Content-Addressable Memories and Transformable Logic Circuits Based on Ferroelectric Reconfigurable Transistors for In-Memory Computing.

As a promising alternative to the von Neumann architecture, in-memory computing holds the promise of delivering a high computing capacity while consuming low power. In this paper, we show that the ferroelectric reconfigurable transistor can serve as a versatile logic-in-memory unit that can perform logic operations and data storage concurrently. When functioning as memory, a ferroelectric reconfigurable transistor can implement content-addressable memory (CAM) with a 1-transistor-per-bit density. With the switchable polarity of the ferroelectric reconfigurable transistor, XOR/XNOR-like matching operation in CAM is realized in a single transistor, which can offer a significant improvement in area and energy efficiency compared to conventional CAMs. NAND- and NOR-arrays of CAMs are also demonstrated, which enable multibit matching in a single reading operation. In addition, the NOR array of CAM cells effectively measures the Hamming distance between the input query and the stored entries. When functioning as a logic element, a ferroelectric reconfigurable transistor can be switched between n- and p-type modes. Utilizing the switchable polarity of these ferroelectric Schottky barrier transistors, we demonstrate reconfigurable logic gates with NAND/NOR dual functions, whose input-output mapping can be transformed in real time without changing the layout, and the configuration is nonvolatile.

Changing trends in the minimally invasive surgery for chronic pancreatitis.

Chronic pancreatitis is a debilitating pancreatic inflammatory disease characterized by intractable pain resulting in poor quality of life. Conventional management of pancreatic pain consists of a step-up approach with medications and lifestyle modifications followed by endoscopic intervention. Traditionally surgery is reserved for patients who do not improve with other interventions. However, recent studies suggest that early surgical intervention is more beneficial as it can mitigate the progression of the pathological process and prevent loss of pancreatic function. Despite the widespread adoption of minimally invasive approaches in various gastrointestinal surgical disorders, minimally invasive surgery for chronic pancreatitis is slow to evolve. Technical difficulty due to severe inflammatory changes has been the major impediment to the widespread usage of minimally invasive surgery in chronic pancreatitis. With this background, the present review aimed to critically analyze the available evidence on the minimally invasive treatment of chronic pancreatitis. A Pub Med search of all relevant articles was performed using the appropriate keywords, parentheses, and Boolean operators. Most initial laparoscopic series have reported the feasibility of lateral pancreaticojejunostomy, considered an adequate procedure only in a small proportion of patients. The pancreatic head is the pacemaker of pain, so adequate decompression is critical for long-term pain relief. Recent studies have documented the feasibility of minimally invasive duodenum-preserving pancreatic head resection. With improvements in laparoscopic instrumentation and technological advances, minimally invasive surgery for chronic pancreatitis is gaining momentum. However, more high-quality evidence is required to document the superiority of minimally invasive surgery for chronic pancreatitis.

Appraisal of gastric stump carcinoma and current state of affairs.

Gastric stump carcinoma, also known as remnant gastric carcinoma, is a malignancy arising in the remnant stomach following gastrectomy for a benign or malignant condition. Enterogastric reflux and preexisting risk factors in a patient with gastric cancer are the major contributors to the development of gastric stump carcinoma. The occurrence of gastric stump carcinoma is time-dependent and seen earlier in patients operated on for malignant rather than benign diseases. The tumor location is predominantly at the anastomotic site towards the stomach. However, it can occur anywhere in the remnant stomach. The pattern of lymph node involvement and the type of surgery required is distinctly different compared to primary gastric cancer. Gastric stump carcinoma is traditionally considered a malignancy with a dismal outcome. However, recent advances in diagnostic and therapeutic strategies have improved outcomes. Recent advances in molecular profiling of gastric stump carcinoma have identified distinct molecular subtypes, thereby providing novel therapeutic targets. Also, reports of gastric stump carcinoma following pancreatoduodenectomy and bariatric surgery highlight the need for more research to standardize the diagnosis, staging, and treatment of these tumors. The present review aims to provide an overview of gastric stump carcinoma highlighting the differences in clinicopathological profile and management compared to primary gastric carcinoma.

CORRIGENDUM: Early experience with robot-assisted Frey's procedure surgical outcome and technique: Indian perspective.

[This corrects the article on p. 145 in vol. 25, PMID: 36601487.].

Regenerating zebrafish scales express a subset of evolutionary conserved genes involved in human skeletal disease.

BACKGROUND: Scales are mineralised exoskeletal structures that are part of the dermal skeleton. Scales have been mostly lost during evolution of terrestrial vertebrates whilst bony fish have retained a mineralised dermal skeleton in the form of fin rays and scales. Each scale is a mineralised collagen plate that is decorated with both matrix-building and resorbing cells. When removed, an ontogenetic scale is quickly replaced following differentiation of the scale pocket-lining cells that regenerate a scale. Processes promoting de novo matrix formation and mineralisation initiated during scale regeneration are poorly understood. Therefore, we performed transcriptomic analysis to determine gene networks and their pathways involved in dermal scale regeneration. RESULTS: We defined the transcriptomic profiles of ontogenetic and regenerating scales of zebrafish and identified 604 differentially expressed genes (DEGs). These were enriched for extracellular matrix, ossification, and cell adhesion pathways, but not in enamel or dentin formation processes indicating that scales are reminiscent to bone. Hypergeometric tests involving monogenetic skeletal disorders showed that DEGs were strongly enriched for human orthologues that are mutated in low bone mass and abnormal bone mineralisation diseases (P< 2× 10-3). The DEGs were also enriched for human orthologues associated with polygenetic skeletal traits, including height (P< 6× 10-4), and estimated bone mineral density (eBMD, P< 2× 10-5). Zebrafish mutants of two human orthologues that were robustly associated with height (COL11A2, P=6× 10-24) or eBMD (SPP1, P=6× 10-20) showed both exo- and endo- skeletal abnormalities as predicted by our genetic association analyses; col11a2Y228X/Y228X mutants showed exoskeletal and endoskeletal features consistent with abnormal growth, whereas spp1P160X/P160X mutants predominantly showed mineralisation defects. CONCLUSION: We show that scales have a strong osteogenic expression profile comparable to other elements of the dermal skeleton, enriched in genes that favour collagen matrix growth. Despite the many differences between scale and endoskeletal developmental processes, we also show that zebrafish scales express an evolutionarily conserved sub-population of genes that are relevant to human skeletal disease.

Early experience with robot-assisted Frey's procedure surgical outcome and technique: Indian perspective.

Purpose: Robotic surgery for pancreatic diseases is currently on the rise, feasible, well-accepted, and safe. Frequently performed procedures in relation to pancreatic diseases include distal pancreatectomy and pancreatoduodenectomy. The literature commonly describes robotic lateral pancreaticojejunostomy; however, data on robot-assisted Frey's is scarce. Methods: We herein, describe our series and technique of robot-assisted Frey's procedure at our tertiary care center between November 2019 and March 2022, and its short-term outcomes in comparison to the open Frey's. Patients with chronic pancreatitis having intractable pain, dilated duct, and no evidence of inflammatory head mass or malignancy were included in the study for robot-assisted Frey's. Results: In our study, out of 32 patients, nine patients underwent robot assisted Frey's procedure. The duration of surgery was significantly longer in robotic group (570 minutes vs. 360 minutes, p = 0.003). The medians of intraoperative blood loss and postoperative analgesic requirement were lower in robotic group, but the difference was not statistically significant (250 mL vs. 350 mL, p = 0.400 and 3 days vs. 4 days, p = 0.200, respectively). The median length of hospital stay was shorter in the robotic group, though not significant (6 days vs. 7 days, p = 0.540). At a median follow-up of 28 months, there was no significant difference in the postoperative complications and short-term outcomes between the two groups. Conclusion: Robotic surgery offers benefits of laparoscopic surgery in addition it has better visualization, magnification, dexterity, and ergonomics. Frey's procedure is possible robotically with acceptable outcomes in selected patients.

Antithrombin III Supplementation in a Premature Infant: Is There a Target Antithrombin Level?

The optimal antithrombin (AT) activity for low-molecular-weight heparin efficacy and the benefits of antithrombin III (ATIII) supplementation in premature infants diagnosed with venous thromboembolism are unknown. Currently, there are no neonatal-specific guidelines directing the appropriate target AT activity during supplementation. This case report describes a critically ill premature infant with a progressive, occlusive inferior vena cava thrombus who received supplemental ATIII during enoxaparin treatment. The patient did not achieve therapeutic anti-Xa levels despite increasing enoxaparin dosing to 3 mg/kg every 12 hours. ATIII supplementation sufficient to attain an AT activity of >40%, in combination with an enoxaparin dosing of >2 mg/kg every 12 hours, was needed to achieve therapeutic anti-Xa levels. Future large studies are needed to determine if there is an optimal target AT activity for critically ill premature infants.

Repurposing eflornithine to treat a patient with a rare ODC1 gain-of-function variant disease.

Background: Polyamine levels are intricately controlled by biosynthetic, catabolic enzymes and antizymes. The complexity suggests that minute alterations in levels lead to profound abnormalities. We described the therapeutic course for a rare syndrome diagnosed by whole exome sequencing caused by gain-of-function variants in the C-terminus of ornithine decarboxylase (ODC), characterized by neurological deficits and alopecia. Methods: N-acetylputrescine levels with other metabolites were measured using ultra-performance liquid chromatography paired with mass spectrometry and Z-scores established against a reference cohort of 866 children. Results: From previous studies and metabolic profiles, eflornithine was identified as potentially beneficial with therapy initiated on FDA approval. Eflornithine normalized polyamine levels without disrupting other pathways. She demonstrated remarkable improvement in both neurological symptoms and cortical architecture. She gained fine motor skills with the capacity to feed herself and sit with support. Conclusions: This work highlights the strategy of repurposing drugs to treat a rare disease. Funding: No external funding was received for this work.

Chromosome arm aneuploidies shape tumour evolution and drug response.

Chromosome arm aneuploidies (CAAs) are pervasive in cancers. However, how they affect cancer development, prognosis and treatment remains largely unknown. Here, we analyse CAA profiles of 23,427 tumours, identifying aspects of tumour evolution including probable orders in which CAAs occur and CAAs predicting tissue-specific metastasis. Both haematological and solid cancers initially gain chromosome arms, while only solid cancers subsequently preferentially lose multiple arms. 72 CAAs and 88 synergistically co-occurring CAA pairs multivariately predict good or poor survival for 58% of 6977 patients, with negligible impact of whole-genome doubling. Additionally, machine learning identifies 31 CAAs that robustly alter response to 56 chemotherapeutic drugs across cell lines representing 17 cancer types. We also uncover 1024 potential synthetic lethal pharmacogenomic interactions. Notably, in predicting drug response, CAAs substantially outperform  mutations and focal deletions/amplifications combined. Thus, CAAs predict cancer prognosis, shape tumour evolution, metastasis and drug response, and may advance precision oncology.

Handlebar Hernia with Triple Herniation and Perforation: A Case Report and Literature Review.

Blunt trauma abdomen is a very common entity but traumatic abdominal wall hernia is not that common. Herniation through abdominal wall usually occurs following trauma with seat belt, motor cycle, bicycle handle bar etc. Handlebar hernia is a less known variety of traumatic abdominal wall hernia as a consequence of injury with handlebar of a bicycle. It is difficult to diagnose and one should have high index of suspicion. Management in traumatic abdominal wall hernia is individualized based on various factors. We herein present an interesting case of a14-year-old boy, who sustained blunt trauma abdomen from bicycle handlebar leading to triple herniation and perforation of the small bowel and hematoma of the mesentery. Patient was resuscitated and operated with a favorable outcome. Blunt trauma abdomen is a very common and the possibility of traumatic abdominal wall hernia should always be borne in mind.

Translocation Breakpoints Preferentially Occur in Euchromatin and Acrocentric Chromosomes.

Chromosomal translocations drive the development of many hematological and some solid cancers. Several factors have been identified to explain the non-random occurrence of translocation breakpoints in the genome. These include chromatin density, gene density and CCCTC-binding factor (CTCF)/cohesin binding site density. However, such factors are at least partially interdependent. Using 13,844 and 1563 karyotypes from human blood and solid cancers, respectively, our multiple regression analysis only identified chromatin density as the primary statistically significant predictor. Specifically, translocation breakpoints preferentially occur in open chromatin. Also, blood and solid tumors show markedly distinct translocation signatures. Strikingly, translocation breakpoints occur significantly more frequently in acrocentric chromosomes than in non-acrocentric chromosomes. Thus, translocations are probably often generated around nucleoli in the inner nucleoplasm, away from the nuclear envelope. Importantly, our findings remain true both in multivariate analyses and after removal of highly recurrent translocations. Finally, we applied pairwise probabilistic co-occurrence modeling. In addition to well-known highly prevalent translocations, such as those resulting in BCR-ABL1 (BCR-ABL) and RUNX1-RUNX1T1 (AML1-ETO) fusion genes, we identified significantly underrepresented translocations with putative fusion genes, which are probably subject to strong negative selection during tumor evolution. Taken together, our findings provide novel insights into the generation and selection of translocations during cancer development.

Discovering vesicle traffic network constraints by model checking.

A eukaryotic cell contains multiple membrane-bound compartments. Transport vesicles move cargo between these compartments, just as trucks move cargo between warehouses. These processes are regulated by specific molecular interactions, as summarized in the Rothman-Schekman-Sudhof model of vesicle traffic. The whole structure can be represented as a transport graph: each organelle is a node, and each vesicle route is a directed edge. What constraints must such a graph satisfy, if it is to represent a biologically realizable vesicle traffic network? Graph connectedness is an informative feature: 2-connectedness is necessary and sufficient for mass balance, but stronger conditions are required to ensure correct molecular specificity. Here we use Boolean satisfiability (SAT) and model checking as a framework to discover and verify graph constraints. The poor scalability of SAT model checkers often prevents their broad application. By exploiting the special structure of the problem, we scale our model checker to vesicle traffic systems with reasonably large numbers of molecules and compartments. This allows us to test a range of hypotheses about graph connectivity, which can later be proved in full generality by other methods.

Genetic characterization of Australian Mycoplasma bovis isolates through whole genome sequencing analysis.

Mycoplasma bovis is a major pathogen in cattle causing mastitis, arthritis and pneumonia. First isolated in Australian cattle in 1970, M. bovis has persisted causing serious disease in infected herds. To date, genetic analysis of Australian M. bovis isolates has not been performed. With whole genome sequencing (WGS) becoming a common tool for genetic characterization, this method was utilized to determine the degree of genetic diversity among Australian M. bovis isolates collected over a nine year period (2006-2015) from various geographical locations, anatomical sites, and from clinically affected and non-clinical carrier animals. Eighty-two M. bovis isolates underwent WGS from which single nucleotide polymorphism (SNP) analysis, comparative genomics and analysis of virulence genes was completed. SNP analysis identified a single M. bovis strain circulating throughout Australia with marked genomic similarity. Comparative genomics suggested minimal variation in gene content between isolates from clinical and carrier animals, and between isolates recovered from different anatomical sites. A total of 50 virulence genes from the virulence factors database (VFDB) were identified as highly similar in the Australian isolates, while the presence of variable surface lipoprotein (vsp) genes was greatly reduced compared to reference strain M. bovis PG45. These results highlight that, while the introduction of multiple M. bovis strains has been prevented, elimination of the current strain has not been successful. The persistence of this strain may be due to the significant role that carrier animals play in harboring the pathogen. The similarity of clinical and non-clinical isolates suggests host and environmental factors play a significant role in determining host pathogen outcomes.

Mesenteric Lymph Node Hamartoma (Castleman's Disease) in Association with Superior Mesenteric Arteriovenous Fistula.

We present a case of 21-year-old female patient with history of pain abdomen and abdominal distension. The patient also had oedema of the limbs, puffiness of the face, pallor and palpable mass in the abdomen. Ultrasonography of the abdomen and computed tomographic angiogram was done and it showed presence of vascular mass along with arteriovenous malformation in the mesentry of small gut between distal branches of superior mesenteric artery and vein. Surgical excision of the mass with ligation and division of the arteriovenous malformation was done through midline laparotomy. Histopathological examination was consistent with the diagnosis of Castleman's disease. The Patient recovered well and was discharged after seven days.

Targeting lipid esterases in mycobacteria grown under different physiological conditions using activity-based profiling with tetrahydrolipstatin (THL).

Tetrahydrolipstatin (THL) is bactericidal but its precise target spectrum is poorly characterized. Here, we used a THL analog and activity-based protein profiling to identify target proteins after enrichment from whole cell lysates of Mycobacterium bovis Bacillus Calmette-Guérin cultured under replicating and non-replicating conditions. THL targets α/ß-hydrolases, including many lipid esterases (LipD, G, H, I, M, N, O, V, W, and TesA). Target protein concentrations and total esterase activity correlated inversely with cellular triacylglycerol upon entry into and exit from non-replicating conditions. Cellular overexpression of lipH and tesA led to decreased THL susceptibility thus providing functional validation. Our results define the target spectrum of THL in a biological species with particularly diverse lipid metabolic pathways. We furthermore derive a conceptual approach that demonstrates the use of such THL probes for the characterization of substrate recognition by lipases and related enzymes.