Radio-pathological characteristics of primary neuroendocrine breast carcinoma: Series of 4 cases.

Neuroendocrine breast cancers (NEBCs) are a rare and distinct subtype of breast tumors, characterized by their neuroendocrine differentiation. Despite accounting for less than 1% of all breast cancers, NEBCs present unique diagnostic and therapeutic challenges due to their heterogeneous nature and variable prognosis. Accurate imaging plays a crucial role in the diagnosis, treatment planning, and follow-up of NEBCs, yet remains a complex area due to the rarity of these tumors and overlapping features with more common breast cancers. We present a series of 4 cases of primary NEBC, emphasizing the imaging features and their histopathological correlations. All patients presented with breast lump. Diagnostic Mammography followed by Ultrasound was performed in each case. All 4 cases were categorized as Breast Imaging- Reporting and Data System (BI-RADS)-4. Trucut biopsy was performed and histopathological analysis revealed the diagnosis of NEBC. Patients underwent Surgery followed by Chemotherapy, Hormonal Therapy or Radiation therapy alone or in combination with each other depending upon the histopathological characteristics.

MANCR lncRNA Modulates Cell-Cycle Progression and Metastasis by Cis-Regulation of Nuclear Rho-GEF.

A significant number of the genetic alterations observed in cancer patients lie within nonprotein-coding segments of the genome, including regions coding for long noncoding RNAs (lncRNAs). LncRNAs display aberrant expression in breast cancer (BrCa), but the functional implications of this altered expression remain to be elucidated. By performing transcriptome screen in a triple negative BrCa (TNBC) isogenic 2D and 3D spheroid model, we observed aberrant expression of >1000 lncRNAs during BrCa progression. The chromatin-associated lncRNA MANCR shows elevated expression in metastatic TNBC. MANCR is upregulated in response to cellular stress and modulates DNA repair and cell proliferation. MANCR promotes metastasis as MANCR-depleted cells show reduced cell migration, invasion, and wound healing in vitro, and reduced metastatic lung colonization in xenograft experiments in vivo. Transcriptome analyses reveal that MANCR modulates expression and pre-mRNA splicing of genes, controlling DNA repair and checkpoint response. MANCR promotes the transcription of NET1A, a Rho-GEF that regulates DNA damage checkpoint and metastatic processes in cis, by differential promoter usage. Experiments suggest that MANCR regulates the expression of cancer-associated genes by modulating the association of various transcription factors and RNA-binding proteins. Our results identified the metastasis-promoting activities of MANCR in TNBC by cis-regulation of gene expression.

5-Azacytidine- and retinoic-acid-induced reprogramming of DCCs into dormancy suppresses metastasis via restored TGF-ß-SMAD4 signaling.

Disseminated cancer cells (DCCs) in secondary organs can remain dormant for years to decades before reactivating into overt metastasis. Microenvironmental signals leading to cancer cell chromatin remodeling and transcriptional reprogramming appear to control onset and escape from dormancy. Here, we reveal that the therapeutic combination of the DNA methylation inhibitor 5-azacytidine (AZA) and the retinoic acid receptor ligands all-trans retinoic acid (atRA) or AM80, an RARα-specific agonist, promotes stable dormancy in cancer cells. Treatment of head and neck squamous cell carcinoma (HNSCC) or breast cancer cells with AZA+atRA induces a SMAD2/3/4-dependent transcriptional program that restores transforming growth factor ß (TGF-ß)-signaling and anti-proliferative function. Significantly, either combination, AZA+atRA or AZA+AM80, strongly suppresses HNSCC lung metastasis formation by inducing and maintaining solitary DCCs in a SMAD4+/NR2F1+ non-proliferative state. Notably, SMAD4 knockdown is sufficient to drive resistance to AZA+atRA-induced dormancy. We conclude that therapeutic doses of AZA and RAR agonists may induce and/or maintain dormancy and significantly limit metastasis development.

NiSi: A New Venue for Antiferromagnetic Spintronics.

Envisaging antiferromagnetic spintronics pivots on two key criteria of high transition temperature and tuning of underlying magnetic order using straightforward application of magnetic field or electric current. Here, it is shown that NiSi metal can provide suitable new platform in this quest. First, the study unveils high-temperature antiferromagnetism in single-crystal NiSi with Néel temperature, TN ⩾ 700 K. Antiferromagnetic order in NiSi is accompanied by non-centrosymmetric magnetic character with small ferromagnetic component in the a-c plane. Second, it is found that NiSi manifests distinct magnetic and electronic hysteresis responses to field applications due to the disparity in two moment directions. While magnetic hysteresis is characterized by one-step switching between ferromagnetic states of uncompensated moment, electronic behavior is ascribed to metamagnetic switching phenomena between non-collinear spin configurations. Importantly, the switching behaviors persist to high temperature. The properties underscore the importance of NiSi in the pursuit of antiferromagnetic spintronics.

MacroH2A impedes metastatic growth by enforcing a discrete dormancy program in disseminated cancer cells.

MacroH2A variants have been linked to inhibition of metastasis through incompletely understood mechanisms. Here, we reveal that solitary dormant disseminated cancer cells (DCCs) display increased levels of macroH2A variants in head and neck squamous cell carcinoma PDX in vivo models and patient samples compared to proliferating primary or metastatic lesions. We demonstrate that dormancy-inducing transforming growth factor-ß2 and p38α/ß pathways up-regulate macroH2A expression and that macroH2A variant overexpression is sufficient to induce DCC dormancy and suppress metastasis in vivo. Notably, inducible expression of the macroH2A2 variant in vivo suppresses metastasis via a reversible growth arrest of DCCs. This state does not require the dormancy-regulating transcription factors DEC2 and NR2F1; instead, transcriptomic analysis reveals that macroH2A2 overexpression inhibits cell cycle and oncogenic signaling programs, while up-regulating dormancy and senescence-associated inflammatory cytokines. We conclude that the macroH2A2-enforced dormant phenotype results from tapping into transcriptional programs of both quiescence and senescence to limit metastatic outgrowth.

Double Anchoring Technique of Occipito-Cervical Fixation Using Innovative Occipital Plate: A Preliminary Study.

Background: Occipito-cervical fixation (OCF) provides immediate rigid fixation to cranio-vertebral junction (CVJ); however, in current practice, the optimal occipito-cervical fixation method is arguable. Aim: The aim of this study was to test the safety and efficacy of a newly designed inside-outside occipital (OC) plate system for the treatment of cranio-vertebral junction instability. Material and Methods: Thirty-two patients of CVJ instability were treated using this new OC plate system. Safety and efficacy of this new OC plate was evaluated radiologically and clinically. Results: Follow-up period ranged from 9 to 23 months. During the follow-up, no implant failure, recurrent subluxation, or newly developed instability at adjacent levels occurred, except in one patient in whom C2 screw pullout occurred due to trauma. All patients showed a satisfactory fusion at three months follow-up examination. Conclusions: These preliminary results suggest that this OC plate system is a simple, safe, and effective method for providing immediate internal rigid fixation of the CV junction. Long-term results are needed to determine the superiority of this OC plate over other methods of occipital fixation.

Transfacetal Screw Fixation for Subaxial Cervical Spine.

Background and Introduction: In the modern era of spine surgery for subaxial cervical spine, transfacetal screw fixation has evolved enormously. Transfacetal screw fixation for subaxial cervical spine is a biomechanically effective technique. In this fixation, four cortical surfaces of the facets are purchased by the transfacetal screws. Objectives: In this video, we demonstrated the surgical technique of posterior transfacetal screw fixation. Surgical Technique: Transfacetal screw fixation of subaxial cervical spine was done along with posterior decompression. The entry point of transfacetal screw was defined as 1 mm caudal to mid-point of lateral mass, and screws were directed perpendicular to facet joint in the sagittal plane and straight in the coronal plane. Bone chips were placed over decorticated lateral mass after decompression. Result: Patient had uneventful recovery and maintained good status at follow up. Conclusion: In subaxial cervical spine, transfacetal screw fixation is a biomechanically effective, rigid, and an inexpensive technique to obtain immediate rigid fixation.

Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells.

Metastases are initiated by disseminated tumor cells (DTCs) that colonize distant organs. Growing evidence suggests that the microenvironment of the primary tumor primes DTCs for dormant or proliferative fates. However, the manner in which this occurs remains poorly understood. Here, using the Window for High-Resolution Intravital Imaging of the Lung (WHRIL), we study the live lung longitudinally and follow the fate of individual DTCs that spontaneously disseminate from orthotopic breast tumors. We find that spontaneously DTCs have increased levels of retention, increased speed of extravasation, and greater survival after extravasation, compared to experimentally metastasized tumor cells. Detailed analysis reveals that a subset of macrophages within the primary tumor induces a pro-dissemination and pro-dormancy DTC phenotype. Our work provides insight into how specific primary tumor microenvironments prime a subpopulation of cells for expression of proteins associated with dissemination and dormancy.

Prostate Cancer Dormancy and Reactivation in Bone Marrow.

Prostate cancer has a variable clinical course, ranging from curable local disease to lethal metastatic spread. Eradicating metastatic cells is a unique challenge that is rarely met with the available therapies. Thus, targeting prostate cancer cells in earlier disease states is a crucial window of opportunity. Interestingly, cancer cells migrate from their primary site during pre-cancerous and malignant phases to seed secondary organs. These cells, known as disseminated cancer cells (DCCs), may remain dormant for months or decades before activating to form metastases. Bone marrow, a dormancy-permissive site, is the major organ for housed DCCs and eventual metastases in prostate cancer. The dynamic interplay between DCCs and the primary tumor microenvironment (TME), as well as that between DCCs and the secondary organ niche, controls the conversion between states of dormancy and activation. Here, we discuss recent discoveries that have improved our understanding of dormancy signaling and the role of the TME in modulating the epigenetic reprogramming of DCCs. We offer potential strategies to target DCCs in prostate cancer.

Magnetic charge's relaxation propelled electricity in two-dimensional magnetic honeycomb lattice.

Emerging new concepts, such as magnetic charge dynamics in two-dimensional magnetic material, can provide novel mechanism for spin-based electrical transport at macroscopic length. In artificial spin ice of single domain elements, magnetic charge's relaxation can create an efficient electrical pathway for conduction by generating fluctuations in local magnetic field that couple with conduction electron spins. In a first demonstration, we show that the electrical conductivity is propelled by more than an order of magnitude at room temperature due to magnetic charge defects sub-picosecond relaxation in artificial magnetic honeycomb lattice. The direct evidence to the proposed electrical conduction mechanism in two-dimensional frustrated magnet points to the untapped potential for spintronic applications in this system.

Social-ecological analysis of timely rice planting in Eastern India.

Timely crop planting is a foundation for climate-resilient rice-wheat systems of the Eastern Gangetic Plains-a global food insecurity and poverty hotspot. We hypothesize that the capacity of individual farmers to plant on time varies considerably, shaped by multifaceted enabling factors and constraints that are poorly understood. To address this knowledge gap, two complementary datasets were used to characterize drivers and decision processes that govern the timing of rice planting in this region. The first dataset was a large agricultural management survey (rice-wheat: n = 15,245; of which rice: n = 7597) from a broad geographic region that was analyzed by machine learning methods. The second dataset was a discussion-based survey (n = 112) from a more limited geography that we analyzed with graph theory tools to elicit nuanced information on planting decisions. By combining insights from these methods, we show for the first time that differences in rice planting times are primarily shaped by ecosystem and climate factors while social factors play a prominent secondary role. Monsoon onset, surface and groundwater availability, and land type determine village-scale mean planting times whereas, for resource-constrained farmers who tend to plant later ceteris paribus, planting is further influenced by access to farm machinery, seed, fertilizer, and labor. Also, a critical threshold for economically efficient pumping appears at a groundwater depth of around 4.5 m; below this depth, farmers do not irrigate and delay planting. Without collective action to spread risk through synchronous timely planting, ecosystem factors such as threats posed by pests and wild animals may further deter early planting by individual farmers. Accordingly, we propose a three-pronged strategy that combines targeted strengthening of agricultural input chains, agroadvisory development, and coordinated rice planting and wildlife conservation to support climate-resilient agricultural development in the Eastern Gangetic Plains.

Vitamin D levels in paediatric intensive care unit patients and its relation to severity of illness: An Indian experience.

Vitamin D deficiency is a common disorder that is associated with morbidity and mortality in the general population. We conducted a cross-sectional study of 384 children admitted to paediatric intensive care to determine its prevalence and association with severity of illness and outcome in critically ill children. The severity of illness was evaluated using the paediatric risk of mortality score (PRISM III), on admission, at 24 and 48 h. Vitamin D deficiency was observed in 175 children (45.6%) and was associated with higher severity of illness, need for mechanical ventilation and increased mortality.

Bone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGFß2.

In the bone marrow (BM) microenvironment, where breast cancer (BC) disseminated tumour cells (DTCs) can remain dormant for decades, NG2+/Nestin+ mesenchymal stem cells (MSCs) promote hematopoietic stem cell quiescence. Here, we reveal that periarteriolar BM-resident NG2+/Nestin+ MSCs can also instruct BC DTCs to enter dormancy. NG2+/Nestin+ MSCs produce TGFß2 and BMP7 and activate a quiescence pathway dependent on TGFBRIII and BMPRII, which via p38-kinase result in p27 induction. Genetic depletion of MSCs or conditional knock-out of TGFß2 in MSCs using an NG2-CreER driver led to bone metastatic outgrowth of otherwise dormant p27+/Ki67- DTCs. Also ER+ BC patients without systemic recurrence displayed higher frequency of TGFß2 and BMP7 detection in the BM. Our results provide a direct proof that HSC dormancy niches control BC DTC dormancy and suggest that aging or extrinsic factors that affect the NG2+/Nestin+ MSC niche homeostasis may result in a break from dormancy and BC bone relapse.

Intercomparison of crop establishment methods for improving yield and profitability in the rice-wheat system of Eastern India.

Conventionally managed rice-wheat systems of the eastern Indo-Gangetic Plains (E-IGP) that rely on soil puddling for rice and intensive tillage for wheat are low-yielding and resource-inefficient, leading to low profitability. While a host of alternative tillage and crop establishment (TCE) methods have been advocated as solutions for sustainably enhancing productivity and profitability, few systematic comparisons of these methods are reported. To address this gap, a three-year field study was conducted in Bihar, India with the goal of identifying TCE methods for rice-wheat systems that are high yielding, less resource-intensive, and more profitable. The following systems were evaluated: 1) puddled transplanted rice (PTR) followed by (fb) conventional tillage wheat (CTW) or zero-tillage wheat (ZTW); 2) machine transplanted rice in non-puddled soil (MTR) fb ZTW; 3) the system of rice intensification (SRI) fb system of wheat intensification (SWI); and 4) dry-seeded rice (DSR) fb ZTW. Rice cultivar duration (short versus medium-duration) was incorporated as a subplot treatment in all systems. Rice yields were similar with all methods, except DSR yield was 11 % lower and MTR yield was 7% higher than PTR in the third year. Cost of production was US$ 149 and 77 ha-1 lower in DSR and MTR, respectively, and US$ 84 ha-1 higher in SRI than PTR. The gross margin and benefit-cost (B:C) ratio was highest in MTR followed by DSR and lowest in SRI. In wheat, ZT resulted in a higher yield than CTW, especially when ZTW was cultivated after non-puddled rice (e.g., DSR or MTR). ZTW reduced production costs by US$ 69 ha-1, whereas SWI increased it by US$ 139 ha-1 relative to CTW. The higher yield and lower cost of production resulted in a higher gross margin (US$ 82-355 ha-1 and US$ 129-409 ha-1 higher than CTW and SWI, respectively) and a higher B:C ratio in ZTW treatments than CTW and SWI. At the system level, MTR or DSR followed by ZTW had both superior crop yields and consistently higher gross margins (US $133 to 382 ha-1) than other practices. On the other hand, the SRI fb SWI system had no yield advantage and poorer economic performance than conventional practices. In all systems, the inclusion of a medium-duration rice hybrid resulted in higher rice and system yields. These results suggest that significant gains in profitability are possible with emerging TCE practices in rice-wheat systems, but alternatives such as the SRI and SWI will likely erode farmer incomes.

ORCA/LRWD1 Regulates Homologous Recombination at ALT-Telomeres by Modulating Heterochromatin Organization.

Telomeres are maintained by telomerase or in a subset of cancer cells by a homologous recombination (HR)-based mechanism, Alternative Lengthening of Telomeres (ALT). The mechanisms regulating telomere-homeostasis in ALT cells remain unclear. We report that a replication initiator protein, Origin Recognition Complex-Associated (ORCA/LRWD1), by localizing at the ALT-telomeres, modulates HR activity. ORCA's localization to the ALT-telomeres is facilitated by its interaction to SUMOylated shelterin components. The loss of ORCA in ALT-positive cells elevates the levels of two mediators of HR, RPA and RAD51, and consistent with this, we observe increased ALT-associated promyelocytic leukemia body formation and telomere sister chromatid exchange. ORCA binds to RPA and modulates the association of RPA to telomeres. Finally, the loss of ORCA causes global chromatin decondensation, including at the telomeres. Our results demonstrate that ORCA acts as an inhibitor of HR by modulating RPA binding to ssDNA and inducing chromatin compaction.