Miracle-dz/UniFAR-FTUs huggingface dataset:
20.10 A 68.1-to-96.4GHz variable-gain low-noise amplifier in 28nm CMOS

To allow a maximum theoretical data-rate of 25Gb/s over a 1km distance using 64QAM, an E-Band system should feature a 20dBm-output-power TX and an RX with 10dB maximum noise figure (NF) over two bands of 5GHz from 71 to 76GHz and 81 to 86GHz [1]. To minimize the NF of a fully integrated RX front-end and to compensate for the low conversion gain and high noise of the following mixer, a broadband LNA with a gain in excess of 20dB showing a flat NF over more than a 15GHz bandwidth is required. Moreover, a variable-gain LNA design would be beneficial to accommodate environmental variability (e.g. atmospherics condition, rain, etc.). Prior works on CMOS car-radar transceivers have shown the feasibility of low-noise amplifiers at 79GHz. However, the bandwidth of these systems is limited to about 10GHz [2,3], which is not enough. This paper presents a 28nm-bulk-CMOS LNA for E-Band applications that employs transformer-based 4th-order inter-stage matching networks to achieve a 29.6dB gain over a 28.3GHz -3dB bandwidth (BW-3dB), resulting in a GBW product in excess of 0.8THz. The gain is variable from 29.6 to 18dB allowing an input-referred 1dB compression point (ICP1dB) that ranges from -28.1dBm at the highest gain to -12.3dBm at the lowest gain. The measured minimum in-band NF is 6.4dB, and the NF varies by less than 2dB from 68.1 to 90GHz. The LNA covers the two bands from 71 to 76GHz and from 81 to 86GHz with an almost uniform gain and NF and with a wide margin over desired specifications to compensate for PVT variations and model inaccuracy.
A novel Cd8‐cis‐regulatory element preferentially directs expression in CD44hiCD62L+ CD8+ T cells and in CD8αα+ dendritic cells

CD8 coreceptor expression is dynamically regulated during thymocyte development and is tightly controlled by the activity of at least 5 different cis‐regulatory elements. Despite the detailed characterization of the Cd8 loci, the regulation of the complex expression pattern of CD8 cannot be fully explained by the activity of the known Cd8 enhancers. In this study, we revisited the Cd8ab gene complex with bioinformatics and transgenic reporter gene expression approaches to search for additional Cd8 cis‐regulatory elements. This led to the identification of an ECR (ECR‐4), which in transgenic reporter gene expression assays, directed expression preferentially in CD44hiCD62L+ CD8+ T cells, including innate‐like CD8+ T cells. ECR‐4, designated as Cd8 enhancer E8VI, was bound by Runx/CBFβ complexes and Bcl11b, indicating that E8VI is part of the cis‐regulatory network that recruits transcription factors to the Cd8ab gene complex in CD8+ T cells. Transgenic reporter expression was maintained in LCMV‐specific CD8+ T cells upon infection, although short‐term, in vitro activation led to a down‐regulation of E8VI activity. Finally, E8VI directed transgene expression also in CD8αα+ DCs but not in CD8αα‐expressing IELs. Taken together, we have identified a novel Cd8 enhancer that directs expression in CD44hiCD62L+ CD8+ T cells, including innate‐like and antigen‐specific effector/memory CD8+ T cells and in CD8αα+ DCs, and thus, our data provide further insight into the cis‐regulatory networks that control CD8 expression.
26.7 A 10mm3 syringe-implantable near-field radio system on glass substrate

We present a millimeter-scale near-field radio system for ultra-low-power (ULP) healthcare sensor nodes. It is specifically designed for `syringe implantation' which minimizes invasiveness of implantation. Designing a millimeter-scale wireless node for implanted healthcare is challenging because: 1) the antenna is constrained to the diameter of the syringe needle, which significantly constrains the link distance through RF. 2) The energy/power are strictly limited by the millimeter-scale form-factor where thin-film batteries can source only <;10μAh and sustain <;50μA peak current. Recent works [1-4] have demonstrated near-field transceivers for millimeter-scale implants. Passive backscatter radios consume low power but they are only operable at very short distances (e.g., 3.5cm) due to excessive path loss and self-jamming at the reader [1-2]. Although active radios can provide >10cm distance, their high power consumption (45mW [3]) and/or large antenna size (2.3cm×2.4cm [4]) make them impractical for implanted healthcare applications.
microRNAs function in CD8+T cell biology

During an immune response, CD8+T cells can differentiate into multiple types of effector and memory cells that are important components of immune surveillance. However, their dysregulation has been implicated in infection with viruses or intracellular bacteria and tumorigenesis. miRNAs have been identified as crucial regulators of gene expression, and they perform this function by repressing specific target genes at the post‐transcriptional level. Most miRNAs expressed in a given cell type serve the function to impede broadly cell‐type‐inappropriate gene expression and potently deepen a pre‐existing differentiation program. It is increasingly recognized that miRNAs directly modulate the concentration of many regulatory proteins that are required for the development of immune cells in the thymus and their responses in the periphery. This review outlines our current understanding of the function of miRNAs in CD8+T cell biology as it impacts expression of protein‐coding genes in the context of proper development, infection, as well as oncogenesis. In addition, we conclude with a perspective on future challenges and the clinical relevance of miRNA biology.
Shipping living donor kidneys and transplant recipient outcomes

Kidney paired donation (KPD) is an important tool to facilitate living donor kidney transplantation (LDKT). Concerns remain over prolonged cold ischemia times (CIT) associated with shipping kidneys long distances through KPD. We examined the association between CIT and delayed graft function (DGF), allograft survival, and patient survival for 1267 shipped and 205 nonshipped/internal KPD LDKTs facilitated by the National Kidney Registry in the United States from 2008 to 2015, compared to 4800 unrelated, nonshipped, non‐KPD LDKTs. Shipped KPD recipients had a median CIT of 9.3 hours (range = 0.25‐23.9 hours), compared to 1.0 hour for internal KPD transplants and 0.93 hours for non‐KPD LDKTs. Each hour of CIT was associated with a 5% increased odds of DGF (adjusted odds ratio: 1.05, 95% confidence interval [CI], 1.02‐1.09, P < .01). However, there was not a significant association between CIT and all‐cause graft failure (adjusted hazard ratio [aHR]: 1.01, 95% CI: 0.98‐1.04, P = .4), death‐censored graft failure ( [aHR]: 1.02, 95% CI, 0.98‐1.06, P = .4), or mortality (aHR 1.00, 95% CI, 0.96‐1.04, P > .9). This study of KPD‐facilitated LDKTs found no evidence that long CIT is a concern for reduced graft or patient survival. Studies with longer follow‐up are needed to refine our understanding of the safety of shipping donor kidneys through KPD.
Anti‐inflammatory roles of p38α MAPK in macrophages are context dependent and require IL‐10

The p38 MAPK pathway was originally identified as a master regulator of proinflammatory cytokine production by myeloid cells. Numerous drugs targeting this kinase showed promise in preclinical models of inflammatory disease, but so far, none have shown efficacy in clinical trials. The reasons behind this are unclear, but may, in part, be explained by emerging anti‐inflammatory functions of this kinase or overly refined selectivity of second‐generation pharmacologic inhibitors. Here, we show that p38α signaling in macrophages plays pro‐ and anti‐inflammatory functions in vivo and in vitro, with the outcome depending on the stimulus, output, kinetics, or mode of kinase inhibition (genetic vs. pharmacologic). Different pharmacologic inhibitors of p38 exhibit opposing effects, with second‐generation inhibitors acting more specifically but inhibiting anti‐inflammatory functions. Functionally, we show that the anti‐inflammatory functions of p38α in macrophages are critically dependent on production of IL‐10. Accordingly, in the absence of IL‐10, inhibition of p38α signaling in macrophages is protective in a spontaneous model of colitis. Taken together, our results shed light on the limited clinical efficacy of drugs targeting p38 and suggest that their therapeutic efficacy can be significantly enhanced by simultaneous modulation of p38‐dependent anti‐inflammatory mediators, such as IL‐10.
Observations on the ex situ perfusion of livers for transplantation

Normothermic ex situ liver perfusion might allow viability assessment of livers before transplantation. Perfusion characteristics were studied in 47 liver perfusions, of which 22 resulted in transplants. Hepatocellular damage was reflected in the perfusate transaminase concentrations, which correlated with posttransplant peak transaminase levels. Lactate clearance occurred within 3 hours in 46 of 47 perfusions, and glucose rose initially during perfusion in 44. Three livers required higher levels of bicarbonate support to maintain physiological pH, including one developing primary nonfunction. Bile production did not correlate with viability or cholangiopathy, but bile pH, measured in 16 of the 22 transplanted livers, identified three livers that developed cholangiopathy (peak pH < 7.4) from those that did not (pH > 7.5). In the 11 research livers where it could be studied, bile pH > 7.5 discriminated between the 6 livers exhibiting >50% circumferential stromal necrosis of septal bile ducts and 4 without necrosis; one liver with 25‐50% necrosis had a maximum pH 7.46. Liver viability during normothermic perfusion can be assessed using a combination of transaminase release, glucose metabolism, lactate clearance, and maintenance of acid‐base balance. Evaluation of bile pH may offer a valuable insight into bile duct integrity and risk of posttransplant ischemic cholangiopathy.
Association of eukaryotic translation initiation factor eIF2B with fully solubilized CXCR4

Chemokine receptors are key regulators of leukocyte trafficking but also have an important role in development, tumor growth, and metastasis. Among the chemokine receptors, CXCR4 is the only one that leads to perinatal death when genetically ablated in mice, indicating a more‐widespread function in development. To identify pathways that are activated downstream of CXCR4, a solubilization protocol was elaborated, which allows for the isolation of the endogenous receptor from human cells in its near‐native conformation. Solubilized CXCR4 is recognized by the conformation‐sensitive monoclonal antibody 12G5 and retains the ability to bind CXCL12 in solution, which was abolished in the presence of receptor antagonists. Mass spectrometry of CXCR4 immunoprecipitates revealed a specific interaction with the pentameric eukaryotic translation initiation factor 2B. The observation that the addition of CXCL12 leads to the dissociation of eukaryotic translation initiation factor 2B from CXCR4 suggests that stimulation of the receptor may trigger the local protein synthesis required for efficient cell movement.
Novel transglutaminase-1 mutations and genotype–phenotype investigations of 104 patients with autosomal recessive congenital ichthyosis in the USA

Background: Autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary disorder of cornification. Mutations in the transglutaminase-1 (TGM1) gene, which encodes for the epidermal enzyme transglutaminase-1 (TGase-1), are one of the causes of ARCI. Methods: The TGM1 mutation spectrum was characterised and genotype–phenotype correlations investigated in 104 patients with ARCI ascertained through the National Registry for Ichthyosis and Related Disorders in the USA. Methods: Germline mutations in TGM1 were identified in 55% (57/104) of patients with ARCI. Arginine residues in TGase-1 were mutated in 39% (22/57) of patients overall and 54% (20/37) of those with missense mutations. In total, 55% (12/22) of missense mutations were within CpG dinucleotides and 92% (11/12) of these mutations were C→T or G→A transitions. The genotype–phenotype investigation found that ARCI with TGM1 mutations was significantly associated with presence of collodion membrane at birth (p = 0.006), ectropion (p = 0.001), plate-like scales (p = 0.005) and alopecia (p = 0.001). Patients who had at least one mutation predicted to truncate TGase-1 were more likely to have more severe hypohidrosis (p = 0.001) and overheating (p = 0.0007) at onset of symptoms than were those with exclusively TGM1 missense mutations. A logistic model was developed, which predicted that individuals with collodion membrane, alopecia and/or eye problems are about four times more likely to have TGM1 mutations than patients without these findings. Conclusion: This is the largest investigation of patients with ARCI to date. It expands the TGM1 mutation spectrum and confirms that despite genetic and phenotypic heterogeneity in ARCI, TGM1 is the main causative gene for this disorder. The high frequency of mutated arginine codons in TGM1 may be due to the deamination of CpG dinucleotides.
Conservative management of a large rotator cuff tear to increase functional abilities: A case report

The purpose of this case report was to explore the application of conservative management in an individual with a large rotator cuff tear. Often patients with such an extensive injury are recommended for surgery. The patient was a 76-years-old female with a primary diagnosis of a large tear in the supraspinatus, after falling down her steps. The patient underwent physical therapy 3 times a week for 7 weeks (19 visits). The interventions consisted of modalities and therapeutic exercise. Outcome measures included the Shoulder pain and Disability Index (SPADI), and the Short Form-12 (SF-12). Each was implemented at the initial examination, 3 1/2 weeks, and 7 weeks. The SPADI increased, showing a 78% improvement in function. There was an overall increase in the physical component scale of the SF-12 by the 7th week, showing an 86% increase from the initial score. The use of conservative treatment may be an effective method for restoring function in patients with large rotator cuff tears. The great percentile changes as shown by the outcome measures suggests overall functional improvements in this patient. There have been few studies to support the use of conservative treatment for patients with large rotator cuff tears. However, further research needs to be done on this type of intervention with different levels of pre-injury function.
Phagocytosis of apoptotic or necrotic cells differentially regulates the transcriptional expression of IL‐12 family members in dendritic cells

Uptake of apoptotic cells by DCs is considered to contribute to induction and maintenance of immunological tolerance. TolDCs are sought after as cellular therapy in transplantation and autoimmunity and can be generated in vitro using GCs. In this study, we investigated how uptake of dead cells affects the production and expression of different members of the IL‐12 family by immature DCs or TolDCs. We show that compared to regular immature DCs, TolDCs display elevated levels of PS‐recognizing bridge molecule receptors αvβ5 and CD36, and have enhanced phagocytic abilities with accelerated uptake of apoptotic cells. We confirm that apoptotic cell uptake results in diminished production of IL‐12p40 and IL‐12p70 by DCs. We now show that this also results in increased expression of IL‐12p35 and Ebi3. TolDCs completely lack expression of IL‐12p40 yet have enhanced levels of Ebi3 and IL‐12p35. Uptake by TolDCs of apoptotic or necrotic cells does not affect the expression of Ebi3/IL‐12p35 and also does not increase IL‐12p40. This is distinct from the culture of immature DCs with necrotic cells, which is sufficient to induce IL‐12p40 secretion. Conversely, ingestion of apoptotic cells by DCs leads to increased expression of IL‐12p35 and Ebi3 without affecting IL‐12p40. In conclusion, we have shown that uptake of apoptotic versus necrotic cells by DCs differentially regulates members of the IL‐12 family. Apoptotic cells favor expression of Ebi3 and IL‐12p35, and we propose that differential regulation of the IL‐12 family is an additional mechanism in determining the immune response to dying cells.
Sexual dimorphisms in leukocyte trafficking in a mouse peritonitis model

Sexual dimorphisms exist in the incidence and severity of many diseases, with females demonstrating relative protection from inflammatory conditions. The extent and mechanisms by which excessive leukocyte recruitment underlies these differences are not well established, and better understanding is essential for the development of targeted therapies. Here, we set out to compare the male and female inflammatory response in a murine zymosan‐induced peritonitis model and to understand how leukocyte subsets are mobilized from storage pools in both sexes. This work shows that female C57BL/6 mice recruit fewer classical monocytes and neutrophils during zymosan‐induced peritonitis. In addition, sex differences were evident in the circulation, as female mice showed reduced neutrophilia and monocytosis vs. male counterparts, despite having similar mobilization from BM stores. Importantly, we show that storage and trafficking of splenic leukocytes during acute inflammation are distinct between the sexes. Male mice have greater splenic stores of neutrophils and classical and nonclassical monocytes, despite similar spleen sizes, signifying another source of potential pathogenic leukocytes. This work demonstrates that males and females have distinct leukocyte‐trafficking profiles in acute inflammation and suggests that the spleen, not the BM, plays a role in determining sex differences in the available pool of immune cells. Such dimorphisms demonstrate the importance of considering gender in assay development, drug design, and clinical trials.
Polymorphisms at 16p13 are associated with systemic lupus erythematosus in the Chinese population

Background Chromosomal region 16p13 has been reported to harbour variants associated with several autoimmune diseases, including type I diabetes, rheumatoid arthritis and multiple sclerosis. Objective To test whether variants in the 16p13 region are also associated with systemic lupus erythematosus (SLE) by performing a candidate locus study in the Chinese Han population. Methods Tag single nucleotide polymorphisms (SNPs) encompassing 50 kb upstream and downstream of the 250 kb linkage disequilibrium block, previously implicated in several autoimmune diseases, were analysed in 1047 patients with SLE and 1205 controls. The SNP showing the strongest association with SLE was then replicated in an independent cohort of 1643 cases and 5930 controls. Results and conclusions The association between SNP rs12599402 and SLE reached the genome-wide significance level (p<5 × 10−8). The SNP was likely to tag the same functional variant as previously reported in European populations. The results suggested that the chromosomal region at 16p13 contains common susceptibility genes for different immune-mediated disorders.
Overexpression of progelatinase B/proMMP‐9 affects migration regulatory pathways and impairs chronic lymphocytic leukemia cell homing to bone marrow and spleen

This study addresses the role of (pro)MMP‐9 overexpression in CLL cell migration. We have used primary CLL cells and CLL‐derived MEC‐1 cells transfected with empty (mock cells) or proMMP‐9‐encoding (MMP‐9 cells) lentiviral vectors. The constitutive (pro)MMP‐9 expression in mock cells and primary CLL cells was similar, whereas in MMP‐9 cells, expression resembled that of CLL cells incubated with proMMP‐9. In xenograft models, in NOD/SCID mice, MMP‐9‐MEC‐1 transfectants showed significantly reduced homing to bone marrow and spleen compared with mock cells. Likewise, incubation of primary CLL cells with proMMP‐9, before injection into mice, inhibited their homing to these organs. This inhibition was specific, dose‐dependent, and observed in all CLL tested, independently of prognostic markers or disease stage. Additionally, the MMP‐9 catalytic activity was only partially involved, as the inactive mutant proMMP‐9MutE had a partial effect. MMP‐9 cells also showed impaired migration in vitro, which was reverted by reducing (pro)MMP‐9 expression with siRNAs. CLL migration thus requires optimal (pro)MMP‐9 expression levels, below or above which migration is hampered. Biochemical analysis of the (pro)MMP‐9 effect indicated that MMP‐9 cells or primary CLL cells incubated with proMMP‐9 had reduced activation of migration regulatory molecules, including RhoAGTPase, Akt, ERK, and FAK. In contrast, p190RhoGAP (RhoA inhibitor) and PTEN (Akt/ERK/FAK inhibitor) were up‐regulated in MMP‐9 cells. Reduction of (pro)MMP‐9 expression by siRNAs restored RhoA activity and diminished PTEN levels. Our results reveal a novel function for (pro)MMP‐9 in modulating signaling pathways leading to CLL cell arrest. Therefore, local high (pro)MMP‐9 expression may contribute to malignant cell retention in lymphoid organs and disease progression.
Uptake of breast cancer prevention and screening trials

Background Uptake of cancer trials and in particular prevention trials has been disappointing globally. Methods Uptake to three randomised chemotherapy breast cancer prevention trials and two dietary prevention trials in women at increased familial risk were assessed and compared with uptake of screening trials across a range of risk categories. Results Uptake of drug prevention trials remains low at 5.3–13.6%, but is significantly higher in the high (12%) compared to very high risk group (8.4%) for IBIS1 and IBIS2 combined (p=0.004). Recruitment to two dietary prevention studies via mail shot was also disappointingly low at 6.2% and 12.5%. In contrast uptake to two mammography screening trials was >90% in all risk categories. Conclusions More work must be done to improve recruitment to prevention trials if they are to be seen as viable alternatives to risk reducing surgery. Impact Trial designs and decision aids need to be developed to improve recruitment.
Cranial meningiomas in 411 neurofibromatosis type 2 (NF2) patients with proven gene mutations: clear positional effect of mutations, but absence of female severity effect on age at onset

Background Meningiomas have been reported to occur in approximately 50% of neurofibromatosis type 2 (NF2) patients. The NF2 gene is commonly biallelically inactivated in both schwannomas and meningiomas. The spectrum of NF2 mutations consists mainly of truncating (nonsense and frameshift) mutations. A smaller number of patients have missense mutations, which are associated with a milder disease phenotype. Methods This study analysed the cumulative incidence and gender effects as well as the genotype–phenotype correlation between the position of the NF2 mutation and the occurrence of cranial meningiomas in a cohort of 411 NF2 patients with proven NF2 mutations. Results and conclusion Patients with mutations in exon 14 or 15 were least likely to develop meningiomas. Cumulative risk of cranial meningioma to age 50 years was 70% for exons 1–3, 81% for exons 4–6, 49% for exons 7–9, 56% for exons 10–13, and 28% for exons 14–15. In the cohort of 411 patients, no overall gender bias was found for occurrence of meningioma in NF2 disease. Cumulative incidence of meningioma was close to 80% by 70 years of age for both males and females, but incidence by age 20 years was slightly increased in males (male 25%, female 18%; p=0.023). Conversely, an increased risk of meningiomas in women with mosaic NF2 disease was also found.