bluuebunny/crossref_metadata_2025 huggingface dataset:
Second moments of work and heat for a single-particle stochastic heat engine in a breathing harmonic potential
Authors: Iida Shinji , Negoro Koki , Yamada Kanta
Published: March 2022

We consider a simple model of a stochastic heat engine, which consists of a single Brownian particle moving in a one-dimensional periodically breathing harmonic potential. The overdamped limit is assumed. Expressions for the second moments (variances and covariances) of heat and work are obtained in the form of integrals, whose integrands contain functions satisfying certain differential equations. The results in the quasi-static limit are simple functions of the temperatures of hot and cold thermal baths. The coefficient of variation of the work is suggested to give an approximate probability for the work to exceed a given threshold. During the derivation, we get the expression of the cumulant-generating function.
Drivers of and barriers to adoption of improved sunflower varieties amongst smallholder farmers in Singida, Tanzania: A double-hurdle approach
Authors: Tibamanya Felister Y , Henningsen Arne , Milanzi Mursali A
Published: March 2022

Yield-enhancing agricultural technologies, like improved crop varieties, are widely promoted in developing countries to improve the food security, income, and welfare of farm households. Nonetheless, farm households show low adoption rates of these technologies. To gain more insight into the drivers of and the barriers to the adoption of improved crop varieties, we study the adoption of improved sunflower varieties by smallholder farmers in Tanzania. Unlike most earlier studies, we distinguish between the initial adoption and the extent of adoption. Additionally, we investigate the roles of market constraints and liquidity constraints, which are largely ignored in previous adoption studies. We find that risk aversion and liquidity constraints are barriers to adoption, whilst radios and extension service are important information channels for new technologies. Our results can help to improve policies, development programmes, and business decisions and finally to enhance agricultural productivity and farm household welfare.
Financial Market Ethics
Authors: Easley David , O’Hara Maureen
Published: March 2022

We develop a model of psychological-games-played-on-a-network to demonstrate a role for endogenously determined, rationally chosen ethics. Our analysis produces sharp results about contagion of nonethical or ethical behavior and the possible equilibrium configurations of each type of behavior. We find, and quantify, critical densities for clusters of each type of behavior that determine everything about contagion. We introduce society as a third player to investigate ethical failures as externalities. We use these results to show how regulations and network structure can affect whether clusters of ethical behavior can survive and how large they can be in a financial market setting.
An antibody-escape estimator for mutations to the SARS-CoV-2 receptor-binding domain
Authors: Greaney Allison J , Starr Tyler N , Bloom Jesse D
Published: March 2022

A key goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance is to rapidly identify viral variants with mutations that reduce neutralization by polyclonal antibodies elicited by vaccination or infection. Unfortunately, direct experimental characterization of new viral variants lags their sequence-based identification. Here we help address this challenge by aggregating deep mutational scanning data into an ‘escape estimator’ that estimates the antigenic effects of arbitrary combinations of mutations to the virus’s spike receptor-binding domain. The estimator can be used to intuitively visualize how mutations impact polyclonal antibody recognition and score the expected antigenic effect of combinations of mutations. These scores correlate with neutralization assays performed on SARS-CoV-2 variants and emphasize the ominous antigenic properties of the recently described Omicron variant. An interactive version of the estimator is at https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/escape-calc/ (last accessed 11 March 2022), and we provide a Python module for batch processing. Currently the calculator uses primarily data for antibodies elicited by Wuhan-Hu-1-like vaccination or infection and so is expected to work best for calculating escape from such immunity for mutations relative to early SARS-CoV-2 strains.
Two AMP-Binding Domain Proteins from Rhizophagus irregularis Involved in Import of Exogenous Fatty Acids
Authors: Brands Mathias , Dörmann Peter
Published: March 2022

Arbuscular mycorrhizal fungi (AMF) colonize roots, where they provide nutrients in exchange for sugars and lipids. Because AMF lack genes for cytosolic fatty acid de novo synthase (FAS), they depend on host-derived fatty acids. AMF colonization is accompanied by expression of specific lipid genes and synthesis of sn-2 monoacylglycerols (MAGs). It is unknown how host-derived fatty acids are taken up by AMF. We describe the characterization of two AMP-binding domain protein genes from Rhizophagus irregularis, RiFAT1 and RiFAT2, with sequence similarity to Saccharomyces cerevisiae fatty acid transporter 1 (FAT1). Uptake of 13C-myristic acid (14:0) and, to a lesser extent, 13C-palmitic acid (16:0) was enhanced after expression of RiFAT1 or RiFAT2 in S. cerevisiae Δfat1 cells. The uptake of 2H-labeled fatty acids from 2H-myristoylglycerol or 2H-palmitoylglycerol was also increased after RiFAT1 and RiFAT2 expression in Δfat, but intact 2H-MAGs were not detected. RiFAT1 and RiFAT2 expression was induced in colonized roots compared with extraradical mycelium. 13C-label in the AMF-specific palmitvaccenic acid (16:1Δ11) and eicosatrienoic acid (20:3) were detected in colonized roots only when 13C2-acetate was supplemented but not 13C-fatty acids, demonstrating that de novo synthesized, host-derived fatty acids are rapidly taken up by R. irregularis from the roots. The results show that RiFAT1 and RiFAT2 are involved in the uptake of myristic acid (14:0) and palmitic acid (16:0), while fatty acids from MAGs are only taken up after hydrolysis. Therefore, the two proteins might be involved in fatty acid import into the fungal arbuscules in colonized roots.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Interaction of Fusarium Wilt Race 4 with Root-Knot Nematode Increases Disease Severity in Cotton
Authors: Wagner Tanya A. , Duke Sara E. , Davie Shayla M. , Magill Clint , Liu Jinggao
Published: March 2022

Fusarium wilt, caused by Fusarium oxysporum f. sp. vasinfectum, is a severe disease of cotton (Gossypium spp.). Strains of the wilt pathogen in the United States, such as race 1, require the presence of nematodes such as southern root-knot nematode (Meloidogyne incognita) to cause appreciable disease. The exception is the race 4 strain of the wilt pathogen, which can attack cotton without concomitant infection by plant-parasitic nematodes and was first identified in California in 2001 and in Texas and New Mexico since 2017. The effects of the interaction between M. incognita and race 1 or race 4 on wilt severity and nematode reproduction on two Gossypium hirsutum cultivars, Acala 44 and FM 966, and a G. barbadense cultivar, Pima S-4, were directly compared in growth chamber assays. All three cultivars were susceptible to M. incognita. Suppression of nematode reproduction by the wilt pathogen was detected only for race 4 on all three cultivars on a per plant basis but not on a per gram root tissue basis. The control, M. incognita alone, and race 1 alone treatments caused no symptoms. Inoculation with race 1 and M. incognita caused moderate wilt symptoms in ‘Acala 44’ and ‘FM 966’ and mild symptoms in ‘Pima S-4’. However, race 4 treatment caused severe wilt in ‘Pima S-4’ and moderate wilt severity in ‘Acala 44’ and ‘FM 966’. The symptom severity of ‘Acala 44’ and ‘FM 966’ further increased in the presence of M. incognita. Thus, race 4 is not only capable of causing wilt in the absence of M. incognita but can also interact with the nematode to further increase disease severity. Though control of wilt caused by race 1 can be achieved mainly through breeding for nematode resistance, it will be imperative to incorporate both southern root-knot nematode and race 4 resistance to effectively control the disease should race 4 expand into southern root-knot nematode-infested fields.
Benefit of Primary Tumor Resection in Stage IV, Grade 1 and 2, Pancreatic Neuroendocrine Tumors
Authors: Kjaer Josefine , Clancy Thomas E. , Thornell Anders , Andersson Niklas , Hellman Per , Crona Joakim , Welin Staffan , Sulciner Megan , Powell Brittany , Brais Lauren , Astone Kristina , Baddoo William , Doherty Gerhard , Chan Jennifer A. , Norlén Olov , Stålberg Peter
Published: March 2022

Objective:

To determine the association of primary tumor resection in stage IV pancreatic neuroendocrine tumors (Pan-NET) and survival in a propensity-score matched study.

Background:

Pan-NET are often diagnosed with stage IV disease. The oncologic benefit from primary tumor resection in this scenario is debated and previous studies show contradictory results.

Methods:

Patients from 3 tertiary referral centers from January 1, 1985, through December 31, 2019: Uppsala University Hospital (Uppsala, Sweden), Sahlgrenska University Hospital (Gothenburg, Sweden), and Brigham and Women’s Hospital/Dana-Farber Cancer Institute (Boston, USA) were assessed for eligibility. Patients with sporadic, grade 1 and 2, stage IV pan-NET, with baseline 2000–2019 were divided between those undergoing primary tumor resection combined with oncologic treatment (surgery group [SG]), and those who received oncologic treatment without primary tumor resection (non-SG). A propensity-score matching was performed to account for the variability in the extent of metastatic disease and comorbidity. Primary outcome was overall survival.

Results:

Patients with stage IV Pan-NET (n = 733) were assessed for eligibility, 194 were included. Patients were divided into a SG (n = 65) and a non-SG (n = 129). Two isonumerical groups with 50 patients in each group remained after propensity-score matching. The 5-year survival was 65.4% (95% CI, 51.5-79.3) in the matched SG and 47.8% (95% CI, 30.6-65.0) in the matched non-SG (log-rank, P = 0.043).

Conclusions:

Resection of the primary tumor in patients with stage IV Pan-NET and G1/G2 grade was associated with prolonged overall survival compared to nonoperative management. A surgically aggressive regime should be considered where resection is not contraindicated.
Practical Review of the Current Management of Fournier’s Gangrene
Authors: Huayllani Maria T. , Cheema Amandip S. , McGuire Matthew J. , Janis Jeffrey E.
Published: March 2022

Background:

Fournier’s gangrene is a fulminant disease. If diagnosed and treated early, mortality can be minimized, but morbidity can still be important with extensive soft tissue defects affecting form and function. We aimed to perform a comprehensive review and provide the current evidenced-based management to treat this condition.

Methods:

A review was conducted to identify relevant published articles involving Fournier’s gangrene in PubMed on September 8, 2021. Search keywords included “{[(Fournier’s gangrene) AND (reconstruction)] OR [Fournier’s gangrene]} AND [(repair) OR (management)].”

Results:

A total of 108 articles met the inclusion criteria. The comorbidities most frequently associated included diabetes, hypertension, and obesity. Pillars of treatment involve urgent debridement, fluid resuscitation, IV antibiotics, and reconstruction. Several variables must be considered, including time to debridement, duration of antibiotics, debridement, and an individualized approach to choose a reconstructive option. Skin grafts and multiple types of flaps are commonly used for reconstruction.

Conclusions:

Treatment of Fournier’s gangrene should be initiated as early as possible. Surgeons’ expertise, patient preference, and resources available are essential factors that should direct the election of reconstruction.
A Novel Method to Improve the Identification of Time of Intubation for Retrospective EHR Data Analysis During a Time of Resource Strain, the COVID-19 Pandemic
Authors: Makhnevich Alexander , Gandomi Amir , Wu Yiduo , Qiu Michael , Jafari Daniel , Rolston Daniel , Tsegaye Adey , Hajizadeh Negin ,   the Northwell ARDS Collaborative
Published: March 2022

Accurate determinations of the time of intubation (TOI) are critical for retrospective electronic health record (EHR) data analyses. In a retrospective study, the authors developed and validated an improved query (Ti) to identify TOI across numerous settings in a large health system, using EHR data, during the COVID-19 pandemic. Further, they evaluated the affect of Ti on peri-intubation patient parameters compared to a previous method—ventilator parameters (Tv). Ti identified an earlier TOI for 84.8% (n = 1666) of cases with a mean (SD) of 3.5 hours (15.5), resulting in alternate values for: partial pressure of arterial oxygen (PaO2) in 18.4% of patients (mean 43.95 mmHg [54.24]); PaO2/fractional inspired oxygen (FiO2) in 17.8% of patients (mean 48.29 [69.81]), and oxygen saturation/FiO2 in 62.7% (mean 16.75 [34.14]), using the absolute difference in mean values within the first 4 hours of intubation. Differences in PaO2/FiO2 using Ti versus Tv resulted in the reclassification of 7.3% of patients into different acute respiratory distress syndrome (ARDS) severity categories.
The Whole Health Transformation at the Veterans Health Administration
Authors: Kligler Benjamin , Hyde Justeen , Gantt Cynthia , Bokhour Barbara
Published: March 2022

The Veterans Health Administration is undergoing a system-wide transformation to a Whole Person/Whole Health approach to care. The Whole Health model of care is described including early outcome data on utilization and effectiveness. The paper describes the first 10 years of this transformation and provides lessons learned during that process regarding large-scale system change.
Heterogeneity and origins of myeloid cells
Authors: Yáñez Alberto , Bono Cristina , Goodridge Helen S.
Published: March 2022

Purpose of review

Myeloid cells – granulocytes, monocytes, macrophages and dendritic cells (DCs) – are innate immune cells that play key roles in pathogen defense and inflammation, as well as in tissue homeostasis and repair. Over the past 5 years, in part due to more widespread use of single cell omics technologies, it has become evident that these cell types are significantly more heterogeneous than was previously appreciated. In this review, we consider recent studies that have demonstrated heterogeneity among neutrophils, monocytes, macrophages and DCs in mice and humans. We also discuss studies that have revealed the sources of their heterogeneity.

Recent findings

Recent studies have confirmed that ontogeny is a key determinant of diversity, with specific subsets of myeloid cells arising from distinct progenitors. However, diverse microenvironmental cues also strongly influence myeloid fate and function. Accumulating evidence therefore suggests that a combination of these mechanisms underlies myeloid cell diversity.

Consideration of the heterogeneity of myeloid cells is critical for understanding their diverse activities, such as the role of macrophages in tissue damage versus repair, or tumor growth versus elimination. Insights into these mechanisms are informing the design of novel therapeutic approaches.
Multiresistant organisms: bacteria and beyond
Authors: Sole Amparo
Published: March 2022

Purpose of review

Infections with multiresistant organisms are an emerging problem, cause early mortality post lung transplantation and are sometimes associated with graft dysfunction. Frequently they raise questions about the selection of lung transplant candidates and therapeutic management post lung transplantation. There are no guidelines and management must be individualized. This review summarizes the available therapeutic options in cases of multidrug-resistant (MDR) organisms and outcomes after lung transplant.

Recent findings

Improvements in diagnosis, new and more effective drugs and the experience gained in the management of these infections in lung transplantation, lead to a more optimistic horizon than that found a decade ago.

Update on the management of Burkholderia cepacia complex, Mycobacterium abscessus complex, Aspergillus spp., Scedosporium spp. and Lomentospora prolificans infections. This review clarifies current posttransplant outcomes and adds a little hope in these scenarios.
Palliative Care in Severe and Persistent Mental Illness
Authors: Riley Kiernan , Hupcey Judith E. , Kowalchik Kalei
Published: March 2022

Severe and persistent mental illnesses refer to a group of psychiatric disorders causing severe dysfunction in patients and include diagnoses such as schizophrenia, bipolar disorder, and major depression. Patients with severe and persistent mental illnesses have a complex symptomatology and face complicated medical disparities creating a difficult care process and reduced quality of life. Palliative care, a holistic approach to care that aims to reduce symptoms and stress of illness in persons living with chronic diagnoses, is appropriate within this population to address the complexity of care needs but is currently underutilized. The purpose of this review was to systematically review the literature to determine what is currently known about palliative care utilization in the severe and persistently mentally ill population. The databases systematically searched include PubMed, Cumulative Index for Nursing and Allied Health Literature, PsycINFO, and MEDLINE, to find all articles relevant to the research question. Keywords include “palliative care,” “end-of-life care,” and “severe and persistent mental illness,” including all subsets. Literature was reviewed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The results of this systematic review helped synthesize current information about this developing topic to inform clinicians on how to best integrate palliative care to this population.
Clinicopathologic Evaluation of CTNNB1 Mutations in High-Intermediate Risk Endometrial Endometrioid Carcinoma
Authors: Haag Jennifer G. , Wolsky Rebecca J. , Moroney Marisa R. , Sheren Jamie , Sheeder Jeanelle , Bitler Benjamin G. , Corr Bradley R.
Published: March 2022

CTNNB1 mutations convey increased risk of recurrence in low-risk endometrial endometrioid carcinoma (EEC). Results from previous high-intermediate risk (HIR) cohorts are mixed. The aims of this study were to correlate CTNNB1 mutational status with clinical outcomes and to evaluate the relationship between CTNNB1 mutations and the 4 prognostic subgroups defined by The Cancer Genome Atlas in HIR EEC. CTNNB1 mutational status was determined by Sanger sequencing of exon 3 of the CTNNB1 gene. Mismatch repair, POLE, p53, and L1 cell-adhesion molecule (L1CAM) status were also evaluated. Descriptive statistics and survival analyses were performed. Eighty-eight cases of HIR EEC were identified, of which 22 (25%) were CTNNB1 mutant (CTNNB1-mut) and 66 (75%) were wild-type (CTNNB1-WT). Median follow-up was 60 mo. Recurrence occurred in 13/88 (15%) patients. Recurrence rates were not significantly different between patients with CTNNB1-mut and CTNNB1-WT tumors (14% vs. 15%, P=0.86). Recurrence-free survival and overall survival were not significantly different (recurrence-free survival hazard ratio: 0.97, 95% confidence interval: 0.27–3.52, P=0.96; overall survival hazard ratio: 0.23, 95% confidence interval: 0.03–1.71, P=0.15). Mismatch repair deficiency was more prevalent in CTNNB1-WT compared with CTNNB1-mut tumors (46% vs. 14%, P=0.01); prevalence of POLE mutations and aberrant p53 were not significantly different. In contrast to patients with low-risk EEC, no differences in recurrence or survival were found in patients with HIR EEC with CTNNB1-mut compared with CTNNB1-WT tumors.
Microscopic Sertoliform Sex Cord Proliferations: A Rare Incidental Finding Associated With Endometriosis and Ovarian Epithelial Neoplasia
Authors: Talia Karen L. , McCluggage W. Glenn
Published: March 2022

Microscopic sex cord proliferations are a rare incidental finding seen in association with ovarian and uterine stromal or epithelial neoplasms and more uncommonly non-neoplastic conditions such as endometriosis and adenomyosis. They may also occur in the absence of other pathology, as an incidental finding in the ovaries of pregnant women and in heterotopic locations such as the fallopian tube. Most reports of this phenomenon describe adult granulosa cell tumor-like morphology. Herein, we describe 4 cases of microscopic sex cord proliferations with Sertoliform features, occurring in the stromal component of endometriosis or in the wall of an epithelial ovarian neoplasm; 2 of the patients with endometriosis had concurrent endometrioid adenocarcinoma (1 uterine corpus, 1 ovary). The proliferations were positive with sex cord markers inhibin and calretinin. As far as we are aware, such Sertoliform proliferations have not been reported previously in endometriosis and have only rarely been described in association with ovarian epithelial neoplasia. It is likely that such proliferations represent a benign non-neoplastic phenomenon. Awareness of this phenomenon is important in order to avoid misdiagnosis as a sex cord or other neoplasm. In reporting this unusual phenomenon, we review incidental sex cord and sex cord-like proliferations in the female genital tract.
Genetic Influence on Neurodevelopment in Nonsyndromic Craniosynostosis
Authors: Timberlake Andrew T. , Junn Alexandra , Flores Roberto , Staffenberg David A. , Lifton Richard P. , Persing John A.
Published: March 2022

Background:

Nonsyndromic craniosynostosis is one of the most common anomalies treated by craniofacial surgeons. Despite optimal surgical management, nearly half of affected children have subtle neurocognitive deficits. Whereas timing and type of surgical intervention have been studied, the possibility of genetic influence on neurodevelopment in nonsyndromic craniosynostosis patients remains unexplored.

Methods:

The authors performed whole-exome sequencing for 404 case-parent trios with sporadic nonsyndromic craniosynostosis. Statistical analyses were performed to assess the burden of de novo mutations in cases compared to both expectation and 1789 healthy control trios. Individuals with and without each mutation class were analyzed, and the presence or absence of various types of neurodevelopmental delay were recorded alongside demographic information.

Results:

The authors identified a highly significant burden of damaging de novo mutations in mutation-intolerant [probability of loss of function intolerance (pLI) >0.9] genes in nonsyndromic craniosynostosis probands (p = 5.9 × 10−6). Children with these mutations had a two-fold higher incidence of neurodevelopmental delay (p = 0.001) and a more than 20-fold greater incidence of intellectual disability (p = 7.2 × 10−7), and were 3.6-fold more likely to have delays that persisted past 5 years of age (p = 4.4 × 10−4) in comparison with children with nonsyndromic craniosynostosis without these mutations. Transmitted loss of function mutations in high-pLI genes also conferred a 1.9-fold greater risk of neurodevelopmental delay (p = 4.5 ×10−4).

Conclusions:

These findings implicate genetic lesions concurrently impacting neurodevelopment and cranial morphogenesis in the pathoetiology of nonsyndromic craniosynostosis and identify a strong genetic influence on neurodevelopmental outcomes in affected children. These findings may eventually prove useful in determining which children with nonsyndromic craniosynostosis are most likely to benefit from surgical intervention.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Hypertelorbitism Corrected by Facial Bipartition Improves Exotropia
Authors: Chen Kevin , Duvvuri Priya , Gibstein Alex , Nakfoor Bruce , Fisher Mark , Kawamoto Henry , Bradley James P.
Published: March 2022

Background:

The purpose of this study was to detail perioperative ophthalmologic evaluations to characterize functional ocular outcomes after facial bipartition surgery.

Methods:

Patients with hypertelorbitism who underwent facial bipartition surgery were studied specifically for eye motility disorders by separating patients into rare craniofacial clefts (midline and paramedian) (n = 34) and craniofacial dysostosis (Apert, Crouzon, and Pfeiffer) (n = 74). Preoperative and postoperative (12 months) ophthalmologic examinations (with depth perception tests), computed tomography scans, and magnetic resonance imaging scans were analyzed.

Results:

Among craniofacial cleft patients, mean interdacryon distance was reduced from 39 ± 4 mm to 17 ± 2 mm, with strabismus improved from 88 percent (exotropia 82 percent) preoperatively to only 29 percent postoperatively. Depth perception improved to a lesser degree, with abnormal tests at a rate of 79 percent preoperatively to 56 percent postoperatively. Wider hypertelorbitism had a higher degree of strabismus. Among craniofacial dysostotic patients, mean interdacryon distance was reduced from 37 ± 3 mm to 17 ± 2 mm, and strabismus improved from 55 percent to only 14 percent. Depth perception improved to a lesser degree, with 68 percent abnormal tests preoperatively and 46 percent postoperatively. Apert patients had more V-pattern strabismus and exotropia (79 percent) than did other craniofacial dysostosis patients (42 percent).

Conclusions:

The authors’ data indicate that facial bipartition for hypertelorbitism—known to improve periorbital aesthetics—also improves eye motility disturbances. Thus, vision problems related to exotropia should be considered a functional indication for facial bipartition surgery in patients with hypertelorbitism.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Reasons for PrEP Discontinuation After Navigation at Sexual Health Clinics: Interactions Among Systemic Barriers, Behavioral Relevance, and Medication Concerns
Authors: Unger Zoe D. , Golub Sarit A. , Borges Christine , Edelstein Zoe R. , Hedberg Trevor , Myers Julie
Published: March 2022

Background:

Pre-exposure prophylaxis (PrEP) for HIV prevention requires engagement throughout the PrEP care continuum. Using data from a PrEP navigation program, we examine reasons for PrEP discontinuation.

Setting:

Participants were recruited from New York City Health Department Sexual Health Clinics with PrEP navigation programs.

Methods:

Participants completed a survey and up to 3 interviews about PrEP navigation and use. This analysis includes 94 PrEP initiators that were PrEP-naive before their clinic visit, started PrEP during the study, and completed at least 2 interviews. Interview transcripts were reviewed to assess reasons for PrEP discontinuation.

Results:

Approximately half of PrEP initiators discontinued PrEP during the study period (n = 44; 47%). Most participants (71%) noted systemic issues (insurance or financial problems, clinic or pharmacy logistics, and scheduling barriers) as reasons for discontinuation. One-third cited medication concerns (side effects, potential long-term side effects, and medication beliefs; 32%) and behavioral factors (low relevance of PrEP because of sexual behavior change; 34%) as contributing reasons. Over half (53.5%) highlighted systemic issues alone, while an additional 19% attributed discontinuation to systemic issues in combination with other factors. Of those who discontinued, approximately one-third (30%) restarted PrEP during the follow-up period, citing resolution of systemic issues or behavior change that increased PrEP relevance.

Conclusions:

PrEP continuation is dependent on interacting factors and often presents complex hurdles for patients to navigate. To promote sustained engagement in PrEP care, financial, clinic, and pharmacy barriers must be addressed and counseling and navigation should acknowledge factors beyond sexual risk that influence PrEP use.
Effect of WeChat Messaging on Improving the Quality of Bowel Preparation for Outpatient Colonoscopy
Authors: Wang Ce , Xie Xiao-Li , Hou Dong-Cang , Sun Chang , He Wen-Ying
Published: March 2022

With the most active users of any social media platform in China, WeChat has become the preferred platform for public announcements and is widely used in the fields of medicine and nursing (Hong, Zhou, Fang, & Shi, 2017
;
Zeng, Deng, Wang, & Liu, 2016). The aim of this study was to evaluate the effect of WeChat messaging on bowel preparation for outpatient colonoscopy. A total of 150 outpatients scheduled for colonoscopy in a Grade III level A hospital were randomly assigned to the experimental group (n = 73) or the control group (n = 72). Both groups received routine guidance from the day of the scheduling appointment through the day of colonoscopy. In addition, the experimental group received colonoscopy-related information and individualized guidance daily through WeChat from the day of the appointment. After the colonoscopy, the diet and medication compliance, satisfaction, anxiety, and bowel cleanliness were compared. Post-intervention, there were significant differences in bowel cleanliness, satisfaction, diet and medication compliance, and anxiety between the two groups. WeChat messaging can help improve diet and medication compliance, patient satisfaction, and the success rate and thoroughness of colonoscopy, as well as alleviate the anxiety of patients scheduled for outpatient colonoscopy.
A Novel High-throughput Droplet Digital PCR-based Indel Quantification Method for the Detection of Circulating Donor-derived Cell-free DNA After Kidney Transplantation
Authors: Verhoeven Jeroen G.H.P. , Boer Karin , Peeters Annemiek M.A. , Clahsen-van Groningen Marian C. , Roodnat Joke I. , van de Wetering Jacqueline , Nieboer Daan , Bost Douglas A. , Baan Carla C. , Hesselink Dennis A.
Published: March 2022

Background.

Donor-derived cell-free DNA (ddcfDNA) is a promising minimally invasive biomarker for acute rejection (AR) in kidney transplant recipients. To assess the diagnostic value of ddcfDNA as a marker for AR, ddcfDNA was quantified at multiple time points after kidney transplantation with a novel high-throughput droplet digital PCR indel method that allowed for the absolute quantification of ddcfDNA.

Methods.

In this study, ddcfDNA in plasma samples from 223 consecutive kidney transplant recipients was analyzed pretransplantation; at 3, 7, and 180 d after transplantation; and at time of for-cause biopsies obtained within the first 180 d after transplantation.

Results.

Median (interquartile range) ddcfDNA concentration was significantly higher on day 3 (58.3 [17.7-258.3] copies/mL) and day 7 (25.0 [10.4-70.8] copies/mL) than on day 180 after transplantation (4.2 [0.0-8.3] copies/mL; P < 0.001 and P < 0.001, respectively). At time of biopsy-proven AR (BPAR), between day 11 and day 180 after transplantation, ddcfDNA concentration was significantly higher (50.0 [25.0-108.3] copies/mL) than those when biopsies showed non-AR (0.0 [0.0-15.6] copies/mL; P < 0.05). ddcfDNA concentration within the first 10 d after transplantation showed no significant difference between recipients with BPAR and those with non-AR in their biopsy or between recipients with BPAR and ddcfDNA measured at day 3 and day 7.

Conclusions.

Unfortunately, ddcfDNA concentration is not a good biomarker to detect AR within the first 10 d after transplantation; however, BPAR occurring after 10 d after transplantation can be detected in kidney transplant recipients by ddcfDNA using a novel and unique high-throughput droplet digital PCR indel method.
An Assessment of Ineligible Donor Use in Solid Organ Transplant
Authors: DeRoos Luke J. , Tapper Elliot B. , Lavieri Mariel S. , Hutton David W. , Parikh Neehar D.
Published: March 2022

Background.

In the United States, the demand for organ transplants far outpaces available organs. The use of Organ Procurement and Transplantation Network–defined ineligible donors is an immediate method for increasing donations. However, the use of ineligible donors varies across organ procurement organizations (OPOs), and its association with recipient survival remains unclear.

Methods.

We evaluated ineligible donor use from 2008 to 2020 by OPO and its association with graft and recipient survival across demographics.

Results.

In this study of 297 223 organ donations, 42 184 (14%) did not meet eligibility criteria as defined by the Organ Procurement and Transplantation Network. Log-rank tests on Kaplan-Meier curves suggested differences in graft and patient survival between eligible and ineligible recipients for kidney and liver transplants (P ≤ 0.01 for all). Recipients of ineligible kidney and liver donations saw a 2.20% and 9.38% decrease in 10-y graft survival probability, respectively. There were no statistically significant graft and patient survival differences for recipients of ineligible heart, lung, and pancreas donations. Multivariate proportional hazard models showed eligibility was associated with kidney, liver, and lung graft survival (P ≤ 0.02 for all). However, if OPOs increased ineligible donor use to meet the current 75th percentile use rate, there could be as many as 1000 transplants and 6291 life-years gained annually.

Conclusions.

Ineligible donor use can provide significant survival benefit for patients who would otherwise never receive a transplant. Methods to reduce regional heterogeneity in ineligible donor use could increase the number of transplants and improve outcomes for waiting patients.
Neurocognitive and psychiatric post-coronavirus disease 2019 conditions: pathogenic insights of brain dysfunction following severe acute respiratory syndrome coronavirus 2 infection
Authors: García-Grimshaw Miguel , Sankowski Roman , Valdés-Ferrer Sergio Iván
Published: March 2022

Purpose of review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), can trigger a myriad of neuropsychiatric manifestations. As a 2-year-old disease (at the writing of this manuscript), its long-term cognitive and neuropsychiatric implications, known as post-COVID-19 conditions, are incompletely recognized and mechanistically obscure.

Recent findings

Fatigue, anxiety, depression, posttraumatic stress disorder, and cognitive dysfunction are reported more frequently in COVID-19 survivors than in matching, non-COVID-19 population. Risk factors are unclear, including comorbidities, age at COVID-19 onset, or disease severity; women, however, have been reported to be at increased risk than men. Although the frequency of these symptoms decreases over time, at least one in five will have persistent cognitive and neuropsychiatric manifestations one year after recovering from COVID-19.

Neurocognitive and psychiatric post-COVID-19 long-term conditions are frequent and complex multifactorial sequelae. Several acute and chronic factors such as hypoxemia, cerebral thrombotic and inflammatory endothelial damage, and disruption of the blood-brain barrier (leading to parenchymal translocation of pro-inflammatory molecules, cytokines, and cytotoxic T lymphocytes) are involved, leading to microglial activation and astrogliosis. As an evolving topic, evidence derived from prospective studies will expand our understanding of post-COVID-19 these long-term outcomes.
A critical appraisal of the singularity theorems
Authors: Senovilla José M. M.
Published: March 2022

The 2020 Nobel prize in Physics has revived the interest in the singularity theorems and, in particular, in the Penrose theorem published in 1965. In this short paper, I briefly review the main ideas behind the theorems and then proceed to an evaluation of their hypotheses and implications. I will try to dispel some common misconceptions about the theorems and their conclusions, as well as to convey some of their rarely mentioned consequences. In particular, a discussion of space–time extensions in relation to the theorems is provided. The nature of the singularity inside black holes is also analysed.

This article is part of the theme issue ‘The future of mathematical cosmology, Volume 1’.
Reformulating scalar–tensor field theories as scalar–scalar field theories using a novel geometry
Authors: Horndeski Gregory W.
Published: March 2022

In this paper, I shall show how the notions of Finsler geometry can be used to construct a similar geometry using a scalar field,
f
, on the cotangent bundle of a differentiable manifold
M
. This will enable me to use the second vertical derivatives of
f
, along with the differential of a scalar field
φ
on
M
, to construct a Lorentzian metric on
M
that depends upon
φ
. I refer to a field theory based upon a manifold with such a Lorentzian structure as a scalar–scalar field theory. We shall study such a theory when
f
is chosen so that the resultant metric on
M
has the form of a Friedmann–Lemaître–Robertson–Walker metric, and the Lagrangian has a particularly simple form. It will be shown that the scalar–scalar theory determined by the Lagrangian can generate self-inflating universes, which can be pieced together to form multiverses with non-Hausdorff topologies, in which the global time function multifurcates at
t
 = 0. Some of the universes in these multiverses begin explosively, and then settle down to a period of much quieter accelerated expansion, which can be followed by a collapse to its original, pre-expansion state.

This article is part of the theme issue ‘The future of mathematical cosmology, Volume 1’.
Geometrical origins of the universe dark sector: string-inspired torsion and anomalies as seeds for inflation and dark matter
Authors: Mavromatos Nick E.
Published: March 2022

In a modest attempt to present potentially new paradigms in cosmology, including its inflationary epoch, and initiate discussions, I review in this article some novel, string-inspired cosmological models, which entail a purely geometrical origin of the dark sector of the Universe but also of its observed matter-antimatter asymmetry. The models contain gravitational (string-model independent, Kalb–Ramond (KR)) axion fields coupled to primordial gravitational anomalies via CP-violating interactions. The anomaly terms are four-space–time-dimensional remnants of the Green–Schwarz counterterms appearing in the definition of the field strength of the spin-one antisymmetric tensor field of the (bosonic) massless gravitational string multiplet, which also plays the role of a totally antisymmetric component of torsion. I show how in such cosmologies the presence of primordial gravitational waves can lead to anomaly condensates and dynamical inflation of a ‘running-vacuum-model’ type, without external inflatons, but also to leptogenesis in the radiation era due to anomaly induced Lorentz and CPT violating KR axion backgrounds. I also discuss how the torsion-related KR-axion could acquire a mass during the QCD epoch, thus playing the role of (a component of) dark matter. Phenomenological considerations of the inflationary and post-inflationary (in particular, modern) eras of the model are briefly discussed, including its potential for alleviating the observed tensions in the cosmological data of the current epoch.

This article is part of the theme issue ‘The future of mathematical cosmology, Volume 1’.
Localized outbreaks of Pseudomonas aeruginosa belonging to international high-risk clones in a south Indian hospital
Authors: Pulusu Chanakya Pachi , Manivannan Bhavani , Raman Sai Suguna , Singh Sanjay , Khamari Balaram , Lama Manmath , Peketi Arun Sai Kumar , Datta Chandreyee , Prasad Kashi Nath , Nagaraja Valakunja , Pradeep Bulagonda Eswarappa
Published: March 2022

Introduction.

Pseudomonas aeruginosa

is now considered as a major bacterial pathogen associated with hospital infections. Frequently, multidrug-resistant (MDR) and extensively drug-resistant (XDR)

P. aeruginosa

are being encountered. Unusual increase in the

P. aeruginosa

infections led to the suspicion of outbreaks in the urology ward and cardiothoracic and vascular surgery intensive care unit (CTVS-ICU).

Hypothesis. We hypothesize that the localized outbreaks may have originated from environmental sources within the hospital premises. An alternative possibility is the transmission from a previously infected patient or hospital attendant. Understanding the drug-resistance profile and genome characteristics of these clinical samples would determine the likely source of infection and spread.

Aim. To perform epidemiological and molecular investigations on the suspected outbreaks of

P. aeruginosa

in the study centre and identify potential sources of infection.

Methodology. Fourteen drug-resistant

P. aeruginosa

isolated from patients of the urology ward, CTVS-ICU and tap waters collected during the suspected outbreaks were subjected to microbiological and genomic analysis. Comparative genome (CG) analysis of these 14 study genomes with 284 complete

P. aeruginosa

genomes was performed.

Results. Multilocus sequence typing analysis revealed that the isolates belonged to five different sequence types (ST235, ST357, ST639, ST654 and ST1203) and clustered into three distinct groups while two CTVS-ICU isolates remained as singletons. Genome analysis distinguished that the outbreaks in the urology ward and CTVS-ICU are independent, epidemiologically unrelated to each other and with the tap-water isolates.

Conclusion. This study highlights the presence of distinct, clonally unrelated, drug-resistant

P. aeruginosa

within a hospital setting. The genome analysis of the two localized outbreaks revealed their distinct genetic background and phylogenetically unrelated origin. Vigilant screening and effective implementation of infection control measures led to the successful containment of potential environmental reservoirs of

P. aeruginosa

within the premises.
Immunogenicity and safety of a recombinant adenovirus type-5 COVID-19 vaccine in adults: data from a randomised, double-blind, placebo-controlled, single-dose, phase 3 trial in Russia
Authors: Lioznov Dmitry , Amosova Irina , Sheetikov Savely A. , Zornikova Ksenia V. , Serdyuk Yana , Efimov Grigory A. , Tsyferov Mikhail , Khmelevskii Mikhail , Afanasiev Andrei , Khomyakova Nadezhda , Zubkov Dmitry , Tikhonov Anton , Zhu Tao , Barreto Luis , Dzutseva Vitalina
Published: March 2022

Background

To determine the immunogenicity, efficacy, reactogenicity, and safety of a single dose of recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV, 5 × 1010 viral particles per 0.5 mL dose), we conducted a single-dose, randomised, double-blind, placebo-controlled, parallel group (3:1 Ad5-nCoV:placebo), phase 3 trial (Prometheus).

Methods

From 11-September-2020 to 05-May-2021, across six sites in the Russian Federation, 496 participants were injected with either placebo or Ad5-nCoV expressing the full-length spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results

Seroconversion (the primary endpoint) rates of 78.5% (95% CI: 73.9; 82.6) against receptor binding domain (RBD), 90.6% (95% CI: 87.2; 93.4) against S protein and 59% (95% CI: 53.3; 64.6) against neutralising SARS-CoV2 antibodies 28 days post-vaccination. Geometric mean titres (GMTs) were also elevated for antibodies against the RBD (405.32 [95% CI: 361.58; 454.46]) and S protein (678.86 [95% CI: 607.44; 754.40]) compared to the GMT of neutralising antibodies against SARS-CoV-2 (16.73 [95% CI: 15.36; 18.22]). Using an IFN-γ ELISpot assay after stimulating the cells with full-length S protein we showed that the Ad5-nCoV vaccine induced the most robust cellular immune response on Days 14 and 28. Up to Day 28, the primary and all secondary endpoints of the Ad5-nCoV vaccine were statistically superior to the placebo (р <0.001). Systemic reactions were reported in 113 of 496 (22.8%) participants (Ad5-nCoV, 26.9%; Placebo, 10.5%), and local reactions were reported in 108 (21.8%) participants (Ad5-nCoV, 28.5%; Placebo, 1.6%). These were generally mild and resolved within 7 days after vaccination. Of the six serious adverse events reported, none of the events were vaccine related. There were no deaths or premature withdrawals.

Conclusion

A single-dose of Ad5-nCoV vaccine induced a marked specific humoral and cellular immune response with a favourable safety profile.

Trial Registration

ClinicalTrials.gov: NCT04540419
Stack Mapping Anchor Points (SMAP): a versatile suite of tools for read-backed haplotyping
Authors: Schaumont Dries , Veeckman Elisabeth , Van der Jeugt Felix , Haegeman Annelies , van Glabeke Sabine , Bawin Yves , Lukasiewicz Joanna , Blugeon Sebastien , Barre Philippe , Leyva-Pérez Maria de la O , Byrne Stephen , Dawyndt Peter , Ruttink Tom
Published: March 2022

Here we present SMAP, a software package that implements a suite of computational tools to extract multi-allelic haplotypes using read-backed haplotyping. SMAP tools first perform accurate read processing and analyze read mapping distributions across sample sets. Then, two complementary modules can be invoked for haplotype calling: SMAP haplotype-sites combines known Single Nucleotide Polymorphisms (SNPs) and/or read mapping position polymorphisms (SMAPs) to reconstruct compressed, read-reference-encoded haplotype strings. In contrast, SMAP haplotype-window works independent of prior knowledge of polymorphisms, groups reads by locus, defines a window enclosed between two custom border sequences, and retains the entire corresponding DNA sequence as haplotype. Haplotype-window is, among many applications, especially useful for high-throughput CRISPR/Cas mutation screens. Either way, SMAP creates a single integrated haplotype call table across all loci and samples. SMAP haplotyping is extremely versatile and can be applied to highly multiplex amplicon sequencing (HiPlex), Shotgun (e.g. whole genome shotgun (WGS) sequencing, probe capture and RNA-Seq), or Genotyping-by-Sequencing (GBS) data; and to Illumina short reads, PacBio and MinION long reads. SMAP creates discrete genotype calls for individuals of any ploidy or quantitative haplotype frequency spectra for Pool-Seq data, and can scale from tens to thousands of loci and/or samples. SMAP, including the source code written in Python is available at https://gitlab.com/truttink/smap, and a detailed user manual and guidelines for accurate read processing is available at https://ngs-smap.readthedocs.io/, under the GNU Affero General Public License v3.0.
Fast analyzing, exploring and sharing quantitative omics data using omicsViewer
Authors: Meng Chen
Published: March 2022

To facilitate the biological interpretation of omics data, we developed a general omics data visualization platform termed omicsViewer, enabling interactive visualization of statistical results and performing downstream analyses directly in response to features and samples selected. Multiple hypotheses and parameters can be evaluated in a few clicks. In addition, users can share the platform and statistical results with collaborators and the public in different ways.

Availability and Implementation

The project page ishttps://github.com/mengchen18/omicsViewer

Contact

chen.meng@tum.de