Miracle-dz/UniFAR-FTUs huggingface dataset:
Heterogeneity of Circulating Tumor Cell–Associated Genomic Gains in Breast Cancer and Its Association with the Host Immune Response

As breast cancers progress, they become more heterogeneous for multiple regions amplified in circulating tumor cells, and intratumoral spatial heterogeneity is associated with the immune landscape. Tumor cells that preferentially enter circulation include the precursors of metastatic cancer. Previously, we characterized circulating tumor cells (CTC) from patients with breast cancer and identified a signature of genomic regions with recurrent copy-number gains. Through FISH, we now show that these CTC-associated regions are detected within the matched untreated primary tumors of these patients (21% to 69%, median 55.5%, n = 19). Furthermore, they are more prevalent in the metastases of patients who died from breast cancer after multiple rounds of treatment (70% to 100%, median 93%, samples n = 41). Diversity indices revealed that higher spatial heterogeneity for these regions within primary tumors is associated with increased dissemination and metastasis. An identified subclone with multiple regions gained (MRG clone) was enriched in a posttreatment primary breast carcinoma as well as multiple metastatic tumors and local breast recurrences obtained at autopsy, indicative of a distinct early subclone with the capability to resist multiple lines of treatment and eventually cause death. In addition, multiplex immunofluorescence revealed that tumor heterogeneity is significantly associated with the degree of infiltration of B lymphocytes in triple-negative breast cancer, a subtype with a large immune component. Collectively, these data reveal the functional potential of genetic subclones that comprise heterogeneous primary breast carcinomas and are selected for in CTCs and posttreatment breast cancer metastases. In addition, they uncover a relationship between tumor heterogeneity and host immune response in the tumor microenvironment. Significance: As breast cancers progress, they become more heterogeneous for multiple regions amplified in circulating tumor cells, and intratumoral spatial heterogeneity is associated with the immune landscape.
Diabetes mellitus promoted lymph node metastasis in gastric cancer: a 15–year single-institution experience

Abstract Background: Previous studies have revealed that diabetes mellitus (DM) promotes disease progress of gastric cancer (GC). This study aimed to further investigating whether DM advanced lymph nodes (LNs) metastasis in GC. Methods: The clinicopathologic data of GC patients with >15 examined LN (ELN) between October 2004 and December 2019 from a prospectively maintained database were included. The observational outcomes included the number (N3b status) and anatomical distribution (N3 stations) of metastatic LN (MLN). Results: A total of 2142 eligible patients were included in the study between October 2004 and December 2019. N3 stations metastasis (26.8% in DM vs. 19.3% in non-DM, P = 0.026) and N3b status (18.8% in DM vs. 12.8% in non-DM, P = 0.039) were more advanced in the DM group, and multivariate logistic regression analyses confirmed that DM was an independent factor of developing N3 stations metastasis (odds ratio [OR] = 1.771, P = 0.011) and N3b status (OR = 1.752, P = 0.028). Also, multivariate analyses determined DM was independently associated with more MLN (β = 1.424, P = 0.047). The preponderance of N3 stations metastasis (DM vs. non-DM, T1–2: 2.2% vs. 4.9%, T3: 29.0% vs. 20.3%, T4a: 38.9% vs. 25.8%, T4b: 50.0% vs. 36.6%; ELN16–29: 8.6% vs. 10.4%, ELN30–44: 27.9% vs. 20.5%, ELN ≥ 45: 37.7% vs. 25.3%), N3b status (DM vs. non-DM, T1–2: 0% vs. 1.7%, T3: 16.1% vs. 5.1%, T4a: 27.8% vs. 19.1%, T4b: 44.0% vs. 28.0%; ELN16–29: 8.6% vs. 7.9%, ELN30–44: 18.0% vs. 11.8%, ELN ≥ 45: 26.4% vs. 17.3%), and the number of MLN (DM vs. non-DM, T1–2: 0.4 vs. 1.1, T3: 8.6 vs. 5.2, T4a: 9.7 vs. 8.6, T4b: 17.0 vs. 12.8; ELN16–29: 3.6 vs. 4.6, ELN30–44: 5.8 vs. 5.5, ELN ≥ 45: 12.0 vs. 7.7) of DM group increased with the advancement of primary tumor depth stage and raising of ELN. Conclusions: DM was an independent risk factor for promoting LN metastasis. The preponderance of LN involvement in the DM group was aggravated with the advancement of tumor depth.
Routine Vaccination Coverage — Worldwide, 2020

Endorsed by the World Health Assembly in 2020, the Immunization Agenda 2030 (IA2030) strives to reduce morbidity and mortality from vaccine-preventable diseases across the life course (1). This report, which updates a previous report (2), presents global, regional,* and national vaccination coverage estimates and trends as of 2020. Changes are described in vaccination coverage and the numbers of unvaccinated and undervaccinated children as measured by receipt of the first and third doses of diphtheria, tetanus, and pertussis-containing vaccine (DTP) in 2020, when the COVID-19 pandemic began, compared with 2019. Global estimates of coverage with the third dose of DTP (DTP3) and a polio vaccine (Pol3) decreased from 86% in 2019 to 83% in 2020. Similarly, coverage with the first dose of measles-containing vaccine (MCV1) dropped from 86% in 2019 to 84% in 2020. The last year that coverage estimates were at 2020 levels was 2009 for DTP3 and 2014 for both MCV1 and Pol3. Worldwide, 22.7 million children (17% of the target population) were not vaccinated with DTP3 in 2020 compared with 19.0 million (14%) in 2019. Children who did not receive the first DTP dose (DTP1) by age 12 months (zero-dose children) accounted for 95% of the increased number. Among those who did not receive DTP3 in 2020, approximately 17.1 million (75%) were zero-dose children. Global coverage decreased in 2020 compared with 2019 estimates for the completed series of Haemophilus influenzae type b (Hib), hepatitis B vaccine (HepB), human papillomavirus vaccine (HPV), and rubella-containing vaccine (RCV). Full recovery from COVID-19-associated disruptions will require targeted, context-specific strategies to identify and catch up zero-dose and undervaccinated children, introduce interventions to minimize missed vaccinations, monitor coverage, and respond to program setbacks (3).
Barriers to Healthy Eating and Diabetes Diet Education: Divergent Perspectives of Patients and Their Providers

Patients report that adhering to diet is the most challenging aspect of diabetes management. Provision of diet education is often delegated to health care providers, despite a lack of nutrition education and training and limited awareness of environmental and cultural challenges faced by patients. Aim. We examined perceived barriers to diet self-management among low-income minority patients with type 2 diabetes and their health care providers within a single ecosystem, to test whether providers understood patient barriers. Method. We surveyed 149 members of a safety-net clinic (99 patients, 50 providers), using barriers derived from the literature. Binomial logistic regression was applied to investigate relationships between barriers and patients’ sociodemographic variables and Pearson’s χ2 was used to compare differences in perceived barriers between patients and providers. Results. Providers expressed divergent perceptions of patients’ barriers to healthy eating, including more total barriers and little agreement with patients on their relative importance. Largest differences in providers’ perceptions of patient barriers included poor motivation, high use of fast food, inadequate family support, and lack of cooking skills—all suggesting patient inadequacy. In contrast, patients showed evidence of high motivation—in rate of blood glucose measurement and desire for diet education. Patients identified primary care providers as a main source of nutrition education, yet providers indicated lack of time for diet discussion and preferred other staff do the teaching. Conclusion. The findings from this study strongly suggest that health systems need to consider patient, provider, and system barriers when implementing nutrition education and management programs.
Risk factors of recurrence after endovascular embolization of posterior communicating artery aneurysms

Background and objective To determine the risk factors for recurrence after endovascular embolization of posterior communicating artery aneurysms (PcomA). Methods We retrospectively analyzed a cohort of 163 patients harboring 172 PocmAs who were treated with endovascular embolization from January 2019 to December 2020. The patients were divided into recurrence and stable groups depending on outcome. Univariate and logistic regression analyses were performed to determine the potential risk factors of recurrence during follow-up. Results Of the total 163 patients harboring 172 aneurysms, 107 were treated with simple coil occlusion and 65 were treated with stent-assisted coil embolization. There were significant differences in aneurysm sizes and use of non-stent-assisted coil embolizations between the groups (P < 0.05). The incidence of saccular aneurysm and Raymond grade were significantly higher in the recurrent group than in the stable group (P < 0.01). After variable selection, Raymond grade, aneurysm size, saccular aneurysm and non-stent-assisted coil embolization were included in further analysis. Binary logistic regression analysis revealed significant associations with non-stent-assisted coil embolization (P = 0.007), packing density (P < 0.001) and Raymond grades II (P < 0.001) and III (P = 0.002). Conclusion Non-stent-assisted coil embolization, as well as packing density and Raymond grades II grade III are associated with recurrence after endovascular treatment of PcomA.
The open pan-genome architecture and virulence landscape of Mycobacterium bovis

Animal tuberculosis (TB) is an emergent disease caused by Mycobacterium bovis , one of the animal-adapted ecotypes of the Mycobacterium tuberculosis complex (MTC). In this work, whole-genome comparative analyses of 70 M . bovis were performed to gain insights into the pan-genome architecture. The comparison across M. bovis predicted genome composition enabled clustering into the core- and accessory-genome components, with 2736 CDS for the former, while the accessory moiety included 3897 CDS, of which 2656 are restricted to one/two genomes only. These analyses predicted an open pan-genome architecture, with an average of 32 CDS added by each genome and show the diversification of discrete M. bovis subpopulations supported by both core- and accessory-genome components. The functional annotation of the pan-genome classified each CDS into one or several COG (Clusters of Orthologous Groups) categories, revealing ‘transcription’ (total average CDSs, n=258), ‘lipid metabolism and transport’ (n=242), ‘energy production and conversion’ (n=214) and ‘unknown function’ (n=876) as the most represented. The closer analysis of polymorphisms in virulence-related genes in a restrict group of M. bovis from a multi-host system enabled the identification of clade-monomorphic non-synonymous SNPs, illustrating clade-specific virulence landscapes and correlating with disease severity. This first comparative pan-genome study of a diverse collection of M. bovis encompassing all clonal complexes indicates a high percentage of accessory genes and denotes an open, dynamic non-conservative pan-genome structure, with high evolutionary potential, defying the canons of MTC biology. Furthermore, it shows that M. bovis can shape its virulence repertoire, either by acquisition and loss of genes or by SNP-based diversification, likely towards host immune evasion, adaptation and persistence.
A longitudinal study on symptom duration and 60-day clinical course in non-hospitalised COVID-19 cases in Berlin, Germany, March to May, 2020

Background Detailed information on symptom duration and temporal course of patients with mild COVID-19 was scarce at the beginning of the COVID-19 pandemic. Aim We aimed to determine the longitudinal course of clinical symptoms in non-hospitalised COVID-19 patients in Berlin, Germany. Methods Between March and May 2020, 102 confirmed COVID-19 cases in home isolation notified in Berlin, Germany, were sampled using total population sampling. Data on 25 symptoms were collected during telephone consultations (a maximum of four consultations) with each patient. We collected information on prevalence and duration of symptoms for each day of the first 2 weeks after symptom onset and for day 30 and 60 after symptom onset. Results Median age was 35 years (range 18–74), 57% (58/102) were female, and 37% (38/102) reported having comorbidities. During the first 2 weeks, most common symptoms were malaise (94%, 92/98), headache (71%, 70/98), and rhinitis (69%, 68/98). Malaise was present for a median of 11 days (IQR 7–14 days) with 35% (34/98) of cases still reporting malaise on day 14. Headache and muscle pain mostly occurred during the first week, whereas dysosmia and dysgeusia mostly occurred during the second week. Symptoms persisted in 41% (39/95) and 20% (18/88) of patients on day 30 and 60, respectively. Conclusion Our study shows that a significant proportion of non-hospitalised COVID-19 cases endured symptoms for at least 2 months. Further research is needed to assess the frequency of long-term adverse health effects in non-hospitalised COVID-19 patients.
Response-Adapted Postinduction Strategy in Patients With Advanced-Stage Follicular Lymphoma: The FOLL12 Study

PURPOSE We compared 2 years of rituximab maintenance (RM) with a response-adapted postinduction approach in patients with follicular lymphoma who responded to induction immunochemotherapy. METHODS We randomly assigned treatment-naïve, advanced-stage, high-tumor burden follicular lymphoma patients to receive standard RM or a response-adapted postinduction approach on the basis of metabolic response and molecular assessment of minimal residual disease (MRD). The experimental arm used three types of postinduction therapies: for complete metabolic response (CMR) and MRD-negative patients, observation; for CMR and MRD-positive (end of induction or follow-up) patients, four doses of rituximab (one per week, maximum three courses) until MRD-negative; and for non-CMR patients, one dose of ibritumomab tiuxetan followed by standard RM. The study was designed as noninferiority trial with progression-free survival (PFS) as the primary end point. RESULTS Overall, 807 patients were randomly assigned. After a median follow-up of 53 months (range, 1-92 months), patients in the standard arm had a significantly better PFS than those in the experimental arm (3-year PFS 86% v 72%; P < .001). The better PFS of the standard versus experimental arm was confirmed in all the study subgroups except non-CMR patients (n = 65; P = .274). The 3-year overall survival was 98% (95% CI, 96 to 99) and 97% (95% CI, 95 to 99) in the reference and experimental arms, respectively (P = .238). CONCLUSION A metabolic and molecular response-adapted therapy as assessed in the FOLL12 study was associated with significantly inferior PFS compared with 2-year RM. The better efficacy of standard RM was confirmed in the subgroup analysis and particularly for patients achieving both CMR and MRD-negative.
Refractive index sensing using the metal layer in DVD-R discs

In recent years, grating based bio-sensors have received much attention due to their promising applications in integrated sensing devices. However, production of high quality, large scale and low cost metal gratings is still challenging. Here, we introduce an extremely simple and low cost method to fabricate metal gratings by peeling off the metal layer from a DVD-R disc. An atomic force microscope image shows that the metal layer is a high quality grating, the period and depth of which are 740 nm and 86 nm, respectively. Based on the fabricated metal grating, refractive index sensing is experimentally achieved using two configurations, where either the resonant wavelength or the modulated laser power is measured. The sensitivity of the sensor by wavelength modulation reaches as high as 637 nmRIU−1, which is comparable with or even higher than that of the existing grating coupled sensors. Our method largely reduces the cost to fabricate high quality metal gratings and will promote the development of grating based SPR sensors.
Compost as an untapped niche for thermotolerant yeasts capable of high‐temperature ethanol production

Efficient bioethanol production from lignocellulosic biomass requires thermotolerant yeasts capable of utilizing multiple sugars, tolerating inhibitors and fermenting at high temperatures. In this study, 98 thermotolerant yeasts were isolated from nine compost samples. We selected 37 yeasts that belonged to 11 species; 31 grew at 45°C; 6 strains grew at 47°C, while 9 yeasts could utilize multiple sugars. Many yeast isolates showed high ethanol production in the range of 12–24 g l−1, with fermentation efficiencies of 47–94% at 40°C using 5% glucose. Kluyveromyces marxianus CSV3.1 and CSC4.1 (47°C), Pichia kudriavzevii CSUA9.3 (45°C) produced 21, 22 and 23 g l−1 of ethanol with efficiencies of 83, 87 and 90%, respectively, using 5% glucose. Among these yeasts, K. marxianus CSC4.1 and P. kudriavzevii CSUA9.3 exhibited high tolerance against furfural, 5‐HMF, acetic acid and ethanol. These two strains produced high amounts of ethanol from alkali‐treated RS, with 84 and 87% efficiency via separate hydrolysis and fermentation; 76 and 74% via simultaneous saccharification and fermentation at 47 and 45°C, respectively. Therefore, this study demonstrates compost as a potential anthropogenic niche for multiple sugar‐utilizing, inhibitor‐tolerant ethanologenic yeasts suitable for high‐temperature ethanol production via SHF of rice straw.
Assessment of the Subchannel Code CTF for Single- and Two-Phase Flows

Abstract As part of the Consortium for Advanced Simulation of Light Water Reactors, the subchannel code CTF is being used for single-phase and two-phase flow analysis under light water reactor operating conditions. Accurate determination of flow distribution, pressure drop, and void content is crucial for predicting margins to thermal crisis and ensuring more efficient plant performance. In preparation for the intended applications, CTF has been validated against data from experimental facilities comprising the General Electric (GE) 3 × 3 bundle, the boiling water reactor full-size fine-mesh bundle tests (BFBTs), the Risø tube, and the pressurized water reactor subchannel and bundle tests (PSBTs). Meanwhile, the licensed, well-recognized subchannel code VIPRE-01 was used to generate a baseline set of simulations for the targeted tests and solution parameters were compared to the CTF results. The flow split verification problem and single-phase GE 3 × 3 results are essentially in perfect agreement between the two codes. For the two-phase GE 3 × 3 cases, flow and quality discrepancies arise in the annular-mist flow regime, yet significant improvement is observed in CTF when void drift and two-phase turbulent mixing enhancement are considered. The BFBT pressure drop benchmark shows close agreement between predicted and measured results in general, although considerable overprediction by CTF is observed at relatively high void locations of the facility. This overestimation tendency is confirmed by the Risø cases. While overall statistics are satisfactory, both BFBT and PSBT bubbly-to-churn flow void contents are markedly overpredicted by CTF. The issues with two-phase closures such as turbulent mixing, interfacial and wall friction, and subcooled boiling heat transfer need to be addressed. Preliminary sensitivity studies are presented herein, but more advanced models and code stability analysis require further investigation.
Multimeric Anti-DR5 IgM Agonist Antibody IGM-8444 Is a Potent Inducer of Cancer Cell Apoptosis and Synergizes with Chemotherapy and BCL-2 Inhibitor ABT-199

Death receptor 5 (DR5) is an attractive target for cancer therapy due to its broad upregulated expression in multiple cancers and ability to directly induce apoptosis. Though anti-DR5 IgG antibodies have been evaluated in clinical trials, limited efficacy has been attributed to insufficient receptor crosslinking. IGM-8444 is an engineered, multivalent agonistic IgM antibody with 10 binding sites to DR5 that induces cancer cell apoptosis through efficient DR5 multimerization. IGM-8444 bound to DR5 with high avidity and was substantially more potent than an IgG with the same binding domains. IGM-8444 induced cytotoxicity in a broad panel of solid and hematologic cancer cell lines but did not kill primary human hepatocytes in vitro, a potential toxicity of DR5 agonists. In multiple xenograft tumor models, IGM-8444 monotherapy inhibited tumor growth, with strong and sustained tumor regression observed in a gastric PDX model. When combined with chemotherapy or the BCL-2 inhibitor ABT-199, IGM-8444 exhibited synergistic in vitro tumor cytotoxicity and enhanced in vivo efficacy, without augmenting in vitro hepatotoxicity. These results support the clinical development of IGM-8444 in solid and hematologic malignancies as a monotherapy and in combination with chemotherapy or BCL-2 inhibition.
To mention or not to mention? The inclusion of self-reported most traumatic and most positive memories in the life story

ABSTRACT Many theories on Posttraumatic Stress Disorder (PTSD) make assumptions on the relationship between PTSD and centrality of traumas to the life story and identity. Although the Centrality of Event Scale (CES) is a popular measure of centrality of personally experienced events to the life story, no studies have examined whether self-rated “central” events are mentioned, when individuals recount their lives. It is also unknown if mentioning specific event types in the life story is related to psychological health or life story coherence. We asked 386 adults to write their life stories, nominate their most traumatic and positive events, rate these events on the CES, and complete measures of PTSD and depression. Two-thirds of the sample mentioned at least one event, with the positive event being mentioned twice as often as the trauma. Mentioned events were more central than non-mentioned events. Participants who mentioned their trauma scored higher on symptoms of PTSD and depression than participants who only mentioned their positive event, but did not write less coherent life stories. Further, death- and illness-related traumas were mentioned more often than accidents and disasters. Findings are discussed in relation to theories on trauma memory in PTSD.