities; however, this method also requires separate bioreactors for each parental homodimer, resulting in complex manufacturing campaigns. This work describes a new bioprocess for electrostatic steering-based multispecifics. This strategy couples two unique components. First, the two separate cell lines are co-cultured, resulting in simultaneous production of both parental homodimers in a single bioreactor. The second component utilizes a column-based redox reaction, wherein the homodimers are captured and the disulfide bonds reduced while bound to the protein A resin using a reductant wash. The column is then eluted and neutralized to allow the reduced parental homodimers to heterodimerize and finally, the addition of an oxidant enables the disulfide bond reformation to complete the formation of the multispecific. This new process is robust and efficient across bench and manufacturing scales, with well-controlled impurity profiles. Through this strategy, the new multispecific bioprocess is more similar to a typical antibody-like bioprocess, enabling more efficient use of clinical and commercial manufacturing resources, while resulting in the production of complex multispecific molecules with minimal product-related impurities.