Higher-Form Symmetries under Weak Measurement.

We aim to address the following question: if we start with a quantum state with a spontaneously broken higher-form symmetry, what is the fate of the system under weak local quantum measurements? We demonstrate that under certain conditions, a phase transition can be driven by weak measurements, which suppresses the spontaneous breaking of the 1-form symmetry and weakens the 1-form symmetry charge fluctuation. We analyze the nature of the transitions employing the tool of duality, and we demonstrate that some of the transitions driven by weak measurement enjoy a line of fixed points with self-duality.

Exploring the key deteriorative microorganisms on ancient ivories unearthed from the Sanxingdui Ruins site during temporary cold storage.

Introduction: The ancient ivories unearthed from the Sanxingdui Ruins site are valuable cultural relics, however, the microbial biodeterioration on ivories during temporary cold storage poses a great threat to their later long-term preservation. Methods: Here, the combination of high-throughput sequencing and biochemical assays was applied for the in-depth investigation of the key deteriorative microorganisms colonizing on the ivories and the tracing of their origin, as well as the assessment of the ethanol disinfection impact on the microbial communities on ivories. Results: It was observed that the surfaces of ivories were scattered by the fungal patches of white, dark grey, and hedge green colors during cold storage. The high-throughput sequencing results showed that the genera Mortierella (38.51%), Ilyonectria (14.43%), Penicillium (1.15%), and Aspergillus (1.09%) were the dominant fungi, while Pseudomonas (22.63%), Sphingopyxis (3.06%), and Perlucidibaca (2.92%) were the dominant bacteria on ivories. The isolated Aspergillus A-2 resulted in the highest amount of calcium releasing from the degradation of hydroxyapatite (HAP), the main component of ivory, by the organic acids produced, including oxalic acid and citric acid. The fast expectation-maximization for microbial source tracking (FEAST) analysis revealed that the majority of the fungi (57.45%) and bacteria (71.84%) colonizing on the ivories were derived from the soils surrounding ivories in the sacrifice pits, indicating soils as the primary source for the spoilage microbes growing on ivories. The dominant strains could degrade cellulose, the key components of wet cotton towels commonly applied on ivories for moisture maintenance, aiding the spoilage microbes colonizing on ivories. Notably, the ivory disinfection with 75% ethanol during the cleansing significantly decreased the relative abundance of the dominant genera of Ilyonectria, Aspergillus, and Pseudomonas, with Mortierella becoming the dominant one on ivories. Discussion: Together, the fungi, particularly Aspergillus and Penicillium, played a significant role in the microbial biodeterioration of unearthed ancient ivories by producing the organic acids. These results may improve the control of the microbial biodeterioration and develop more efficient strategies for the long-time conservation of unearthed ancient ivories and other cultural relics.

Construction and validation of a deep learning prognostic model based on digital pathology images of stage III colorectal cancer.

BACKGROUND: TNM staging is the main reference standard for prognostic prediction of colorectal cancer (CRC), but the prognosis heterogeneity of patients with the same stage is still large. This study aimed to classify the tumor microenvironment of patients with stage III CRC and quantify the classified tumor tissues based on deep learning to explore the prognostic value of the developed tumor risk signature (TRS). METHODS: A tissue classification model was developed to identify nine tissues (adipose, background, debris, lymphocytes, mucus, smooth muscle, normal mucosa, stroma, and tumor) in whole-slide images (WSIs) of stage III CRC patients. This model was used to extract tumor tissues from WSIs of 265 stage III CRC patients from The Cancer Genome Atlas and 70 stage III CRC patients from the Sixth Affiliated Hospital of Sun Yat-sen University. We used three different deep learning models for tumor feature extraction and applied a Cox model to establish the TRS. Survival analysis was conducted to explore the prognostic performance of TRS. RESULTS: The tissue classification model achieved 94.4 % accuracy in identifying nine tissue types. The TRS showed a Harrell's concordance index of 0.736, 0.716, and 0.711 in the internal training, internal validation, and external validation sets. Survival analysis showed that TRS had significant predictive ability (hazard ratio: 3.632, p = 0.03) for prognostic prediction. CONCLUSION: The TRS is an independent and significant prognostic factor for PFS of stage III CRC patients and it contributes to risk stratification of patients with different clinical stages.

Softness-Aided Mild Hyperthermia Boosts Stiff Nanomedicine by Regulating Tumor Mechanics.

Aberrant tumor mechanical microenvironment (TMME), featured with overactivated cancer-associated fibroblasts (CAFs) and excessive extracellular matrix (ECM), severely restricts penetration and accumulation of cancer nanomedicines, while mild-hyperthermia photothermal therapy (mild-PTT) has been developed to modulate TMME. However, photothermal agents also encounter the barriers established by TMME, manifesting in limited penetration and heterogeneous distribution across tumor tissues and ending with attenuated efficiency in TMME regulation. Herein, it is leveraged indocyanine green (ICG)-loaded soft nanogels with outstanding deformability, for efficient tumor penetration and uniform distribution, in combination with mild-PTT to achieve potent TMME regulation by inhibiting CAFs and degrading ECM. As a result, doxorubicin (DOX)-loaded stiff nanogels gain greater benefits in tumor penetration and antitumor efficacy than soft counterparts from softness-mediated mild-PTT. This study reveals the crucial role of nanomedicine mechanical properties in tumor distribution and provides a novel strategy for overcoming the barriers of solid tumors with soft deformable nanogels.

Effect of pooled tracheal sample testing on the probability of Mycoplasma hyopneumoniae detection.

Tracheal pooling for Mycoplasma hyopneumoniae (M. hyopneumoniae) DNA detection allows for decreased diagnostic cost, one of the main constraints in surveillance programs. The objectives of this study were to estimate the sensitivity of pooled-sample testing for the detection of M. hyopneumoniae in tracheal samples and to develop probability of M. hyopneumoniae detection estimates for tracheal samples pooled by 3, 5, and 10. A total of 48 M. hyopneumoniae PCR-positive field samples were pooled 3-, 5-, and 10-times using field M. hyopneumoniae DNA-negative samples and tested in triplicate. The sensitivity was estimated at 0.96 (95% credible interval [Cred. Int.]: 0.93, 0.98) for pools of 3, 0.95 (95% Cred. Int: 0.92, 0.98) for pools of 5, and 0.93 (95% Cred. Int.: 0.89, 0.96) for pools of 10. All pool sizes resulted in PCR-positive if the individual tracheal sample Ct value was < 33. Additionally, there was no significant decrease in the probability of detecting at least one M. hyopneumoniae-infected pig given any pool size (3, 5, or 10) of tracheal swabs. Furthermore, this manuscript applies the probability of detection estimates to various real-life diagnostic testing scenarios. Combining increased total animals sampled with pooling can be a cost-effective tool to maximize the performance of M. hyopneumoniae surveillance programs.

Mild Thermotherapy-Assisted GelMA/HA/MPDA@Roxadustat 3D-Printed Scaffolds with Combined Angiogenesis-Osteogenesis Functions for Bone Regeneration.

Early reconstruction of the vascular network is a prerequisite to the effective treatment of substantial bone defects. Traditional 3D printed tissue engineering scaffolds designed to repair large bone defects do not effectively regenerate the vascular network, and rely only on the porous structure within the scaffold for nutrient transfer and metabolic waste removal. This leads to delayed bone restoration and hence functional recovery. Therefore, strategies for generation scaffolds with the capacity to efficiently regenerate vascularization should be developed. This study loads roxarestat (RD), which can stabilize HIF-1α expression in a normoxic environment, onto the mesopore polydopamine nanoparticles (MPDA@RD) to enhance the reconstruction of vascular network in large bone defects. Subsequently, MPDA@RD is mixed with GelMA/HA hydrogel bioink to fabricate a multifunctional hydrogel scaffold (GHM@RD) through 3D printing. In vitro results show that the GHM@RD scaffolds achieve good angiogenic-osteogenic coupling by activating the PI3K/AKT/HSP90 pathway in BMSCs and the PI3K/AKT/HIF-1α pathway in HUVECs under mild thermotherapy. In vivo experiments reveal that RD and mild hyperthermia synergistically induce early vascularization and bone regeneration of critical bone defects. In conclusion, the designed GHM@RD drug delivery scaffold with mild hyperthermia holds great therapeutic value for future treatment of large bone defects.

Comprehensive quantifications of tumour microenvironment to predict the responsiveness to immunotherapy and prognosis for paediatric neuroblastomas.

Treatment strategies for paediatric neuroblastoma as well as many other cancers are limited by the unfavourable tumour microenvironment (TME). In this study, the TMEs of neuroblastoma were grouped by their genetic signatures into four distinct subtypes: immune enriched, immune desert, non-proliferative and fibrotic. An Immune Score and a Proliferation Score were constructed based on the molecular features of the subtypes to quantify the immune microenvironment or malignancy degree of cancer cells in neuroblastoma, respectively. The Immune Score correlated with a patient's response to immunotherapy; the Proliferation Score was an independent prognostic biomarker for neuroblastoma and proved to be more accurate than the existing clinical predictors. This double scoring system was further validated and the conserved molecular pattern associated with immune landscape and malignancy degree was confirmed. Axitinib and BI-2536 were confirmed as candidate drugs for neuroblastoma by the double scoring system. Both in vivo and in vitro experiments demonstrated that axitinib-induced pyroptosis of neuroblastoma cells activated anti-tumour immunity and inhibited tumour growth; BI-2536 induced cell cycle arrest at the S phase in neuroblastoma cells. The comprehensive double scoring system of neuroblastoma may predict prognosis and screen for therapeutic strategies which could provide personalized treatments.

Optimization Design of Mix Proportion for Fly Ash-Silica Fume-Basalt Fiber-Polypropylene Fiber Concrete under Steam Curing Condition.

To enhance the physical and mechanical characteristics of steam-cured concrete, an orthogonal experimental design was utilized to examine the effects of varying contents of fly ash (0 wt%, 10 wt%, 15 wt%, 20 wt%), silica fume (0 wt%, 5 wt%, 10 wt%, 15 wt%), basalt fiber (0 vol%, 0.05 vol%, 0.1 vol%, 0.2 vol%), and polypropylene fiber (0 vol%, 0.05 vol%, 0.1 vol%, 0.2 vol%) on its mechanical properties. Utilizing range and variance analyses, this study identified four preliminary optimized compositions of concrete incorporating fly ash, silica fume, basalt fiber, and polypropylene fiber. On this basis, in order to determine the optimal mix proportion, the mechanical performances, the pore characteristics, and the microstructure of four optimized mix proportions were analyzed. According to the results of macroscopic, fine, and microscopic multi-scale tests, the addition of 15 wt% fly ash, 10 wt% silica ash, 0.2 vol% basalt fiber, and 0.1 vol% polypropylene fiber to the steamed concrete is the best to improve the performance of the steamed concrete. Compared to ordinary concrete, the compressive strength increases by 28%, the tensile strength increases by 40%, and the porosity decreases by 47.2%.

Synergistic Effects of Boron and Rare Earth Elements on the Microstructure and Stress Rupture Properties in a Ni-Based Superalloy.

The synergistic effects of boron (B) and rare earth (RE) elements on the microstructure and stress rupture properties were investigated in a Ni-based superalloy. The stress rupture lifetime at 650 °C/873 MPa significantly increased with the addition of B as a single element. Furthermore, the stress rupture lifetime reached its peak (303 h), with a certain amount of B and RE added together in test alloys. Although the grain size and morphology of the γ' phase varied a little with the change in B and RE addition, they were not considered to be the main reasons for stress rupture performance. The enhancement in stress rupture lifetime was mostly attributed to the segregation of the B and RE elements, which increased the binding force of the grain boundary and improved its strength and plasticity. In addition, the enrichment of B and RE inhabited the precipitation of carbides along grain boundaries. Furthermore, nano-scale RE precipitates containing sulfur (S) and phosphorus (P) were observed to be distributed along the grain boundaries. The purification of grain boundaries by B and RE elements was favorable to further improve the stress rupture properties.

A Review on the Carbonation of Steel Slag: Properties, Mechanism, and Application.

Steel slag is a by-product of the steel industry and usually contains a high amount of f-CaO and f-MgO, which will result in serious soundness problems once used as a binding material and/or aggregates. To relieve this negative effect, carbonation treatment was believed to be one of the available and reliable methods. By carbonation treatment of steel slag, the phases of f-CaO and f-MgO can be effectively transformed into CaCO3 and MgCO3, respectively. This will not only reduce the expansive risk of steel slag to improve the utilization of steel slag further but also capture and store CO2 due to the mineralization process to reduce carbon emissions. In this study, based on the physical and chemical properties of steel slag, the carbonation mechanism, factors affecting the carbonation process, and the application of carbonated steel slag were reviewed. Eventually, the research challenge was also discussed.

In vitro digestion mimicking conditions in adults and elderly reveals digestive characteristics of pork from different cooking ways.

This study aimed to investigate the impact of three cooking ways (sous vide (SV), frying (FR) and roasting (RO)) on pork protein digestion characteristics under conditions simulating healthy adult (control, C) and elderly individuals with achlorhydria (EA). Changes in degree of hydrolysis (DH), SDS-PAGE profiles, zeta potential, particle size and secondary structure during digestion were evaluated. Our results revealed the EA condition markedly affected the protein digestion process of pork with different cooking ways. The DH values of SV (25.62%), FR (21.38%) and RO (19.40%) under the EA condition were significantly lower than those of under the control condition (38.32%, 33.00% and 30.86%, respectively). Moreover, differences were also observed among three cooking ways under the EA condition. For a given cooking way, the differences between control and EA conditions gradually diminished from the gastric to the intestinal phase. Under a certain digestion condition, SV maintained the highest degree of digestion throughout the process, particularly under the EA condition. Therefore, we conclude that pork cooked by sous vide is more recommendable for the elderly considering protein digestibility.

Blocking SLC7A11 attenuates the proliferation of esophageal squamous cell carcinoma cells.

The role of ferroptosis-associated gene SLC7A11 in esophageal cancer progression is largely unknown, therefore, the effects of blocking SLC7A11 on esophageal squamous cell carcinoma (ESCC) cells are evaluated. Results showed that SLC7A11 was overexpressed in ESCC tissues both in mRNA and protein levels. Blocking SLC7A11 using Erastin suppressed the proliferation and colony formation of ESCC cells, decreased cellular ATP levels, and improved ROS production. Sixty-three SLC7A11-binding proteins were identified using the IP-MS method, and these proteins were enriched in four signaling pathways, including spliceosome, ribosome, huntington disease, and diabetic cardiomyopathy. The deubiquitinase inhibitors PR-619, GRL0617, and P 22077 could reduce at least 40% protein expression level of SLC7A11 in ESCC cells, and PR-619 and GRL0617 exhibited suppressive effects on the cell viability and colony formation ability of KYSE30 cells, respectively. Erastin downregulated GPX4 and DHODH and also reduced the levels of ß-catenin, p-STAT3, and IL-6 in ESCC cells. In conclusion, SLC7A11 was overexpressed in ESCC, and blocking SLC7A11 using Erastin mitigated malignant phenotypes of ESCC cells and downregulated key ferroptosis-associated molecules GPX4 and DHODH. The therapeutic potential of targeting SLC7A11 should be further evaluated in the future.

Network meta-analysis for an ordinal outcome when outcome categorization varies across trials.

BACKGROUND: Binary outcomes are likely the most common in randomized controlled trials, but ordinal outcomes can also be of interest. For example, rather than simply collecting data on diseased versus healthy study subjects, investigators may collect information on the severity of disease, with no disease, mild, moderate, and severe disease as possible levels of the outcome. While some investigators may be interested in all levels of the ordinal variable, others may combine levels that are not of particular interest. Therefore, when research synthesizers subsequently conduct a network meta-analysis on a network of trials for which an ordinal outcome was measured, they may encounter a network in which outcome categorization varies across trials. METHODS: The standard method for network meta-analysis for an ordinal outcome based on a multinomial generalized linear model is not designed to accommodate the multiple outcome categorizations that might occur across trials. In this paper, we propose a network meta-analysis model for an ordinal outcome that allows for multiple categorizations. The proposed model incorporates the partial information provided by trials that combine levels through modification of the multinomial likelihoods of the affected arms, allowing for all available data to be considered in estimation of the comparative effect parameters. A Bayesian fixed effect model is used throughout, where the ordinality of the outcome is accounted for through the use of the adjacent-categories logit link. RESULTS: We illustrate the method by analyzing a real network of trials on the use of antibiotics aimed at preventing liver abscesses in beef cattle and explore properties of the estimates of the comparative effect parameters through simulation. We find that even with the categorization of the levels varying across trials, the magnitudes of the biases are relatively small and that under a large sample size, the root mean square errors become small as well. CONCLUSIONS: Our proposed method to conduct a network meta-analysis for an ordinal outcome when the categorization of the outcome varies across trials, which utilizes the adjacent-categories logit link, performs well in estimation. Because the method considers all available data in a single estimation, it will be particularly useful to research synthesizers when the network of interest has only a limited number of trials for each categorization of the outcome.

Glucose Responsive Coacervate Protocells from Microfluidics for Diabetic Wound Healing.

The hyperglycemic pathophysiological environment in diabetic wounds is a major obstacle that impedes the healing process. Glucose-responsive wound healing materials are a promising approach to address this challenge. In this study, complex coacervate-based protocells are introduced for diabetic wound healing. By employing a microfluidic chip with an external mechanical vibrator, uniform coacervate microdroplets are generated via electrostatic interactions between diethylaminoethyl-dextran and double-stranded DNA. The spontaneous assembly of a phospholipid membrane on the droplet surface enhances its biocompatibility. Glucose oxidase and copper peroxide nanodots are integrated into microdroplets, enabling a glucose-responsive cascade that produces hydroxyl radicals as antibacterial agents. These features contribute to efficient antibacterial activity and wound healing in diabetic mice. The present protocells facilitate intelligent wound management, and the design of cascade catalytic coacervates can contribute to the development of various smart vehicles for drug delivery.

Polarization-driven band topology evolution in twisted MoTe2 and WSe2.

Motivated by recent experimental observations of opposite Chern numbers in R-type twisted MoTe2 and WSe2 homobilayers, we perform large-scale density-functional-theory calculations with machine learning force fields to investigate moiré band topology across a range of twist angles in both materials. We find that the Chern numbers of the moiré frontier bands change sign as a function of twist angle, and this change is driven by the competition between moiré ferroelectricity and piezoelectricity. Our large-scale calculations, enabled by machine learning methods, reveal crucial insights into interactions across different scales in twisted bilayer systems. The interplay between atomic-level relaxation effects and moiré-scale electrostatic potential variation opens new avenues for the design of intertwined topological and correlated states, including the possibility of mimicking higher Landau level physics in the absence of magnetic field.

Prognostic relevance of ventricular arrhythmias in surgical patients with gastrointestinal tumors.

BACKGROUND: Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases. Among which, ventricular arrhythmia is a prevalent clinical concern. This suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal tumors. AIM: To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving surgery. METHODS: We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor resection. These patients were evaluated by a 24-h ambulatory electrocardiogram (ECG) at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2020. Additionally, 41 general healthy age-matched and sex-matched controls were included. Patients were categorized into survival and non-survival groups. The primary endpoint was all-cause mortality, and secondary endpoints included major adverse cardiovascular events (MACEs). RESULTS: Colorectal tumors comprised 90% of cases. Preoperative ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors, 100 (76.92%) exhibited varying degrees of premature ventricular contractions (PVCs). Ten patients (7.69%) manifested non-sustained ventricular tachycardia (NSVT). The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG [27 (21.3) vs 1 (2.5), P = 0.012] and 24-h ambulatory ECG [14 (1.0, 405) vs 1 (0, 6.5), P < 0.001]. Non-survivors had a higher PVC count than survivors [150.50 (7.25, 1690.50) vs 9 (0, 229.25), P = 0.020]. During the follow-up period, 24 patients died and 11 patients experienced MACEs. Univariate analysis linked PVC > 35/24 h to all-cause mortality, and NSVT was associated with MACE. However, neither PVC burden nor NSVT independently predicted outcomes according to multivariate analysis. CONCLUSION: Patients with gastrointestinal tumors exhibited elevated PVCs. PVCs > 35/24 h and NSVT detected by 24-h ambulatory ECG were prognostically significant but were not found to be independent predictors.

Smart diabetic foot ulcer scoring system.

Current assessment methods for diabetic foot ulcers (DFUs) lack objectivity and consistency, posing a significant risk to diabetes patients, including the potential for amputations, highlighting the urgent need for improved diagnostic tools and care standards in the field. To address this issue, the objective of this study was to develop and evaluate the Smart Diabetic Foot Ulcer Scoring System, ScoreDFUNet, which incorporates artificial intelligence (AI) and image analysis techniques, aiming to enhance the precision and consistency of diabetic foot ulcer assessment. ScoreDFUNet demonstrates precise categorization of DFU images into "ulcer," "infection," "normal," and "gangrene" areas, achieving a noteworthy accuracy rate of 95.34% on the test set, with elevated levels of precision, recall, and F1 scores. Comparative evaluations with dermatologists affirm that our algorithm consistently surpasses the performance of junior and mid-level dermatologists, closely matching the assessments of senior dermatologists, and rigorous analyses including Bland-Altman plots and significance testing validate the robustness and reliability of our algorithm. This innovative AI system presents a valuable tool for healthcare professionals and can significantly improve the care standards in the field of diabetic foot ulcer assessment.

Loss of RBM45 inhibits breast cancer progression by reducing the SUMOylation of IRF7 to promote IFNB1 transcription.

Type I interferons exhibit anti-proliferative and anti-cancer activities, but their detailed regulatory mechanisms in cancer have not been fully elucidated yet. RNA binding proteins are master orchestrators of gene regulation, which are closely related to tumor progression. Here we show that the upregulated RNA binding protein RBM45 correlates with poor prognosis in breast cancer. Depletion of RBM45 suppresses breast cancer progression both in cultured cells and xenograft mouse models. Mechanistically, RBM45 ablation inhibits breast cancer progression through regulating type I interferon signaling, particularly by elevating IFN-ß production. Importantly, RBM45 recruits TRIM28 to IRF7 and stimulates its SUMOylation, thereby repressing IFNB1 transcription. Loss of RBM45 reduced the SUMOylation of IRF7 by reducing the interaction between TRIM28 and IRF7 to promote IFNB1 transcription, leading to the inhibition of breast cancer progression. Taken together, our finding uncovers a vital role of RBM45 in modulating type I interferon signaling and cancer aggressive progression, implicating RBM45 as a potential therapeutic target in breast cancer.

Prenatal exposure to low-dose bisphenol A disrupts hippocampal DNA methylation and demethylation in male rat offspring.

Earlier research has demonstrated that developmental exposure to bisphenol A (BPA) has persistent impacts on both adult brain growth and actions. It has been suggested that BPA might obstruct the methylation coding of the genes in the brain. In this study, the methylation changes in the hippocampus tissue of male rat pups were examined following prenatal BPA exposure. Pregnant Sprague-Dawley rats were treated with either vehicle (tocopherol-stripped corn oil) or BPA (4, 40, or 400 µg/kg·body weight/day) throughout the entire duration of gestation and lactation. At 3 weeks of age, the male rat offspring were euthanized, and the hippocampus were dissected out for analysis. The expression levels of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) and DNA demethylases (TET1, Gadd45a, Gadd45b, and Apobec1) were analyzed in the hippocampus by means of quantitative real-time polymerase chain reaction and Western blotting, respectively. The results showed that prenatal exposure to BPA upregulated the expression of enzymes associated with DNA methylation and demethylation processes in the hippocampus of male rat offspring. These findings suggest that prenatal exposure to a low dose of BPA could potentially disrupt the balance of methylation and demethylation in the hippocampus, thereby perturbing epigenetic modifications. This may represent a neurotoxicity mechanism of BPA.

BRAIxDet: Learning to detect malignant breast lesion with incomplete annotations.

Methods to detect malignant lesions from screening mammograms are usually trained with fully annotated datasets, where images are labelled with the localisation and classification of cancerous lesions. However, real-world screening mammogram datasets commonly have a subset that is fully annotated and another subset that is weakly annotated with just the global classification (i.e., without lesion localisation). Given the large size of such datasets, researchers usually face a dilemma with the weakly annotated subset: to not use it or to fully annotate it. The first option will reduce detection accuracy because it does not use the whole dataset, and the second option is too expensive given that the annotation needs to be done by expert radiologists. In this paper, we propose a middle-ground solution for the dilemma, which is to formulate the training as a weakly- and semi-supervised learning problem that we refer to as malignant breast lesion detection with incomplete annotations. To address this problem, our new method comprises two stages, namely: (1) pre-training a multi-view mammogram classifier with weak supervision from the whole dataset, and (2) extending the trained classifier to become a multi-view detector that is trained with semi-supervised student-teacher learning, where the training set contains fully and weakly-annotated mammograms. We provide extensive detection results on two real-world screening mammogram datasets containing incomplete annotations and show that our proposed approach achieves state-of-the-art results in the detection of malignant breast lesions with incomplete annotations.