bluuebunny/crossref_metadata_2025 huggingface dataset:
Do Women Contribute More Effort than Men to a Real Public Good?
Authors: Alger Ingela , Juarez Laura , Juarez-Torres Miriam , Miquel-Florensa Josepa
Published: January 2023

This study presents evidence from a lab-in-the-field experiment, conducted in eight small, rural villages in Mexico, in which subjects choose to exert real effort to fund real health centers in their own and other localities. The results show that women are more willing than men to exert effort to fund the health center in another locality, relative to the one in their locality. This gender gap is mostly due to women who have some trust in the way the government spends taxes, and to those who benefit from a government program that targets women and fosters healthcare use. These results also suggest that women might be aware of their higher willingness to exert effort for a public good that does not benefit them directly, compared to men, because they seem to reduce their individual effort the more female their environment is.
Loss of Adgra3 causes obstructive azoospermia with high penetrance in male mice
Authors: Nybo Maja L. , Kvam Jone M. , Nielsen John E. , Frederiksen Hanne , Spiess Katja , Jensen Kristian H. R. , Gadgaard Sarina , Walser Anna L. S. , Thomsen Jesper S. , Cowin Pamela , Juul Anders , Blomberg Jensen Martin , Rosenkilde Mette M.
Published: January 2023

The adhesion receptor ADGRA3 (GPR125) is a known spermatogonial stem cell marker, but its impact on male reproduction and fertility has not been examined. Using a mouse model lacking Adgra3 (Adgra3−/−), we show that 55% of the male mice are infertile from puberty despite having normal spermatogenesis and epididymal sperm count. Instead, male mice lacking Adgra3 exhibited decreased estrogen receptor alpha expression and transient dilation of the epididymis. Combined with an increased estradiol production, this indicates a post‐pubertal hormonal imbalance and fluid retention. Dye injection revealed a blockage between the ejaculatory duct and the urethra, which is rare in mice suffering from infertility, thereby mimicking the etiologies of obstructive azoospermia found in human male infertility. To summarize, male reproductive tract development is dependent on ADGRA3 function that in concert with estrogen signaling may influence fluid handling during sperm maturation and storage.
High and low permeability of human pluripotent stem cell–derived blood–brain barrier models depend on epithelial or endothelial features
Authors: Girard Stéphane D. , Julien‐Gau Ingrid , Molino Yves , Combes Benjamin F. , Greetham Louise , Khrestchatisky Michel , Nivet Emmanuel
Published: January 2023

The search for reliable human blood–brain barrier (BBB) models represents a challenge for the development/testing of strategies aiming to enhance brain delivery of drugs. Human‐induced pluripotent stem cells (hiPSCs) have raised hopes in the development of predictive BBB models. Differentiating strategies are thus required to generate endothelial cells (ECs), a major component of the BBB. Several hiPSC‐based protocols have reported the generation of in vitro models with significant differences in barrier properties. We studied in depth the properties of iPSCs byproducts from two protocols that have been established to yield these in vitro barrier models. Our analysis/study reveals that iPSCs derivatives endowed with EC features yield high permeability models while the cells that exhibit outstanding barrier properties show principally epithelial cell‐like (EpC) features. We found that models containing EpC‐like cells express tight junction proteins, transporters/efflux pumps and display a high functional tightness with very low permeability, which are features commonly shared between BBB and epithelial barriers. Our study demonstrates that hiPSC‐based BBB models need extensive characterization beforehand and that a reliable human BBB model containing EC‐like cells and displaying low permeability is still needed.
Approach for Neglected Calcaneal Fracture-Dislocation and Associated Complications
Authors: Carter Kendal , Sahli-Carter Hannah , Carter Hughey C.
Published: January 2023

Calcaneal fractures lead to significant debility that can be increased due to delayed or improper surgical repair and are commonly complicated by nonunion. This report explores a unique case of neglected calcaneal fracture with malalignment complicated by subluxing peroneal tendons, arthritis of the hindfoot, and tear of the peroneal retinaculum. The operative intervention consisted of open Achilles tendon lengthening, bone block distraction arthrodesis of the subtalar joint with talonavicular and calcaneocuboid fusion, along with repair of subluxing peroneal tendons with fibular groove deepening. Postoperative imaging at 25 weeks revealed intact hardware, stable alignment, and complete osseous arthrodesis of involved joints, which was also redemonstrated at 1-year postoperative. Reports of reconstructive options for neglected calcaneal fractures that restore mobility, such as this case, are important due to the significant patient burden these injuries impose and the paucity of viably restorative options currently available.

Level of Evidence: Level-IV.
Tirzepatide for Weight Loss: Can Medical Therapy “Outweigh” Bariatric Surgery?
Authors: Novograd Joel , Mullally Jamie A. , Frishman William H.
Published: January 2023

The worldwide prevalence of obesity has been increasing progressively over the past few decades and is predicted to continue to rise in coming years. Unfortunately, this epidemic is also affecting increasing rates of children and adolescents, posing a serious global health concern. Increased adiposity is associated with various comorbidities and increased mortality risk. Conversely, weight loss and chronic weight management are associated with improvements in overall morbidity and mortality. The pathophysiology of obesity is multifactorial with complex interactions between genetic and environmental factors. The foundation of most weight loss plans is lifestyle modification including dietary change and exercise. However, lifestyle modification alone is often insufficient to achieve clinically meaningful weight loss due to physiological mechanisms that limit weight reduction and promote weight regain. Therefore, research has focused on adjunctive pharmacotherapy to enable patients to achieve greater weight loss and improved chronic weight maintenance compared to lifestyle modification alone. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin hormone analogs that have proven effective for the management of type 2 diabetes mellitus as well as obesity and overweight. Tirzepatide is a novel “twincretin” that functions as a dual glucose-dependent insulinotropic polypeptide and GLP-1 RA. Tirzepatide was recently approved by the Food and Drug Administration for the management of type 2 diabetes. Similar to previously approved GLP-1RAs, weight loss is a common side effect of tirzepatide which prompted research focused on its use as a primary weight loss therapy. Although this drug has not yet been approved as an antiobesity medication, there are several phase 3 clinical trials that have demonstrated superior weight loss efficacy compared with previously approved medications. This review article will discuss the discovery and mechanism of tirzepatide, as well as the completed and ongoing trials that may lead to its approval as an adjunctive pharmacotherapy for weight loss.
Interface Fluid Syndrome After Descemet Membrane Endothelial Keratoplasty in Patients With History of LASIK
Authors: Izquierdo Luis , Ben-Shaul Or , Larco Pablo , Pereira Nicolas , Mannis Mark J. , Henriquez Maria A.
Published: January 2023

Purpose:

The aim of this study was to evaluate the visual, pachymetric, tomographic, and biomicroscopic findings in a series of cases with laser in situ keratomileusis (LASIK) flap interface fluid syndrome (IFS) after Descemet membrane endothelial keratoplasty (DMEK).

Methods:

Six cases were included in this study; all patients had a history of LASIK and underwent DMEK for the treatment of bullous keratopathy. After uneventful surgery, all patients presented with corneal edema and IFS under the LASIK flap, which was demonstrated with anterior segment optical coherence tomography (AS-OCT). Visual acuity, clinical findings, pachymetry, endothelial cell count, and AS-OCT were documented during the management of these cases.

Results:

IFS appears 2.33 days (±1.03) after DMEK. One case improved with conservative treatment. In 5 cases, the LASIK flap was lifted, the fluid was drained, and the flap was replaced. The mean best-corrected visual acuity after fluid drainage was 0.44 logMAR (range 0.18–1.0) and mean central corneal thickness was 538 μm ± 160. Total resolution of the IFS was achieved at 14.5 days (range 4–30) after DMEK. AS-OCT showed resolution of the flap interface in 5 of 6 cases, while 1 patient required second DMEK due to reaccumulation of the interface fluid.

Conclusions:

IFS can occur after DMEK in patients with previous LASIK. AS-OCT is a valuable tool for monitoring these cases preoperatively and postoperatively. Early surgical management is often needed to achieve resolution.
Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial
Authors: Roilides Emmanuel , Ashouri Negar , Bradley John S. , Johnson Matthew G. , Lonchar Julia , Su Feng-Hsiu , Huntington Jennifer A. , Popejoy Myra W. , Bensaci Mekki , De Anda Carisa , Rhee Elizabeth G. , Bruno Christopher J.
Published: January 2023

Background:

Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, active against multidrug-resistant Gram-negative pathogens, is approved for treatment of adults with complicated urinary tract infections (cUTI). Safety and efficacy of ceftolozane/tazobactam in pediatric participants with cUTI, including pyelonephritis, were assessed.

Methods:

This phase 2 study (NCT03230838) compared ceftolozane/tazobactam with meropenem for treatment of cUTI in participants from birth to <18 years of age. The primary objective was safety and tolerability. Key secondary end points included clinical cure and per-participant microbiologic response rates at end of treatment (EOT) and test of cure (TOC) visits.

Results:

The microbiologic modified intent-to-treat (mMITT) population included 95 participants (ceftolozane/tazobactam, n = 71; meropenem, n = 24). The most common diagnosis and pathogen were pyelonephritis (ceftolozane/tazobactam, 84.5%; meropenem, 79.2%) and Escherichia coli (ceftolozane/tazobactam, 74.6%; meropenem, 87.5%); 5.7% (ceftolozane/tazobactam) and 4.8% (meropenem) of E. coli isolates were extended-spectrum β-lactamase-producers. Rates of adverse events were similar between treatment groups (any: ceftolozane/tazobactam, 59.0% vs. meropenem, 60.6%; drug-related: ceftolozane/tazobactam, 14.0% vs. meropenem, 15.2%; serious: ceftolozane/tazobactam, 3.0% vs. meropenem, 6.1%). Rates of clinical cure for ceftolozane/tazobactam and meropenem at EOT were 94.4% and 100% and at TOC were 88.7% and 95.8%, respectively. Rates of microbiologic eradication for ceftolozane/tazobactam and meropenem at EOT were 93.0% and 95.8%, and at TOC were 84.5% and 87.5%, respectively.

Conclusions:

Ceftolozane/tazobactam had a favorable safety profile in pediatric participants with cUTI; rates of clinical cure and microbiologic eradication were high and similar to meropenem. Ceftolozane/tazobactam is a safe and effective new treatment option for children with cUTI, especially due to antibacterial-resistant Gram-negative pathogens.
Teledermatology during the COVID 19 pandemic in a developing country – Could this be the answer to improving the reach of dermatology care?
Authors: Gold-Olufadi Shakirat , Jesuyajolu Damilola , Cole-Adeife Olufolakemi , Emokpare Didi , Enigbokan Omololu
Published: January 2023

Introduction:

The COVID-19 pandemic has changed the way telemedicine is utilized globally, with most countries reporting an increase in its adoption. The first review of teledermatology in Nigeria reported poor service use. This present report outlines an improvement in the adoption of telemedicine and factors that may account for this increased utilization.

Methods:

We performed a retrospective review of all patients who registered through two telemedicine platforms to access dermatology services during a 1-year period. Data were collated with an online questionnaire and analyzed with SPSS software.

Results:

Sixty patients booked appointments through the platform, with 38 and 22 patients booking virtual and physical consultations, respectively. The response rate was 68.4% and 50.0% for those that booked virtual and physical consultations, respectively, with no significant age difference between the groups. More women booked appointments, and all respondents were educated to at least college level. The majority learned about booking a dermatologist appointment through social media. There was no difference in the clinical outcome between patients who booked a virtual or physical consultation.

Conclusion:

More patients are resorting to teledermatology services because of the convenience; however, most of these patients are situated in urban areas. Because this study showed no significant differences in the clinical outcome between patients who booked virtual and physical consultations, the adoption of teledermatology may be the answer to increasing coverage of dermatology services in developing countries where specialists are limited. Efforts must be made to increase the reach of teledermatology to rural areas.
Indications for and results of renal autotransplantation
Authors: Han David S. , Johnson Jeffrey P. , Schulster Michael L. , Shah Ojas
Published: January 2023

Purpose of review

To understand the indications and outcomes of renal autotransplantation, and when to consider this unique procedure for patients.

Recent findings

Renal autotransplantation confers acceptably low rates of graft failure and prevents need for long-term dialysis. Renal autotransplantation remains an important management strategy in very select patients for complex renovascular disease, ureteral stricture disease, ureteral trauma, upper urinary tract urothelial carcinoma, renal cell carcinoma, and Loin-Pain Hematuria Syndrome. With advancements in minimally invasive procedures, the application of renal autotransplantation for refractory stone disease is rare but exists. Robot-assisted laparoscopic renal autotransplantation demonstrates reproducible graft success and complication rates with improved perioperative outcomes (ex. hospital length of stay) – though comparative studies are lacking. Patients would benefit from a multidisciplinary approach from renal transplant surgeons, vascular surgeons, urologists, nephrologists, dieticians, pain management providers, social workers, and psychiatrists.

In experienced hands, renal autotransplantation is a reasonable treatment approach for complex and refractory renal vascular disease, Loin-Pain Hematuria Syndrome, ureteral strictures and trauma, upper urinary tract malignancy, and stone disease in highly select patients.
Routine, Opt-Out, Emergency Department Syphilis Testing Increases HIV Preexposure Prophylaxis Uptake
Authors: Stanford Kimberly A. , Almirol Ellen , Eller Dylan , Hazra Aniruddha , Schneider John
Published: January 2023

Background

Many people vulnerable to HIV do not perceive themselves at risk or consider preexposure prophylaxis (PrEP). This study hypothesizes that syphilis diagnosis through universal, emergency department (ED) screening would increase PrEP uptake.

Methods

This prospective cohort study enrolled patients tested for syphilis through ED screening between July 2019 and July 2021. Participants completed a survey about behaviors, HIV and PrEP knowledge, and opinions at the time of enrollment. All were offered PrEP if they met Centers for Disease Control and Prevention guidelines for PrEP use. Information about PrEP use and HIV status was collected 6 months later. Bivariate analysis was used to compare outcomes between groups testing positive versus negative for syphilis.

Results

The study enrolled 97 participants, 49 with syphilis and 48 testing negative. Overall, 11 (11.3%) started PrEP, all in the syphilis group, despite 28 (58.3%) in the negative group having indications for PrEP. Participants with syphilis less frequently reported low perceived HIV risk than syphilis-negative participants who reported HIV transmission behaviors (83.7% vs. 92.9%). Participants reporting moderate to high HIV risk perception were significantly more likely to start PrEP (odds ratio, 10.5; 95% confidence interval, 1.41–78.1; P = 0.02). At 6 months, 3 participants remained on PrEP (follow-up data available for 63.5% of PrEP-eligible participants).

Conclusions

Syphilis diagnosis was associated with increased perception of HIV risk and increased PrEP initiation. Individuals who otherwise might not seek testing for syphilis because of perceived low risk may be identified through routine screening, thus providing an important opportunity to link more people to HIV prevention and PrEP services.
Short-term Accrual 2019 European League Against Rheumatism/American College of Rheumatology Domains and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage in Lupus Patients With and Without Nephritis at Disease Onset
Authors: Munhoz Gabriela A. , Aikawa Nadia E. , Silva Clovis A. , Pasoto Sandra G. , Pedrosa Tatiana N. , Seguro Luciana P. C. , Bonfa Eloisa , Borba Eduardo F.
Published: January 2023

Objective

To determine in a historical inception cohort the impact of lupus nephritis at disease onset in short-term accrual 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) domains. The possible association with treatment and damage was also investigated.

Methods

One hundred thirty-three consecutive adult systemic lupus erythematosus patients according to the 2019 EULAR/ACR criteria were divided according to the presence (RENAL-lupus) or absence of renal involvement (NONRENAL-lupus) at disease onset. The 2019 EULAR/ACR score and Systemic Lupus International Collaborating Clinics/ACR (SDI) were longitudinally evaluated over 3 years.

Results

RENAL-lupus (n = 49 [36.8%]) and NONRENAL-lupus (n = 84 [63.2%]) were similar regarding age (p = 0.704), female sex (p = 0.313), and black race (p = 0.506). At study entry, RENAL-lupus had higher 2019 EULAR/ACR total domains (30 [12–42] vs. 22 [10–36], p < 0.001) and used more often glucocorticoid (p < 0.001), mycophenolate mofetil (p = 0.007), and cyclophosphamide (p = 0.001). After 3 years, a stable number of domain scores was observed for the RENAL-lupus (30 [12–42] vs. 30 [12–42], p = 0.125), whereas an increase was observed for the NONRENAL-lupus (22 [10–36] vs. 23 [10–40], p < 0.001) compared with baseline. Accordingly, RENAL-lupus patients had a lower frequency of additional domains (3/49 [6.1%] vs. 37/84 [44.0%], p < 0.0001). New kidney involvement occurred in 15 (44.1%) of 34 patients of the NONRENAL-lupus. Both groups evolved with a comparable increase in frequency of patients with damage (SDI ≥1) at the end of the study (23/49 [46.9%] vs. 34/89 [40.54%], p = 0.585) with a similar median of SDI (1 [0–4] vs. 0 [0–2], p = 0.132).

Conclusions

The distinct pattern of accrual 2019 EULAR/ACR domains in patients with and without nephritis at disease onset suggests that close surveillance for additional organ involvement, including kidney, is mandatory in NONRENAL lupus in the first 3 years of disease. The unexpected comparable early damage in both groups despite milder disease and less intense immunosuppression in NONRENAL lupus reinforces the need for new and tailored therapies for these patients.
Variations in Risk of Cancer and Death From Cancer According to Kidney Allograft Function, Graft Loss, and Return to Dialysis
Authors: Au Eric H.K. , Chapman Jeremy R. , Teixeira-Pinto Armando , Craig Jonathan C. , Wong Germaine
Published: January 2023

Background.

Cancer incidence and mortality may change with varying kidney allograft function and after graft loss. We aimed to quantify cancer incidence and mortality during periods with a functioning graft and after graft loss.

Methods.

We included all adult Australians aged 20 and above who commenced kidney replacement therapy between 1982 and 2014 using data from Australia and New Zealand Dialysis and Transplant Registry. We calculated the standardized incidence ratios and standardized mortality ratios (standardized against the Australian general population) for dialysis patients and transplant recipients during periods with a functioning graft and after graft loss.

Results.

A total of 44 765 dialysis patients without transplants, 13 443 with first kidney transplants, 2951 after first graft loss, 1010 with second transplants, and 279 after second graft loss were followed for 274 660 patient-years. Cancer incidence and mortality (per 100 000 patient-years) were 1564 and 760 in dialysis patients, 1564 and 689 in recipients of first transplants, 1188 and 390 after first graft loss, 1525 and 693 after second transplants, and 1645 and 779 after second graft loss. Cancer standardized incidence ratios and standardized mortality ratios (95% confidence intervals) were 1.15 (1.11-1.20) and 1.29 (1.21-1.36) for dialysis patients, 2.03 (1.94-2.13) and 2.50 (2.33-2.69) for recipients following their first transplant, 1.55 (1.29-1.85) and 1.40 (1.00-1.90) after first graft loss, 2.18 (1.79-2.63) and 3.00 (2.23-3.96) for second transplants, 2.59 (1.56-4.04) and 3.82 (1.75-7.25) after second graft loss.

Conclusions.

In kidney transplant recipients, cancer incidence and mortality are highest during periods with a functioning graft and remained higher than in the general population even after graft loss.
ABO-incompatible Pediatric Liver Transplantation With Antibody and B-cell Depletion-free Immunosuppressive Protocol in High Consanguinity Communities
Authors: Shagrani Mohammad , Kumar Kishwer , Baker Alastair , Al-Awwami Moheeb , Alhussaini Hussa , Almanea Hadeel , Alhumaidan Hind , Iorio Raffaele , Al-Khabbaz Hana , Burdelski Martin , Troisi Roberto I. , Broering Dieter C.
Published: January 2023

Background.

The success of orthotopic liver transplantation as a life-saving treatment has led to new indications and a greater competition for organ grafts. Pediatric patients with acute liver-related crises can benefit from orthotopic liver transplantation, but organ availability in the limited time can be a major obstacle. Crossing ABO blood group barriers could increase the organs available to such patients

Methods.

From November 2010 to June 2015, 176 children aged 0.2−to18 y were transplanted in the King Faisal Specialist Hospital and Research Center. Out of those, 19 children were transplanted across blood group barriers (ABO incompatible). The underlying diseases were biliary atresia (n = 6); progressive familial intrahepatic cholestasis type 2 (n = 4); Crigler-Najjar syndrome (n = 3); hepatoblastoma (n = 2); and urea cycle disorder, Caroli disease, cryptogenic cirrhosis, and neonatal sclerosing cholangitis (n = 1 each). Immunosuppression consisted of basiliximab, mycophenolate, tacrolimus, and steroids. Pretransplant prophylactic plasmapheresis, high-dose immunoglobulins, and rituximab were not administered.

Results.

The grafts were from living donors (n = 17) and deceased donors (n = 2). Living donor morbidity was nil. The recipient median age was 21 mo (5−70 mo). After a median follow-up of 44 mo, 2 recipients (10%) died because of sepsis, 1 because of uncontrolled acute myeloid leukemia. The overall rejection rate was 7%, and no grafts were lost because of antibody-mediated rejection (AMR). HLA matching was 3.8 of 6 (A, B, DR), and there were 2 patients presented with acute cellular rejection, 1 patient with AMR, and 1 patient with biliary strictures.

Conclusions.

ABO incompatible liver transplantation is a feasible and life-saving option even with antibody and B-cell depletion-free protocol without increasing the risks for AMR. We speculate that this excellent result is most likely because of presence of relatively low titer ABO isoagglutinins and the high HLA match compatibility caused by habit of longstanding interfamilial marriages as typical of Saudi Arabia.
Differences Between Centers in Psychosocial Evaluations for Living Kidney Donors Do Not Influence Outcome: Results From an Observational Multicenter Study
Authors: Ludwig Gundula , Geiger Irene , Götzmann Lutz , Jordan Katja-Daniela , Döbbel Susanne , Klaghofer Richard , Salathé Michelle , Stillhard Urs , Meinlschmidt Gunther , Kiss Alexander , Venetz Jean-Pierre , Steiger Jürg , Hirt-Minkowski Patricia
Published: January 2023

Background.

Rather little is known about how psychosocial evaluations for living kidney donation (LKD) are performed. We aimed to explore whether Swiss transplant centers (STCs) vary regarding the rate of living kidney donors refused for psychosocial reasons, the psychosocial evaluation process, and the characteristics of the donors.

Methods.

We investigated 310 consecutive candidates for LKD in 4 of 6 existing STC during mandatory psychosocial evaluations. We registered (i) sociodemographic data, (ii) the type of the decision-making process regarding LKD (ie, snap decision, postponed, deliberate, other), (iii) the evaluator’s perception of the donor’s emotional bonding and his/her conflicts with the recipient, (iv) the donor’s prognosis from a psychosocial perspective, (v) time taken for the psychosocial evaluation, and (vi) its result (eligible, eligible with additional requirements, not eligible).

Results.

Centers had comparable proportions of noneligible donors (2.9%–6.0%) but differed significantly in the percentage of donors accepted with additional requirements (3.4%–66%, P < 0.001). Significant differences emerged between centers regarding the time needed for evaluation (75–160 min [interquartile range (IQR) 75–180 min] per single exploration, P < 0.001), the perception of the donor’s emotional bonding (visual analogue scale [VAS] 8–9 [IQR 6–10], P < 0.001), his/her conflicts with the recipient (VAS 1.5–2 [IQR 0–3], P = 0.006), the donor’s psychosocial prognosis (VAS 8–9 [IQR 7–10], P < 0.001), and the type of decision concerning LKD (59%–82% with snap decision “yes,” P = 0.008). However, despite differences in the psychosocial evaluation process, the rates of patients accepted for transplantation (eligible and eligible with additional requirements versus noneligible) were comparable across STC (P = 0.72).

Conclusions.

Our results emphasize that it is more important to establish clear guidelines to identify potential psychosocial risks than to stringently standardize the procedure for psychosocial evaluation of living kidney donors.
Outcomes of Primary Simultaneous Pancreas-kidney Transplants by Induction Agent in the United States
Authors: Cerise Adam , Shaker Tamer , LeNguyen Phuoc , Dinesh Anant , Ramanathan Karthik , Humphreville Vanessa , Jackson Scott , Kandaswamy Raja , Riad Samy
Published: January 2023

Background.

Long-term outcome data by induction type in simultaneous pancreas-kidney (SPK) is limited.

Methods.

Utilizing the Scientific Registry of Transplant Recipients, we examined all primary SPK transplants between 2000 and 2020, excluding crossmatch-positive recipients. We grouped recipients according to induction regimen into 3 groups: rabbit anti-thymocyte globulin (r-ATG) (n = 5678), alemtuzumab (n = 1199), and interleukin-2 receptor antagonist (IL-2RA; n = 1593). We analyzed the 10-y recipient and composite (kidney and pancreas) graft survival using the Kaplan-Meier survival function. Cox-proportion hazard models were generated to examine the association between induction type, the 10-y recipient, and graft survival. Models were adjusted for recipient age, sex, ethnicity, HLA-mismatch, diabetes type, dialysis dependency, cold-ischemia time, local versus imported organs, panel reactive antibody, steroid maintenance, and Pancreas Donor Risk Index.

Results.

r-ATG was associated with the lowest 1-y kidney and pancreas rejection rates compared with other agents (P < 0.001). In the univariable analysis, induction type was not associated with recipient (log-rank P = 0.11) or graft survival (log-rank P = 0.36). In the multivariable model for the composite graft survival, alemtuzumab use was associated with 22% increased kidney or pancreas graft loss compared with r-ATG (adjusted hazard ratio, 1.22; 95% confidence interval, 1.05–1.42), whereas IL-2RA use was not a predictor of graft survival. Induction type did not influence recipient survival in the adjusted model.

Conclusions.

r-ATG use was associated with the lowest SPK rejection rates. Compared with r-ATG, alemtuzumab but not IL-2RA was associated with worse long-term death-censored SPK graft outcome. Our analysis supports the common use of r-ATG for induction in US primary SPK recipients.
Steps to individuality in biology and culture
Authors: Davison Dinah R. , Michod Richard E.
Published: January 2023

Did human culture arise through an evolutionary transition in individuality (ETI)? To address this question, we examine the steps of biological ETIs to see how they could apply to the evolution of human culture. For concreteness, we illustrate the ETI stages using a well-studied example, the evolution of multicellularity in the volvocine algae. We then consider how those stages could apply to a cultural transition involving integrated groups of cultural traditions and the hominins that create and transmit traditions. We focus primarily on the early Pleistocene and examine hominin carnivory and the cultural change from Oldowan to Acheulean technology. We usePanbehaviour as an outgroup comparison. We summarize the important similarities and differences we find between ETI stages in the biological and cultural realms. As we are not cultural anthropologists, we may overlook or be mistaken in the processes we associate with each step. We hope that by clearly describing these steps to individuality and illustrating them with cultural principles and processes, other researchers may build upon our initial exercise. Our analysis supports the hypothesis that human culture has undergone an ETI beginning with aPan-like ancestor, continuing during the Pleistocene, and culminating in modern human culture.

This article is part of the theme issue ‘Human socio-cultural evolution in light of evolutionary transitions’.
Draft genome sequence of Enterobacter cloacae ST473 harbouring blaCMH-3 isolated from a human patient diagnosed with recurrent bacteriuria in Nigeria
Authors: David Ebuka Elijah , Igwenyi Ikechuku Okorie , Iroha Ifeanyichukwu Romanus , Martins Layla Farage , Uceda-Campos Guillermo , da Silva Aline Maria
Published: January 2023

Enterobacter cloacae is among the most frequently isolated species described in clinical infections and is commonly associated with a multidrug resistance (MDR) phenotype. We present the draft genome sequence of a MDR E. cloacae isolated in Nigeria from the urine sample of an adult male outpatient diagnosed with asymptomatic recurrent bacteriuria. The isolate was found to be resistant to ceftriaxone, cefotaxime, cefepime and levofloxacin. Genome analysis revealed the presence of the beta-lactamase chromosomal gene blaCMH-3 which may be responsible for the antibiotic resistance observed in the recurrent E. cloacae urinary tract infection.
A guide to Agrobacterium-mediated transformation of the chytrid fungus Spizellomyces punctatus
Authors: Prostak Sarah M , Medina Edgar M , Kalinka Erik , Fritz-Laylin Lillian K
Published: January 2023

Chytrid fungi play key ecological roles in aquatic ecosystems, and some species cause a devastating skin disease in frogs and salamanders. Despite their importance, little is known about the basic cell biology of chytrids. Additionally, chytrids occupy a unique phylogenetic position– sister to the well-studied Dikarya (yeasts, sac fungi, and their multicellular relatives) and related to animals– making chytrids useful for studying important evolutionary questions. A major barrier to understanding chytrid biology has been a lack of genetic tools with which to test molecular hypotheses. Medina and colleagues recently developed a protocol for Agrobacterium-mediated transformation of Spizellomyces punctatus. In this manuscript, we describe the general procedure including planning and expected results. We also provide in-depth, step-by-step protocols and video guides for performing the entirety of this transformation procedure.
De-novo genome assembly for Akanthomyces muscarius, a biocontrol agent of insect agricultural pests
Authors: Erdos Zoltan , Studholme David John , Raymond Ben , Sharma Manmohan
Published: January 2023

The entomopathogenic fungus Akanthomyces muscarius is used as a biological control agent for the management of insect pests in agriculture. It also presents a potential model for studying host-pathogen interactions and the evolution of virulence in a laboratory setting. Here, we present the first high-quality genome sequence for A. muscarius. We used long- and short-read sequencing to assemble a sequence of 36.1 Mb with an N50 of 4.9 Mb. Genome annotation predicts 12,347 genes, with 96.6 % completeness based on the core Hypocrealen gene set (Benchmarking Universal Single-Copy Orthologs). The first high-quality assembly and annotation of A. muscarius presented in this study provide a powerful tool for further research on this commercially important species.
The DataHarmonizer: a tool for faster data harmonization, validation, aggregation and analysis of pathogen genomics contextual information
Authors: Gill Ivan S. , Griffiths Emma J. , Dooley Damion , Cameron Rhiannon , Savić Kallesøe Sarah , John Nithu Sara , Sehar Anoosha , Gosal Gurinder , Alexander David , Chapel Madison , Croxen Matthew A. , Delisle Benjamin , Di Tullio Rachelle , Gaston Daniel , Duggan Ana , Guthrie Jennifer L. , Horsman Mark , Joshi Esha , Kearny Levon , Knox Natalie , Lau Lynette , LeBlanc Jason J. , Li Vincent , Lyons Pierre , MacKenzie Keith , McArthur Andrew G. , Panousis Emily M. , Palmer John , Prystajecky Natalie , Smith Kerri N. , Tanner Jennifer , Townend Christopher , Tyler Andrea , Van Domselaar Gary , Hsiao William W. L.
Published: January 2023

Pathogen genomics is a critical tool for public health surveillance, infection control, outbreak investigations as well as research. In order to make use of pathogen genomics data, they must be interpreted using contextual data (metadata). Contextual data include sample metadata, laboratory methods, patient demographics, clinical outcomes and epidemiological information. However, the variability in how contextual information is captured by different authorities and how it is encoded in different databases poses challenges for data interpretation, integration and their use/re-use. The DataHarmonizer is a template-driven spreadsheet application for harmonizing, validating and transforming genomics contextual data into submission-ready formats for public or private repositories. The tool’s web browser-based JavaScript environment enables validation and its offline functionality and local installation increases data security. The DataHarmonizer was developed to address the data sharing needs that arose during the COVID-19 pandemic, and was used by members of the Canadian COVID Genomics Network (CanCOGeN) to harmonize SARS-CoV-2 contextual data for national surveillance and for public repository submission. In order to support coordination of international surveillance efforts, we have partnered with the Public Health Alliance for Genomic Epidemiology to also provide a template conforming to its SARS-CoV-2 contextual data specification for use worldwide. Templates are also being developed for One Health and foodborne pathogens. Overall, the DataHarmonizer tool improves the effectiveness and fidelity of contextual data capture as well as its subsequent usability. Harmonization of contextual information across authorities, platforms and systems globally improves interoperability and reusability of data for concerted public health and research initiatives to fight the current pandemic and future public health emergencies. While initially developed for the COVID-19 pandemic, its expansion to other data management applications and pathogens is already underway.
Strength training rescues mitochondrial dysfunction in skeletal muscle of patients with myotonic dystrophy type 1
Authors: Leo Valeria Di , Lawless Conor , Roussel Marie-Pier , Gomes Tiago B. , Gorman Gráinne S. , Russell Oliver M. , Tuppen Helen A. L. , Duchesne Elise , Vincent Amy E.
Published: January 2023

Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder, for which no cure exists. This study investigates the effects of 12-week strength training on mitochondrial oxidative phosphorylation in skeletal muscle in a cohort of DM1 patients (n=11, males) in comparison to untrained sex-matched healthy subjects. Immunofluorescence was used to assess protein levels of key respiratory chain subunits of complex I (CI) and complex IV (CIV), and markers of mitochondrial mass and cell membrane in individual myofibers sampled from biopsies. We classified each patient myofiber as having normal, low or high levels of CI and CIV and compared the proportions of affected fibers before and after exercise training. The significance of changes observed between pre- and post-exercise training within patients was estimated using a permutation test.

At baseline, DM1 patients present with significantly decreased mitochondrial mass, and isolated or combined CI and CIV deficiency. After strength training, in most patients a significant increase in mitochondrial mass was observed, and all patients showed a significant increase in CI and/or CIV protein levels. Remarkably, 12-week strength training is sufficient to partially rescue mitochondrial dysfunction in DM1 patients, suggesting exercise as an inexpensive and accessible therapy option.
The safety and relative effectiveness of non-psychoactive cannabinoid formulations for the improvement of sleep: a double-blinded, randomized controlled trial
Authors: Saleska Jessica Londeree , Bryant Corey , Kolobaric Antonija , Colwell Christopher S. , Loewy Derek , Chen Jeff , Pauli Emily K.
Published: January 2023

The objective of this randomized, double-blinded controlled trial was to evaluate the safety and relative effects of different formulations containing Cannabidiol (CBD) and melatonin, with and without the addition of minor cannabinoids, on sleep. Participants (N=1,793 adults experiencing symptoms of sleep disturbance) were assigned to receive a 4-week supply of 1 of 6 products (all capsules) containing either 15mg CBD or 5mg melatonin, alone or in combination with minor cannabinoids. Sleep disturbance was assessed using Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A, administered via weekly online surveys. All formulations exhibited a favorable safety profile (12% of participants reported a side effect and none were severe) and led to significant improvements in sleep disturbance (p<0.001 in within-group comparisons). Most participants (56% to 75%) across all formulations experienced a clinically important improvement in their sleep quality. There were no significant differences in effect, however, between 15mg CBD isolate and formulations containing 15mg CBD and 15mg Cannabinol (CBN), alone or in combination with 5 mg Cannabichromene (CBC). There were also no significant differences in effect between 15mg CBD isolate and formulations containing 5 mg melatonin, alone or in combination with 15mg CBD and 15mg CBN. Our findings suggest that chronic use of a low dose of CBD is safe and could improve sleep quality, though these effects do not exceed that of 5 mg melatonin. Moreover, the addition of low doses of CBN and CBC may not improve the effect of formulations containing CBD or melatonin isolate.
A lizard is never late: squamate genomics as a recent catalyst for understanding sex chromosome and microchromosome evolution
Authors: Pinto Brendan J. , Gamble Tony , Smith Chase H. , Wilson Melissa A.
Published: January 2023

In 2011, the first high-quality genome assembly of a squamate reptile (lizard or snake) was published for the green anole. Dozens of genome assemblies were subsequently published over the next decade, yet these assemblies were largely inadequate for answering fundamental questions regarding genome evolution in squamates due to their lack of contiguity or annotation. As the “genomics age” was beginning to hit its stride in many organismal study systems, progress in squamates was largely stagnant following the publication of the green anole genome. In fact,zerohigh-quality (chromosome-level) squamate genomes were published between the years 2012–2017. However, since 2018, an exponential increase in high-quality genome assemblies has materialized with 24 additional high-quality genomes published for species across the squamate tree of life. As the field of squamate genomics is rapidly evolving, we provide a systematic review from an evolutionary genomics perspective. We collated a near-complete list of publicly available squamate genome assemblies from more than half-a-dozen international and third-party repositories and systematically evaluated them with regard to their overall quality, phylogenetic breadth, and usefulness for continuing to provide accurate and efficient insights into genome evolution across squamate reptiles. This review both highlights and catalogs the currently available genomic resources in squamates and their ability to address broader questions in vertebrates, specifically sex chromosome and microchromosome evolution, while addressing why squamates may have received less historical focus and has caused their progress in genomics to lag behind peer taxa.
A Novel Monoclonal Antibody Targeting a Large Surface of the Receptor Binding Motif Shows Pan-neutralizing SARS-CoV-2 Activity Including BQ.1.1 Variant
Authors: de Campos-Mata Leire , Trinité Benjamin , Modrego Andrea , Vaquero Sonia Tejedor , Pradenas Edwards , Melero Natalia Rodrigo , Carlero Diego , Marfil Silvia , Pons-Grífols Anna , Bueno-Carrasco María Teresa , Santiago César , Tarrés-Freixas Ferran , Urrea Victor , Izquierdo Nuria , Riveira-Muñoz Eva , Ballana Ester , Pérez Mónica , Vergara-Alert Júlia , Segalés Joaquim , Carolis Carlo , Arranz Rocío , Blanco Julià , Magri Giuliana
Published: January 2023

In the present study we report the functional and structural characterization of 17T2, a new highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody (mAb) isolated from a convalescent COVID-19 individual infected during the first wave of the COVID-19 pandemic. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA memory B cell and developed as a human recombinant IgG1. Functional characterization revealed that 17T2 mAb has a high and exceptionally broad neutralizing activity against all SARS-CoV-2 spike variants tested, including BQ.1.1. Moreover, 17T2 mAb hasin vivoprophylactic activity against Omicron BA.1.1 infection in K18-hACE2 transgenic mice. 3D reconstruction from cryogenic-electron microscopy (cryo-EM) showed that 17T2 binds the Omicron BA.1 spike protein with the RBD domains in “up” position and recognizes an epitope overlapping with the receptor binding motif, as it is the case for other structurally similar neutralizing mAbs, including S2E12. Yet, unlike S2E12, 17T2 retained its high neutralizing activity against all Omicron sublineages tested, probably due to a larger contact area with the RBD, which could confer a higher resilience to spike mutations. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 mAb as a potential candidate for future therapeutic and prophylactic interventions.
Reliable imputation of spatial transcriptome with uncertainty estimation and spatial regularization
Authors: Qiao Chen , Huang Yuanhua
Published: January 2023

Abstract

Imputation of missing features in spatial transcriptomics is urgently demanded due to technology limitations, while most existing computational methods suffer from moderate accuracy and cannot estimate the reliability of the imputation. To fill the research gaps, we introduce a computational model, TransImp, that imputes the missing feature modality in spatial transcriptomics by mapping it from single-cell reference. Uniquely, we derived a set of attributes that can accurately predict imputation uncertainty, hence enabling us to select reliably imputed genes. Also, we introduced a spatial auto-correlation metric as a regularization to avoid overestimating spatial patterns. Multiple datasets from various platforms have demonstrated that our approach significantly improves the reliability of downstream analyses in detecting spatial variable genes and interacting ligand-receptor pairs. Therefore, TransImp offers a way towards a reliable spatial analysis of missing features for both matched and unseen modalities, e.g., nascent RNAs.
Safety of bivalent omicron-containing mRNA-booster vaccines: a nationwide cohort study
Authors: Andersson Niklas Worm , Thiesson Emilia Myrup , Vinsløv Hansen Jørgen , Hviid Anders
Published: January 2023

Background

Safety data to support bivalent omicron-containing mRNA-booster vaccination are lacking.

Methods

In a Danish nationwide cohort study from 1 January 2021 to 10 December 2022, we examined the association between bivalent omicron-containing mRNA-booster vaccination as a fourth Covid-19 vaccine dose and risk of adverse events in individuals aged ≥50 years. Using incidence rate ratios estimated with Poisson regression, we compared the rates of hospital visits for 27 different adverse events in a 28-day main risk period following vaccination with a bivalent omicron-containing mRNA-booster vaccine as a fourth dose to reference period rates from day 29 after the third or fourth vaccine dose and onward. Secondary analyses included stratifying by sex, age, and vaccine type and assessing the associations using self-controlled case series and observed vs. expected cohort analyses.

Results

1,740,417 individuals (mean age 67.8 years, standard deviation 10.7) received a bivalent omicron-containing mRNA-booster vaccine as a fourth dose. Fourth dose vaccination with a bivalent omicron-containing booster did not statistically significantly increase the rate of any of the 27 adverse outcomes within 28 days, nor when analyzed according to age, sex, vaccine type, or using alternative analytical approaches. However, post-hoc analysis detected signals for myocarditis (statistically significantly so in females), although the outcome was very rare and findings were based on few cases. No risk of cerebrovascular infarction was found.

Conclusions

Bivalent omicron-containing mRNA-booster vaccination as a fourth dose was not associated with an increased risk of 27 different adverse events in 50+-year-olds.