Functional protein mining with conformal guarantees.

Molecular structure prediction and homology detection offer promising paths to discovering protein function and evolutionary relationships. However, current approaches lack statistical reliability assurances, limiting their practical utility for selecting proteins for further experimental and in-silico characterization. To address this challenge, we introduce a statistically principled approach to protein search leveraging principles from conformal prediction, offering a framework that ensures statistical guarantees with user-specified risk and provides calibrated probabilities (rather than raw ML scores) for any protein search model.

RNA language models predict mutations that improve RNA function.

Structured RNA lies at the heart of many central biological processes, from gene expression to catalysis. RNA structure prediction is not yet possible due to a lack of high-quality reference data associated with organismal phenotypes that could inform RNA function. We present GARNET (Gtdb Acquired RNa with Environmental Temperatures), a new database for RNA structural and functional analysis anchored to the Genome Taxonomy Database (GTDB).

Comparative analysis of treatment modalities for solitary, small (≤3 cm) hepatocellular carcinoma: A systematic review and network meta-analysis of oncologic outcomes.

Background: Solitary hepatocellular carcinoma measuring ≤3 cm represents approximately 30% of hepatocellular carcinoma cases, yet treatment guidelines lack robust evidence. This study compares oncologic outcomes after ablation, liver resection, and liver transplantation for solitary, small hepatocellular carcinoma.

Methods: We systematically searched databases up to 7 February 2022, for studies including adults with solitary hepatocellular carcinoma ≤3 cm treated by any ablation, liver resection, or liver transplantation.

Structure-guided discovery of ancestral CRISPR-Cas13 ribonucleases.

The RNA-guided ribonuclease CRISPR-Cas13 enables adaptive immunity in bacteria and programmable RNA manipulation in heterologous systems. Cas13s share limited sequence similarity, hindering discovery of related or ancestral systems. To address this, we developed an automated structural-search pipeline to identify an ancestral clade of Cas13 (Cas13an) and further trace Cas13 origins to defense-associated ribonucleases.

Normothermic Machine Perfusion and Normothermic Regional Perfusion of DCD Kidneys Before Transplantation: A Systematic Review.

Background: To overcome organ shortages, donation after circulatory death (DCD) kidneys are being increasingly used for transplantation. Prior research suggests that DCD kidneys have inferior outcomes compared with kidneys donated after brain death. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) may enhance the preservation of DCD kidneys and improve transplant outcomes.

The extracellular matrix integrates mitochondrial homeostasis.

Cellular homeostasis is intricately influenced by stimuli from the microenvironment, including signaling molecules, metabolites, and pathogens. Functioning as a signaling hub within the cell, mitochondria integrate information from various intracellular compartments to regulate cellular signaling and metabolism. Multiple studies have shown that mitochondria may respond to various extracellular signaling events.

Rapid DNA unwinding accelerates genome editing by engineered CRISPR-Cas9.

Thermostable clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas9) enzymes could improve genome-editing efficiency and delivery due to extended protein lifetimes. However, initial experimentation demonstrated Geobacillus stearothermophilus Cas9 (GeoCas9) to be virtually inactive when used in cultured human cells. Laboratory-evolved variants of GeoCas9 overcome this natural limitation by acquiring mutations in the wedge (WED) domain that produce >100-fold-higher genome-editing levels.

Non-Thermal Solar Wind Electron Velocity Distribution Function.

The quiet-time solar wind electrons feature non-thermal characteristics when viewed from the perspective of their velocity distribution functions. They typically have an appearance of being composed of a denser thermal "core" population plus a tenuous energetic "halo" population. At first, such a feature was empirically fitted with the kappa velocity space distribution function, but ever since the ground-breaking work by Tsallis, the space physics community has embraced the potential implication of the kappa distribution as reflecting the non-extensive nature of the space plasma.

Kidney Transplantation Outcomes From Uncontrolled Donation After Circulatory Death: A Systematic Review and Meta-analysis.

Background: Uncontrolled donation after circulatory death (uDCD) is a potential additional source of donor kidneys. This study reviewed uDCD kidney transplant outcomes to determine if these are comparable to controlled donation after circulatory death (cDCD).

Methods: MEDLINE, Cochrane, and Embase databases were searched.

Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes.

RNA-guided endonucleases form the crux of diverse biological processes and technologies, including adaptive immunity, transposition, and genome editing. Some of these enzymes are components of insertion sequences (IS) in the IS200/IS605 and IS607 transposon families. Both IS families encode a TnpA transposase and a TnpB nuclease, an RNA-guided enzyme ancestral to CRISPR-Cas12s.

CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes.

CRISPR-Cas enzymes enable RNA-guided bacterial immunity and are widely used for biotechnological applications including genome editing. In particular, the Class 2 CRISPR-associated enzymes (Cas9, Cas12 and Cas13 families), have been deployed for numerous research, clinical and agricultural applications. However, the immense genetic and biochemical diversity of these proteins in the public domain poses a barrier for researchers seeking to leverage their activities.

Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes.

RNA-guided endonucleases form the crux of diverse biological processes and technologies, including adaptive immunity, transposition, and genome editing. Some of these enzymes are components of insertion sequences (IS) in the IS200/IS605 and IS607 transposon families. Both IS families encode a TnpA transposase and TnpB nuclease, an RNA-guided enzyme ancestral to CRISPR-Cas12.

Outcomes of endovascular, open surgical and autotransplantation techniques for renal artery aneurysm repair: a systematic review and meta-analysis.

Background: Renal artery aneurysms (RAA) can be repaired with endovascular exclusion (EVR), open repair (OR), or ex-vivo repair with renal autotransplantation (ERAT). This systematic review compares repair indications, aneurysm characteristics, and complications following these interventions.

Methods: A systematic review of databases including MEDLINE, PUBMED, and EMBASE by two independent reviewers for studies from January 2000-November 2022.

Outcomes of liver transplantation in non-alcoholic steatohepatitis (NASH) versus non-NASH associated hepatocellular carcinoma.

Background: Non-alcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC) is a rising indication for liver transplantation. This unique population, with multiple comorbidities, has potential for worse post-transplant outcomes. We compared post-transplant survival of NASH and non-NASH HCC patients using a large cohort.

Impact of muscle mass on survival of patients with hepatocellular carcinoma after liver transplantation beyond the Milan criteria.

Background: Access to the liver transplant waitlist for patients with hepatocellular carcinoma (HCC) depends on tumour presentation, biology, and response to treatments. The Milan Criteria (MC) represent the benchmark for expanded criteria that incorporate additional prognostic factors. The purpose of this study was to determine the added value of skeletal muscle index (SMI) in HCC patients beyond the MC.

Insulating jackets thermally protect kidneys in an ex vivo model of second warm ischemia.

Background: Kidney transplantation is the current optimal treatment for suitable patients with end-stage renal disease. The second warm ischemic time (SWIT) is known to negatively impact delayed graft function, and long-term graft survival, and methods are required to ameliorate the impacts of SWIT on transplantation outcomes.

Materials And Methods: This study primarily focused on determining the effect of a novel thermally insulating jacket on the thermal profile of the human kidney and quantifying the reduction in thermal energy experienced using this device (KPJ™).

Optimal common limb length in Roux-en-Y gastric bypass surgery: is it important for an ideal outcome? - a systematic review.

Background: In Roux-en-Y gastric bypass (RYGB) surgery the common limb length (CLL) is thought to significantly impact on nutritional and metabolic outcomes. However, there has been little focus on establishing routine standardized CLL measurements and its subsequent effect on weight loss and nutritional status. This review aimed to determine the effect of variations of CLL in RYGB surgery on post-operative outcomes, particularly nutritional status, while considering the need for routine CLL measurements in addition to measuring biliopancreatic limb and alimentary limb lengths.

Trends in liver transplantation for autoimmune liver diseases: a Canadian study.

Background: To our knowledge, no analysis of data from liver transplantation registries exists in Canada. We aimed to describe temporal trends in the number of liver transplantation procedures, patient characteristics and posttransplantation outcomes for autoimmune liver diseases (AILDs) in Canada.

Methods: We used administrative data from the Canadian Organ Replacement Register, which contains liver transplantation information from 6 centres in Canada.

Utilizing the same incision for staged renal transplant in patients with polycystic kidney disease requiring hand-assisted laparoscopic nephrectomy.

Backgrounds: Many autosomal dominant polycystic kidney disease (ADPKD) patients undergo nephrectomy and subsequent renal transplantation. We report our outcomes after hand-assisted laparoscopic nephrectomy (HALN) where a Rutherford-Morrison incision is used as a hand-port site and kidney extraction site, as well the future incision site for staged transplantation.

Methods: A retrospective review was performed on all adult nephrectomies for ADPKD by the Transplant Surgery department at Westmead Hospital between June 2011 and June 2021.

Right Lobe Versus Left Lobe Living Donor Liver Transplantation: A Systematic Review and Meta-analysis of Donor and Recipient Outcomes.

Background: Living donor liver transplantation (LDLT) is an established treatment for advanced liver disease. Whether right lobe (RL) or left lobe (LL) LDLT provides the best outcomes for donors and recipients remains contentious.

Methods: MedLine, Embase, PubMed, and Cochrane Central were searched to identify studies comparing RL- and LL-LDLT and reporting donor and/or recipient outcomes.

Outcomes of Adult Liver Retransplantation: A Canadian National Database Analysis.

Background: Liver retransplantation remains as the only treatment for graft failure. This investigation aims to assess the incidence, post-transplant outcomes, and risk factors in liver retransplantation recipients in Canada.

Materials And Methods: The Canadian Organ Replacement Register was used to obtain and analyse data on all adult liver retransplant recipients, matched donors, transplant-specific variables, and post-transplant outcomes from January 2000 to December 2018.

Long-term outcomes of laparoscopic liver resection for hepatocellular carcinoma: A propensity score matched analysis of a high-volume North American center.

Background: Laparoscopic liver resections for malignancy are increasing worldwide, and yet data from North America are lacking. We aimed to assess the long-term outcomes of patients undergoing laparoscopic liver resection and open liver resection as a treatment for hepatocellular carcinoma.

Methods: Patients undergoing liver resection for hepatocellular carcinoma between January 2008 and December 2019 were retrospectively studied.