Token-Mixer: Bind Image and Text in One Embedding Space for Medical Image Reporting.

Medical image reporting focused on automatically generating the diagnostic reports from medical images has garnered growing research attention. In this task, learning cross-modal alignment between images and reports is crucial. However, the exposure bias problem in autoregressive text generation poses a notable challenge, as the model is optimized by a word-level loss function using the teacher-forcing strategy. To this end, we propose a novel Token-Mixer framework that learns to bind image and text in one embedding space for medical image reporting. Concretely, Token-Mixer enhances the cross-modal alignment by matching image-to-text generation with text-to-text generation that suffers less from exposure bias. The framework contains an image encoder, a text encoder and a text decoder. In training, images and paired reports are first encoded into image tokens and text tokens, and these tokens are randomly mixed to form the mixed tokens. Then, the text decoder accepts image tokens, text tokens or mixed tokens as prompt tokens and conducts text generation for network optimization. Furthermore, we introduce a tailored text decoder and an alternative training strategy that well integrate with our Token-Mixer framework. Extensive experiments across three publicly available datasets demonstrate Token-Mixer successfully enhances the image-text alignment and thereby attains a state-of-the-art performance. Related codes are available at https://github.com/yangyan22/Token-Mixer.

Injectable Bombyx mori (B. mori) silk fibroin/MXene conductive hydrogel for electrically stimulating neural stem cells into neurons for treating brain damage.

Brain damage is a common tissue damage caused by trauma or diseases, which can be life-threatening. Stem cell implantation is an emerging strategy treating brain damage. The stem cell is commonly embedded in a matrix material for implantation, which protects stem cell and induces cell differentiation. Cell differentiation induction by this material is decisive in the effectiveness of this treatment strategy. In this work, we present an injectable fibroin/MXene conductive hydrogel as stem cell carrier, which further enables in-vivo electrical stimulation upon stem cells implanted into damaged brain tissue. Cell differentiation characterization of stem cell showed high effectiveness of electrical stimulation in this system, which is comparable to pure conductive membrane. Axon growth density of the newly differentiated neurons increased by 290% and axon length by 320%. In addition, unfavored astrocyte differentiation is minimized. The therapeutic effect of this system is proved through traumatic brain injury model on rats. Combined with in vivo electrical stimulation, cavities formation is reduced after traumatic brain injury, and rat motor function recovery is significantly promoted.

Discovery of a Novel Class of PROTACs as Potent and Selective Estrogen Receptor α Degraders to Overcome Endocrine-Resistant Breast Cancer In Vitro and In Vivo.

The estrogen receptor (ER) is a well-established target for endocrine therapies of ER-positive breast cancer (ER+ BC), but endocrine resistance limits the efficacy of clinical drugs. Using proteolysis targeting chimera (PROTAC) technology to degrade ERα may be an effective alternative to endocrine therapies. Herein, we disclose a novel series of potent and selective ERα PROTACs based on an oxabicycloheptane sulfonamide (OBHSA) scaffold, with no associated ERß degradation. These PROTACs showed significant antiproliferation and ERα degradation activities against a broad spectrum of ER+ BC cells including tamoxifen-resistant and ERα mutant cell lines. Genomics analysis confirmed that these PROTACs inhibited the nascent RNA synthesis of ERα target genes and impaired genome-wide ERα binding. Compound ZD12 exhibited excellent antitumor potency and ERα degradation activity in both tamoxifen-sensitive and -resistant BC mice models, which are superior to fulvestrant. This study demonstrates the potential of these PROTACs as novel drug candidates for endocrine-resistant BC treatment.

CDK12 and Integrator-PP2A complex modulates LEO1 phosphorylation for processive transcription elongation.

Cyclin-dependent kinase 12 (CDK12) interacts with cyclin K to form a functional nuclear kinase that promotes processive transcription elongation through phosphorylation of the C-terminal domain of RNA polymerase II (Pol II). To gain a comprehensive understanding of CDK12's cellular function, we used chemical genetic and phosphoproteomic screening to identify a landscape of nuclear human CDK12 substrates, including regulators of transcription, chromatin organization, and RNA splicing. We further validated LEO1, a subunit of the polymerase-associated factor 1 complex (PAF1C), as a bona fide cellular substrate of CDK12. Acute depletion of LEO1, or substituting LEO1 phosphorylation sites with alanine, attenuated PAF1C association with elongating Pol II and impaired processive transcription elongation. Moreover, we discovered that LEO1 interacts with and is dephosphorylated by the Integrator-PP2A complex (INTAC) and that INTAC depletion promotes the association of PAF1C with Pol II. Together, this study reveals an uncharacterized role for CDK12 and INTAC in regulating LEO1 phosphorylation, providing important insights into gene transcription and its regulation.

Case report: Rapid recurrence of a chronic subdural haematoma associated with prostate cancer metastasis to a haematoma capsule.

Background: Chronic subdural haematoma (CSDH) has various causes, including trauma, coagulopathies, and intracranial hypotension. However, CSDH associated with extracranial malignancy is rare. Here, we report an extremely rare case of CSDH due to prostate cancer metastasis to a haematoma capsule. Case Description: A 79-year-old man with a history of prostate cancer had a progressive decline in consciousness during hospitalization for cancer treatment. CSDH was diagnosed from computed tomography (CT) imaging. We urgently performed burr hole drainage, and the patient's symptoms improved rapidly after surgery. After removing the drainage tube, the patient's symptoms worsened again, and the repeat head CT suggested recurrence of CSDH. In a second operation, most of the haematoma capsule was excised under craniotomy, and the thickened haematoma capsule was sent for routine pathologic examination. Pathological findings confirmed the metastasis of prostate cancer to the haematoma capsule, which we believed to be related to a rapid recurrence of CSDH. After the second operation, the disease course progressed without CSDH recurrence. Conclusions: For patients with malignant tumours diagnosed with CSDH, the possibility of metastasis to a haematoma capsule needs to be considered. Burr holes and drainage can easily lead to a rapid relapse. Excision of the haematoma capsule is the key to successful treatment.

Case Report: Clinical and Procedural Implications of Ommaya Reservoir Implantation in Cystic Brain Metastases Followed by Radiosurgery Treatment.

Background: Therapy for large or deep cystic brain metastases is a troublesome procedure in clinical departments. Stereotactic cyst aspiration, combined with Gamma Knife radiosurgery, can be an effective treatment for cystic brain metastases. However, there is still a possibility that a reaccumulation of cystic fluid may lead to poor efficacy or even reoperation. Case presentation: We present a case of a 67-year-old man who was diagnosed with lung cancer brain metastasis. The intracranial lesion seen on imaging appeared to be cystic and located deep inside the brain with associated limb dysfunction. The patient did not respond well to chemotherapy and underwent cyst aspiration with Ommaya reservoir implantation under neuronavigation. Repeated cystic fluid reaccumulation and exacerbation of symptoms occurred during treatment. We performed repeated aspiration via the Ommaya reservoir to control the symptoms and combined it with radiotherapy. During the follow-up period of 14 months, the intracranial tumor was effectively and satisfactorily controlled. Conclusions: We highlight that Ommaya reservoir implantation during stereotactic cyst aspiration is necessary to prevent fluid reaccumulation, thereby avoiding the need for a second surgical procedure.

Case Report: Primary Indolent Epstein-Barr Virus-Positive T-Cell Lymphoproliferative Disease Involving the Central Nervous System.

Background: T-cell lymphoproliferative disease (T-LPD), characterized by primary Epstein-Barr virus (EBV) infection and clonal proliferation of T cells, occurs both in systemic and non-lymphatic organs. However, isolated indolent EBV-positive T-LPD involving the central nervous system has not been reported. Case Presentation: A 48-year-old male who complained of headache, blurred vision, and weakness of the left lower limb for 1 month was hospitalized in our department. Neither neurological deficit nor palpable lymphadenopathy had been found. Bone marrow and laboratory tests had shown no abnormality as well. Enhanced MRI demonstrated enhanced cotton-like lesions up to 20 mm in diameter located in the right frontal, temporal, parietal and left parietal, occipital lobes with perifocal edema. Neuronavigation-assisted mini-craniotomy was performed to achieve total excision of the right temporal superficial lesion and identify the diagnosis. Pathological and EBV analysis described the lesion as indolent EBV-positive T-cell lymphoproliferative disease of the central nervous system (CNS). Then, a therapeutic regimen including whole-brain irradiation, chemotherapy, prednisolone, and aciclovir was given. Serial radiological imaging showed no signal of recurrence at 5 months' follow-up. Conclusion: Primary indolent T-LPD in the central nervous system is quite rare, and it needs to be distinguished from aggressive cerebral T-cell lymphoma, metastatic tumors, and other CNS lesions.

Contralateral Subdural Hematoma Following Surgical Evacuation of Acute Subdural Hematoma: Super-Early Intervention and Clinical Implications.

BACKGROUND: Contralateral acute subdural hematoma (ASDH) is an uncommon but devastating complication during craniotomy and hematoma evacuation. It can lead to extremely poor outcomes if not treated properly and promptly. CASE DESCRIPTION: We present a case of a 49-year-old male who suffered contralateral ASDH during surgical evacuation of ASDH on the left side. Before the operation, we noticed slight contralateral ASDH on preoperative cranial computed tomography and were aware of its enlargement during operation. Decompression with a burr-hole craniotomy promptly followed by a decompressive craniectomy was performed to prevent contralateral ASDH. Unfortunately, we found intraoperative brain swelling, which indicated the development of a contralateral hematoma. The patient was reoperated and eventually had a poor prognosis. CONCLUSIONS: We highlight that super-early intervention of contralateral hematoma is important to improve the prognosis of these patients.

Bisphenol AP is anti-estrogenic and may cause adverse effects at low doses relevant to human exposure.

A recent increase in the use of bisphenol A (BPA) alternatives to manufacture plastics has led to safety concerns. Here, we evaluated the estrogenic and anti-estrogenic activities of bisphenol AP (BPAP), a poorly studied BPA alternative, using in vitro, in vivo and in silico tools. BPAP exhibited weak estrogenicity but strong anti-estrogenicity (IC50 = 2.35 µM) in a GeneBLAzer™ ß-lactamase reporter gene assay. BPAP, when administered alone or in combination with E2 (50 µg kg-1 bw d-1) for 3 d, significantly decreased the uterine weights of post-weaning CD-1 mice at doses of 10 mg kg-1 bw d-1 and higher. When administered alone to prepubertal CD-1 mice for 10 d, BPAP significantly decreased the uterine weights at doses of 80 µg kg-1 bw d-1 and higher. Toxicogenomic analysis showed that BPAP regulated an opposite patterns of gene expression than that of E2 in mouse uteri. In a glucose tolerance test using male mice, BPAP was found to disrupt the blood glucose homeostasis at low doses relevant to human exposure (1 and 100 µg kg-1 bw d-1). Our results suggest that BPAP should be of great concern which might affect the sexual development in immature feminine and disrupt the blood glucose homeostasis at very low doses.

Highly stretchable gold nanobelts with sinusoidal structures for recording electrocorticograms.

Rationally designed sinusoidal gold nanobelts are fabricated as stretchable electrodes, and they do not show obvious change of resistance under large deformation after 10,000 cyclic stretching/relaxing processes. As a proof of concept, they are successfully used to record intracranial electroencephalogram or electrocorticogram signals from rats.

Dispersed, porous nanoislands landing on stretchable nanocrack gold films: maintenance of stretchability and controllable impedance.

Stretchable electronic devices have great potential for serving as bioelectrical interfaces due to their better deformability and modulus match with biological organs. However, surface modification, which is usually applied to enhance the capability of sensing and stimulating, as well as biocompatibility, may cause problems since their stretchability highly depends on the surface structure. In this work, stretchable nanocrack gold (SNCG) electrodes were fabricated, which can be stretched by a maximum 120% uniaxial strain while maintaining their electrical conductivity. We found that the electrodes lost their stretchability after surface modification of an additional continuous platinum layer, which was found to selectively weld or fully cover the nanocracks, consequently eliminating its crack structure. To address this issue, we designed a complex structure of dispersed, porous nanoislands landing on the SNCG film, which was further demonstrated as capable of maintaining the stretchability of electrodes while allowing the reshaping of cracks. Moreover, stretchable microelectrode arrays were then developed with this complex structure. Animal experiments demonstrated their capability of conformally wrapping on a rat brain cortex and effectively monitoring an intracranial electroencephalogram under deformation. In addition, their impedance can be precisely controlled by modulating the dispersity, diameter, and aspect ratio of individual nanoislands. This complex structure has great potential for developing highly stretchable, multiplexing sensors, allowing stiff materials to land on a stretchable conducting surface with maintenance of stretchability and controllable functional area.

Imbalanced expression of mitogen-activated protein kinase phosphatase-1 and phosphorylated extracellular signal-regulated kinases in lung squamous cell carcinoma.

OBJECTIVE: Mitogen-activated protein kinases (MAPKs) are correlated with a more malignant phenotype in many cancers. This study was designed to evaluate the predictive value of the expression of MAPK phosphatase-1 (MKP-1) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK(1/2)), as the key regulatory mechanism of the MAPKs, in lung squamous cell carcinoma (SCC). METHODS: We assessed the expressions of MKP-1 and p-ERK(1/2) in twenty subjects at different differentiation degree of SCC and five normal lungs by immunohistochemistry and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. RESULTS: Immunohistochemistry and real-time RT-PCR assay showed that the expression of MKP-1 was gradually decreased as tissue type went from normal lung tissues to increasingly undifferentiated carcinoma, and it was negatively correlated with tumor differentiation (P<0.01). However, the expression of p-ERK(1/2) or ERK(1/2) was gradually increased as tissue type went from normal lung tissues to increasingly undifferentiated carcinoma, and it was positively correlated with tumor differentiation (P<0.01). CONCLUSIONS: Our data indicates the relevance of MKP-1 and p-ERK(1/2) in SCC as a potential positive and negative prognostic factor. The imbalanced expression of MKP-1 and p-ERK(1/2) may play a role in the development of SCC and these two molecules may be new targets for the therapy and prognosis of SCC.