bluuebunny/crossref_metadata_2025 huggingface dataset:
Cancer among kidney transplant recipients >20 years after transplantation: post-transplant lymphoproliferative disorder remains the most common cancer type in the ultra long-term
Authors: Fuhrmann Julia D , Valkova Kristyna , von Moos Seraina , Wüthrich Rudolf P , Müller Thomas F , Schachtner Thomas
Published: January 2022

Background

Cancer risk is increased by 2- to 4-fold in kidney transplant recipients (KTRs) compared with the general population. Little attention, however, has been given to KTRs with ultra long-term survival >20 years.

Methods

We studied 293 of 1241 KTRs (23.6%), transplanted between 1981 and 1999, who showed kidney allograft survival >20 years. These long-term survivors were analysed for cancer development, cancer type, cancer-associated risk factors and patient and allograft outcomes.

Results

By 10, 20 and 30 years post-transplantation, these long-term KTRs showed a cancer rate of 4.4%, 14.6% and 33.2%, and a non-melanoma skin cancer (NMSC) rate of 10.3%, 33.5% and 76.8%, respectively. By recipients’ ages of 40, 60 and 80 years, KTRs showed a cancer rate of 3.4%, 14.5% 55.2%, and a NMSC rate of 1.7%, 31.6% and 85.2%, respectively. By 30 years post-transplantation, post-transplant lymphoproliferative disorder (PTLD) showed the highest incidence of 8.5%, followed by renal cell carcinoma (RCC) with 5.1%. Risk factors associated with the development of cancer were only recipient age (P = 0.016). Smoking history was associated with the risk of lung cancer (P = 0.018). Risk factors related to the development of NMSC included recipient age (P = 0.001) and thiazide diuretics (P = 0.001). Cancer increased the risk of death by 2.4-fold (P = 0.002), and PTLD increased the risk of kidney allograft loss by 6.5-fold (P = 0.001). No differences were observed concerning the development of donor-specific antibodies (P > 0.05).

Conclusions

In long-term KTRs, cancer is a leading cause of death. PTLD remains the most common cancer type followed by RCC. These results emphasize the need for focused long-term cancer surveillance protocols.
Authors’ attitude toward adopting a new workflow to improve the computability of phenotype publications
Authors: Cui Hong , Ford Bruce , Starr Julian , Reznicek Anton , Zhang Limin , Macklin James A
Published: January 2022

Critical to answering large-scale questions in biology is the integration of knowledge from different disciplines into a coherent, computable whole. Controlled vocabularies such as ontologies represent a clear path toward this goal. Using survey questionnaires, we examined the attitudes of biologists toward adopting controlled vocabularies in phenotype publications. Our questions cover current experience and overall attitude with controlled vocabularies, the awareness of the issues around ambiguity and inconsistency in phenotype descriptions and post-publication professional data curation, the preferred solutions and the effort and desired rewards for adopting a new authoring workflow. Results suggest that although the existence of controlled vocabularies is widespread, their use is not common. A majority of respondents (74%) are frustrated with ambiguity in phenotypic descriptions, and there is a strong agreement (mean agreement score 4.21 out of 5) that author curation would better reflect the original meaning of phenotype data. Moreover, the vast majority (85%) of researchers would try a new authoring workflow if resultant data were more consistent and less ambiguous. Even more respondents (93%) suggested that they would try and possibly adopt a new authoring workflow if it required 5% additional effort as compared to normal, but higher rates resulted in a steep decline in likely adoption rates. Among the four different types of rewards, two types of citations were the most desired incentives for authors to produce computable data. Overall, our results suggest the adoption of a new authoring workflow would be accelerated by a user-friendly and efficient software-authoring tool, an increased awareness of the challenges text ambiguity creates for external curators and an elevated appreciation of the benefits of controlled vocabularies.
Outcome of esophageal atresia: inborn versus outborn patients
Authors: Schlee Denise , Theilen Till-Martin , Fiegel Henning , Hutter Martin , Rolle Udo
Published: January 2022

Esophageal atresia (EA) is a rare congenital disease which is usually not of the detected prenatally. Due to the lack of prenatal diagnosis, some newborns with EA are born outside of specialized centers. Nevertheless, centralized care of EA has been proposed, even if a clear volume–outcome association in EA management remains unconfirmed. Furthermore, whether outcomes differ between outborn and inborn patients with EA has not been systematically investigated. Therefore, this single-center, retrospective study aimed to investigate EA management and outcomes with a special focus on inborn versus outborn patients. The following data were extracted from the medical records of infants with EA from 2009 to 2019: EA type, associated anomalies, complications, and long-term outcome. Patients were allocated into inborn and outborn groups. Altogether, 57 patients were included. Five patients were excluded (referral before surgery, loss of data, death before surgery [n = 1], and incorrect diagnosis [diverticulum, n = 1]). Among all patients, the overall survival rate was 96%, with no mortalities among outborn patients. The overall hospitalization period was shorter for outborn patients. The median follow-up durations were 3.8 years and 3.2 years for inborn and outborn patients, respectively. Overall, 15% of patients underwent delayed primary anastomosis (long-gap atresia [n = 4] and other reasons [n = 4]). Early complications included three anastomotic leakages and one post-operative fistula; 28% of patients developed strictures, which required dilatation, and 38% of patients showed relevant gastroesophageal reflux, which required fundoplication, without any differences between the groups. The two groups had comparable low mortality and expected high morbidity with no significant differences in outcome. The outborn group showed nonsignificant trends toward lower morbidity and shorter hospitalization periods, which might be explained by the overall better clinical status.
Transvalvular jet velocity, aortic valve area, mortality, and cardiovascular outcomes
Authors: Alcón Blanca , Martínez-Legazpi Pablo , Stewart Simon , Gonzalez-Mansilla Ana , Cuadrado Víctor , Strange Geoff , Yotti Raquel , Cascos Enric , Delgado-Montero Antonia , Prieto-Arévalo Raquel , Mombiela Teresa , Rodríguez-González Elena , Espinosa M Ángeles , Postigo Andrea , Gutiérrez-Ibanes Enrique , Pérez-Vallina Manuel , Fernández-Avilés Francisco , Playford David , Bermejo Javier
Published: January 2022

Aims

The interplay between aortic stenosis (AS), cardiovascular events, and mortality is poorly understood. In addition, how echocardiographic indices compare for predicting outcomes remains unexplored for the full range of AS severity.

Methods and results

We prospectively calculated peak jet velocity (Vmax) and aortic valve area (AVA) in 5994 adult subjects with and without AS. We linked ultrasound data to 5-year mortality and clinical events obtained from electronic medical records. Proportional-hazard and negative binomial regression models were adjusted for relevant covariables such as age, sex, comorbidities, stroke-volume, LV ejection fraction, left valve regurgitation, aortic valve sclerosis or calcification, and valve replacement. We observed a strong linear relationship between Vmax and all-cause mortality (hazard ratio: 1.26, 95% confidence interval: 1.19–1.33 per 100 cm/s), cardiovascular events, as well as incidental and recurrent heart failure (HF). Adjusted risks were highly significant even at Vmax values in the range of 150–200 cm/s, risk curves separating very early after the index exam. Vmax was not associated with coronary, arrhythmic, cerebrovascular, or non-cardiovascular events. Although risks were confirmed when AVA was entered in place of Vmax, the risks estimated for categories based on the two indices were mismatched, even in patients with normal flow. An external cohort comprising 112 690 patients confirmed augmented risks of all-cause and cardiovascular mortality starting at values of Vmax and AVA in the range of mild AS.

Conclusions

Aortic stenosis is strongly associated to all-cause mortality, cardiovascular mortality, and cardiac events, specifically HF. Risks increase in parallel to the degree of outflow obstruction but are apparent very early in patients with mild disease. Criteria for grading AS based on Vmax and AVA are mismatched in terms of outcomes.
Rethinking the roles of ELT in English-medium education in multilingual university settings: an introduction
Authors: Dafouz Emma , Gray John
Published: January 2022

The Introduction to this Special Issue on ELT and English-medium education in multilingual university settings provides a picture of the dynamic backdrop to the issues addressed by our contributing writers. We begin with a reflection on the nature of ELT and then move to a discussion of the specific nature of English-medium education in higher education globally. The Introduction underlines the importance of respecting and drawing on students’ multilingual repertoires, and the opportunities this affords for decolonising ELT in university settings.
High-Quality Reference Genome for an Arid-Adapted Mammal, the Banner-Tailed Kangaroo Rat (Dipodomys spectabilis)
Authors: Harder Avril M , Walden Kimberly K O , Marra Nicholas J , Willoughby Janna R
Published: January 2022

Kangaroo rats in the genus Dipodomys are found in a variety of habitat types in western North America, including deserts, arid and semiarid grasslands, and scrublands. Many Dipodomys species are experiencing strong population declines due to increasing habitat fragmentation, with two species listed as federally endangered in the United States. The precarious state of many Dipodomys populations, including those occupying extreme environments, make species of this genus valuable subjects for studying the impacts of habitat degradation and fragmentation on population genomic patterns and for characterizing the genomic bases of adaptation to harsh conditions. To facilitate exploration of such questions, we assembled and annotated a reference genome for the banner-tailed kangaroo rat (Dipodomys spectabilis) using PacBio HiFi sequencing reads, providing a more contiguous genomic resource than two previously assembled Dipodomys genomes. Using the HiFi data for D. spectabilis and publicly available sequencing data for two other Dipodomys species (Dipodomys ordii and Dipodomys stephensi), we demonstrate the utility of this new assembly for studies of congeners by conducting inference of historic effective population sizes (Ne) and linking these patterns to the species’ current extinction risk statuses. The genome assembly presented here will serve as a valuable resource for population and conservation genomic studies of Dipodomys species, comparative genomic research within mammals and rodents, and investigations into genomic adaptation to extreme environments and changing landscapes.
SARS-CoV-2 Placentitis Associated With B.1.617.2 (Delta) Variant and Fetal Distress or Demise
Authors: Shook Lydia L , Brigida Sara , Regan James , Flynn James P , Mohammadi Abbas , Etemad Behzad , Siegel Molly R , Clapp Mark A , Li Jonathan Z , Roberts Drucilla J , Edlow Andrea G
Published: January 2022

There is limited information on the specific impact of maternal infection with the SARS-CoV-2 B.1.617.2 (delta) variant on pregnancy outcomes. We present 2 cases of intrauterine fetal demise and 1 case of severe fetal distress in the setting of maternal infection with delta-variant SARS-CoV-2. In all cases, fetal demise or distress occurred within 14 days of COVID-19 diagnosis. Evaluation revealed maternal viremia, high nasopharyngeal viral load, evidence of placental infection with delta-variant SARS-CoV-2, and hallmark features of SARS-CoV-2 placentitis. We suggest that delta-variant SARS-CoV-2 infection during pregnancy warrants vigilance for placental dysfunction and fetal compromise regardless of disease severity.
Vertebral Trabecular Bone Mechanical Properties Vary Among Functional Groups of Cetaceans
Authors: Ingle D N , Porter M E
Published: January 2022

Synopsis

Since their appearance in the fossil record 34 million years ago, modern cetaceans (dolphins, whales, and porpoises) have radiated into diverse habitats circumglobally, developing vast phenotypic variations among species. Traits such as skeletal morphology and ecologically linked behaviors denote swimming activity; trade-offs in flexibility and rigidity along the vertebral column determine patterns of caudal oscillation. Here, we categorized 10 species of cetaceans (families Delphinidae and Kogiidae; N = 21 animals) into functional groups based on vertebral centra morphology, swimming speeds, diving behavior, and inferred swimming patterns. We quantified trabecular bone mechanical properties (yield strength, apparent stiffness, and resilience) among functional groups and regions of the vertebral column (thoracic, lumbar, and caudal). We extracted 6 mm3 samples from vertebral bodies and tested them in compression in 3 orientations (rostrocaudal, dorsoventral, and mediolateral) at 2 mm min−1. Overall, bone from the pre-fluke/fluke boundary had the greatest yield strength and resilience, indicating that the greatest forces are translated to the tail during caudal oscillatory swimming. Group 1, composed of 5 shallow-diving delphinid species, had the greatest vertebral trabecular bone yield strength, apparent stiffness, and resilience of all functional groups. Conversely, Group 3, composed of 2 deep-diving kogiid species, had the least strong, stiff, and resilient bone, while Group 2 (3 deep-diving delphinid species) exhibited intermediate values. These data suggest that species that incorporate prolonged glides during deep descents in the water column actively swim less, and place relatively smaller loads on their vertebral columns, compared with species that execute shallower dives. We found that cetacean vertebral trabecular bone properties differed from the properties of terrestrial mammals; for every given bone strength, cetacean bone was less stiff by comparison. This relative lack of material rigidity within vertebral bone may be attributed to the non-weight-bearing locomotor modes of fully aquatic mammals.
Generalizable EHR-R-REDCap pipeline for a national multi-institutional rare tumor patient registry
Authors: Shalhout Sophia Z , Saqlain Farees , Wright Kayla , Akinyemi Oladayo , Miller David M
Published: January 2022

Objective

To develop a clinical informatics pipeline designed to capture large-scale structured Electronic Health Record (EHR) data for a national patient registry.

Materials and Methods

The EHR-R-REDCap pipeline is implemented using R statistical software to remap and import structured EHR data into the Research Electronic Data Capture (REDCap)-based multi-institutional Merkel Cell Carcinoma (MCC) Patient Registry using an adaptable data dictionary.

Results

Clinical laboratory data were extracted from EPIC Clarity across several participating institutions. Laboratory values (Labs) were transformed, remapped, and imported into the MCC registry using the EHR labs abstraction (eLAB) pipeline. Forty-nine clinical tests encompassing 482 450 results were imported into the registry for 1109 enrolled MCC patients. Data-quality assessment revealed highly accurate, valid labs. Univariate modeling was performed for labs at baseline on overall survival (N = 176) using this clinical informatics pipeline.

Conclusion

We demonstrate feasibility of the facile eLAB workflow. EHR data are successfully transformed and bulk-loaded/imported into a REDCap-based national registry to execute real-world data analysis and interoperability.
Social-Jetlagged Consumers and Decreased Conspicuous Consumption
Authors: Yin Yunlu , Huang Zhongqiang (Tak)
Published: January 2022

People’s schedules are jointly determined by their biological clock and social clock. However, their social clock often deviates from the biological clock (e.g., having to get up earlier than one’s natural wake-up time for work or study, having to stay up to work night shifts or meet a project deadline)—a phenomenon known as “social jetlag.” How does social jetlag impact consumer behavior? Using field data and experiments, we show that social jetlag decreases conspicuous consumption because consumers experiencing social jetlag are less interested in social interaction. This effect is weakened when social interaction occurs among familiar others rather than strangers, when conspicuous consumption does not draw social attention, and when consumers expect to use a luxury product in a private setting.
Boron neutron capture therapy and add-on bevacizumab in patients with recurrent malignant glioma
Authors: Furuse Motomasa , Kawabata Shinji , Wanibuchi Masahiko , Shiba Hiroyuki , Takeuchi Koji , Kondo Natsuko , Tanaka Hiroki , Sakurai Yoshinori , Suzuki Minoru , Ono Koji , Miyatake Shin-Ichi
Published: January 2022

Background

Although boron neutron capture therapy has shown excellent survival data, previous studies have shown an increase in radiation necrosis against recurrent malignant glioma. Herein, we proposed that bevacizumab may reduce radiation injury from boron neutron capture therapy by re-irradiation. We evaluated the efficacy and safety of a boron neutron capture therapy and add-on bevacizumab combination therapy in patients with recurrent malignant glioma.

Methods

Patients with recurrent malignant glioma were treated with reactor-based boron neutron capture therapy. Treatment with bevacizumab (10 mg/kg) was initiated 1–4 weeks after boron neutron capture therapy and was administered every 2–3 weeks until disease progression. Initially diagnosed glioblastomas were categorized as primary glioblastoma, whereas other forms of malignant glioma were categorized as non-primary glioblastoma.

Results

Twenty-five patients (14 with primary glioblastoma and 11 with non-primary glioblastoma) were treated with boron neutron capture therapy and add-on bevacizumab. The 1-year survival rate for primary glioblastoma and non-primary glioblastoma was 63.5% (95% confidence interval: 33.1–83.0) and 81.8% (95% confidence interval: 44.7–95.1), respectively. The median overall survival was 21.4 months (95% confidence interval: 7.0–36.7) and 73.6 months (95% confidence interval: 11.4–77.2) for primary glioblastoma and non-primary glioblastoma, respectively. The median progression-free survival was 8.3 months (95% confidence interval: 4.2–12.1) and 15.6 months (95% confidence interval: 3.1–29.8) for primary glioblastoma and non-primary glioblastoma, respectively. Neither pseudoprogression nor radiation necrosis were identified during bevacizumab treatment. Alopecia occurred in all patients. Six patients experienced adverse events ≥grade 3.

Conclusions

Boron neutron capture therapy and add-on bevacizumab provided a long overall survival and a long progression-free survival in recurrent malignant glioma compared with previous studies on boron neutron capture therapy alone. The add-on bevacizumab may reduce the detrimental effects of boron neutron capture therapy, including pseudoprogression and radiation necrosis. Further studies of the combination therapy with a larger sample size and a randomized controlled design are warranted.
Cumulative Advanced Breast Cancer Risk Prediction Model Developed in a Screening Mammography Population
Authors: Kerlikowske Karla , Chen Shuai , Golmakani Marzieh K , Sprague Brian L , Tice Jeffrey A , Tosteson Anna N A , Rauscher Garth H , Henderson Louise M , Buist Diana S M , Lee Janie M , Gard Charlotte C , Miglioretti Diana L
Published: January 2022

Background

Estimating advanced breast cancer risk in women undergoing annual or biennial mammography could identify women who may benefit from less or more intensive screening. We developed an actionable model to predict cumulative 6-year advanced cancer (prognostic pathologic stage II or higher) risk according to screening interval.

Methods

We included 931 186 women aged 40-74 years in the Breast Cancer Surveillance Consortium undergoing 2 542 382 annual (prior mammogram within 11-18 months) or 752 049 biennial (prior within 19-30 months) screening mammograms. The prediction model includes age, race and ethnicity, body mass index, breast density, family history of breast cancer, and prior breast biopsy subdivided by menopausal status and screening interval. We used fivefold cross-validation to internally validate model performance. We defined higher than 95th percentile as high risk (>0.658%), higher than 75th percentile to 95th or less percentile as intermediate risk (0.380%-0.658%), and 75th or less percentile as low to average risk (<0.380%).

Results

Obesity, high breast density, and proliferative disease with atypia were strongly associated with advanced cancer. The model is well calibrated and has an area under the receiver operating characteristics curve of 0.682 (95% confidence interval = 0.670 to 0.694). Based on women’s predicted advanced cancer risk under annual and biennial screening, 69.1% had low or average risk regardless of screening interval, 12.4% intermediate risk with biennial screening and average risk with annual screening, and 17.4% intermediate or high risk regardless of screening interval.

Conclusion

Most women have low or average advanced cancer risk and can undergo biennial screening. Intermediate-risk women may consider annual screening, and high-risk women may consider supplemental imaging in addition to annual screening.
Low-grade appendiceal mucinous neoplasm (LAMN) as a mimicker of perforated diverticulitis: a case report
Authors: Shean Christopher , Balasooriya Janaka , Fergusson James
Published: January 2022

The differential diagnosis of abdominal pain is wide as both benign and malignant pathologies must be considered. There are currently no published case reports of low-grade appendiceal mucinous neoplasms (LAMNs) mimicking perforated diverticulitis. LAMNs are a heterogenous group of tumours, with no consensus treatment algorithm based on stage and histology. In this case report, we discuss a patient who presented emergently with generalized peritonism, with a diagnosis of perforated diverticulitis made on computed tomography scan. At laparotomy, a perforated appendix was identified, with histopathology identifying a perforated LAMN. This case highlights the importance of considering this rare but increasing incidence tumour when operative management is being planned.
Structural diversity, biosynthesis, and function of plant falcarin-type polyacetylenic lipids
Authors: Santos Patrícia , Busta Lucas , Yim Won Cheol , Cahoon Edgar B , Kosma Dylan K
Published: January 2022

The polyacetylenic lipids falcarinol, falcarindiol, and associated derivatives, termed falcarins, have a widespread taxonomical distribution in the plant kingdom and have received increasing interest for their demonstrated health-promoting properties as anti-cancer and anti-inflammatory agents. These fatty acid-derived compounds are also linked to plant pathogen resistance through their potent antimicrobial properties. Falcarin-type polyacetylenes, which contain two conjugated triple bonds, are derived from structural modifications of the common fatty acid oleic acid. In the past half century, much progress has been made in understanding the structural diversity of falcarins in the plant kingdom, whereas limited progress has been made on elucidating falcarin function in plant–pathogen interactions. More recently, an understanding of the biosynthetic machinery underlying falcarin biosynthesis has emerged. This review provides a concise summary of the current state of knowledge on falcarin structural diversity, biosynthesis, and plant defense properties. We also present major unanswered questions about falcarin biosynthesis and function.
Low-Cost Model for Battlefield Wound and Hemorrhage Training
Authors: Bates James T , Kelly Christopher W , Lane Joshua E
Published: January 2022

Introduction

Exsanguination is the leading cause of preventable death on the battlefield and in austere environments. Multiple courses have been developed to save lives by stopping hemorrhage. Training for this requires simulation models; however, many models are expensive, preventing the further expansion of this life-saving training. We present a low-cost model for hemorrhage training and realistic moulage based on simple medical supplies and grocery store meats.

Materials and Methods

Wound packing training was completed by use of a block of pork shoulder roast with an incision simulating a wound and IV tubing connected to a syringe with fake blood. Hemostasis was obtained with proper wound packing by the student, causing the bleeding to be tamponaded. Wound moulage utilized remaining supplies of pork roast being attached to patient actors or mannequins and adorned with fake blood creating wounds with the appearance and feel of real tissues.

Results

Tactical Combat Casualty Care (TCCC) training was completed at a small military medical facility with a start-up cost of less than $70 and a single course as cheap as $15. These methods have been utilized to establish other TCCC training centers while keeping costs low.

Conclusions

We present low-cost models for simulating massive hemorrhage for wound packing with pork roast and realistic moulage. These methods can be utilized for other hemorrhage training courses such as TCCC, Advanced Wilderness Life Support, and Stop the Bleed.
The suitability of micronuclei as markers of relative biological effect
Authors: Heaven Charlotte J , Wanstall Hannah C , Henthorn Nicholas T , Warmenhoven John-William , Ingram Samuel P , Chadwick Amy L , Santina Elham , Honeychurch Jamie , Schmidt Christine K , Kirkby Karen J , Kirkby Norman F , Burnet Neil G , Merchant Michael J
Published: January 2022

Micronucleus (MN) formation is routinely used as a biodosimeter for radiation exposures and has historically been used as a measure of DNA damage in cells. Strongly correlating with dose, MN are also suggested to indicate radiation quality, differentiating between particle and photon irradiation. The “gold standard” for measuring MN formation is Fenech’s cytokinesis-block micronucleus (CBMN) cytome assay, which uses the cytokinesis blocking agent cytochalasin-B. Here, we present a comprehensive analysis of the literature investigating MN induction trends in vitro, collating 193 publications, with 2476 data points. Data were collected from original studies that used the CBMN assay to quantify MN in response to ionizing radiation in vitro. Overall, the meta-analysis showed that individual studies mostly have a linear increase of MN with dose [85% of MN per cell (MNPC) datasets and 89% of percentage containing MN (PCMN) datasets had an R2 greater than 0.90]. However, there is high variation between studies, resulting in a low R2 when data are combined (0.47 for MNPC datasets and 0.60 for PCMN datasets). Particle type, species, cell type, and cytochalasin-B concentration were suggested to influence MN frequency. However, variation in the data meant that the effects could not be strongly correlated with the experimental parameters investigated. There is less variation between studies when comparing the PCMN rather than the number of MNPC. Deviation from CBMN protocol specified timings did not have a large effect on MN induction. However, further analysis showed less variation between studies following Fenech’s protocol closely, which provided more reliable results. By limiting the cell type and species as well as only selecting studies following the Fenech protocol, R2 was increased to 0.64 for both measures. We therefore determine that due to variation between studies, MN are currently a poor predictor of radiation-induced DNA damage and make recommendations for futures studies assessing MN to improve consistency between datasets.
Educating the Public on the Health Risks of Very Low Nicotine Content Cigarettes: Results From a US-Based Convenience Sample
Authors: Differding MacKenzie , Katz Sherri Jean , Strayer Lori G , White Cassidy , Strasser Andrew A , Donny Eric C , Hatsukami Dorothy K , Carroll Dana Mowls
Published: January 2022

Introduction

US FDA issued an advance notice of proposed rulemaking to reduce nicotine in cigarettes. To maximize the benefits of this potential standard, very low nicotine content (VLNC) cigarettes must be communicated in a way that does not result in misperceptions.

Aims and Methods

Adults (n = 567 who smoke; n = 610 non-smokers) from an online platform were randomized to a control message previously associated with accurate addictiveness perceptions of VLNC cigarettes but health misperceptions or to one of five messages that also included messaging on nicotine morbidity effects or VLNC cigarettes morbidity or mortality effects. p value <.01 was significant.

Results

In participants who smoke, perceived lung cancer risk (responses: 1, very little risk to 10, very high risk) if smoked VLNC cigarettes regularly was higher in conditions that communicated mortality effects of VLNC cigarettes compared to the control (7.12–7.18 vs. 5.97, p values < .01). In non-smokers, perceived lung cancer risk was higher in all five message conditions when compared with the control (7.58–8.22 vs. 6.35, p values < .01). Proportion who responded accurately (ie, False) to the statement Cigarettes with 95% less nicotine are safer than cigarettes with normal nicotine levels was higher in conditions describing VLNC morbidity or mortality effects when compared with the control in both participants who smoke (52.04–67.37% vs. 30.85%, p values < .01) and do not smoke (62.50–72.38% vs. 32.00%, p values < .01).

Conclusions

Messaging on mortality effects of VLNC cigarettes (ie, cigarettes with 95% less nicotine are as deadly as current cigarettes) was associated with more accurate perceptions of the health risks of VLNC cigarettes than the control; however, misperceptions remained in one-third of participants.

Implications

One approach to communicating a VLNC cigarette standard to the public is to include messaging on the mortality effects of VLNC cigarettes. However, further study and possible refinement of this message condition are recommended since approximately one-third of participants exposed to this message still perceived VLNC cigarettes to be safer than normal nicotine content cigarettes.
Small Business Lending in Financial Crises: The Role of Government-Guaranteed Loans
Authors: Hackney John
Published: January 2022

This paper examines whether the presence of government-guaranteed lenders helps alleviate small business financial constraints during financial crises. The results indicate that during the 2007–09 financial crisis, areas with a greater share of Small Business Administration 7(a) lenders experienced: (1) a 2.2% increase in small business loan volume, (2) a 3.7% increase in small firm employment and 3.5% increase in establishments, and (3) lower loan default rates. Bank–county–year analysis suggests that SBA banks increase their share of lending when they are capital-constrained, and when local median income is lower. Instrumental variable analysis utilizing SBA program characteristics confirms the baseline results. The findings suggest that targeted government support can play a beneficial role in the presence of private credit market frictions, especially when bank capital is limited and small business financial constraints are severe.
Anesthesia and Developing Brains: Unanswered Questions and Proposed Paths Forward
Authors: Ing Caleb , Warner David O. , Sun Lena S. , Flick Randall P. , Davidson Andrew J. , Vutskits Laszlo , McCann Mary Ellen , O’Leary James , Bellinger David C. , Rauh Virginia , Orser Beverley A. , Suresh Santhanam , Andropoulos Dean B.
Published: January 2022

Anesthetic agents disrupt neurodevelopment in animal models, but evidence in humans is mixed. The morphologic and behavioral changes observed across many species predicted that deficits should be seen in humans, but identifying a phenotype of injury in children has been challenging. It is increasingly clear that in children, a brief or single early anesthetic exposure is not associated with deficits in a range of neurodevelopmental outcomes including broad measures of intelligence. Deficits in other domains including behavior, however, are more consistently reported in humans and also reflect findings from nonhuman primates. The possibility that behavioral deficits are a phenotype, as well as the entire concept of anesthetic neurotoxicity in children, remains a source of intense debate. The purpose of this report is to describe consensus and disagreement among experts, summarize preclinical and clinical evidence, suggest pathways for future clinical research, and compare studies of anesthetic agents to other suspected neurotoxins.
Ovarian insufficiency and secondary amenorrhea in a patient with a novel variant within GDF9 gene
Authors: Marinakis Nikolaos M. , Tsoutsou Eirini , Sofocleous Christalena , Veltra Danai , Papaefthimiou Petros , Lytras Aristides , Traeger-Synodinos Joanne , Kanaka-Gantenbein Christina
Published: January 2022

Objective:

Premature ovarian insufficiency is a heterogeneous condition that can be caused by several factors, such as genetic, environmental, etc. and represents one of the main causes of female infertility. One of the genes implicated is GDF9, which encodes a member of the transforming growth factor-beta superfamily that participates in the coordination of somatic cell activity, female fertility, including folliculogenesis, and oocyte maturation. Damaging variants in GDF9-encoded growth factors can cause the production of inhibin, perturb oocyte granulosa cell microenvironments, and obstruct follicle development. A novel GDF9 variant is herein reported to consolidate the role of GDF9 in ovarian function and female fertility.

Methods:

A 38-year-old female was referred for the investigation of secondary amenorrhea. Eventually, she was referred for genetic evaluation whereby conventional karyotyping and Fragile-X molecular testing were normal. Whole Exome Sequencing was performed, followed by targeted Sanger sequencing in all family members for variant confirmation and evaluation.

Results:

In this study we report a patient presenting with secondary amenorrhea due to premature ovarian failure and a pituitary lesion with radiological characteristics compatible with a Rathke cyst or a macroadenoma, residing between the adenohypophysis and neurohypophysis. Whole Exome Sequencing revealed a novel heterozygous stoploss variant c.1364A>C, p.(*455Serext*8) in the GDF9 gene.

Conclusions:

Should the predicted elongated GDF9 protein and differentially configurated GDF9 mature protein molecule form unstable dimers, rapid proteolytic degradation may take place and inhibit homo/heterodimer formation.
Time series proteome profile analysis reveals a protective role of citrate synthase in angiotensin II-induced atrial fibrillation
Authors: Teng Fei , Han Xiao , Yu Peng , Li Pang-Bo , Li Hui-Hua , Zhang Yun-Long
Published: January 2022

Background:

Angiotensin (Ang) II and elevated blood pressure are considered to be the main risk factors for atrial fibrillation. However, the proteome profiles and key mediators/signaling pathways involved in the development of Ang II-induced atrial fibrillation remain unclear.

Methods:

Male wild-type C57BL/6 mice (10-week old) were infused with Ang II (2000 ng/kg per min) for 1, 2, or 3 weeks, respectively. Time series proteome profiling of atrial tissues was performed using isobaric tags for relative and absolute quantitation and liquid chromatography coupled with tandem mass spectrometry.

Results:

We identified a total of 1566 differentially expressed proteins (DEPs) in the atrial tissues at weeks 1, 2, and 3 after Ang II infusion. These DEPs were predominantly involved in mitochondrial oxidation-reduction and tricarboxylic acid cycle in Ang II-infused atria. Moreover, coexpression network analysis revealed that citrate synthase, a rate-limiting enzyme in the tricarboxylic acid cycle, was localized at the center of the mitochondrial oxidation-reduction process, and its expression was significantly downreguated in Ang II-infused atria at different time points. Cardiomyocyte-specific overexpresion of citrate synthase markedly reduced atrial fibrillation susceptibility and atrial remodeling in mice. These beneficial effects were associated with increased ATP production and mitochondrial oxidative phosphorylation system complexes I–V expression and inhibition of oxidative stress.

Conclusion:

The current study defines the dynamic changes of the DEPs involved in Ang II-induced atrial fibrillation, and identifies that citrate synthase plays a protective role in regulating atrial fibrillation development, and increased citrate synthase expression may represent a potential therapeutic option for atrial fibrillation treatment.
Chimeric antigen receptor T-cell therapy in acute myeloid leukemia
Authors: Koedam Jan , Wermke Martin , Ehninger Armin , Cartellieri Marc , Ehninger Gerhard
Published: January 2022

Purpose of review

Treatment outcome of relapsed or refractory AML patients remains dismal and new treatment options are needed. Adoptive cell therapy using CAR-T cells is a potentially interesting approach in this.

Recent findings

Several potentially interesting AML targets are being investigated with CAR-T therapy with over 60 clinical trials listed on clinicaltrials.gov. The first clinical data are only just emerging with mixed results, once more proving that further research is needed.

Adoptive cell therapy using chimeric antigen receptor T cells is being investigated in AML through many clinical trials. So far, no AML-specific antigen has been identified, requiring additional strategies to mitigate on-target off-tumor toxicity and to increase efficacy. Focus point is to acquire control over the CAR T cells once administered. Strategies to do so include biodegradable CARs, inducible CARs, suicide-switch containing CARs and two-component modular CARs. Limited and mixed results are available, confirming the risk of lasting toxicity for nonswitchable CARs. Initial results of modular CARs suggest toxicity can be mitigated whilst maintaining CAR activity by the use of modular CAR concepts that allows for ‘ON’ and ‘OFF’ switching.
HIV, Aging, and Comorbidities Research in Clinical Cohorts: 3 Lessons Learned Using Examples From the CNICS Cohort
Authors: Crane Heidi M. , Drumright Lydia
Published: January 2022

Background:

Owing to ongoing improvements in antiretroviral therapy, people with HIV (PWH) are achieving near-normal lifespans with many surviving into middle and old age. Despite this success, PWH have a higher than expected risk of developing non-AIDS comorbidities, multimorbidity, and functional decline at ages younger than those without HIV.

Methods:

As part of the Inter-CFAR (Center for AIDS Research) Symposium, HIV and Aging in the era of Antiretroviral Therapy and COVID-19, we presented a research update from HIV clinical cohorts and specifically described 3 lessons learned from the Centers for AIDS Research Network of Integrated Clinical Systems cohort that are important for HIV and aging research moving forward.

Results:

Adjudicated outcomes are particularly beneficial for less common comorbidities such as myocardial infarction. Multiple ascertainment approaches increase sensitivity over using diagnoses alone (89% vs. 44%). Adjudication eliminates false-positive events and allows myocardial infarction types to be identified. Comorbidity research has often relied on composite outcomes, such as all cardiovascular diseases, often to increase power. Mechanistic differences across outcomes demonstrate the importance of moving away from many composite outcomes. Timely data are needed to ensure findings are relevant to improve care or outcomes for the population of PWH who are currently aging.

Conclusions:

A better understanding of the causes, mechanisms, prevention and treatment of functional decline, comorbidities, and multimorbidities is a crucial research focus as PWH are aging. Clinical cohorts with timely, comprehensive harmonized clinical data and carefully adjudicated outcomes are ideally positioned to improve understanding of these questions.
Brief Report: Transgender Women and Preexposure Prophylaxis Care: High Preexposure Prophylaxis Adherence in a Real-World Health Care Setting in New York City
Authors: Starbuck Lila , Golub Sarit A. , Klein Augustus , Harris Alexander B. , Guerra Amiyah , Rincon Christopher , Radix Asa E.
Published: January 2022

Background:

Transgender women and trans feminine individuals (TGW/TFI) are a high priority population for the provision of HIV preexposure prophylaxis (PrEP) care within the United States, but there is limited research that focuses specifically on PrEP adherence within this population.

Setting:

Observational study of patients prescribed PrEP at a community-based health center.

Methods:

We enrolled 100 TGW/TFI PrEP patients at a community health center during clinic visits. Adherence data were collected at 3 time points, using self-report surveys, patient interviews, and urine assays measuring tenofovir. Data were summarized descriptively.

Results:

The sample was diverse in age, race/ethnicity, and socioeconomic characteristics. Participants demonstrated strong PrEP adherence; at least 80% of the sample reported 90% or greater adherence at each time point. Concordance between self-report and urine assay was high. Among patients who reported taking PrEP within the past 48 hours, 82%–92% had detectable urine tenofovir. However, many patients reported PrEP stop periods of 4 or more days (28%–39% per time point).

Conclusions:

Our data highlight TGW/TFI's capacity to adhere to daily PrEP and sustain PrEP use over time. The concordance between patient self-report and urine TFV levels suggest that providers can trust patient reports of PrEP adherence behavior and support the use of adherence conversations in clinical settings, without the need for point of care biological monitoring. Findings also underscore the importance of continued attention to drivers of PrEP stops at the patient, clinic, and systems levels and the development of strategies that support sustained PrEP use.
An Auxiliary Cranioparietal Anchorage System to Improve the Stability of the Rigid External Distraction Device in Children With Crouzon Syndrome
Authors: Liu Jing , Tong Haizhou , Wang Yongqian , Li Haidong , Wu Di , Yin Ningbei , Song Tao
Published: January 2022

Rigid external distraction (RED) device instability because of thin skulls in syndromic craniosynostosis patients remains challenging. The authors propose the use of an auxiliary cranioparietal anchorage system to improve RED device stability in patients with Crouzon syndrome. Five consecutive patients with Crouzon syndrome underwent Le Fort III osteotomy with midface advancement using a modified external device. Cephalometric analysis and three-dimensional computed tomography images were evaluated preoperatively and after device removal. Mechanical analyses of the RED device with and without the auxiliary cranioparietal anchorage system were performed. Both postoperative photographs and follow-up computed tomographs showed obvious midfacial advancement with no intracranial pin perforation or external frame migration. Mechanical analysis showed that the new system reduced the possibility of postoperative external frame migration. The auxiliary cranioparietal anchorage system might be considered an adjunct to the RED device in patients with Crouzon syndrome to avoid postoperative complications.
Environment in the lung of cystic fibrosis patients stimulates the expression of biofilm phenotype in Mycobacterium abscessus
Authors: Keefe Bailey F. , Bermudez Luiz E.
Published: January 2022

Introduction. Pulmonary infections caused by organisms of the

Mycobacterium abscessus

complex are increasingly prevalent in populations at risk, such as patients with cystic fibrosis, bronchiectasis and emphysema.

Hypothesis.

M. abscessus

infection of the lung is not observed in immunocompetent individuals, which raises the possibility that the compromised lung environment is a suitable niche for the pathogen to thrive in due to the overproduction of mucus and high amounts of host cell lysis.

Aim. Evaluate the ability of

M. abscessus

to form biofilm and grow utilizing in vitro conditions as seen in immunocompromised lungs of patients.

Methodology. We compared biofilm formation and protein composition in the presence and absence of synthetic cystic fibrosis medium (SCFM) and evaluated the bacterial growth when exposed to human DNA.

Results.

M. abscessus

is capable of forming biofilm in SCFM. By eliminating single components found in the medium, it became clear that magnesium works as a signal for the biofilm formation, and chelation of the divalent cations resulted in the suppression of biofilm formation. Investigation of the specific proteins expressed in the presence of SCFM and in the presence of SCFM lacking magnesium revealed many different proteins between the conditions.

M. abscessus

also exhibited growth in SCFM and in the presence of host cell DNA, although the mechanism of DNA utilization remains unclear.

Conclusions.
In vitro conditions mimicking the airways of patients with cystic fibrosis appear to facilitate

M. abscessus

establishment of infection, and elimination of magnesium from the environment may affect the ability of the pathogen to establish infection.
Transcriptomic analysis of Pseudomonas ogarae F113 reveals the antagonistic roles of AmrZ and FleQ during rhizosphere adaption
Authors: Blanco-Romero Esther , Durán David , Garrido-Sanz Daniel , Rivilla Rafael , Martín Marta , Redondo-Nieto Miguel
Published: January 2022

Rhizosphere colonization by bacteria involves molecular and cellular mechanisms, such as motility and chemotaxis, biofilm formation, metabolic versatility, or biosynthesis of secondary metabolites, among others. Nonetheless, there is limited knowledge concerning the main regulatory factors that drive the rhizosphere colonization process. Here we show the importance of the AmrZ and FleQ transcription factors for adaption in the plant growth-promoting rhizobacterium (PGPR) and rhizosphere colonization model

Pseudomonas ogarae

F113. RNA-Seq analyses of

P. ogarae

F113 grown in liquid cultures either in exponential and stationary growth phase, and rhizosphere conditions, revealed that rhizosphere is a key driver of global changes in gene expression in this bacterium. Regarding the genetic background, this work has revealed that a mutation in fleQ causes considerably more alterations in the gene expression profile of this bacterium than a mutation in amrZ under rhizosphere conditions. The functional analysis has revealed that in

P. ogarae

F113, the transcription factors AmrZ and FleQ regulate genes involved in diverse bacterial functions. Notably, in the rhizosphere, these transcription factors antagonistically regulate genes related to motility, biofilm formation, nitrogen, sulfur, and amino acid metabolism, transport, signalling, and secretion, especially the type VI secretion systems. These results define the regulon of two important bifunctional transcriptional regulators in pseudomonads during the process of rhizosphere colonization.