GENCODE: reference annotation for the human and mouse genomes in 2023.

GENCODE produces high quality gene and transcript annotation for the human and mouse genomes. All GENCODE annotation is supported by experimental data and serves as a reference for genome biology and clinical genomics. The GENCODE consortium generates targeted experimental data, develops bioinformatic tools and carries out analyses that, along with externally produced data and methods, support the identification and annotation of transcript structures and the determination of their function. Here, we present an update on the annotation of human and mouse genes, including developments in the tools, data, analyses and major collaborations which underpin this progress. For example, we report the creation of a set of non-canonical ORFs identified in GENCODE transcripts, the LRGASP collaboration to assess the use of long transcriptomic data to build transcript models, the progress in collaborations with RefSeq and UniProt to increase convergence in the annotation of human and mouse protein-coding genes, the propagation of GENCODE across the human pan-genome and the development of new tools to support annotation of regulatory features by GENCODE. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org.

Evaluation of different isotope dilution mass spectrometry strategies for the characterization of naturally abundant and isotopically labelled peptide standards.

Natural abundance and isotopically labelled tryptic peptides are routinely employed as standards in quantitative proteomics. The certification of the peptide content is usually carried out by amino acid analysis using isotope dilution mass spectrometry (IDMS) after the acid hydrolysis of the peptide. For the validation and traceability of the amino acid analysis procedure, expensive certified peptides must be employed. In this work we evaluate different IDMS alternatives which will reduce the amount of certified peptide required for validation of the amino acid analysis procedure. In this context, the characterization of both natural and isotopically labelled synthetic angiotensin I peptides was carried out. First, we applied a fast procedure for peptide hydrolysis based on microwave-assisted digestion and employed two certified peptide reference materials SRM 998 angiotensin I and CRM 6901-b C-peptide for validation of the hydrolysis procedure. The amino acids proline, leucine, isoleucine, valine, tyrosine, arginine and phenylalanine were evaluated for their suitability for peptide certification by IDMS by both liquid chromatography with tandem mass spectrometry (LC-MS/MS) and gas chromatography with mass spectrometry (GC)-MS/MS. Then, natural angiotensin I and 13C1-labelled angiotensin I were synthesized in-house and purified by preparative liquid chromatography. The concentration of the 13C1-labelled angiotensin I peptide was established by reverse IDMS in its native form using SRM 998 angiotensin I as reference. The concentration of the natural synthesized peptide was determined by IDMS both using the 13C1-labelled peptide in its native form and by amino acid analysis showing comparable results. Finally, the synthetic naturally abundant angiotensin I peptide was employed as "in-house" standard for the validation of subsequent peptide characterization procedures. Therefore, the novelty of this work relies on, first, the development of a faster hydrolysis procedure assisted by focused microwaves, providing complete hydrolysis in 150 min, and secondly, a validation strategy combining GC-MS and LC-MS/MS that allowed us to certify the purity of an in-house-synthesized peptide standard that can be employed as quality control in further experiments.

GENCODE 2021.

The GENCODE project annotates human and mouse genes and transcripts supported by experimental data with high accuracy, providing a foundational resource that supports genome biology and clinical genomics. GENCODE annotation processes make use of primary data and bioinformatic tools and analysis generated both within the consortium and externally to support the creation of transcript structures and the determination of their function. Here, we present improvements to our annotation infrastructure, bioinformatics tools, and analysis, and the advances they support in the annotation of the human and mouse genomes including: the completion of first pass manual annotation for the mouse reference genome; targeted improvements to the annotation of genes associated with SARS-CoV-2 infection; collaborative projects to achieve convergence across reference annotation databases for the annotation of human and mouse protein-coding genes; and the first GENCODE manually supervised automated annotation of lncRNAs. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org.

Chiral Ligands Based on Binaphthyl Scaffolds for Pd-Catalyzed Enantioselective C-H Activation/Cycloaddition Reactions.

We report the first examples of the use of a new class of ligands (NOBINAc) for performing asymmetric C-H activations using palladium catalysts. These ligands combine the axial chirality of binaphthyl scaffolds with the bifunctional and bidentate coordination properties of mono-N-protected amino acids (MPAAs), which are well-known to favor Pd-promoted C-H activations via concerted metalation-deprotonation mechanisms. We demonstrate that our new ligands enable substantially higher enantioselectivities than MPAAs in the assembly of 2-benzazepines through formal (5 + 2) cycloadditions between homobenzyltriflamides or o-methylbenzyltriflamides and allenes.

Discovery of high-confidence human protein-coding genes and exons by whole-genome PhyloCSF helps elucidate 118 GWAS loci.

The most widely appreciated role of DNA is to encode protein, yet the exact portion of the human genome that is translated remains to be ascertained. We previously developed PhyloCSF, a widely used tool to identify evolutionary signatures of protein-coding regions using multispecies genome alignments. Here, we present the first whole-genome PhyloCSF prediction tracks for human, mouse, chicken, fly, worm, and mosquito. We develop a workflow that uses machine learning to predict novel conserved protein-coding regions and efficiently guide their manual curation. We analyze more than 1000 high-scoring human PhyloCSF regions and confidently add 144 conserved protein-coding genes to the GENCODE gene set, as well as additional coding regions within 236 previously annotated protein-coding genes, and 169 pseudogenes, most of them disabled after primates diverged. The majority of these represent new discoveries, including 70 previously undetected protein-coding genes. The novel coding genes are additionally supported by single-nucleotide variant evidence indicative of continued purifying selection in the human lineage, coding-exon splicing evidence from new GENCODE transcripts using next-generation transcriptomic data sets, and mass spectrometry evidence of translation for several new genes. Our discoveries required simultaneous comparative annotation of other vertebrate genomes, which we show is essential to remove spurious ORFs and to distinguish coding from pseudogene regions. Our new coding regions help elucidate disease-associated regions by revealing that 118 GWAS variants previously thought to be noncoding are in fact protein altering. Altogether, our PhyloCSF data sets and algorithms will help researchers seeking to interpret these genomes, while our new annotations present exciting loci for further experimental characterization.

Mechanically Reconfigurable Waveguide Filter Based on Glide Symmetry at Millimetre-Wave Bands.

This paper presents the design and fabrication of a mechanically reconfigurable filter at W band based on the concept of glide symmetry. The tunability is achieved by breaking and regenerating the glide symmetry. The filters are made of two glide-symmetric pieces that can be displaced in a certain direction, and therefore, break the symmetry. The high filtering capacity of these designs is demonstrated by simulation and measurement and can also be adjusted mechanically. The transmission level in the manufactured filter varies from a value between -1 and -2 dB when the filter is in the glide symmetry position to values close to -40 dB in the stop-band when it is in the broken symmetry position. The transmission band obtained in the symmetrical mode is around 20%, but, after breaking the symmetry, it is split into two passbands of 6.5% and 11% separated by a stop-band of 6%. The position, bandwidth, filtering level and filter roll-off can be adjusted for both modes of operation by appropriately selecting the unit cell design parameters and the number of unit cells.

3D Inductive Frequency Selective Structures Using Additive Manufacturing and Low-Cost Metallization.

The use of additive manufacturing and different metallization techniques for prototyping radio frequency components such as antennas and waveguides are rising owing to their high precision and low costs. Over time, additive manufacturing has improved so that its utilization is accepted in satellite payloads and military applications. However, there is no record of the frequency response in the millimeter-wave band for inductive 3D frequency selective structures implemented by different metallization techniques. For this reason, three different prototypes of dielectric 3D frequency selective structures working in the millimeter-wave band are designed, simulated, and manufactured using VAT photopolymerization. These prototypes are subsequently metallized using metallic paint atomization and electroplating. The manufactured prototypes have been carefully selected, considering their design complexity, starting with the simplest, the square aperture, the medium complexity, the woodpile structure, and the most complex, the torus structure. Then, each structure is measured before and after the metallization process using a measurement bench. The metallization used for the measurement is nickel spray flowed by the copper electroplating. For the electroplating, a detailed table showing the total area to be metallized and the current applied is also provided. Finally, the effectiveness of both metallization techniques is compared with the simulations performed using CST Microwave Studio. Results indicate that a shifted and reduced band-pass is obtained in some structures. On the other hand, for very complex structures, as in the torus case, band-pass with lower loss is obtained using copper electroplating, thus allowing the manufacturing of inductive 3D frequency selective structures in the millimeter-wave band at a low cost.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations for Surgical Technique for Spinal Cord Stimulation.

INTRODUCTION: The field of neurostimulation for the treatment of chronic pain is a rapidly developing area of medicine. Although neurostimulation therapies have advanced significantly as a result of technologic improvements, surgical planning, device placement, and postoperative care are of equal importance to optimize outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for these often-overlooked areas of neurostimulation practice. MATERIALS AND METHODS: Authors were chosen based on their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from the last NACC publication in 2017 to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on evidence strength and consensus when evidence was scant. RESULTS: This NACC project provides guidance on preoperative assessment, intraoperative techniques, and postoperative management in the form of consensus points with supportive evidence. These results are based on grade of evidence, strength of consensus, and expert opinion. CONCLUSIONS: The NACC has given guidance for a surgical plan that encompasses the patient journey from the planning stage through the surgical experience and postoperative care. The overall recommendations are designed to improve efficacy and the safety of patients undergoing these neuromodulation procedures and are intended to apply throughout the international community.

A New, Conservative Treatment for Perianal Fistula that May Halve the Need for Surgical Intervention: Case Series.

PURPOSE: In the last two decades, many sphincter preservation techniques have been proposed for the treatment of anal fistula. Since 2011, our surgical team has treated fistulas by sealing them with platelet-rich fibrin (PRF). This is performed actually as an outpatient process, without anaesthesia. METHODS: Patients were treated with PRF sealant, during the period June 2012-March 2017. The fibrin preparation is applied in the fistulous tract, with no need for any type of anaesthesia, and so the patient can go home immediately afterwards, without further observation. RESULTS: After an average follow-up of 26.49 months, the perianal fistula had healed completely in 52.86% of the patients (n = 37), who each received an average of 1.92 sealant operations. In another 10 cases, the sealing was initially successful, but a relapse occurred during the follow-up period. CONCLUSION: The outpatient treatment of perianal fistula with PRF is totally harmless, is very low cost and achieves very acceptable results. In our opinion, therefore, this could be considered an appropriate initial treatment for perianal fistula, with surgical treatment being reserved if this approach is unsuccessful, thereby avoiding many complications and producing significant economic savings for the health system.

Kinetic Resolution of Allyltriflamides through a Pd-Catalyzed C-H Functionalization with Allenes: Asymmetric Assembly of Tetrahydropyridines.

Enantioenriched, six-membered azacycles are essential structural motifs in many products of pharmaceutical or agrochemical interest. Here we report a simple and practical method for enantioselective assembly of tetrahydropyridines, which is paired to a kinetic resolution of α-branched allyltriflamides. The reaction consists of a formal (4+2) cycloaddition between the allylamine derivatives and allenes and is initiated by a palladium(II)-catalyzed C-H activation process. Both the chiral allylamide precursors and the tetrahydropyridine adducts were successfully obtained in high yields, with excellent enantioselectivity (up to 99% ee) and selectivity values of up to 127.

Complex spectral filters in silicon waveguides based on cladding-modulated Bragg gratings.

Spectral filters are important building blocks for many applications in integrated photonics, including datacom and telecom, optical signal processing and astrophotonics. Sidewall-corrugated waveguide grating is typically the preferred option to implement spectral filters in integrated photonic devices. However, in the high-index contrast silicon-on-insulator (SOI) platform, designs with corrugation sizes of only a few tens of nanometers are often required, which hinders their fabrication. In this work, we propose a novel geometry to design complex Bragg filters with an arbitrary spectral response in silicon waveguides with laterally coupled Bragg loading segments. The waveguide core is designed to operate with a delocalized mode field, which helps reduce sensitivity to fabrication errors and increase accuracy on synthesized coupling coefficients and the corresponding spectral shape control. We present an efficient design strategy, based on the layer-peeling and layer-adding algorithms, that allows to readily synthesize an arbitrary target spectrum for our cladding-modulated Bragg gratings. The proposed filter concept and design methodology are validated by designing and experimentally demonstrating a complex spectral filter in an SOI platform, with 20 non-uniformly spaced spectral notches with a 3-dB linewidth as small as 210 pm.

Added value of cerebrospinal fluid multimarker analysis in diagnosis and progression of dementia.

BACKGROUND AND PURPOSE: Recently, some emerging cerebrospinal fluid (CSF) markers have been proposed as diagnostic tools for Alzheimer disease (AD) that can have an effect on disease progression. We analyze the accuracy of these CSF markers for diagnosis of AD in reference to brain amyloid positron emission tomography (PET). We also investigated whether they help in differentiating AD from other dementias and examined their influence in tracing the progression to dementia. METHODS: Amyloid-ß (Aß) 1-42, total tau (t-tau), phosphorylated tau, Aß40 , Aß38 , beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1), neurogranin (ng), phosphorylated neurofilament heavy-chain, and α-synuclein (α-syn) CSF levels were analyzed in 319 subjects, among whom 57 also underwent an amyloid PET scan. We also analyzed longitudinal clinical data from 239 subjects. RESULTS: Emerging CSF markers, especially ng/BACE-1 ratio (area under the curve = 0.77) and their combinations with core AD CSF markers (all AUCs >0.85), showed high accuracy to discriminate amyloid PET positivity. Subjects with AD had higher CSF BACE-1, ng, and α-syn levels than those with non-AD dementia. CSF t-tau/α-syn ratio was higher in subjects with dementia with Lewy bodies than in those with frontotemporal dementia. Most emerging/core AD ratios predicted a faster conversion from mild cognitive impairment (MCI) stage to AD and appeared to be helpful when core AD CSF markers were discordant. In addition, the rate of cognitive decline was associated with all CSF core AD markers, several emerging/core AD two-marker ratios, and CSF ng levels. CONCLUSIONS: These results suggest that emerging biomarkers in conjunction with core AD markers improve diagnosis of AD, are associated with the conversion from MCI into AD, and predict a faster progression of dementia.

Sexual segregation in the foraging behaviour of a slightly dimorphic seabird: Influence of the environment and fishery activity.

Sexual segregation in foraging strategies has been little studied in marine species with slight sexual size dimorphism (SSD), particularly regarding the role of environmental conditions and fishery activities. Sexual differences in fishery attendance are of particular concern because uneven mortality associated with bycatch may exacerbate impacts in wildlife populations. Using a seabird species with slight SSD, the Scopoli's shearwater Calonectris diomedea, we assessed sexual differences in foraging strategies and evaluated whether annual environmental conditions and fishery activity shaped such differences. We used a 4-year dataset combining bird GPS tracking, stable isotope analysis, the North Atlantic Oscillation index (NAO, as main proxy of the annual environmental conditions), and fishing vessel positioning data (Vessel Monitoring System, VMS) from the North Western Mediterranean, a region under intense fishery pressure. From 2012 to 2015, we tracked 635 foraging trips from 78 individuals. Females showed a greater foraging effort, a lower fishery attendance, a lower trophic level, and a narrower isotopic niche width than males. Moreover, in years with unfavourable environmental conditions, both sexes showed a lower fishery attendance and increased foraging effort compared to the year with most favourable conditions. Our results revealed that environmental conditions influence space use, feeding resources and fishery attendance differently in males and females, overall suggesting competitive exclusion of females by males from main foraging areas and feeding resources, particularly in unfavourable environmental conditions. We highlight the importance of evaluating sexual segregation under disparate environmental conditions, particularly in species with slight SSD, since segregation may pass otherwise unnoticed if only years with similar environmental conditions are considered. The higher fishery attendance of males likely explains the male-biased bycatch ratio for this species. Thus, inter-sexual differences in foraging strategies can lead to an unbalanced exposure to relevant threats and have implications for the conservation of long-lived species.

La segregación sexual en especies con dimorfismo sexual poco acusado ha sido escasamente estudiada, particularmente en relación al papel de las condiciones ambientales y las pesquerías en las estrategias de búsqueda de alimento. Diferencias entre sexos en la asociación con pesquerías son de especial interés, ya que el impacto de las capturas accidentales sobre la dinámica poblacional podría magnificarse. En este trabajo exploramos las diferencias entre sexos en las estrategias de búsqueda de alimento en la pardela cenicienta (Calonectris diomedea) en el noroeste del Mediterráneo, y evaluamos si cambios anuales en las condiciones ambientales y las pesquerías modulan dichas diferencias. Utilizamos cuatro años de datos, integrando el seguimiento GPS de las aves, el análisis de isótopos estables, el índice NAO, y el seguimiento remoto de barcos pesqueros que operan en la zona (datos VMS). Entre 2012 y 2015 obtuvimos 635 viajes de alimentación de 78 individuos. Encontramos diferencias en las estrategias de búsqueda de alimento entre sexos a pesar del dimorfismo sexual poco acusado de esta especie. En comparación con los machos, las hembras mostraron mayor esfuerzo (viajes más largos en tiempo y distancia), menor asociación con barcos de pesca, menor nivel trófico (es decir, valores de δ15 N en plasma que apuntan a un menor consumo de descartes) y un nicho isotópico más estrecho. Nuestros resultados revelaron que las condiciones ambientales influyen en las diferencias sexuales en las estrategias de búsqueda y uso de recursos de alimentación, así como en la interacción con pesquerías. En general, esto sugiere cierta exclusión competitiva de machos hacia hembras, particularmente en años desfavorables. Incluir años con condiciones ambientales dispares en el análisis puede ayudar a determinar la segregación sexual en especies con dimorfismo sexual poco acusado. Además, en especies longevas, las diferencias sexuales en las estrategias de búsqueda de alimento pueden conllevar diferente exposición a ciertas amenazas como las capturas accidentales en artes de pesca, lo que debe considerarse en el diseño de estrategias de conservación.

Aggressiveness of end-of-life cancer care: what happens in clinical practice?

PURPOSE: End-of-life cancer care varies widely, and very few centers evaluate it systematically. Our objective was to assess indicators of the aggressiveness of end-of-life cancer care in clinical practice. METHODS: An observational, longitudinal, and retrospective cohort study was conducted at a tertiary hospital. Eligible patients were at least 18 years old, had a solid tumor, were followed up by the Oncology Department, and had died because of cancer or associated complications during 2017. We used the criteria of Earle et al. (J Clin Oncol 21(6):1133-1138, 2003) to assess the aggressiveness of care. Multivariate logistic regression analyses were performed to characterize factors associated with aggressiveness of therapy. RESULTS: The study population comprised 684 patients. Eighty-eight patients (12.9%) received anti-cancer treatment during the last 14 days of their lives, and 62 patients (9.1%) started a new treatment line in the last 30 days. During the last month of life, 102 patients (14.9%) visited the ER, 80 patients (11.7%) were hospitalized more than once, and 26 (3.8%) were admitted to the ICU. A total of 326 patients (47.7%) died in the acute care unit. A total of 417 patients (61.0%) were followed by the Palliative Care Unit, and in 54 cases (13.0%), this care started during the last 3 days of life. CONCLUSIONS: The use of anti-cancer therapies and health care services in our clinical practice, except for the ICU, did not meet the Earle criteria for high-quality care. Concerning hospice care, more than half of the patients received hospice services before death, although in some cases, this care started close to the time of death.

GENCODE reference annotation for the human and mouse genomes.

The accurate identification and description of the genes in the human and mouse genomes is a fundamental requirement for high quality analysis of data informing both genome biology and clinical genomics. Over the last 15 years, the GENCODE consortium has been producing reference quality gene annotations to provide this foundational resource. The GENCODE consortium includes both experimental and computational biology groups who work together to improve and extend the GENCODE gene annotation. Specifically, we generate primary data, create bioinformatics tools and provide analysis to support the work of expert manual gene annotators and automated gene annotation pipelines. In addition, manual and computational annotation workflows use any and all publicly available data and analysis, along with the research literature to identify and characterise gene loci to the highest standard. GENCODE gene annotations are accessible via the Ensembl and UCSC Genome Browsers, the Ensembl FTP site, Ensembl Biomart, Ensembl Perl and REST APIs as well as https://www.gencodegenes.org.

Temporal stability and clinical validation of the Spanish version of the female sexual function inventory (FSFI).

The Female Sexual Function Index is one of the most common instruments used to evaluate the female sexual function. The present study aimed to analyze the test-retest reliability, internal consistency, and discriminant validity of the index in clinical samples and to determine a specific and sensitive cutoff point for the Spanish version of the Female Sexual Function Index. For that purpose, a sample consisting of 117 Colombian women was recruited to evaluate test-retest reliability, and a second sample, consisting of 185 women, was divided into diagnosis and no-diagnosis groups based on DSM-5 criteria. Results showed adequate test-retest reliability after four weeks, and satisfactory evidence of internal consistency was obtained for subscale and overall scores. The inventory was found to have an adequate criterion validity, and it confirmed the differences between diagnosis and no-diagnosis groups. The instrument's cutoff point was determined to be 26 points, with a specificity of 73.9%, a sensitivity of 87.7%, and an area under the curve of 85.9 (CI = 80.0-91.7). These results confirm that the Spanish version of the FSFI is an adequate tool for evaluating female sexual dysfunction based on DSM-5 criteria.

A Risk-Based Screening Approach to Patients Needing Surgery During the De-Escalation Phase of COVID-19 Pandemic.

Since the outbreak of COVID-19 pandemic, many national and international surgical societies have produced guidelines regarding the management of surgical patients. During the mitigation phase of the pandemic, most documents suggested to consider postponing elective procedures, unless this might have impacted the life expectancy of patients. As awareness and knowledge about COVID-19 are gradually increasing, and as we enter a phase when surgical services are resuming their activities, surgical strategies have to adapt to this rapidly evolving scenario. This is particularly relevant when considering screening policies and the associated findings. We herein describe a risk-based approach to the management of patients with surgical diseases, which might be useful in order to limit the risks for healthcare workers and patients, while allowing for resuming elective surgical practice safely.

3D-Printed Surgical Steel Curettes for the Treatment of Perianal Fistula.

Need. The diversity of approaches proposed for the treatment of complex perianal fistulas reflects the fact that no method has yet been shown to be fully satisfactory. We believe the successful treatment of this condition is directly proportional to the amount of fibrous tissue that can be removed. Technical solution. We use a kit of small curettes, of different thicknesses and sizes, incorporating spicules that enable the physician to remove fibrous tissue from the fistula tract. The small size and varying thicknesses of the curettes enable them to mould to the curves of the fistula tract and to remove tissue by deroofing from the shallowest to the deepest layers, thus excising the entire fibrous tract. Our hospital has recently incorporated into clinical practice a new model of 3D-printed surgical steel curette, flanked by 2 lateral rings through which the suture is threaded. The central part of the curette contains radially graduated discs, the tips of which perform the debriding action, removing the fibrous tissue from the tract. Proof of concept. By using these curettes in conjunction with our standard technique (plugging the tract with platelet-rich fibrin), we have improved the success rate from 67% to 88%. Next steps. We have contacted several companies with a view to marketing this product. Conclusion. The results obtained are significantly better than those offered by the techniques in current use for the treatment of complex fistulas, without prejudice to outcomes such as anal continence and morbidity and mortality.

Experimental demonstration of metamaterial anisotropy engineering for broadband on-chip polarization beam splitting.

Subwavelength metamaterials exhibit a strong anisotropy that can be leveraged to implement high-performance polarization handling devices in silicon-on-insulator. Whereas these devices benefit from single-etch step fabrication, many of them require small feature sizes or specialized cladding materials. The anisotropic response of subwavelength metamaterials can be further engineered by tilting its constituent elements away from the optical axis, providing an additional degree of freedom in the design. In this work, we demonstrate this feature through the design, fabrication and experimental characterization of a robust multimode interference polarization beam splitter based on tilted subwavelength gratings. A 110-nm minimum feature size and a standard silicon dioxide cladding are maintained. The resulting device exhibits insertion loss as low as 1 dB, an extinction ratio better than 13 dB in a 120-nm bandwidth, and robust tolerances to fabrication deviations.

Polarization splitting directional coupler using tilted subwavelength gratings.

On-chip polarization splitters are key elements for coherent optical communication systems and polarization diversity circuits. These devices are often implemented with directional couplers that are symmetric for one polarization and strongly asymmetric for the other polarization. To achieve this asymmetry, highly dissimilar waveguides are used in each coupler arm, often requiring additional material layers or etch steps. Here we demonstrate polarization splitting with a directional coupler composed of two fully etched subwavelength waveguides, differing only in the tilt angle of the silicon segments. Our device exhibits deep-UV compatible feature sizes, is 14 µm long, and covers a 72 nm bandwidth with insertion losses below 1 dB and an extinction ratio in excess of 15 dB.