Screening Project Research Articles

Self-supervised learning-enhanced deep learning method for identifying myopic maculopathy in high myopia patients

Accurate detection and timely care for patients with high myopia present significant challenges. We developed a deep learning (DL) system enhanced by a self-supervised learning (SSL) approach to improve the automatic diagnosis of myopic maculopathy (MM). Using a dataset of 7,906 images from the Shanghai High Myopia Screening Project and a public validation set of 1,391 images from MMAC2023, our method significantly outperformed conventional techniques. Internally, it achieved 96.8% accuracy, 83.1% sensitivity, and 95.6% specificity, with AUC values of 0.982 and 0.999. Externally, it maintained 89.0% accuracy, 71.7% sensitivity, and 87.8% specificity, with AUC values of 0.978 and 0.973. The model's Cohen's kappa values exceeded 0.8, indicating substantial agreement with retinal experts. Our SSL-enhanced DL approach offers high accuracy and potential to enhance large-scale myopia screenings, demonstrating broader significance in improving early detection and treatment of MM.

Improved Efficiency of the Clinical Diagnostic Criteria for Familial Hypercholesterolemia in Children: A Comparison of the Japan Atherosclerosis Society Guidelines of 2017 and 2022.

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels, which increases the risk of premature coronary artery disease. Early detection and treatment are vital, especially in children. To improve FH diagnosis in children, the Japan Atherosclerosis Society (JAS) released new guidelines in July 2022. This study assessed and compared the sensitivity and specificity of the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. From September 2020 to March 2023, 69 children with elevated plasma LDL-C levels (≥ 140 mg/dL) were included in a pediatric FH screening project in Kagawa. The children were evaluated using genetic testing alongside the clinical diagnostic criteria from the JAS pediatric FH guidelines of 2017 and 2022. Using the JAS pediatric FH 2017 criteria, eight children were diagnosed as FH-positive and 61 children as FH-negative. The JAS pediatric FH 2022 criteria identified 15 children with definite FH, 31 with probable FH, and 23 with possible FH. Genetic testing detected FH pathogenic variants in 24 children. The sensitivity and specificity for the JAS pediatric FH 2017 criteria were 0.292 and 0.978, respectively. For the JAS pediatric FH 2022 criteria, the sensitivity was 0.542 for definite FH with a specificity of 0.956, and 0.917 for probable FH with a specificity of 0.467. The clinical diagnostic criteria of the JAS pediatric FH 2022 guidelines demonstrated improved diagnostic efficiency compared with those of 2017, as evidenced by the increased sensitivity while preserving specificity.

A robust, simple, and efficient convergence workflow for GW calculations

A robust, simple, and efficient convergence workflow for GW calculations in plane-wave-based codes is derived from more than 7000 GW calculations on a diverse dataset of 70 semiconducting and insulating solids divided into 60 bulk and 10 2D materials. The workflow can significantly accelerate material screening projects and high-precision single-system studies. Our method is based on two main results: The convergence of the two interdependent parameters in the numerical implementation of the dynamically screened Coulomb interaction W in a plane-wave basis set is accelerated by a ‘cheap first, expensive later’ coordinate search that maintains the same accuracy as a state-of-the-art convergence algorithm, but converges faster. In addition, we empirically establish the practical independence of the k-point grid and the aforementioned parameterization of W. Incorporating both results into one workflow dramatically speeds up convergence.

Thirty-Nine Percent of Patients with a Ruptured Abdominal Aortic Aneurysm (AAA) Have an Incidentally Detected AAA Prior to Rupture

IntroductionAbdominal aortic aneurysm (AAA) screening has been offered to 65-year-old men living in Oslo, Norway, since May 2011. A significant number of AAA-related deaths occurred in individuals who are not eligible for screening. The primary aim of this study was to describe the group of patients admitted to Oslo University Hospital with a ruptured AAA after the implementation of the local AAA screening project. The following parameters were investigated: AAA detection prior to rupture, surveillance status, eligibility for screening and comorbidities. We also sought to compare outcomes (repair rates and 30-day mortality) between patients with and without an AAA detected prior to rupture. MethodsThis cohort study included patients admitted acutely to Oslo University Hospital due to a symptomatic or ruptured AAA in the period January 2011 to December 2022. Data on demographics, prior AAA detection, surveillance status, treatment and mortality were collected retrospectively through electronic medical records. ResultsWe identified 200 patients with a symptomatic or ruptured AAA, among which 79 (40%) had an AAA detected prior to rupture – one (1%) through screening and 78 (39%) incidentally. Up to 30% of the incidentally detected AAAs were not under any surveillance. Six patients were found eligible for screening: one had attended, three were non-attenders and two had not been invited. Patients with an incidentally detected AAA prior to rupture had a more advanced age and a significantly higher degree of comorbidities than patients without a previously detected AAA, and the repair rates in these groups were 56% and 84% respectively (p < 0.001). Adjusted for comorbidities and risk factors, the odds ratio for repair among patients with incidentally detected AAA was 0.56 (p = 0.292). The 30-day mortality was not significantly different between the two groups (p = 0.097). ConclusionMost patients with a ruptured AAA were not eligible for screening, but 39% of the patients had an incidentally detected AAA prior to rupture. Standardized reporting and follow-up of incidentally detected AAAs is thus identified as an additional measure to organized screening in the effort to reduce AAA-related mortality.

Bat algorithm based on kinetic adaptation and elite communication for engineering problems

AbstractThe Bat algorithm, a metaheuristic optimization technique inspired by the foraging behaviour of bats, has been employed to tackle optimization problems. Known for its ease of implementation, parameter tunability, and strong global search capabilities, this algorithm finds application across diverse optimization problem domains. However, in the face of increasingly complex optimization challenges, the Bat algorithm encounters certain limitations, such as slow convergence and sensitivity to initial solutions. In order to tackle these challenges, the present study incorporates a range of optimization components into the Bat algorithm, thereby proposing a variant called PKEBA. A projection screening strategy is implemented to mitigate its sensitivity to initial solutions, thereby enhancing the quality of the initial solution set. A kinetic adaptation strategy reforms exploration patterns, while an elite communication strategy enhances group interaction, to avoid algorithm from local optima. Subsequently, the effectiveness of the proposed PKEBA is rigorously evaluated. Testing encompasses 30 benchmark functions from IEEE CEC2014, featuring ablation experiments and comparative assessments against classical algorithms and their variants. Moreover, real‐world engineering problems are employed as further validation. The results conclusively demonstrate that PKEBA exhibits superior convergence and precision compared to existing algorithms.

Clinical impact of the rapid genomic screening platform for non-small cell lung cancer in Asia-Pacific (LC-SCRUM-AP).

8637 Background: In 2013, a lung cancer genomic screening project (LC-SCRUM-Asia) started in Japan and expanded to other Asia-Pacific countries in October 2022 (LC-SCRUM-AP). The objective of this study is to clarify the characteristics of genomic profile in Asia-Pacific countries outside of Japan and to elucidate the clinical significance of rapid genomic screening. Methods: To shorten the turnaround time (TAT), a central laboratory was set in each participating country. Samples are analyzed by a multi-gene PCR assay and a rapid next-generation sequencing assay. Clinical, pathological and genomic data are stocked as a clinical-genomic database in each participating country, which is combined with Japanese database and the integrated clinical-genomic database of the Asia-Pacific region was established. Results: A multi-gene PCR assay data was available in 7879 samples from 4 Asia-Pacific countries (Taiwan/Thailand/Malaysia/Japan = 126/65/30/7658 pts). The rates of driver alterations in never-smokers with non-squamous histology were similar in the 4 Asia-Pacific countries: 83%, 80%, 89% and 75% in Taiwan, Thailand, Malaysia, and Japan, respectively. The pattern of genomic profile was also similar among these 4 countries. The median TAT was 4 days and 5 days in Japanese cohort and Taiwan/Thailand/Malaysia cohort, respectively. In Taiwan/Thailand/Malaysia cohort (n = 221), the genomic analysis successful rate was 99.5%. The rates of genomic alterations detected: EGFR (35%) of which ex20ins (6%), KRAS (10%) of which G12C (4%), ALK fusions (6%), ROS1 fusions (4%), RETfusions (0.5%), HER2ex20ins (4%), MET ex14skip (3%), BRAF V600E (1.5%), and NTRK3 fusions (0.5%). Oncogenic driver alterations were detected in 149 pts, of which 102 (68%) pts received targeted therapies approved in each country. 14 patients were enrolled into clinical trials of the investigational drugs, of which 5 were for targeting rare driver alterations. Conclusions: LC-SCRUM-AP is the first international genomic screening platform established in the Asia-Pacific region, which enables the efficient detection of rare driver alterations with a short TAT, contributing to the high implementation rate of targeted therapies. The similar pattern of genomic profile in the 4 Asia-Pacific countries indicates the utility of this screening platform as the basis for the clinical trials for NSCLC with rare driver alterations. We plan to further expand the number of institutions and participating countries.

Performance of P16INK4a immunocytochemical stain in facilitating cytology interpretation of HSIL for HPV-positive women aged 50 and above.

Few articles have focused on the cytological misinterpretation of high-grade squamous intraepithelial lesion (HSIL). Due to estrogen deficiency, cervical epithelial cells in postmenopausal women tend to show atrophic change that looks like HSIL on Papanicolaou-stained cytology slides, resulting in a higher rate of cytological misinterpretation. P16INK4a immunocytochemical staining (P16 cytology) can effectively differentiate diseased cells from normal atrophic ones with less dependence on cell morphology. To evaluate the role of P16 cytology in differentiating cytology HSIL from benign atrophy in women aged 50 years and above. Included in this analysis were women in a cervical cancer screening project conducted in central China who tested positive for high-risk human papillomavirus (hr-HPV) and returned back for triage with complete data of primary HPV testing, liquid-based cytology (LBC) analysis, P16 immuno-stained cytology interpretation, and pathology diagnosis. The included patients were grouped by age: ≥50 (1,127 cases) and <50 years (1,430 cases). The accuracy of LBC and P16 cytology in the detection of pathology ≥HSIL was compared between the two groups, and the role of P16 immuno-stain in differentiating benign cervical lesions from cytology ≥HSIL was further analyzed. One hundred sixty-seven women (14.8%; 167/1,127) in the ≥50 group and 255 (17.8%, 255/1,430) in the <50 group were pathologically diagnosed as HSIL (Path-HSIL). LBC [≥Atypical Squamous Cell Of Undetermined Significance (ASCUS)] and P16 cytology (positive) respectively detected 63.9% (163/255) and 90.2% (230/255) of the Path-≥HSIL cases in the <50 group and 74.3% (124/167) and 93.4% (124/167) of the Path-≥HSIL cases in the ≥50 group. LBC matched with pathology in 105 (41.2%) of the 255 Path-≥HSIL cases in the <50 group and 93 (55.7%) of the 167 Path-≥HSIL cases in the ≥50 group. There were five in the <50 group and 14 in the ≥50 group that were Path-≤LSIL cases, which were interpreted by LBC as HSIL, but negative in P16 cytology. P16 cytology facilitates differentiation of Path-≤LSIL from LBC-≥HSIL for women 50 years of age and above. It can be used in the lower-resource areas, where qualified cytologists are insufficient, as the secondary screening test for women aged ≥50 to avoid unnecessary biopsies and misinterpretation of LBC primary or secondary screening.

Comparing patterns of recent and remote Mycobacterium tuberculosis infection determined using the QuantiFERON-TB Gold Plus assay in a high TB burden setting.

One quarter of the world's population is estimated to be infected with Mycobacterium tuberculosis. Identifying recent TB infection (TBI) offers an avenue to targeted TB preventative therapy provision, and prevention to disease progression. However, detecting recent TBI remains challenging. The QuantiFERON-TB Gold Plus assay (QFT-Plus) claims to have improved sensitivity in detecting recent TBI, by the addition of the TB2 antigen tube to the TB1 tube used in previous tests. TB2 detects CD8-mediated interferon gamma response, a potential marker of recent infection. We compared QFT-Plus TB1 and TB2 responses in individuals with recent and remote infection in high-burden settings. The Tuberculosis Reduction through Expanded Antiretroviral Treatment and TB Screening (TREATS) Project followed a cohort of adolescents and young people (AYP) aged 15-24 years in Zambia and South Africa to determine TBI incidence measured by QFT-Plus over 24 months. We categorised individuals with QTF-Plus positive result into recent and remote infection. We compared their TB1 and TB2 responses and the antigen tube differential [TB2-TB1], an indicator of CD8-activity, using logistic regression. At baseline, 3876 AYP, 1852/3876 (47.8%) were QFT-Plus positive whilst 2024/3876 (52.2%) QFT-Plus negative. Of the QFT-Plus baseline positives, 1069/1852 (57.7%) tested positive at both 12 and 24 months-remote infection. Of the QFT-Plus baseline negatives, 274/2024(13.3%) converted within a 12-month period- recent infection. TB1 and TB2 responses were higher in remote than recent infection. In recent infection, TB2 responses were greater than TB1 responses. The mean differential was 0.01 IU/ml in recent and -0.22 IU/ml in remote infection, (p = 0.145). The quantitative QFT-Plus results did not appear to reflect a marked distinction between recent and remote infection. Further analysis of the responses of infected individuals who developed disease is required to determine whether any signal in QFT-Plus results may predict progression to disease.

Abstract PO1-13-02: Circulating tumor DNA mutation landscape in HR+/HER2− patients with mBC treated with cyclin-dependent kinase 4/6 inhibitors in the SCRUM-Japan MONSTAR-SCREEN study

Abstract Introduction: Combination of cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6i) + endocrine therapy (ET) is recommended as first- or second-line treatment (1L or 2L Tx) for hormone receptor-positive, human epidermal growth factor receptor-2-negative metastatic breast cancer (HR+/HER2− mBC). In this study, we assessed cancer-specific genetic alterations in circulating tumor DNA (ctDNA) and tissues in abemaciclib-treated patients with HR+/HER2− mBC in Japan. Methods: MONSTAR-SCREEN is a multicenter study and part of a nation-wide cancer genome screening project for patients with advanced solid tumors (SCRUM Japan). Regardless of the Tx line, the current analysis included abemaciclib-treated patients with HR+/HER2− mBC (N=97). Data were collected between Jan 2020 and Dec 2021. Blood samples collected at ≤21 days before abemaciclib initiation (baseline; n=77) and at disease progression or Tx discontinuation (paired post-Tx; n=33) were tested with the FoundationOne® Liquid Companion Diagnostic panel. Additionally, archival or fresh tissue biopsy samples (n=79) were tested with the FoundationOne® Companion Diagnostic panel. Patient characteristics, baseline genetic alterations, neoplastic burden (measured by shedding rate and maximum variant allele frequency [VAF]), and alterations at clinical progression were reported. Results: The total population (N=97) included patients with next generation sequencing ctDNA and/or tissue data. All were female with median age of 57 years (interquartile range 50, 67). Bone, either alone or with other sites, was the most common metastatic site (61%). 78% of patients received abemaciclib in the first or second line of Tx (LoT). Fulvestrant with or without gonadotropin-releasing hormone (55%), letrozole (24%), and anastrozole (11%) were the most common concomitant drugs. Among patients with baseline ctDNA data (n=77), 30% and 21% had received prior ET and prior chemotherapy, respectively. In baseline ctDNA samples, PIK3CA (37%) and TP53 (28%) alterations were detected most frequently across all LoT; while ESR1 (16%), GATA3 (11%), and FGF3/4/19 (9%) were more frequently detected in samples from later LoT. The frequency of ESR1 alterations (p&amp;lt; 0.01), shedding rate, and maximum VAF (both p&amp;lt; 0.05) were significantly higher in prior ET recipients than those who did not receive prior ET. Frequency of post-Tx ESR1 alterations numerically decreased from baseline in patients on fulvestrant (23% to 18%) and numerically increased in patients on aromatase inhibitors (27% to 45%). Other genes showed either a numeric increase or similar alteration frequency between the baseline and post-tx. Newly acquired post-Tx alterations were detected in FGF3/4/19 (18%); PIK3CA, TP53, and RB1 (all 15%) and ESR1 (12%). The table shows PIK3CA and ESR1 alterations detected at baseline and post-Tx. In the tissue samples (n=79), TP53 (32% vs 20%) and ESR1 (14% vs 7%) alterations were numerically more frequent in metastatic versus primary lesions. Other gene alteration frequencies were similar. Conclusion: PIK3CA alterations were the most frequently detected genetic alterations in both pre- and post- abemaciclib Tx patients with HR+/HER2− mBC. Patients with prior ET had more frequent ESR1 alterations and higher neoplastic burden. Evidence from this study provides insight into the ctDNA dynamics and potential resistance mechanisms in patients with HR+/HER2− mBC. PIK3CA and ESR1 alterations detected in circulating tumor DNA at baseline and post abemaciclib treatment Citation Format: Masaya Hattori, Victoria Serelli-Lee, Yoichi Naito, Takashi Yamanaka, Hiroyuki Yasojima, Rikiya Nakamura, Takao Fujisawa, Mitsuho Imai, Yoshiaki Nakamura, Hideaki Bando, Tsutomu Kawaguchi, Takayuki Yoshino, Hiroji Iwata. Circulating tumor DNA mutation landscape in HR+/HER2− patients with mBC treated with cyclin-dependent kinase 4/6 inhibitors in the SCRUM-Japan MONSTAR-SCREEN study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-13-02.

Evaluation of the “Burgenland PREvention trial of colorectal cancer Disease with ImmunologiCal Testing” (B-PREDICT)—a population-based colorectal cancer screening program

BackgroundThe colorectal cancer (CRC) screening program B-PREDICT is a population based invited two stage screening project using a faecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. B-PREDICT was compared with the opportunistic screening colonoscopy (OPP-COL), performed in course of the nationwide screening program.MethodsWithin B-PREDICT all residents of the Austrian federal state Burgenland, aged between 40 and 80 are annually invited to FIT testing. All individuals who underwent initial colonoscopy in Burgenland between 01/2003 and 12/2014, were included in this study. Individuals from the FIT-triggered invited screening program B-PREDICT were compared with those from the non-FIT triggered OPP-COL.Results15 133 individuals from B-PREDICT were compared to 10 045 individuals with OPP-COL. CRC detection rates were 1.34% (CI-95%, [1.15; 1.52]) in B-PREDICT compared to 0.54% in OPP-COL (95%-CI, [0.39; 0.68] p < 0.001). The decrease in the age standardized incidence rates of CRC was more pronounced in the population screened with FIT than in the general population screened with colonoscopy. Changes in incidence rates per year were -4.4% (95%-CI, [-5.1; -3.7]) vs. -1.8% (95%-CI, [-1.9; -1.6] p < 0.001).ConclusionsB-PREDICT shows a two-fold higher detection rate of CRC as well as HRA compared to OPP-COL.

Demobilising Opposition to European Integration: The Principle of Subsidiarity and the Creation of the European Union, 1988–1992

By analysing new archival evidence, this article reveals how in the late 1980s, the legal principle of subsidiarity came to be seen as a tool for demobilising opposition to further European integration. At the same time, it also became a projection screen for competing visions for Europe's future: while the European Commission saw subsidiarity as an important foundation for a future European federation and the German government as an essential part of a ‘Europe of the regions’, the British government hoped to use it to achieve a renationalisation of the European Community. The French government was much more sceptical towards subsidiarity, pointing to the paradox that subsidiarity actually required a strong central authority to achieve its decentralising ends. The article concludes by arguing that the debate on subsidiarity reveals how ambitious and yet contested European integration had become by the early 1990s.

Geographical distance, investment strategies and performance of venture capital: evidence from Chinese enterprises

ABSTRACT A growing body of evidence suggests that geographical distance plays an important role for venture capital (VC) investment. This study explores whether and how the geographical distance between the lead VC firms (VCFs) and the invested entrepreneurial firms (IEFs) influences the investment strategies of VCFs and their performance. The results show: (1) The geographical distance has a significant positive effect on the performance of VC investments. (2) As distance increases, lead VCFs will tend to be conservative on investments by improving project screening criteria and adopting syndication strategies and multiple-rounds of staged financing, which can dramatically improve the successful exit from the invested projects. This study has useful theory and policy implications for VCFs, entrepreneurial firms and local governments.

An Audio - Visual Virtual Personal Assistant

Current traits in smart assistants and smart home automation are currently attracting the interests of customers and researchers. Speech enabled smart virtual assistants (named smart speakers) offer a wide sort of network orientated services and, in some instances, can connect to smart environments, accordingly improving them with new and effective user interfaces. But, such gadgets also reveal new desires and a few weaknesses. Specially, they constitute faceless and blind assistants, not able to reveal a face, and therefore an emotion, and not able to ‘see’ the person. For this reason, the interaction is impaired and, in a few cases, ineffective. One of the goals of artificial intelligence is the realization of natural talk among humans and machines. In latest years, the dialogue systems, known as interactive conversational systems are the fastest developing vicinity in AI. Many companies have used the dialogue systems technology to set up various sorts of VPAs based on their application areas, including Apple’s Siri, Amazon Alexa, etc. To triumph over such troubles, in this project we combine a number of advance techniques. The proposed Assistant is powerful and resource-efficient, interactive and customizable. We use the multi-modal dialogue structures and screen projection which process two or more combined user input modes, which includes speech, image, video, touch, manual gestures, body movements with the intention to design the NextGeneration of VPAs. The new version of VPAs can be used to increase the interaction between humans and machines by the usage of distinctive technologies, consisting of gesture recognition, image/video recognition, speech recognition, dialogue system, conversational information base, and the overall knowledge base. Furthermore, this VPA device can be utilized in different areas such as education, medical assistance, disabilities systems, home automation and security access control.

Utility of bronchoscopically obtained frozen cytology pellets for next-generation sequencing

BackgroundNext-generation sequencing (NGS) is essential for lung cancer treatment. It is important to collect sufficient tissue specimens, but sometimes we cannot obtain large enough samples for NGS analysis. We investigated the yield of NGS analysis by frozen cytology pellets using an Oncomine Comprehensive Assay or Oncomine Precision Assay.MethodsWe retrospectively enrolled patients with lung cancer who underwent bronchoscopy at Kobe University Hospital and were enrolled in the Lung Cancer Genomic Screening Project for Individualized Medicine. We investigated the amount of extracted DNA and RNA and determined the NGS success rates. We also compared the amount of DNA and RNA by bronchoscopy methods. To create the frozen cytology pellets, we first effectively collected the cells and then quickly centrifuged and cryopreserved them.ResultsA total of 132 patients were enrolled in this study between May 2016 and December 2022; of them, 75 were subjected to frozen cytology pellet examinations and 57 were subjected to frozen tissue examinations. The amount of DNA and RNA obtained by frozen cytology pellets was nearly equivalent to frozen tissues. Frozen cytology pellets collected by endobronchial ultrasound-guided transbronchial needle aspiration yielded significantly more DNA than those collected by transbronchial biopsy methods. (P < 0.01) In RNA content, cytology pellets were not inferior to frozen tissue. The success rate of NGS analysis with frozen cytology pellet specimens was comparable to the success rate of NGS analysis with frozen tissue specimens.ConclusionsOur study showed that frozen cytology pellets may have equivalent diagnostic value to frozen tissue for NGS analyses. Bronchial cytology specimens are usually used only for cytology, but NGS analysis is possible if enough cells are collected to create pellet specimens. In particular, the frozen cytology pellets obtained by endobronchial ultrasound-guided transbronchial needle aspiration yielded sufficient amounts of DNA.Trial registrationThis was registered with the University Medical Hospital Information Network in Japan (UMINCTR registration no. UMIN000052050).

Clinical Effectiveness of Newborn Screening for Spinal Muscular Atrophy

There is increasing evidence that early diagnosis and treatment are key for outcomes in infants with spinal muscular atrophy (SMA), and newborn screening programs have been implemented to detect the disease before onset of symptoms. However, data from controlled studies that reliably confirm the benefits of newborn screening are lacking. To compare data obtained on patients with SMA diagnosed through newborn screening and those diagnosed after clinical symptom onset. This nonrandomized controlled trial used data from the SMARTCARE registry to evaluate all children born between January 2018 and September 2021 with genetically confirmed SMA and up to 3 SMN2 copies. The registry includes data from 70 participating centers in Germany, Austria, and Switzerland. Data analysis was performed in February 2023 so that all patients had a minimal follow-up of 18 months. Patients born in 2 federal states in Germany underwent screening in a newborn screening pilot project. All other patients were diagnosed after clinical symptom onset. All patients received standard care within the same health care system. The primary end point was the achievement of motor milestones. A total of 234 children (123 [52.6%] female) were identified who met inclusion criteria and were included in the analysis: 44 (18.8%) in the newborn screening cohort and 190 children (81.2%) in the clinical symptom onset cohort. The mean (SD) age at start of treatment with 1 of the approved disease-modifying drugs was 1.3 (2.2) months in the newborn screening cohort and 10.7 (9.1) months in the clinical symptom onset cohort. In the newborn screening cohort, 40 of 44 children (90.9%) gained the ability to sit independently vs 141 of 190 (74.2%) in the clinical symptom onset cohort. For independent ambulation, the ratio was 28 of 40 (63.6%) vs 28 of 190 (14.7%). This nonrandomized controlled trial demonstrated effectiveness of newborn screening for infants with SMA in the real-world setting. Functional outcomes and thus the response to treatment were significantly better in the newborn screening cohort compared to the unscreened clinical symptom onset group. German Clinical Trials Register: DRKS00012699.

Evaluation of a population-wide, systematic screening initiative for tuberculosis on Daru island, Western Province, Papua New Guinea

BackgroundA population-wide, systematic screening initiative for tuberculosis (TB) was implemented on Daru island in the Western Province of Papua New Guinea, where TB is known to be highly prevalent. The initiative used a mobile van equipped with a digital X-ray device, computer-aided detection (CAD) software to identify TB-related abnormalities on chest radiographs, and GeneXpert machines for follow-on diagnostic testing. We describe the results of the TB screening initiative, evaluate its population-level impact and examine risk factors associated with TB detection.MethodsThrough a retrospective review of screening data, we assessed the effectiveness of the screening by examining the enrolment coverage and the proportion of people with TB among screened subjects. A cascade analysis was performed to illustrate the flow of participants in the screening algorithm. We conducted univariate and multivariate analyses to identify factors associated with TB. Furthermore, we estimated the number of additional cases detected by the project by examining the trend of routine TB case notifications during the intervention period, compared to the historical baseline cases and trend-adjusted expected cases.ResultsOf the island’s 18,854 residents, 8,085 (42.9%) were enrolled and 7,970 (98.6%) had chest X-ray interpreted by the CAD4TB software. A total of 1,116 (14.0%) participants were considered to have abnormal CXR. A total of 69 Xpert-positive cases were diagnosed, resulting in a detection rate of 853 per 100 000 population screened. 19.4% of people with TB had resistance to rifampicin. People who were in older age groups (aOR 6.6, 95%CI: 1.5–29.1 for the 45–59 age group), were severely underweight (aOR 2.5, 95%CI:1.0-6.1) or underweight (aOR 2.1, 95%CI: 1.1–3.8), lived in households < 5 people (aOR 3.4, 95%CI:1.8–6.6) and had a past history of TB (aOR 2.1, 95%CI: 1.2–3.6) were more likely to have TB. The number of bacteriologically confirmed TB notified during the intervention period was 79.3% and 90.8% higher than baseline notifications and forecasted notifications, respectively.ConclusionThe screening project demonstrated its effectiveness with the high Xpert-positive TB prevalence among the participants and by successfully yielding additional cases of bacteriologically confirmed TB including rifampicin-resistant TB. The results and lessons learnt from the project should inform future TB screening initiatives in Papua New Guinea.

Genomic profiling and clinical utility of circulating tumor DNA in metastatic prostate cancer: SCRUM-Japan MONSTAR SCREEN project

BackgroundCirculating tumor DNA (ctDNA) testing has emerged as a novel tool for cancer precision medicine. This study investigated the genomic profiling and clinical utility of ctDNA in metastatic prostate cancer.MethodsThis is a nation-wide prospective observational study. Patients treated with systemic treatment for metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC) were included. ctDNA was analyzed using FoundationOne Liquid®CDx at enrollment. In a subset of patients, ctDNA after disease progression and tissue prior to the initiation of treatment were examined using FoundationOne Liquid®CDx and FoundationOne®CDx, respectively.ResultsThe frequency of AR alterations and homologous recombination repair (HRR) defect was higher in mCRPC compared with mCSPC. Tumor mutational burden was correlated between tissue and ctDNA at pre-treatment, as well as ctDNA between at pre-treatment and at post-treatment. Patients with HRR defect were associated with shorter time to castration resistance in androgen deprivation therapy/combined androgen blockade, but not in androgen receptor pathway inhibitor, compared with patients without HRR defect in mCSPC. Time to treatment failure in patients with AR amplification or AR mutation was shorter compared with patients without AR alterations in mCRPC.ConclusionsThis study revealed valuable findings for the clinical care of metastatic prostate cancer. Especially, predictive factors such as HRR defect in mCSPC should be validated in the future.

Genomic Landscape of Circulating Tumor DNA in Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Treated With Abemaciclib: Data From the SCRUM-Japan Cancer Genome Screening Project.

To understand the mutational landscape of circulating tumor DNA (ctDNA) and tumor tissue of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) treated with abemaciclib + endocrine therapy (ET). Blood samples for ctDNA and/or tissue samples were collected from abemaciclib-treated patients with HR+/HER2- MBC enrolled in the SCRUM-Japan MONSTAR-SCREEN project. Blood samples were collected before abemaciclib initiation (baseline) and at disease progression/abemaciclib discontinuation (post abemaciclib treatment). Clinical and genomic characteristics including neoplastic burden (measured by shedding rate and maximum variant allele frequency [VAF]) were assessed at baseline. Genomic alterations in ctDNA were compared in paired baseline and post abemaciclib treatment samples. All patients (N = 97) were female (median age, 57 years [IQR, 50-67]). In baseline ctDNA (n = 77), PIK3CA (37%), TP53 (28%), ESR1 (16%), and GATA3 (11%) were the most frequently mutated genes. Baseline tissue samples (n = 79) showed similar alteration frequencies. Among patients with baseline ctDNA data, 30% had received previous ET. ESR1 alteration frequency (35% v 8%; P < .01), median shedding rate (3 v 2), and maximum somatic VAF (4 v 0.8; both P < .05) were significantly higher in ctDNA from patients with previous ET than those without previous ET. In paired ctDNA samples (n = 33), PIK3CA and ESR1 alteration frequencies were higher after abemaciclib treatment than at baseline, though not statistically significant. Among the post-treatment alterations, those newly acquired were detected most frequently in FGF3/4/19 (18%); PIK3CA, TP53, CCND1, and RB1 (all 15%); and ESR1 (12%). We summarized the ctDNA and cancer tissue mutational landscape, including overall neoplastic burden and PIK3CA and ESR1 hotspot mutations in abemaciclib-treated patients with HR+/HER2- MBC. The data provide insights that could help optimize treatment strategies in this population.

Contributions of the National Medicinal Plants Board (NMPB), Ministry of Ayush in the medicinal plants sector - An appraisal

The Government of India set up the National Medicinal Plants Board (NMPB) to promote the medicinal plants sector on November 24, 2000, under the Chairmanship of the Union Minister of Health and Family Welfare. The board is a nonstatuary coordinating body and is now a section of the Ministry of Ayush (MoA). The primary mandate of NMPB is to develop an appropriate mechanism for coordination between various ministries/departments/organizations and implementation of support policies/programs for overall (conservation, cultivation, trade, and export) growth of the medicinal plants sector both at the central/state and international level. NMPB, under its Central Sector Scheme (CSS) on “Conservation, Development and Sustainable Management of Medicinal Plants,” provides project-based financial support to explore various aspects of medicinal plants. Different scheme components of NMPB are functioning, such as Conservation, Research and Development (R&amp;D), Information, Education, and Communication and Training, Herbal Gardens, Marketing and Trade, and International Cooperation. NMPB implements various programs/policies through its 37 State Medicinal Plants Boards at different state/UT levels, 6 Regional Cum Facilitation Centers at the region level, and also through various State Forest Departments/Horticulture Departments/Agriculture Departments. NMPB is also assisted by the Project Screening Committees, Project Approval Committee, and other Committees constituted as per the requirement of the CSS guideline. The present article deals with the overall contribution of NMPB to the medicinal plant sectors since its inception. The article places interest in outcomes that would gradually help the country meet its international obligation in various aspects of medicinal plants/sectors.

Expanding TheCellVision.org: a central repository for visualizing and mining high-content cell imaging projects.

We previously constructed TheCellVision.org, a central repository for visualizing and mining data from yeast high-content imaging projects. At its inception, TheCellVision.org housed two high-content screening (HCS) projects providing genome-scale protein abundance and localization information for the budding yeast Saccharomyces cerevisiae, as well as a comprehensive analysis of the morphology of its endocytic compartments upon systematic genetic perturbation of each yeast gene. Here, we report on the expansion of TheCellVision.org by the addition of two new HCS projects and the incorporation of new global functionalities. Specifically, TheCellVision.org now hosts images from the Cell Cycle Omics project, which describes genome-scale cell cycle-resolved dynamics in protein localization, protein concentration, gene expression, and translational efficiency in budding yeast. Moreover, it hosts PIFiA, a computational tool for image-based predictions of protein functional annotations. Across all its projects, TheCellVision.org now houses >800,000 microscopy images along with computational tools for exploring both the images and their associated datasets. Together with the newly added global functionalities, which include the ability to query genes in any of the hosted projects using either yeast or human gene names, TheCellVision.org provides an expanding resource for single-cell eukaryotic biology.