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BACKGROUND: Poor person-centered maternal care (PCMC) contributes to high maternal mortality and morbidity, directly and indirectly, through lack of, delayed, inadequate, unnecessary, or harmful care. While evidence on poor PCMC prevalence, as well as inequities, expanded in the last decade, there is still a significant gap in evidence-based interventions to address PCMC. We describe the protocol for a trial to test the effectiveness of the Caring for Providers to Improve Patient Experience (CPIPE) intervention, which includes five strategies, targeting provider stress and bias as intermediate factors to improve PCMC and address inequities. METHODS: The trial will assess the effect of CPIPE on PCMC, as well as on intermediate and distal outcomes, using a two-arm cluster randomized controlled trial in 40 health facilities in Migori and Homa Bay Counties in Kenya and Upper East and Northeast Regions in Ghana. Twenty facilities in each country will be randomized to 10 intervention and 10 control sites. The primary intervention targets are all healthcare workers who provide maternal health services. The intervention impact will be assessed among healthcare workers in the study health facilities and among women who give birth in the study health facilities. The primary outcome is PCMC measured with the PCMC scale, via multiple cross-sectional surveys of mothers who gave birth in the preceding 12 weeks in study facilities at baseline (prior to the intervention), midline (6 months after intervention start), and endline (12 months post-baseline) (N = 2000 across both countries at each time point). Additionally, 400 providers in the study facilities across both countries will be followed longitudinally at baseline, midline, and endline, to assess intermediate outcomes. The trial incorporates a mixed-methods design; survey data alongside in-depth interviews (IDIs) with healthcare facility leaders, providers, and mothers to qualitatively explore factors influencing the outcomes. Finally, we will collect process and cost data to assess intervention fidelity and cost-effectiveness. DISCUSSION: This trial will be the first to rigorously assess an intervention to improve PCMC that addresses both provider stress and bias and will advance the evidence base for interventions to improve PCMC and contribute to equity in maternal and neonatal health. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06085105. Protocol version and date: v2-11-07-23.

Context.-The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. Objective.-To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. Design.-A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. Results.-Among 35 pathologists, the [kappa] statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314-0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the "inverted tubule" pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. Conclusions.-We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules. (Arch Pathol Lab Med. 2024;148:1119-1125; doi: 10.5858/arpa.2023-0163-OA), Histologic grading of invasive breast carcinoma (IBC) represents a morphologic assessment of the degree of tumor differentiation and is routinely reported in the pathologic assessment of IBC. Histologic grade is [...]

Emotional intelligence (EI) has a positive correlation with the academic performance of medical students. However, why there is a positive correlation needs further exploration. We hypothesized that the capability of answering higher-order knowledge questions (HOQs) is higher in students with higher EI. Hence, we assessed the correlation between EI and the capability of medical students to answer HOQs in physiology. First-year undergraduate medical students (n = 124) from an Indian medical college were recruited as a convenient sample. EI was assessed by the Schutte Self-Report Emotional Intelligence Test (SSEIT), a 33-item self-administered validated questionnaire. A specially designed objective examination with 15 lower-order and 15 higher-order multiple-choice questions was conducted. The correlation between the examination score and the EI score was tested by Pearson's correlation coefficient. Data from 92 students (33 females and 59 males) with a mean age of 20.14±1.87 yr were analyzed. Overall, students got a percentage of 53.37±14.07 in the examination, with 24.46±9.1 in HOQs and 28.91±6.58 in lower-order knowledge questions (LOQs). They had a mean score of 109.58±46.2 in SSEIT. The correlation coefficient of SSEIT score with total marks was r ¼ 0.29 (P ¼ 0.0037), with HOQs was r ¼ 0.41 (P < 0.0001), and with LOQs was r = 0.14 (P = 0.19). Hence, there is a positive correlation between EI and the capability of medical students to answer HOQs in physiology. This study may be the foundation for further exploration of the capability of answering HOQs in other subjects.

Abstract Background Townes-Brocks Syndrome (TBS), an autosomal dominant disorder, is known to cause hearing loss amongst other expressions including anomalies that affect the external ear, hands, feet, anus, and kidneys. Case presentation This report describes a case of a four-year-old male of Iranian origin with TBS diagnosed with bilateral profound sensorineural hearing loss who underwent unilateral cochlear implantation in Tanzania. Along with sensorineural hearing loss, the child has dysplastic external ears, ulnar deviation of the thumbs, and overlapping toes. Radiological evaluation revealed cochlear hypoplasia with an enlarged vestibular aqueduct. This is the first known published case of TBS with a cochlear implant in East Africa and details the child’s history, audiological findings, surgical procedure, and post-surgical outcomes. The patient has shown a remarkable increase in Infant–Toddler Meaningful Auditory Integration Scale (IT-MAIS) scores and aided sound-field thresholds at 3 months and 6 months post-switch on. Conclusion This case advocates for encouraging intervention via cochlear implantation and increased awareness of such syndromes. It also adds to the literature on TBS, and its relation to sensorineural hearing loss and inner ear malformations.

INTRODUCTION: The role of social support in antiretroviral therapy (ART) uptake and retention among pregnant and postpartum women in Ghanas capital, Accra, has received limited attention in the literature. This cross-sectional study extends existing knowledge by investigating the role of social support in ART adherence and retention among pregnant and postpartum women in Accra. METHODS: We implemented a cross-sectional study in eleven (11) public health facilities. Convenience sampling approach was used to recruit 180 participants, out of which 176 with completed data were included in the study. ART adherence in the three months preceding the survey (termed consistent uptake), and ART retention were the outcomes of interest. Initial analysis included descriptive statistics characterized by frequencies and percentages to describe the study population. In model building, we included all variables that had p-values of 0.2 or lesser in the bivariate analysis to minimize negative confounding. Overall, a two-sided p-value of

BACKGROUND: Adherence to antiretroviral therapy (ART) can substantially reduce morbidity and mortality among women living with HIV (WLWH) and prevent vertical transmission of HIV. However, in sub-Saharan Africa (SSA), more than 50% of new mothers discontinue ART and HIV care after childbirth. The role of water insecurity (WI) in ART adherence is not well-explored. We examined the relationship between WI and ART adherence among pregnant and postpartum WLWH in Greater Accra region of Ghana. METHODS: Using a cross-sectional survey, we recruited 176 pregnant and postpartum WLWH on ART across 11 health facilities. We examined the association between WI (measured using the Household Water Insecurity Experience Scale, and categorized as moderate and severe WI compard to low WI) and poor ART adherence (defined as scoring a below average observed CASE index score). Bivariate analysis was performed using chi-square test followed by multivariate logistic regression models. We included all variables with p-values less than 0.20 in the multivariate analysis. RESULTS: Most (79.5%) of the pregnant and postpartum WLWH enrolled on ART, were urban residents. Over 2/3 were aged 30 years and older. Overall, 33.5% of respondents had poor ART adherence. Proportion of poor ART adherence was 19.4% among those with low WI, 44.4% in those with moderate WI, and 40.0% among those with high WI. Respondents with moderate household water insecurity had a greater odds of reporting poor ART adherence, as compared to those with low water insecurity (adjusted Odds ratio (aOR) = 2.76, 95%CI: 1.14-6.66, p = 0.024), even after adjusting for food insecurity. Similarly, respondents with high WI had a greater odds of reporting poor ART adherence, as compared to those with low water insecurity (aOR = 1.49, 95%CI: 0.50-4.48, p = 0.479), even after adjusting for food insecurity. CONCLUSION: Water insecurity is prevalent among pregnant and postpartum WLWH and is a significant risk factor for poor ART adherence. Governments and other stakeholders working in HIV care provision should prioritize water security programming for WLWH along the HIV care continuum.

Abstract Background Reports on the impact of COVID-19 pandemic on the quality of malaria care and burden in sub Saharan Africa have provided a mixed picture to date. The impact of the 2nd (Delta) and 3rd (Omicron) COVID-19 waves on outpatient malaria indicators and case management practices was assessed at three public health facilities with varying malaria transmission intensities in Uganda. Methods Individual level data from all patients presenting to the out-patient departments (OPD) of the three facilities (Kasambya, Walukuba and Lumino) between January 2019 and February 2022 were included in the analysis. Outcomes of interest included total number of outpatient (OPD) visits, proportion of patients suspected to have malaria, proportion of suspected malaria cases tested with a malaria diagnostic test, test positivity rates (TPR) and proportion of malaria cases prescribed artemether-lumefantrine (AL). Using the pre-COVID-19 trends between January 2019 and February 2020, interrupted time series analysis was used to predict the expected trends for these study outcomes during the 2nd wave (May 2021–August 2021) and 3rd wave (November 2021–February 2022). The observed trends of the study outcomes were compared with the expected trends. Results There were no significant differences between the observed versus expected overall outpatient visits in the 2nd wave, however, a significant decline in OPD attendance was observed during the 3rd wave (15,101 vs 31,154; incidence rate ratio (IRR) = 0.48 [0.41–0.56]). No significant differences in the overall observed versus expected proportions of suspected malaria cases and test positivity rates in both COVID waves. However, a significant decrease in the overall proportion of suspected malaria cases tested with a malaria diagnostic test was observed during the 3rd wave (99.86% vs 99.99%; relative percent ratio [RPR] = 0.99 [0.99–0.99]). Finally, a significant decline in the overall proportion of malaria cases prescribed AL was observed during the 2nd wave (94.99% vs 99.85%; RPR = 0.95 [0.92–0.98]) but not the 3rd wave. Conclusion Significant declines in OPD attendance and suspected malaria cases tested with malaria diagnostic test were observed during the 3rd COVID-19 wave, while AL prescription significantly reduced during the 2nd COVID-19 wave. These findings add to the body of knowledge highlighting the adverse impact of COVID-19 pandemic on the malaria which could explain the increase in the malaria burden observed during this period.

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1. We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2, selected using World Health Organization recommendations for growth standards3. Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5. The atlas was produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6-8. The atlas corresponds structurally to published magnetic resonance images9, but with finer anatomical details in deep grey matter. The between-study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment.

Abstract Background Poor person-centered maternal care (PCMC) contributes to high maternal mortality and morbidity, directly and indirectly, through lack of, delayed, inadequate, unnecessary, or harmful care. While evidence on poor PCMC prevalence, as well as inequities, expanded in the last decade, there is still a significant gap in evidence-based interventions to address PCMC. We describe the protocol for a trial to test the effectiveness of the “Caring for Providers to Improve Patient Experience” (CPIPE) intervention, which includes five strategies, targeting provider stress and bias as intermediate factors to improve PCMC and address inequities. Methods The trial will assess the effect of CPIPE on PCMC, as well as on intermediate and distal outcomes, using a two-arm cluster randomized controlled trial in 40 health facilities in Migori and Homa Bay Counties in Kenya and Upper East and Northeast Regions in Ghana. Twenty facilities in each country will be randomized to 10 intervention and 10 control sites. The primary intervention targets are all healthcare workers who provide maternal health services. The intervention impact will be assessed among healthcare workers in the study health facilities and among women who give birth in the study health facilities. The primary outcome is PCMC measured with the PCMC scale, via multiple cross-sectional surveys of mothers who gave birth in the preceding 12 weeks in study facilities at baseline (prior to the intervention), midline (6 months after intervention start), and endline (12 months post-baseline) (N = 2000 across both countries at each time point). Additionally, 400 providers in the study facilities across both countries will be followed longitudinally at baseline, midline, and endline, to assess intermediate outcomes. The trial incorporates a mixed-methods design; survey data alongside in-depth interviews (IDIs) with healthcare facility leaders, providers, and mothers to qualitatively explore factors influencing the outcomes. Finally, we will collect process and cost data to assess intervention fidelity and cost-effectiveness. Discussion This trial will be the first to rigorously assess an intervention to improve PCMC that addresses both provider stress and bias and will advance the evidence base for interventions to improve PCMC and contribute to equity in maternal and neonatal health. Trial registration ClinicalTrials.gov: NCT06085105. Protocol version and date: v2-11-07-23

Abstract Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance of METI on ST data generated from various tumor tissues, including gastric, lung, and bladder cancers, as well as premalignant tissues. We also conduct a quantitative comparison of METI with existing clustering and cell deconvolution tools, demonstrating METI’s robust and consistent performance.

Abstract Cancer cells with BRCA1/2 deficiencies are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We evaluated the efficacy of talazoparib in DNA-Damage Repair (DDR)-altered patients. In this phase II trial, patients were enrolled onto one of four cohorts based on molecular alterations: (1) somatic BRCA1/2, (2) other homologous recombination repair pathway, (3) PTEN and (4) germline BRCA1/2. The primary endpoint was a clinical benefit rate (CBR): complete response, partial response or stable disease ≥24 weeks. 79 patients with a median of 4 lines of therapy were enrolled. CBR for cohorts 1–4 were: 32.5%, 19.7%, 9.4% and 30.6%, respectively. PTEN mutations correlated with reduced survival and a trend towards shorter time to progression.Talazoparib demonstrated clinical benefit in selected DDR-altered patients. PTEN mutations/loss patients derived limited clinical benefit. Further study is needed to determine whether PTEN is prognostic or predictive of response to PARP inhibitors.

Teaching and learning of foundational math have emerged as concerns in India, and might be connected with the problems of large classroom sizes and inappropriate curriculum resources. To address these problems of practice, ABC School explored the use of blended learning in three Grade 2 mathematics classrooms (n = 108), while a control group of three Grade 2 classrooms (n = 113) received traditional instruction and curricular resources. A quasi-experimental mixed-methods design was used to determine the differences in teaching, student engagement, and learning after eight months. Standardized test scores showed a significantly higher increase in the performance of the treatment group compared to the control group. Also, the treatment group experienced higher levels of learner-centered pedagogy, measured in terms of the extent of differentiated instruction, timely and precise feedback, and student engagement. This study contributes to the small pool of international experimental studies on blended learning in elementary grade classrooms, and supports a growing belief among researchers that the approach holds promise for school reform in developing countries.

BACKGROUND: Approximately 15-20% of advanced gastric and gastro-oesophageal junction cancers overexpress HER2. In DESTINY-Gastric01, the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan improved response and overall survival versus chemotherapy in patients from Japan and South Korea with locally advanced or metastatic HER2-positive gastric or gastro-oesophageal junction cancer whose disease progressed after two lines of previous therapy including trastuzumab. Here, we report primary and updated analyses of the single-arm, phase 2 DESTINY-Gastric02 trial, which aimed to examine trastuzumab deruxtecan in patients living in the USA and Europe. METHODS: DESTINY-Gastric02 is a single-arm, phase 2 study in adult patients from 24 study sites in the USA and Europe (Belgium, Spain, Italy, and the UK). Eligible patients were aged at least 18 years and had an Eastern Cooperative Oncology Group performance status of 0 or 1, pathologically documented unresectable or metastatic gastric or gastro-oesophageal junction cancer, progressive disease on or after first-line therapy with a trastuzumab-containing regimen, with at least one measurable lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and centrally confirmed HER2-positive disease on a postprogression biopsy. Patients were given 6·4 mg/kg of trastuzumab deruxtecan intravenously every 3 weeks until disease progression, withdrawal by patient, physician decision, or death. The primary endpoint was confirmed objective response rate by independent central review. The primary endpoint and safety were assessed in the full analysis set (ie, participants who received at least one dose of study drug). Here, we report the primary analysis of this study, with a data cutoff of April 9, 2021, and an updated analysis, with a data cutoff of Nov 8, 2021. This trial is registered with ClinicalTrials.gov, NCT04014075, and is ongoing. FINDINGS: Between Nov 26, 2019, and Dec 2, 2020, 89 patients were screened and 79 were enrolled and subsequently treated with trastuzumab deruxtecan (median age 60·7 years [IQR 52·0-68·3], 57 [72%] of 79 were male, 22 [28%] were female, 69 [87%] were White, four [5%] were Asian, one [1%] was Black or African American, one [1%] was Native Hawaiian or Pacific Islander, one had missing race, and three [4%] were other races). At the primary analysis (median follow-up 5·9 months [IQR 4·6-8·6 months]), confirmed objective response was reported in 30 (38% [95% CI 27·3-49·6]) of 79 patients, including three (4%) complete responses and 27 (34%) partial responses, as assessed by independent central review. As of data cutoff for the updated analysis (median follow-up 10·2 months [IQR 5·6-12·9]), a confirmed objective response was reported in 33 (42% [95% CI 30·8-53·4]) of 79 patients, including four (5%) complete responses and 29 (37%) partial responses, as assessed by independent central review. The most common grade 3 or worse treatment-emergent adverse events were anaemia (11 [14%]), nausea (six [8%]), decreased neutrophil count (six [8%]), and decreased white blood cell count (five [6%]). Drug-related serious treatment-emergent adverse events occurred in ten patients (13%). Deaths determined to be associated with study treatment occurred in two patients (3%) and were due to interstitial lung disease or pneumonitis. INTERPRETATION: These clinically meaningful results support the use of trastuzumab deruxtecan as second-line therapy in patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer. FUNDING: Daiichi Sankyo and AstraZeneca.

Critical Discourse Studies (CDS) has increasingly served to examine the content of textbooks. Given momentum by critical social inquiry pertaining to textbook content, this study looks at peer-reviewed literature drawn from three scholarly databases (JSTOR, ERIC, and SAGE; cross-referenced with searches on Google Scholar) that use CDS for those investigations. Reviewing the selected literature, this study asks: What are the most represented approaches of CDS used for examining textbooks? What contextual themes appear to draw the most attention? In what fields of study are the examined textbooks situated? How do these emergent themes appear to be connected? What areas of research appear lacking in the collected literature? The findings illustrate that, while the methods of CDS and types of textbooks examined are diverse, the lion's share of contextual attention and critical utility appears to be given to foundational approaches to CDS and textbooks used for English language teaching. Further research directions on textbooks from a CDS perspective are discussed.