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Abstract Background Isolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues. Methods ROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment. Discussion ROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy. Trial registration NCT05230251 (ClinicalTrials.gov).

Code-mixing is a phenomenon where at least two languages are combined in a hybrid manner in the context of a single conversation. The use of mixed language is widespread in multilingual and multicultural countries and poses significant challenges for the development of automated language processing tools. In Taiwan’s electronic health record (EHR) systems, unstructured EHR texts are usually represented in a mixture of English and Chinese which increases the difficulty for de-identification and synthetization of protected health information (PHI). We explored this problem by applying several state-of-the-art pre-trained mono- and multilingual language models and propose to exploit the principle-based approach (PBA) for the tasks of PHI recognition and resynthesis on a code-mixed EHR corpus annotated with 6 main categories and 25 subcategories of PHIs. A hierarchical principle slot schema is defined in the PBA to encode knowledge of code-mixed PHIs and utilize slots to learn from the training set to assemble principles for recognizing PHI mentions and synthesizing surrogates simultaneously. In addition, a semantic disambiguation process is implemented to disambiguate ambiguous PHI categories in the de-identification process and to dynamically extend the knowledge encoded in PBA during the knowledge augmentation process. The experiment results demonstrate that the proposed method can achieve the best micro- and macro-F-scores in comparison to the other mono- and multilingual language models fine-tuned on our code-mixed corpus.

Abstract Purpose Localized prostate cancer (PCa) in patients is characterized by a dominant focus in the gland (dominant intraprostatic lesion, DIL). Accurate DIL identification may enable more accurate diagnosis and therapy through more precise targeting of biopsy, radiotherapy and focal ablative therapies. The goal of this study is to validate the performance of [18F]DCFPyL PET and CT perfusion (CTP) for detecting and localizing DIL against digital histopathological images. Methods Multi-modality image sets: in vivo T2-weighted (T2w)-MRI, 22-min dynamic [18F]DCFPyL PET/CT, CTP, and 2-h post-injection PET/MR were acquired in patients prior to radical prostatectomy. The explanted gland with implanted fiducial markers was imaged with T2w-MRI. All images were co-registered to the pathologist-annotated digital images of whole-mount mid-gland histology sections using fiducial markers and anatomical landmarks. Regions of interest encompassing DIL and non-DIL tissue were drawn on the digital histopathological images and superimposed on PET and CTP parametric maps. Logistic regression with backward elimination of parameters was used to select the most sensitive parameter set to distinguish DIL from non-DIL voxels. Leave-one-patient-out cross-validation was performed to determine diagnostic performance. Results [18F]DCFPyL PET and CTP parametric maps of 15 patients were analyzed. SUVLate and a model combining Ki and k4 of [18F]DCFPyL achieved the most accurate performance distinguishing DIL from non-DIL voxels. Both detection models achieved an AUC of 0.90 and an error rate of

Background and purpose: Prostate specific membrane antigen positron emission tomography imaging (PSMA-PET) has demonstrated potential for intra-prostatic lesion localization. We leveraged our existing database of co-registered PSMA-PET imaging with cross sectional digitized pathology to model dose coverage of histologically-defined prostate cancer when tailoring brachytherapy dose escalation based on PSMA-PET imaging. Materials and methods: Using a previously-developed automated approach, we created segmentation volumes delineating underlying dominant intraprostatic lesions for ten men with co-registered pathology-imaging datasets. To simulate realistic high-dose-rate brachytherapy (HDR-BT) treatments, we registered the PSMA-PET-defined segmentation volumes and underlying cancer to 3D trans-rectal ultrasound images of HDR-BT cases where 15 Gray (Gy) was delivered. We applied dose/volume optimization to focally target the dominant intraprostatic lesion identified on PSMA-PET. We then compared histopathology dose for all high-grade cancer within whole-gland treatment plans versus PSMA-PET-targeted plans. Histopathology dose was analyzed for all clinically significant cancer with a Gleason score of 7or greater. Results: The standard whole-gland plans achieved a median [interquartile range] D98 of 15.2 [13.8–16.4] Gy to the histologically-defined cancer, while the targeted plans achieved a significantly higher D98 of 16.5 [15.0–19.0] Gy (p = 0.007). Conclusion: This study is the first to use digital histology to confirm the effectiveness of PSMA-PET HDR-BT dose escalation using automatically generated contours. Based on the findings of this study, PSMA-PET lesion dose escalation can lead to increased dose to the ground truth histologically defined cancer.

Abstract Purpose Identification of the dominant intraprostatic lesion(s) (DILs) can facilitate diagnosis and treatment by targeting biologically significant intra-prostatic foci. A PSMA ligand, [18F]DCFPyL (2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid), is better than choline-based [18F]FCH (fluorocholine) in detecting and localizing DIL because of higher tumour contrast, particularly when imaging is delayed to 1 h post-injection. The goal of this study was to investigate whether the different imaging performance of [18F]FCH and [18F]DCFPyL can be explained by their kinetic behaviour in prostate cancer (PCa) and to evaluate whether DIL can be accurately detected and localized using a short duration dynamic positron emission tomography (PET). Methods 19 and 23 PCa patients were evaluated with dynamic [18F]DCFPyL and [18F]FCH PET, respectively. The dynamic imaging protocol with each tracer had a total imaging time of 22 min and consisted of multiple frames with acquisition times from 10 to 180 s. Tumour and benign tissue regions identified by sextant biopsy were compared using standardized uptake value (SUV) and tracer kinetic parameters from kinetic analysis of time-activity curves. Results For [18F]DCFPyL, logistic regression identified K i and k 4 as the optimal model to discriminate tumour from benign tissue (84.2% sensitivity and 94.7% specificity), while only SUV was predictive for [18F]FCH (82.6% sensitivity and 87.0% specificity). The higher k 3 (binding) of [18F]FCH than [18F]DCFPyL explains why [18F]FCH SUV can differentiate tumour from benign tissue within minutes of injection. Superior [18F]DCFPyL tumour contrast was due to the higher k 4/k 3 (more rapid washout) in benign tissue compared to tumour tissue. Conclusions DIL was detected with good sensitivity and specificity using 22-min dynamic [18F]DCFPyL PET and avoids the need for delayed post-injection imaging timepoints. The dissimilar in vivo kinetic behaviour of [18F]DCFPyL and [18F]FCH could explain their different SUV images. Clinical Trial Registration NCT04009174 (ClinicalTrials.gov).

Purpose: Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT. Methods and Materials: A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed and EMBASE were searched from inception through September 2019. Outcome measures included local control (LC), biochemical relapse free survival (BRFS), and ≥grade 3 genitourinary (GU)/gastrointestinal (GI) toxicity. EBRT and SBRT data were collected separately. Meta-regression explored disease and toxicity outcomes as a function of equivalent dose in 2 Gy fractions (EQD2), length of follow-up, and partial versus whole prostate reirradiation. Results: Nineteen studies representing 13 cohorts were included (428 patients). Weighted mean follow-up was 26.1 months. Median re-RT EQD2 was 77.1 Gy (α/β = 1.5), with 92% of patients receiving SBRT, 52.1% of patients receiving partial prostate re-RT, and 30.1% of patients receiving androgen deprivation therapy with re-RT. LC was 83.2% (95% confidence interval [CI], 75.5%-90.9%) and BRFS was 59.3% (47.9%-70.7%). Reported late toxicity ≥grade 3 was 3.4% (95% CI, 1.0%-5.8%) for GU and 2.0% (95% CI, 0.1%-4.0%) for GI. Meta-regression found higher LC, BRFS, and reported GU/GI toxicity with increasing EQD2, with partial prostate re-RT associated with less reported GU/GI toxicity and no detriment to LC and BRFS. Conclusions: Salvage re-RT using EBRT, particularly with SBRT, is an emerging technique to treat isolated local failure of prostate cancer. With short-term follow-up, LC, BRFS, and reported toxicities appear reasonable, although further follow-up is required before definitive statements on late toxicities can be made. Our review is limited by incomplete reporting of androgen deprivation therapy use in the primary literature. Further prospective studies and longer follow-up are needed before considering re-RT as standard practice.

Abstract Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.

Purpose: Prostate cancer is multifocal. However, there often exists a single dominant focus in the gland responsible for driving the biology of the disease. Dose escalation to the dominant lesion is a proposed strategy to increase tumor control. We applied radiobiological modeling to evaluate the dosimetric feasibility and benefit of dominant intraprostatic lesion simultaneous in-field boosts (DIL-SIB) to the gross tumor volume (GTV), defined using a novel molecular positron emission tomography (PET) probe (18F-DCFPyL) directed against prostate specific membrane antigen (PSMA). Methods and Materials: Patients with clinically localized, biopsy-proven prostate cancer underwent preoperative [18F]-DCFPyL PET/computed tomography (CT). DIL-SIB plans were generated by importing the PET/CT into the RayStation treatment planning system. GTV-PET for the DIL-SIB was defined by the highest %SUVmax (percentage of maximum standardized uptake value) that generated a biologically plausible volume. Volumetric arc–based plans incorporating prostate plus DIL-SIB treatment were generated. Tumor control probability (TCP) and normal tissue complication probability (NTCP) with fractionation schemes and boost doses specified in the FLAME (Investigate the Benefit of a Focal Lesion Ablative Microboost in Prostate Cancer; NCT01168479), PROFIT (Prostate Fractionated Irradiation Trial; NCT00304759), PACE (Prostate Advances in Comparative Evidence; NCT01584258), and hypoFLAME (Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer 2.0; NCT02853110) protocols were compared. Results: Comparative DIL-SIB plans for 6 men were generated from preoperative [18F]-DCFPyL PET/CT. Median boost GTV volume was 1.015 cm3 (0.42-1.83 cm3). Median minimum (D99%) DIL-SIB dose for F35BS, F20BS, F5BS, and F5BSH were 97.3 Gy, 80.8 Gy, 46.5 Gy, and 51.5Gy. TCP within the GTV ranged from 84% to 88% for the standard plan and 95% to 96% for the DIL-SIB plans. Within the rest of the prostate, TCP ranged from 89% to 91% for the standard plans and 90% to 92% for the DIL-SIB plans. NTCP for the rectum NTCP was similar for the DIL-SIB plans (0.3%-2.7%) compared with standard plans (0.7%-2.6%). Overall, DIL-SIB plans yielded higher uncomplicated TCP (NTCP, 90%-94%) versus standard plans (NTCP, 83%-85%). Conclusions: PSMA PET provides a novel approach to define GTV for SIB-DIL dose escalation. Work is ongoing to validate PSMA PET-delineated GTV through correlation to coregistered postprostatectomy digitized histopathology.

Introduction: The use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) has been associated with improved bladder cancer outcomes. The objective of this study was to perform a systematic review of the literature and investigate the effects of these medications on survival from our own retrospective database. Methods: A systematic literature search of PubMed and the Cochrane database was conducted and 34 relevant articles identified. No randomised control trials were identified. After exclusion, five observational studies were included in our analysis. Since there was a paucity of data, we then performed a retrospective cohort study using clinical data from our electronic medical record. All patients who underwent radical cystectomy, with or without adjuvant chemotherapy, at a single tertiary care centre in Ontario, Canada between 2001 and 2016 were identified. Results: Our literature review found that ACEI or ARB use in upper urinary tract and lower urinary tract non-muscle invasive bladder cancer was associated with increased 5-year recurrence-free, cancer-specific, and overall survival. Our own analysis identified 464 patients who underwent radical cystectomy for muscle-invasive bladder cancer during the study period. Ninety-nine individuals received ACEI or ARB treatment during this time. Cox-proportion hazards modelling suggested that the use of ACEI or ARB was not significantly associated with a survival benefit. Conclusions: We are unable to support or oppose the use of ACEI or ARB as adjuvant treatment in bladder cancer due to the heterogeneity and quality of published data. Our own study data do not support the use of these medications as adjuvant therapy for muscle-invasive bladder cancer. A randomised control trial in this area of research is required.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20410-x

Abstract Ethnomedicinal plants are thought to have better prospects of harboring endophytes that produce natural products with pharmacological activities. This study aimed to investigate the antiplasmodial and anticancer properties of secondary metabolites of endophytic fungi from three medicinal plants. The endophytic fungi included Lasiodiplodia theobromae isolated from Cola acuminata, Curvularia lunata Bv4 isolated from Bambusa vulgaris, and Curvularia lunata Eg7 isolated from Elaeis guineensis. The identification of the fungi was based on the internal transcribed spacer (ITS-rDNA) sequence. The fungi were subjected to solid-state fermentation and the secondary metabolites were extracted with ethyl acetate. In vitro antiplasmodial screening of extracts was performed using the SYBR green I-based fluorescence assay on the chloroquine-resistant Plasmodium falciparum strain DD2. The cytotoxicity of the extracts on human red blood cells and Jurkat (leukemia) cells was assessed using the tetrazolium-based colorimetric MTT assay. Gas chromatography-mass spectrometry (GC–MS) analysis was used to identify the constituents of the fungal extracts. The extract of L. theobromae showed the best antiplasmodial activity against chloroquine-resistant P. falciparum (IC50 = 5.4 µg/mL) and was not harmful to erythrocytes (CC50 > 100 µg/mL). All three fungal extracts showed a weak cytotoxic effect against Jukart cell lines (CC50 > 100 µg/mL). GC–MS analysis of the three endophytic fungal extracts revealed the presence of forty major bioactive compounds, including: oxalic acid, isobutyl nonyl ester, 2,4-di-tert-butylphenol, and hexadecanoic acid, among others. The endophytic fungi from the medicinal plants in this study were promising sources of bioactive compounds that could be further evaluated as novel drugs for the treatment of malaria caused by P. falciparum-resistant strains.

The discovery of the first artificial plastic in 1869 (earlier called celluloid) by John Hyatt was a bid to replace the use of Ivory for ornaments and artistry, which endangered animals like the elephant. John Hyatt discovered plastics by dissolving camphor in nitrocellulose and alcohol in heat. While this invention piqued the interest of scientists to have considered it a groundbreaking scientific discovery, little attention was paid to the aftermath effects of its usage. Hence, as the use of plastics continued to burgeon over the past decades, plastics have now begun to pose a serious threat to marine and land inhabitants. This threat encompasses the competition for space, water contamination, and environmental toxins release, contributing to the pollution of inhabitable lands. Unfortunately, third-world countries are consistently impacted worse as the global demand, production, and distribution of new plastics are increasingly becoming disproportionate to the rate of degradation and recycling. Consequently, many disciplines and research institutes have constantly invested time and resources in developing new technologies to combat non-biodegradable plastic waste. However, since the conventional methods of degrading plastics have been found to be less eco-friendly, there has been a paradigm shift towards using biological techniques to serve as better alternatives. In this study, an overview of the conventional and modern biological and non-biological pathways for degrading plastics are elucidated with concluding views on the microbial degradative pathway as a viable means for developing countries.

BackgroundRetaining clients on antiretroviral therapy (ART) is challenging, especially during the first year on ART. Mobile health (mHealth) interventions show promise to close retention gaps. We aimed to assess reach (who received the intervention?) and effectiveness (did it work?) of a hybrid two-way texting (2wT) intervention to improve ART retention at a large public clinic in Lilongwe, Malawi.MethodsBetween August 2021-June 2023, in a quasi-experimental study, outcomes were compared between two cohorts of new ART clients: 1) those opting into 2wT who received automated, weekly motivation short messaging service (SMS) messages and response-requested appointment reminders; and 2) a matched historical cohort receiving standard of care (SoC). Reach was defined as "the proportion clients ≤6 months of ART initiation eligible for 2wT". 2wT effectiveness was assessed in time-to-event analysis. Retention was presented in a Kaplan-Meier plot and compared between 2wT and SoC using a log-rank test. The effect of 2wT on ART dropout (lost to follow-up or stopped ART) was estimated using Fine-Gray competing risk regression models, adjusting for sex, age and WHO HIV stage at ART initiation.ResultsOf 1,146 clients screened, 501 were eligible for 2wT, a reach of 44%. Lack of phone (393/645; 61%) and illiteracy (149/645; 23%) were the most common ineligibility reasons. Among 468 participants exposed to 2wT, 12-month probability of ART retention was 91% (95% CI: 88% - 94%) compared to 76% (95% CI: 72% - 80%) among 468 SoC participants (pConclusions2wT did not reach all clients. For those who opted-in, 2wT significantly increased 12-month ART retention. Expansion of 2wT as a complement to other retention interventions should be considered in other low-resource, routine ART settings.

Islam has become a major force in Malaysian politics. Some arguments focusing on PAS as the institutional manifestation of politicized Islam in Malaysia, are presented.

It is time for Nigeria to feed Nigerians with the aim of actualizing the United Nation’s Sustainable Development Goals in the area of zero hunger (food security). Recent statistics show increasing food insecurity issues; the global COVID 19 pandemic has further worsened the country’s food (in)security situation. This study econometrically assessed the nexus of agricultural credit and sustainable food production in Nigeria. Secondary data on variables of interest were gotten from World Development Indicators (WDI) of the World Bank and other relevant bodies. The data were analyzed using Unit Root Test (URT) and the Fully Modified Ordinary Least Square (FMOLS). The study revealed that Agricultural Credit Guarantee Scheme Fund (ACGSF) and loan to agriculture from the commercial banks statistically and positively influenced food security within the study period. Lending interest rate and official exchange rate inversely influenced food security. The study concluded that credit is key to achieving self-sufficiency in food production. The post estimation tests on the models confirmed that policy implications from this study are applicable to improving food security. Proper and efficient policy mix to support agricultural production including provision of credit was recommended.

Summary: This study evaluates the medicinal and therapeutic importance of aqueous pulp extract of Irvingia gabonensis (APEIG) fruit on some biochemical indices in adult male albino rats. Thirty-six adult male rats were grouped into 3 groups of 12 rats each. Group 1 was the control, while groups 2 and 3 received 100 and 200 mg/kg body weight of the extract respectively. The quantitative and qualitative phytochemical constituents present in the APEIG were alkaloids, flavonoids, and terpenoids in moderate amounts, while saponins, tannins, glycosides, sterols, and phenols were detected in trace amounts. The treatment lasted for 21 days and biochemical parameters were analyzed following standard procedures. Results obtained indicated a reduction in the bodyweight of the treated groups. The serum cholesterol, LDL, and VLDL concentrations were significantly moderated in the treatment groups, although, the serum HDL concentration was elevated dose-dependently on days 14 and 21. Alkaline phosphatase (ALP) was elevated in the treatment groups on days 7 and 14 while aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, urea, uric acid, total protein, and albumin were not affected by the administration of (APEIG) on days 7, 14 and 21. Serum bilirubin was significantly lowered in the treatment groups on days 7, 14, and 21 while fasting blood glucose (FBS) of the treated groups was moderate. The results revealed that the administration of APEIG had promising medicinal potentials and could be harnessed in disease management.

Background: The toxicological effects of monosodium glutamate (MSG), widely used as a food additive, are a major public health challenge. This research aimed to investigate the nephroprotective effects of methanol and n-hexane extracts of Piper nigrum (MEPN and HEPN, respectively) against MSG-induced renal toxicity in rats. Materials and methods: The phytochemicals, vitamins, and in vitro antioxidant activities were determined using standard protocols. Acute toxicity was determined with thirty-two Swiss albino mice, while thirty male Wistar albino rats were used for the nephroprotective study. The rats were randomly distributed into 6 experimental groups (n = 5). Group 1 (baseline) was not induced or treated; groups 2–6 were given 2 g/kg body weight of MSG. Additionally, group 2 received normal saline; groups 3–6 were given 250 and 500 mg/kg body weight of MEPN and HEPN, respectively. MSG was administered alone for 21 days, after which MSG was concomitantly administered with the extracts for additional 28 days. After treatment, biochemical tests were done on the serum, and a histopathological examination was determined with the kidney. Results: Both extracts scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and reduced ferric ions to ferrous ions in the Ferric Reducing Antioxidant Power (FRAP) assay, with MEPN having higher efficacy. The extracts also ameliorated lipid peroxidation and increased the activities of superoxide dismutase and catalase, as well as the level of reduced glutathione. In addition, intervention with MEPN and HEPN provided nephroprotective effects by decreasing urea and creatinine levels and also improved the histo-architecture of the kidney. This efficacy could be due to the rich phytochemicals and antioxidant vitamins previously identified in the plant. Conclusions: These findings are critical in focusing attention on abolishing the use of MSG in our food sector and highlights the health benefits of incorporating P. nigrum into our food to avert food and drug toxicity.

BackgroundEarly retention of people living with HIV (PLHIV) in antiretroviral therapy (ART) programs is critical to improve individual clinical outcomes and viral load suppression. Although many mobile health (mHealth) interventions aim to improve retention in care, there is still lack of evidence on mHealth success or failure, including from patient's perspectives. We describe the human-centered design (HCD) process and assess patient usability and acceptability of a two-way texting (2wT) intervention to improve early retention among new ART initiates at Lighthouse Trust clinic in Lilongwe, Malawi.MethodsAn iterative HCD approach focused on patient and provider users' needs, incorporating feedback from multidisciplinary teams to adapt 2wT for the local, public clinic context. We present mixed-methods usability and acceptability results from 100 participants, 50 at 3-months and 50 at 6-months, post 2wT enrollment, and observations of these same patients completing core tasks of the 2wT system.ResultsAmong the 100 usability respondents, 95% were satisfied with visit reminders, and 88% would recommend reminders and motivational messages to friends; however, 17% were worried about confidentiality. In observation of participant task completion, 94% were able to successfully confirm visit attendance and 73% could request appointment date change. More participants in 4-6 months group completed tasks correctly compared to 1-3 months group, although not significantly different (78% vs. 66%, p = 0.181). Qualitative results were overwhelmingly positive, but patients did note confusion with transfer reporting and concern that 2wT would not reach patients without mobile phones or with lower literacy.ConclusionThe 2wT app for early ART retention appears highly usable and acceptable, hopefully creating a solid foundation for lifelong engagement in care. The HCD approach put the local team central in this process, ensuring that both patients' and Lighthouse's priorities, policies, and practices were forefront in 2wT optimization, raising the likelihood of 2wT success in other routine program contexts.